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Medication Safety Issues
Sound-alike/look-alike issues:
Clarithromycin may be confused with Claritin®, clindamycin, erythromycin
Pronunciation
(kla RITH roe mye sin)
U.S. Brand Names
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Children:
Acute otitis media (H. influenzae, M. catarrhalis, or S. pneumoniae)
Community-acquired pneumonia due to susceptible Mycoplasma pneumoniae, S. pneumoniae, or Chlamydia pneumoniae (TWAR)
Pharyngitis/tonsillitis due to susceptible S. pyogenes, acute maxillary sinusitis due to susceptible H. influenzae, S. pneumoniae, or Moraxella catarrhalis, uncomplicated skin/skin structure infections due to susceptible S. aureus, S. pyogenes, and mycobacterial infections
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, H. parainfluenzae, M. catarrhalis, or S. pneumoniae
Community-acquired pneumonia due to susceptible H. influenzae, H. parainfluenzae, Mycoplasma pneumoniae, S. pneumoniae, or Chlamydia pneumoniae (TWAR), Moraxella catarrhalis
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
Use: Dental
Alternate oral antibiotic for prevention of infective endocarditis in individuals allergic to penicillins or ampicillin, when amoxicillin cannot be used; alternate antibiotic in the treatment of common orofacial infections caused by aerobic gram-positive cocci and susceptible anaerobes
Use: Unlabeled/Investigational
Pertussis (CDC guidelines); alternate antibiotic for prophylaxis of infective endocarditis in patients who are allergic to penicillin and undergoing surgical or dental procedures (ACC/AHA guidelines)
Pregnancy Risk Factor
C
Pregnancy Considerations
Clarithromycin crosses the placenta. Although no teratogenic effects have been reported in humans, adverse fetal effects have been documented in animal studies; therefore, clarithromycin is classified as pregnancy category C. The manufacturer recommends that clarithromycin not be used in a pregnant woman unless there are no alternative therapies. No adequate and well-controlled studies have been completed in pregnant women.
Lactation
Excretion in breast milk unknown/use caution
Breast-Feeding Considerations
It is not known if clarithromycin is excreted in human breast milk, but other macrolides are excreted in human milk and clarithromycin is known to be excreted into animal milk. The manufacturer recommends that caution be exercised when administering clarithromycin to breast-feeding women.
No data is available on infants exposed via human milk. Other macrolides are considered compatible with breast-feeding and clarithromycin is used therapeutically in infants. Nondose-related effects could include modification of bowel flora.
Contraindications
Hypersensitivity to clarithromycin, erythromycin, or any macrolide antibiotic; use with ergot derivatives, pimozide, cisapride
Warnings/Precautions
Concerns related to adverse effects:
• Altered cardiac conduction: Macrolides have been associated with rare QTc prolongation and ventricular arrhythmias, including torsade de pointes; use with caution in patients at risk of prolonged cardiac repolarization.
• 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:
• Coronary artery disease (CAD): Use with caution in patients with CAD; postmarketing safety trial suggests increased risk of cardiovascular mortality with short-term clarithromycin use (vs placebo) in patients with stable CAD. However, more smokers were randomized to the clarithromycin arm.
• Myasthenia gravis: Use with caution in patients with myasthenia gravis; exacerbation of symptoms and new onset of symptoms has occurred.
• Renal impairment: Dosage adjustment required with severe renal impairment; decreased dosage or prolonged dosing interval may be appropriate.
Concurrent drug therapy issues:
• Colchicine: Colchicine toxicity (including fatalities) has been reported with concomitant use. Use caution in the elderly and patients with renal impairment.
Special populations:
• Pediatrics: Safety and efficacy have not been established in children <6 months of age.
Dosage form specific issues:
• Extended release formulation: The extended release formulation consists of drug within a nondeformable matrix; following drug release/absorption, the matrix/shell is expelled in the stool. The use of nondeformable products in patients with known stricture/narrowing of the GI tract has been associated with symptoms of obstruction.
Adverse Reactions
1% to 10%:
Central nervous system: Headache (adults and children 2%)
Dermatologic: Rash (children 3%)
Gastrointestinal: Abnormal taste (adults 3% to 7%), diarrhea (adults 3% to 6%; children 6%), vomiting (children 6%), nausea (adults 3%), abdominal pain (adults 2%; children 3%), dyspepsia (adults 2%)
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, behavioral changes, bilirubin increased, confusion, disorientation, GGT increased, glossitis, hallucinations, hearing loss (reversible), hepatic dysfunction, hepatic failure, hepatitis, hypoglycemia, insomnia, interstitial nephritis, jaundice, leukopenia, manic behavior, neutropenia, oral moniliasis, pancreatitis, psychosis, QT prolongation, seizure, serum creatinine increased, Stevens-Johnson syndrome, stomatitis, thrombocytopenia, tinnitus, tongue discoloration, tooth discoloration (reversible), torsade de pointes, toxic epidermal necrolysis, transaminases increased, tremor, urticaria, ventricular tachycardia, ventricular arrhythmia, vertigo
Metabolism/Transport Effects
Substrate of CYP3A4 (major); Inhibits CYP1A2 (weak), 3A4 (strong)
Drug Interactions
Alfentanil: Macrolide Antibiotics may decrease the metabolism of Alfentanil. Risk D: Consider therapy modification
Alfuzosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alfuzosin. Risk X: Avoid combination
Alfuzosin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Almotriptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Almotriptan. Management: Limit initial almotriptan dose to 6.25mg and maximum dose to 12.5mg/24-hrs when used with a strong CYP3A4 inhibitor. Avoid concurrent use in patients with impaired hepatic or renal function. Risk D: Consider therapy modification
Alosetron: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alosetron. Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): Macrolide Antibiotics may decrease the metabolism of Antifungal Agents (Azole Derivatives, Systemic). Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Macrolide Antibiotics. Risk D: Consider therapy modification
Antineoplastic Agents (Vinca Alkaloids): Macrolide Antibiotics may increase the serum concentration of Antineoplastic Agents (Vinca Alkaloids). Macrolides may also increase the distribution of Vinca Alkaloids into certain cells and/or tissues. Management: Consider an alternative to using a macrolide antibiotic when possible in order to avoid the potential for increased vinca alkaloid toxicity. Risk D: Consider therapy modification
Artemether: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Benzodiazepines (metabolized by oxidation): Macrolide Antibiotics may decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification
BusPIRone: Macrolide Antibiotics may decrease the metabolism of BusPIRone. Risk D: Consider therapy modification
Calcium Channel Blockers: Macrolide Antibiotics may decrease the metabolism of Calcium Channel Blockers. Exceptions: Clevidipine. Risk D: Consider therapy modification
CarBAMazepine: Macrolide Antibiotics may decrease the metabolism of CarBAMazepine. Risk D: Consider therapy modification
Cardiac Glycosides: Macrolide Antibiotics may increase the serum concentration of Cardiac Glycosides. Risk D: Consider therapy modification
Chloroquine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Ciclesonide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ciclesonide. Specifically, concentrations of the active des-ciclesonide metabolite may be increased. Risk C: Monitor therapy
Cilostazol: Macrolide Antibiotics may decrease the metabolism of Cilostazol. Risk D: Consider therapy modification
Ciprofloxacin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Cisapride: Macrolide Antibiotics may decrease the metabolism of Cisapride. Risk X: Avoid combination
Clopidogrel: Macrolide Antibiotics may diminish the therapeutic effect of Clopidogrel. Risk C: Monitor therapy
Clozapine: Macrolide Antibiotics may decrease the metabolism of Clozapine. Risk D: Consider therapy modification
Colchicine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Colchicine. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a strong CYP3A4 inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Risk D: Consider therapy modification
Corticosteroids (Systemic): Macrolide Antibiotics may decrease the metabolism of Corticosteroids (Systemic). Risk D: Consider therapy modification
CycloSPORINE: Macrolide Antibiotics may decrease the metabolism of CycloSPORINE. 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
CYP3A4 Substrates: CYP3A4 Inhibitors (Strong) may decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dabigatran Etexilate: P-Glycoprotein Inhibitors may increase the serum concentration of Dabigatran Etexilate. Risk X: Avoid combination
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Disopyramide: Macrolide Antibiotics may enhance the QTc-prolonging effect of Disopyramide. Macrolide Antibiotics may decrease the metabolism of Disopyramide. Risk X: Avoid combination
Dronedarone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronedarone. Risk X: Avoid combination
Dronedarone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Dronedarone. Risk X: Avoid combination
Dutasteride: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dutasteride. Risk C: Monitor therapy
Eletriptan: Macrolide Antibiotics may decrease the metabolism of Eletriptan. Risk D: Consider therapy modification
Eplerenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eplerenone. Risk X: Avoid combination
Eplerenone: Macrolide Antibiotics may decrease the metabolism of Eplerenone. Risk C: Monitor therapy
Ergot Derivatives: Macrolide Antibiotics may enhance the adverse/toxic effect of Ergot Derivatives. Specifically leading the development of ergotism. Exceptions: Cabergoline. Risk D: Consider therapy modification
Etravirine: May decrease the serum concentration of Macrolide Antibiotics. Clarithromycin AUC is reduced and levels of the active metabolite (14-hydroxy-clarithromycin) are modestly increased. Management: For the treatment of Mycobacterium avium complex, consider changing to alternative agent, such as azithromycin. Risk D: Consider therapy modification
Everolimus: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Everolimus. Risk X: Avoid combination
FentaNYL: CYP3A4 Inhibitors (Strong) may increase the serum concentration of FentaNYL. Risk D: Consider therapy modification
Fesoterodine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fesoterodine. Management: Avoid fesoterodine doses greater than 4mg daily in patients who are also receiving strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Gadobutrol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk D: Consider therapy modification
GlipiZIDE: Clarithromycin may increase the serum concentration of GlipiZIDE. Risk C: Monitor therapy
GlyBURIDE: Clarithromycin may increase the serum concentration of GlyBURIDE. Risk C: Monitor therapy
Halofantrine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Halofantrine. Risk X: Avoid combination
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
HMG-CoA Reductase Inhibitors: Macrolide Antibiotics may decrease the metabolism of HMG-CoA Reductase Inhibitors. Exceptions: Fluvastatin; Pravastatin; Rosuvastatin. Risk D: Consider therapy modification
Ixabepilone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ixabepilone. Risk D: Consider therapy modification
Lumefantrine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Maraviroc: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc. Management: When used with a strong CYP3A4 inhibitor, the adult dose of maraviroc should be decreased to 150 mg twice daily. Risk D: Consider therapy modification
Nilotinib: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Nilotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib. Risk X: Avoid combination
Nisoldipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nisoldipine. Risk X: Avoid combination
Paricalcitol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Paricalcitol. Risk C: Monitor therapy
P-Glycoprotein Substrates: P-Glycoprotein Inhibitors may increase the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: Macrolide Antibiotics may decrease the metabolism of Phosphodiesterase 5 Inhibitors. Risk D: Consider therapy modification
Pimecrolimus: CYP3A4 Inhibitors (Strong) may decrease the metabolism of Pimecrolimus. Risk C: Monitor therapy
Pimozide: Macrolide Antibiotics may enhance the QTc-prolonging effect of Pimozide. Macrolide Antibiotics may decrease the metabolism of Pimozide. QTc prolongation is a risk. Risk X: Avoid combination
Pimozide: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Pimozide. Risk X: Avoid combination
Prasugrel: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Prasugrel. Risk C: Monitor therapy
Protease Inhibitors: May diminish the therapeutic effect of Clarithromycin. Specifically, certain protease inhibitors may decrease formation of the active 14-hydroxy-clarithromycin metabolite, which may negatively impact clarithromycin effectiveness vs. H. influenzae and other non-MAC infections. Protease Inhibitors may increase the serum concentration of Clarithromycin. Clarithromycin dose adjustment in renally impaired patients may be needed. Clarithromycin may increase the serum concentration of Protease Inhibitors. Risk D: Consider therapy modification
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: Macrolide Antibiotics may decrease the metabolism of QuiNIDine. Risk D: Consider therapy modification
QuiNINE: Macrolide Antibiotics may increase the serum concentration of QuiNINE. Risk X: Avoid combination
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
Ranolazine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ranolazine. Risk X: Avoid combination
Repaglinide: Macrolide Antibiotics may increase the serum concentration of Repaglinide. Risk C: Monitor therapy
Rifamycin Derivatives: Macrolide Antibiotics may decrease the metabolism of Rifamycin Derivatives. Exceptions: Rifapentine. Risk D: Consider therapy modification
Rivaroxaban: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rivaroxaban. Risk X: Avoid combination
Salmeterol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Salmeterol. Risk X: Avoid combination
Saxagliptin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Saxagliptin. Management: Limit saxagliptin dosage to 2.5 mg/day and monitor for increased saxagliptin levels/effects (e.g., hypoglycemia) with concomitant use of a strong CYP3A4 inhibitor. Monitor for decreased saxagliptin levels/effects if discontinuing CYP3A4 inhibitor. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: Macrolide Antibiotics may decrease the metabolism of Selective Serotonin Reuptake Inhibitors. Exceptions: Fluvoxamine; PARoxetine. Risk C: Monitor therapy
Silodosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Silodosin. Risk X: Avoid combination
Sirolimus: Macrolide Antibiotics may decrease the metabolism of Sirolimus. Risk D: Consider therapy modification
Sorafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sorafenib. Risk C: Monitor therapy
Tacrolimus: Macrolide Antibiotics may increase the serum concentration of Tacrolimus. Risk C: Monitor therapy
Tadalafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tadalafil. Management: Erectile dysfunction: tadalafil max = 2.5 mg/day (daily use) or 10 mg/72 hrs (as needed use). Avoid use of tadalafil for treatment of pulmonary arterial hypertension in patients also receiving a strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Temsirolimus: Macrolide Antibiotics may enhance the adverse/toxic effect of Temsirolimus. Levels of sirolimus, the active metabolite, may be increased, likely due to inhibition of CYP-mediated metabolism. Risk D: Consider therapy modification
Tetrabenazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Tetrabenazine. Risk X: Avoid combination
Theophylline Derivatives: Macrolide Antibiotics may decrease the metabolism of Theophylline Derivatives. Exceptions: Dyphylline. Risk D: Consider therapy modification
Thioridazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination
Tolvaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolvaptan. Risk X: Avoid combination
Topotecan: P-Glycoprotein Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Macrolide Antibiotics may increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy
Zidovudine: Clarithromycin may enhance the myelosuppressive effect of Zidovudine. Clarithromycin may decrease the serum concentration of Zidovudine. Management: Monitor response to zidovudine closely when used with clarithromycin, and consider staggering zidovudine and clarithromycin doses when possible in order to minimize the potential for interaction. Risk D: Consider therapy modification
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
Zopiclone: Macrolide Antibiotics may increase the serum concentration of Zopiclone. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Food: Immediate release: Food delays rate, but not extent of absorption; Extended release: Food increases clarithromycin AUC by ~30% relative to fasting conditions.
Herb/Nutraceutical: St John's wort may decrease clarithromycin levels.
Storage
Store tablets and granules for oral suspension at controlled room temperature. Reconstituted oral suspension should not be refrigerated because it might gel. Microencapsulated particles of clarithromycin in suspension is stable for 14 days when stored at room temperature.
Mechanism of Action
Exerts its antibacterial action by binding to 50S ribosomal subunit resulting in inhibition of protein synthesis. The 14-OH metabolite of clarithromycin is twice as active as the parent compound against certain organisms.
Pharmacodynamics/Kinetics
Absorption: Immediate release: Rapid; food delays rate, but not extent of absorption
Distribution: Widely into most body tissues except CNS
Protein binding: 42% to 50%
Metabolism: Partially hepatic via CYP3A4; converted to 14-OH clarithromycin (active metabolite)
Bioavailability: ~50%
Half-life elimination: Immediate release: Clarithromycin: 3-7 hours; 14-OH-clarithromycin: 5-9 hours
Time to peak: Immediate release: 2-3 hours
Excretion: Primarily urine (20% to 40% as unchanged drug; additional 10% to 15% as metabolite)
Clearance: Approximates normal GFR
Dosage
Usual dosage range:
Children ?6 months: Oral: 7.5 mg/kg every 12 hours (maximum: 500 mg/dose)
Adults: Oral: 250-500 mg every 12 hours or 1000 mg (two 500 mg extended release tablets) once daily for 7-14 days
Indication-specific dosing:
Children: Oral:
Community-acquired pneumonia, sinusitis, bronchitis, skin infections: 15 mg/kg/day divided every 12 hours for 10 days
Mycobacterial infection (prevention and treatment): 7.5 mg/kg (up to 500 mg) twice daily. Note: Safety of clarithromycin for MAC not studied in children <20 months.
Pertussis (unlabeled use; CDC guidelines):
Children 1-5 months: 15 mg/kg/day divided every 12 hours for 7 days
Children ?6 months: 15 mg/kg/day divided every 12 hours for 7 days (maximum: 1 g/day)
Prophylaxis against infective endocarditis (unlabeled use): 15 mg/kg 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.
Adults: Oral:
Acute exacerbation of chronic bronchitis:
M. catarrhalis 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: 500 mg every 12 hours for 7-14 days or 1000 mg (two 500 mg extended release tablets) once daily for 7 days
H. parainfluenzae: 500 mg every 12 hours for 7 days or 1000 mg (two 500 mg extended release tablets) once daily for 7 days
Acute maxillary sinusitis: 500 mg every 12 hours or 1000 mg (two 500 mg extended release tablets) once daily for 14 days
Mycobacterial infection (prevention and treatment): 500 mg twice daily (use with other antimycobacterial drugs, eg, ethambutol or rifampin)
Peptic ulcer disease: Eradication of Helicobacter pylori: Dual or triple combination regimens with bismuth subsalicylate, amoxicillin, an H2-receptor antagonist, or proton-pump inhibitor: 500 mg every 8-12 hours for 10-14 days
Pertussis (unlabeled use; CDC guidelines): 500 mg twice daily for 7 days
Pharyngitis, tonsillitis: 250 mg every 12 hours for 10 days
Pneumonia:
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
H. parainfluenzae and M. catarrhalis: 1000 mg (two 500 mg extended release tablets) once daily for 7 days
Prophylaxis against infective endocarditis (unlabeled use): 500 mg 30-60 minutes prior to 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.
Skin and skin structure infection, uncomplicated: 250 mg every 12 hours for 7-14 days
Elderly: Pharmacokinetics are similar to those in younger adults; may have age-related reductions in renal function; monitor and adjust dose if necessary
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
Dental Usual Dosing
Prophylaxis against infective endocarditis (unlabeled use): Oral:
Children: 15 mg/kg 30-60 minutes before procedure
Adults: 500 mg 30-60 minutes prior to 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.
Administration: Oral
Clarithromycin immediate release tablets and oral solution may be given with or without meals. Give every 12 hours rather than twice daily to avoid peak and trough variation.
Biaxin® XL: Should be given with food. Do not crush or chew extended release tablet.
Monitoring Parameters
CBC with differential, BUN, creatinine; perform culture and sensitivity studies prior to initiating drug therapy
Dietary Considerations
Clarithromycin immediate release tablets and oral solution may be given with or without meals. May be taken with milk. Biaxin® XL should be taken with food.
Patient Education
Do not take any new prescription or OTC medications or herbal products during therapy without consulting prescriber. Take exactly as prescribed and complete full course of therapy, even if feeling better. Tables and suspension may be taken with or without meals or milk. Extended release formulation (XL) should be taken with meals; do not break or chew extended release tablets. Maintain adequate hydration unless instructed to restrict fluids. May cause nausea, heartburn, or abnormal taste (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); diarrhea (yogurt, Bifidobacterium bifidum, Lactobacillus acidophilus, Saccharomyces boulardii may help); or headaches or abdominal pain (consult prescriber for analgesic). Report rapid heartbeat or palpitations, persistent fever or chills, easy bruising or bleeding, joint pain, severe persistent diarrhea, skin rash, sores in mouth, foul-smelling urine, or other adverse effects. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.
Geriatric Considerations
Considered one of the drugs of choice in the outpatient treatment of community-acquired pneumonia in elderly. After doses of 500 mg every 12 hours for 5 days, 12 healthy elderly subjects had significantly increased Cmax and Cmin, elimination half-lives of clarithromycin and 14-OH clarithromycin compared to 12 healthy young subjects. These changes were attributed to a significant decrease in renal clearance; at a dose of 1000 mg twice daily, 100% of 13 elderly subjects experienced an adverse event compared to only 10% taking 500 mg twice daily.
Cardiovascular Considerations
Because of potential drug interactions, serious arrhythmias may occur when clarithromycin and other macrolides are used in combination with cisapride. Clarithromycin may also increase theophylline, some HMG-CoA reductase inhibitors, digoxin, warfarin, and cyclosporine levels (among others). Clarithromycin may be used in penicillin-allergic patients for prevention of bacterial endocarditis.
The FDA issued an alert for clarithromycin (Biaxin®, Abbott Laboratories) on December 8, 2005. These actions were based upon results of a Danish trial (CLARICOR) that was recently published online in the British Medical Journal (Jesperson, 2005). This was a multicenter, double-blind, randomized, placebo-controlled trial evaluating the effects of clarithromycin (500 mg daily for 14 days) on mortality in patients with stable coronary artery disease. Over 13,000 patients having a discharge diagnosis (from 1993-99) of myocardial infarction or angina pectoris were recruited for the trial. The primary outcome was a composite of all cause mortality, MI, or unstable angina during the three-year follow up. The secondary outcome measure consisted of cardiovascular mortality, MI, or unstable angina. Two thousand one hundred and seventy two patients were randomized to clarithromycin and 2200 to placebo. The groups were well matched except there were more smokers in the clarithromycin group. Compliance was over 90% in both groups. There was no difference between the two groups with regard to the composite outcomes (primary or secondary). All cause mortality was significantly higher in the clarithromycin group (HR 1.27; CI 1.03-1.54; p = 0.03) as a result of a higher cardiovascular mortality (HR 1.45; CI 1.09-1.92; p = 0.01). When a multivariant analysis was done, all cause mortality was insignificantly increased (HR 1.21; CI 0.99-1.48; p = 0.07), but cardiovascular mortality continued to be significantly increased in the clarithromycin group (HR 1.38; CI 1.03-1.85; p = 0.03). One hundred and eighty four patients died in the clarithromycin group (89 from cardiovascular events) and 159 patients died in the placebo group (70 from cardiovascular events). The authors conclude that short-term clarithromycin therapy in patients with stable coronary artery disease may cause significantly higher cardiovascular mortality. This result came as a surprise to the authors who were not evaluating the safety of clarithromycin in patients with CAD. Further study is needed to evaluate the clinical validity of this unexpected finding.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Abnormal taste.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
Clarithromycin is one of the drugs confirmed to prolong the QT interval and is accepted as having a risk of causing torsade de pointes. In terms of epinephrine, it is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval. Until more information is obtained, it is suggested that the clinician consult with the physician prior to the use of a vasoconstrictor in suspected patients, and that the vasoconstrictor (epinephrine, mepivacaine and levonordefrin [Carbocaine® 2% with Neo-Cobefrin®]) be used with caution. See Dental Health Professional Considerations.
Dental Comment
The FDA issued a special alert in December 2005 stating that short-term therapy with clarithromycin in patients with stable coronary artery disease may cause significantly higher cardiovascular mortality. The use of 500 mg clarithromycin daily for 14 days in patients with the above condition resulted in significantly higher all-cause mortality compared to patients taking placebo. This information is provided to the dental practitioner on the possible association between short-term use of clarithromycin for infections and increases in mortality in patients with a history of stable coronary artery disease.
Clarithromycin is known to prolong the QT interval. The QT interval is measured as the time and distance between the Q point of the QRS complex and the end of the T wave in the ECG tracing. After adjustment for heart rate, the QT interval is defined as prolonged if it is more than 450 msec in men and 460 msec in women. A long QT syndrome was first described in the 1950s and 60s as a congenital syndrome involving QT interval prolongation and syncope and sudden death. Some of the congenital long QT syndromes were characterized by a peculiar electrocardiographic appearance of the QRS complex involving a premature atria beat followed by a pause, then a subsequent sinus beat showing marked QT prolongation and deformity. This type of cardiac arrhythmia was originally termed “torsade de pointes” (translated from the French as “twisting of the points”). Clarithromycin is considered as having a risk of causing torsade de pointes. Since it is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval, a medical consult is suggested.
Mental Health: Effects on Mental Status
Macrolides have been reported to cause nightmares, confusion, anxiety, and mood lability
Mental Health: Effects on Psychiatric Treatment
Contraindicated with pimozide; increases carbamazepine and triazolam levels; monitor for signs of toxicity
Nursing: Physical Assessment/Monitoring
Assess results of culture and sensitivity tests and patient's allergy history prior to therapy. Use with caution in presence of severe renal impairment, myasthenia gravis, or coronary artery disease. Assess for potential adverse interactions or toxicity with any other prescription, OTC, or herbal products patient may be taking. Evaluate results of laboratory monitoring with long-term use. Assess therapeutic effectiveness (according to purpose for use) and adverse reactions. Teach patient proper use, possible side effects/appropriate interventions, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Granules for oral suspension: 125 mg/5 mL (50 mL, 100 mL); 250 mg/5 mL (50 mL, 100 mL)
Biaxin®: 125 mg/5 mL (50 mL, 100 mL); 250 mg/5 mL (50 mL, 100 mL) [fruit punch flavor]
Tablet: 250 mg, 500 mg
Biaxin®: 250 mg, 500 mg
Tablet, extended release: 500 mg
Biaxin® XL: 500 mg
Pricing: U.S. (www.drugstore.com)
Suspension (reconstituted) (Clarithromycin)
125 mg/5 mL (50): $27.99
125 mg/5 mL (100): $41.91
250 mg/5 mL (50): $42.71
250 mg/5 mL (100): $76.72
Tablet, 24-hour (Biaxin XL)
500 mg (20): $121.03
Tablet, 24-hour (Biaxin XL Pac)
500 mg (14): $92.51
Tablet, 24-hour (Clarithromycin)
500 mg (60): $289.99
Tablets (Biaxin)
250 mg (60): $352.13
500 mg (20): $115.38
Tablets (Clarithromycin)
250 mg (30): $109.99
500 mg (30): $109.99
References
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International Brand Names
Lexi-Comp.com
Last full review/revision September 2009
Content last modified September 2009
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