Dosing and uses of Biaxin, Biaxin XL (clarithromycin)
Adult dosage forms and strengths
oral suspension
- 125mg/5mL
- 250mg/5mL
tablet
- 250mg
- 500mg
tablet, extended release
- 500mg
Acute Exacerbation of Chronic Bronchitis
250-500 mg PO q12hr for 7-14 days
Extended release: 1000 mg PO once daily for 7 days
Acute Maxillary Sinusitis
500 mg PO q12hr for 14 days
Extended release: 1000 mg PO once daily for 14 days
Mycobacterial Infection
Prophylaxis and treatment
500 mg PO q12hr for 7-14 days
Use with antimycobacterial drugs such as rifampin and ethambutoL
Peptic Ulcer Disease
500 mg PO q8-12hr for 10-14 days
Administer as part of 2- or 3-drug combination regimen with bismuth subsalicylate, amoxicillin, H2 receptor antagonist, or proton pump inhibitor
Pharyngitis, Tonsillitis
250 mg PO q12hr for 10 days
Community-Acquired Pneumonia
250 mg PO q12hr for 7-14 days
Extended release: 1000 mg PO once daily for 7 days
Pertusis (Off-label)
500 mg PO twice daily for 7 days
Skin/Skin Structure Infection
250 mg PO q12hr for 7-14 days
Endocarditis
Prophylaxis
500 mg PO 30-60 minutes before surgical procedure
Crohn Disease (Orphan)
Treatment of pediatric Crohn disease in combination with rifabutin and clofazimine
Orphan indication sponsor
- RedHill Biopharma Ltd; 42 Givati St; Israel
Dosing Modifications
Renal impairment (CrCl <30 mL/min): Reduce normal dose by 50%
In combination with atazanavir: CrCl 30-60 mL/min decrese, dose by 50%; CrCl <30 mL/min, decrease dose by 75%
Dosing Considerations
Susceptible organisms
- Actinobacillus actinomycetemcomitans, Actinomyces israelii, Actinomyces naeslundii, Actinomyces odontolyticus, Afipia felis, Arachnia propionica, Bartonella henselae, Bartonella quintana, Chlamydia pneumoniae (TWAR agent), Bordetella pertussis, Borrelia recurrentis, Calymmatobacterium granulomatis, Campylobacter jejuni, Chlamydia spp, Haemophilus ducreyi, Haemophilus influenzae, Helicobacter pylori, Legionella pneumophila, Mycobacterium avium complex (MAC), Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium genavense, Mycobacterium gordonae, Mycobacterium kansasii, Mycobacterium leprae, Mycobacterium marinum, Mycobacterium scrofulaceum, Mycobacterium simiae, Mycobacterium szulgai, Mycobacterium ulcerans, Mycobacterium xenopi, Mycoplasma pneumoniae, Moraxella (Branhamella) catarrhalis, Staphylococcus aureus, Streptococcus (group C, G), Streptococcus agalactiae (group B), Streptococcus bovis (group D), Streptococcus intermedius group (Streptococcus anginosus, Streptococcus intermedius, Streptococcus constellatus), Streptococcus pneumoniae (penicillin sensitive; minimal inhibitory concentration [MIC] <0.1 mcg/mL), Streptococcus pyogenes (group A), viridans streptococci, Ureaplasma urealyticum
- H pylori (with lansoprazole and amoxicillin)
- First-line: A felis, B henselae, B quintana, B pertussis, C jejuni, C pneumoniae, H ducreyi, H pylori, Legionella spp, MAC, M chelonae, M fortuitum, M genavense, M gordonae, M marinum, M scrofulaceum, M simiae, M xenopi; no unanimity on others (eg, H influenzae)
Pediatric dosage forms and strengths
oral suspension
- 125mg/5mL
- 250mg/5mL
tablet
- 250mg
- 500mg
Extended-release tablets: Safety and efficacy not established in children
Community-Acquired Pneumonia, Sinusitis, Bronchitis, Skin Infections
15 mg/kg/day PO divided q12hr for 10 days
Mycobacterial Infection
Prophylaxis and treatment
7.5 mg/kg PO q12hr; individual dose not to exceed 500 mg
<20 months: Safety of clarithromycin for MAC not studied
Endocarditis
Prophylaxis
15 mg/kg PO 30-60 minutes before surgical procedure; individual dose not to exceed 500 mg
Streptococcal Pharyngitis
7 mg/kg q12hr for 10 days; individual dose not to exceed 500 mg
Pertussis
<1 month: Safety and efficacy not established
1-6 months: 7.5 mg/kg/dose PO q12hr for 7 days
>6 months: 7.5 mg/kg/dose PO q12hr for 7 days
Biaxin, Biaxin XL (clarithromycin) adverse (side) effects
>10%
Gastrointestinal (GI) effects, general (13%)
1-10%
Abnormal taste (adults, 3-7%)
Diarrhea (3-6%)
Nausea (adults, 3-6%)
Vomiting (adults, 1%; children, 6%)
Elevated blood urea nitrogen (BUN; 4%)
Abdominal pain (adults, 2%; children, 3%)
Rash (children, 3%)
Dyspepsia (2%)
Heartburn (adults, 2%)
Headache (2%)
Elevated prothrombin time (PT; 1%)
<1%
Anaphylaxis
Anorexia
Anxiety
Clostridium difficile colitis
Dizziness
Dyspnea
Elevated liver function tests
Glossitis
Hallucinations
Hepatic dysfunction
Hepatitis
Hypoglycemia
Increased alkaline phosphatase
Increased aspartate aminotransferase
Increased bilirubin
Increased serum creatinine
Jaundice
Leukopenia
Manic behavior
Neuromuscular blockade
Neutropenia
Pancreatitis
Psychosis
QT prolongation
Seizures
Stevens-Johnson syndrome
Thrombocytopenia
Postmarketing Reports
Blood and lymphatic system disorders: Thrombocytopenia, agranulocytosis
Cardiac disorders: Torsades de pointes, ventricular tachycardia, ventricular arrhythmia
Ear and labyrinth disorders: Deafness was reported chiefly in elderly women and was usually reversible
Gastrointestinal disorders: Pancreatitis acute, tongue discoloration, tooth discoloration
Hepatobiliary disorders: Hepatic failure, jaundice hepatocellular
Immune system disorders: Anaphylactic reaction, angioedema
Infections and infestations: Pseudomembranous colitis
Investigations: Prothrombin time prolonged, white blood cell count decreased, international normalized ratio increased; abnormal urine color has been reported, associated with hepatic failure
Metabolism and nutrition disorders: Hypoglycemia has been reported in patients taking oral hypoglycemic agents or insulin
Musculoskeletal and connective tissue disorders: Myopathy, rhabdomyolysis was reported and in some of the reports, clarithromycin was administered concomitantly with statins, fibrates, colchicine or allopurinoL
Nervous system disorders: Convulsion, ageusia, parosmia, anosmia, paraesthesia Psychiatric disorders:
Psychotic disorder, confusional state, depersonalization, depression, disorientation, manic behavior, hallucination, abnormal behavior, abnormal dreams
Renal and urinary disorders: Nephritis interstitial, renal failure
Skin and subcutaneous tissue disorders: Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS), Henoch-Schonlein purpura, acne
Vascular disorders: Hemorrhage
Other: Reports of colchicine toxicity, some resulting in death, with concomitant use of clarithromycin and colchicine, especially in the elderly, some of which occurred in patients with renal insufficiency
Warnings
Contraindications
Documented hypersensitivity
Coadministration with pimozide, cisapride, ergotamine, and dihydroergotamine
History of cholestatic jaundice or hepatic dysfunction associated with previous use of clarithromycin
Coadministration with colchicine in patients with renal or hepatic impairment
Coadministration with HMG-CoA reductase inhibitors (statins) that are extensively metabolized by CYP3A4 (lovastatin, simvastatin), due to the increased risk of myopathy, including rhabdomyolysis
Cautions
Severe renal impairment
Oral solution must not be refrigerated
Not for use in pregnancy, except when there is no alternative therapy; apprise patient about potential hazard to fetus if pregnancy occurs while in therapy
Use for endocarditis prophylaxis is appropriate only for high-risk patients, per American Heart Association (AHA) guidelines
Associated with QT interval prolongation and infrequent cases of arrhythmias, including torsade de pointes; avoid using with ongoing proarrhythmic conditions (eg, uncorrected hypokalemia or hypomagnesemia), clinically significant bradycardia; do not coadminister with class IA (eg, quinidine, procainamide) or class III (dofetilide, amiodarone, sotalol) antiarrhythmics
Elderly patients may be more susceptible to drug-associated QT prolongation
Use caution in patients with coronary artery disease; postmarketing trials suggest increased risk of cardiovascular mortality
Discontinue immediately if severe hypersensitivity reactions occur (eg, anaphylaxis, Stevens-Johnson syndrome, TEN, drug reaction with eosinophilia and systemic symptoms [DRESS] syndrome, Henoch-Schonlein purpura)
Clostridium difficile associated diarrhea reported with use of nearly all antibacterial agents, including clarithromycin
May cause kidney injury when administered concomitantly with calcium channel blockers metabolized by CYP3A4
Do not coadminister with ranitidine/bismuth citrate with history of acute porphyria or if CrCl <25 mL/min
Coadministration with quetiapine may result in quetiapine related toxicities including neuroleptic malignant syndrome, QT prolongation, somnolence, orthostatic hypotension, altered state of consciousness
Exacerbation of myasthenia gravis or new onset of symptoms reported
Hepatic dysfunction
- Increased liver enzyme activity and hepatocellular or cholestatic hepatitis, with or without jaundice, have been reported; this may be severe and is usually reversible
- In some instances, hepatic failure with fatal outcome has been reported, generally in association with serious underlying diseases or concomitant medications
- Discontinue clarithromycin immediately if signs and symptoms of hepatitis occur (eg, anorexia, jaundice, dark urine, pruritus, or tender abdomen)
Pregnancy and lactation
Pregnancy category: C
Lactation: Drug is excreted in breast milk; use with caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Biaxin, Biaxin XL (clarithromycin)
Mechanism of action
Semisynthetic macrolide antibiotic that reversibly binds to P site of 50S ribosomal subunit of susceptible organisms and may inhibit RNA-dependent protein synthesis by stimulating dissociation of peptidyl t-RNA from ribosomes, thereby inhibiting bacterial growth
Absorption
Highly stable in presence of gastric acid (unlike erythromycin); food delays but does not affect extent of absorption
Bioavailability: 50%
Peak plasma time: 2-3 hr (immediate release); 5-8 hr (extended release)
Distribution
Distributed widely into most body tissues except central nervous system (CNS)
Protein bound: 42-50%
Metabolism
Partially metabolized by CYP3A4
Metabolites: 14-OH clarithromycin (active)
Elimination
Half-life: Immediate release, 3-7 hr; active metabolite, 5-9 hr
Renal clearance: Approximates normal glomerular filtration rate (GFR)
Excretion: Urine (30-55%)
