Zanmbeel

Monday, August 2, 2010

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

Amphotericin B lipid complex

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.

Amphotericin B cholesteryl sulfate complex

Amphotericin B (conventional)

MEDICATION SAFETY ISSUES
Safety issues:
Conventional amphotericin formulations (Amphocin®, Fungizone®) may be confused with lipid-based formulations (AmBisome®, Abelcet®, Amphotec®).
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 (intrathecal administration) among its list of drugs which have a heightened risk of causing significant patient harm when used in error.

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: NSAID (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.

Test dose: I.V.: 1 mg infused over 20-30 minutes. Many clinicians believe a test dose is unnecessary.

Susceptible fungal infections: I.V.: Adults: 0.05-1.5 mg/kg/day; 1-1.5 mg/kg over 4-6 hours every other day may be given once therapy is established; aspergillosis, rhinocerebral mucormycosis, often require 1-1.5 mg/kg/day; do not exceed 1.5 mg/kg/day
Aspergillosis, disseminated: I.V.: 0.6-0.7 mg/kg/day for 3-6 months
Bone marrow transplantation (prophylaxis): I.V.: Low-dose amphotericin B 0.1-0.25 mg/kg/day has been administered after bone marrow transplantation to reduce the risk of invasive fungal disease.
Candidemia (neutropenic or non-neutropenic): I.V.: 0.5-1 mg/kg/day until 14 days after last positive blood culture and resolution of signs and symptoms (Pappas, 2009)
Candidiasis, chronic, disseminated: I.V.: 0.5-0.7 mg/kg/day for 3-6 months and resolution of radiologic lesions (Pappas, 2009)
Dematiaceous fungi: I.V.: 0.7 mg/kg/day in combination with an azole
Endocarditis: I.V.: 0.6-1 mg/kg/day (with or without flucytosine) for 6 weeks after valve replacement; Note: If isolates susceptible and/or clearance demonstrated, guidelines recommend step-down to fluconazole; also for long-term suppression therapy if valve replacement is not possible (Pappas, 2009)
Endophthalmitis, fungal:
Intravitreal (unlabeled use): 10 mcg in 0.1 mL (in conjunction with systemic therapy)
I.V.: 0.7-1 mg/kg/day (with or without flucytosine) for at least 4-6 weeks (Pappas, 2009)
Esophageal: I.V.: 0.3-0.7 mg/kg/day for 14-21 days after clinical improvement
Histoplasmosis: Chronic, severe pulmonary or disseminated: I.V.: 0.5-1 mg/kg/day for 7 days, then 0.8 mg/kg every other day (or 3 times/week) until total dose of 10-15 mg/kg; may continue itraconazole as suppressive therapy (lifelong for immunocompromised patients)
Meningitis:
Candidal: I.V.: 0.7-1 mg/kg/day (with or without flucytosine) for at least 4 weeks; Note: Liposomal amphotericin favored by IDSA guidelines based on decreased risk of nephrotoxicity and potentially better CNS penetration (Pappas, 2009)
Cryptococcal or Coccidioides: I.T.: Initial: 25-300 mcg every 48-72 hours; increase to 500 mcg to 1 mg as tolerated; maximum total dose: 15 mg has been suggested
Histoplasma: I.V.: 0.5-1 mg/kg/day for 7 days, then 0.8 mg/kg every other day (or 3 times/week) for 3 months total duration; follow with fluconazole suppressive therapy for up to 12 months
Meningoencephalitis, cryptococcal: I.V.:
HIV positive: 0.7-1 mg/kg/day (plus flucytosine 100 mg/kg/day) for 2 weeks, then change to oral fluconazole for at least 10 weeks; alternatively, amphotericin and flucytosine may be continued uninterrupted for 6-10 weeks
HIV negative: 0.5-0.7 mg/kg/day (plus flucytosine) for 2 weeks
Oropharyngeal candidiasis: I.V.: 0.3 mg/kg/day for 7-14 days (Pappas, 2009)
Osteoarticular candidiasis: I.V.: 0.5-1 mg/kg/day for several weeks, followed by fluconazole for 6-12 months (osteomyelitis) or 6 weeks (septic arthritis)
Penicillium marneffei: I.V.: 0.6 mg/kg/day for 2 weeks
Pneumonia: Cryptococcal (mild-to-moderate): I.V.:
HIV positive: 0.5-1 mg/kg/day
HIV negative: 0.5-0.7 mg/kg/day (plus flucytosine) for 2 weeks
Sporotrichosis: Pulmonary, meningeal, osteoarticular or disseminated: I.V.: Total dose of 1-2 g, then change to oral itraconazole or fluconazole for suppressive therapy
Urinary tract candidiasis (Pappas, 2009):
Fungus balls: I.V.: 0.5-0.7 mg/kg/day with or without flucytosine 25 mg/kg 4 times daily
Pyelonephritis: I.V.: 0.5-0.7 mg/kg/day with or without flucytosine 25 mg/kg 4 times daily for 2 weeks
Symptomatic cystitis: I.V.: 0.3-0.6 mg/kg/day for 1-7 days
Bladder irrigation: Irrigate with 50 mcg/mL solution instilled periodically or continuously for 5-10 days or until cultures are clear for fluconazole-resistant Candida

DOSING: PEDIATRIC — Note: Premedication: For patients who experience infusion-related immediate reactions, premedicate with the following drugs 30-60 minutes prior to drug administration: NSAID (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.

(For additional information see "Amphotericin B (conventional): Pediatric drug information")

Test dose: I.V.: Infants and Children: 0.1 mg/kg/dose to a maximum of 1 mg; infuse over 30-60 minutes. Many clinicians believe a test dose is unnecessary.

Susceptible fungal infections: I.V.: Infants and Children: Maintenance dose: 0.25-1 mg/kg/day given once daily; infuse over 2-6 hours. Once therapy has been established, amphotericin B can be administered on an every-other-day basis at 1-1.5 mg/kg/dose; cumulative dose: 1.5-2 g over 6-10 weeks
Note: Duration of therapy varies with nature of infection: Usual duration is 4-12 weeks or cumulative dose of 1-4 g.

Meningitis, coccidioidal or cryptococcal: I.T.: Children: 25-100 mcg every 48-72 hours; increase to 500 mcg as tolerated

DOSING: ELDERLY — Refer to adult dosing.

DOSING: RENAL IMPAIRMENT
If renal dysfunction is due to the drug, the daily total can be decreased by 50% or the dose can be given every other day. I.V. therapy may take several months.

Poorly dialyzed; no supplemental dose is necessary when using hemo- or peritoneal dialysis or continuous renal replacement therapy (CRRT).

Administration in dialysate: 1-2 mg/L of peritoneal dialysis fluid either with or without low-dose I.V. amphotericin B (a total dose of 2-10 mg/kg given over 7-14 days). Precipitate may form in ionic dialysate solutions.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, powder for reconstitution, as desoxycholate: 50 mg

DOSAGE FORMS: CONCISE
Injection, powder for reconstitution: 50 mg

GENERIC EQUIVALENT AVAILABLE — Yes

ADMINISTRATION — May be infused over 4-6 hours. 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. Bolus infusion of normal saline immediately preceding, or immediately preceding and following amphotericin B may reduce drug-induced nephrotoxicity. Risk of nephrotoxicity increases with amphotericin B doses >1 mg/kg/day. Infusion of admixtures more concentrated than 0.25 mg/mL should be limited to patients absolutely requiring volume contraction.

COMPATIBILITY
Solution compatibility:
Compatible: Heparin sodium, hydrocortisone, sodium bicarbonate.
Incompatible: Ampicillin, calcium gluconate, carbenicillin, cimetidine, dopamine, gentamicin, lidocaine, potassium chloride, sodium chloride, tetracycline, verapamil.

USE — Treatment of severe systemic and central nervous system infections caused by susceptible fungi such as Candida species, Histoplasma capsulatum, Cryptococcus neoformans, Aspergillus species, Blastomyces dermatitidis, Torulopsis glabrata, and Coccidioides immitis; fungal peritonitis; irrigant for bladder fungal infections; used in fungal infection in patients with bone marrow transplantation, amebic meningoencephalitis, ocular aspergillosis (intraocular injection), candidal cystitis (bladder irrigation), chemoprophylaxis (low-dose I.V.), immunocompromised patients at risk of aspergillosis (intranasal/nebulized), refractory meningitis (intrathecal), coccidioidal arthritis (intra-articular/I.M.).

Low-dose amphotericin B has been administered after bone marrow transplantation to reduce the risk of invasive fungal disease.

ADVERSE REACTIONS SIGNIFICANT
Systemic:

>10%:
Cardiovascular: Hypotension, tachypnea
Central nervous system: Fever, chills, headache (less frequent with I.T.), malaise
Endocrine & metabolic: Hypokalemia, hypomagnesemia
Gastrointestinal: Anorexia, nausea (less frequent with I.T.), vomiting (less frequent with I.T.), diarrhea, heartburn, cramping epigastric pain
Hematologic: Normochromic-normocytic anemia
Local: Pain at injection site with or without phlebitis or thrombophlebitis (incidence may increase with peripheral infusion of admixtures)
Neuromuscular & skeletal: Generalized pain, including muscle and joint pains (less frequent with I.T.)
Renal: Decreased renal function and renal function abnormalities including azotemia, renal tubular acidosis, nephrocalcinosis (>0.1 mg/mL)

1% to 10%:
Cardiovascular: Hypertension, flushing
Central nervous system: Delirium, arachnoiditis, pain along lumbar nerves (especially I.T. therapy)
Genitourinary: Urinary retention
Hematologic: Leukocytosis
Neuromuscular & skeletal: Paresthesia (especially with I.T. therapy)

<1% (Limited to important or life-threatening): Acute liver failure, agranulocytosis, anuria, bone marrow suppression, cardiac arrest, coagulation defects, convulsions, dyspnea, hearing loss, leukopenia, maculopapular rash, renal failure, renal tubular acidosis, thrombocytopenia, vision changes

CONTRAINDICATIONS — Hypersensitivity to amphotericin or any component of the formulation

WARNINGS / PRECAUTIONS
Boxed warnings: Error prevention: See "Other warnings/precautions" below. Fungal infections: See "Disease-related concerns" below.

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.

Disease-related concerns: Fungal infections: [U.S. Boxed Warning]: Should be used primarily for treatment of progressive, potentially life-threatening fungal infections, not noninvasive forms of infection. Renal impairment: Use with caution in patients with renal impairment.

Concurrent drug therapy issues: Nephrotoxic drugs: Avoid use with other nephrotoxic drugs; drug-induced renal toxicity usually improves with interrupting therapy, decreasing dosage, or increasing dosing interval.

Special populations: Neutropenic patients: Pulmonary reactions may occur in neutropenic patients receiving leukocyte transfusions; separation of the infusions as much as possible is advised.

Other warnings/precautions: Error prevention: [U.S. Boxed warning]: Verify the product name and dosage if dose exceeds 1.5 mg/kg.

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

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)

REFERENCE RANGE — Therapeutic: 1-2 mcg/mL (SI: 1-2.2 µmol/L)

CANADIAN BRAND NAMES — Fungizone®

INTERNATIONAL BRAND NAMES — Amphocil (MX); Fungizone (PL); Terix (MX)

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: Minimal amounts enter the aqueous humor, bile, CSF (inflamed or noninflamed meninges), amniotic fluid, pericardial fluid, pleural fluid, and synovial fluid

Protein binding, plasma: 90%

Half-life elimination: Biphasic: Initial: 15-48 hours; Terminal: 15 days

Time to peak: Within 1 hour following a 4- to 6-hour dose

Excretion: Urine (2% to 5% as biologically active form); ~40% eliminated over a 7-day period and may be detected in urine for at least 7 weeks after discontinued उसे.

Amphotericin B (conventional)

Amoxicillin and clavulanate potassium

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Augmentin® may be confused with Azulfidine®

U.S. BRAND NAMES — Amoclan; Augmentin ES-600®; Augmentin XR®; Augmentin®

PHARMACOLOGIC CATEGORY
Antibiotic, Penicillin

DOSING: ADULTS — Note: Dose is based on the amoxicillin component; see "Augmentin® Product-Specific Considerations" table.

Susceptible infections: Children >40 kg and Adults: Oral: 250-500 mg every 8 hours or 875 mg every 12 hours

Augmentin® Product-Specific Considerations

125 mg: Chewable tablet: q8h dosing Suspension:

" q8h dosing
" For adults having difficulty swallowing tablets, 125 mg/5 mL suspension may be substituted for 500 mg tablet.

200 mg: Chewable tablet:

" q12h dosing
" Contains phenylalanine Suspension:

" q12h dosing
" For adults having difficulty swallowing tablets, 200 mg/5 mL suspension may be substituted for 875 mg tablet.

250 mg: Chewable tablet:

" q8h dosing
" Contains phenylalanine
" Tablet and chewable tablet are not interchangeable due to differences in clavulanic acid. Suspension:

" q8h dosing
" For adults having difficulty swallowing tablets, 250 mg/5 mL suspension may be substituted for 500 mg tablet. Tablet:

" q8h dosing
" Not for use in patients <40 kg
" Tablet and chewable tablet are not interchangeable due to differences in clavulanic acid.

400 mg: Chewable tablet:

" q12h dosing
" Contains phenylalanine Suspension:

" q12h dosing
" For adults having difficulty swallowing tablets, 400 mg/5 mL suspension may be substituted for 875 mg tablet.

500 mg: Tablet: q8h or q12h dosing

600 mg: Suspension:

" q12h dosing
" Not for use in adults or children ≥ 40 kg
" 600 mg/5 mL suspension is not equivalent to or interchangeable with 200 mg/5 mL or 400 mg/5 mL due to differences in clavulanic acid.

875 mg: Tablet:

" q12h dosing
" Not for use in Clcr <30 mL/minute

1000 mg: Extended release tablet:

" q12h dosing
" Not for use in children <16 years of age
" Not interchangeable with two 500 mg tablets
" Not for use if Clcr <30 mL/minute or hemodialysis

Acute bacterial sinusitis: Oral: Extended release tablet: Two 1000 mg tablets every 12 hours for 10 days

Bite wounds (animal/human): Oral: 875 mg every 12 hours or 500 mg every 8 hours

Chronic obstructive pulmonary disease: Oral: 875 mg every 12 hours or 500 mg every 8 hours

Diabetic foot: Oral: Extended release tablet: Two 1000 mg tablets every 12 hours for 7-14 days

Diverticulitis, perirectal abscess: Oral: Extended release tablet: Two 1000 mg tablets every 12 hours for 7-10 days

Erysipelas: Oral: 875 mg every 12 hours or 500 mg every 8 hours

Febrile neutropenia: Oral: 875 mg every 12 hours

Pneumonia:
Aspiration: Oral: 875 mg every 12 hours
Community-acquired: Oral: Extended release tablet: Two 1000 mg tablets every 12 hours for 7-10 days

Pyelonephritis (acute, uncomplicated): Oral: 875 mg every 12 hours or 500 mg every 8 hours

Skin abscess: Oral: 875 mg every 12 hours

DOSING: PEDIATRIC — Note: Dose is based on the amoxicillin component; see "Augmentin® Product-Specific Considerations" table.

(For additional information see "Amoxicillin and clavulanate potassium: Pediatric drug information")

Susceptible infections: Infants <3 months: Oral: 30 mg/kg/day divided every 12 hours using the 125 mg/5 mL suspension

Lower respiratory tract infections, severe infections, sinusitis: Children ≥ 3 months and <40 kg: Oral: 45 mg/kg/day divided every 12 hours or 40 mg/kg/day divided every 8 hours

Mild-to-moderate infections: Children ≥ 3 months and <40 kg: Oral: 25 mg/kg/day divided every 12 hours or 20 mg/kg/day divided every 8 hours

Otitis media (Augmentin ES-600®): Children ≥ 3 months and <40 kg: Oral: 90 mg/kg/day divided every 12 hours for 10 days in children with severe illness and when coverage for ß-lactamase positive H. influenzae and M. catarrhalis is needed.

Children >40 kg: Refer to adult dosing.

DOSING: ELDERLY — Refer to adult dosing.

DOSING: RENAL IMPAIRMENT
Clcr <30 mL/minute: Do not use 875 mg tablet or extended release tablets.

Clcr 10-30 mL/minute: 250-500 mg every 12 hours

Clcr <10 mL/minute: 250-500 every 24 hours

Hemodialysis: Moderately dialyzable (20% to 50%)
250-500 mg every 24 hours; administer dose during and after dialysis. Do not use extended release tablets.

Peritoneal dialysis: Moderately dialyzable (20% to 50%)
Amoxicillin: Administer 250 mg every 12 hours
Clavulanic acid: Dose for Clcr <10 mL/minute

Continuous arteriovenous or venovenous hemofiltration effects:
Amoxicillin: ~50 mg of amoxicillin/L of filtrate is removed
Clavulanic acid: Dose for Clcr <10 mL/minute

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Powder for oral suspension: 200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine]; 400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine]; 600: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL (75 mL, 125 mL, 200 mL)
Amoclan:
200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine 7 mg/5 mL and potassium 0.14 mEq/5 mL; fruit flavor]
400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine 7 mg/5 mL and potassium 0.29 mEq/5 mL; fruit flavor]
600: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL (75 mL, 125 mL) [contains phenylalanine 7 mg/5 mL, potassium 0.248 mEq/5 mL; orange flavor]
Augmentin®:
125: Amoxicillin 125 mg and clavulanate potassium 31.25 mg per 5 mL (75 mL, 100 mL, 150 mL) [contains potassium 0.16 mEq/5 mL; banana flavor]
200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine 7 mg/5 mL and potassium 0.14 mEq/5 mL; orange flavor] [DSC]
250: Amoxicillin 250 mg and clavulanate potassium 62.5 mg per 5 mL (75 mL, 100 mL, 150 mL) [contains potassium 0.32 mEq/5 mL; orange flavor]
400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine 7 mg/5 mL and potassium 0.29 mEq/5 mL; orange flavor] [DSC]
Augmentin ES-600®: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL (75 mL, 125 mL, 200 mL) [contains phenylalanine 7 mg/5 mL and potassium 0.23 mEq/5 mL; strawberry cream flavor]

Tablet: 250: Amoxicillin 250 mg and clavulanate potassium 125 mg; 500: Amoxicillin 500 mg and clavulanate potassium 125 mg; 875: Amoxicillin 875 mg and clavulanate potassium 125 mg
Augmentin®:
250: Amoxicillin 250 mg and clavulanate potassium 125 mg [contains potassium 0.63 mEq/tablet]
500: Amoxicillin 500 mg and clavulanate potassium 125 mg [contains potassium 0.63 mEq/tablet]
875: Amoxicillin 875 mg and clavulanate potassium 125 mg [contains potassium 0.63 mEq/tablet]

Tablet, chewable: 200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg [contains phenylalanine]; 400: Amoxicillin 400 mg and clavulanate potassium 57 mg [contains phenylalanine]

Tablet, extended release:
Augmentin XR®: 1000: Amoxicillin 1000 mg and clavulanate acid 62.5 mg [contains potassium 12.6 mg (0.32 mEq) and sodium 29.3 mg (1.27 mEq) per tablet; packaged in either a 7-day or 10-day package]

DOSAGE FORMS: CONCISE
Powder for oral suspension: 200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL; 400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL; 600: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL
Amoclan:
200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL
400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL
600: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL
Augmentin®:
125: Amoxicillin 125 mg and clavulanate potassium 31.25 mg per 5 mL
250: Amoxicillin 250 mg and clavulanate potassium 62.5 mg per 5 mL
Augmentin ES-600®: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL

Tablet: 500: Amoxicillin 500 mg and clavulanate potassium 125 mg; 875: Amoxicillin 875 mg and clavulanate potassium 125 mg
Augmentin®:
250: Amoxicillin 250 mg and clavulanate potassium 125 mg
500: Amoxicillin 500 mg and clavulanate potassium 125 mg
875: Amoxicillin 875 mg and clavulanate potassium 125 mg

Tablet, chewable: 200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg; 400: Amoxicillin 400 mg and clavulanate potassium 57 mg

Tablet, extended release:
Augmentin XR®: 1000: Amoxicillin 1000 mg and clavulanate acid 62.5 mg

GENERIC EQUIVALENT AVAILABLE — Yes: Excludes extended release

ADMINISTRATION — Administer around-the-clock to promote less variation in peak and trough serum levels. Administer with food to decrease stomach upset; shake suspension well before use. Extended release tablets should be administered with food.

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.

USE — Treatment of otitis media, sinusitis, and infections caused by susceptible organisms involving the lower respiratory tract, skin and skin structure, and urinary tract; spectrum same as amoxicillin with additional coverage of beta-lactamase producing B. catarrhalis, H. influenzae, N. gonorrhoeae, and S. aureus (not MRSA). The expanded coverage of this combination makes it a useful alternative when amoxicillin resistance is present and patients cannot tolerate alternative treatments.

ADVERSE REACTIONS SIGNIFICANT
>10%: Gastrointestinal: Diarrhea (3% to 34%; incidence varies upon dose and regimen used)

1% to 10%:
Dermatologic: Diaper rash, skin rash, urticaria
Gastrointestinal: Abdominal discomfort, loose stools, nausea, vomiting
Genitourinary: Vaginitis, vaginal mycosis
Miscellaneous: Moniliasis

<1% (Limited to important or life-threatening): Alkaline phosphatase increased, cholestatic jaundice, flatulence, headache, hepatic dysfunction, hepatitis, liver function tests increased, prothrombin time increased, thrombocytosis, vasculitis (hypersensitivity)

Additional adverse reactions seen with ampicillin-class antibiotics: Agitation, agranulocytosis, alkaline phosphatase increased, anaphylaxis, anemia, angioedema, anxiety, behavioral changes, bilirubin increased, black "hairy" tongue, confusion, convulsions, crystalluria, dizziness, enterocolitis, eosinophilia, erythema multiforme, exanthematous pustulosis, exfoliative dermatitis, gastritis, glossitis, hematuria, hemolytic anemia, hemorrhagic colitis, indigestion, insomnia, hyperactivity, interstitial nephritis, leukopenia, mucocutaneous candidiasis, pruritus, pseudomembranous colitis, serum sickness-like reaction, Stevens-Johnson syndrome, stomatitis, transaminases increased, thrombocytopenia, thrombocytopenic purpura, tooth discoloration, toxic epidermal necrolysis

CONTRAINDICATIONS — Hypersensitivity to amoxicillin, clavulanic acid, penicillin, or any component of the formulation; history of cholestatic jaundice or hepatic dysfunction with amoxicillin/clavulanate potassium therapy; Augmentin XR™ : severe renal impairment (Clcr <30 mL/minute) and hemodialysis patients

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. Low incidence of cross-allergy with cephalosporins exists. Diarrhea: Incidence of diarrhea is higher than with amoxicillin alone. Hepatic effects: Although rare, hepatic dysfunction is more common in elderly and/or males, and occurs more frequently with prolonged treatment, and may occur after therapy is complete. 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: Hepatic impairment: Use with caution in patients with hepatic impairment. 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.

Dosage form specific issues: Clavulanic acid content: Due to differing content of clavulanic acid, not all formulations are interchangeable. Phenylalanine: Some products contain phenylalanine.

DRUG INTERACTIONS
Allopurinol: May enhance the potential for allergic or hypersensitivity reactions to Amoxicillin. 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, amoxicillin/clavulanate is classified as pregnancy category B. Both amoxicillin and clavulanic acid cross the placenta. There is no documented increased risk of teratogenic effects caused by amoxicillin/clavulanate. A potential increased risk of necrotizing enterocolitis in the newborn has been noted after maternal use of amoxicillin/clavulanate for preterm labor or premature prolonged rupture of membranes. When used during pregnancy, pharmacokinetic changes have been observed with amoxicillin alone (refer to the Amoxicillin monograph for details).

LACTATION — Enters breast milk/use caution

BREAST-FEEDING CONSIDERATIONS — Amoxicillin is found in breast milk. The manufacturer recommends that caution be used if administered to breast-feeding women. The use of amoxicillin/clavulanate may be safe while breast-feeding; however, the risk of adverse events in the infant may be increased when compared to the use of amoxicillin alone. The risk of adverse events may be related to maternal dose. Nondose-related effects could include modification of bowel flora and allergic sensitization of the infant.

DIETARY CONSIDERATIONS — May be taken with meals or on an empty stomach; take with meals to increase absorption and decrease GI intolerance; may mix with milk, formula, or juice. Extended release tablets should be taken with food. Some products contain phenylalanine. If you have phenylketonuria or PKU, avoid use. All dosage forms contain potassium.

PRICING — (data from drugstore.com)
Chewable (Amoxicillin-Pot Clavulanate)
400-57 mg (20): $63.79

Suspension (reconstituted) (Amoxicillin-Pot Clavulanate)
600-42.9 mg/5 mL (75): $35.99

Tablet, 12-hour (Augmentin XR)
1000-62.5 mg (28): $116.70

Tablets (Amoxicillin-Pot Clavulanate)
250-125 mg (30): $116.54
500-125 mg (20): $45.99
875-125 mg (20): $31.99

Tablets (Augmentin)
250-125 mg (30): $118.99
500-125 mg (30): $166.71
875-125 mg (20): $145.99

MONITORING PARAMETERS — Assess patient at beginning and throughout therapy for infection; with prolonged therapy, monitor renal, hepatic, and hematologic function periodically; monitor for signs of anaphylaxis during first dose

CANADIAN BRAND NAMES — Alti-Amoxi-Clav; Apo-Amoxi-Clav®; Augmentin®; Clavulin®; Novo-Clavamoxin; ratio-Aclavulanate

INTERNATIONAL BRAND NAMES — Acarbixin (MX); Aclam (ID); Ambilan (PE); AMK (TH); Amobay Cl (MX); Amocla (KP); Amocla Duo (KP); Amoclan (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Amoclav (DE); Amoksiclav (TH); Amoksiklav (CL, PL); Amolanic (KP); Amolanic Duo (KP); Amoxa (KP); Amoxi Plus (PY); Amoxiclav (MX); Amoxiclav-BID (MX); Amoxiclav-Teva (IL); Amoxsiklav Forte (TH); Amoxxlin (KP); Amoxyclav (IL); Augamox (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); AugMaxcil (ZA); Augmentan (DE); Augmentin (AE, AT, AU, BB, BE, BF, BG, BH, BJ, BM, BS, BZ, CH, CI, CR, CY, CZ, DE, DK, DO, EG, ES, ET, FI, FR, GB, GH, GM, GN, GR, GT, GY, HK, HN, IE, IL, IN, IQ, IR, IT, JM, JO, JP, KE, KP, KW, LB, LR, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, NL, NO, OM, PA, PE, PK, PL, PT, QA, RU, SA, SC, SD, SE, SL, SN, SR, SV, SY, TH, TN, TR, TT, TZ, UG, UY, VE, YE, ZA, ZM, ZW); Augmentine (ES); Augmex (PH); Augpen (TH); Augurcin (PH); Bactiv (PH); Bactoclav (PH); Bioclavid (AE, BH, CY, DE, DK, EG, IL, IQ, IR, JO, KW, LB, LY, OM, PH, QA, SA, SE, SY, YE); Bioclavid Forte (PH); Cavumox (MY, TH); Cax (PH); Clacillin Duo Dry Syrup (KP); Clamax (KP); Clamentin (ZA); Clamohexal (AU); Clamohexal Duo (AU); Clamovid (HK, MY, SG); Clamoxin (MX); Clamoxyl (AU); Clamoxyl Duo 400 (AU); Clamoxyl DuoForte (AU); Clavamox (DE, ID, IN); Clavant (MX); Clavar (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Claventin (IL); Clavinex (CN, EC); Clavipen (MX); Clavmex (PH); Clavodar (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Clavoxil (BR); Clavoxine (EC); Clavucyd (MX); Clavulin (BF, BJ, CI, CO, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, MX, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Clavulin Duo Forte (AU); Clavulox Duo (AR, PY); Clavumox (DE, PE, ZA); Clavuser (MX); Cramon Duo (KP); Curam (AU, CO, CR, DO, GT, HK, MY, NI, PA, PE, PL, SG, SV, TH, TW); Danoclav (ID); Darzitil Plus (AR); E-Moxclav (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Enhancin (SG); Exten (PH); Fleming (HK); Forcid (PL); Fugentin (SG); Fullicilina Plus (AR); Gimaclav (MX); Hibiotic (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Klamonex (KP); Klavic (PH); Klavocin (PL); Kmoxilin (KP); Lansiclav (ID); Moxiclav (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, SG, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Moxicle (KP, TH); Moxlin (MX); Natravox (PH); Novamox (BR); Nufaclav (ID); Penhance (PH); Quali-Mentin (HK); Ramoclav (PL); Ranclav (TH, ZA); Riclasip (MX); Servamox (MX); Sinufin (MX); Spektramox (SE); Sullivan (PH); Suplentin (PH); Synermox (NZ); Taromentin (PL); Velamox CL (PE); Vestaclav (MY); Viaclav (ID); Vulamox (CO, ID)

MECHANISM OF ACTION — Clavulanic acid binds and inhibits beta-lactamases that inactivate amoxicillin resulting in amoxicillin having an expanded spectrum of activity. Amoxicillin 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 — Amoxicillin pharmacokinetics are not affected by clavulanic acid.

Amoxicillin: See Amoxicillin monograph.

Clavulanic acid:
Protein binding: ~25%
Metabolism: Hepatic
Half-life elimination: 1 hour
Time to peak: 1 hour
Excretion: Urine (30% to 40% as unchanged drug)

PATIENT INFORMATION — Take entire course of medication. Take extended release tablets with food. Report diarrhea promptly. Females should report onset of symptoms of candidal vaginitis

Pages

Monday, August 2, 2010