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Symfi (efavirenz / lamivudine / tenofovir) Disease Interactions

There are 12 disease interactions with Symfi (efavirenz / lamivudine / tenofovir):

Major

Emtricitabine/tenofovir (applies to Symfi) hepatitis B

Major Potential Hazard, Moderate plausibility. Applicable conditions: Infectious Hepatitis

Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF) and may occur with discontinuation of other products containing these agents. It is recommended that patients with HIV-1 be tested for the presence of chronic hepatitis B virus (HBV) infection before or when initiating antiretroviral therapy. Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue FTC and or TDF, or other products containing these drugs. If appropriate, anti-hepatitis B therapy may be warranted according to clinical practices, especially in patients with advanced liver disease or cirrhosis, since post-treatment exacerbation of hepatitis may lead to hepatic decompensation and liver failure.

Major

NRTIs (applies to Symfi) hepatotoxicity

Major Potential Hazard, Moderate plausibility. Applicable conditions: Alcoholism, Liver Disease, Alcoholism, Liver Disease

Hepatotoxicity including lactic acidosis, severe hepatomegaly with steatosis, fulminant hepatitis, and hepatic failure has been associated with the use of some nucleoside reverse transcriptase inhibitors (NRTIs) alone or in combination with other antiretroviral agents. Therapy with NRTIs should be administered cautiously in patients with preexisting liver disease, a history of alcohol abuse, or hepatitis. Therapy should be suspended if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur. The use of abacavir is contraindicated in patients with moderate to severe hepatic impairment as its safety and efficacy has not been established on these patients.

References

  1. Dolin R, Lambert JS, Morse GD, et al "2',3'-dideoxyinosine in patients with AIDS or AIDS-related complex." Rev Infect Dis 12 (1990): s540-51
  2. Montaner JSG, Rachlis A, Beaulieu R, Gill J, Schlech W, Phillips P, Auclair C, Boulerice F, Schindzielorz A, Smaldone L, Wainber "Safety profile of didanosine among patients with advanced HIV disease who are intolerant to or deteriorate despite zidovudine therapy: results of the canadian open ddi treatment program." J Acquir Immune Defic Syndr 7 (1994): 924-30
  3. "Product Information. Retrovir (zidovudine)." Glaxo Wellcome, Research Triangle Park, NC.
  4. "Product Information. Viread (tenofovir)." Gilead Sciences, Foster City, CA.
  5. Lai KK, Gang DL, Zawacki JK, Cooley TP "Fulminant hepatic failure associated with 2',3'-dideoxyinosine (ddI)." Ann Intern Med 115 (1991): 283-4
  6. Chen SC, Barker SM, Mitchell DH, et al "Concurrent zidovudine-induced myopathy and hepatoxicity in patients treated for human immunodeficiency virus (HIV) infection." Pathology 24 (1992): 109-11
  7. Shriner K, Goetz MB "Severe hepatoxicity in a patient receiving both acetaminophen and zidovudine." Am J Med 93 (1992): 94-6
  8. Gradon JD, Chapnick EK, Sepkowitz DV "Zidovudine-induced hepatitis." J Intern Med 231 (1992): 317-8
  9. Boubaker K, Flepp M, Sudre P, et al. "Hyperlactatemia and Antiretroviral Therapy: The Swiss HIV Cohort Study." Clin Infect Dis 33 (2001): 1931-7
  10. Miller KD, Cameron M, Wood LV, Dalakas MC, Kovacs JA "Lactic acidosis and hepatic steatosis associated with use of stavudine: report of four cases." Ann Intern Med 133 (2000): 192-6
  11. "Product Information. HIVID (zalcitabine)." Roche Laboratories, Nutley, NJ.
  12. Dubin G, Braffman MN "Zidovudine-induced hepatotoxicity." Ann Intern Med 110 (1989): 85-6
  13. Lonergan JT, Behling C, Pfander H, Hassanein TI, Mathews WC "Hyperlactatemia and hepatic abnormalities in 10 human immunodeficiency virus-infected patients receiving nucleoside analogue combination regimens." Clin Infect Dis 31 (2000): 162-6
  14. Shintaku M, Nasu K, Shimizu T "Fulminant hepatic failure in an AIDS patient: possible zidovudine- induced hepatotoxicity." Am J Gastroenterol 88 (1993): 464-6
  15. Yarchoan R, Mitsuya H, Pluda JM, et al "The National Cancer Institute phase I study of 2',3'-dideoxyinosine administration in adults with AIDS-related complex: analysis of activity and toxicity profiles." Rev Infect Dis 12 (1990): s522-33
  16. Kronenberg A, Riehle HM, Gunthard HF "Liver failure after long-term nucleoside antiretroviral therapy." Lancet 358 (2001): 759-601
  17. Pike IM, Nicaise C "The didanosine Expanded Access Program: safety analysis." Clin Infect Dis 16 (1993): S63-8
  18. Coghlan ME, Sommadossi JP, Jhala NC, Many WJ, Saag MS, Johnson VA "Symptomatic lactic acidosis in hospitalized antiretroviral-treated patients with human immunodeficiency virus infection: a report of 12 cases." Clin Infect Dis 33 (2001): 1914-21
  19. Pai VB, Koranyi K, Nahata MC "Acute hepatitis and bleeding possibly induced by zidovudine and ritonavir in an infant with HIV infection." Pharmacotherapy 20 (2000): 1135-40
  20. "Product Information. Videx (didanosine)." Bristol-Myers Squibb, Princeton, NJ.
  21. "Product Information. Ziagen (abacavir)." Glaxo Wellcome, Research Triangle Pk, NC.
  22. Lhouri S, Cushing H "Lactic acidosis secondary to nucleoside analog antiretroviral therapy." Infect Med 17 (2000): 547-54
View all 22 references
Major

NRTIs (applies to Symfi) pancreatitis

Major Potential Hazard, Moderate plausibility. Applicable conditions: Hyperlipidemia, Alcoholism

The reverse transcriptase inhibitors, didanosine (ddI), zalcitabine (ddC), stavudine (d4T) and lamivudine (3TC), may cause pancreatitis. The incidence is generally low but is approximately 7% with ddI, and up to 15% in pediatric patients given 3TC. Patients with a history of or known risk factors for pancreatitis, such as alcohol abuse or hypertriglyceridemia, should be monitored closely during therapy with these agents. Therapy should be discontinued at the first signs or symptoms suggestive of pancreatitis (e.g., nausea, vomiting, abdominal pain, hyperamylasemia with dysglycemia, rising triglycerides, decreasing serum calcium), and preferably permanently discontinued if clinical pancreatitis develops.

References

  1. "Product Information. Zerit (stavudine)." Bristol-Myers Squibb, Princeton, NJ.
  2. van Leeuwen R, Katlama C, Kitchen V, Boucher CA, Tubiana R, McBride M, Ingrand D, Weber J, Hill A, McDade H, et al "Evaluation of safety and efficacy of 3TC (lamivudine) in patients with asymptomatic or mildly symptomatic human immunodeficiency virus infection: a phase I/II study." J Infect Dis 171 (1995): 1166-71
  3. Dolin R, Lambert JS, Morse GD, et al "2',3'-dideoxyinosine in patients with AIDS or AIDS-related complex." Rev Infect Dis 12 (1990): s540-51
  4. van Leeuwen R, Lange JM, Hussey EK, Donn KH, Hall ST, Harker AJ, Jonker P, Danner SA "The safety and pharmacokinetics of a reverse transcriptase inhibitor, 3TC, in patients with HIV infection: a phase I study." AIDS 6 (1992): 1471-5
  5. Yarchoan R, Mitsuya H, Pluda JM, et al "The National Cancer Institute phase I study of 2',3'-dideoxyinosine administration in adults with AIDS-related complex: analysis of activity and toxicity profiles." Rev Infect Dis 12 (1990): s522-33
  6. Matthews SJ, Cersosimo RJ, Spivack ML "Zidovudine and other reverse transcriptase inhibitors in the management of human immunodeficiency virus-related disease." Pharmacotherapy 11 (1991): 419-49
  7. Shelton MJ, O'Donnell AM, Morse GD "Didanosine." Ann Pharmacother 26 (1992): 660-70
  8. "Product Information. Videx (didanosine)." Bristol-Myers Squibb, Princeton, NJ.
  9. Moore RD, Fortgang I, Keruly J, Chaisson RE "Adverse events from drug therapy for human immunodeficiency virus disease." Am J Med 101 (1996): 34-40
  10. Whittington R, Brogden RN "Zalcitabine: a review of its pharmacology and clinical potential in acquired immunodeficiency syndrome (AIDS)." Drugs 44 (1992): 656-83
  11. "Product Information. HIVID (zalcitabine)." Roche Laboratories, Nutley, NJ.
  12. Grasela TH, Walawander CA, Beltangady M, Knupp CA, Martin RR, Dunkle LM, Barbhaiya RH, Pittman KA, Dolin R, Valentine FT, "Analysis of potential risk factors associated with the development of pancreatitis in phase i patients with AIDS or AIDS-related complex receiving didanosine." J Infect Dis 169 (1994): 1250-5
  13. Schindzielorz A, Pike I, Daniels M, Pacelli L, Smaldone L "Rates and risk factors for adverse events associated with didanosine in the expanded access program." Clin Infect Dis 19 (1994): 1076-83
  14. Montaner JSG, Rachlis A, Beaulieu R, Gill J, Schlech W, Phillips P, Auclair C, Boulerice F, Schindzielorz A, Smaldone L, Wainber "Safety profile of didanosine among patients with advanced HIV disease who are intolerant to or deteriorate despite zidovudine therapy: results of the canadian open ddi treatment program." J Acquir Immune Defic Syndr 7 (1994): 924-30
  15. Maxson CJ, Greenfield SM, Turner JL "Acute pancreatitis as a common complication of 2',3'-dideoxyinosine therapy in the acquired immunodeficiency syndrome." Am J Gastroenterol 87 (1992): 708-13
  16. Pike IM, Nicaise C "The didanosine Expanded Access Program: safety analysis." Clin Infect Dis 16 (1993): S63-8
  17. Bouvet E, Casalino E, Prevost MH, Vachon F "Fatal case of 2',3'-dideoxyinosine-associated pancreatitis." Lancet 336 (1990): 1515
  18. "Product Information. Epivir (lamivudine)." Glaxo Wellcome, Research Triangle Park, NC.
View all 18 references
Major

NRTIs (applies to Symfi) renal dysfunction

Major Potential Hazard, High plausibility.

Patients with clinically significant renal impairment may be at greater risk for toxicities and adverse effects from nucleoside reverse transcriptase inhibitors (NRTIs) due to decreased drug clearance. Dosage adjustments are recommended. In addition, these patients should be monitored closely during NRTI therapy, and dosages adjusted further if necessary.

References

  1. "Product Information. Retrovir (zidovudine)." Glaxo Wellcome, Research Triangle Park, NC.
  2. "Product Information. Epivir (lamivudine)." Glaxo Wellcome, Research Triangle Park, NC.
  3. "Product Information. HIVID (zalcitabine)." Roche Laboratories, Nutley, NJ.
  4. "Product Information. Zerit (stavudine)." Bristol-Myers Squibb, Princeton, NJ.
View all 4 references
Major

Tenofovir (applies to Symfi) renal dysfunction

Major Potential Hazard, High plausibility.

Tenofovir is primarily eliminated by the kidney via glomerular filtration and active tubular secretion. Renal impairment, including acute renal failure and Fanconi syndrome, has been reported with tenofovir use. Close monitoring of renal function and lengthening the dosing interval are recommended for patients with creatinine clearance less than 50 mL/min. Creatinine clearance should be calculated in all patients before starting tenofovir treatment and during treatment when clinically appropriate. Routine monitoring of serum creatinine and phosphorus is recommended for patients at risk of or with a history of renal dysfunction. Safety and effectiveness have not been evaluated in patients with renal insufficiency using dose adjustments; therefore, the benefit of tenofovir treatment should be weighed against the risk of renal toxicity. Tenofovir should be avoided in patients who are currently using or have recently used nephrotoxic drugs.

References

  1. "Product Information. Viread (tenofovir)." Gilead Sciences, Foster City, CA.
Moderate

Efavirenz (applies to Symfi) cholesterol

Moderate Potential Hazard, Moderate plausibility. Applicable conditions: Hyperlipidemia

Increases in total cholesterol and triglycerides have resulted during treatment with efavirenz. Lipid levels monitoring should be performed before starting treatment and at periodic intervals during therapy.

References

  1. "Product Information. Sustiva (efavirenz)." DuPont Pharmaceuticals, Wilmington, DE.
Moderate

Efavirenz (applies to Symfi) liver disease

Moderate Potential Hazard, High plausibility.

Efavirenz is primarily metabolized by the liver. Patients with liver disease may be at greater risk for adverse effects from efavirenz due to decreased drug clearance. Therapy with efavirenz should be administered cautiously in patients with liver disease. In addition, elevations in serum transaminases to greater than five times the upper limit of normal as well as acute liver failure requiring transplantation have occurred during therapy with efavirenz, most often in patients with a prior history of Hepatitis B and/or C. Monitoring of liver function tests is recommended in these patients.

References

  1. "Product Information. Sustiva (efavirenz)." DuPont Pharmaceuticals, Wilmington, DE.
Moderate

Efavirenz (applies to Symfi) mental symptoms

Moderate Potential Hazard, Low plausibility. Applicable conditions: Psychosis, History - Psychiatric Disorder, Drug Abuse/Dependence, Alcoholism, Depression

During clinical trials, there have been infrequent reports of delusions and inappropriate behavior associated with the use of efavirenz, predominantly in patients with a history of mental illness or substance abuse. Severe acute depression, including suicide attempts and suicidal ideation, has also been reported but was not limited to efavirenz treated patients. Therapy with efavirenz should be administered cautiously in patients with a current or past history of psychiatric illness, emotional instability, or substance abuse. If symptoms develop or worsen during treatment, discontinuation of efavirenz may be necessary.

References

  1. "Product Information. Sustiva (efavirenz)." DuPont Pharmaceuticals, Wilmington, DE.
Moderate

Efavirenz (applies to Symfi) QT prolongation

Moderate Potential Hazard, Moderate plausibility. Applicable conditions: Long QT Syndrome

QTc prolongation has been observed with the use of efavirenz. Alternatives to efavirenz should be considered when administered to patients at higher risk of torsade de pointes or when coadministered with a medication with known risk of torsade de pointes.

Moderate

Efavirenz (applies to Symfi) seizures

Moderate Potential Hazard, Moderate plausibility.

Convulsions have been observed in adult and pediatric patients receiving efavirenz, generally in the presence of known medical history of seizures. Caution should be taken with any patient with a history of seizures. Anticonvulsant medication such as phenytoin and phenobarbital may require periodic monitoring of plasma levels.

Moderate

Tenofovir (applies to Symfi) bone toxicity

Moderate Potential Hazard, Moderate plausibility. Applicable conditions: Osteoporosis, Vitamin D Deficiency

Osteomalacia and reduced bone mineral density have been reported in animal toxicology studies involving tenofovir exposures 6- to 12-fold those observed in humans. The mechanism of bone toxicity has not been established, and it is not known if long-term use of tenofovir disoproxil fumarate will cause bone abnormalities in humans.

References

  1. "Product Information. Viread (tenofovir)." Gilead Sciences, Foster City, CA.
Minor

Tenofovir (applies to Symfi) liver disease

Minor Potential Hazard, Low plausibility.

There are no data concerning the use of tenofovir disoproxil fumarate in patients with hepatic impairment. Tenofovir and tenofovir disoproxil are not metabolized by liver enzymes. However, since tenofovir is not entirely eliminated by the kidney (70% to 80%), tenofovir pharmacokinetics may be altered in patients with impaired hepatic function.

References

  1. "Product Information. Viread (tenofovir)." Gilead Sciences, Foster City, CA.

Symfi (efavirenz / lamivudine / tenofovir) drug interactions

There are 771 drug interactions with Symfi (efavirenz / lamivudine / tenofovir)

Symfi (efavirenz / lamivudine / tenofovir) alcohol/food interactions

There are 4 alcohol/food interactions with Symfi (efavirenz / lamivudine / tenofovir)

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.