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Drug Interactions between Atripla and Byetta

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

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Interactions between your drugs

Moderate

efavirenz tenofovir

Applies to: Atripla (efavirenz / emtricitabine / tenofovir) and Atripla (efavirenz / emtricitabine / tenofovir)

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

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Moderate

efavirenz emtricitabine

Applies to: Atripla (efavirenz / emtricitabine / tenofovir) and Atripla (efavirenz / emtricitabine / tenofovir)

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

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Moderate

tenofovir exenatide

Applies to: Atripla (efavirenz / emtricitabine / tenofovir) and Byetta (exenatide)

MONITOR: Drugs that affect renal function and/or hydration status may potentiate the adverse renal effects of exenatide. The mechanism of interaction is unknown. Exenatide has not been found to be directly nephrotoxic in preclinical or clinical studies. However, there have been reports of altered renal function, including increased serum creatinine, renal impairment, worsened chronic renal failure, and acute renal failure during postmarketing use. In some cases, hemodialysis or kidney transplantation was required. Some of these events occurred in patients receiving one or more pharmacologic agents known to affect renal function or hydration status (e.g., ACE inhibitors, nonsteroidal anti-inflammatory drugs, diuretics), and some occurred in patients who had been experiencing nausea, vomiting or diarrhea, with or without dehydration. Most cases were reversible with supportive treatment and discontinuation of potentially causative agents, including exenatide.

MANAGEMENT: Clinicians should be aware of the potential for increased adverse renal effects of exenatide during coadministration with drugs that are known to affect renal function or hydration status.

References

  1. (2005) "Product Information. Byetta (exenatide)." Amylin Pharmaceuticals Inc

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Drug and food interactions

Moderate

efavirenz food

Applies to: Atripla (efavirenz / emtricitabine / tenofovir)

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. (2001) "Product Information. Sustiva (efavirenz)." DuPont Pharmaceuticals

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Moderate

exenatide food

Applies to: Byetta (exenatide)

ADJUST DOSING INTERVAL: Exenatide slows gastric emptying and may reduce the extent and rate of absorption of concomitantly administered oral medications. When acetaminophen 1000 mg was administered simultaneously with exenatide 10 mcg and also one hour, 2 hours, and 4 hours after exenatide injection, acetaminophen systemic exposure (AUC) was decreased by 21%, 23%, 24%, and 14%, respectively; peak plasma concentration (Cmax) was decreased by 37%, 56%, 54%, and 41%, respectively; and time to peak plasma concentration (Tmax) was increased from 0.6 hours in the control period to 0.9 hours, 4.2 hours, 3.3 hours, and 1.6 hours, respectively. These values were not significantly changed when acetaminophen was given one hour before exenatide injection.

MANAGEMENT: Concomitantly administered oral medications that are dependent on threshold concentrations for efficacy (e.g., antibiotics, contraceptives) or that require rapid gastrointestinal absorption (e.g., hypnotics, pain medications) should be administered at least 1 hour before exenatide. If such medications are to be administered with food, patients should be advised to take them with a meal or snack when exenatide is not administered.

References

  1. (2005) "Product Information. Byetta (exenatide)." Amylin Pharmaceuticals Inc

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Minor

tenofovir food

Applies to: Atripla (efavirenz / emtricitabine / tenofovir)

Food enhances the oral absorption and bioavailability of tenofovir, the active entity of tenofovir disoproxil fumarate. According to the product labeling, administration of the drug following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of tenofovir by approximately 14% and 40%, respectively, compared to administration in the fasting state. However, administration with a light meal did not significantly affect the pharmacokinetics of tenofovir compared to administration in the fasting state. Food delays the time to reach tenofovir Cmax by approximately 1 hour. Tenofovir disoproxil fumarate may be administered without regard to meals.

References

  1. (2001) "Product Information. Viread (tenofovir)." Gilead Sciences

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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.


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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.