clarithromycin

REMS

Respiratory tract infections including streptococcal pharyngitis, sinusitis, bronchitis, and pneumonia.
Treatment and prevention of disseminated
Mycobacterium avium
complex (MAC) (in combination with ethambutol).
Treatment of the following pediatric infections:
- Otitis media,
- Sinusitis,
- Pharyngitis,
- Skin/skin structure infections.
Part of a combination regimen for ulcer disease due to
Helicobacter pylori
.
Endocarditis prophylaxis.

Action ⬆ ⬇

Inhibits protein synthesis at the level of the 50S bacterial ribosome.

Therapeutic effects:

Bacteriostatic action.

Spectrum:

Active against these gram-positive aerobic bacteria:
- Staphylococcus aureus,
- S. pneumoniae,
- S. pyogenes (group A strep).
Active against these gram-negative aerobic bacteria:
- Haemophilus influenzae,
- Moraxella catarrhalis.
Also active against:
- Mycoplasma,
- Legionella,
- H. pylori,
- M. avium.

Pharmacokinetics ⬆ ⬇

Absorption: Rapidly absorbed (50%) after oral administration.

Distribution: Widely distributed; tissue levels may exceed those in serum.

Protein Binding: 65–70%.

Metabolism/Excretion: 10–15% converted by the liver to 14-hydroxyclarithromycin, which has anti-infective activity; 20–30% excreted unchanged in urine. Metabolized by and also inhibits the CYP3A enzyme system.

Half-Life: Dose-dependent and prolonged with renal dysfunction 250-mg dose: 3–4 hr; 500-mg dose: 5–7 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	2 hr	12 hr
PO-XL	unknown	4 hr	24 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to clarithromycin, erythromycin, or other macrolide anti-infectives;
History of cholestatic jaundice or hepatic dysfunction with clarithromycin;
Concurrent use of pimozide, ergotamine, dihydroergotamine, lomitapide, lovastatin, simvastatin, disopyramide, quinidine, procainamide, dofetilide, amiodarone, or sotalol;
Concurrent use of colchicine in patients with hepatic or renal impairment;
QT interval prolongation, hypokalemia, hypomagnesemia, or bradycardia;
OB: Avoid use during pregnancy unless no alternatives are available.

Use Cautiously in:

Coronary artery disease (may ↑ risk of mortality);
Severe liver or renal impairment (dose adjustment required if CCr <30 mL/min);
Myasthenia gravis;
Lactation: Use while breastfeeding only if potential maternal benefit outweighs potential risk to infant;
Pedi: Children 6 mo (safety and effectiveness not established);
Geri: Older adults may have risk of QT interval prolongation.

Adv. Reactions/Side Effects ⬆ ⬇

CV: QT interval prolongation, TORSADES DE POINTES

Derm: ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS, DRUG RASH WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), pruritus, rash, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS

GI: CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD), abdominal pain/discomfort, abnormal taste, diarrhea, dyspepsia, HEPATOTOXICITY, nausea

Neuro: headache

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA)

Interactions ⬆ ⬇

Drug-drug:

Clarithromycin is an inhibitor of the CYP3A enzyme system. Concurrent use with other agents metabolized by this system can ↑ levels and risk of toxicity.
May prolong the QT interval and ↑ risk of arrhythmias withpimozide; concurrent use contraindicated.
May ↑ levels of ergotamine and dihydroergotamine and risk for acute ergot toxicity; concurrent use contraindicated.
Disopyramide, quinidine, procainamide, dofetilide, sotalol, and amiodarone may ↑ risk of QT interval prolongation; concurrent use should be avoided
↑risk of rhabdomyolysis with lovastatin and simvastatin; concurrent use contraindicated
↑risk of hepatotoxicity with lomitapide; concurrent use contraindicated.
May ↑ serum levels and the risk of toxicity from carbamazepine, some benzodiazepines (midazolam, triazolam, alprazolam), cyclosporine, disopyramide, quinidine, ergot alkaloids, felodipine, omeprazole, tacrolimus, digoxin, quetiapine, or theophylline.
May ↑ levels and effects of omeprazole.
Ritonavir↑ blood levels (↓ clarithromycin dose in patients with CCr <60 mL/min).
↑levels and risk of myopathy from atorvastatin and pravastatin; use lowest dose of these agents; do not exceed atorvastatin dose of 20 mg/day or pravastatin dose of 40 mg/day.
May ↑ or ↓ effects of zidovudine.
Blood levels are ↑ by fluconazole.
Blood levels may be ↓ by rifampin, rifabutin, efavirenz, and nevirapine.
May ↑ levels and risk of toxicity from colchicine; ↓ colchicine dose in patients with normal renal and hepatic function; concurrent use is contraindicated in patients with renal or hepatic impairment.
May ↑ calcium channel blocker levels and the risk for hypotension, bradycardia, and lactic acidosis.
Concomitant use with calcium channel blockers metabolized by CYP3A4, including verapamil, diltiazem, amlodipine, and nifedipine may ↑ the risk of acute kidney injury, especially in patients older than 65 yr.
May ↑ warfarin levels and the risk for bleeding.
May ↑ blood levels and effects of sildenafil, tadalafil, and vardenafil; concurrent use not recommended.
May ↑ levels of tolterodine.
Concurrent use with atazanavir may ↑ clarithromycin and atazanavir levels; ↓ clarithromycin dose by 50%.
Concurrent use with itraconazole may ↑ clarithromycin and itraconazole levels.

Route/Dosage ⬆ ⬇

PO (Adults ): Pharyngitis/tonsillitis: 250 mg every 12 hr for 10 days; Acute maxillary sinusitis: 500 mg every 12 hr for 14 days or 1000 mg once daily for 14 days as XL tablets; Acute exacerbation of chronic bronchitis: 250–500 mg every 12 hr for 7–14 days or 1000 mg once daily for 7 days as XL tablets; Community-acquired pneumonia: 250 mg every 12 hr for 7–14 days or 1000 mg once daily for 7 days as XL tablets; Skin/skin structure infections: 250 mg every 12 hr for 7–14 days; H. pylori
: 500 mg 2–3 times daily with a proton pump inhibitor (lansoprazole or omeprazole) with or without amoxicillin for 10–14 days; Endocarditis prophylaxis: 500 mg 1 hr before procedure; MAC prophylaxis/treatment: 500 mg twice daily, for active infection another antimycobacterial is required.
PO (Children ≥6 mo): Most infections: 15 mg/kg/day divided every 12 hr for 7–14 days (up to 500 mg/dose for MAC). Endocarditis prophylaxis: 15 mg/kg 1 hr before procedure.

Renal Impairment

PO (Adults ): CCr <30 mL/min: 250 mg 1–2 times daily, a 500-mg initial dose may be used.
PO (Children ): CCr <30 mL/min: ↓dose by 50% or double dosing interval.

Availability ⬆ ⬇

(Generic available)

Immediate-release tablets: 250 mg; 500 mg
Extended-release tablets: 500 mg
Oral suspensionfruit punch and vanilla flavors: 125 mg/5 mL; 250 mg/5 mL
In combination with: amoxicillin and lansoprazole as part of a compliance package; amoxicillin and omeprazole as part of a compliance package (Omeclamox-Pak); vonoprazan and amoxicillin as part of a compliance package (Voquezna Triple Pak).

Assessment ⬆ ⬇

Assess patient for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and during therapy.
Obtain specimens for culture and sensitivity before initiating therapy. First dose may be given before receiving results.
Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of CDAD. May begin up to several wk after cessation of therapy.
Assess patient for skin rash frequently during therapy. Discontinue clarithromycin at first sign of rash; may be life-threatening. Stevens-Johnson syndrome may develop. Treat symptomatically; may recur once treatment is stopped.
Ulcers: Assess patient for epigastric or abdominal pain and frank or occult blood in the stool, emesis, or gastric aspirate.

Lab Test Considerations:

May rarely cause ↑ serum AST, ALT, total bilirubin, and alkaline phosphatase concentrations.
- May occasionally cause ↑ BUN.

Implementation ⬆ ⬇

PO: Administer around the clock, without regard to meals; may be administered with milk. Food slows but does not decrease the extent of absorption.
- Administer XL tablets with food or milk. DNC: Swallow whole; do not crush, break, or chew.
- Shake suspension well before administration. Store suspension at room temperature; do not refrigerate.
- Do not administer within 4 hr of zidovudine.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication around the clock and to finish the drug completely as directed, even if feeling better. Take missed doses as soon as possible, unless almost time for next dose. Do not double doses. Advise patient that sharing of this medication may be dangerous.
May cause dizziness, vertigo, confusion and disorientation. Caution patient to avoid driving and other activities requiring alertness until response to medication is known.
Advise patient to report the signs of superinfection (black, furry overgrowth on the tongue; vaginal itching or discharge; loose or foul-smelling stools).
Instruct patient to notify health care professional if rash, or fever and diarrhea develop, especially if stool contains blood, pus, or mucus. Advise patient not to treat diarrhea without consulting health care professional.
Caution patients taking zidovudine that clarithromycin and zidovudine must be taken at least 4 hr apart.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Rep: May cause fetal harm. Advise patient to notify health care professional immediately if pregnancy is planned or suspected or if breastfeeding.
Instruct the patient to notify health care professional if symptoms do not improve within a few days.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇