U.S. BRAND NAMES — Unasyn®
PHARMACOLOGIC CATEGORY
Antibiotic, Penicillin
DOSING: ADULTS — Doses expressed as ampicillin/sulbactam combination.
Susceptible infections: I.M., I.V.: 1.5-3 g every 6 hours (maximum: Unasyn® 12 g)
Amnionitis, cholangitis, diverticulitis, endometritis, endophthalmitis, epididymitis/orchitis, liver abscess, osteomyelitis (diabetic foot), peritonitis: I.V.: 3 g every 6 hours
Endocarditis: I.V.: 3 g every 6 hours with gentamicin or vancomycin for 4-6 weeks
Orbital cellulitis: I.V.: 1.5 g every 6 hours
Parapharyngeal space infections: I.V.: 3 g every 6 hours
Pasteurella multocida(human, canine/feline bites): I.V.: 1.5-3 g every 6 hours
Pelvic inflammatory disease: I.V.: 3 g every 6 hours with doxycycline
Peritonitis (CAPD): Intraperitoneal:
Anuric, intermittent: 3 g every 12 hours
Anuric, continuous: Loading dose: 1.5 g; maintenance dose: 150 mg
Pneumonia:
Aspiration, community-acquired: I.V.: 1.5-3 g every 6 hours
Hospital-acquired: I.V.: 3 g every 6 hours
Urinary tract infections, pyelonephritis: I.V.: 3 g every 6 hours for 14 days
DOSING: PEDIATRIC
(For additional information see "Ampicillin and sulbactam: Pediatric drug information")
Susceptible infections: Children ≥ 1 year: I.V.: 100-400 mg ampicillin/kg/day divided every 6 hours (maximum: 8 g ampicillin/day, 12 g Unasyn®). Note: The American Academy of Pediatrics recommends a dose of up to 300 mg/kg/day for severe infection in infants >1 month of age.
Epiglottitis: Children ≥ 1 year: I.V.: 100-200 mg ampicillin/kg/day divided in 4 doses
Mild-to-moderate infections: Children ≥ 1 year: I.V.: 100-200 mg ampicillin/kg/day (150-300 mg Unasyn®) divided every 6 hours (maximum: 8 g ampicillin/day, 12 g Unasyn®)
Peritonsillar and retropharyngeal abscess: Children ≥ 1 year: I.V.: 50 mg ampicillin/kg/dose every 6 hours
Severe infections: Children ≥ 1 year: I.V.: 200-400 mg ampicillin/kg/day divided every 6 hours (maximum: 8 g ampicillin/day, 12 g Unasyn®)
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT
Clcr 15-29 mL/minute: Administer every 12 hours
Clcr 5-14 mL/minute: Administer every 24 hours
Hemodialysis: Give dose after hemodialysis
Continuous ambulatory peritoneal dialysis (CAPD): 3 g every 24 hours
Continuous renal replacement therapy (CRRT): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug levels in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1 L/hour) and should not supersede clinical judgment:
CVVH: 3 g every 12 hours
CVVHD/CVVHDF: 3 g every 8 hours
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution: 1.5 g: Ampicillin 1 g and sulbactam 0.5 g [contains sodium 115 mg (5 mEq)/1.5 g)]; 3 g: Ampicillin 2 g and sulbactam 1 g [contains sodium 115 mg (5 mEq)/1.5 g)]; 15 g: Ampicillin 10 g and sulbactam 5 g [bulk package; contains sodium 115 mg (5 mEq)/1.5 g]
Unasyn®:
1.5 g: Ampicillin 1 g and sulbactam 0.5 g [contains sodium 115 mg (5 mEq)/1.5 g)]
3 g: Ampicillin 2 g and sulbactam 1 g [contains sodium 115 mg (5 mEq)/1.5 g)]
15 g: Ampicillin 10 g and sulbactam 5 g [bulk package; contains sodium 115 mg (5 mEq)/1.5 g)]
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution: 1.5 g [ampicillin 1 g and sulbactam 0.5 g]; 3 g [ampicillin 2 g and sulbactam 1 g]; 15 g [ampicillin 10 g and sulbactam 5 g]
Unasyn®: 1.5 g [ampicillin 1 g and sulbactam 0.5 g]; 3 g [ampicillin 2 g and sulbactam 1 g]; 15 g [ampicillin 10 g and sulbactam 5 g]; 15 g [ampicillin 10 g and sulbactam 5 g
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer around-the-clock to promote less variation in peak and trough serum levels. Administer by slow injection over 10-15 minutes or I.V. over 15-30 minutes. Ampicillin and gentamicin should not be mixed in the same I.V. tubing.
Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate aminoglycosides in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.
COMPATIBILITY — Stable in NS; variable stability (consult detailed reference) in D51/2NS, D5W, LR.
Y-site administration: Compatible: Amifostine, aztreonam, cefepime, docetaxel, enalaprilat, etoposide, famotidine, filgrastim, fluconazole, fludarabine, gatifloxacin, gemcitabine, granisetron, heparin, insulin (regular), linezolid, meperidine, morphine, paclitaxel, remifentanil, tacrolimus, teniposide, theophylline, thiotepa. Incompatible: Aminoglycosides (gentamicin, tobramycin), amphotericin B cholesteryl sulfate complex, ciprofloxacin, idarubicin, ondansetron, sargramostim. Variable (consult detailed reference): Cisatracurium, diltiazem, vancomycin.
Compatibility when admixed: Compatible: Aztreonam. Incompatible: Aminoglycosides.
USE — Treatment of susceptible bacterial infections involved with skin and skin structure, intra-abdominal infections, gynecological infections; spectrum is that of ampicillin plus organisms producing beta-lactamases such as S. aureus, H. influenzae, E. coli, Klebsiella, Acinetobacter, Enterobacter, and anaerobes
ADVERSE REACTIONS SIGNIFICANT — Also see Ampicillin.
>10%: Local: Pain at injection site (I.M.)
1% to 10%:
Dermatologic: Rash
Gastrointestinal: Diarrhea
Local: Pain at injection site (I.V.), thrombophlebitis
Miscellaneous: Allergic reaction (may include serum sickness, urticaria, bronchospasm, hypotension, etc)
<1% (Limited to important or life-threatening): Abdominal distension, candidiasis, chest pain, chills, dysuria, edema, epistaxis, erythema, facial swelling, fatigue, flatulence, glossitis, hairy tongue, headache, interstitial nephritis, itching, liver enzymes increased, malaise, mucosal bleeding, nausea, pseudomembranous colitis, seizure, substernal pain, throat tightness, thrombocytopenia, urine retention, vomiting
CONTRAINDICATIONS — Hypersensitivity to ampicillin, sulbactam, penicillins, or any component of the formulations
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylactoid/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity, history of sensitivity to multiple allergens, or previous IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria). Use with caution in asthmatic patients. Rash: Appearance of a rash should be carefully evaluated to differentiate a nonallergic ampicillin rash from a hypersensitivity reaction; rash occurs in 5% to 10% of children and is a generalized dull red, maculopapular rash, generally appearing 3-14 days after the start of therapy. It normally begins on the trunk and spreads over most of the body. It may be most intense at pressure areas, elbows, and knees. Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns: Infectious mononucleosis: A high percentage of patients with infectious mononucleosis have developed rash during therapy; ampicillin-class antibiotics not recommended in these patients. Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended.
Special populations: Pediatrics: Safety and efficacy have not been established in children <1 year of age.
DRUG INTERACTIONS
Allopurinol: May enhance the potential for allergic or hypersensitivity reactions to Ampicillin. Risk C: Monitor therapy
Atenolol: Ampicillin may decrease the bioavailability of Atenolol. Risk C: Monitor therapy
Fusidic Acid: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Methotrexate: Penicillins may decrease the excretion of Methotrexate. Risk C: Monitor therapy
Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy
Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification
Uricosuric Agents: May decrease the excretion of Penicillins. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Adverse events have not been observed in animal studies; therefore, ampicillin/sulbactam is classified as pregnancy category B. Both ampicillin and sulbactam cross the placenta. When used during pregnancy, pharmacokinetic changes have been observed with ampicillin alone (refer to the Ampicillin monograph for details).
LACTATION — Enters breast milk/use caution
BREAST-FEEDING CONSIDERATIONS — Ampicillin and sulbactam are both excreted into breast milk in low concentrations. The manufacturer recommends that caution be used if administering to lactating women. Nondose-related effects could include modification of bowel flora and allergic sensitization of the infant. The maternal dose of sulbactam does not need altered in the postpartum period. Also refer to the Ampicillin monograph.
DIETARY CONSIDERATIONS — Sodium content of 1.5 g injection: 115 mg (5 mEq)
MONITORING PARAMETERS — With prolonged therapy, monitor hematologic, renal, and hepatic function; monitor for signs of anaphylaxis during first dose
CANADIAN BRAND NAMES — Unasyn®
INTERNATIONAL BRAND NAMES — Ampibactan (VE); Amplisul (EC); Ansulina (TW); Baccillin (KP); Bactacin (KP); Bactesyn (ID); Easyn (MY); Picyn (ID); Prixin (PY); Rukasyn (KP); Sulbaccin (TH); Sulbacin (IN, KP, MY, PH); Sultamicilina (AR); Ubacillin (KP); Ubactam (KP); Unacid (DE); Unacim (FR); Unasyn (AE, AT, BF, BH, BJ, BR, CI, CL, CN, CO, CR, CY, CZ, EC, EE, EG, ET, GH, GM, GN, GT, HK, HN, ID, IL, IQ, IR, IT, JO, KE, KP, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, NI, OM, PA, PE, PH, QA, SA, SC, SD, SL, SN, SV, SY, TN, TW, TZ, UG, YE, ZA, ZM, ZW); Unasyna (AR, UY)
MECHANISM OF ACTION — The addition of sulbactam, a beta-lactamase inhibitor, to ampicillin extends the spectrum of ampicillin to include some beta-lactamase-producing organisms; inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
PHARMACODYNAMICS / KINETICS
Ampicillin: See Ampicillin.
Sulbactam:
Distribution: Bile, blister, and tissue fluids
Protein binding: 38%
Half-life elimination: Normal renal function: 1-1.3 hours
Excretion: Urine (~75% to 85% as unchanged drug) within 8 hours
Monday, August 2, 2010
Ampicillin and sulbactam
U.S. BRAND NAMES — Unasyn®
PHARMACOLOGIC CATEGORY
Antibiotic, Penicillin
DOSING: ADULTS — Doses expressed as ampicillin/sulbactam combination.
Susceptible infections: I.M., I.V.: 1.5-3 g every 6 hours (maximum: Unasyn® 12 g)
Amnionitis, cholangitis, diverticulitis, endometritis, endophthalmitis, epididymitis/orchitis, liver abscess, osteomyelitis (diabetic foot), peritonitis: I.V.: 3 g every 6 hours
Endocarditis: I.V.: 3 g every 6 hours with gentamicin or vancomycin for 4-6 weeks
Orbital cellulitis: I.V.: 1.5 g every 6 hours
Parapharyngeal space infections: I.V.: 3 g every 6 hours
Pasteurella multocida(human, canine/feline bites): I.V.: 1.5-3 g every 6 hours
Pelvic inflammatory disease: I.V.: 3 g every 6 hours with doxycycline
Peritonitis (CAPD): Intraperitoneal:
Anuric, intermittent: 3 g every 12 hours
Anuric, continuous: Loading dose: 1.5 g; maintenance dose: 150 mg
Pneumonia:
Aspiration, community-acquired: I.V.: 1.5-3 g every 6 hours
Hospital-acquired: I.V.: 3 g every 6 hours
Urinary tract infections, pyelonephritis: I.V.: 3 g every 6 hours for 14 days
DOSING: PEDIATRIC
(For additional information see "Ampicillin and sulbactam: Pediatric drug information")
Susceptible infections: Children ≥ 1 year: I.V.: 100-400 mg ampicillin/kg/day divided every 6 hours (maximum: 8 g ampicillin/day, 12 g Unasyn®). Note: The American Academy of Pediatrics recommends a dose of up to 300 mg/kg/day for severe infection in infants >1 month of age.
Epiglottitis: Children ≥ 1 year: I.V.: 100-200 mg ampicillin/kg/day divided in 4 doses
Mild-to-moderate infections: Children ≥ 1 year: I.V.: 100-200 mg ampicillin/kg/day (150-300 mg Unasyn®) divided every 6 hours (maximum: 8 g ampicillin/day, 12 g Unasyn®)
Peritonsillar and retropharyngeal abscess: Children ≥ 1 year: I.V.: 50 mg ampicillin/kg/dose every 6 hours
Severe infections: Children ≥ 1 year: I.V.: 200-400 mg ampicillin/kg/day divided every 6 hours (maximum: 8 g ampicillin/day, 12 g Unasyn®)
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT
Clcr 15-29 mL/minute: Administer every 12 hours
Clcr 5-14 mL/minute: Administer every 24 hours
Hemodialysis: Give dose after hemodialysis
Continuous ambulatory peritoneal dialysis (CAPD): 3 g every 24 hours
Continuous renal replacement therapy (CRRT): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug levels in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1 L/hour) and should not supersede clinical judgment:
CVVH: 3 g every 12 hours
CVVHD/CVVHDF: 3 g every 8 hours
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution: 1.5 g: Ampicillin 1 g and sulbactam 0.5 g [contains sodium 115 mg (5 mEq)/1.5 g)]; 3 g: Ampicillin 2 g and sulbactam 1 g [contains sodium 115 mg (5 mEq)/1.5 g)]; 15 g: Ampicillin 10 g and sulbactam 5 g [bulk package; contains sodium 115 mg (5 mEq)/1.5 g]
Unasyn®:
1.5 g: Ampicillin 1 g and sulbactam 0.5 g [contains sodium 115 mg (5 mEq)/1.5 g)]
3 g: Ampicillin 2 g and sulbactam 1 g [contains sodium 115 mg (5 mEq)/1.5 g)]
15 g: Ampicillin 10 g and sulbactam 5 g [bulk package; contains sodium 115 mg (5 mEq)/1.5 g)]
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution: 1.5 g [ampicillin 1 g and sulbactam 0.5 g]; 3 g [ampicillin 2 g and sulbactam 1 g]; 15 g [ampicillin 10 g and sulbactam 5 g]
Unasyn®: 1.5 g [ampicillin 1 g and sulbactam 0.5 g]; 3 g [ampicillin 2 g and sulbactam 1 g]; 15 g [ampicillin 10 g and sulbactam 5 g]; 15 g [ampicillin 10 g and sulbactam 5 g
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer around-the-clock to promote less variation in peak and trough serum levels. Administer by slow injection over 10-15 minutes or I.V. over 15-30 minutes. Ampicillin and gentamicin should not be mixed in the same I.V. tubing.
Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate aminoglycosides in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.
COMPATIBILITY — Stable in NS; variable stability (consult detailed reference) in D51/2NS, D5W, LR.
Y-site administration: Compatible: Amifostine, aztreonam, cefepime, docetaxel, enalaprilat, etoposide, famotidine, filgrastim, fluconazole, fludarabine, gatifloxacin, gemcitabine, granisetron, heparin, insulin (regular), linezolid, meperidine, morphine, paclitaxel, remifentanil, tacrolimus, teniposide, theophylline, thiotepa. Incompatible: Aminoglycosides (gentamicin, tobramycin), amphotericin B cholesteryl sulfate complex, ciprofloxacin, idarubicin, ondansetron, sargramostim. Variable (consult detailed reference): Cisatracurium, diltiazem, vancomycin.
Compatibility when admixed: Compatible: Aztreonam. Incompatible: Aminoglycosides.
USE — Treatment of susceptible bacterial infections involved with skin and skin structure, intra-abdominal infections, gynecological infections; spectrum is that of ampicillin plus organisms producing beta-lactamases such as S. aureus, H. influenzae, E. coli, Klebsiella, Acinetobacter, Enterobacter, and anaerobes
ADVERSE REACTIONS SIGNIFICANT — Also see Ampicillin.
>10%: Local: Pain at injection site (I.M.)
1% to 10%:
Dermatologic: Rash
Gastrointestinal: Diarrhea
Local: Pain at injection site (I.V.), thrombophlebitis
Miscellaneous: Allergic reaction (may include serum sickness, urticaria, bronchospasm, hypotension, etc)
<1% (Limited to important or life-threatening): Abdominal distension, candidiasis, chest pain, chills, dysuria, edema, epistaxis, erythema, facial swelling, fatigue, flatulence, glossitis, hairy tongue, headache, interstitial nephritis, itching, liver enzymes increased, malaise, mucosal bleeding, nausea, pseudomembranous colitis, seizure, substernal pain, throat tightness, thrombocytopenia, urine retention, vomiting
CONTRAINDICATIONS — Hypersensitivity to ampicillin, sulbactam, penicillins, or any component of the formulations
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylactoid/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity, history of sensitivity to multiple allergens, or previous IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria). Use with caution in asthmatic patients. Rash: Appearance of a rash should be carefully evaluated to differentiate a nonallergic ampicillin rash from a hypersensitivity reaction; rash occurs in 5% to 10% of children and is a generalized dull red, maculopapular rash, generally appearing 3-14 days after the start of therapy. It normally begins on the trunk and spreads over most of the body. It may be most intense at pressure areas, elbows, and knees. Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns: Infectious mononucleosis: A high percentage of patients with infectious mononucleosis have developed rash during therapy; ampicillin-class antibiotics not recommended in these patients. Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended.
Special populations: Pediatrics: Safety and efficacy have not been established in children <1 year of age.
DRUG INTERACTIONS
Allopurinol: May enhance the potential for allergic or hypersensitivity reactions to Ampicillin. Risk C: Monitor therapy
Atenolol: Ampicillin may decrease the bioavailability of Atenolol. Risk C: Monitor therapy
Fusidic Acid: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Methotrexate: Penicillins may decrease the excretion of Methotrexate. Risk C: Monitor therapy
Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy
Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification
Uricosuric Agents: May decrease the excretion of Penicillins. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Adverse events have not been observed in animal studies; therefore, ampicillin/sulbactam is classified as pregnancy category B. Both ampicillin and sulbactam cross the placenta. When used during pregnancy, pharmacokinetic changes have been observed with ampicillin alone (refer to the Ampicillin monograph for details).
LACTATION — Enters breast milk/use caution
BREAST-FEEDING CONSIDERATIONS — Ampicillin and sulbactam are both excreted into breast milk in low concentrations. The manufacturer recommends that caution be used if administering to lactating women. Nondose-related effects could include modification of bowel flora and allergic sensitization of the infant. The maternal dose of sulbactam does not need altered in the postpartum period. Also refer to the Ampicillin monograph.
DIETARY CONSIDERATIONS — Sodium content of 1.5 g injection: 115 mg (5 mEq)
MONITORING PARAMETERS — With prolonged therapy, monitor hematologic, renal, and hepatic function; monitor for signs of anaphylaxis during first dose
CANADIAN BRAND NAMES — Unasyn®
INTERNATIONAL BRAND NAMES — Ampibactan (VE); Amplisul (EC); Ansulina (TW); Baccillin (KP); Bactacin (KP); Bactesyn (ID); Easyn (MY); Picyn (ID); Prixin (PY); Rukasyn (KP); Sulbaccin (TH); Sulbacin (IN, KP, MY, PH); Sultamicilina (AR); Ubacillin (KP); Ubactam (KP); Unacid (DE); Unacim (FR); Unasyn (AE, AT, BF, BH, BJ, BR, CI, CL, CN, CO, CR, CY, CZ, EC, EE, EG, ET, GH, GM, GN, GT, HK, HN, ID, IL, IQ, IR, IT, JO, KE, KP, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, NI, OM, PA, PE, PH, QA, SA, SC, SD, SL, SN, SV, SY, TN, TW, TZ, UG, YE, ZA, ZM, ZW); Unasyna (AR, UY)
MECHANISM OF ACTION — The addition of sulbactam, a beta-lactamase inhibitor, to ampicillin extends the spectrum of ampicillin to include some beta-lactamase-producing organisms; inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
PHARMACODYNAMICS / KINETICS
Ampicillin: See Ampicillin.
Sulbactam:
Distribution: Bile, blister, and tissue fluids
Protein binding: 38%
Half-life elimination: Normal renal function: 1-1.3 hours
Excretion: Urine (~75% to 85% as unchanged drug) within 8 hours
PHARMACOLOGIC CATEGORY
Antibiotic, Penicillin
DOSING: ADULTS — Doses expressed as ampicillin/sulbactam combination.
Susceptible infections: I.M., I.V.: 1.5-3 g every 6 hours (maximum: Unasyn® 12 g)
Amnionitis, cholangitis, diverticulitis, endometritis, endophthalmitis, epididymitis/orchitis, liver abscess, osteomyelitis (diabetic foot), peritonitis: I.V.: 3 g every 6 hours
Endocarditis: I.V.: 3 g every 6 hours with gentamicin or vancomycin for 4-6 weeks
Orbital cellulitis: I.V.: 1.5 g every 6 hours
Parapharyngeal space infections: I.V.: 3 g every 6 hours
Pasteurella multocida(human, canine/feline bites): I.V.: 1.5-3 g every 6 hours
Pelvic inflammatory disease: I.V.: 3 g every 6 hours with doxycycline
Peritonitis (CAPD): Intraperitoneal:
Anuric, intermittent: 3 g every 12 hours
Anuric, continuous: Loading dose: 1.5 g; maintenance dose: 150 mg
Pneumonia:
Aspiration, community-acquired: I.V.: 1.5-3 g every 6 hours
Hospital-acquired: I.V.: 3 g every 6 hours
Urinary tract infections, pyelonephritis: I.V.: 3 g every 6 hours for 14 days
DOSING: PEDIATRIC
(For additional information see "Ampicillin and sulbactam: Pediatric drug information")
Susceptible infections: Children ≥ 1 year: I.V.: 100-400 mg ampicillin/kg/day divided every 6 hours (maximum: 8 g ampicillin/day, 12 g Unasyn®). Note: The American Academy of Pediatrics recommends a dose of up to 300 mg/kg/day for severe infection in infants >1 month of age.
Epiglottitis: Children ≥ 1 year: I.V.: 100-200 mg ampicillin/kg/day divided in 4 doses
Mild-to-moderate infections: Children ≥ 1 year: I.V.: 100-200 mg ampicillin/kg/day (150-300 mg Unasyn®) divided every 6 hours (maximum: 8 g ampicillin/day, 12 g Unasyn®)
Peritonsillar and retropharyngeal abscess: Children ≥ 1 year: I.V.: 50 mg ampicillin/kg/dose every 6 hours
Severe infections: Children ≥ 1 year: I.V.: 200-400 mg ampicillin/kg/day divided every 6 hours (maximum: 8 g ampicillin/day, 12 g Unasyn®)
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT
Clcr 15-29 mL/minute: Administer every 12 hours
Clcr 5-14 mL/minute: Administer every 24 hours
Hemodialysis: Give dose after hemodialysis
Continuous ambulatory peritoneal dialysis (CAPD): 3 g every 24 hours
Continuous renal replacement therapy (CRRT): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug levels in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1 L/hour) and should not supersede clinical judgment:
CVVH: 3 g every 12 hours
CVVHD/CVVHDF: 3 g every 8 hours
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution: 1.5 g: Ampicillin 1 g and sulbactam 0.5 g [contains sodium 115 mg (5 mEq)/1.5 g)]; 3 g: Ampicillin 2 g and sulbactam 1 g [contains sodium 115 mg (5 mEq)/1.5 g)]; 15 g: Ampicillin 10 g and sulbactam 5 g [bulk package; contains sodium 115 mg (5 mEq)/1.5 g]
Unasyn®:
1.5 g: Ampicillin 1 g and sulbactam 0.5 g [contains sodium 115 mg (5 mEq)/1.5 g)]
3 g: Ampicillin 2 g and sulbactam 1 g [contains sodium 115 mg (5 mEq)/1.5 g)]
15 g: Ampicillin 10 g and sulbactam 5 g [bulk package; contains sodium 115 mg (5 mEq)/1.5 g)]
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution: 1.5 g [ampicillin 1 g and sulbactam 0.5 g]; 3 g [ampicillin 2 g and sulbactam 1 g]; 15 g [ampicillin 10 g and sulbactam 5 g]
Unasyn®: 1.5 g [ampicillin 1 g and sulbactam 0.5 g]; 3 g [ampicillin 2 g and sulbactam 1 g]; 15 g [ampicillin 10 g and sulbactam 5 g]; 15 g [ampicillin 10 g and sulbactam 5 g
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer around-the-clock to promote less variation in peak and trough serum levels. Administer by slow injection over 10-15 minutes or I.V. over 15-30 minutes. Ampicillin and gentamicin should not be mixed in the same I.V. tubing.
Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate aminoglycosides in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.
COMPATIBILITY — Stable in NS; variable stability (consult detailed reference) in D51/2NS, D5W, LR.
Y-site administration: Compatible: Amifostine, aztreonam, cefepime, docetaxel, enalaprilat, etoposide, famotidine, filgrastim, fluconazole, fludarabine, gatifloxacin, gemcitabine, granisetron, heparin, insulin (regular), linezolid, meperidine, morphine, paclitaxel, remifentanil, tacrolimus, teniposide, theophylline, thiotepa. Incompatible: Aminoglycosides (gentamicin, tobramycin), amphotericin B cholesteryl sulfate complex, ciprofloxacin, idarubicin, ondansetron, sargramostim. Variable (consult detailed reference): Cisatracurium, diltiazem, vancomycin.
Compatibility when admixed: Compatible: Aztreonam. Incompatible: Aminoglycosides.
USE — Treatment of susceptible bacterial infections involved with skin and skin structure, intra-abdominal infections, gynecological infections; spectrum is that of ampicillin plus organisms producing beta-lactamases such as S. aureus, H. influenzae, E. coli, Klebsiella, Acinetobacter, Enterobacter, and anaerobes
ADVERSE REACTIONS SIGNIFICANT — Also see Ampicillin.
>10%: Local: Pain at injection site (I.M.)
1% to 10%:
Dermatologic: Rash
Gastrointestinal: Diarrhea
Local: Pain at injection site (I.V.), thrombophlebitis
Miscellaneous: Allergic reaction (may include serum sickness, urticaria, bronchospasm, hypotension, etc)
<1% (Limited to important or life-threatening): Abdominal distension, candidiasis, chest pain, chills, dysuria, edema, epistaxis, erythema, facial swelling, fatigue, flatulence, glossitis, hairy tongue, headache, interstitial nephritis, itching, liver enzymes increased, malaise, mucosal bleeding, nausea, pseudomembranous colitis, seizure, substernal pain, throat tightness, thrombocytopenia, urine retention, vomiting
CONTRAINDICATIONS — Hypersensitivity to ampicillin, sulbactam, penicillins, or any component of the formulations
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylactoid/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity, history of sensitivity to multiple allergens, or previous IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria). Use with caution in asthmatic patients. Rash: Appearance of a rash should be carefully evaluated to differentiate a nonallergic ampicillin rash from a hypersensitivity reaction; rash occurs in 5% to 10% of children and is a generalized dull red, maculopapular rash, generally appearing 3-14 days after the start of therapy. It normally begins on the trunk and spreads over most of the body. It may be most intense at pressure areas, elbows, and knees. Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns: Infectious mononucleosis: A high percentage of patients with infectious mononucleosis have developed rash during therapy; ampicillin-class antibiotics not recommended in these patients. Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended.
Special populations: Pediatrics: Safety and efficacy have not been established in children <1 year of age.
DRUG INTERACTIONS
Allopurinol: May enhance the potential for allergic or hypersensitivity reactions to Ampicillin. Risk C: Monitor therapy
Atenolol: Ampicillin may decrease the bioavailability of Atenolol. Risk C: Monitor therapy
Fusidic Acid: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Methotrexate: Penicillins may decrease the excretion of Methotrexate. Risk C: Monitor therapy
Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy
Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification
Uricosuric Agents: May decrease the excretion of Penicillins. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Adverse events have not been observed in animal studies; therefore, ampicillin/sulbactam is classified as pregnancy category B. Both ampicillin and sulbactam cross the placenta. When used during pregnancy, pharmacokinetic changes have been observed with ampicillin alone (refer to the Ampicillin monograph for details).
LACTATION — Enters breast milk/use caution
BREAST-FEEDING CONSIDERATIONS — Ampicillin and sulbactam are both excreted into breast milk in low concentrations. The manufacturer recommends that caution be used if administering to lactating women. Nondose-related effects could include modification of bowel flora and allergic sensitization of the infant. The maternal dose of sulbactam does not need altered in the postpartum period. Also refer to the Ampicillin monograph.
DIETARY CONSIDERATIONS — Sodium content of 1.5 g injection: 115 mg (5 mEq)
MONITORING PARAMETERS — With prolonged therapy, monitor hematologic, renal, and hepatic function; monitor for signs of anaphylaxis during first dose
CANADIAN BRAND NAMES — Unasyn®
INTERNATIONAL BRAND NAMES — Ampibactan (VE); Amplisul (EC); Ansulina (TW); Baccillin (KP); Bactacin (KP); Bactesyn (ID); Easyn (MY); Picyn (ID); Prixin (PY); Rukasyn (KP); Sulbaccin (TH); Sulbacin (IN, KP, MY, PH); Sultamicilina (AR); Ubacillin (KP); Ubactam (KP); Unacid (DE); Unacim (FR); Unasyn (AE, AT, BF, BH, BJ, BR, CI, CL, CN, CO, CR, CY, CZ, EC, EE, EG, ET, GH, GM, GN, GT, HK, HN, ID, IL, IQ, IR, IT, JO, KE, KP, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, NI, OM, PA, PE, PH, QA, SA, SC, SD, SL, SN, SV, SY, TN, TW, TZ, UG, YE, ZA, ZM, ZW); Unasyna (AR, UY)
MECHANISM OF ACTION — The addition of sulbactam, a beta-lactamase inhibitor, to ampicillin extends the spectrum of ampicillin to include some beta-lactamase-producing organisms; inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
PHARMACODYNAMICS / KINETICS
Ampicillin: See Ampicillin.
Sulbactam:
Distribution: Bile, blister, and tissue fluids
Protein binding: 38%
Half-life elimination: Normal renal function: 1-1.3 hours
Excretion: Urine (~75% to 85% as unchanged drug) within 8 hours
Ampicillin
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Ampicillin may be confused with aminophylline
PHARMACOLOGIC CATEGORY
Antibiotic, Penicillin
DOSING: ADULTS
Usual dosage range:
Oral: 250-500 mg every 6 hours
I.M., I.V.: 250-500 mg every 6 hours
Actinomycosis: I.V.: 50 mg/kg/day for 4-6 weeks then oral amoxicillin
Cholangitis (acute): I.V.: 2 g every 4 hours with gentamicin
Diverticulitis: I.M., I.V.: 2 g every 6 hours with metronidazole
Endocarditis:
Infective: I.V.: 12 g/day via continuous infusion or divided every 4 hours
Prophylaxis: Dental, oral, or respiratory tract procedures: I.M., I.V.: 2 g within 30-60 minutes prior to procedure in patients not allergic to penicillin and unable to take oral amoxicillin. Intramuscular injections should be avoided in patients who are receiving anticoagulant therapy. In these circumstances, orally administered regimens should be given whenever possible. Intravenously administered antibiotics should be used for patients who are unable to tolerate or absorb oral medications. Note: American Heart Association (AHA) guidelines now recommend prophylaxis only in patients undergoing invasive procedures and in whom underlying cardiac conditions may predispose to a higher risk of adverse outcomes should infection occur.
Prophylaxis in total joint replacement patient: I.M., I.V.: 2 g 1 hour prior to the procedure
Genitourinary and gastrointestinal tract procedures: I.M., I.V.:
High-risk patients: 2 g within 30 minutes prior to procedure, followed by ampicillin 1 g (or amoxicillin 1g orally) 6 hours later; must be used in combination with gentamicin. Note: As of April 2007, routine prophylaxis for GI/GU procedures is no longer recommended by the AHA.
Moderate-risk patients: 2 g within 30 minutes prior to procedure
Group B strep prophylaxis (intrapartum): I.V.: 2 g initial dose, then 1 g every 4 hours until delivery
Listeria infections: I.V.: 2 g every 4 hours (consider addition of aminoglycoside)
Sepsis/meningitis: I.M., I.V.: 150-250 mg/kg/day divided every 3-4 hours (range: 6-12 g/day)
Urinary tract infections (enterococcus suspected): I.V.: 1-2 g every 6 hours with gentamicin
DOSING: PEDIATRIC
(For additional information see "Ampicillin: Pediatric drug information")
Usual dosage range: Infants and Children:
Oral: 50-100 mg/kg/day in doses divided every 6 hours (maximum: 2-4 g/day)
I.M., I.V.: 100-400 mg/kg/day in divided doses every 6 hours (maximum: 12 g/day)
Endocarditis prophylaxis: Infants and Children: I.M., I.V.:
Dental, oral, or respiratory tract procedures: 50 mg/kg within 30-60 minutes prior to procedure in patients not allergic to penicillin and unable to take oral amoxicillin. Intramuscular injections should be avoided in patients who are receiving anticoagulant therapy. In these circumstances, orally administered regimens should be given whenever possible. Intravenously administered antibiotics should be used for patients who are unable to tolerate or absorb oral medications.
Note: American Heart Association (AHA) guidelines now recommend prophylaxis only in patients undergoing invasive procedures and in whom underlying cardiac conditions may predispose to a higher risk of adverse outcomes should infection occur.
Genitourinary and gastrointestinal tract procedures:
High-risk patients: 50 mg/kg (maximum: 2 g) within 30 minutes prior to procedure, followed by ampicillin 25 mg/kg (or amoxicillin 25 mg/kg orally) 6 hours later; must be used in combination with gentamicin. Note: As of April 2007, routine prophylaxis for GI/GU procedures is no longer recommended by the AHA.
Moderate-risk patients: 50 mg/kg within 30 minutes prior to procedure.
Mild-to-moderate infections: Infants and Children:
Oral: 50-100 mg/kg/day in doses divided every 6 hours (maximum: 2-4 g/day)
I.M., I.V.: 100-150 mg/kg/day in divided doses every 6 hours (maximum: 2-4 g/day)
Severe infections/meningitis: Infants and Children: I.M., I.V.: 200-400 mg/kg/day in divided doses every 6 hours (maximum: 6-12 g/day)
DOSING: ELDERLY — Administer usual adult dose unless renal function is markedly reduced.
DOSING: RENAL IMPAIRMENT
Clcr >50 mL/minute: Administer every 6 hours
Clcr 10-50 mL/minute: Administer every 6-12 hours
Clcr <10 mL/minute: Administer every 12-24 hours
Hemodialysis: Moderately dialyzable (20% to 50%); administer dose after dialysis
Peritoneal dialysis: Moderately dialyzable (20% to 50%)
Administer 250 mg every 12 hours
Continuous arteriovenous or venovenous hemofiltration effects: Dose as for Clcr 10-50 mL/minute; ~50 mg of ampicillin per liter of filtrate is removed
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule: 250 mg, 500 mg
Injection, powder for reconstitution, as sodium: 125 mg, 250 mg, 500 mg, 1 g, 2 g, 10 g
Powder for oral suspension: 125 mg/5 mL (100 mL, 200 mL); 250 mg/5 mL (100 mL, 200 mL)
DOSAGE FORMS: CONCISE
Capsule: 250 mg, 500 mg
Injection, powder for reconstitution: 125 mg, 250 mg, 500 mg, 1 g, 2 g, 10 g
Powder for oral suspension: 125 mg/5 mL, 250 mg/5 mL
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer around-the-clock to promote less variation in peak and trough serum levels.
Oral: Administer on an empty stomach (ie, 1 hour prior to, or 2 hours after meals) to increase total absorption.
I.V.: Administer over 3-5 minutes (125-500 mg) or over 10-15 minutes (1-2 g). More rapid infusion may cause seizures. Ampicillin and gentamicin should not be mixed in the same I.V. tubing.
Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate aminoglycosides in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.
COMPATIBILITY — Incompatible in D5W, D5NS, D10W, fat emulsion 10%, hetastarch 6%, LR; variable stability (consult detailed reference) in NS.
Y-site administration: Compatible: Acyclovir, amifostine, aztreonam, clarithromycin, cyclophosphamide, docetaxel, doxorubicin liposome, enalaprilat, esmolol, etoposide, famotidine, filgrastim, fludarabine, foscarnet, gatifloxacin, gemcitabine, granisetron, heparin, heparin with hydrocortisone sodium succinate, insulin (regular), labetalol, levofloxacin, linezolid, magnesium sulfate, melphalan, meperidine, morphine, multivitamins, ofloxacin, perphenazine, phytonadione, potassium chloride, propofol, remifentanil, tacrolimus, teniposide, theophylline, thiotepa, tolazoline, vitamin B complex with C. Incompatible: Amphotericin B cholesteryl sulfate complex, epinephrine, fluconazole, hydralazine, midazolam, ondansetron, sargramostim, verapamil, vinorelbine. Variable (consult detailed reference): Calcium gluconate, cisatracurium, diltiazem, hetastarch, hydromorphone, vancomycin.
Compatibility in syringe: Compatible: Chloramphenicol, colistimethate, diatrizoate meglumine 52%, diatrizoate sodium 8%, diatrizoate sodium 60%, heparin, iohexol, iopamidol, iothalamate meglumine 60%, ioxaglate meglumine 39.3%, ioxaglate 19.6%, procaine. Incompatible: Erythromycin lactobionate, gentamicin, hydromorphone, kanamycin, lincomycin, metoclopramide. Variable (consult detailed reference): Lidocaine, polymyxin B sulfate, streptomycin.
Compatibility when admixed: Compatible: Clindamycin, erythromycin lactobionate, floxacillin, furosemide. Incompatible: Amikacin, chlorpromazine, dopamine, gentamicin, hydralazine, prochlorperazine. Variable (consult detailed reference): Aztreonam, cefepime, cimetidine, heparin, hydrocortisone sodium succinate, metronidazole, metronidazole with sodium bicarbonate, ranitidine, sodium bicarbonate, verapamil.
USE — Treatment of susceptible bacterial infections (nonbeta-lactamase-producing organisms); treatment or prophylaxis of infective endocarditis; susceptible bacterial infections caused by streptococci, pneumococci, nonpenicillinase-producing staphylococci, Listeria, meningococci; some strains of H. influenzae, Salmonella, Shigella, E. coli, Enterobacter, and Klebsiella
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Central nervous system: Fever, penicillin encephalopathy, seizure
Dermatologic: Erythema multiforme, exfoliative dermatitis, rash, urticaria
Note: Appearance of a rash should be carefully evaluated to differentiate (if possible) nonallergic ampicillin rash from hypersensitivity reaction. Incidence is higher in patients with viral infection, Salmonella infection, lymphocytic leukemia, or patients that have hyperuricemia.
Gastrointestinal: Black hairy tongue, diarrhea, enterocolitis, glossitis, nausea, pseudomembranous colitis, sore mouth or tongue, stomatitis, vomiting, oral candidiasis
Hematologic: Agranulocytosis, anemia, hemolytic anemia, eosinophilia, leukopenia, thrombocytopenia purpura
Hepatic: AST increased
Renal: Interstitial nephritis (rare)
Respiratory: Laryngeal stridor
Miscellaneous: Anaphylaxis, serum sickness-like reaction
CONTRAINDICATIONS — Hypersensitivity to ampicillin, any component of the formulation, or other penicillins
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylactoid/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity, history of sensitivity to multiple allergens, or previous IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria). Use with caution in asthmatic patients. Rash: Appearance of a rash should be carefully evaluated to differentiate a nonallergic ampicillin rash from a hypersensitivity reaction; rash occurs in 5% to 10% of children and is a generalized dull red, maculopapular rash, generally appearing 3-14 days after the start of therapy. It normally begins on the trunk and spreads over most of the body. It may be most intense at pressure areas, elbows, and knees. Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns: Infectious mononucleosis: A high percentage of patients with infectious mononucleosis have developed rash during therapy; ampicillin-class antibiotics not recommended in these patients. Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended.
DRUG INTERACTIONS
Allopurinol: May enhance the potential for allergic or hypersensitivity reactions to Ampicillin. Risk C: Monitor therapy
Atenolol: Ampicillin may decrease the bioavailability of Atenolol. Risk C: Monitor therapy
Fusidic Acid: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Methotrexate: Penicillins may decrease the excretion of Methotrexate. Risk C: Monitor therapy
Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy
Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification
Uricosuric Agents: May decrease the excretion of Penicillins. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Food decreases ampicillin absorption rate; may decrease ampicillin serum concentration.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Adverse events have not been observed in animal studies; therefore, ampicillin is classified as pregnancy category B. Ampicillin crosses the human placenta, providing detectable concentrations in the cord serum and amniotic fluid. Most studies have not identified a teratogenic potential for ampicillin use during pregnancy. Two possible associations (congenital heart disease and cleft palate) have been noted; each of these was observed in a single study, was not substantiated by other studies, and may have been chance associations. Ampicillin is recommended for use in pregnant women for the management of premature rupture of membranes. Ampicillin is considered an acceptable alternative to penicillin for the prevention of early-onset Group B Streptococcal (GBS) disease in newborns.
The volume of distribution of ampicillin is increased during pregnancy and the half-life is decreased. As a result, serum concentrations in pregnant patients are approximately 50% of those in nonpregnant patients receiving the same dose. Higher doses may be needed during pregnancy. Although oral absorption is not altered during pregnancy, oral ampicillin is poorly-absorbed during labor.
LACTATION — Enters breast milk/use caution
BREAST-FEEDING CONSIDERATIONS — Ampicillin is excreted in breast milk. The manufacturer recommends that caution be exercised when administering ampicillin to nursing women. Due to the low concentrations in human milk, minimal toxicity would be expected in the nursing infant. Nondose-related effects could include modification of bowel flora and allergic sensitization.
DIETARY CONSIDERATIONS — Take on an empty stomach 1 hour before or 2 hours after meals.
Sodium content of 5 mL suspension (250 mg/5 mL): 10 mg (0.4 mEq)
Sodium content of 1 g: 66.7 mg (3 mEq)
PRICING — (data from drugstore.com)
Capsules (Ampicillin)
250 mg (30): $12.99
250 mg (90): $31.95
500 mg (100): $49.99
MONITORING PARAMETERS — With prolonged therapy, monitor renal, hepatic, and hematologic function periodically; observe signs and symptoms of anaphylaxis during first dose
CANADIAN BRAND NAMES — Apo-Ampi®; Novo-Ampicillin; Nu-Ampi
INTERNATIONAL BRAND NAMES — Alphacin (AU, NZ); Alphapen (MX); Ambiopi (ID); Amcopen (PK); Amfipen (AE, BH, CY, EG, GB, IE, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Amipenix (JP); Ampecu (EC); Ampen (VE); Ampenolet (GR); Ampiblan (CO); Ampicher (EC); Ampicil (BR); Ampicilina (EC); Ampicillin (PL); Ampicin (PH); Ampiclox (SG); Ampico (PH); Ampicyn (AU); Ampidar (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Ampifen (NL); Ampiflex (PE); Ampiger (BR); Ampilag (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Ampilin (IN); Ampillin (MY); Ampimedin (PY); Ampipen (IN, ZA); Ampitenk (AR); Ampitrex (PH); Ampivral (CO); Ampliblan (CO); Ampolin (TW); Amsapen (MX); Ancillin (TW); Binotal (AT, BR, CO, EC, MX, UY); Biocil (MY); Bridopen (PH); Brupen (MX); Camicil (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Cilisod (TW); Citicil (IT); Clovillin (PH); Dhacillin (HK, MY); Dibacilina (MX); Doktacillin (SE); Duacillin (MY); Eurocin (PH); Excillin (PH); Extrapen (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Flamicina (MX); Gramcil (PH); Ibimycin (AU); Intramed (ZA); Iwacillin (JP); Julphapen (PE); Magnapen (PE); Marovilina (MX); Maxipen (CO); Microcilin (PH); Omnipen (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, MX, OM, PE, QA, SA, SY, YE); Pamecil (BF, BJ, CI, ET, GH, GM, GN, HK, KE, LR, MA, ML, MR, MU, MW, MY, NE, NG, SC, SD, SG, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Panacta (PH); Pelitin (TW); Penbritin (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, HK, IE, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Penibrin (IL); Pentrexyl (BE, BF, BJ, CI, DK, ET, GB, GH, GM, GN, GR, IT, KE, LR, MA, ML, MR, MU, MW, MX, NE, NG, NL, NO, PE, SC, SD, SL, SN, TH, TN, TZ, UG, ZA, ZM, ZW); Petercillin (ZA); Picaplin (TW); Polypen (PH); Primapen (ID); Promecilina (MX); Radiocillina (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Rimacillin (AE, BB, BF, BH, BJ, BM, BS, BZ, CI, CY, EG, ET, GH, GM, GN, GY, IL, IQ, IR, JM, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, NL, OM, QA, SA, SC, SD, SL, SN, SR, SY, TN, TT, TZ, UG, YE, ZA, ZM, ZW); Roscillin (IN); Sanpicillin (ID); Semicillin (HN); Shacillin (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Sintelin (PE); Standacillin (AE, BG, BH, CY, EE, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Standcillin (MY); Synthocilin (IN); Totapen (FR); Tricil (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Trifalicina (AR); Trilaxin (PH); Vacillin (TH); Viccillin (ID); Vidopen (GB, IE); Virucil (CO); Winpicillin (TW)
MECHANISM OF ACTION — Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
PHARMACODYNAMICS / KINETICS
Absorption: Oral: 50%
Distribution: Bile, blister, and tissue fluids; penetration into CSF occurs with inflamed meninges only, good only with inflammation (exceeds usual MICs)
Normal meninges: Nil; Inflamed meninges: 5% to 10%
Protein binding: 15% to 25%
Half-life elimination:
Children and Adults: 1-1.8 hours
Anuria/end-stage renal disease: 7-20 hours
Time to peak: Oral: Within 1-2 hours
Excretion: Urine (~90% as unchanged drug) within 24 hours
PATIENT INFORMATION — Report diarrhea promptly; take entire course of medication; females should report onset of symptoms of candidal vaginitis
Sound-alike/look-alike issues:
Ampicillin may be confused with aminophylline
PHARMACOLOGIC CATEGORY
Antibiotic, Penicillin
DOSING: ADULTS
Usual dosage range:
Oral: 250-500 mg every 6 hours
I.M., I.V.: 250-500 mg every 6 hours
Actinomycosis: I.V.: 50 mg/kg/day for 4-6 weeks then oral amoxicillin
Cholangitis (acute): I.V.: 2 g every 4 hours with gentamicin
Diverticulitis: I.M., I.V.: 2 g every 6 hours with metronidazole
Endocarditis:
Infective: I.V.: 12 g/day via continuous infusion or divided every 4 hours
Prophylaxis: Dental, oral, or respiratory tract procedures: I.M., I.V.: 2 g within 30-60 minutes prior to procedure in patients not allergic to penicillin and unable to take oral amoxicillin. Intramuscular injections should be avoided in patients who are receiving anticoagulant therapy. In these circumstances, orally administered regimens should be given whenever possible. Intravenously administered antibiotics should be used for patients who are unable to tolerate or absorb oral medications. Note: American Heart Association (AHA) guidelines now recommend prophylaxis only in patients undergoing invasive procedures and in whom underlying cardiac conditions may predispose to a higher risk of adverse outcomes should infection occur.
Prophylaxis in total joint replacement patient: I.M., I.V.: 2 g 1 hour prior to the procedure
Genitourinary and gastrointestinal tract procedures: I.M., I.V.:
High-risk patients: 2 g within 30 minutes prior to procedure, followed by ampicillin 1 g (or amoxicillin 1g orally) 6 hours later; must be used in combination with gentamicin. Note: As of April 2007, routine prophylaxis for GI/GU procedures is no longer recommended by the AHA.
Moderate-risk patients: 2 g within 30 minutes prior to procedure
Group B strep prophylaxis (intrapartum): I.V.: 2 g initial dose, then 1 g every 4 hours until delivery
Listeria infections: I.V.: 2 g every 4 hours (consider addition of aminoglycoside)
Sepsis/meningitis: I.M., I.V.: 150-250 mg/kg/day divided every 3-4 hours (range: 6-12 g/day)
Urinary tract infections (enterococcus suspected): I.V.: 1-2 g every 6 hours with gentamicin
DOSING: PEDIATRIC
(For additional information see "Ampicillin: Pediatric drug information")
Usual dosage range: Infants and Children:
Oral: 50-100 mg/kg/day in doses divided every 6 hours (maximum: 2-4 g/day)
I.M., I.V.: 100-400 mg/kg/day in divided doses every 6 hours (maximum: 12 g/day)
Endocarditis prophylaxis: Infants and Children: I.M., I.V.:
Dental, oral, or respiratory tract procedures: 50 mg/kg within 30-60 minutes prior to procedure in patients not allergic to penicillin and unable to take oral amoxicillin. Intramuscular injections should be avoided in patients who are receiving anticoagulant therapy. In these circumstances, orally administered regimens should be given whenever possible. Intravenously administered antibiotics should be used for patients who are unable to tolerate or absorb oral medications.
Note: American Heart Association (AHA) guidelines now recommend prophylaxis only in patients undergoing invasive procedures and in whom underlying cardiac conditions may predispose to a higher risk of adverse outcomes should infection occur.
Genitourinary and gastrointestinal tract procedures:
High-risk patients: 50 mg/kg (maximum: 2 g) within 30 minutes prior to procedure, followed by ampicillin 25 mg/kg (or amoxicillin 25 mg/kg orally) 6 hours later; must be used in combination with gentamicin. Note: As of April 2007, routine prophylaxis for GI/GU procedures is no longer recommended by the AHA.
Moderate-risk patients: 50 mg/kg within 30 minutes prior to procedure.
Mild-to-moderate infections: Infants and Children:
Oral: 50-100 mg/kg/day in doses divided every 6 hours (maximum: 2-4 g/day)
I.M., I.V.: 100-150 mg/kg/day in divided doses every 6 hours (maximum: 2-4 g/day)
Severe infections/meningitis: Infants and Children: I.M., I.V.: 200-400 mg/kg/day in divided doses every 6 hours (maximum: 6-12 g/day)
DOSING: ELDERLY — Administer usual adult dose unless renal function is markedly reduced.
DOSING: RENAL IMPAIRMENT
Clcr >50 mL/minute: Administer every 6 hours
Clcr 10-50 mL/minute: Administer every 6-12 hours
Clcr <10 mL/minute: Administer every 12-24 hours
Hemodialysis: Moderately dialyzable (20% to 50%); administer dose after dialysis
Peritoneal dialysis: Moderately dialyzable (20% to 50%)
Administer 250 mg every 12 hours
Continuous arteriovenous or venovenous hemofiltration effects: Dose as for Clcr 10-50 mL/minute; ~50 mg of ampicillin per liter of filtrate is removed
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule: 250 mg, 500 mg
Injection, powder for reconstitution, as sodium: 125 mg, 250 mg, 500 mg, 1 g, 2 g, 10 g
Powder for oral suspension: 125 mg/5 mL (100 mL, 200 mL); 250 mg/5 mL (100 mL, 200 mL)
DOSAGE FORMS: CONCISE
Capsule: 250 mg, 500 mg
Injection, powder for reconstitution: 125 mg, 250 mg, 500 mg, 1 g, 2 g, 10 g
Powder for oral suspension: 125 mg/5 mL, 250 mg/5 mL
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer around-the-clock to promote less variation in peak and trough serum levels.
Oral: Administer on an empty stomach (ie, 1 hour prior to, or 2 hours after meals) to increase total absorption.
I.V.: Administer over 3-5 minutes (125-500 mg) or over 10-15 minutes (1-2 g). More rapid infusion may cause seizures. Ampicillin and gentamicin should not be mixed in the same I.V. tubing.
Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate aminoglycosides in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.
COMPATIBILITY — Incompatible in D5W, D5NS, D10W, fat emulsion 10%, hetastarch 6%, LR; variable stability (consult detailed reference) in NS.
Y-site administration: Compatible: Acyclovir, amifostine, aztreonam, clarithromycin, cyclophosphamide, docetaxel, doxorubicin liposome, enalaprilat, esmolol, etoposide, famotidine, filgrastim, fludarabine, foscarnet, gatifloxacin, gemcitabine, granisetron, heparin, heparin with hydrocortisone sodium succinate, insulin (regular), labetalol, levofloxacin, linezolid, magnesium sulfate, melphalan, meperidine, morphine, multivitamins, ofloxacin, perphenazine, phytonadione, potassium chloride, propofol, remifentanil, tacrolimus, teniposide, theophylline, thiotepa, tolazoline, vitamin B complex with C. Incompatible: Amphotericin B cholesteryl sulfate complex, epinephrine, fluconazole, hydralazine, midazolam, ondansetron, sargramostim, verapamil, vinorelbine. Variable (consult detailed reference): Calcium gluconate, cisatracurium, diltiazem, hetastarch, hydromorphone, vancomycin.
Compatibility in syringe: Compatible: Chloramphenicol, colistimethate, diatrizoate meglumine 52%, diatrizoate sodium 8%, diatrizoate sodium 60%, heparin, iohexol, iopamidol, iothalamate meglumine 60%, ioxaglate meglumine 39.3%, ioxaglate 19.6%, procaine. Incompatible: Erythromycin lactobionate, gentamicin, hydromorphone, kanamycin, lincomycin, metoclopramide. Variable (consult detailed reference): Lidocaine, polymyxin B sulfate, streptomycin.
Compatibility when admixed: Compatible: Clindamycin, erythromycin lactobionate, floxacillin, furosemide. Incompatible: Amikacin, chlorpromazine, dopamine, gentamicin, hydralazine, prochlorperazine. Variable (consult detailed reference): Aztreonam, cefepime, cimetidine, heparin, hydrocortisone sodium succinate, metronidazole, metronidazole with sodium bicarbonate, ranitidine, sodium bicarbonate, verapamil.
USE — Treatment of susceptible bacterial infections (nonbeta-lactamase-producing organisms); treatment or prophylaxis of infective endocarditis; susceptible bacterial infections caused by streptococci, pneumococci, nonpenicillinase-producing staphylococci, Listeria, meningococci; some strains of H. influenzae, Salmonella, Shigella, E. coli, Enterobacter, and Klebsiella
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Central nervous system: Fever, penicillin encephalopathy, seizure
Dermatologic: Erythema multiforme, exfoliative dermatitis, rash, urticaria
Note: Appearance of a rash should be carefully evaluated to differentiate (if possible) nonallergic ampicillin rash from hypersensitivity reaction. Incidence is higher in patients with viral infection, Salmonella infection, lymphocytic leukemia, or patients that have hyperuricemia.
Gastrointestinal: Black hairy tongue, diarrhea, enterocolitis, glossitis, nausea, pseudomembranous colitis, sore mouth or tongue, stomatitis, vomiting, oral candidiasis
Hematologic: Agranulocytosis, anemia, hemolytic anemia, eosinophilia, leukopenia, thrombocytopenia purpura
Hepatic: AST increased
Renal: Interstitial nephritis (rare)
Respiratory: Laryngeal stridor
Miscellaneous: Anaphylaxis, serum sickness-like reaction
CONTRAINDICATIONS — Hypersensitivity to ampicillin, any component of the formulation, or other penicillins
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylactoid/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity, history of sensitivity to multiple allergens, or previous IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria). Use with caution in asthmatic patients. Rash: Appearance of a rash should be carefully evaluated to differentiate a nonallergic ampicillin rash from a hypersensitivity reaction; rash occurs in 5% to 10% of children and is a generalized dull red, maculopapular rash, generally appearing 3-14 days after the start of therapy. It normally begins on the trunk and spreads over most of the body. It may be most intense at pressure areas, elbows, and knees. Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns: Infectious mononucleosis: A high percentage of patients with infectious mononucleosis have developed rash during therapy; ampicillin-class antibiotics not recommended in these patients. Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended.
DRUG INTERACTIONS
Allopurinol: May enhance the potential for allergic or hypersensitivity reactions to Ampicillin. Risk C: Monitor therapy
Atenolol: Ampicillin may decrease the bioavailability of Atenolol. Risk C: Monitor therapy
Fusidic Acid: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Methotrexate: Penicillins may decrease the excretion of Methotrexate. Risk C: Monitor therapy
Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy
Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification
Uricosuric Agents: May decrease the excretion of Penicillins. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Food decreases ampicillin absorption rate; may decrease ampicillin serum concentration.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Adverse events have not been observed in animal studies; therefore, ampicillin is classified as pregnancy category B. Ampicillin crosses the human placenta, providing detectable concentrations in the cord serum and amniotic fluid. Most studies have not identified a teratogenic potential for ampicillin use during pregnancy. Two possible associations (congenital heart disease and cleft palate) have been noted; each of these was observed in a single study, was not substantiated by other studies, and may have been chance associations. Ampicillin is recommended for use in pregnant women for the management of premature rupture of membranes. Ampicillin is considered an acceptable alternative to penicillin for the prevention of early-onset Group B Streptococcal (GBS) disease in newborns.
The volume of distribution of ampicillin is increased during pregnancy and the half-life is decreased. As a result, serum concentrations in pregnant patients are approximately 50% of those in nonpregnant patients receiving the same dose. Higher doses may be needed during pregnancy. Although oral absorption is not altered during pregnancy, oral ampicillin is poorly-absorbed during labor.
LACTATION — Enters breast milk/use caution
BREAST-FEEDING CONSIDERATIONS — Ampicillin is excreted in breast milk. The manufacturer recommends that caution be exercised when administering ampicillin to nursing women. Due to the low concentrations in human milk, minimal toxicity would be expected in the nursing infant. Nondose-related effects could include modification of bowel flora and allergic sensitization.
DIETARY CONSIDERATIONS — Take on an empty stomach 1 hour before or 2 hours after meals.
Sodium content of 5 mL suspension (250 mg/5 mL): 10 mg (0.4 mEq)
Sodium content of 1 g: 66.7 mg (3 mEq)
PRICING — (data from drugstore.com)
Capsules (Ampicillin)
250 mg (30): $12.99
250 mg (90): $31.95
500 mg (100): $49.99
MONITORING PARAMETERS — With prolonged therapy, monitor renal, hepatic, and hematologic function periodically; observe signs and symptoms of anaphylaxis during first dose
CANADIAN BRAND NAMES — Apo-Ampi®; Novo-Ampicillin; Nu-Ampi
INTERNATIONAL BRAND NAMES — Alphacin (AU, NZ); Alphapen (MX); Ambiopi (ID); Amcopen (PK); Amfipen (AE, BH, CY, EG, GB, IE, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Amipenix (JP); Ampecu (EC); Ampen (VE); Ampenolet (GR); Ampiblan (CO); Ampicher (EC); Ampicil (BR); Ampicilina (EC); Ampicillin (PL); Ampicin (PH); Ampiclox (SG); Ampico (PH); Ampicyn (AU); Ampidar (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Ampifen (NL); Ampiflex (PE); Ampiger (BR); Ampilag (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Ampilin (IN); Ampillin (MY); Ampimedin (PY); Ampipen (IN, ZA); Ampitenk (AR); Ampitrex (PH); Ampivral (CO); Ampliblan (CO); Ampolin (TW); Amsapen (MX); Ancillin (TW); Binotal (AT, BR, CO, EC, MX, UY); Biocil (MY); Bridopen (PH); Brupen (MX); Camicil (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Cilisod (TW); Citicil (IT); Clovillin (PH); Dhacillin (HK, MY); Dibacilina (MX); Doktacillin (SE); Duacillin (MY); Eurocin (PH); Excillin (PH); Extrapen (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Flamicina (MX); Gramcil (PH); Ibimycin (AU); Intramed (ZA); Iwacillin (JP); Julphapen (PE); Magnapen (PE); Marovilina (MX); Maxipen (CO); Microcilin (PH); Omnipen (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, MX, OM, PE, QA, SA, SY, YE); Pamecil (BF, BJ, CI, ET, GH, GM, GN, HK, KE, LR, MA, ML, MR, MU, MW, MY, NE, NG, SC, SD, SG, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Panacta (PH); Pelitin (TW); Penbritin (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, HK, IE, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Penibrin (IL); Pentrexyl (BE, BF, BJ, CI, DK, ET, GB, GH, GM, GN, GR, IT, KE, LR, MA, ML, MR, MU, MW, MX, NE, NG, NL, NO, PE, SC, SD, SL, SN, TH, TN, TZ, UG, ZA, ZM, ZW); Petercillin (ZA); Picaplin (TW); Polypen (PH); Primapen (ID); Promecilina (MX); Radiocillina (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Rimacillin (AE, BB, BF, BH, BJ, BM, BS, BZ, CI, CY, EG, ET, GH, GM, GN, GY, IL, IQ, IR, JM, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, NL, OM, QA, SA, SC, SD, SL, SN, SR, SY, TN, TT, TZ, UG, YE, ZA, ZM, ZW); Roscillin (IN); Sanpicillin (ID); Semicillin (HN); Shacillin (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Sintelin (PE); Standacillin (AE, BG, BH, CY, EE, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Standcillin (MY); Synthocilin (IN); Totapen (FR); Tricil (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Trifalicina (AR); Trilaxin (PH); Vacillin (TH); Viccillin (ID); Vidopen (GB, IE); Virucil (CO); Winpicillin (TW)
MECHANISM OF ACTION — Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
PHARMACODYNAMICS / KINETICS
Absorption: Oral: 50%
Distribution: Bile, blister, and tissue fluids; penetration into CSF occurs with inflamed meninges only, good only with inflammation (exceeds usual MICs)
Normal meninges: Nil; Inflamed meninges: 5% to 10%
Protein binding: 15% to 25%
Half-life elimination:
Children and Adults: 1-1.8 hours
Anuria/end-stage renal disease: 7-20 hours
Time to peak: Oral: Within 1-2 hours
Excretion: Urine (~90% as unchanged drug) within 24 hours
PATIENT INFORMATION — Report diarrhea promptly; take entire course of medication; females should report onset of symptoms of candidal vaginitis
Ampicillin
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Ampicillin may be confused with aminophylline
PHARMACOLOGIC CATEGORY
Antibiotic, Penicillin
DOSING: ADULTS
Usual dosage range:
Oral: 250-500 mg every 6 hours
I.M., I.V.: 250-500 mg every 6 hours
Actinomycosis: I.V.: 50 mg/kg/day for 4-6 weeks then oral amoxicillin
Cholangitis (acute): I.V.: 2 g every 4 hours with gentamicin
Diverticulitis: I.M., I.V.: 2 g every 6 hours with metronidazole
Endocarditis:
Infective: I.V.: 12 g/day via continuous infusion or divided every 4 hours
Prophylaxis: Dental, oral, or respiratory tract procedures: I.M., I.V.: 2 g within 30-60 minutes prior to procedure in patients not allergic to penicillin and unable to take oral amoxicillin. Intramuscular injections should be avoided in patients who are receiving anticoagulant therapy. In these circumstances, orally administered regimens should be given whenever possible. Intravenously administered antibiotics should be used for patients who are unable to tolerate or absorb oral medications. Note: American Heart Association (AHA) guidelines now recommend prophylaxis only in patients undergoing invasive procedures and in whom underlying cardiac conditions may predispose to a higher risk of adverse outcomes should infection occur.
Prophylaxis in total joint replacement patient: I.M., I.V.: 2 g 1 hour prior to the procedure
Genitourinary and gastrointestinal tract procedures: I.M., I.V.:
High-risk patients: 2 g within 30 minutes prior to procedure, followed by ampicillin 1 g (or amoxicillin 1g orally) 6 hours later; must be used in combination with gentamicin. Note: As of April 2007, routine prophylaxis for GI/GU procedures is no longer recommended by the AHA.
Moderate-risk patients: 2 g within 30 minutes prior to procedure
Group B strep prophylaxis (intrapartum): I.V.: 2 g initial dose, then 1 g every 4 hours until delivery
Listeria infections: I.V.: 2 g every 4 hours (consider addition of aminoglycoside)
Sepsis/meningitis: I.M., I.V.: 150-250 mg/kg/day divided every 3-4 hours (range: 6-12 g/day)
Urinary tract infections (enterococcus suspected): I.V.: 1-2 g every 6 hours with gentamicin
DOSING: PEDIATRIC
(For additional information see "Ampicillin: Pediatric drug information")
Usual dosage range: Infants and Children:
Oral: 50-100 mg/kg/day in doses divided every 6 hours (maximum: 2-4 g/day)
I.M., I.V.: 100-400 mg/kg/day in divided doses every 6 hours (maximum: 12 g/day)
Endocarditis prophylaxis: Infants and Children: I.M., I.V.:
Dental, oral, or respiratory tract procedures: 50 mg/kg within 30-60 minutes prior to procedure in patients not allergic to penicillin and unable to take oral amoxicillin. Intramuscular injections should be avoided in patients who are receiving anticoagulant therapy. In these circumstances, orally administered regimens should be given whenever possible. Intravenously administered antibiotics should be used for patients who are unable to tolerate or absorb oral medications.
Note: American Heart Association (AHA) guidelines now recommend prophylaxis only in patients undergoing invasive procedures and in whom underlying cardiac conditions may predispose to a higher risk of adverse outcomes should infection occur.
Genitourinary and gastrointestinal tract procedures:
High-risk patients: 50 mg/kg (maximum: 2 g) within 30 minutes prior to procedure, followed by ampicillin 25 mg/kg (or amoxicillin 25 mg/kg orally) 6 hours later; must be used in combination with gentamicin. Note: As of April 2007, routine prophylaxis for GI/GU procedures is no longer recommended by the AHA.
Moderate-risk patients: 50 mg/kg within 30 minutes prior to procedure.
Mild-to-moderate infections: Infants and Children:
Oral: 50-100 mg/kg/day in doses divided every 6 hours (maximum: 2-4 g/day)
I.M., I.V.: 100-150 mg/kg/day in divided doses every 6 hours (maximum: 2-4 g/day)
Severe infections/meningitis: Infants and Children: I.M., I.V.: 200-400 mg/kg/day in divided doses every 6 hours (maximum: 6-12 g/day)
DOSING: ELDERLY — Administer usual adult dose unless renal function is markedly reduced.
DOSING: RENAL IMPAIRMENT
Clcr >50 mL/minute: Administer every 6 hours
Clcr 10-50 mL/minute: Administer every 6-12 hours
Clcr <10 mL/minute: Administer every 12-24 hours
Hemodialysis: Moderately dialyzable (20% to 50%); administer dose after dialysis
Peritoneal dialysis: Moderately dialyzable (20% to 50%)
Administer 250 mg every 12 hours
Continuous arteriovenous or venovenous hemofiltration effects: Dose as for Clcr 10-50 mL/minute; ~50 mg of ampicillin per liter of filtrate is removed
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule: 250 mg, 500 mg
Injection, powder for reconstitution, as sodium: 125 mg, 250 mg, 500 mg, 1 g, 2 g, 10 g
Powder for oral suspension: 125 mg/5 mL (100 mL, 200 mL); 250 mg/5 mL (100 mL, 200 mL)
DOSAGE FORMS: CONCISE
Capsule: 250 mg, 500 mg
Injection, powder for reconstitution: 125 mg, 250 mg, 500 mg, 1 g, 2 g, 10 g
Powder for oral suspension: 125 mg/5 mL, 250 mg/5 mL
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer around-the-clock to promote less variation in peak and trough serum levels.
Oral: Administer on an empty stomach (ie, 1 hour prior to, or 2 hours after meals) to increase total absorption.
I.V.: Administer over 3-5 minutes (125-500 mg) or over 10-15 minutes (1-2 g). More rapid infusion may cause seizures. Ampicillin and gentamicin should not be mixed in the same I.V. tubing.
Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate aminoglycosides in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.
COMPATIBILITY — Incompatible in D5W, D5NS, D10W, fat emulsion 10%, hetastarch 6%, LR; variable stability (consult detailed reference) in NS.
Y-site administration: Compatible: Acyclovir, amifostine, aztreonam, clarithromycin, cyclophosphamide, docetaxel, doxorubicin liposome, enalaprilat, esmolol, etoposide, famotidine, filgrastim, fludarabine, foscarnet, gatifloxacin, gemcitabine, granisetron, heparin, heparin with hydrocortisone sodium succinate, insulin (regular), labetalol, levofloxacin, linezolid, magnesium sulfate, melphalan, meperidine, morphine, multivitamins, ofloxacin, perphenazine, phytonadione, potassium chloride, propofol, remifentanil, tacrolimus, teniposide, theophylline, thiotepa, tolazoline, vitamin B complex with C. Incompatible: Amphotericin B cholesteryl sulfate complex, epinephrine, fluconazole, hydralazine, midazolam, ondansetron, sargramostim, verapamil, vinorelbine. Variable (consult detailed reference): Calcium gluconate, cisatracurium, diltiazem, hetastarch, hydromorphone, vancomycin.
Compatibility in syringe: Compatible: Chloramphenicol, colistimethate, diatrizoate meglumine 52%, diatrizoate sodium 8%, diatrizoate sodium 60%, heparin, iohexol, iopamidol, iothalamate meglumine 60%, ioxaglate meglumine 39.3%, ioxaglate 19.6%, procaine. Incompatible: Erythromycin lactobionate, gentamicin, hydromorphone, kanamycin, lincomycin, metoclopramide. Variable (consult detailed reference): Lidocaine, polymyxin B sulfate, streptomycin.
Compatibility when admixed: Compatible: Clindamycin, erythromycin lactobionate, floxacillin, furosemide. Incompatible: Amikacin, chlorpromazine, dopamine, gentamicin, hydralazine, prochlorperazine. Variable (consult detailed reference): Aztreonam, cefepime, cimetidine, heparin, hydrocortisone sodium succinate, metronidazole, metronidazole with sodium bicarbonate, ranitidine, sodium bicarbonate, verapamil.
USE — Treatment of susceptible bacterial infections (nonbeta-lactamase-producing organisms); treatment or prophylaxis of infective endocarditis; susceptible bacterial infections caused by streptococci, pneumococci, nonpenicillinase-producing staphylococci, Listeria, meningococci; some strains of H. influenzae, Salmonella, Shigella, E. coli, Enterobacter, and Klebsiella
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Central nervous system: Fever, penicillin encephalopathy, seizure
Dermatologic: Erythema multiforme, exfoliative dermatitis, rash, urticaria
Note: Appearance of a rash should be carefully evaluated to differentiate (if possible) nonallergic ampicillin rash from hypersensitivity reaction. Incidence is higher in patients with viral infection, Salmonella infection, lymphocytic leukemia, or patients that have hyperuricemia.
Gastrointestinal: Black hairy tongue, diarrhea, enterocolitis, glossitis, nausea, pseudomembranous colitis, sore mouth or tongue, stomatitis, vomiting, oral candidiasis
Hematologic: Agranulocytosis, anemia, hemolytic anemia, eosinophilia, leukopenia, thrombocytopenia purpura
Hepatic: AST increased
Renal: Interstitial nephritis (rare)
Respiratory: Laryngeal stridor
Miscellaneous: Anaphylaxis, serum sickness-like reaction
CONTRAINDICATIONS — Hypersensitivity to ampicillin, any component of the formulation, or other penicillins
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylactoid/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity, history of sensitivity to multiple allergens, or previous IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria). Use with caution in asthmatic patients. Rash: Appearance of a rash should be carefully evaluated to differentiate a nonallergic ampicillin rash from a hypersensitivity reaction; rash occurs in 5% to 10% of children and is a generalized dull red, maculopapular rash, generally appearing 3-14 days after the start of therapy. It normally begins on the trunk and spreads over most of the body. It may be most intense at pressure areas, elbows, and knees. Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns: Infectious mononucleosis: A high percentage of patients with infectious mononucleosis have developed rash during therapy; ampicillin-class antibiotics not recommended in these patients. Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended.
DRUG INTERACTIONS
Allopurinol: May enhance the potential for allergic or hypersensitivity reactions to Ampicillin. Risk C: Monitor therapy
Atenolol: Ampicillin may decrease the bioavailability of Atenolol. Risk C: Monitor therapy
Fusidic Acid: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Methotrexate: Penicillins may decrease the excretion of Methotrexate. Risk C: Monitor therapy
Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy
Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification
Uricosuric Agents: May decrease the excretion of Penicillins. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Food decreases ampicillin absorption rate; may decrease ampicillin serum concentration.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Adverse events have not been observed in animal studies; therefore, ampicillin is classified as pregnancy category B. Ampicillin crosses the human placenta, providing detectable concentrations in the cord serum and amniotic fluid. Most studies have not identified a teratogenic potential for ampicillin use during pregnancy. Two possible associations (congenital heart disease and cleft palate) have been noted; each of these was observed in a single study, was not substantiated by other studies, and may have been chance associations. Ampicillin is recommended for use in pregnant women for the management of premature rupture of membranes. Ampicillin is considered an acceptable alternative to penicillin for the prevention of early-onset Group B Streptococcal (GBS) disease in newborns.
The volume of distribution of ampicillin is increased during pregnancy and the half-life is decreased. As a result, serum concentrations in pregnant patients are approximately 50% of those in nonpregnant patients receiving the same dose. Higher doses may be needed during pregnancy. Although oral absorption is not altered during pregnancy, oral ampicillin is poorly-absorbed during labor.
LACTATION — Enters breast milk/use caution
BREAST-FEEDING CONSIDERATIONS — Ampicillin is excreted in breast milk. The manufacturer recommends that caution be exercised when administering ampicillin to nursing women. Due to the low concentrations in human milk, minimal toxicity would be expected in the nursing infant. Nondose-related effects could include modification of bowel flora and allergic sensitization.
DIETARY CONSIDERATIONS — Take on an empty stomach 1 hour before or 2 hours after meals.
Sodium content of 5 mL suspension (250 mg/5 mL): 10 mg (0.4 mEq)
Sodium content of 1 g: 66.7 mg (3 mEq)
PRICING — (data from drugstore.com)
Capsules (Ampicillin)
250 mg (30): $12.99
250 mg (90): $31.95
500 mg (100): $49.99
MONITORING PARAMETERS — With prolonged therapy, monitor renal, hepatic, and hematologic function periodically; observe signs and symptoms of anaphylaxis during first dose
CANADIAN BRAND NAMES — Apo-Ampi®; Novo-Ampicillin; Nu-Ampi
INTERNATIONAL BRAND NAMES — Alphacin (AU, NZ); Alphapen (MX); Ambiopi (ID); Amcopen (PK); Amfipen (AE, BH, CY, EG, GB, IE, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Amipenix (JP); Ampecu (EC); Ampen (VE); Ampenolet (GR); Ampiblan (CO); Ampicher (EC); Ampicil (BR); Ampicilina (EC); Ampicillin (PL); Ampicin (PH); Ampiclox (SG); Ampico (PH); Ampicyn (AU); Ampidar (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Ampifen (NL); Ampiflex (PE); Ampiger (BR); Ampilag (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Ampilin (IN); Ampillin (MY); Ampimedin (PY); Ampipen (IN, ZA); Ampitenk (AR); Ampitrex (PH); Ampivral (CO); Ampliblan (CO); Ampolin (TW); Amsapen (MX); Ancillin (TW); Binotal (AT, BR, CO, EC, MX, UY); Biocil (MY); Bridopen (PH); Brupen (MX); Camicil (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Cilisod (TW); Citicil (IT); Clovillin (PH); Dhacillin (HK, MY); Dibacilina (MX); Doktacillin (SE); Duacillin (MY); Eurocin (PH); Excillin (PH); Extrapen (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Flamicina (MX); Gramcil (PH); Ibimycin (AU); Intramed (ZA); Iwacillin (JP); Julphapen (PE); Magnapen (PE); Marovilina (MX); Maxipen (CO); Microcilin (PH); Omnipen (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, MX, OM, PE, QA, SA, SY, YE); Pamecil (BF, BJ, CI, ET, GH, GM, GN, HK, KE, LR, MA, ML, MR, MU, MW, MY, NE, NG, SC, SD, SG, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Panacta (PH); Pelitin (TW); Penbritin (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, HK, IE, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Penibrin (IL); Pentrexyl (BE, BF, BJ, CI, DK, ET, GB, GH, GM, GN, GR, IT, KE, LR, MA, ML, MR, MU, MW, MX, NE, NG, NL, NO, PE, SC, SD, SL, SN, TH, TN, TZ, UG, ZA, ZM, ZW); Petercillin (ZA); Picaplin (TW); Polypen (PH); Primapen (ID); Promecilina (MX); Radiocillina (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Rimacillin (AE, BB, BF, BH, BJ, BM, BS, BZ, CI, CY, EG, ET, GH, GM, GN, GY, IL, IQ, IR, JM, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, NL, OM, QA, SA, SC, SD, SL, SN, SR, SY, TN, TT, TZ, UG, YE, ZA, ZM, ZW); Roscillin (IN); Sanpicillin (ID); Semicillin (HN); Shacillin (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Sintelin (PE); Standacillin (AE, BG, BH, CY, EE, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Standcillin (MY); Synthocilin (IN); Totapen (FR); Tricil (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Trifalicina (AR); Trilaxin (PH); Vacillin (TH); Viccillin (ID); Vidopen (GB, IE); Virucil (CO); Winpicillin (TW)
MECHANISM OF ACTION — Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
PHARMACODYNAMICS / KINETICS
Absorption: Oral: 50%
Distribution: Bile, blister, and tissue fluids; penetration into CSF occurs with inflamed meninges only, good only with inflammation (exceeds usual MICs)
Normal meninges: Nil; Inflamed meninges: 5% to 10%
Protein binding: 15% to 25%
Half-life elimination:
Children and Adults: 1-1.8 hours
Anuria/end-stage renal disease: 7-20 hours
Time to peak: Oral: Within 1-2 hours
Excretion: Urine (~90% as unchanged drug) within 24 hours
PATIENT INFORMATION — Report diarrhea promptly; take entire course of medication; females should report onset of symptoms of candidal vaginitis
Sound-alike/look-alike issues:
Ampicillin may be confused with aminophylline
PHARMACOLOGIC CATEGORY
Antibiotic, Penicillin
DOSING: ADULTS
Usual dosage range:
Oral: 250-500 mg every 6 hours
I.M., I.V.: 250-500 mg every 6 hours
Actinomycosis: I.V.: 50 mg/kg/day for 4-6 weeks then oral amoxicillin
Cholangitis (acute): I.V.: 2 g every 4 hours with gentamicin
Diverticulitis: I.M., I.V.: 2 g every 6 hours with metronidazole
Endocarditis:
Infective: I.V.: 12 g/day via continuous infusion or divided every 4 hours
Prophylaxis: Dental, oral, or respiratory tract procedures: I.M., I.V.: 2 g within 30-60 minutes prior to procedure in patients not allergic to penicillin and unable to take oral amoxicillin. Intramuscular injections should be avoided in patients who are receiving anticoagulant therapy. In these circumstances, orally administered regimens should be given whenever possible. Intravenously administered antibiotics should be used for patients who are unable to tolerate or absorb oral medications. Note: American Heart Association (AHA) guidelines now recommend prophylaxis only in patients undergoing invasive procedures and in whom underlying cardiac conditions may predispose to a higher risk of adverse outcomes should infection occur.
Prophylaxis in total joint replacement patient: I.M., I.V.: 2 g 1 hour prior to the procedure
Genitourinary and gastrointestinal tract procedures: I.M., I.V.:
High-risk patients: 2 g within 30 minutes prior to procedure, followed by ampicillin 1 g (or amoxicillin 1g orally) 6 hours later; must be used in combination with gentamicin. Note: As of April 2007, routine prophylaxis for GI/GU procedures is no longer recommended by the AHA.
Moderate-risk patients: 2 g within 30 minutes prior to procedure
Group B strep prophylaxis (intrapartum): I.V.: 2 g initial dose, then 1 g every 4 hours until delivery
Listeria infections: I.V.: 2 g every 4 hours (consider addition of aminoglycoside)
Sepsis/meningitis: I.M., I.V.: 150-250 mg/kg/day divided every 3-4 hours (range: 6-12 g/day)
Urinary tract infections (enterococcus suspected): I.V.: 1-2 g every 6 hours with gentamicin
DOSING: PEDIATRIC
(For additional information see "Ampicillin: Pediatric drug information")
Usual dosage range: Infants and Children:
Oral: 50-100 mg/kg/day in doses divided every 6 hours (maximum: 2-4 g/day)
I.M., I.V.: 100-400 mg/kg/day in divided doses every 6 hours (maximum: 12 g/day)
Endocarditis prophylaxis: Infants and Children: I.M., I.V.:
Dental, oral, or respiratory tract procedures: 50 mg/kg within 30-60 minutes prior to procedure in patients not allergic to penicillin and unable to take oral amoxicillin. Intramuscular injections should be avoided in patients who are receiving anticoagulant therapy. In these circumstances, orally administered regimens should be given whenever possible. Intravenously administered antibiotics should be used for patients who are unable to tolerate or absorb oral medications.
Note: American Heart Association (AHA) guidelines now recommend prophylaxis only in patients undergoing invasive procedures and in whom underlying cardiac conditions may predispose to a higher risk of adverse outcomes should infection occur.
Genitourinary and gastrointestinal tract procedures:
High-risk patients: 50 mg/kg (maximum: 2 g) within 30 minutes prior to procedure, followed by ampicillin 25 mg/kg (or amoxicillin 25 mg/kg orally) 6 hours later; must be used in combination with gentamicin. Note: As of April 2007, routine prophylaxis for GI/GU procedures is no longer recommended by the AHA.
Moderate-risk patients: 50 mg/kg within 30 minutes prior to procedure.
Mild-to-moderate infections: Infants and Children:
Oral: 50-100 mg/kg/day in doses divided every 6 hours (maximum: 2-4 g/day)
I.M., I.V.: 100-150 mg/kg/day in divided doses every 6 hours (maximum: 2-4 g/day)
Severe infections/meningitis: Infants and Children: I.M., I.V.: 200-400 mg/kg/day in divided doses every 6 hours (maximum: 6-12 g/day)
DOSING: ELDERLY — Administer usual adult dose unless renal function is markedly reduced.
DOSING: RENAL IMPAIRMENT
Clcr >50 mL/minute: Administer every 6 hours
Clcr 10-50 mL/minute: Administer every 6-12 hours
Clcr <10 mL/minute: Administer every 12-24 hours
Hemodialysis: Moderately dialyzable (20% to 50%); administer dose after dialysis
Peritoneal dialysis: Moderately dialyzable (20% to 50%)
Administer 250 mg every 12 hours
Continuous arteriovenous or venovenous hemofiltration effects: Dose as for Clcr 10-50 mL/minute; ~50 mg of ampicillin per liter of filtrate is removed
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule: 250 mg, 500 mg
Injection, powder for reconstitution, as sodium: 125 mg, 250 mg, 500 mg, 1 g, 2 g, 10 g
Powder for oral suspension: 125 mg/5 mL (100 mL, 200 mL); 250 mg/5 mL (100 mL, 200 mL)
DOSAGE FORMS: CONCISE
Capsule: 250 mg, 500 mg
Injection, powder for reconstitution: 125 mg, 250 mg, 500 mg, 1 g, 2 g, 10 g
Powder for oral suspension: 125 mg/5 mL, 250 mg/5 mL
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer around-the-clock to promote less variation in peak and trough serum levels.
Oral: Administer on an empty stomach (ie, 1 hour prior to, or 2 hours after meals) to increase total absorption.
I.V.: Administer over 3-5 minutes (125-500 mg) or over 10-15 minutes (1-2 g). More rapid infusion may cause seizures. Ampicillin and gentamicin should not be mixed in the same I.V. tubing.
Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate aminoglycosides in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.
COMPATIBILITY — Incompatible in D5W, D5NS, D10W, fat emulsion 10%, hetastarch 6%, LR; variable stability (consult detailed reference) in NS.
Y-site administration: Compatible: Acyclovir, amifostine, aztreonam, clarithromycin, cyclophosphamide, docetaxel, doxorubicin liposome, enalaprilat, esmolol, etoposide, famotidine, filgrastim, fludarabine, foscarnet, gatifloxacin, gemcitabine, granisetron, heparin, heparin with hydrocortisone sodium succinate, insulin (regular), labetalol, levofloxacin, linezolid, magnesium sulfate, melphalan, meperidine, morphine, multivitamins, ofloxacin, perphenazine, phytonadione, potassium chloride, propofol, remifentanil, tacrolimus, teniposide, theophylline, thiotepa, tolazoline, vitamin B complex with C. Incompatible: Amphotericin B cholesteryl sulfate complex, epinephrine, fluconazole, hydralazine, midazolam, ondansetron, sargramostim, verapamil, vinorelbine. Variable (consult detailed reference): Calcium gluconate, cisatracurium, diltiazem, hetastarch, hydromorphone, vancomycin.
Compatibility in syringe: Compatible: Chloramphenicol, colistimethate, diatrizoate meglumine 52%, diatrizoate sodium 8%, diatrizoate sodium 60%, heparin, iohexol, iopamidol, iothalamate meglumine 60%, ioxaglate meglumine 39.3%, ioxaglate 19.6%, procaine. Incompatible: Erythromycin lactobionate, gentamicin, hydromorphone, kanamycin, lincomycin, metoclopramide. Variable (consult detailed reference): Lidocaine, polymyxin B sulfate, streptomycin.
Compatibility when admixed: Compatible: Clindamycin, erythromycin lactobionate, floxacillin, furosemide. Incompatible: Amikacin, chlorpromazine, dopamine, gentamicin, hydralazine, prochlorperazine. Variable (consult detailed reference): Aztreonam, cefepime, cimetidine, heparin, hydrocortisone sodium succinate, metronidazole, metronidazole with sodium bicarbonate, ranitidine, sodium bicarbonate, verapamil.
USE — Treatment of susceptible bacterial infections (nonbeta-lactamase-producing organisms); treatment or prophylaxis of infective endocarditis; susceptible bacterial infections caused by streptococci, pneumococci, nonpenicillinase-producing staphylococci, Listeria, meningococci; some strains of H. influenzae, Salmonella, Shigella, E. coli, Enterobacter, and Klebsiella
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Central nervous system: Fever, penicillin encephalopathy, seizure
Dermatologic: Erythema multiforme, exfoliative dermatitis, rash, urticaria
Note: Appearance of a rash should be carefully evaluated to differentiate (if possible) nonallergic ampicillin rash from hypersensitivity reaction. Incidence is higher in patients with viral infection, Salmonella infection, lymphocytic leukemia, or patients that have hyperuricemia.
Gastrointestinal: Black hairy tongue, diarrhea, enterocolitis, glossitis, nausea, pseudomembranous colitis, sore mouth or tongue, stomatitis, vomiting, oral candidiasis
Hematologic: Agranulocytosis, anemia, hemolytic anemia, eosinophilia, leukopenia, thrombocytopenia purpura
Hepatic: AST increased
Renal: Interstitial nephritis (rare)
Respiratory: Laryngeal stridor
Miscellaneous: Anaphylaxis, serum sickness-like reaction
CONTRAINDICATIONS — Hypersensitivity to ampicillin, any component of the formulation, or other penicillins
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylactoid/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity, history of sensitivity to multiple allergens, or previous IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria). Use with caution in asthmatic patients. Rash: Appearance of a rash should be carefully evaluated to differentiate a nonallergic ampicillin rash from a hypersensitivity reaction; rash occurs in 5% to 10% of children and is a generalized dull red, maculopapular rash, generally appearing 3-14 days after the start of therapy. It normally begins on the trunk and spreads over most of the body. It may be most intense at pressure areas, elbows, and knees. Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns: Infectious mononucleosis: A high percentage of patients with infectious mononucleosis have developed rash during therapy; ampicillin-class antibiotics not recommended in these patients. Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended.
DRUG INTERACTIONS
Allopurinol: May enhance the potential for allergic or hypersensitivity reactions to Ampicillin. Risk C: Monitor therapy
Atenolol: Ampicillin may decrease the bioavailability of Atenolol. Risk C: Monitor therapy
Fusidic Acid: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Methotrexate: Penicillins may decrease the excretion of Methotrexate. Risk C: Monitor therapy
Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy
Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification
Uricosuric Agents: May decrease the excretion of Penicillins. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Food decreases ampicillin absorption rate; may decrease ampicillin serum concentration.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Adverse events have not been observed in animal studies; therefore, ampicillin is classified as pregnancy category B. Ampicillin crosses the human placenta, providing detectable concentrations in the cord serum and amniotic fluid. Most studies have not identified a teratogenic potential for ampicillin use during pregnancy. Two possible associations (congenital heart disease and cleft palate) have been noted; each of these was observed in a single study, was not substantiated by other studies, and may have been chance associations. Ampicillin is recommended for use in pregnant women for the management of premature rupture of membranes. Ampicillin is considered an acceptable alternative to penicillin for the prevention of early-onset Group B Streptococcal (GBS) disease in newborns.
The volume of distribution of ampicillin is increased during pregnancy and the half-life is decreased. As a result, serum concentrations in pregnant patients are approximately 50% of those in nonpregnant patients receiving the same dose. Higher doses may be needed during pregnancy. Although oral absorption is not altered during pregnancy, oral ampicillin is poorly-absorbed during labor.
LACTATION — Enters breast milk/use caution
BREAST-FEEDING CONSIDERATIONS — Ampicillin is excreted in breast milk. The manufacturer recommends that caution be exercised when administering ampicillin to nursing women. Due to the low concentrations in human milk, minimal toxicity would be expected in the nursing infant. Nondose-related effects could include modification of bowel flora and allergic sensitization.
DIETARY CONSIDERATIONS — Take on an empty stomach 1 hour before or 2 hours after meals.
Sodium content of 5 mL suspension (250 mg/5 mL): 10 mg (0.4 mEq)
Sodium content of 1 g: 66.7 mg (3 mEq)
PRICING — (data from drugstore.com)
Capsules (Ampicillin)
250 mg (30): $12.99
250 mg (90): $31.95
500 mg (100): $49.99
MONITORING PARAMETERS — With prolonged therapy, monitor renal, hepatic, and hematologic function periodically; observe signs and symptoms of anaphylaxis during first dose
CANADIAN BRAND NAMES — Apo-Ampi®; Novo-Ampicillin; Nu-Ampi
INTERNATIONAL BRAND NAMES — Alphacin (AU, NZ); Alphapen (MX); Ambiopi (ID); Amcopen (PK); Amfipen (AE, BH, CY, EG, GB, IE, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Amipenix (JP); Ampecu (EC); Ampen (VE); Ampenolet (GR); Ampiblan (CO); Ampicher (EC); Ampicil (BR); Ampicilina (EC); Ampicillin (PL); Ampicin (PH); Ampiclox (SG); Ampico (PH); Ampicyn (AU); Ampidar (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Ampifen (NL); Ampiflex (PE); Ampiger (BR); Ampilag (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Ampilin (IN); Ampillin (MY); Ampimedin (PY); Ampipen (IN, ZA); Ampitenk (AR); Ampitrex (PH); Ampivral (CO); Ampliblan (CO); Ampolin (TW); Amsapen (MX); Ancillin (TW); Binotal (AT, BR, CO, EC, MX, UY); Biocil (MY); Bridopen (PH); Brupen (MX); Camicil (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Cilisod (TW); Citicil (IT); Clovillin (PH); Dhacillin (HK, MY); Dibacilina (MX); Doktacillin (SE); Duacillin (MY); Eurocin (PH); Excillin (PH); Extrapen (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Flamicina (MX); Gramcil (PH); Ibimycin (AU); Intramed (ZA); Iwacillin (JP); Julphapen (PE); Magnapen (PE); Marovilina (MX); Maxipen (CO); Microcilin (PH); Omnipen (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, MX, OM, PE, QA, SA, SY, YE); Pamecil (BF, BJ, CI, ET, GH, GM, GN, HK, KE, LR, MA, ML, MR, MU, MW, MY, NE, NG, SC, SD, SG, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Panacta (PH); Pelitin (TW); Penbritin (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, HK, IE, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Penibrin (IL); Pentrexyl (BE, BF, BJ, CI, DK, ET, GB, GH, GM, GN, GR, IT, KE, LR, MA, ML, MR, MU, MW, MX, NE, NG, NL, NO, PE, SC, SD, SL, SN, TH, TN, TZ, UG, ZA, ZM, ZW); Petercillin (ZA); Picaplin (TW); Polypen (PH); Primapen (ID); Promecilina (MX); Radiocillina (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Rimacillin (AE, BB, BF, BH, BJ, BM, BS, BZ, CI, CY, EG, ET, GH, GM, GN, GY, IL, IQ, IR, JM, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, NL, OM, QA, SA, SC, SD, SL, SN, SR, SY, TN, TT, TZ, UG, YE, ZA, ZM, ZW); Roscillin (IN); Sanpicillin (ID); Semicillin (HN); Shacillin (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Sintelin (PE); Standacillin (AE, BG, BH, CY, EE, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Standcillin (MY); Synthocilin (IN); Totapen (FR); Tricil (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Trifalicina (AR); Trilaxin (PH); Vacillin (TH); Viccillin (ID); Vidopen (GB, IE); Virucil (CO); Winpicillin (TW)
MECHANISM OF ACTION — Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
PHARMACODYNAMICS / KINETICS
Absorption: Oral: 50%
Distribution: Bile, blister, and tissue fluids; penetration into CSF occurs with inflamed meninges only, good only with inflammation (exceeds usual MICs)
Normal meninges: Nil; Inflamed meninges: 5% to 10%
Protein binding: 15% to 25%
Half-life elimination:
Children and Adults: 1-1.8 hours
Anuria/end-stage renal disease: 7-20 hours
Time to peak: Oral: Within 1-2 hours
Excretion: Urine (~90% as unchanged drug) within 24 hours
PATIENT INFORMATION — Report diarrhea promptly; take entire course of medication; females should report onset of symptoms of candidal vaginitis
Amphotericin B lipid complex
MEDICATION SAFETY ISSUES
Safety issues:
Lipid-based amphotericin formulations (Abelcet®) may be confused with conventional formulations (Amphocin®, Fungizone®)
Large overdoses have occurred when conventional formulations were dispensed inadvertently for lipid-based products. Single daily doses of conventional amphotericin formulation never exceed 1.5 mg/kg.
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
U.S. BRAND NAMES — Abelcet®
PHARMACOLOGIC CATEGORY
Antifungal Agent, Parenteral
DOSING: ADULTS — Note: Premedication: For patients who experience infusion-related immediate reactions, premedicate with the following drugs 30-60 minutes prior to drug administration: A nonsteroidal anti-inflammatory agent +/- diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered.
Usual dosage: I.V.: 2.5-5 mg/kg/day as a single infusion
DOSING: PEDIATRIC — Refer to adult dosing.
(For additional information see "Amphotericin B lipid complex: Pediatric drug information")
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — The effects of renal impairment on drug pharmacokinetics or pharmacodynamics are currently unknown. The dose of amphotericin B lipid complex may be adjusted or drug administration may have to be interrupted in patients with acute kidney dysfunction to reduce the magnitude of renal impairment.
Hemodialysis: Supplemental dose is not necessary.
Peritoneal dialysis: Supplemental dose is not necessary.
Continuous renal replacement therapy (CRRT): No supplemental dosage necessary
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, suspension [preservative free]:
Abelcet®: 5 mg/mL (20 mL)
DOSAGE FORMS: CONCISE
Injection, suspension [preservative free]:
Abelcet®: 5 mg/mL (20 mL)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — For patients who experience nonanaphylactic infusion-related reactions, premedicate 30-60 minutes prior to drug administration with a nonsteroidal anti-inflammatory agent +/- diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered.
Administer at an infusion rate of 2.5 mg/kg/hour (over 2 hours). Invert infusion container several times prior to administration and every 2 hours during infusion if it exceeds 2 hours.
COMPATIBILITY
Incompatible with any blood products, intravenous drugs, or intravenous fluids other than D5W when admixed or as Y-site administration.
USE — Treatment of aspergillosis or any type of progressive fungal infection in patients who are refractory to or intolerant of conventional amphotericin B therapy
USE - UNLABELED / INVESTIGATIONAL — Effective in patients with serious Candida species infections
ADVERSE REACTIONS SIGNIFICANT — Nephrotoxicity and infusion-related hyperpyrexia, rigor, and chilling are reduced relative to amphotericin deoxycholate.
>10%:
Central nervous system: Chills, fever
Renal: Serum creatinine increased
Miscellaneous: Multiple organ failure
1% to 10%:
Cardiovascular: Hypotension, cardiac arrest
Central nervous system: Headache, pain
Dermatologic: Rash
Endocrine & metabolic: Bilirubinemia, hypokalemia, acidosis
Gastrointestinal: Nausea, vomiting, diarrhea, gastrointestinal hemorrhage, abdominal pain
Renal: Renal failure
Respiratory: Respiratory failure, dyspnea, pneumonia
CONTRAINDICATIONS — Hypersensitivity to amphotericin or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylaxis: Has been reported with amphotericin B-containing drugs; facilities for cardiopulmonary resuscitation should be available during administration due to the possibility of anaphylactic reaction. If severe respiratory distress occurs, the infusion should be immediately discontinued; during the initial dosing, the drug should be administered under close clinical observation. Infusion reactions: Acute reactions (including fever and chills) may occur 1-3 hours after starting an intravenous infusion. These reactions are usually more common with the first few doses and generally diminish with subsequent doses.
Special populations: Neutropenic patients: Pulmonary reactions may occur in neutropenic patients receiving leukocyte transfusions; separation of the infusions as much as possible is advised.
DRUG INTERACTIONS
Aminoglycosides: Amphotericin B may enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May diminish the therapeutic effect of Amphotericin B. Risk C: Monitor therapy
Colistimethate: Amphotericin B may enhance the nephrotoxic effect of Colistimethate. Risk D: Consider therapy modification
Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy
CycloSPORINE: Amphotericin B may enhance the nephrotoxic effect of CycloSPORINE. Risk C: Monitor therapy
Flucytosine: Amphotericin B may enhance the adverse/toxic effect of Flucytosine. This may be related to the adverse effects of amphotericin B on renal function. Risk C: Monitor therapy
Gallium Nitrate: Amphotericin B may enhance the nephrotoxic effect of Gallium Nitrate. Risk X: Avoid combination
Saccharomyces boulardii: Antifungal Agents may diminish the therapeutic effect of Saccharomyces boulardii. Risk D: Consider therapy modification
PREGNANCY RISK FACTOR — B (show table)
LACTATION — Enters breast milk/contraindicated
BREAST-FEEDING CONSIDERATIONS — Due to limited data, consider discontinuing nursing during therapy.
MONITORING PARAMETERS — Renal function (monitor frequently during therapy), electrolytes (especially potassium and magnesium), liver function tests, temperature, PT/PTT, CBC; monitor input and output; monitor for signs of hypokalemia (muscle weakness, cramping, drowsiness, ECG changes, etc)
CANADIAN BRAND NAMES — Abelcet®; Amphotec®
INTERNATIONAL BRAND NAMES — Abelcet (AR, AT, BE, BR, CZ, DK, FI, FR, GB, GR, HN, IE, NL, NO, NZ, SE); Ambisome (AU, FR, HK, IL, KP); Ampholip (IN)
MECHANISM OF ACTION — Binds to ergosterol altering cell membrane permeability in susceptible fungi and causing leakage of cell components with subsequent cell death. Proposed mechanism suggests that amphotericin causes an oxidation-dependent stimulation of macrophages.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: Increases with higher doses; reflects increased uptake by tissues (131 L/kg with 5 mg/kg/day)
Half-life elimination: ~24 hours
Excretion: Clearance: Increases with higher doses (5 mg/kg/day): 400 mL/hour/kg
Safety issues:
Lipid-based amphotericin formulations (Abelcet®) may be confused with conventional formulations (Amphocin®, Fungizone®)
Large overdoses have occurred when conventional formulations were dispensed inadvertently for lipid-based products. Single daily doses of conventional amphotericin formulation never exceed 1.5 mg/kg.
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
U.S. BRAND NAMES — Abelcet®
PHARMACOLOGIC CATEGORY
Antifungal Agent, Parenteral
DOSING: ADULTS — Note: Premedication: For patients who experience infusion-related immediate reactions, premedicate with the following drugs 30-60 minutes prior to drug administration: A nonsteroidal anti-inflammatory agent +/- diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered.
Usual dosage: I.V.: 2.5-5 mg/kg/day as a single infusion
DOSING: PEDIATRIC — Refer to adult dosing.
(For additional information see "Amphotericin B lipid complex: Pediatric drug information")
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — The effects of renal impairment on drug pharmacokinetics or pharmacodynamics are currently unknown. The dose of amphotericin B lipid complex may be adjusted or drug administration may have to be interrupted in patients with acute kidney dysfunction to reduce the magnitude of renal impairment.
Hemodialysis: Supplemental dose is not necessary.
Peritoneal dialysis: Supplemental dose is not necessary.
Continuous renal replacement therapy (CRRT): No supplemental dosage necessary
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, suspension [preservative free]:
Abelcet®: 5 mg/mL (20 mL)
DOSAGE FORMS: CONCISE
Injection, suspension [preservative free]:
Abelcet®: 5 mg/mL (20 mL)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — For patients who experience nonanaphylactic infusion-related reactions, premedicate 30-60 minutes prior to drug administration with a nonsteroidal anti-inflammatory agent +/- diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered.
Administer at an infusion rate of 2.5 mg/kg/hour (over 2 hours). Invert infusion container several times prior to administration and every 2 hours during infusion if it exceeds 2 hours.
COMPATIBILITY
Incompatible with any blood products, intravenous drugs, or intravenous fluids other than D5W when admixed or as Y-site administration.
USE — Treatment of aspergillosis or any type of progressive fungal infection in patients who are refractory to or intolerant of conventional amphotericin B therapy
USE - UNLABELED / INVESTIGATIONAL — Effective in patients with serious Candida species infections
ADVERSE REACTIONS SIGNIFICANT — Nephrotoxicity and infusion-related hyperpyrexia, rigor, and chilling are reduced relative to amphotericin deoxycholate.
>10%:
Central nervous system: Chills, fever
Renal: Serum creatinine increased
Miscellaneous: Multiple organ failure
1% to 10%:
Cardiovascular: Hypotension, cardiac arrest
Central nervous system: Headache, pain
Dermatologic: Rash
Endocrine & metabolic: Bilirubinemia, hypokalemia, acidosis
Gastrointestinal: Nausea, vomiting, diarrhea, gastrointestinal hemorrhage, abdominal pain
Renal: Renal failure
Respiratory: Respiratory failure, dyspnea, pneumonia
CONTRAINDICATIONS — Hypersensitivity to amphotericin or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylaxis: Has been reported with amphotericin B-containing drugs; facilities for cardiopulmonary resuscitation should be available during administration due to the possibility of anaphylactic reaction. If severe respiratory distress occurs, the infusion should be immediately discontinued; during the initial dosing, the drug should be administered under close clinical observation. Infusion reactions: Acute reactions (including fever and chills) may occur 1-3 hours after starting an intravenous infusion. These reactions are usually more common with the first few doses and generally diminish with subsequent doses.
Special populations: Neutropenic patients: Pulmonary reactions may occur in neutropenic patients receiving leukocyte transfusions; separation of the infusions as much as possible is advised.
DRUG INTERACTIONS
Aminoglycosides: Amphotericin B may enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May diminish the therapeutic effect of Amphotericin B. Risk C: Monitor therapy
Colistimethate: Amphotericin B may enhance the nephrotoxic effect of Colistimethate. Risk D: Consider therapy modification
Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy
CycloSPORINE: Amphotericin B may enhance the nephrotoxic effect of CycloSPORINE. Risk C: Monitor therapy
Flucytosine: Amphotericin B may enhance the adverse/toxic effect of Flucytosine. This may be related to the adverse effects of amphotericin B on renal function. Risk C: Monitor therapy
Gallium Nitrate: Amphotericin B may enhance the nephrotoxic effect of Gallium Nitrate. Risk X: Avoid combination
Saccharomyces boulardii: Antifungal Agents may diminish the therapeutic effect of Saccharomyces boulardii. Risk D: Consider therapy modification
PREGNANCY RISK FACTOR — B (show table)
LACTATION — Enters breast milk/contraindicated
BREAST-FEEDING CONSIDERATIONS — Due to limited data, consider discontinuing nursing during therapy.
MONITORING PARAMETERS — Renal function (monitor frequently during therapy), electrolytes (especially potassium and magnesium), liver function tests, temperature, PT/PTT, CBC; monitor input and output; monitor for signs of hypokalemia (muscle weakness, cramping, drowsiness, ECG changes, etc)
CANADIAN BRAND NAMES — Abelcet®; Amphotec®
INTERNATIONAL BRAND NAMES — Abelcet (AR, AT, BE, BR, CZ, DK, FI, FR, GB, GR, HN, IE, NL, NO, NZ, SE); Ambisome (AU, FR, HK, IL, KP); Ampholip (IN)
MECHANISM OF ACTION — Binds to ergosterol altering cell membrane permeability in susceptible fungi and causing leakage of cell components with subsequent cell death. Proposed mechanism suggests that amphotericin causes an oxidation-dependent stimulation of macrophages.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: Increases with higher doses; reflects increased uptake by tissues (131 L/kg with 5 mg/kg/day)
Half-life elimination: ~24 hours
Excretion: Clearance: Increases with higher doses (5 mg/kg/day): 400 mL/hour/kg
Amphotericin B lipid complex
MEDICATION SAFETY ISSUES
Safety issues:
Lipid-based amphotericin formulations (Abelcet®) may be confused with conventional formulations (Amphocin®, Fungizone®)
Large overdoses have occurred when conventional formulations were dispensed inadvertently for lipid-based products. Single daily doses of conventional amphotericin formulation never exceed 1.5 mg/kg.
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
U.S. BRAND NAMES — Abelcet®
PHARMACOLOGIC CATEGORY
Antifungal Agent, Parenteral
DOSING: ADULTS — Note: Premedication: For patients who experience infusion-related immediate reactions, premedicate with the following drugs 30-60 minutes prior to drug administration: A nonsteroidal anti-inflammatory agent +/- diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered.
Usual dosage: I.V.: 2.5-5 mg/kg/day as a single infusion
DOSING: PEDIATRIC — Refer to adult dosing.
(For additional information see "Amphotericin B lipid complex: Pediatric drug information")
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — The effects of renal impairment on drug pharmacokinetics or pharmacodynamics are currently unknown. The dose of amphotericin B lipid complex may be adjusted or drug administration may have to be interrupted in patients with acute kidney dysfunction to reduce the magnitude of renal impairment.
Hemodialysis: Supplemental dose is not necessary.
Peritoneal dialysis: Supplemental dose is not necessary.
Continuous renal replacement therapy (CRRT): No supplemental dosage necessary
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, suspension [preservative free]:
Abelcet®: 5 mg/mL (20 mL)
DOSAGE FORMS: CONCISE
Injection, suspension [preservative free]:
Abelcet®: 5 mg/mL (20 mL)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — For patients who experience nonanaphylactic infusion-related reactions, premedicate 30-60 minutes prior to drug administration with a nonsteroidal anti-inflammatory agent +/- diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered.
Administer at an infusion rate of 2.5 mg/kg/hour (over 2 hours). Invert infusion container several times prior to administration and every 2 hours during infusion if it exceeds 2 hours.
COMPATIBILITY
Incompatible with any blood products, intravenous drugs, or intravenous fluids other than D5W when admixed or as Y-site administration.
USE — Treatment of aspergillosis or any type of progressive fungal infection in patients who are refractory to or intolerant of conventional amphotericin B therapy
USE - UNLABELED / INVESTIGATIONAL — Effective in patients with serious Candida species infections
ADVERSE REACTIONS SIGNIFICANT — Nephrotoxicity and infusion-related hyperpyrexia, rigor, and chilling are reduced relative to amphotericin deoxycholate.
>10%:
Central nervous system: Chills, fever
Renal: Serum creatinine increased
Miscellaneous: Multiple organ failure
1% to 10%:
Cardiovascular: Hypotension, cardiac arrest
Central nervous system: Headache, pain
Dermatologic: Rash
Endocrine & metabolic: Bilirubinemia, hypokalemia, acidosis
Gastrointestinal: Nausea, vomiting, diarrhea, gastrointestinal hemorrhage, abdominal pain
Renal: Renal failure
Respiratory: Respiratory failure, dyspnea, pneumonia
CONTRAINDICATIONS — Hypersensitivity to amphotericin or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylaxis: Has been reported with amphotericin B-containing drugs; facilities for cardiopulmonary resuscitation should be available during administration due to the possibility of anaphylactic reaction. If severe respiratory distress occurs, the infusion should be immediately discontinued; during the initial dosing, the drug should be administered under close clinical observation. Infusion reactions: Acute reactions (including fever and chills) may occur 1-3 hours after starting an intravenous infusion. These reactions are usually more common with the first few doses and generally diminish with subsequent doses.
Special populations: Neutropenic patients: Pulmonary reactions may occur in neutropenic patients receiving leukocyte transfusions; separation of the infusions as much as possible is advised.
DRUG INTERACTIONS
Aminoglycosides: Amphotericin B may enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May diminish the therapeutic effect of Amphotericin B. Risk C: Monitor therapy
Colistimethate: Amphotericin B may enhance the nephrotoxic effect of Colistimethate. Risk D: Consider therapy modification
Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy
CycloSPORINE: Amphotericin B may enhance the nephrotoxic effect of CycloSPORINE. Risk C: Monitor therapy
Flucytosine: Amphotericin B may enhance the adverse/toxic effect of Flucytosine. This may be related to the adverse effects of amphotericin B on renal function. Risk C: Monitor therapy
Gallium Nitrate: Amphotericin B may enhance the nephrotoxic effect of Gallium Nitrate. Risk X: Avoid combination
Saccharomyces boulardii: Antifungal Agents may diminish the therapeutic effect of Saccharomyces boulardii. Risk D: Consider therapy modification
PREGNANCY RISK FACTOR — B (show table)
LACTATION — Enters breast milk/contraindicated
BREAST-FEEDING CONSIDERATIONS — Due to limited data, consider discontinuing nursing during therapy.
MONITORING PARAMETERS — Renal function (monitor frequently during therapy), electrolytes (especially potassium and magnesium), liver function tests, temperature, PT/PTT, CBC; monitor input and output; monitor for signs of hypokalemia (muscle weakness, cramping, drowsiness, ECG changes, etc)
CANADIAN BRAND NAMES — Abelcet®; Amphotec®
INTERNATIONAL BRAND NAMES — Abelcet (AR, AT, BE, BR, CZ, DK, FI, FR, GB, GR, HN, IE, NL, NO, NZ, SE); Ambisome (AU, FR, HK, IL, KP); Ampholip (IN)
MECHANISM OF ACTION — Binds to ergosterol altering cell membrane permeability in susceptible fungi and causing leakage of cell components with subsequent cell death. Proposed mechanism suggests that amphotericin causes an oxidation-dependent stimulation of macrophages.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: Increases with higher doses; reflects increased uptake by tissues (131 L/kg with 5 mg/kg/day)
Half-life elimination: ~24 hours
Excretion: Clearance: Increases with higher doses (5 mg/kg/day): 400 mL/hour/kg
Safety issues:
Lipid-based amphotericin formulations (Abelcet®) may be confused with conventional formulations (Amphocin®, Fungizone®)
Large overdoses have occurred when conventional formulations were dispensed inadvertently for lipid-based products. Single daily doses of conventional amphotericin formulation never exceed 1.5 mg/kg.
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
U.S. BRAND NAMES — Abelcet®
PHARMACOLOGIC CATEGORY
Antifungal Agent, Parenteral
DOSING: ADULTS — Note: Premedication: For patients who experience infusion-related immediate reactions, premedicate with the following drugs 30-60 minutes prior to drug administration: A nonsteroidal anti-inflammatory agent +/- diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered.
Usual dosage: I.V.: 2.5-5 mg/kg/day as a single infusion
DOSING: PEDIATRIC — Refer to adult dosing.
(For additional information see "Amphotericin B lipid complex: Pediatric drug information")
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — The effects of renal impairment on drug pharmacokinetics or pharmacodynamics are currently unknown. The dose of amphotericin B lipid complex may be adjusted or drug administration may have to be interrupted in patients with acute kidney dysfunction to reduce the magnitude of renal impairment.
Hemodialysis: Supplemental dose is not necessary.
Peritoneal dialysis: Supplemental dose is not necessary.
Continuous renal replacement therapy (CRRT): No supplemental dosage necessary
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, suspension [preservative free]:
Abelcet®: 5 mg/mL (20 mL)
DOSAGE FORMS: CONCISE
Injection, suspension [preservative free]:
Abelcet®: 5 mg/mL (20 mL)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — For patients who experience nonanaphylactic infusion-related reactions, premedicate 30-60 minutes prior to drug administration with a nonsteroidal anti-inflammatory agent +/- diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered.
Administer at an infusion rate of 2.5 mg/kg/hour (over 2 hours). Invert infusion container several times prior to administration and every 2 hours during infusion if it exceeds 2 hours.
COMPATIBILITY
Incompatible with any blood products, intravenous drugs, or intravenous fluids other than D5W when admixed or as Y-site administration.
USE — Treatment of aspergillosis or any type of progressive fungal infection in patients who are refractory to or intolerant of conventional amphotericin B therapy
USE - UNLABELED / INVESTIGATIONAL — Effective in patients with serious Candida species infections
ADVERSE REACTIONS SIGNIFICANT — Nephrotoxicity and infusion-related hyperpyrexia, rigor, and chilling are reduced relative to amphotericin deoxycholate.
>10%:
Central nervous system: Chills, fever
Renal: Serum creatinine increased
Miscellaneous: Multiple organ failure
1% to 10%:
Cardiovascular: Hypotension, cardiac arrest
Central nervous system: Headache, pain
Dermatologic: Rash
Endocrine & metabolic: Bilirubinemia, hypokalemia, acidosis
Gastrointestinal: Nausea, vomiting, diarrhea, gastrointestinal hemorrhage, abdominal pain
Renal: Renal failure
Respiratory: Respiratory failure, dyspnea, pneumonia
CONTRAINDICATIONS — Hypersensitivity to amphotericin or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylaxis: Has been reported with amphotericin B-containing drugs; facilities for cardiopulmonary resuscitation should be available during administration due to the possibility of anaphylactic reaction. If severe respiratory distress occurs, the infusion should be immediately discontinued; during the initial dosing, the drug should be administered under close clinical observation. Infusion reactions: Acute reactions (including fever and chills) may occur 1-3 hours after starting an intravenous infusion. These reactions are usually more common with the first few doses and generally diminish with subsequent doses.
Special populations: Neutropenic patients: Pulmonary reactions may occur in neutropenic patients receiving leukocyte transfusions; separation of the infusions as much as possible is advised.
DRUG INTERACTIONS
Aminoglycosides: Amphotericin B may enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May diminish the therapeutic effect of Amphotericin B. Risk C: Monitor therapy
Colistimethate: Amphotericin B may enhance the nephrotoxic effect of Colistimethate. Risk D: Consider therapy modification
Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy
CycloSPORINE: Amphotericin B may enhance the nephrotoxic effect of CycloSPORINE. Risk C: Monitor therapy
Flucytosine: Amphotericin B may enhance the adverse/toxic effect of Flucytosine. This may be related to the adverse effects of amphotericin B on renal function. Risk C: Monitor therapy
Gallium Nitrate: Amphotericin B may enhance the nephrotoxic effect of Gallium Nitrate. Risk X: Avoid combination
Saccharomyces boulardii: Antifungal Agents may diminish the therapeutic effect of Saccharomyces boulardii. Risk D: Consider therapy modification
PREGNANCY RISK FACTOR — B (show table)
LACTATION — Enters breast milk/contraindicated
BREAST-FEEDING CONSIDERATIONS — Due to limited data, consider discontinuing nursing during therapy.
MONITORING PARAMETERS — Renal function (monitor frequently during therapy), electrolytes (especially potassium and magnesium), liver function tests, temperature, PT/PTT, CBC; monitor input and output; monitor for signs of hypokalemia (muscle weakness, cramping, drowsiness, ECG changes, etc)
CANADIAN BRAND NAMES — Abelcet®; Amphotec®
INTERNATIONAL BRAND NAMES — Abelcet (AR, AT, BE, BR, CZ, DK, FI, FR, GB, GR, HN, IE, NL, NO, NZ, SE); Ambisome (AU, FR, HK, IL, KP); Ampholip (IN)
MECHANISM OF ACTION — Binds to ergosterol altering cell membrane permeability in susceptible fungi and causing leakage of cell components with subsequent cell death. Proposed mechanism suggests that amphotericin causes an oxidation-dependent stimulation of macrophages.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: Increases with higher doses; reflects increased uptake by tissues (131 L/kg with 5 mg/kg/day)
Half-life elimination: ~24 hours
Excretion: Clearance: Increases with higher doses (5 mg/kg/day): 400 mL/hour/kg
Amphotericin B cholesteryl sulfate complex
MEDICATION SAFETY ISSUES
Safety issues:
Lipid-based amphotericin formulations (Amphotec®) may be confused with conventional formulations (Amphocin®, Fungizone®)
Large overdoses have occurred when conventional formulations were dispensed inadvertently for lipid-based products. Single daily doses of conventional amphotericin formulation never exceed 1.5 mg/kg.
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
U.S. BRAND NAMES — Amphotec®
PHARMACOLOGIC CATEGORY
Antifungal Agent, Parenteral
DOSING: ADULTS
Note: Premedication: For patients who experience chills, fever, hypotension, nausea, or other nonanaphylactic infusion-related immediate reactions, premedicate with the following drugs 30-60 minutes prior to drug administration: A nonsteroidal (eg, ibuprofen, choline magnesium trisalicylate) with or without diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered.
Usual dosage: I.V.: 3-4 mg/kg/day (infusion of 1 mg/kg/hour); maximum: 7.5 mg/kg/day
A regimen of 6 mg/kg/day has been used for treatment of life-threatening invasive mold infections in immunocompromised patients; maximum: 7.5 mg/kg/day.
Initially infuse at 1 mg/kg/hour. Rate of infusion may be increased with subsequent doses to 3 mg/kg/hour as patient tolerance allows. Treatment should continue as patient tolerance allows, until complete resolution of microbiologic and clinical evidence of fungal disease.
DOSING: PEDIATRIC — Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution:
Amphotec®: 50 mg, 100 mg
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution:
Amphotec®: 50 mg, 100 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Avoid injection faster than 1 mg/kg/hour. For a patient who experiences chills, fever, hypotension, nausea, or other nonanaphylactic infusion-related reactions, premedicate with the following drugs 30-60 minutes prior to drug administration: A nonsteroidal (eg, ibuprofen, choline magnesium trisalicylate) with or without diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered. If severe respiratory distress occurs, the infusion should be immediately discontinued.
COMPATIBILITY — Stable in D5W; incompatible with NS.
Y-site administration: Compatible: Acyclovir, aminophylline, cefoxitin, ceftizoxime, clindamycin, dexamethasone sodium phosphate, fentanyl, furosemide, ganciclovir, granisetron, hydrocortisone sodium succinate, ifosfamide, lorazepam, mannitol, methotrexate, methylprednisolone sodium succinate, nitroglycerin, sufentanil, trimethoprim/sulfamethoxazole, vinblastine, vincristine, zidovudine. Incompatible: Alfentanil, amikacin, ampicillin, ampicillin/sulbactam, atenolol, aztreonam, bretylium, buprenorphine, butorphanol, calcium chloride, calcium gluconate, carboplatin, cefazolin, cefepime, cefoperazone, ceftazidime, ceftriaxone, chlorpromazine, cimetidine, cisatracurium, cisplatin, cyclophosphamide, cyclosporine, cytarabine, diazepam, digoxin, diphenhydramine, dobutamine, dopamine, doxorubicin, doxorubicin liposome, droperidol, enalaprilat, esmolol, famotidine, fluconazole, fluorouracil, gatifloxacin, gentamicin, haloperidol, heparin, hydromorphone, hydroxyzine, imipenem/cilastatin, labetalol, leucovorin, lidocaine, magnesium sulfate, meperidine, mesna, metoclopramide, metoprolol, metronidazole, midazolam, mitoxantrone, morphine, nalbuphine, naloxone, ofloxacin, ondansetron, paclitaxel, pentobarbital, phenobarbital, phenytoin, piperacillin, piperacillin/tazobactam, potassium chloride, prochlorperazine, promethazine, propranolol, ranitidine, remifentanil, sodium bicarbonate, ticarcillin, ticarcillin/clavulanate, tobramycin, vancomycin, vecuronium, verapamil, vinorelbine.
USE — Treatment of invasive aspergillosis in patients who have failed amphotericin B deoxycholate treatment, or who have renal impairment or experience unacceptable toxicity which precludes treatment with amphotericin B deoxycholate in effective doses.
USE - UNLABELED / INVESTIGATIONAL — Effective in patients with serious Candida species infections
ADVERSE REACTIONS SIGNIFICANT
>10%: Central nervous system: Chills, fever
1% to 10%:
Cardiovascular: Hypotension, tachycardia
Central nervous system: Headache
Dermatologic: Rash
Endocrine & metabolic: Hypokalemia, hypomagnesemia
Gastrointestinal: Nausea, diarrhea, abdominal pain
Hematologic: Thrombocytopenia
Hepatic: LFT change
Neuromuscular & skeletal: Rigors
Renal: Creatinine increased
Respiratory: Dyspnea
Note: Amphotericin B colloidal dispersion has an improved therapeutic index compared to conventional amphotericin B, and has been used safely in patients with amphotericin B-related nephrotoxicity; however, continued decline of renal function has occurred in some patients.
CONTRAINDICATIONS — Hypersensitivity to amphotericin B or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylaxis: Has been reported with amphotericin B-containing drugs; facilities for cardiopulmonary resuscitation should be available during administration due to the possibility of anaphylactic reaction. If severe respiratory distress occurs, the infusion should be immediately discontinued. During the initial dosing, the drug should be administered under close clinical observation. Infusion reactions: Sometimes severe, usually subside with continued therapy - manage with decreased rate of infusion and pretreatment with antihistamines/corticosteroids.
Special populations: Neutropenic patients: Pulmonary reactions may occur in neutropenic patients receiving leukocyte transfusions; separation of the infusions as much as possible is advised.
DRUG INTERACTIONS
Aminoglycosides: Amphotericin B may enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May diminish the therapeutic effect of Amphotericin B. Risk C: Monitor therapy
Colistimethate: Amphotericin B may enhance the nephrotoxic effect of Colistimethate. Risk D: Consider therapy modification
Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy
CycloSPORINE: Amphotericin B may enhance the nephrotoxic effect of CycloSPORINE. Risk C: Monitor therapy
Flucytosine: Amphotericin B may enhance the adverse/toxic effect of Flucytosine. This may be related to the adverse effects of amphotericin B on renal function. Risk C: Monitor therapy
Gallium Nitrate: Amphotericin B may enhance the nephrotoxic effect of Gallium Nitrate. Risk X: Avoid combination
Saccharomyces boulardii: Antifungal Agents may diminish the therapeutic effect of Saccharomyces boulardii. Risk D: Consider therapy modification
PREGNANCY RISK FACTOR — B (show table)
LACTATION — Excretion in breast milk unknown/contraindicated
BREAST-FEEDING CONSIDERATIONS — Due to limited data, consider discontinuing nursing during therapy.
MONITORING PARAMETERS — Liver function tests, electrolytes, BUN, Cr, temperature, CBC, I/O, signs of hypokalemia (muscle weakness, cramping, drowsiness, ECG changes)
CANADIAN BRAND NAMES — Amphotec®
INTERNATIONAL BRAND NAMES — Amphocil (AT, AU, BR, CZ, DK, FI, GB, HK, HN, IL, IT, MX, MY, NL, SE, TH, TW)
MECHANISM OF ACTION — Binds to ergosterol altering cell membrane permeability in susceptible fungi and causing leakage of cell components with subsequent cell death. Proposed mechanism suggests that amphotericin causes an oxidation-dependent stimulation of macrophages (Lyman, 1992).
PHARMACODYNAMICS / KINETICS
Distribution: Vd: Total volume increases with higher doses, reflects increasing uptake by tissues (with 4 mg/kg/day = 4 L/kg); predominantly distributed in the liver; concentrations in kidneys and other tissues are lower than observed with conventional amphotericin B
Half-life elimination: 28-29 hours; prolonged with higher दोसेस.
Safety issues:
Lipid-based amphotericin formulations (Amphotec®) may be confused with conventional formulations (Amphocin®, Fungizone®)
Large overdoses have occurred when conventional formulations were dispensed inadvertently for lipid-based products. Single daily doses of conventional amphotericin formulation never exceed 1.5 mg/kg.
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
U.S. BRAND NAMES — Amphotec®
PHARMACOLOGIC CATEGORY
Antifungal Agent, Parenteral
DOSING: ADULTS
Note: Premedication: For patients who experience chills, fever, hypotension, nausea, or other nonanaphylactic infusion-related immediate reactions, premedicate with the following drugs 30-60 minutes prior to drug administration: A nonsteroidal (eg, ibuprofen, choline magnesium trisalicylate) with or without diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered.
Usual dosage: I.V.: 3-4 mg/kg/day (infusion of 1 mg/kg/hour); maximum: 7.5 mg/kg/day
A regimen of 6 mg/kg/day has been used for treatment of life-threatening invasive mold infections in immunocompromised patients; maximum: 7.5 mg/kg/day.
Initially infuse at 1 mg/kg/hour. Rate of infusion may be increased with subsequent doses to 3 mg/kg/hour as patient tolerance allows. Treatment should continue as patient tolerance allows, until complete resolution of microbiologic and clinical evidence of fungal disease.
DOSING: PEDIATRIC — Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution:
Amphotec®: 50 mg, 100 mg
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution:
Amphotec®: 50 mg, 100 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Avoid injection faster than 1 mg/kg/hour. For a patient who experiences chills, fever, hypotension, nausea, or other nonanaphylactic infusion-related reactions, premedicate with the following drugs 30-60 minutes prior to drug administration: A nonsteroidal (eg, ibuprofen, choline magnesium trisalicylate) with or without diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered. If severe respiratory distress occurs, the infusion should be immediately discontinued.
COMPATIBILITY — Stable in D5W; incompatible with NS.
Y-site administration: Compatible: Acyclovir, aminophylline, cefoxitin, ceftizoxime, clindamycin, dexamethasone sodium phosphate, fentanyl, furosemide, ganciclovir, granisetron, hydrocortisone sodium succinate, ifosfamide, lorazepam, mannitol, methotrexate, methylprednisolone sodium succinate, nitroglycerin, sufentanil, trimethoprim/sulfamethoxazole, vinblastine, vincristine, zidovudine. Incompatible: Alfentanil, amikacin, ampicillin, ampicillin/sulbactam, atenolol, aztreonam, bretylium, buprenorphine, butorphanol, calcium chloride, calcium gluconate, carboplatin, cefazolin, cefepime, cefoperazone, ceftazidime, ceftriaxone, chlorpromazine, cimetidine, cisatracurium, cisplatin, cyclophosphamide, cyclosporine, cytarabine, diazepam, digoxin, diphenhydramine, dobutamine, dopamine, doxorubicin, doxorubicin liposome, droperidol, enalaprilat, esmolol, famotidine, fluconazole, fluorouracil, gatifloxacin, gentamicin, haloperidol, heparin, hydromorphone, hydroxyzine, imipenem/cilastatin, labetalol, leucovorin, lidocaine, magnesium sulfate, meperidine, mesna, metoclopramide, metoprolol, metronidazole, midazolam, mitoxantrone, morphine, nalbuphine, naloxone, ofloxacin, ondansetron, paclitaxel, pentobarbital, phenobarbital, phenytoin, piperacillin, piperacillin/tazobactam, potassium chloride, prochlorperazine, promethazine, propranolol, ranitidine, remifentanil, sodium bicarbonate, ticarcillin, ticarcillin/clavulanate, tobramycin, vancomycin, vecuronium, verapamil, vinorelbine.
USE — Treatment of invasive aspergillosis in patients who have failed amphotericin B deoxycholate treatment, or who have renal impairment or experience unacceptable toxicity which precludes treatment with amphotericin B deoxycholate in effective doses.
USE - UNLABELED / INVESTIGATIONAL — Effective in patients with serious Candida species infections
ADVERSE REACTIONS SIGNIFICANT
>10%: Central nervous system: Chills, fever
1% to 10%:
Cardiovascular: Hypotension, tachycardia
Central nervous system: Headache
Dermatologic: Rash
Endocrine & metabolic: Hypokalemia, hypomagnesemia
Gastrointestinal: Nausea, diarrhea, abdominal pain
Hematologic: Thrombocytopenia
Hepatic: LFT change
Neuromuscular & skeletal: Rigors
Renal: Creatinine increased
Respiratory: Dyspnea
Note: Amphotericin B colloidal dispersion has an improved therapeutic index compared to conventional amphotericin B, and has been used safely in patients with amphotericin B-related nephrotoxicity; however, continued decline of renal function has occurred in some patients.
CONTRAINDICATIONS — Hypersensitivity to amphotericin B or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylaxis: Has been reported with amphotericin B-containing drugs; facilities for cardiopulmonary resuscitation should be available during administration due to the possibility of anaphylactic reaction. If severe respiratory distress occurs, the infusion should be immediately discontinued. During the initial dosing, the drug should be administered under close clinical observation. Infusion reactions: Sometimes severe, usually subside with continued therapy - manage with decreased rate of infusion and pretreatment with antihistamines/corticosteroids.
Special populations: Neutropenic patients: Pulmonary reactions may occur in neutropenic patients receiving leukocyte transfusions; separation of the infusions as much as possible is advised.
DRUG INTERACTIONS
Aminoglycosides: Amphotericin B may enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May diminish the therapeutic effect of Amphotericin B. Risk C: Monitor therapy
Colistimethate: Amphotericin B may enhance the nephrotoxic effect of Colistimethate. Risk D: Consider therapy modification
Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy
CycloSPORINE: Amphotericin B may enhance the nephrotoxic effect of CycloSPORINE. Risk C: Monitor therapy
Flucytosine: Amphotericin B may enhance the adverse/toxic effect of Flucytosine. This may be related to the adverse effects of amphotericin B on renal function. Risk C: Monitor therapy
Gallium Nitrate: Amphotericin B may enhance the nephrotoxic effect of Gallium Nitrate. Risk X: Avoid combination
Saccharomyces boulardii: Antifungal Agents may diminish the therapeutic effect of Saccharomyces boulardii. Risk D: Consider therapy modification
PREGNANCY RISK FACTOR — B (show table)
LACTATION — Excretion in breast milk unknown/contraindicated
BREAST-FEEDING CONSIDERATIONS — Due to limited data, consider discontinuing nursing during therapy.
MONITORING PARAMETERS — Liver function tests, electrolytes, BUN, Cr, temperature, CBC, I/O, signs of hypokalemia (muscle weakness, cramping, drowsiness, ECG changes)
CANADIAN BRAND NAMES — Amphotec®
INTERNATIONAL BRAND NAMES — Amphocil (AT, AU, BR, CZ, DK, FI, GB, HK, HN, IL, IT, MX, MY, NL, SE, TH, TW)
MECHANISM OF ACTION — Binds to ergosterol altering cell membrane permeability in susceptible fungi and causing leakage of cell components with subsequent cell death. Proposed mechanism suggests that amphotericin causes an oxidation-dependent stimulation of macrophages (Lyman, 1992).
PHARMACODYNAMICS / KINETICS
Distribution: Vd: Total volume increases with higher doses, reflects increasing uptake by tissues (with 4 mg/kg/day = 4 L/kg); predominantly distributed in the liver; concentrations in kidneys and other tissues are lower than observed with conventional amphotericin B
Half-life elimination: 28-29 hours; prolonged with higher दोसेस.
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