Lamivudine + Zidovudine interactions

Food & lifestyle

• high-fat foods

  Minor

  Absorption

  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.

  What to do: 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.

  4 sources

  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 (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

Conditions

Conditions in which Lamivudine + Zidovudine needs care, as documented in this source.

• Bone Marrow Failure Disorders

  Major

  Zidovudine (AZT) may cause bone marrow toxicity, most commonly manifested as granulocytopenia and anemia, particularly in patients with advanced, symptomatic HIV disease. Thrombocytopenia not related to HIV may also occasionally occur. Zidovudine should be given with extreme caution to patients with preexisting bone marrow depression (indicated by a granulocyte count below 1000 cells/mm3 or hemoglobin less than 9.5 g/dL) or blood dyscrasias. Routine blood counts are recommended, and generally should occur more frequently in patients with advanced HIV disease. Dosage reductions may be necessary.

  4 sources

  1. Goldsmith JC, Irvine W "Reversible agranulocytosis related to azidothymidine therapy." Am J Hematol 30 (1989): 263-4
  2. Baum MK, Javier JJ, Mantero-Atienza E, et al. "Zidovudine-associated adverse reactions in a longitudinal study of asymptomatic HIV-1-infected homosexual males." J Acquir Immune Defic Syndr 4 (1991): 1218-26
  3. "Product Information. Retrovir (zidovudine)." Glaxo Wellcome (2001):
  4. 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

• Kidney Diseases

  Major

  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.

  4 sources

  1. "Product Information. HIVID (zalcitabine)." Roche Laboratories (2001):
  2. "Product Information. Retrovir (zidovudine)." Glaxo Wellcome (2001):
  3. "Product Information. Zerit (stavudine)." Bristol-Myers Squibb (2001):
  4. "Product Information. Epivir (lamivudine)." Glaxo Wellcome (2001):

• Kidney Diseases

  Major

  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.

  4 sources

  1. "Product Information. HIVID (zalcitabine)." Roche Laboratories (2001):
  2. "Product Information. Retrovir (zidovudine)." Glaxo Wellcome (2001):
  3. "Product Information. Zerit (stavudine)." Bristol-Myers Squibb (2001):
  4. "Product Information. Epivir (lamivudine)." Glaxo Wellcome (2001):

• Liver Diseases

  Major

  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.

  24 sources

  1. 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
  2. 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
  3. Lai KK, Gang DL, Zawacki JK, Cooley TP "Fulminant hepatic failure associated with 2',3'-dideoxyinosine (ddI)." Ann Intern Med 115 (1991): 283-4
  4. Dubin G, Braffman MN "Zidovudine-induced hepatotoxicity." Ann Intern Med 110 (1989): 85-6
  5. Shriner K, Goetz MB "Severe hepatoxicity in a patient receiving both acetaminophen and zidovudine." Am J Med 93 (1992): 94-6
  6. Gradon JD, Chapnick EK, Sepkowitz DV "Zidovudine-induced hepatitis." J Intern Med 231 (1992): 317-8
  7. 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
  8. "Product Information. Videx (didanosine)." Bristol-Myers Squibb (2002):

  Show all 24 sourcesShow fewer sources

  9. "Product Information. HIVID (zalcitabine)." Roche Laboratories (2001):
  10. "Product Information. Retrovir (zidovudine)." Glaxo Wellcome (2001):
  11. Pike IM, Nicaise C "The didanosine Expanded Access Program: safety analysis." Clin Infect Dis 16 (1993): S63-8
  12. Shintaku M, Nasu K, Shimizu T "Fulminant hepatic failure in an AIDS patient: possible zidovudine- induced hepatotoxicity." Am J Gastroenterol 88 (1993): 464-6
  13. 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
  14. "Product Information. Epivir (lamivudine)." Glaxo Wellcome (2001):
  15. "Product Information. Ziagen (abacavir)." Glaxo Wellcome (2001):
  16. 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
  17. Lhouri S, Cushing H "Lactic acidosis secondary to nucleoside analog antiretroviral therapy." Infect Med 17 (2000): 547-54
  18. 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
  19. 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
  20. Kronenberg A, Riehle HM, Gunthard HF "Liver failure after long-term nucleoside antiretroviral therapy." Lancet 358 (2001): 759-601
  21. Boubaker K, Flepp M, Sudre P, et al. "Hyperlactatemia and Antiretroviral Therapy: The Swiss HIV Cohort Study." Clin Infect Dis 33 (2001): 1931-7
  22. 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
  23. "Product Information. Viread (tenofovir)." Gilead Sciences (2001):
  24. "Product Information. Baraclude (entecavir)." Bristol-Myers Squibb (2005):

• Liver Diseases

  Major

  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.

  24 sources

  1. 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
  2. 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
  3. Lai KK, Gang DL, Zawacki JK, Cooley TP "Fulminant hepatic failure associated with 2',3'-dideoxyinosine (ddI)." Ann Intern Med 115 (1991): 283-4
  4. Dubin G, Braffman MN "Zidovudine-induced hepatotoxicity." Ann Intern Med 110 (1989): 85-6
  5. Shriner K, Goetz MB "Severe hepatoxicity in a patient receiving both acetaminophen and zidovudine." Am J Med 93 (1992): 94-6
  6. Gradon JD, Chapnick EK, Sepkowitz DV "Zidovudine-induced hepatitis." J Intern Med 231 (1992): 317-8
  7. 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
  8. "Product Information. Videx (didanosine)." Bristol-Myers Squibb (2002):

  Show all 24 sourcesShow fewer sources

  9. "Product Information. HIVID (zalcitabine)." Roche Laboratories (2001):
  10. "Product Information. Retrovir (zidovudine)." Glaxo Wellcome (2001):
  11. Pike IM, Nicaise C "The didanosine Expanded Access Program: safety analysis." Clin Infect Dis 16 (1993): S63-8
  12. Shintaku M, Nasu K, Shimizu T "Fulminant hepatic failure in an AIDS patient: possible zidovudine- induced hepatotoxicity." Am J Gastroenterol 88 (1993): 464-6
  13. 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
  14. "Product Information. Epivir (lamivudine)." Glaxo Wellcome (2001):
  15. "Product Information. Ziagen (abacavir)." Glaxo Wellcome (2001):
  16. 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
  17. Lhouri S, Cushing H "Lactic acidosis secondary to nucleoside analog antiretroviral therapy." Infect Med 17 (2000): 547-54
  18. 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
  19. 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
  20. Kronenberg A, Riehle HM, Gunthard HF "Liver failure after long-term nucleoside antiretroviral therapy." Lancet 358 (2001): 759-601
  21. Boubaker K, Flepp M, Sudre P, et al. "Hyperlactatemia and Antiretroviral Therapy: The Swiss HIV Cohort Study." Clin Infect Dis 33 (2001): 1931-7
  22. 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
  23. "Product Information. Viread (tenofovir)." Gilead Sciences (2001):
  24. "Product Information. Baraclude (entecavir)." Bristol-Myers Squibb (2005):

• Muscular Diseases

  Major

  Prolonged use of certain nucleoside reverse transcriptase inhibitors (NRTIs) such as zidovudine and telbivudine may commonly cause myopathy, including rare cases of rhabdomyolysis. The myopathy may be dose-related and is characterized by persistent, unexplained muscle aches and/or weakness in conjunction with increases in creatine phosphokinase (CPK) values. Therapy with these NRTIs should be administered cautiously in patients with preexisting myopathy or a myoneural disorder, since it may delay the recognition or confound the diagnosis of a drug-induced musculoskeletal effect. Patients should be advised to report promptly any unusual muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. NRTI therapy should be interrupted if drug-related myopathy is suspected, and discontinued if myopathy is diagnosed.

  2 sources

  1. "Product Information. Retrovir (zidovudine)." Glaxo Wellcome (2001):
  2. "Product Information. Tyzeka (telbivudine)." IDEC Pharmaceuticals Corporation (2006):

• Pancreatitis

  Major

  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.

  18 sources

  1. Shelton MJ, O'Donnell AM, Morse GD "Didanosine." Ann Pharmacother 26 (1992): 660-70
  2. 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
  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. Bouvet E, Casalino E, Prevost MH, Vachon F "Fatal case of 2',3'-dideoxyinosine-associated pancreatitis." Lancet 336 (1990): 1515
  5. 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
  6. Whittington R, Brogden RN "Zalcitabine: a review of its pharmacology and clinical potential in acquired immunodeficiency syndrome (AIDS)." Drugs 44 (1992): 656-83
  7. 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
  8. "Product Information. Videx (didanosine)." Bristol-Myers Squibb (2002):

  Show all 18 sourcesShow fewer sources

  9. "Product Information. HIVID (zalcitabine)." Roche Laboratories (2001):
  10. Pike IM, Nicaise C "The didanosine Expanded Access Program: safety analysis." Clin Infect Dis 16 (1993): S63-8
  11. 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
  12. "Product Information. Zerit (stavudine)." Bristol-Myers Squibb (2001):
  13. 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
  14. 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
  15. 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
  16. 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
  17. "Product Information. Epivir (lamivudine)." Glaxo Wellcome (2001):
  18. 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