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Drug Interactions between Atripla and halofantrine

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

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Interactions between your drugs

Major

efavirenz halofantrine

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

CONTRAINDICATED: Halofantrine can cause dose-related prolongation of the QT interval at recommended therapeutic doses. QTc interval prolongation and death have been reported during combination use of halofantrine and mefloquine. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death.

MANAGEMENT: Coadministration of halofantrine with other drugs that can prolong the QT interval is considered contraindicated. The manufacturer recommends performing an ECG before initiating halofantrine therapy and monitoring cardiac rhythm during and for 8 to 12 hours after completion of therapy.

References

  1. (2021) "Product Information. Mefloquine Hydrochloride (mefloquine)." Hikma USA (formerly West-Ward Pharmaceutical Corporation)
  2. Giao PT, de Vries PJ (2001) "Pharmacokinetic interactions of antimalarial agents." Clin Pharmacokinet, 40, p. 343-73
  3. (2003) "Product Information. Halfan (halofantrine)." GlaxoSmithKline
  4. Nosten F, ter Kuile FO, Luxemburger C, et al. (1993) "Cardiac effects of antimalarial treatment with halofantrine." Lancet, 341, p. 1054-6
  5. (2001) "Sudden death in a traveler following halofantrine administration--Togo, 2000." MMWR Morb Mortal Wkly Rep, 50, 169-70, 179
  6. Abernethy DR, Wesche DL, Barbey JT, et al. (2001) "Stereoselective halofantrine disposition and effect: concentration-related QTc prolongation." Br J Clin Pharmacol, 51, p. 231-7
  7. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  8. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  9. Cerner Multum, Inc. "Australian Product Information."
View all 9 references

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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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Drug and food interactions

Major

halofantrine food

Applies to: halofantrine

GENERALLY AVOID: Grapefruit juice may increase the plasma concentration of halofantrine. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. After administration of 500 mg with 250 mL regular-strength grapefruit juice daily for 3 days, average halofantrine AUC increased 2.8-fold and peak plasma concentrations increased 3.2-fold, compared to water, in healthy subjects (n=12). QT interval prolongation increased from an average of 17 ms with water to 31 ms with grapefruit juice. Halofantrine, even at recommended doses, can cause dose-related prolongation of the QT interval, resulting in an elevated risk of potentially fatal ventricular arrhythmias including ventricular tachycardia and torsade de pointes.

ADJUST DOSING INTERVAL: The presence of food may increase the absorption and toxicity of halofantrine. Peak plasma concentrations increased seven-fold and AUC increased three-fold in healthy subjects when halofantrine was administered with high-fat food.

MANAGEMENT: The authors of the study recommend that grapefruit juice be avoided during halofantrine therapy. The manufacturer recommends performing an ECG before initiating halofantrine therapy and cardiac monitoring during and for 8 to 12 hours after completion of therapy. Halofantrine should be taken on an empty stomach at least 1 hour before or 2 hours after food.

References

  1. Giao PT, de Vries PJ (2001) "Pharmacokinetic interactions of antimalarial agents." Clin Pharmacokinet, 40, p. 343-73
  2. (2003) "Product Information. Halfan (halofantrine)." GlaxoSmithKline
  3. Charbit B, Becquemont L, Lepere B, Peytavin G, Funck-Bretano C (2002) "Pharmacokinetic and pharmacodynamic interaction between grapefruit juice and halofantrine." Clin Pharmacol Ther, 72, p. 514-23
  4. Abernethy DR, Wesche DL, Barbey JT, et al. (2001) "Stereoselective halofantrine disposition and effect: concentration-related QTc prolongation." Br J Clin Pharmacol, 51, p. 231-7
View all 4 references

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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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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.

See also

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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

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