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Ritonavir Disease Interactions

There are 5 disease interactions with ritonavir.

Major

PIs (applies to ritonavir) hemophilia

Major Potential Hazard, Low plausibility. Applicable conditions: Coagulation Defect

There have been postmarketing reports of increased bleeding, including spontaneous skin hematomas and hemarthrosis, in types A and B hemophiliac patients treated with protease inhibitors. However, a causal relationship has not been established. In some patients, additional Factor VIII was given. In more than half of the reported cases, protease inhibitor therapy was continued or reintroduced following an interruption. Hemophiliacs and patients with other coagulation defects should be monitored closely for bleeding during protease inhibitor therapy.

References

  1. "Product Information. Invirase (saquinavir)." Roche Laboratories (2001):
  2. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical (2001):
  3. "Product Information. Crixivan (indinavir)." Merck & Co., Inc (2001):
  4. "Product Information. Viracept (nelfinavir)." Agouron Pharma Inc (2001):
  5. "Product Information. Agenerase (amprenavir)." Glaxo Wellcome (2001):
  6. "Product Information. Kaletra (lopinavir-ritonavir)." Abbott Pharmaceutical (2001):
  7. "Product Information. Fortovase (saquinavir)." Roche Laboratories (2001):
  8. "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb (2003):
  9. "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline (2003):
  10. "Product Information. Aptivus (tipranavir)." Boehringer-Ingelheim (2005):
  11. "Product Information. Prezista (darunavir)." Ortho Biotech Inc (2006):
View all 11 references
Major

Ritonavir (applies to ritonavir) hepatotoxicity

Major Potential Hazard, High plausibility. Applicable conditions: Liver Disease

Hepatotoxicity, including jaundice, hepatitis and hepatic transaminase elevations exceeding five times the upper limit of normal, has been reported in patients receiving ritonavir alone and in combination with nucleoside reverse transcriptase inhibitors or other protease inhibitors. In addition, ritonavir is primarily metabolized by the liver and may accumulate in patients with hepatic impairment. Therapy with ritonavir should be administered cautiously in patients with preexisting liver disease, liver enzyme abnormalities, or hepatitis. Ritonavir is not recommended for patients with severe hepatic impairment.

References

  1. Markowitz M, Saag M, Powderly WG, Hurley AM, Hsu A, Valdes JM, Henry D, Sattler F, La Marca A, Leonard JM, et al. "A preliminary study of ritonavir, an inhibitor of HIV-1 protease, to treat HIV-1 infection." N Engl J Med 333 (1995): 1534-9
  2. Danner SA, Carr A, Leonard JM, Lehman LM, Gudiol F, Gonzales J, Raventos A, Rubio R, Bouza E, Pintado V, et al. "A short-term study of the safety, pharmacokinetics, and efficacy of ritonavir, an inhibitor of HIV-1 protease. European-Australian Collaborative Ritonavir Study Group." N Engl J Med 333 (1995): 1528-33
  3. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical (2001):
  4. Sommadossi JP "HIV protease inhibitors: pharmacologic and metabolic distinctions." AIDS 13 (1999): s29-40
  5. 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
View all 5 references
Moderate

PIs (applies to ritonavir) hyperglycemia

Moderate Potential Hazard, Moderate plausibility. Applicable conditions: Abnormal Glucose Tolerance, Diabetes Mellitus

New onset diabetes mellitus, exacerbation of preexisting diabetes mellitus, glucose intolerance, hyperglycemia, and some cases of diabetic ketoacidosis have been reported during postmarketing surveillance in HIV-infected patients treated with protease inhibitors (PIs). In some cases, glucose abnormalities/hyperglycemia persisted despite discontinuation of PI therapy. Frequently, insulin resistance may accompany fat redistribution and serum lipid elevations in what is collectively termed the HIV-associated lipodystrophy syndrome. Although a causal relationship has not been established, these metabolic disturbances have most often occurred in HIV-infected patients during treatment with potent antiretroviral regimens containing PIs. Monitoring patients for hyperglycemia, new onset diabetes mellitus, or exacerbation of diabetes mellitus should be considered during PI therapy. Dosage adjustments in insulin or oral hypoglycemic medications may be necessary in patients with diabetes.

References

  1. "Product Information. Invirase (saquinavir)." Roche Laboratories (2001):
  2. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical (2001):
  3. "Product Information. Crixivan (indinavir)." Merck & Co., Inc (2001):
  4. "Product Information. Viracept (nelfinavir)." Agouron Pharma Inc (2001):
  5. Dube MP, Johnson DL, Currier JS, Leedom JM "Protease inhibitor-associated hyperglycaemia." Lancet 350 (1997): 713-4
  6. Walli R, Demant T "Impaired glucose tolerance and protease inhibitors." Ann Intern Med 129 (1998): 837-8
  7. "Product Information. Agenerase (amprenavir)." Glaxo Wellcome (2001):
  8. Mauss S, Wolf E, Jaeger H "Impaired glucose tolerance in HIV-positive patients receiving and those not receiving protease inhibitors." Ann Intern Med 130 (1999): 162-3
  9. Kaufman MB, Simionatto C "A review of protease inhibitor-induced hyperglycemia." Pharmacotherapy 19 (1999): 114-7
  10. Struble K, Piscitelli SC "Syndromes of abnormal fat redistribution and metabolic complications in HIV-infected patients." Am J Health Syst Pharm 56 (1999): 2343-8
  11. Qaqish RB, Fisher E, Rublein J, Wohl DA "HIV-associated lipodystrophy syndrome." Pharmacotherapy 20 (2000): 13-22
  12. Pujol RM, Domingo P, XavierMatiasGuiu, Francia E, Sanbeat MA, Alomar A, Vazquez G "HIV-1 protease inhibitor-associated partial lipodystrophy: Clinicopathologic review of 14 cases." J Am Acad Dermatol 42 (2000): 193-8
  13. Tsiodras S, Mantzoros C, Hammer S, Samore M "Effects of protease inhibitors on hyperglycemia, hyperlipidemia, and lipodystrophy - A 5-year cohort study." Arch Intern Med 160 (2000): 2050-6
  14. Carr A "HIV protease inhibitor-related lipodystrophy syndrome." Clin Infect Dis 30 (2000): s135-42
  15. "Product Information. Kaletra (lopinavir-ritonavir)." Abbott Pharmaceutical (2001):
  16. "Product Information. Fortovase (saquinavir)." Roche Laboratories (2001):
  17. Hardy H, Esch LD, Morse GD "Glucose disorders associated with HIV and its drug therapy." Ann Pharmacother 35 (2001): 343-51
  18. Noor MA, Lo JC, Mulligan K, Schwarz JM, Halvorsen RA, Schambelan M, Grunfeld C "Metabolic effects of indinavir in healthy HIV-seronegative men." Aids 15 (2001): f11-8
  19. "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb (2003):
  20. Brambilla AM, Novati R, Calori G, et al. "Stavudine or indinavir-containing regimens are associated with an increased risk of diabetes mellitus in HIV-infected individuals." AIDS 17 (2003): 1993-5
  21. "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline (2003):
  22. "Product Information. Aptivus (tipranavir)." Boehringer-Ingelheim (2005):
  23. "Product Information. Prezista (darunavir)." Ortho Biotech Inc (2006):
View all 23 references
Moderate

PIs (applies to ritonavir) hyperlipidemia

Moderate Potential Hazard, High plausibility. Applicable conditions: Ischemic Heart Disease, History - Myocardial Infarction

Hyperlipidemia has been observed in 10% of patients receiving ritonavir during clinical trials. Increases of 30% to 40% from baseline have been reported for total cholesterol and 200% to 300% or more for triglycerides. These effects have also been reported during postmarketing experience with other protease inhibitors (PIs) but may be the most dramatic with ritonavir. The clinical significance of these elevations is unclear. Severe hyperlipidemia is known to sometimes cause pancreatitis. In addition, some patients have reportedly developed symptomatic atherosclerosis and coronary artery disease after initiating PI treatment. Patients with preexisting hyperlipidemia may require closer monitoring during PI therapy, and adjustments made accordingly in their lipid-lowering regimen. PI therapy should be administered cautiously in patients with coronary artery disease or a history of ischemic heart disease.

References

  1. "Product Information. Invirase (saquinavir)." Roche Laboratories (2001):
  2. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical (2001):
  3. "Product Information. Crixivan (indinavir)." Merck & Co., Inc (2001):
  4. "Product Information. Viracept (nelfinavir)." Agouron Pharma Inc (2001):
  5. Sullivan AK, Feher MD, Nelson MR, Gazzard BG "Marked hypertriglyceridaemia associated with ritonavir therapy." AIDS 12 (1998): 1393-4
  6. Karmochkine M, Raguin G "Severe coronary artery disease in a young HIV-infected man with no cardiovascular risk factor who was treated with indinavir." AIDS 12 (1998): 2499
  7. "Product Information. Agenerase (amprenavir)." Glaxo Wellcome (2001):
  8. Segerer S, Bogner JR, Walli R, Loch O, Goebel FD "Hyperlipidemia under treatment with proteinase inhibitors." Infection 27 (1999): 77-81
  9. Echevarria KL, Hardin TC, Smith JA "Hyperlipidemia associated with protease inhibitor therapy." Ann Pharmacother 33 (1999): 859-63
  10. Flynn TE, Bricker LA "Myocardial infarction in HIV-infected men receiving protease inhibitors." Ann Intern Med 131 (1999): 548
  11. Struble K, Piscitelli SC "Syndromes of abnormal fat redistribution and metabolic complications in HIV-infected patients." Am J Health Syst Pharm 56 (1999): 2343-8
  12. Tsiodras S, Mantzoros C, Hammer S, Samore M "Effects of protease inhibitors on hyperglycemia, hyperlipidemia, and lipodystrophy - A 5-year cohort study." Arch Intern Med 160 (2000): 2050-6
  13. "Product Information. Kaletra (lopinavir-ritonavir)." Abbott Pharmaceutical (2001):
  14. "Product Information. Fortovase (saquinavir)." Roche Laboratories (2001):
  15. Noor MA, Lo JC, Mulligan K, Schwarz JM, Halvorsen RA, Schambelan M, Grunfeld C "Metabolic effects of indinavir in healthy HIV-seronegative men." Aids 15 (2001): f11-8
  16. Costa A, Pulido F, Rubio R, Cepeda C, Torralba M, Costa JR "Lipid changes in HIV-infected patients who started rescue therapy with an amprenavir/ritonavir-based highly active antiretroviral therapy." AIDS 16 (2002): 1983-4
  17. "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb (2003):
  18. "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline (2003):
  19. "Product Information. Aptivus (tipranavir)." Boehringer-Ingelheim (2005):
View all 19 references
Moderate

Ritonavir (applies to ritonavir) heart block

Moderate Potential Hazard, Moderate plausibility. Applicable conditions: Heart Disease

Ritonavir may prolong the PR interval in some patients. Post marketing cases of second or third degree atrioventricular block have been reported. Ritonavir should be administered cautiously in patients with underlying structural heart disease, preexisting conduction abnormalities, ischemic heart disease, and cardiomyopathies as these patients might be at increased risk for developing cardiac conduction abnormalities.

References

  1. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical (2001):

Ritonavir drug interactions

There are 637 drug interactions with ritonavir.

Ritonavir alcohol/food interactions

There are 2 alcohol/food interactions with ritonavir.


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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.