Children:

Pharyngitis/tonsillitis, acute maxillary sinusitis, uncomplicated skin/skin structure infections, and mycobacterial infections due to the above organisms

Acute otitis media (H. influenzae, M. catarrhalis, or S. pneumoniae)

Prevention of disseminated mycobacterial infections due to MAC disease in patients with advanced HIV infection

Adults:

Pharyngitis/tonsillitis due to susceptible S. pyogenes

Acute maxillary sinusitis and acute exacerbation of chronic bronchitis due to susceptible H. influenzae, M. catarrhalis, or S. pneumoniae

Pneumonia due to susceptible H. influenzae, Mycoplasma pneumoniae, S. pneumoniae, or Chlamydia pneumoniae (TWAR);

Uncomplicated skin/skin structure infections due to susceptible S. aureus, S. pyogenes

Disseminated mycobacterial infections due to M. avium or M. intracellulare

Prevention of disseminated mycobacterial infections due to M. avium complex (MAC) disease (eg, patients with advanced HIV infection)

Duodenal ulcer disease due to H. pylori in regimens with other drugs including amoxicillin and lansoprazole or omeprazole, ranitidine bismuth citrate, bismuth subsalicylate, tetracycline, and/or an H2 antagonist

Alternate antibiotic for prophylaxis of bacterial endocarditis in patients who are allergic to penicillin and undergoing surgical or dental procedures

1% to 10%:

Central nervous system: Headache (adults and children 2%)

Dermatologic: Rash (children 3%)

Gastrointestinal: Diarrhea (adults 6%, children 6%); vomiting (children 6%); nausea (adults 3%); abnormal taste (adults 7%); heartburn (adults 2%); abdominal pain (adults 2%, children 3%)

Hepatic: Prothrombin time increased (1%)

Renal: BUN increased (4%)

<1%, postmarketing, and/or case reports (limited to important or life-threatening); Clostridium difficile colitis, alkaline phosphatase increased, anaphylaxis, anorexia, anxiety, AST increased, bilirubin increased, dizziness, dyspnea, glossitis, hallucinations, hearing loss (reversible), hepatic failure, hepatitis, hypoglycemia, jaundice, leukopenia, manic behavior, neuromuscular blockade (case reports), neutropenia, pancreatitis, psychosis, QT prolongation, seizure, serum creatinine increased, Stevens-Johnson syndrome, thrombocytopenia, tongue discoloration, tooth discoloration, torsade de pointes, toxic epidermal necrolysis, tremor, ventricular tachycardia, vertigo, vomiting

Alfentanil (and possibly other narcotic analgesics): Serum levels may be increased by clarithromycin; monitor for increased effect.

Antipsychotic agents (particularly mesoridazine and thioridazine): Risk of QTc prolongation and malignant arrhythmias may be increased.

Benzodiazepines (those metabolized by CYP3A4, including alprazolam, midazolam, triazolam): Serum levels may be increased by clarithromycin; somnolence and confusion have been reported.

Bromocriptine: Serum levels may be increased by clarithromycin; monitor for increased effect.

Buspirone: Serum levels may be increased by clarithromycin; monitor.

Calcium channel blockers (felodipine, verapamil, and potentially others metabolized by CYP3A4): Serum levels may be increased by clarithromycin; monitor.

Carbamazepine: Serum levels may be increased by clarithromycin; monitor.

Cilostazol: Serum levels may be increased by clarithromycin; monitor.

Cisapride: Serum levels may be increased by clarithromycin; serious arrhythmias have occurred; concurrent use contraindicated.

Clindamycin (and lincomycin): Use with clarithromycin may result in pharmacologic antagonism; manufacturer recommends avoiding this combination.

Clozapine: Serum levels may be increased by clarithromycin; monitor.

Colchicine: serum levels/toxicity may be increased by clarithromycin; monitor.

Cyclosporine: Serum levels may be increased by clarithromycin; monitor serum levels.

CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of clarithromycin. Example inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins.

CYP3A4 inhibitors: May increase the levels/effects of clarithromycin. Example inhibitors include azole antifungals, ciprofloxacin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, and verapamil.

CYP3A4 substrates: Clarithromycin may increase the levels/effects of CYP3A4 substrates. Example substrates include benzodiazepines, calcium channel blockers, mirtazapine, nateglinide, nefazodone, tacrolimus, and venlafaxine. Selected benzodiazepines (midazolam and triazolam), cisapride, ergot alkaloids, selected HMG-CoA reductase inhibitors (lovastatin and simvastatin), and pimozide are generally contraindicated with strong CYP3A4 inhibitors.

Delavirdine: Serum levels may be increased by clarithromycin; monitor.

Digoxin: Serum levels may be increased by clarithromycin; digoxin toxicity and potentially fatal arrhythmias have been reported; monitor digoxin levels.

Disopyramide: Serum levels may be increased by clarithromycin; in addition, QTc prolongation and risk of malignant arrhythmia may be increased; avoid combination.

Ergot alkaloids: Concurrent use may lead to acute ergot toxicity (severe peripheral vasospasm and dysesthesia).

Fluconazole: Increases clarithromycin levels and AUC by ~25%

HMG-CoA reductase inhibitors (atorvastatin, lovastatin, and simvastatin); Clarithromycin may increase serum levels of "statins" metabolized by CYP3A4, increasing the risk of myopathy/rhabdomyolysis (does not include fluvastatin and pravastatin). Switch to pravastatin/fluvastatin or suspend treatment during course of clarithromycin therapy.

Loratadine: Serum levels may be increased by clarithromycin; monitor.

Methylprednisolone: Serum levels may be increased by clarithromycin; monitor.

Neuromuscular-blocking agents: May be potentiated by clarithromycin (case reports).

Phenytoin: Serum levels may be increased by clarithromycin; other evidence suggested phenytoin levels may be decreased in some patients; monitor.

Pimozide: Serum levels may be increased, leading to malignant arrhythmias; concomitant use is contraindicated.

Protease inhibitors (amprenavir, nelfinavir, and ritonavir): May increase serum levels of clarithromycin.

QTc-prolonging agents: Concomitant use may increase the risk of malignant arrhythmias.

Quinidine: Serum levels may be increased by clarithromycin; in addition, the risk of QTc prolongation and malignant arrhythmias may be increased during concurrent use.

Quinolone antibiotics (sparfloxacin, gatifloxacin, or moxifloxacin): Concurrent use may increase the risk of malignant arrhythmias.

Rifabutin: Serum levels may be increased by clarithromycin; monitor.

Sildenafil, tadalafil, vardenafil: Serum levels may be increased by clarithromycin. Do not exceed single sildenafil doses of 25 mg in 48 hours, a single tadalafil dose of 10 mg in 72 hours, or a single vardenafil dose of 2.5 mg in 24 hours.

Tacrolimus: Serum levels may be increased by clarithromycin; monitor serum concentration.

Theophylline: Serum levels may be increased by clarithromycin; monitor.

Valproic acid (and derivatives): Serum levels may be increased by clarithromycin; monitor.

Vinblastine (and vincristine): Serum levels may be increased by clarithromycin.

Warfarin: Effects may be potentiated; monitor INR closely and adjust warfarin dose as needed or choose another antibiotic

Zafirlukast: Serum levels may be decreased by clarithromycin; monitor.

Zidovudine: Peak levels (but not AUC) of zidovudine may be increased; other studies suggest levels may be decreased.

Zopiclone: Serum levels may be increased by clarithromycin; monitor.

Food: Delays absorption; total absorption remains unchanged.

Herb/Nutraceutical: St John's wort may decrease clarithromycin levels.

Absorption: Highly stable in presence of gastric acid (unlike erythromycin); food delays but does not affect extent of absorption

Distribution: Widely into most body tissues except CNS

Metabolism: Partially hepatic; converted to 14-OH clarithromycin (active metabolite)

Bioavailability: 50%

Half-life elimination: 5-7 hours

Time to peak: 2-4 hours

Excretion: Primarily urine

Clearance: Approximates normal GFR

Children 6 months: 15 mg/kg/day divided every 12 hours for 10 days

Mycobacterial infection (prevention and treatment): 7.5 mg/kg twice daily, up to 500 mg twice daily

Prophylaxis of bacterial endocarditis: 15 mg/kg 1 hour before procedure (maximum dose: 500 mg)

Adults:

Usual dose: 250-500 mg every 12 hours or 1000 mg (two 500 mg extended release tablets) once daily for for 7-14 days

Upper respiratory tract: 250-500 mg every 12 hours for 10-14 days

Pharyngitis/tonsillitis: 250 mg every 12 hours for 10 days

Acute maxillary sinusitis: 500 mg every 12 hours or 1000 mg (two 500 mg extended release tablets) once daily for 14 days

Lower respiratory tract: 250-500 mg every 12 hours for 7-14 days

Acute exacerbation of chronic bronchitis due to:

M. catarrhalis and S. pneumoniae: 250 mg every 12 hours or 1000 mg (two 500 mg extended release tablets) once daily for 7-14 days

H. influenzae: 500 mg every 12 hours for 7-14 days

Pneumonia due to:

C. pneumoniae, M. pneumoniae, and S. pneumoniae: 250 mg every 12 hours for 7-14 days or 1000 mg (two 500 mg extended release tablets) once daily for 7 days

H. influenzae: 250 mg every 12 hours for 7 days or 1000 mg (two 500 mg extended release tablets) once daily for 7 days

Mycobacterial infection (prevention and treatment): 500 mg twice daily (use with other antimycobacterial drugs, eg, ethambutol, clofazimine, or rifampin)

Prophylaxis of bacterial endocarditis: 500 mg 1 hour prior to procedure

Uncomplicated skin and skin structure: 250 mg every 12 hours for 7-14 days

Helicobacter pylori: Combination regimen with bismuth subsalicylate, tetracycline, clarithromycin, and an H2-receptor antagonist; or combination of omeprazole and clarithromycin; 250 mg twice daily to 500 mg 3 times/day

Dosing adjustment in renal impairment:

Clcr<30 mL/minute: Half the normal dose or double the dosing interval

In combination with ritonavir:

Clcr 30-60 mL/minute: Decrease clarithromycin dose by 50%

Clcr<30 mL/minute: Decrease clarithromycin dose by 75%

Dosing adjustment in hepatic impairment: No dosing adjustment is needed as long as renal function is normal

Elderly: Pharmacokinetics are similar to those in younger adults; may have age-related reductions in renal function; monitor and adjust dose if necessary

Biaxin® XL: Should be given with food. Do not crush or chew extended release tablet.

Granules for oral suspension (Biaxin®): 125 mg/5 mL (50 mL, 100 mL); 250 mg/5 mL (50 mL, 100 mL) [fruit punch flavor]

Tablet [film coated] (Biaxin®): 250 mg, 500 mg

Tablet, extended release [film coated] (Biaxin® XL): 500 mg

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