Clarithromycin is a macrolide antibiotic used to treat a variety of bacterial infections, from skin infections to H. pylori stomach ulcers [1.3.4]. While effective, it is not suitable for everyone. A significant number of individuals have contraindications, meaning the drug should not be used because the risk of harm outweighs any potential benefit. Knowing these restrictions is vital for patient safety.
Absolute Contraindications: When Clarithromycin is Off-Limits
Certain conditions and concomitant medications make the use of clarithromycin strictly contraindicated.
Allergic Reactions
Anyone with a known hypersensitivity to clarithromycin, erythromycin, or any other macrolide antibiotic should not take this medication [1.2.1]. Severe allergic reactions can occur, including anaphylaxis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which are life-threatening skin conditions [1.2.1, 1.5.2].
History of Liver Problems with Clarithromycin
Patients who have previously experienced cholestatic jaundice (a type of liver dysfunction that impairs bile flow) or other hepatic dysfunction associated with prior use of clarithromycin are contraindicated from taking it again [1.2.1, 1.6.2].
Critical Drug Interactions
Clarithromycin is a strong inhibitor of the CYP3A4 enzyme, which is responsible for metabolizing many drugs [1.6.1]. When taken concurrently, clarithromycin can cause levels of other drugs to rise to toxic levels. For this reason, co-administration with the following is contraindicated:
- Cisapride and Pimozide: Used for gastrointestinal and psychiatric conditions, respectively. Taking them with clarithromycin can lead to severe cardiac arrhythmias like QT prolongation, ventricular tachycardia, and torsades de pointes, which can be fatal [1.2.1].
- Lovastatin and Simvastatin: These cholesterol-lowering statins, when combined with clarithromycin, have an increased risk of myopathy (muscle disease) and rhabdomyolysis (muscle breakdown) [1.2.1].
- Ergotamine and Dihydroergotamine: These migraine medications can cause sudden narrowing of blood vessels and reduced blood flow to limbs when taken with clarithromycin [1.4.3].
- Colchicine: When taken by patients with renal (kidney) or hepatic (liver) impairment, the combination with clarithromycin is contraindicated due to the risk of life-threatening colchicine toxicity [1.2.1].
- Lomitapide and Lurasidone: Concomitant use with lomitapide can lead to markedly increased liver enzymes [1.2.1]. With lurasidone, it can result in increased exposure and serious adverse reactions [1.2.2].
Warnings and Precautions for Specific Patient Groups
Beyond absolute contraindications, there are several patient populations who must use clarithromycin with extreme caution or avoid it altogether.
Patients with Heart Conditions
Clarithromycin has been associated with prolongation of the QT interval, an electrical event in the heart [1.8.2]. This can lead to serious arrhythmias. Therefore, it should be avoided in patients with:
- A known history of QT prolongation or ventricular cardiac arrhythmia, including torsades de pointes [1.8.2].
- Uncorrected electrolyte imbalances like low potassium (hypokalemia) or low magnesium (hypomagnesemia) [1.3.2, 1.3.3].
- Clinically significant bradycardia (slow heartbeat) [1.3.2].
- Coronary artery disease. One study noted an increased risk of all-cause mortality a year or more after treatment in patients with coronary artery disease [1.2.1]. The FDA has also issued warnings about an increased risk of heart problems or death in those with heart disease [1.2.4].
Patients with Pre-existing Medical Conditions
- Liver Disease: Since clarithromycin can cause hepatotoxicity, it should be used with caution in patients with pre-existing liver impairment [1.6.2]. If signs of hepatitis develop, such as jaundice, dark urine, or abdominal pain, the drug must be stopped immediately [1.2.1].
- Kidney Disease: For patients with severe renal impairment (creatinine clearance <30 mL/min), a dose reduction of clarithromycin is necessary because the drug is cleared by the kidneys [1.7.3]. This is especially critical as renal impairment increases the risk of toxicity from other drugs, like colchicine [1.7.1].
- Myasthenia Gravis: Clarithromycin can exacerbate the symptoms of myasthenia gravis, a condition causing severe muscle weakness [1.9.5]. Patients have reported worsening weakness and even the new onset of a myasthenic syndrome [1.2.1, 1.9.2]. It is best avoided if possible in this population [1.9.1].
Special Populations
- Pregnancy: Clarithromycin is not recommended for use in pregnant women unless no other alternative therapy is appropriate [1.2.1]. Animal studies have shown adverse effects on fetal development, including malformations [1.10.3].
- Breastfeeding: Clarithromycin passes into breast milk in small amounts [1.10.1]. While it is generally considered acceptable, the infant should be monitored for side effects like diarrhea, thrush, or rash [1.10.1, 1.10.2].
- Elderly: Elderly patients may be more susceptible to drug-associated side effects, particularly QT interval prolongation and hearing loss [1.3.2]. They are also at higher risk for acute kidney injury when clarithromycin is combined with certain calcium channel blockers [1.2.1].
Comparison Table: Clarithromycin vs. Azithromycin
| Feature | Clarithromycin | Azithromycin |
|---|---|---|
| Primary Contraindication | History of cholestatic jaundice with prior use; numerous critical drug interactions (e.g., simvastatin, lovastatin, pimozide) [1.2.1]. | Hypersensitivity to azithromycin, erythromycin, or other macrolides. History of cholestatic jaundice/hepatic dysfunction with prior azithromycin use. |
| CYP3A4 Inhibition | Strong inhibitor, leading to many drug interactions [1.7.1]. | Does not inhibit CYP3A4, resulting in fewer drug interactions [1.7.1]. |
| Heart Rhythm Risk | Associated with QT prolongation and increased risk of cardiac events, especially in patients with heart disease [1.2.1, 1.8.2]. | Also associated with QT prolongation, but often considered to have a slightly better cardiovascular safety profile in some contexts [1.8.1]. |
| Use in Kidney Disease | Dose adjustment required for severe renal impairment (CrCl < 30 mL/min) [1.7.3]. | No dose adjustment is typically needed [1.7.1]. |
| Myasthenia Gravis | Can exacerbate symptoms and should be used with caution [1.9.2, 1.9.5]. | Also carries a risk of exacerbating myasthenia gravis [1.9.1]. |
Conclusion
The decision to prescribe clarithromycin requires careful consideration of a patient's medical history, current medications, and underlying conditions. Individuals with a history of macrolide allergies, specific heart rhythm disorders, and those taking contraindicated drugs like certain statins or pimozide must not take it. Furthermore, caution is paramount for patients with liver or kidney disease, myasthenia gravis, and for elderly individuals. Open communication with a healthcare provider about all health conditions and medications is the best way to ensure this powerful antibiotic is used safely and effectively.
Clarithromycin Package Insert / Prescribing Information - Drugs.com
