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Drug Interactions between efavirenz / lamivudine / tenofovir and Gamimune

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

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Interactions between your drugs

Major

immune globulin intravenous tenofovir

Applies to: Gamimune (immune globulin intravenous) and efavirenz / lamivudine / tenofovir

MONITOR CLOSELY: Coadministration of intravenous immune globulin preparations with nephrotoxic agents may potentiate the risk of renal impairment. Many commercially available intravenous formulations of immune globulin contain sucrose as a stabilizer. Immune globulin products, particularly those that contain sucrose as a stabilizer and administered at daily doses of 350 to 400 mg/kg or greater, have been associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Factors predisposing to acute renal failure include any degree of preexisting renal insufficiency, age greater than 65 years, diabetes mellitus, volume depletion, sepsis, paraproteinemia, and concomitant use of known nephrotoxic drugs.

MANAGEMENT: Intravenous immune globulin preparations should be administered cautiously in patients treated with other potentially nephrotoxic agents (e.g., e.g., aminoglycosides; polypeptide, glycopeptide, and polymyxin antibiotics; amphotericin B; adefovir; cidofovir; tenofovir; foscarnet; cisplatin; deferasirox; gallium nitrate; lithium; mesalamine; certain immunosuppressants; intravenous bisphosphonates; intravenous pentamidine; high intravenous dosages of methotrexate; high dosages and/or chronic use of nonsteroidal anti-inflammatory agents). The manufacturers recommend administering immune globulin infusions at the minimum concentration available and at the minimum rate of infusion feasible in such patients. Clinicians should ensure that patients are not volume depleted prior to the initiation of immune globulin therapy. Monitoring of urine output and renal function tests, including the measurement of blood urea nitrogen (BUN) and serum creatinine, is recommended prior to the initial infusion and at appropriate intervals thereafter. If renal function deteriorates, discontinuation of the product should be considered. Patients should be advised to seek medical attention if they experience symptoms that may indicate nephrotoxicity such as decreased urine output, sudden weight gain, fluid retention, edema, or shortness of breath.

References

  1. "Product Information. Cytogam (cytomegalovirus immune globulin)." CSL Behring LLC (2002):
  2. "Product Information. Respigam (respiratory syncytial virus immune globulin)." Medimmune Inc (2005):
  3. "Product Information. BabyBIG (botulism immune globulin)." FFF Enterprises (2008):
  4. "Product Information. Bivigam (immune globulin intravenous)." Biotest Pharmaceuticals Corporation (2013):
  5. MMWR Morb Mortal Wkly Rep "Renal insufficiency and failure associated with immune globulin intravenous therapy -- United States, 1985-1998. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm4824a3.htm" (2013):
  6. Pusey EY, Levy JB "Nephrotoxicity of intravenous immunoglobulin. http://qjmed.oxfordjournals.org/content/93/11/751.full.pdf+html" (2013):
  7. KDIGO. Kidney Disease Improving Global Outcomes "KDIGO clinical practice guideline for acute kidney injury. http://www.kdigo.org/clinical_practice_guidelines/pdf/KDIGO-AKI-Suppl-Appendices-A-F_March2012.pdf" (2013):
  8. Guo X, Nzerue C "How to prevent, recognize, and treat drug-induced nephrotoxicity. http://www.ccjm.org/content/69/4/289.full.pdf" (2013):
  9. Perazella MA "Renal vulnerability to drug toxicity. http://www.ccjm.org/content/69/4/289.full.pdf" (2013):
  10. Naughton CA "Drug-induced nephrotoxicity. http://www.aafp.org/afp/2008/0915/p743.html" (2013):
  11. Moses S "Nephrotoxic drugs, drug-induced nephrotoxicity. http://www.fpnotebook.com/Renal/Pharm/NphrtxcDrgs.htm" (2013):
View all 11 references

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Moderate

lamiVUDine efavirenz

Applies to: efavirenz / lamivudine / tenofovir and efavirenz / lamivudine / 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. "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

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Moderate

efavirenz tenofovir

Applies to: efavirenz / lamivudine / tenofovir and efavirenz / lamivudine / 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. "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

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Drug and food interactions

Moderate

efavirenz food

Applies to: efavirenz / lamivudine / 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. "Product Information. Sustiva (efavirenz)." DuPont Pharmaceuticals PROD (2001):

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Minor

tenofovir food

Applies to: efavirenz / lamivudine / 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. "Product Information. Viread (tenofovir)." Gilead Sciences (2001):

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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.