Zanmbeel

Monday, August 2, 2010

Amoxapine

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Amoxapine may be confused with amoxicillin, Amoxil®
Asendin may be confused with aspirin

MEDICATION GUIDE — An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088622.pdf, must be dispensed with this medication for each new outpatient prescription and refill.

PHARMACOLOGIC CATEGORY
Antidepressant, Tricyclic (Secondary Amine)

DOSING: ADULTS — Once symptoms are controlled, decrease gradually to lowest effective dose. Maintenance dose is usually given at bedtime to reduce daytime sedation.

Depression: Oral: Initial: 25 mg 2-3 times/day. If tolerated, dosage may be increased to 100 mg 2-3 times/day. May be given in a single bedtime dose when dosage <300 mg/day.
Maximum daily dose: 600 mg (inpatients); 400 mg (outpatients)

DOSING: PEDIATRIC
Depression: Oral:
Children: Not established in children <16 years of age.
Adolescents: Initial: 25-50 mg/day; increase gradually to 100 mg/day. May administer as divided doses or as a single dose at bedtime.

Note: Once symptoms are controlled, decrease gradually to lowest effective dose. Maintenance dose is usually given at bedtime to reduce daytime sedation.

DOSING: ELDERLY — Oral: Initial: 25 mg at bedtime increased by 25 mg weekly for outpatients and every 3 days for inpatients if tolerated; usual dose: 50-150 mg/day, but doses up to 300 mg may be necessary. Note: Once symptoms are controlled, decrease gradually to lowest effective dose. See Geriatric Considerations.

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

Tablet: 25 mg, 50 mg, 100 mg, 150 mg

DOSAGE FORMS: CONCISE
Tablet: 25 mg, 50 mg, 100 mg, 150 mg

GENERIC EQUIVALENT AVAILABLE — Yes

ADMINISTRATION — May be administered with food to decrease GI distress.

USE — Treatment of depression, psychotic depression, depression accompanied by anxiety or agitation

ADVERSE REACTIONS SIGNIFICANT
>10%:
Central nervous system: Drowsiness
Gastrointestinal: Xerostomia, constipation

1% to 10%:
Central nervous system: Anxiety, ataxia, confusion, dizziness, excitement, headache, insomnia, nervousness, restlessness
Dermatologic: Edema, skin rash
Endocrine: Prolactin levels increased
Gastrointestinal: Nausea
Neuromuscular & skeletal: Tremor, weakness
Ocular: Blurred vision
Miscellaneous: Diaphoresis

<1% (Limited to important or life-threatening): Agranulocytosis, allergic reactions, diarrhea, extrapyramidal symptoms, galactorrhea, hypertension, impotence, incoordination, intraocular pressure increased, leukopenia, menstrual irregularity, mydriasis, neuroleptic malignant syndrome, numbness, painful ejaculation, paresthesia, photosensitivity, seizure, SIADH, syncope, tardive dyskinesia, testicular edema, tinnitus, urinary retention, vomiting

CONTRAINDICATIONS — Hypersensitivity to amoxapine or any component of the formulation; use of MAO inhibitors within past 14 days; acute recovery phase following myocardial infarction

WARNINGS / PRECAUTIONS
Boxed warnings: Suicidal thinking/behavior: See "Major psychiatric warnings" below.

Major psychiatric warnings:
• [U.S. Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥ 65 years. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1-2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient's family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. Amoxapine is not FDA approved for use in patients <16 years of age. The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Patients treated with antidepressants should be observed for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy. Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their healthcare provider if any of these symptoms or worsening depression or psychosis occur. May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Patients presenting with depressive symptoms should be screened for bipolar disorder. Amoxapine is not FDA approved for the treatment of bipolar depression.

Concerns related to adverse effects: Anticholinergic effects: May cause anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention); use with caution in patients with decreased gastrointestinal motility, paralytic ileus, urinary retention, BPH, xerostomia, or visual problems. The degree of anticholinergic blockade produced by this agent is moderate relative to other antidepressants. Extrapyramidal symptoms: May cause extrapyramidal symptoms, including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia (risk of these reactions is low). Neuroleptic malignant syndrome (NMS): Use may be associated with NMS; monitor for mental status changes, fever, muscle rigidity, and/or autonomic instability (risk may be increased in patients with Parkinson's disease or Lewy body dementia). Orthostatic hypotension: May cause orthostatic hypotension (risk is moderate relative to other antidepressants); use with caution in patients at risk of this effect or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, hypovolemia, or concurrent medication use which may predispose to hypotension/bradycardia). Sedation: May cause sedation, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). The degree of sedation is moderate relative to other antidepressants.

Disease-related concerns: Cardiovascular disease: Use with caution in patients with a history of cardiovascular disease (including previous MI, stroke, tachycardia, or conduction abnormalities); the risk conduction abnormalities with this agent is moderate relative to other antidepressants. Hepatic impairment: Use with caution in patients with hepatic impairment. Renal impairment: Use with caution in patients with renal impairment. Seizure disorder: Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold. Thyroid dysfunction: Use with caution in patients with hyperthyroidism or those receiving thyroid supplementation.

Concurrent drug therapy issues: Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.

Special populations: Elderly: Use with caution in the elderly.

Other warnings/precautions: Discontinuation of therapy: Therapy should not be abruptly discontinued in patients receiving high doses for prolonged periods. Electroconvulsive therapy: May increase the risks associated with electroconvulsive therapy; consider discontinuing, when possible, prior to ECT treatment.

METABOLISM / TRANSPORT EFFECTS — Substrate of CYP2D6 (major)

DRUG INTERACTIONS
Acetylcholinesterase Inhibitors (Central): Anticholinergics may diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central). Acetylcholinesterase Inhibitors (Central) may diminish the therapeutic effect of Anticholinergics. If the anticholinergic action is a side effect of the agent, the result may be beneficial. Risk C: Monitor therapy

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

Alfuzosin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy

Alpha-/Beta-Agonists (Direct-Acting): Tricyclic Antidepressants may enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Exceptions: Dipivefrin. Risk D: Consider therapy modification

Alpha1-Agonists: Tricyclic Antidepressants may enhance the vasopressor effect of Alpha1-Agonists. Risk D: Consider therapy modification

Alpha2-Agonists: Tricyclic Antidepressants may diminish the antihypertensive effect of Alpha2-Agonists. Exceptions: Apraclonidine; Brimonidine. Risk D: Consider therapy modification

Altretamine: May enhance the orthostatic effect of Tricyclic Antidepressants. Risk C: Monitor therapy

Amphetamines: Tricyclic Antidepressants may enhance the stimulatory effect of Amphetamines. Tricyclic Antidepressants may also potentiate the cardiovascular effects of Amphetamines. Risk C: Monitor therapy

Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Paliperidone. Risk C: Monitor therapy

Artemether: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination

Barbiturates: May increase the metabolism of Tricyclic Antidepressants. Risk D: Consider therapy modification

Beta2-Agonists: Tricyclic Antidepressants may enhance the adverse/toxic effect of Beta2-Agonists. Risk C: Monitor therapy

CarBAMazepine: May increase the metabolism of Tricyclic Antidepressants. Risk C: Monitor therapy

Chloroquine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy

Cimetidine: May decrease the metabolism of Tricyclic Antidepressants. Risk C: Monitor therapy

Cinacalcet: May increase the serum concentration of Tricyclic Antidepressants. Risk C: Monitor therapy

Ciprofloxacin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Risk C: Monitor therapy

CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Risk D: Consider therapy modification

Desmopressin: Tricyclic Antidepressants may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy

Dexmethylphenidate: May decrease the metabolism of Tricyclic Antidepressants. Risk C: Monitor therapy

Dronedarone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Dronedarone. Risk X: Avoid combination

DULoxetine: May decrease the metabolism of Tricyclic Antidepressants. Risk C: Monitor therapy

Gadobutrol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk D: Consider therapy modification

Iobenguane I 123: Tricyclic Antidepressants may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination

Lithium: May enhance the neurotoxic effect of Tricyclic Antidepressants. Risk C: Monitor therapy

Lumefantrine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination

MAO Inhibitors: May enhance the serotonergic effect of Tricyclic Antidepressants. This may cause serotonin syndrome. Risk X: Avoid combination

MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy

Methylphenidate: May decrease the metabolism of Tricyclic Antidepressants. Risk C: Monitor therapy

Nilotinib: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy

Pimozide: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Pimozide. Risk X: Avoid combination

Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification

Propoxyphene: May enhance the CNS depressant effect of Tricyclic Antidepressants. Risk C: Monitor therapy

Protease Inhibitors: May increase the serum concentration of Tricyclic Antidepressants. Risk C: Monitor therapy

QTc-Prolonging Agents: May enhance the adverse/toxic effect of other QTc-Prolonging Agents. Their effects can be additive, causing life-threatening ventricular arrhythmias. Risk D: Consider therapy modification

QuiNIDine: Tricyclic Antidepressants may enhance the QTc-prolonging effect of QuiNIDine. QuiNIDine may decrease the metabolism of Tricyclic Antidepressants. Risk D: Consider therapy modification

QuiNINE: QTc-Prolonging Agents may enhance the QTc-prolonging effect of QuiNINE. QuiNINE may enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination

Selective Serotonin Reuptake Inhibitors: May decrease the metabolism of Tricyclic Antidepressants. Risk D: Consider therapy modification

Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification

Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination

St Johns Wort: May increase the metabolism of Tricyclic Antidepressants. The risk of serotonin syndrome may theoretically be increased. Risk D: Consider therapy modification

Sulfonylureas: Cyclic Antidepressants may enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy

Terbinafine: May decrease the metabolism of Tricyclic Antidepressants. Risk D: Consider therapy modification

Tetrabenazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Tetrabenazine. Risk X: Avoid combination

Thioridazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination

TraMADol: Tricyclic Antidepressants may enhance the neuroexcitatory and/or seizure-potentiating effect of TraMADol. Risk C: Monitor therapy

Valproic Acid: May increase the serum concentration of Tricyclic Antidepressants. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Tricyclic Antidepressants may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Yohimbine: Tricyclic Antidepressants may increase the serum concentration of Yohimbine. Risk C: Monitor therapy

Ziprasidone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Ziprasidone. The risk of a severe arrhythmia may be increased. Risk X: Avoid combination

ETHANOL / NUTRITION / HERB INTERACTIONS
Ethanol: Avoid ethanol (may increase CNS depression).

Food: Grapefruit juice may inhibit the metabolism of some TCAs and clinical toxicity may result.

Herb/Nutraceutical: Avoid valerian, St John's wort, SAMe, kava kava.

PREGNANCY RISK FACTOR — C (show table)

LACTATION — Enters breast milk/contraindicated (AAP rates "of concern")

PRICING — (data from drugstore.com)
Tablets (Amoxapine)
25 mg (60): $25.99
50 mg (60): $28.99
100 mg (30): $35.99
150 mg (30): $38.99

MONITORING PARAMETERS — Monitor blood pressure and pulse rate prior to and during initial therapy evaluate mental status, suicidal ideation (especially at the beginning of therapy or when doses are increased or decreased); monitor weight; ECG in older adults

REFERENCE RANGE — Therapeutic: Amoxapine: 20-100 ng/mL (SI: 64-319 nmol/L); 8-OH amoxapine: 150-400 ng/mL (SI: 478-1275 nmol/L); both: 200-500 ng/mL (SI: 637-1594 nmol/L)

INTERNATIONAL BRAND NAMES — Asendin (ID); Defanyl (FR); Demolox (DK, IN)

MECHANISM OF ACTION — Reduces the reuptake of serotonin and norepinephrine. The metabolite, 7-OH-amoxapine has significant dopamine receptor blocking activity similar to haloperidol.

PHARMACODYNAMICS / KINETICS
Onset of antidepressant effect: Usually occurs after 1-2 weeks, but may require 4-6 weeks

Absorption: Rapid and well absorbed

Distribution: Vd: 0.9-1.2 L/kg; enters breast milk

Protein binding: 80%

Metabolism: Primarily hepatic

Half-life elimination: Parent drug: 11-16 hours; Active metabolite (8-hydroxy): Adults: 30 hours

Time to peak, serum: 1-2 hours

Excretion: Urine (as unchanged drug and metabolites)

PATIENT INFORMATION — Dry mouth may be helped by sips of water, sugarless gum, or hard candy; avoid alcohol; very important to maintain established dosage regimen; photosensitivity to sunlight can occur, do not discontinue abruptly; full effect may not occur for 3-4 weeks; full dosage may be taken at bedtime to avoid daytime sedation

Amoxicillin

EDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Amoxicillin may be confused with amoxapine, Amoxil®, Atarax®
Amoxil® may be confused with amoxapine, amoxicillin

International issues:
Fisamox® [Australia] may be confused with Fosamax® which is a brand name for alendronate in the U.S.
Fisamox® [Australia] may be confused with Vigamox® which is a brand name for moxifloxacin in the U.S.

U.S. BRAND NAMES — Amoxil®; Moxatag™

PHARMACOLOGIC CATEGORY
Antibiotic, Penicillin

DOSING: ADULTS
Usual dosage range: Oral: 250-500 mg every 8 hours or 500-875 mg twice daily or extended-release tablet 775 mg once daily

Anthrax exposure (CDC guidelines): Oral: Note: Postexposure prophylaxis in pregnant or nursing women only with documented susceptible organisms: 500 mg every 8 hours

Ear, nose, throat, genitourinary tract, or skin/skin structure infections:
Mild-to-moderate: Oral: 500 mg every 12 hours or 250 mg every 8 hours
Severe: Oral: 875 mg every 12 hours or 500 mg every 8 hours
Tonsillitis and/or pharyngitis: Oral: Extended release tablet: 775 mg once daily

Helicobacter pylorieradication: Oral: 1000 mg twice daily; requires combination therapy with at least one other antibiotic and an acid-suppressing agent (proton pump inhibitor or H2 blocker)

Lower respiratory tract infections: Oral: 875 mg every 12 hours or 500 mg every 8 hours

Lyme disease: Oral: 500 mg every 6-8 hours (depending on size of patient) for 21-30 days

Prophylaxis against infective endocarditis: Oral: 2 g 30-60 minutes before procedure. 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. As of April 2007, routine prophylaxis for GI/GU procedures is no longer recommended by the AHA.

Prophylaxis in total joint replacement patients undergoing dental procedures which produce bacteremia: 2 g 1 hour prior to procedure

DOSING: PEDIATRIC

(For additional information see "Amoxicillin: Pediatric drug information")
Usual dosage range:
Children ≤ 3 months: Oral: 20-30 mg/kg/day divided every 12 hours
Children >3 months and <40 kg: Oral: 20-50 mg/kg/day in divided doses every 8-12 hours
Children ≥ 12 years: Oral: Extended-release tablet: 775 mg once daily

Acute otitis media: Children >3 months and <40 kg: Oral: 80-90 mg/kg/day divided every 12 hours

Anthrax exposure (CDC guidelines): Children >3 months and <40 kg: Oral: Note: Postexposure prophylaxis only with documented susceptible organisms: 80 mg/kg/day in divided doses every 8 hours (maximum: 500 mg/dose)

Community-acquired pneumonia:
4 months to <5 years: 80-100 mg/kg/day divided every 8 hours
5-15 years: 100 mg/kg/day divided every 8 hours; Note: Treatment with a macrolide or doxycycline (if age >8 years) is preferred due to higher prevalence of atypical pathogens in this age group

Ear, nose, throat, genitourinary tract, or skin/skin structure infections: Children >3 months and <40 kg: Oral:
Mild-to-moderate: 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours
Severe: 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours
Tonsillitis and/or pharyngitis: Children ≥ 12 years: Extended release tablet: 775 mg once daily

Lower respiratory tract infections: Children >3 months and <40 kg: Oral: 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours

Lyme disease: Children >3 months and <40 kg: Oral: 25-50 mg/kg/day divided every 8 hours (maximum: 500 mg)

Prophylaxis against infective endocarditis: Children >3 months and <40 kg: Oral: 50 mg/kg 1 hour before procedure. 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. As of April 2007, routine prophylaxis for GI/GU procedures is no longer recommended by the AHA.

DOSING: ELDERLY — Refer to adult dosing.

DOSING: RENAL IMPAIRMENT
Use of certain dosage forms (eg, extended-release 775 mg tablet and immediate-release 875 mg tablet) should be avoided in patients with Clcr <30 mL/minute or patients requiring hemodialysis
Clcr 10-30 mL/minute: 250-500 mg every 12 hours
Clcr <10 mL/minute: 250-500 mg every 24 hours

Moderately dialyzable (20% to 50%) by hemodialysis or peritoneal dialysis; approximately 50 mg of amoxicillin per liter of filtrate is removed by continuous arteriovenous or venovenous hemofiltration. Dose as per Clcr <10 mL/minute guidelines.

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

Capsule: 250 mg, 500 mg
Amoxil®: 500 mg [DSC]

Powder for suspension, oral: 125 mg/5 mL (80 mL, 100 mL, 150 mL); 200 mg/5 mL (50 mL, 75 mL, 100 mL); 250 mg/5 mL (80 mL, 100 mL, 150 mL); 400 mg/5 mL (50 mL, 75 mL, 100 mL)
Amoxil®: 250 mg/5 mL (100 mL, 150 mL) [contains sodium benzoate; bubble gum flavor] [DSC]; 400 mg/5 mL (100 mL) [contains sodium benzoate; bubble gum flavor] [DSC]

Powder for suspension, oral [drops]:
Amoxil®: 50 mg/mL (30 mL) [contains sodium benzoate; bubble gum flavor] [DSC]

Tablet: 500 mg, 875 mg

Tablet, chewable: 125 mg, 200 mg, 250 mg, 400 mg

Tablet, extended release:
Moxatag™ : 775 mg

DOSAGE FORMS: CONCISE
Capsule: 250 mg, 500 mg

Powder for suspension, oral: 125 mg/5 mL, 200 mg/5 mL, 250 mg/5 mL, 400 mg/5 mL

Tablet: 500 mg, 875 mg

Tablet, chewable: 125 mg, 200 mg, 250 mg, 400 mg

Tablet, extended release:
Moxatag™ : 775 mg

GENERIC EQUIVALENT AVAILABLE — Yes: Excludes drops and extended-release formulation

ADMINISTRATION — Administer around-the-clock to promote less variation in peak and trough serum levels. The appropriate amount of suspension may be mixed with formula, milk, fruit juice, water, ginger ale, or cold drinks; administer dose immediately after mixing.

Moxatag™ extended release tablet: Administer within 1 hour of finishing a meal.

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 upper and lower respiratory tract, skin, and urinary tract; prophylaxis of infective endocarditis in patients undergoing surgical or dental procedures; as part of a multidrug regimen for H. pylori eradication

USE - UNLABELED / INVESTIGATIONAL — Postexposure prophylaxis for anthrax exposure with documented susceptible organisms

ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.

Central nervous system: Agitation, anxiety, behavioral changes, confusion, dizziness, headache, hyperactivity (reversible), insomnia, seizure

Dermatologic: Acute exanthematous pustulosis, erythematous maculopapular rash, erythema multiforme, exfoliative dermatitis, hypersensitivity vasculitis, mucocutaneous candidiasis, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria

Gastrointestinal: Black hairy tongue, diarrhea, hemorrhagic colitis, nausea, pseudomembranous colitis, tooth discoloration (brown, yellow, or gray; rare), vomiting

Hematologic: Agranulocytosis, anemia, eosinophilia, hemolytic anemia, leukopenia,thrombocytopenia, thrombocytopenia purpura

Hepatic: Acute cytolytic hepatitis, ALT increased, AST increased, cholestatic jaundice, hepatic cholestasis

Renal: Crystalluria

Miscellaneous: Anaphylaxis, serum sickness-like reaction

CONTRAINDICATIONS — Hypersensitivity to amoxicillin, penicillin, other beta-lactams, or any component of the formulation

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. 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. In addition, use of certain dosage forms (eg, extended-release 775 mg tablet and immediate-release 875 mg tablet) should be avoided in patients with Clcr <30 mL/minute or patients requiring hemodialysis.

Dosage form specific issues: Phenylalanine: Chewable tablets 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 is classified as pregnancy category B. There is no documented increased risk of adverse pregnancy outcome or teratogenic effects caused by amoxicillin. It is the drug of choice for the treatment of chlamydial infections in pregnancy and for anthrax prophylaxis when penicillin susceptibility is documented.

Due to pregnancy-induced physiologic changes, amoxicillin clearance is increased during pregnancy resulting in lower concentrations and smaller AUCs. Oral ampicillin-class antibiotics are poorly-absorbed during labor.

LACTATION — Enters breast milk/compatible

BREAST-FEEDING CONSIDERATIONS — Very small amounts of amoxicillin are excreted in breast milk. The manufacturer recommends that caution be exercised when administering amoxicillin to nursing women. The AAP considers amoxicillin to be "usually compatible with breastfeeding." Nondose-related effects could include modification of bowel flora and allergic sensitization of the infant.

DIETARY CONSIDERATIONS — May be taken with food. Amoxil® chewable contains phenylalanine 1.82 mg per 200 mg tablet, phenylalanine 3.64 mg per 400 mg tablet.

Moxatag™ : Take within 1 hour of finishing a meal.

PRICING — (data from drugstore.com)
Capsules (Amoxicillin)
250 mg (90): $17.99
500 mg (30): $13.99

Capsules (Amoxil)
500 mg (30): $15.99

Chewable (Amoxicillin)
125 mg (21): $11.99
250 mg (30): $13.99

Chewable (Amoxil)
400 mg (20): $13.99

Suspension (reconstituted) (Amoxicillin)
250 mg/5 mL (150): $14.00
400 mg/5 mL (100): $16.99

Suspension (reconstituted) (Amoxil)
50 mg/mL (30): $8.99
200 mg/5 mL (100): $11.99
250 mg/5 mL (100): $8.99
250 mg/5 mL (150): $8.99
400 mg/5 mL (50): $8.99
400 mg/5 mL (75): $9.99
400 mg/5 mL (100): $11.99

Suspension (reconstituted) (Trimox)
125 mg/5 mL (100): $11.99
250 mg/5 mL (80): $11.99

Tablet, 24-hour (Moxatag)
775 mg (30): $249.98

Tablets (Amoxicillin)
500 mg (100): $49.99
875 mg (30): $26.99

Tablets (Amoxil)
500 mg (21): $12.99
875 mg (21): $27.99

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

CANADIAN BRAND NAMES — Apo-Amoxi®; Gen-Amoxicillin; Lin-Amox; Mylan-Amoxicillin; Novamoxin®; Nu-Amoxi; PHL-Amoxicillin; PMS-Amoxicillin

INTERNATIONAL BRAND NAMES — Acilina (PY); Acimox (MX); Adbiotin (CO); Alfamox (IT); Almodan (GB); Almorsan (AR); Alphamox (AU); Amagesen Solutab (DE); Amicil (MX); Amimox (SE); Amobay (MX); Amoclave (ES); Amoclen (CZ); Amodex (FR); Amoflux (BR); Amohexal (AU); Amolin (JP, TW); Amosine (ID); Amotaks (PL); Amox (AE, BH, CY, EG, IL, IQ, IR, IT, JO, KW, LB, LY, OM, QA, SA, SY, YE); Amoxa (HK); Amoxal (VE); Amoxapen (BB, BM, BS, BZ, GY, JM, NL, SG, SR, TT); Amoxcil (CL); Amoxcillin (TH); Amoxcin (TW); Amoxi (IL); Amoxi TO (TH); Amoxi-basan (DE); Amoxicap (PK); Amoxicilina (CO, EC); Amoxicilline (PL); Amoxiclin (PE); Amoxico (PH); Amoxidal (AR, UY); Amoxidin (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); Amoxifur (MX); Amoxihexal (DE); Amoxil (AE, AU, BB, BF, BH, BJ, BM, BR, BS, BZ, CI, CY, EG, ET, GB, GH, GM, GN, GR, GY, ID, IE, IL, IQ, IR, JM, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, MX, NE, NG, NL, NZ, OM, PE, PL, QA, SA, SC, SD, SL, SN, SR, SY, TN, TT, TZ, UG, YE, ZA, ZM, ZW); Amoxil Duo (AU); Amoxillin (IL, IT); Amoxin (FI); Amoxinova (MX); Amoxipen (IT); Amoxipenil (CN); Amoxisol (MX); Amoxivan (IN); Amoxivet (MX); Amoxsan (ID); Amoxsan Forte (ID); Amoxy-diolan (DE); Amoxycillin (PL); Amoxypen (DE, PE); Apo-Amoxi (MY, PL); Aroxin (SG); Azillin (CH); Bacihexal (PH); Bactamox (VE); Bactox (EE); Bactox Ge (FR); Baymox (HN); Beamoxy (MY); Bimxan (MX); Biotamoxal (AR); Bristamox (EC, FR); Bufamoxy (ID); Cilamox (AU, PH); Clamoxyl (AT, AU, BB, BE, BM, BS, BZ, CH, FR, GY, JM, JP, NL, PE, PT, SR, TT); Dimopen (MX); Duomox (BG, HN, PL); Dymoxin (TH); Efpinex (JP); Ethimox (ID); Farconcil (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Fisamox (AU); Flemoxin (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Flubiotic (ES); Foxolin (KP); Fullcilina (AR); Gexcil (PH); Gimalxina (MX); Gomcillin (KP); Grinsul (AR); Grunamox (EC, PL); Hiconcil (BE, FR, ID, NL, PL); Hidramox (MX); Hipen (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); Ibiamox (AE, AU, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, TH, YE); Ikamoxil (ID); Imacillin (DK, NO, SE); Imadrax (DK); Imaxilin (CO); Isimoxin (IT); Izoltil (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); Jutamox (DE); Lamoxy (IN); Magnimox (PE); Manmox (TH); Maxamox (AU, NZ); Maxcil (ZA); Meixil (TH); Milamox-BIG (TH); Mopen (IT); Mox (IN); Moxacin (AU, NZ); Moxarin (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Moxilen (BF, BJ, CI, ET, GH, GM, GN, HK, KE, LR, MA, ML, MR, MU, MW, MY, NE, NG, SC, SD, SG, SL, SN, TN, TW, TZ, UG, ZA, ZM, ZW); Moxitab (TH); Moxtid (ID); Moxylin (EC); Moxypen (IL, ZA); Moxyvit (IL); Novabritine (BE); Novamox (PH, PL); Novax (ID); Novoxil (BR); Ospamox (AE, AT, BG, BH, CY, DE, EG, HK, ID, IL, IQ, IR, JO, KW, LB, LY, NZ, OM, PE, PL, PT, QA, SA, SY, UY, YE); Pamocil (IT); Pamoxicillin (TW); Pamoxin (KP); Pasetocin (JP); Penamox (MX, NZ, PE); Penbiosyn (PH); Piramox (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); Polymox (MX); Pondnoxcill (TH); Rancil (TH); Ranmoxy (AU, ZA); Ranoxyl (MY, TH); Robamox (ID); Sawacillin (JP); Sawamezin (JP); Servamox (TW); Setmoxil (HK); Shamoxil (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Sia-mox (TH); Simoxil (IT); Solciclina (MX); Solpenox (ID); Sterimox (PH); Supercillin (TW); Teramoxyl (PH); Trifamox (AR, PY); Trimox (TH); Vastamox (PH); Velamox (PE); Widecillin (ID); Winpen (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); Xalyn-Or (MX); Xazexy (PH); Yusimox (ID); Zamoxil (MY); Zerrsox (PH); Zimox (IT)

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: Rapid and nearly complete; food does not interfere
Extended-release tablet: Rate of absorption is slower compared to immediate-release formulations; food decreases the rate but not extent of absorption

Distribution: Widely to most body fluids and bone; poor penetration into cells, eyes, and across normal meninges
Pleural fluids, lungs, and peritoneal fluid; high urine concentrations are attained; also into synovial fluid, liver, prostate, muscle, and gallbladder; penetrates into middle ear effusions, maxillary sinus secretions, tonsils, sputum, and bronchial secretions
CSF:blood level ratio: Normal meninges: <1%; Inflamed meninges: 8% to 90%

Protein binding: 17% to 20%

Metabolism: Partially hepatic

Half-life elimination:
Neonates, full-term: 3.7 hours
Infants and Children: 1-2 hours
Adults: Normal renal function: 0.7-1.4 hours
Clcr <10 mL/minute: 7-21 hours

Time to peak: Capsule: 2 hours; Extended-release tablet: 3.1 hours; Suspension: 1 hour

Excretion: Urine (60% as unchanged drug); lower in neonatesNote: Extended-release tablets: In healthy volunteers, serum drug concentrations were below 0.25 mcg/mL and undetectable at 16 hours following dosing.

PATIENT INFORMATION — Take entire course of medication. Report diarrhea promptly. females should report symptoms of vaginitis. Pediatric drops may be placed on child's tongue or added to formula, milk, etc.

(For additional information see "Amoxicillin: Patient drug information")

PRODUCT AVAILABILITY
Moxatag™ : FDA approved January 2009; availability anticipated in March 2009

Moxatag™ is an extended-release tablet of amoxicillin intended for once-daily administration

Amoxapine

Amobarbital

U.S. BRAND NAMES — Amytal®

PHARMACOLOGIC CATEGORY
Barbiturate

DOSING: ADULTS
Hypnotic: I.M., I.V.: 65-200 mg at bedtime (maximum single dose: 1000 mg)

Sedative: I.M., I.V.: 30-50 mg 2-3 times/day (maximum single dose: 1000 mg)

"Amytal® interview" (unlabeled use): I.V.: 50-100 mg/minute for total dose of 200-1000 mg or until patient experiences drowsiness, impaired attention, slurred speech, or nystagmus

Wada test (unlabeled use): Intra-arterial: 100 mg over 4-5 seconds via percutaneous transfemoral catheter

DOSING: PEDIATRIC

(For additional information see "Amobarbital: Pediatric drug information")
Sedative: I.M., I.V.: 6-12 years: Manufacturer's dosing range: 65-500 mg

Hypnotic (unlabeled use): I.M.: 2-3 mg/kg (maximum: 500 mg)

DOSING: ELDERLY — Refer to adult dosing.

DOSING: RENAL IMPAIRMENT — Dosing should be reduced; specific recommendations not available.

DOSING: HEPATIC IMPAIRMENT — Dosing should be reduced; specific recommendations not available.

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

Injection, powder for reconstitution, as sodium:
Amytal®: 500 mg

DOSAGE FORMS: CONCISE
Injection, powder for reconstitution:
Amytal®: 500 mg

GENERIC EQUIVALENT AVAILABLE — No

ADMINISTRATION
I.M.: Administer deeply into a large muscle. Do not use more than 5 mL at any single site (may cause tissue damage). I.M. dosages should not exceed 500 mg. Use 20% solution to facilitate larger doses.

I.V.: Use only when I.M. administration is not feasible. Administer by slow I.V. injection (maximum: 50 mg/minute in adults).

COMPATIBILITY — Stable in D5LR, D5NS, D5W, D10W, D20W, LR, NS.

Compatibility when admixed: Compatible: Amikacin, aminophylline, sodium bicarbonate. Incompatible: Cefazolin, cimetidine, clindamycin, diphenhydramine, droperidol, hydroxyzine, insulin (regular), levorphanol, meperidine, morphine, norepinephrine, pancuronium, pentazocine, penicillin G potassium, procaine, streptomycin, vancomycin. Variable (consult detailed reference): Atracurium, dimenhydrinate, hydrocortisone sodium succinate, isoproterenol, metaraminol, methyldopate, norepinephrine, succinylcholine.

USE — Hypnotic in short-term treatment of insomnia; reduce anxiety and provide sedation preoperatively

USE - UNLABELED / INVESTIGATIONAL — Therapeutic or diagnostic "Amytal® Interviewing"; Wada test

ADVERSE REACTIONS SIGNIFICANT — Frequency not defined and is reported as barbiturate use (not specifically amobarbital).

Cardiovascular: Bradycardia, hypotension, syncope

Central nervous system: Agitation, anxiety, ataxia, confusion, CNS depression, dizziness, fever, hallucinations, headache, insomnia, nightmares, nervousness, psychiatric disturbances, somnolence, thinking abnormal

Gastrointestinal: Constipation, nausea, vomiting

Hematologic: Megaloblastic anemia (following chronic phenobarbital use)

Hepatic: Liver damage

Local: Injection site reaction

Neuromuscular & skeletal: Hyperkinesia

Respiratory: Apnea, atelectasis (postoperative), hypoventilation

Miscellaneous: Hypersensitivity reaction (including angioedema, rash, and exfoliative dermatitis)

CONTRAINDICATIONS — Hypersensitivity to barbiturates or any component of the formulation; marked hepatic impairment; dyspnea or airway obstruction; porphyria

WARNINGS / PRECAUTIONS
Concerns related to adverse effects: CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Hypersensitivity reactions: Postmarketing studies have indicated that the use of hypnotic/sedative agents for sleep has been associated with hypersensitivity reactions including anaphylaxis as well as angioedema. Paradoxical responses: May cause paradoxical responses, including agitation and hyperactivity, particularly in acute pain, chronic pain and pediatric patients. Sleep-related activities: An increased risk for hazardous sleep-related activities such as sleep-driving; cooking and eating food, and making phone calls while asleep has been noted with sedative-hypnotic medications. Discontinue treatment in patients who report a sleep-driving episode.

Disease-related concerns: Cardiovascular disease: Use with caution in patients with cardiovascular disease; may cause hypotension. Depression: Use with caution in patients with depression or suicidal tendencies. Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use. Hepatic impairment: Use with caution in patients with hepatic impairment, decreased dosage may be needed; contraindicated in severe impairment. Insomnia: Appropriate use: When used as a hypnotic for the treatment of insomnia, effectiveness is limited to ≤ 2 weeks. Renal impairment: Use with caution in patients with renal impairment; decreased dosage may be needed.

Concurrent drug therapy issues: Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.

Special populations: Elderly: Use with caution in the elderly; not recommended for use. Closely monitor elderly or debilitated patients for impaired cognitive or motor performance. Pediatrics: Safety and efficacy have not been established in children <6 years of age; use with caution in children ≥ 6 years of age.

Dosage form specific issues: Alkaline solution: Solution for injection is highly alkaline and extravasation may cause local tissue damage.

Other warnings/precautions: Rapid administration: Rapid I.V. administration may cause respiratory depression, apnea, and hypotension. Withdrawal: Gradual withdrawal is recommended if used over extended periods of time.

RESTRICTIONS — C-II

METABOLISM / TRANSPORT EFFECTS — Induces CYP2A6 (strong)

DRUG INTERACTIONS
Acetaminophen: Barbiturates may increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

Beta-Blockers: Barbiturates may decrease the serum concentration of Beta-Blockers. Exceptions: Atenolol; Levobunolol; Metipranolol; Nadolol. Risk C: Monitor therapy

Calcium Channel Blockers: Barbiturates may increase the metabolism of Calcium Channel Blockers. Exceptions: Clevidipine. Risk D: Consider therapy modification

Chloramphenicol: May decrease the metabolism of Barbiturates. Barbiturates may increase the metabolism of Chloramphenicol. Risk D: Consider therapy modification

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

Contraceptive (Progestins): Barbiturates may diminish the therapeutic effect of Contraceptive (Progestins). Contraceptive failure is possible. Risk D: Consider therapy modification

Corticosteroids (Systemic): Barbiturates may increase the metabolism of Corticosteroids (Systemic). Risk C: Monitor therapy

CycloSPORINE: Barbiturates may increase the metabolism of CycloSPORINE. Risk D: Consider therapy modification

CYP2A6 Substrates: CYP2A6 Inducers (Strong) may increase the metabolism of CYP2A6 Substrates. Risk C: Monitor therapy

Disopyramide: Barbiturates may increase the metabolism of Disopyramide. Risk D: Consider therapy modification

Doxycycline: Barbiturates may decrease the serum concentration of Doxycycline. Risk D: Consider therapy modification

Etoposide: Barbiturates may increase the metabolism of Etoposide. Risk C: Monitor therapy

Etoposide Phosphate: Barbiturates may decrease the serum concentration of Etoposide Phosphate. Barbiturates may increase the metabolism, via CYP isoenzymes, of etoposide phosphate. Risk C: Monitor therapy

Felbamate: May increase the serum concentration of Barbiturates. Risk C: Monitor therapy

Griseofulvin: Barbiturates may decrease the absorption of Griseofulvin. Risk D: Consider therapy modification

LamoTRIgine: Barbiturates may increase the metabolism of LamoTRIgine. Risk D: Consider therapy modification

Meperidine: Barbiturates may enhance the CNS depressant effect of Meperidine. Risk C: Monitor therapy

Methadone: Barbiturates may increase the metabolism of Methadone. Risk D: Consider therapy modification

Oral Contraceptive (Estrogens): Barbiturates may diminish the therapeutic effect of Oral Contraceptive (Estrogens). Contraceptive failure is possible. Risk D: Consider therapy modification

Primidone: May enhance the adverse/toxic effect of Barbiturates. Primidone is converted to phenobarbital, and thus becomes additive with existing barbiturate therapy. Risk C: Monitor therapy

Propafenone: Barbiturates may increase the metabolism of Propafenone. Risk D: Consider therapy modification

Pyridoxine: May increase the metabolism of Barbiturates. Apparent in high pyridoxine doses (eg, 200 mg/day) Risk C: Monitor therapy

QuiNIDine: Barbiturates may increase the metabolism of QuiNIDine. Risk D: Consider therapy modification

Rifamycin Derivatives: May increase the metabolism of Barbiturates. Risk C: Monitor therapy

Teniposide: Barbiturates may increase the metabolism of Teniposide. Risk C: Monitor therapy

Theophylline Derivatives: Barbiturates may increase the metabolism of Theophylline Derivatives. Exceptions: Dyphylline. Risk C: Monitor therapy

Thiazide Diuretics: Barbiturates may enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy

Tricyclic Antidepressants: Barbiturates may increase the metabolism of Tricyclic Antidepressants. Risk D: Consider therapy modification

Valproic Acid: May decrease the metabolism of Barbiturates. Barbiturates may decrease the serum concentration of Valproic Acid. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Barbiturates may increase the metabolism of Vitamin K Antagonists. Risk D: Consider therapy modification

Voriconazole: Barbiturates may decrease the serum concentration of Voriconazole. Risk X: Avoid combination

ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Avoid ethanol (may increase CNS depression).

PREGNANCY RISK FACTOR — D (show table)

PREGNANCY IMPLICATIONS — Barbiturates cross the placenta and distribute in fetal tissue. Teratogenic effects have been reported with 1st trimester exposure. Exposure during the 3rd trimester may lead to symptoms of acute withdrawal following delivery; symptoms may be delayed up to 14 days.

LACTATION — Excretion in breast milk unknown/use caution

BREAST-FEEDING CONSIDERATIONS — Small amounts of barbiturates are excreted in breast milk; information specific for amobarbital is not available.

MONITORING PARAMETERS — Vital signs should be monitored during injection and for several hours after administration.

REFERENCE RANGE
Therapeutic: 1-5 mcg/mL (SI: 4-22 µmol/L)

Toxic: >10 mcg/mL (SI: >44 µmol/L)

Lethal: >50 mcg/mL

CANADIAN BRAND NAMES — Amytal®

INTERNATIONAL BRAND NAMES — Amybital (TW); Amycal (NO); Amytal Sodium (AU); Barbamyl (IL); Dorlotin (HU); Dorlotyn (HU); Eunoctal (FR); Isoamitil Sedante (ES); Isomytal (JP); Neur-Amyl (AU); Placidel (ES); Sodium Amytal (GB); Transital (ES)

MECHANISM OF ACTION — Interferes with transmission of impulses from the thalamus to the cortex of the brain resulting in an imbalance in central inhibitory and facilitatory mechanisms

PHARMACODYNAMICS / KINETICS
Onset of action: I.V.: Within 5 minutes

Distribution: Readily crosses placenta; small amounts enter breast milk

Metabolism: Primarily hepatic via microsomal enzymes

Half-life elimination: 15-40 hours (mean: 25 hours)

Excretion: Urine, feces

Amobarbital

Sunday, August 1, 2010

Amlodipine, valsartan, and hydrochlorothiazide

U.S. BRAND NAMES — Exforge HCT®

PHARMACOLOGIC CATEGORY
Angiotensin II Receptor Blocker
Calcium Channel Blocker
Calcium Channel Blocker, Dihydropyridine
Diuretic, Thiazide

DOSING: ADULTS — Note: Not for initial therapy. Dose is individualized; combination product may be substituted for individual components in patients currently maintained on all three agents separately or in patients not adequately controlled with any two of the following antihypertensive classes: calcium channel blockers, angiotensin II receptor blockers, and diuretics.

Hypertension: Oral: Add-on/switch/replacement therapy: Amlodipine 5-10 mg and Valsartan 160-320 mg and hydrochlorothiazide 12.5-25 mg once daily; dose may be titrated after 2 weeks of therapy. Maximum recommended daily dose: Amlodipine 10 mg/valsartan 320 mg/hydrochlorothiazide 25 mg

DOSING: ELDERLY — Refer to adult dosing.

DOSING: RENAL IMPAIRMENT
Clcr >30 mL/minute: No adjustment needed.

Clcr ≤ 30 mL/minute: Use of combination not recommended; contraindicated in patients with anuria.

DOSING: HEPATIC IMPAIRMENT — Use of combination is not recommended in severe hepatic impairment. Use with caution in mild-to-moderate hepatic impairment; monitor for worsening of hepatic or renal function and adverse reactions.

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

Tablet, oral:
Exforge HCT®:
Amlodipine 5 mg, valsartan 160 mg, and hydrochlorothiazide 12.5 mg
Amlodipine 5 mg, valsartan 160 mg, and hydrochlorothiazide 25 mg
Amlodipine 10 mg, valsartan 160 mg, and hydrochlorothiazide 12.5 mg
Amlodipine 10 mg, valsartan 160 mg, and hydrochlorothiazide 25 mg
Amlodipine 10 mg, valsartan 320 mg, and hydrochlorothiazide 25 mg

DOSAGE FORMS: CONCISE
Tablet, oral:
Exforge HCT®: Amlodipine 5 mg, valsartan 160 mg, and hydrochlorothiazide 12.5 mg; Amlodipine 5 mg, valsartan 160 mg, and hydrochlorothiazide 25 mg; Amlodipine 10 mg, valsartan 160 mg, and hydrochlorothiazide 12.5 mg; Amlodipine 10 mg, valsartan 160 mg, and hydrochlorothiazide 25 mg; Amlodipine 10 mg, valsartan 320 mg, and hydrochlorothiazide 25 mg

GENERIC EQUIVALENT AVAILABLE — No

ADMINISTRATION — Administer with or without food.

USE — Treatment of hypertension (not for initial therapy)

ADVERSE REACTIONS SIGNIFICANT — Reactions/percentages reported with combination product; also refer to individual agents.

>10%: Renal: BUN increased (30%)

2% to 10%:
Cardiovascular: Edema (7%)
Central nervous system: Dizziness (8%), headache (5%), fatigue (2%)
Endocrine & metabolic: Hypokalemia (7%), hyperkalemia (4%)
Gastrointestinal: Dyspepsia (2%), nausea (2%)
Neuromuscular & Skeletal: Back pain (2%), muscle spasms (2%)
Renal: Serum creatinine increased (2%)
Respiratory: Nasopharyngitis (2%)

<2% (Limited to important or life-threatening): Abdominal pain, anorexia, anxiety, appetite increased, arthralgia, asthenia, attention disturbed, bronchitis, chest pain (noncardiac), chills, constipation, cough, CPK increased, dehydration, depression, diabetes mellitus, diarrhea, dyspnea, dysuria, erectile dysfunction, extremity pain, gastritis, hyperhidrosis, hyperlipidemia, hyponatremia, hypotension, influenza, insomnia, joint swelling, lethargy, liver function tests increased, malaise, musculoskeletal pain, musculoskeletal stiffness, nasal congestion, night sweats, orthostatic hypotension, osteoarthritis, paresthesia, pharyngolaryngeal pain, pharyngitis, pollakiuria, postural dizziness, pruritus, rash, respiratory tract infection, rhinitis, somnolence, syncope, tachycardia, taste abnormal, tendonitis, tinnitus, tremor, upper respiratory tract infection, uric acid increased, urinary tract infection, vertigo, viral gastroenteritis, viral infection, vision blurred, vomiting, weakness, weight loss, xerostomia

CONTRAINDICATIONS — Hypersensitivity to sulfonamide-derived drugs; anuria

WARNINGS / PRECAUTIONS
Boxed warnings: Pregnancy: See "Special populations" below.

Concerns related to adverse effects: Angina/MI: Increased angina and/or MI has occurred with initiation or dosage titration of dihydropyridine calcium channel blockers; reflex tachycardia may occur resulting in angina and/or MI in patients with obstructive coronary disease especially in the absence of concurrent beta-blockade. Electrolyte disturbances: Hyperkalemia may occur with angiotensin II receptor antagonists; risk factors include renal dysfunction, diabetes mellitus, and concomitant use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salts. Use cautiously, if at all, with these agents and monitor potassium closely. Thiazide diuretics may cause hypokalemia, hypochloremic alkalosis, hypomagnesemia, and hyponatremia. Hypotension/syncope: Symptomatic hypotension with or without syncope can rarely occur; use caution during initiation, particularly in patients with heart failure, or in post-MI patients or those undergoing surgery or dialysis. Peripheral edema: The most common side effect of amlodipine is peripheral edema; occurs within 2-3 weeks of starting therapy. Photosensitivity: Photosensitization may occur. Renal function deterioration: May be associated with deterioration of renal function and/or increases in serum creatinine, particularly in patients with low renal blood flow (eg, renal artery stenosis, heart failure) whose glomerular filtration rate (GFR) is dependent on efferent arteriolar vasoconstriction by angiotensin II; deterioration may result in oliguria, acute renal failure, and progressive azotemia. Small increases in serum creatinine may occur following initiation; consider discontinuation only in patients with progressive and/or significant deterioration in renal function. Sulfa allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is specifically contraindicated in product labeling. Discontinue if signs of hypersensitivity are noted.

Disease-related concerns: Aortic/mitral stenosis: Do not initiate in patients with significant aortic/mitral stenosis. Asthma: Hypersensitivity to hydrochlorothiazide may be observed more frequently in patients with bronchial asthma. Diabetes: Use hydrochlorothiazide with caution in patients with prediabetes or diabetes mellitus; may see a change in glucose control. Gout: In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated by hydrochlorothiazide. Heart failure: Use of combination product in heart failure has not been studied; use with caution; may need to adjust dose, and/or concurrent diuretic therapy. Hepatic impairment: Avoid use in patients with severe hepatic impairment. In patients with mild-to-moderate hepatic impairment, monitor for worsening of hepatic or renal function, fluid status, electrolytes, and adverse reactions. In cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Hypercholesterolemia: Use with caution in patients with moderate or high cholesterol concentrations; increased cholesterol and triglyceride levels have been reported with thiazides. Hypertrophic cardiomyopathy (HCM) with outflow tract obstruction: Do not initiate in patients with HCM and outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition. Hypovolemia: Avoid use or use a smaller dose in patients who are volume depleted; correct depletion first. Renal artery stenosis: Use valsartan with caution in patients with unstented unilateral/bilateral renal artery stenosis. When unstented bilateral renal artery stenosis is present, use is generally avoided due to the elevated risk of deterioration in renal function unless possible benefits outweigh risks. Renal impairment: Use with caution with pre-existing renal insufficiency. Avoid use in severe renal impairment (Clcr ≤ 30 mL/minute). May precipitate azotemia; discontinue or consider withholding if renal impairment occurs. Contraindicated in patients with anuria. Systemic lupus erythematosus (SLE): Hydrochlorothiazide can cause SLE exacerbation or activation.

Special populations: Pediatrics: Canadian labeling: Use is not approved in patients <18 years of age. Pregnancy: [U.S. Boxed Warning]: Based on human data, drugs that act on the angiotensin system can cause injury and death to the developing fetus when used in the second and third trimesters. Angiotensin receptor blockers should be discontinued as soon as possible once pregnancy is detected.

DRUG INTERACTIONS
ACE Inhibitors: Thiazide Diuretics may enhance the hypotensive effect of ACE Inhibitors. Specifically, postural hypotension which can accompany ACE Inhibitor initiation. Thiazide Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. Risk C: Monitor therapy

ACE Inhibitors: Angiotensin II Receptor Blockers may enhance the adverse/toxic effect of ACE Inhibitors. Risk C: Monitor therapy

Alcohol (Ethyl): May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy

Allopurinol: Thiazide Diuretics may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy

Alpha1-Blockers: May enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy

Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification

Analgesics (Opioid): May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy

Antidiabetic Agents: Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of Calcium Channel Blockers. Risk D: Consider therapy modification

Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy

Barbiturates: May increase the metabolism of Calcium Channel Blockers. Risk D: Consider therapy modification

Barbiturates: May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy

Bile Acid Sequestrants: May decrease the absorption of Thiazide Diuretics. The diuretic response is likewise decreased. Risk D: Consider therapy modification

Calcitriol: Thiazide Diuretics may enhance the hypercalcemic effect of Calcitriol. Risk C: Monitor therapy

Calcium Channel Blockers (Nondihydropyridine): May enhance the hypotensive effect of Calcium Channel Blockers (Dihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor therapy

Calcium Salts: Thiazide Diuretics may decrease the excretion of Calcium Salts. Continued concomitant use can also result in metabolic alkalosis. Risk C: Monitor therapy

Calcium Salts: May diminish the therapeutic effect of Calcium Channel Blockers. Risk C: Monitor therapy

CarBAMazepine: May increase the metabolism of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor therapy

Clopidogrel: Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel. Risk C: Monitor therapy

Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy

Corticosteroids (Systemic): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy

CycloSPORINE: May decrease the metabolism of Calcium Channel Blockers (Dihydropyridine). Nicardipine may likewise inhibit the metabolism of cyclosporine. Cyclosporine dosage adjustments might be needed. Risk C: Monitor therapy

CYP1A2 Substrates: CYP1A2 Inhibitors (Moderate) may decrease the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification

Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy

Dofetilide: Thiazide Diuretics may enhance the QTc-prolonging effect of Dofetilide. Thiazide Diuretics may increase the serum concentration of Dofetilide. Risk X: Avoid combination

Eltrombopag: May increase the serum concentration of OATP1B1/SLCO1B1 Substrates. Management: According to eltrombopag prescribing information, consideration of a preventative dose reduction may be warranted. Risk D: Consider therapy modification

Eplerenone: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy

Fluconazole: May decrease the metabolism of Calcium Channel Blockers. Risk C: Monitor therapy

Grapefruit Juice: May increase the serum concentration of AmLODIPine. Risk C: Monitor therapy

Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy

Lithium: Thiazide Diuretics may decrease the excretion of Lithium. Risk D: Consider therapy modification

Lithium: Angiotensin II Receptor Blockers may increase the serum concentration of Lithium. Management: Lithium dosage reductions will likely be needed following the addition of an angiotensin II receptor antagonist. Risk D: Consider therapy modification

Macrolide Antibiotics: May decrease the metabolism of Calcium Channel Blockers. Exceptions: Azithromycin; Dirithromycin [Off Market]; Spiramycin. Risk D: Consider therapy modification

Magnesium Salts: Calcium Channel Blockers may enhance the adverse/toxic effect of Magnesium Salts. Magnesium Salts may enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy

MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

Nafcillin: May increase the metabolism of Calcium Channel Blockers. Risk D: Consider therapy modification

Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy

Nitroprusside: Calcium Channel Blockers may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May diminish the therapeutic effect of Thiazide Diuretics. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May diminish the therapeutic effect of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function. Risk C: Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy

Phenytoin: Calcium Channel Blockers may decrease the metabolism of Phenytoin. Risk D: Consider therapy modification

Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

Potassium Salts: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy

Potassium-Sparing Diuretics: Angiotensin II Receptor Blockers may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy

Protease Inhibitors: May decrease the metabolism of Calcium Channel Blockers (Dihydropyridine). Risk D: Consider therapy modification

QuiNIDine: Calcium Channel Blockers (Dihydropyridine) may decrease the serum concentration of QuiNIDine. Risk C: Monitor therapy

Quinupristin: May decrease the metabolism of Calcium Channel Blockers. Risk C: Monitor therapy

Rifamycin Derivatives: May increase the metabolism of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers. Risk D: Consider therapy modification

RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification

Tacrolimus: Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of Tacrolimus. Risk C: Monitor therapy

Tolvaptan: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy

Trimethoprim: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy

Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

ETHANOL / NUTRITION / HERB INTERACTIONS — Herb/Nutraceutical: St John's wort may decrease amlodipine levels. Avoid bayberry, blue cohosh, cayenne, ephedra, ginger, ginseng (American), kola, licorice (may diminish antihypertensive effect). Avoid black cohosh, California poppy, coleus, golden seal, hawthorn, mistletoe, periwinkle, quinine, shepherd's purse (may enhance hypotensive effect).

PREGNANCY RISK FACTOR — D (show table)

PREGNANCY IMPLICATIONS — See individual agents.

LACTATION — Excretion in breast milk unknown/not recommended

BREAST-FEEDING CONSIDERATIONS — Excretion of amlodipine and valsartan into breast milk is not known and use during nursing is not recommended; hydrochlorothiazide is excreted in breast milk

DIETARY CONSIDERATIONS — Avoid salt substitutes which contain potassium. May be taken with or without food.

MONITORING PARAMETERS — Blood pressure, orthostasis; baseline and periodic electrolyte panels, renal function; peripheral edema

MECHANISM OF ACTION
Amlodipine inhibits calcium ion from entering the "slow channels" or select voltage-sensitive areas of vascular smooth muscle and myocardium during depolarization, producing a relaxation of coronary vascular smooth muscle and coronary vasodilation; increases myocardial oxygen delivery in patients with vasospastic angina.

Valsartan produces direct antagonism of the angiotensin II (AT2) receptors, unlike the ACE inhibitors. It displaces angiotensin II from the AT1 receptor and produces its blood pressure-lowering effects by antagonizing AT1-induced vasoconstriction, aldosterone release, catecholamine release, arginine vasopressin release, water intake, and hypertrophic responses. This action results in more efficient blockade of the cardiovascular effects of angiotensin II and fewer side effects than the ACE inhibitors.

Hydrochlorothiazide inhibits sodium reabsorption in the distal tubules causing increased excretion of sodium and water as well as potassium and hydrogen ions.

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Monday, August 2, 2010

Amoxapine

Amoxicillin

Amoxapine

Amobarbital

Amobarbital

Sunday, August 1, 2010

Amlodipine, valsartan, and hydrochlorothiazide