Clarithromycin
Clarithromycin, sold under the brand name Biaxin among others, is an antibiotic used to treat various bacterial infections. This includes strep throat, pneumonia, skin infections, H. pylori infection, and Lyme disease, among others. Clarithromycin can be taken by mouth as a pill or liquid.
Common side effects include nausea, vomiting, headaches, and diarrhea. Severe allergic reactions are rare. Liver problems have been reported. It may cause harm if taken during pregnancy. It is in the macrolide class and works by decreasing protein production of some bacteria.
Clarithromycin was developed in 1980 and approved for medical use in 1990. It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system. Clarithromycin is available as a generic medication. The wholesale cost in the developing world is between US$0.13 and $0.79 per dose. In the United States it is moderately expensive at $50–100 for a course of treatment. It is made from erythromycin and is chemically known as 6-O-methylerythromycin.
Medical uses
Clarithromycin is primarily used to treat a number of bacterial infections including pneumonia, Helicobacter pylori, and as an alternative to penicillin in strep throat. Other uses include cat scratch disease and other infections due to bartonella, cryptosporidiosis, as a second line agent in Lyme disease and toxoplasmosis. It may also be used to prevent bacterial endocarditis in those who cannot take penicillin. It is effective against upper and lower respiratory tract infections, skin and soft tissue infections and helicobacter pylori infections associated with duodenal ulcers.Spectrum of bacterial susceptibility
Aerobic Gram-positive bacteria- Staphylococcus aureus
- Streptococcus pneumoniae
- Streptococcus pyogenes
- Haemophilus parainfluenzae
- Haemophilus influenzae
- Moraxella catarrhalis
- Helicobacter pylori
Mycobacterium avium complex consisting of:
Other bacteria
- Chlamydia pneumoniae
- Mycoplasma pneumoniae
Aerobic Gram-positive bacteria
- Streptococcus agalactiae
- Streptococcus
- Viridans group streptococci
Anaerobic Gram-positive bacteria
- Clostridium perfringens
- Peptococcus Niger
- Cutibacterium acnes
- Prevotella melaninogenica
Contraindications
- Clarithromycin should not be taken by people who are allergic to other macrolides or inactive ingredients in the tablets, including microcrystalline cellulose, croscarmelose sodium, magnesium stearate, and povidone
- Clarithromycin should not be used by people with a history of cholestatic jaundice and/or liver dysfunction associated with prior clarithromycin use.
- Clarithromycin should not be used in the setting of hypokalaemia
- Use of clarithromycin with the following medications: cisapride, pimozide, astemizole, terfenadine, ergotamine, ticagrelor, ranolazine or dihydroergotamine is not recommended.
- It should not be used with colchicine in people with kidney or liver impairment.
- Concomitant use with cholesterol medications such as lovastatin or simvastatin.
- Hypersensitivity to clarithromycin or any component of the product, erythromycin, or any macrolide antibiotics.
- QT prolongation or ventricular cardiac arrhythmias, including torsade de pointes.
Side effects
Cardiac
In February 2018, the FDA issued a Safety Communication warning with respect to an increased risk for heart problems or death with the use of clarithromycin, and has recommended that alternative antibiotics be considered in those with heart disease.Clarithromycin can lead to a prolonged QT interval. In patients with long QT syndrome, cardiac disease, or patients taking other QT-prolonging medications, this can increase risk for life-threatening arrhythmias.
In one trial, the use of short-term clarithromycin treatment was correlated with an increased incidence of deaths classified as sudden cardiac deaths in stable coronary heart disease patients not using statins. Some case reports suspect it of causing liver disease.
Liver and kidney
Clarithromycin has been known to cause jaundice, cirrhosis, and kidney problems, including kidney failure.Central nervous system
Common adverse effects of clarithromycin in the central nervous system include dizziness, headaches. Rarely, it can cause ototoxicity, delirium and mania.Infection
A risk of oral candidiasis and vaginal candidiasis, due to the elimination of the yeast's natural bacterial competitors by the antibiotic, has also been noted.Pregnancy and breastfeeding
Clarithromycin should not be used in pregnant women except in situations where no alternative therapy is appropriate. Clarithromycin can cause potential hazard to the fetus hence should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. For lactating mothers it is not known whether clarithromycin is excreted in human milk.Interactions
Clarithromycin inhibits a liver enzyme, CYP3A4, involved in the metabolism of many other commonly prescribed drugs. Taking clarithromycin with other medications that are metabolized by CYP3A4 may lead to unexpected increases or decreases in drug levels.A few of the common interactions are listed below.
Colchicine
Clarithromycin has been observed to have a dangerous interaction with colchicine as the result of inhibition of CYP3A4 metabolism and P-glycoprotein transport. Combining these two drugs may lead to fatal colchicine toxicity, particularly in people with chronic kidney disease.Statins
Taking clarithromycin concurrently with certain statins increases the risk of side effects, such as muscle aches and muscle break down.Calcium channel blockers
Concurrent therapy with calcium channel blocker may increase risk of low blood pressure, kidney failure, and death, compared to pairing calcium channel blockers with azithromycin, a drug similar to clarithromycin but without CYP3A4 inhibition. Administration of clarithromycin in combination with verapamil have been observed to cause low blood pressure, low heart rate, and lactic acidosis.Carbamazepine
Clarithromycin may double the level of carbamazepine in the body by reducing its clearance, which may lead to toxic symptoms of carbamazepine, such as double vision, loss of voluntary body movement, nausea, as well as hyponatremia.HIV medications
Depending on the combination of medications, clarithromycin therapy could be contraindicated, require changing doses of some medications, or be acceptable without dose adjustments. For example, clarithromycin may lead to decreased zidovudine concentrations.Mechanism of action
Clarithromycin prevents bacteria from multiplying by acting as a protein synthesis inhibitor. It binds to 23S rRNA, a component of the 50S subunit of the bacterial ribosome, thus inhibiting the translation of peptides.Pharmacokinetics
Unlike erythromycin, clarithromycin is acid-stable, so can be taken orally without having to be protected from gastric acids. It is readily absorbed, and diffuses into most tissues and phagocytes. Due to the high concentration in phagocytes, clarithromycin is actively transported to the site of infection. During active phagocytosis, large concentrations of clarithromycin are released; its concentration in the tissues can be over 10 times higher than in plasma. Highest concentrations are found in liver, lung tissue, and stool.Metabolism
Clarithromycin has a fairly rapid first-pass metabolism in the liver. Its major metabolites include an inactive metabolite, N-desmethylclarithromycin, and an active metabolite, 14--hydroxyclarithromycin. Compared to clarithromycin, 14--hydroxyclarithromycin is less potent against mycobacterial tuberculosis and the Mycobacterium avium complex. Clarithromycin and its active metabolite are excreted in urine. Of all the drugs in its class, clarithromycin has the best bioavailability at 50%, which makes it amenable to oral administration.Its elimination half-life is about 3 to 4 hours with 250 mg administered every 12 h, but increased to 5 to 7 h with 500 mg administered every 8 to 12 h. With any of these dosing regimens, the steady-state concentration of this metabolite is generally attained within 3 to 4 days.