clarithromycin

Clarithromycin is effective against susceptible bacteria causing the following infections:

• middle ear,
• tonsillitis,
• throat infections,
• laryngitis,
• bronchitis,
• pneumonia, and
• skin infections.

It also is used in treating infections caused by mycobacterium avium, a bacterium closely related to the bacterium that causes tuberculosis. Clarithromycin has been used in combination with omeprazole/sodium bicarbonate (Prilosec) in treating H. Pylori that causes stomach ulcers.

Clarithromycin is a semi-synthetic macrolide antibiotic chemically related to erythromycin and azithromycin (Zithromax). It is effective against a wide variety of bacteria, such as Haemophilus influenzae, Streptococcus pneumoniae, Mycoplasma pneumoniae, Staphylococcus aureus, and mycobacterium avium, and many others. Like all macrolide antibiotics, clarithromycin prevents bacteria from growing by interfering with their ability to make proteins. Due to the differences in the way proteins are made in bacteria and humans, the macrolide antibiotics do not interfere with production of proteins in humans. The FDA approved clarithromycin in October 1991.

• Concomitant administration of clarithromycin with lomitapide is contraindicated due to potential for markedly increased transaminases.
• Concomitant administration of clarithromycin with HMG-CoA reductase inhibitors (statins) that are extensively metabolized by CYP3A4 (lovastatin or simvastatin) is contraindicated, due to the increased risk of myopathy, including rhabdomyolysis.
• Clarithromycin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Cases of torsades de pointes have been spontaneously reported during postmarketing surveillance in patients receiving clarithromycin. Fatalities have been reported.

Clarithromycin generally is well tolerated, and side effects usually are mild and transient. Common side effects of clarithromycin are:

• nausea,
• diarrhea,
• abnormal taste,
• dyspepsia,
• abdominal pain and
• headache.

Other important side effects which are rare, but serious include:

• liver failure,
• abnormal heart beats,
• hearing loss, and
• seizures.

Clarithromycin should be avoided by patients known to be allergic to clarithromycin or other chemically-related macrolide antibiotics, such as erythromycin. Treatment with clarithromycin and other antibiotics can alter the normal bacteria flora of the colon and permit overgrowth of C. difficile, a bacterium responsible for pseudomembranous colitis. Patients who develop pseudomembranous colitis as a result of antibiotics treatment may experience diarrhea, abdominal pain, fever, and sometimes even shock.

Clarithromycin may be taken with or without food. For most infections the recommended adult dose is 250-500 mg of immediate release tablets twice daily or 1000 mg of extended release tablets once daily for 7-14 days.

Clarithromycin interacts with several drugs because it reduces the activity of liver enzymes that breakdown many drugs. This leads to increased blood levels and side effects from the affected drugs. Examples of such interactions include

• olchicine (Colcrys),
• simvastatin (Zocor),
• lovastatin (Mevacor),
• atorvastatin (Lipitor),
• verapamil (Calan),
• amlodipine (Norvasc), and
• diltiazem (Carizem).

Clarithromycin increases blood levels of sildenafil (Viagra, Revatio), tadalafil (Cialis, Adcirca), vardenafil (Levitra), theophylline and carbamazepine (Tegretol), thereby increasing side effects of these drugs.

Ritonavir (Norvir) and atazanavir (Reyataz) increase blood levels of clarithromycin while efavirenz (Sustiva), nevirapine (Viramune), rifampin, decrease blood levels of clarithromycin.

Itraconazole (Sporanox) and saquinavir (Invirase) may increase blood levels of clarithromycin while clarithromycin increases blood levels or both drugs.

The occurrence of abnormal heart beats may increase when clarithromycin is combined with drugs that affect heart beat (for example, amiodarone [Coradone], quinidine [Quinidine Gluconate, Quinidine Sulfate], and disopyramide).

Serious adverse reactions have been reported in patients taking clarithromycin concomitantly with CYP3A4 substrates. These include colchicine toxicity with colchicine; markedly increased transaminases with lomitapide; rhabdomyolysis with simvastatin, lovastatin, and atorvastatin; hypoglycemia and cardiac arrhythmias (e.g., torsades de pointes) with disopyramide; and hypotension and acute kidney injury with calcium channel blockers metabolized by CYP3A4 (e.g., verapamil, amlodipine, diltiazem, nifedipine).

Most reports of acute kidney injury with calcium channel blockers metabolized by CYP3A4 involved elderly patients 65 years of age or older. Use clarithromycin with caution when administered concurrently with medications that induce the cytochrome CYP3A4 enzyme. The use of clarithromycin with lomitapide, simvastatin, lovastatin, ergotamine, or dihydroergotamine is contraindicated.

Based on findings from animal studies, clarithromycin is not recommended for use in pregnant women except in clinical circumstances where no alternative therapy is appropriate. If clarithromycin is used during pregnancy, or if pregnancy occurs while the patient is taking this drug, the patient should be apprised of the potential hazard to the fetus. Clarithromycin demonstrated adverse effects on pregnancy outcome and/or embryo fetal development, including fetal malformations, in pregnant animals administered oral clarithromycin

Clarithromycin is excreted in breast milk. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for clarithromycin and any potential adverse effects on the breast-fed child from clarithromycin or from the underlying maternal condition.

What preparations of clarithromycin are available?

Tablets (immediate or extended release): 250 and 500 mg. Suspension: 125 or 250 mg per 5 ml (teaspoonful).

How should I keep clarithromycin stored?

Tablets and suspension should be stored at room temperature 15 -30 C (59-86 F) in a tightly closed container. The oral suspension should not be refrigerated after mixing and should be used within 14 days.