Skip to main content

Drug Interactions between Combivir and efavirenz

This report displays the potential drug interactions for the following 2 drugs:

Edit list (add/remove drugs)

Interactions between your drugs

Moderate

zidovudine efavirenz

Applies to: Combivir (lamivudine / zidovudine) and efavirenz

MONITOR: Coadministration of efavirenz with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Efavirenz has been associated with hepatotoxicity during postmarketing use. Among reported cases of hepatic failure, a few occurred in patients with no preexisting hepatic disease or other identifiable risk factors.

MANAGEMENT: The risk of hepatic injury should be considered when efavirenz is used in combination with other agents that are potentially hepatotoxic (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; minocycline; nonsteroidal anti-inflammatory agents; other HIV reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice. Monitoring of liver function tests should occur before and during treatment, especially in patients with underlying hepatic disease (including hepatitis B or C coinfection) or marked transaminase elevations. The benefit of continued therapy with efavirenz should be considered against the unknown risks of significant liver toxicity in patients who develop persistent elevations of serum transaminases greater than five times the upper limit of normal.

References

  1. "Product Information. Sustiva (efavirenz)." DuPont Pharmaceuticals PROD (2001):
  2. Elsharkawy AM, Schwab U, McCarron B, et al. "Efavirenz induced acute liver failure requiring liver transplantation in a slow drug metaboliser." J Clin Virol 58 (2013): 331-3

Switch to consumer interaction data

Moderate

lamiVUDine efavirenz

Applies to: Combivir (lamivudine / zidovudine) and efavirenz

MONITOR: Coadministration of efavirenz with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Efavirenz has been associated with hepatotoxicity during postmarketing use. Among reported cases of hepatic failure, a few occurred in patients with no preexisting hepatic disease or other identifiable risk factors.

MANAGEMENT: The risk of hepatic injury should be considered when efavirenz is used in combination with other agents that are potentially hepatotoxic (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; minocycline; nonsteroidal anti-inflammatory agents; other HIV reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice. Monitoring of liver function tests should occur before and during treatment, especially in patients with underlying hepatic disease (including hepatitis B or C coinfection) or marked transaminase elevations. The benefit of continued therapy with efavirenz should be considered against the unknown risks of significant liver toxicity in patients who develop persistent elevations of serum transaminases greater than five times the upper limit of normal.

References

  1. "Product Information. Sustiva (efavirenz)." DuPont Pharmaceuticals PROD (2001):
  2. Elsharkawy AM, Schwab U, McCarron B, et al. "Efavirenz induced acute liver failure requiring liver transplantation in a slow drug metaboliser." J Clin Virol 58 (2013): 331-3

Switch to consumer interaction data

Drug and food interactions

Moderate

efavirenz food

Applies to: efavirenz

ADJUST DOSING INTERVAL: Administration with food increases the plasma concentrations of efavirenz and may increase the frequency of adverse reactions. According to the product labeling, administration of efavirenz capsules (600 mg single dose) with a high-fat/high-caloric meal (894 kcal, 54 g fat, 54% calories from fat) or a reduced-fat/normal-caloric meal (440 kcal, 2 g fat, 4% calories from fat) was associated with mean increases of 39% and 51% in efavirenz peak plasma concentration (Cmax) and 22% and 17% in systemic exposure (AUC), respectively, compared to administration under fasted conditions. For efavirenz tablets, administration of a single 600 mg dose with a high-fat/high-caloric meal (approximately 1000 kcal, 500-600 kcal from fat) resulted in a 79% increase in mean Cmax and a 28% increase in mean AUC of efavirenz relative to administration under fasted conditions.

MANAGEMENT: Efavirenz should be taken on an empty stomach, preferably at bedtime. Dosing at bedtime may improve the tolerability of nervous system symptoms such as dizziness, insomnia, impaired concentration, somnolence, abnormal dreams and hallucinations, although they often resolve on their own after the first 2 to 4 weeks of therapy . Patients should be advised of the potential for additive central nervous system effects when efavirenz is used concomitantly with alcohol or psychoactive drugs, and to avoid driving or operating hazardous machinery until they know how the medication affects them.

References

  1. "Product Information. Sustiva (efavirenz)." DuPont Pharmaceuticals PROD (2001):

Switch to consumer interaction data

Minor

zidovudine food

Applies to: Combivir (lamivudine / zidovudine)

Food may have variable effects on the oral bioavailability of zidovudine. Fatty foods have been reported to decrease the rate and extent of zidovudine absorption following oral administration. In a study of 13 AIDS patients, mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of zidovudine were 2.8 and 1.4 times higher, respectively, in fasting patients than in those administered the medication with breakfast. In addition, variations in plasma zidovudine concentrations were increased when administered in the fed state. In another study of eight patients, the time to reach peak concentration (Tmax) was increased from 0.68 to 1.95 hours, and Cmax was reduced by 50% when zidovudine was administered with a liquid high-fat meal relative to fasting. Protein meals can also delay the absorption and reduce the Cmax of zidovudine, although the extent of absorption is not significantly affected. The clinical significance of these alterations, if any, is unknown. The product labeling states that zidovudine may be taken with or without food.

References

  1. Lotterer E, Ruhnke M, Trautman M, et al. "Decreased and variable systemic availability of zidovudine in patients with AIDS if administered with a meal." Eur J Clin Pharmacol 40 (1991): 305-8
  2. Unadkat JD, Collier AC, Crosby SS, et al. "Pharmacokinetics of oral zidovudine (azidothymidine) in patients with AIDS when administered with and without a high-fat meal." AIDS 4 (1990): 229-32
  3. "Product Information. Retrovir (zidovudine)." Glaxo Wellcome PROD (2001):
  4. Sahai J, Gallicano K, Garber G, et al. "The effect of a protein meal on zidovudine pharmacokinetics in HIV-infected patients." Br J Clin Pharmacol 33 (1992): 657-60
View all 4 references

Switch to consumer interaction data

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.


Report options

Loading...
QR code containing a link to this page

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.