Clarithromycin with Glyburide Interaction Details

Brand Names Associated with Clarithromycin

Brand Names Associated with Glyburide

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 21, 2023

Interaction Effect

Increased plasma glyBURIDE concentrations and an increased risk of hypoglycemia

Interaction Summary

Use caution when prescribing clarithromycin in patients taking glyBURIDE, particularly in patients with compromised renal function. Case reports have described hypoglycemia in elderly patients receiving clarithromycin and glyBURIDE concurrently. A pharmacokinetic study demonstrated a statistically significant, modest increase in glyBURIDE AUC and Cmax in healthy patients concurrently given 250 mg twice daily of oral clarithromycin and 0.875 mg oral glyBURIDE, but no incidences of hypoglycemia were reported . In patients receiving these agents together, consider additional blood glucose monitoring and patient counseling about the signs and symptoms of hypoglycemia and actions to take if the patient becomes hypoglycemic.

Severity

Moderate

Onset

Rapid

Evidence

Established

How To Manage Interaction

Use caution with the concurrent use of clarithromycin and glyBURIDE as this resulted in increased glyBURIDE plasma levels in a pharmacokinetic study and case reports have described acute hypoglycemia in elderly patients. Consider additional blood glucose monitoring when starting clarithromycin therapy in patients taking glyBURIDE and consider additional patient education on the signs and symptoms of hypoglycemia.

Mechanism Of Interaction

Blockade of P-glycoprotein in the intestine preventing efflux of glyBURIDE into the intestinal lumen, or displacement of glyBURIDE from protein binding sites

Literature Reports

A) In a randomized, 3 phase, pharmacokinetic crossover study with healthy subjects (n=12; age range, 20-27 years), concomitant administration of clarithromycin and glyBURIDE modestly increased glyBURIDE AUC and Cmax. Subjects were given either oral clarithromycin 250 mg twice daily, grapefruit juice (200 mL 3 times daily), or placebo for 2 days. On day 3, they received 0.875 mg of oral glyBURIDE and levels were drawn at various intervals for 12 hours. The subjects were given aggressive caloric intake to prevent hypoglycemia as a safety measure. After a 2 week washout period, the patients were reassigned to another arm and the treatment program was repeated. Results showed statistically significant increases of 1.35-fold (95% confidence interval (CI), 1.21 to 1.5) and 1.25-fold (95% CI, 1.21 to 1.5) in AUC and Cmax, respectively, of glyBURIDE in the clarithromycin treatment group compared to placebo (p less than 0.01 for both). The Tmax and half life of glyBURIDE were not significantly altered, which indicated that altered glyBURIDE renal excretion was not involved in the interaction. Since the patients were not having diabetes and were given a high caloric intake, there were no incidences of hypoglycemia and the blood glucose levels in the patients did not significantly differ from the placebo group. Clarithromycin levels were not significantly altered in any of the arms, and grapefruit juice did not significantly alter the AUC and Cmax of glyBURIDE. Postulated mechanisms included inhibition of p-glycoprotein by clarithromycin in the intestine, thus preventing efflux of glyBURIDE into the intestinal lumen; or inhibition of CYP3A4-mediated glyBURIDE metabolism (minor) .

B) A case report described acute hypoglycemia with concomitant administration of clarithromycin in an 82-year-old male with a 4 month history of type 2 diabetes who was taking 5 mg oral glyBURIDE daily. His comorbidities included hypertension, atherosclerotic heart disease, emphysema, bladder cancer, and a mild renal failure with a serum creatinine of 1.6 mg/dL. His usual blood glucose readings were in the low 100s (mg/dL). After a bronchitis diagnosis, he was prescribed 1000 mg of oral clarithromycin daily. Within 48 hours, his blood glucose dropped to 24 mg/dL and he became unresponsive. Administration of intravenous (IV) dextrose resolved the hypoglycemia. However, he became hypoglycemic again 12 hours later and was found unresponsive, with a blood glucose reading in the 0-30 mg/dL range. Repeat administration of IV dextrose resolved the hypoglycemia. Subsequently, glyBURIDE was discontinued and the patient did not experience any additional episodes of hypoglycemia. Displacement of the sulfonylurea from protein binding sites by the clarithromycin or alterations in drug excretion were postulated as probable mechanisms for this interaction .

C) A case report described acute hypoglycemia in an 89-year-old male, receiving oral glyBURIDE (5 mg/day) for type 2 diabetes, following concomitant administration of clarithromycin as part of triple therapy (clarithromycin 1,000 mg/day, amoxicillin 2,000 mg/day, and omeprazole 40 mg/day) treatment for a Helicobacter pylori gastrointestinal infection. Two days after initiation of the triple therapy, the patient presented to the emergency department in a comatose state with a glucose reading of 20 mg/dL. Other medications included leuprolide acetate, citalopram, doxazosin, atenolol, and hydrochlorothiazide/amiloride. The patient had normal renal function and denied any drug overdose. There was no evidence of other causes of hypoglycemia (hepatic, renal, or heart failure, malignancy, or sepsis). Serum glyBURIDE levels were within normal therapeutic range. Discontinuation of glyBURIDE and treatment with intravenous dextrose led to a full recovery. Clarithromycin was replaced with metronidazole, after which the hypoglycemia did not reoccur. Displacement of glyBURIDE from protein binding sties in the plasma by clarithromycin, effectively increasing the free plasma concentration of glyBURIDE, was proposed as the mechanism. As the patient had normal renal function, the impact of clarithromycin on the excretion of glyBURIDE was ruled an unlikely cause of the interaction .

Clarithromycin Overview

• Clarithromycin is used to treat certain bacterial infections, such as pneumonia (a lung infection), bronchitis (infection of the tubes leading to the lungs), and infections of the ears, sinuses, skin, and throat. It also is used to treat and prevent disseminated Mycobacterium avium complex (MAC) infection [a type of lung infection that often affects people with human immunodeficiency virus (HIV)]. It is used in combination with other medications to eliminate H. pylori, a bacterium that causes ulcers. Clarithromycin is in a class of medications called macrolide antibiotics. It works by stopping the growth of bacteria.

• Antibiotics such as clarithromycin will not work for colds, flu, or other viral infections. Taking antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

Glyburide Overview

• Glyburide is used along with diet and exercise, and sometimes with other medications, to treat type 2 diabetes (condition in which the body does not use insulin normally and, therefore, cannot control the amount of sugar in the blood). Glyburide is in a class of medications called sulfonylureas. Glyburide lowers blood sugar by causing the pancreas to produce insulin (a natural substance that is needed to break down sugar in the body) and helping the body use insulin efficiently. This medication will only help lower blood sugar in people whose bodies produce insulin naturally. Glyburide is not used to treat type 1 diabetes (condition in which the body does not produce insulin and, therefore, cannot control the amount of sugar in the blood) or diabetic ketoacidosis (a serious condition that may occur if high blood sugar is not treated).

• Over time, people who have diabetes and high blood sugar can develop serious or life-threatening complications, including heart disease, stroke, kidney problems, nerve damage, and eye problems. Taking medication(s), making lifestyle changes (e.g., diet, exercise, quitting smoking), and regularly checking your blood sugar may help to manage your diabetes and improve your health. This therapy may also decrease your chances of having a heart attack, stroke, or other diabetes-related complications such as kidney failure, nerve damage (numb, cold legs or feet; decreased sexual ability in men and women), eye problems, including changes or loss of vision, or gum disease. Your doctor and other healthcare providers will talk to you about the best way to manage your diabetes.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.