clarithromycin

kla-RITH-roe-mye-sin

Therapeutic Classification: agents for atypical mycobacterium, anti-infectives, antiulcer agents

Pharmacologic Classification: macrolides

REMS

Acute bacterial exacerbation of chronic bronchitis (immediate release and extended release).
Acute maxillary sinusitis (immediate release and extended release).
Community-acquired pneumonia (immediate release and extended release).
Pharyngitis/tonsillitis (immediate release only).
Uncomplicated skin/skin structure infections (immediate release only).
Acute otitis media (immediate release only).
Treatment and prophylaxis of disseminated Mycobacterial avium infections (immediate release only).
Helicobacter pylori infection and duodenal ulcer disease (immediate release only).

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.

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

Distribution: Widely distributed to tissues.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP3A isoenzymes; 10–15% converted by the liver to 14-hydroxyclarithromycin, which has anti-infective activity. 20–30% excreted unchanged in urine.

Half-Life: 250-mg dose: 3–4 hr; 500-mg dose: 5–7 hr.

(plasma concentrations)

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

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 or simvastatin
Concurrent use of colchicine in patients with hepatic or renal impairment;
QT interval prolongation, hypokalemia, hypomagnesemia, or bradycardia;
OB: Pregnancy.

Use Cautiously in:

Coronary artery disease (may ↑ risk of mortality);
Myasthenia gravis;
Severe renal impairment (↓ dose);
Severe hepatic impairment;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Children <6 mo (safety and effectiveness not established);
Geri: Older adults may have ↑ risk of QT interval prolongation.

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 (SJS), TOXIC EPIDERMAL NECROLYSIS

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

Neuro: headache

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA)

Drug-drug:

May prolong the QT interval and ↑ risk of arrhythmias withpimozide; concurrent use contraindicated.
May ↑ levels and risk of toxicity of ergotamine and dihydroergotamine; concurrent use contraindicated.
↑risk of rhabdomyolysis with lovastatin and simvastatin; concurrent use contraindicated
↑risk of hepatotoxicity with lomitapide; concurrent use contraindicated.
May ↑ levels and risk of toxicity of colchicine; concurrent use contraindicated in patients with renal or hepatic impairment. ↓ colchicine dose in patients with normal renal and hepatic function.
Disopyramide, quinidine, procainamide, dofetilide, sotalol, and amiodarone may ↑ risk of QT interval prolongation; avoid concurrent use.
May ↑ levels and risk of toxicity of CYP3A substrates, including carbamazepine, some benzodiazepines (including midazolam, triazolam, alprazolam), cyclosporine, calcium channel blockers, omeprazole, tacrolimus, digoxin, tolterodine, quetiapine, or theophylline.
Ritonavir may ↑ levels and risk of toxicity; ↓ clarithromycin dose if 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.
Fluconazole may ↑ levels and risk of toxicity.
Rifampin, rifabutin, efavirenz, and nevirapine may ↓ levels and effectiveness.
May ↑ levels of and risk of bleeding from warfarin.
May ↑ levels and effects of sildenafil, tadalafil, avanafil, and vardenafil; concurrent use not recommended.
Concurrent use with Atazanavir may ↑ levels and risk of toxicity of clarithromycin and atazanavir; ↓ clarithromycin dose by 50%.
Concurrent use with itraconazole may ↑ levels and risk of toxicity of clarithromycin and itraconazole.

Acute Bacterial Exacerbation of Chronic Bronchitis

PO (Adults ): Immediate release:250–500 mg every 12 hr for 7–14 days. Extended release:1 g once daily for 7 days. Concurrent use with atazanavir: ↓clarithromycin dose by 50%.

Renal Impairment

PO (Adults ): CCr 30–60 mL/min AND concurrent use of atazanavir or ritonavir: ↓clarithromycin dose by 50%. CCr <30 mL/min: ↓dose by 50%. CCr <30 mL/min AND concurrent use of atazanavir or ritonavir: ↓clarithromycin dose by 75%.

Acute Maxillary Sinusitis

PO (Adults ): Immediate release: 500 mg every 12 hr for 14 days. Extended release: 1 g once daily for 14 days. Concurrent use with atazanavir: ↓clarithromycin dose by 50%.

Renal Impairment

PO (Adults ): CCr 30–60 mL/min AND concurrent use of atazanavir or ritonavir: ↓clarithromycin dose by 50%. CCr <30 mL/min: ↓dose by 50%. CCr <30 mL/min AND concurrent use of atazanavir or ritonavir: ↓clarithromycin dose by 75%.

Community-Acquired Pneumonia

PO (Adults ): Immediate release: 250 mg every 12 hr for 7–14 days. Extended release: 1 g once daily for 7 days. Concurrent use with atazanavir: ↓clarithromycin dose by 50%.
PO (Children ≥6 mo): Immediate release: 7.5 mg/kg every 12 hours for 10 days. Concurrent use with atazanavir: ↓clarithromycin dose by 50%.

Renal Impairment

PO (Adults and Children ≥6 mo): CCr 30–60 mL/min AND concurrent use of atazanavir or ritonavir: ↓clarithromycin dose by 50%. CCr <30 mL/min: ↓dose by 50%. CCr <30 mL/min AND concurrent use of atazanavir or ritonavir: ↓clarithromycin dose by 75%.

Uncomplicated Skin/Skin Structure Infections

PO (Adults ): Immediate release: 250 mg every 12 hr for 7–14 days. Concurrent use with atazanavir: ↓clarithromycin dose by 50%.
PO (Children ≥6 mo): Immediate release: 7.5 mg/kg every 12 hours for 10 days. Concurrent use with atazanavir: ↓clarithromycin dose by 50%.

Renal Impairment

PO (Adults and Children ≥6 mo): CCr 30–60 mL/min AND concurrent use of atazanavir or ritonavir: ↓clarithromycin dose by 50%. CCr <30 mL/min: ↓dose by 50%. CCr <30 mL/min AND concurrent use of atazanavir or ritonavir: ↓clarithromycin dose by 75%.

Pharyngitis/Tonsillitis

PO (Adults ): Immediate release: 250 mg every 12 hr for 10 days. Concurrent use with atazanavir: ↓clarithromycin dose by 50%.
PO (Children ≥6 mo): Immediate release: 7.5 mg/kg every 12 hours for 10 days. Concurrent use with atazanavir: ↓clarithromycin dose by 50%.

Renal Impairment

PO (Adults and Children ≥6 mo): CCr 30–60 mL/min AND concurrent use of atazanavir or ritonavir: ↓clarithromycin dose by 50%. CCr <30 mL/min: ↓dose by 50%. CCr <30 mL/min AND concurrent use of atazanavir or ritonavir: ↓clarithromycin dose by 75%.

Acute Otitis Media

PO (Children ≥6 mo): Immediate release: 7.5 mg/kg every 12 hours for 10 days. Concurrent use with atazanavir: ↓clarithromycin dose by 50%.

Renal Impairment

PO (Children ≥6 mo): CCr 30–60 mL/min AND concurrent use of atazanavir or ritonavir: ↓clarithromycin dose by 50%. CCr <30 mL/min: ↓dose by 50%. CCr <30 mL/min AND concurrent use of atazanavir or ritonavir: ↓clarithromycin dose by 75%.

Treatment and Prophylaxis of Disseminated Mycobacterium avium Disease

PO (Adults ): Immediate release: 500 mg every 12 hr. Concurrent use with atazanavir: ↓clarithromycin dose by 50%.
PO (Children ≥6 mo): Immediate release: 7.5 mg/kg every 12 hours. Concurrent use with atazanavir: ↓clarithromycin dose by 50%.

Renal Impairment

PO (Adults and Children ≥6 mo): CCr 30–60 mL/min AND concurrent use of atazanavir or ritonavir: ↓clarithromycin dose by 50%. CCr <30 mL/min: ↓dose by 50%. CCr <30 mL/min AND concurrent use of atazanavir or ritonavir: ↓clarithromycin dose by 75%.

H. pylori Infection

PO (Adults ): Immediate release: 500 mg every 12 hr in combination with amoxicillin or metronidazole (if penicillin allergic), plus a potassium-competitive acid blocker or a high-dose proton pump inhibitor; continue regimen for 14 days. Concurrent use with atazanavir: ↓clarithromycin dose by 50%.

Renal Impairment

PO (Adults ): CCr 30–60 mL/min AND concurrent use of atazanavir or ritonavir: ↓clarithromycin dose by 50%. CCr <30 mL/min: ↓dose by 50%. CCr <30 mL/min AND concurrent use of atazanavir or ritonavir: ↓clarithromycin dose by 75%.

(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).

Assess for resolving infection (WBC and vital signs trends; appearance of wound, sputum, urine, and stool) at beginning and during therapy.
Obtain specimens for culture and sensitivity before initiating therapy. 1st 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 weeks after cessation of therapy.
Assess for rash or signs/symptoms of SJS (fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, and/or eosinophila) periodically during therapy . If rash or signs/symptoms of SJS occur, discontinue clarithromycin and provide supportive care.
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 ↑ serum AST, ALT, total bilirubin, and alkaline phosphatase concentrations.
- May occasionally ↑ BUN.

PO: Administer around the clock, without regard to meals; may be administered with milk. Food slows but does not ↓ 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.

Explain purpose and side effects of clarithromycin. Instruct patient to take around the clock and to complete entire course 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. Advise patient to read Patient Information before starting therapy.
Instruct patient to notify health care professional if symptoms do not improve within a few days.
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.
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 women of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Avoid use in pregnancy.

Resolution of the signs and symptoms of infection. Length of time for complete resolution depends on the organism and site of infection.
Treatment of peptic ulcers caused by Helicobacter pylori.
Endocarditis prophylaxis.

~~Biaxin XL~~

Biaxin

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆ ⬇

Canadian Brand Names ⬆