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Cobicistat / darunavir Disease Interactions

There are 4 disease interactions with cobicistat / darunavir:

Major

Darunavir (applies to cobicistat/darunavir) hepatotoxicity

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

Drug-induced hepatitis has been reported with the use of darunavir/ritonavir. Patients with underlying liver disease including chronic active hepatitis B or C viral infections have an increased risk for liver function abnormalities. Therapy with darunavir should be administered cautiously in patients with preexisting liver disease, liver enzyme abnormalities, or hepatitis. The combination of darunavir/ritonavir is not recommended for use in patients with severe hepatic impairment.

Major

PIs (applies to cobicistat/darunavir) hemophilia

Major Potential Hazard, Moderate 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. Agenerase (amprenavir)." Glaxo Wellcome, Research Triangle Pk, NC.
  2. "Product Information. Viracept (nelfinavir)." Agouron Pharma Inc, La Jolla, CA.
  3. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical, Abbott Park, IL.
  4. "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline, Research Triangle Park, NC.
  5. "Product Information. Fortovase (saquinavir)" Roche Laboratories, Nutley, NJ.
  6. "Product Information. Crixivan (indinavir)." Merck & Co, Inc, West Point, PA.
  7. "Product Information. Kaletra (lopinavir-ritonavir)" Abbott Pharmaceutical, Abbott Park, IL.
  8. "Product Information. Invirase (saquinavir)." Roche Laboratories, Nutley, NJ.
  9. "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb, Princeton, NJ.
  10. "Product Information. Aptivus (tipranavir)." Boehringer-Ingelheim, Ridgefield, CT.
View all 10 references
Moderate

Cobicistat (applies to cobicistat/darunavir) creatinine clearance

Moderate Potential Hazard, Moderate plausibility. Applicable conditions: Renal Dysfunction

Cobicistat has shown to decrease creatinine clearance without affecting actual renal glomerular function and no dose adjustment is required in patients with renal impairment, including those with severe renal impairment. However, this effect should be considered when interpreting changes in estimated creatinine clearance in patients initiating cobicistat when there is presence of renal impairment or in patients receiving other drugs that need to be monitored with estimated creatinine clearance. Patients who experience a confirmed increase of serum creatinine of 0.4 mg/dL from baseline should be closely monitored for renal safety.

Moderate

PIs (applies to cobicistat/darunavir) hyperglycemia

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

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. Hardy H, Esch LD, Morse GD "Glucose disorders associated with HIV and its drug therapy." Ann Pharmacother 35 (2001): 343-51
  2. "Product Information. Viracept (nelfinavir)." Agouron Pharma Inc, La Jolla, CA.
  3. Kaufman MB, Simionatto C "A review of protease inhibitor-induced hyperglycemia." Pharmacotherapy 19 (1999): 114-7
  4. "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline, Research Triangle Park, NC.
  5. 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
  6. "Product Information. Agenerase (amprenavir)." Glaxo Wellcome, Research Triangle Pk, NC.
  7. "Product Information. Kaletra (lopinavir-ritonavir)" Abbott Pharmaceutical, Abbott Park, IL.
  8. "Product Information. Fortovase (saquinavir)" Roche Laboratories, Nutley, NJ.
  9. Dube MP, Johnson DL, Currier JS, Leedom JM "Protease inhibitor-associated hyperglycaemia." Lancet 350 (1997): 713-4
  10. "Product Information. Aptivus (tipranavir)." Boehringer-Ingelheim, Ridgefield, CT.
  11. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical, Abbott Park, IL.
  12. Carr A "HIV protease inhibitor-related lipodystrophy syndrome." Clin Infect Dis 30 (2000): s135-42
  13. 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
  14. Walli R, Demant T "Impaired glucose tolerance and protease inhibitors." Ann Intern Med 129 (1998): 837-8
  15. 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
  16. 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
  17. "Product Information. Invirase (saquinavir)." Roche Laboratories, Nutley, NJ.
  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. Crixivan (indinavir)." Merck & Co, Inc, West Point, PA.
  20. 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
  21. "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb, Princeton, NJ.
  22. Qaqish RB, Fisher E, Rublein J, Wohl DA "HIV-associated lipodystrophy syndrome." Pharmacotherapy 20 (2000): 13-22
View all 22 references

Cobicistat / darunavir drug interactions

There are 550 drug interactions with cobicistat / darunavir

Cobicistat / darunavir alcohol/food interactions

There is 1 alcohol/food interaction with cobicistat / darunavir

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.