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Crixivan (indinavir) Disease Interactions

There are 5 disease interactions with Crixivan (indinavir):

Major

Indinavir (Includes Crixivan) ↔ Nephrolithiasis

Severe Potential Hazard, High plausibility

Applies to: Dehydration, Nephrolithiasis, History - Nephrolithiasis

Crystalluria and nephrolithiasis may occur during treatment with indinavir. The cumulative frequency of nephrolithiasis is substantially higher in pediatric patients (29%) than in adult patients (12.4%; range 4.7% to 34.4% across individual trials) and increases with duration of exposure to indinavir; however, the risk over time remains relatively constant. The incidence is also higher when indinavir is used in combination with ritonavir than when used alone at 800 mg three times a day. In some cases, nephrolithiasis/urolithiasis has been associated with renal insufficiency or acute renal failure and pyelonephritis with or without bacteremia. Therapy with indinavir should be administered cautiously in patients with a current or past history of nephrolithiasis. It is crucial that patients receive adequate hydration. Generally, at least 1.5 L (approximately 48 oz) of fluid per day is recommended for adults during indinavir therapy. Those who are dehydrated may be at increased risk and should be encouraged to consume additional amounts of liquid or given intravenous fluid if necessary. All patients receiving indinavir should be instructed to seek medical attention if they experience potential signs and symptoms of nephrolithiasis/urolithiasis such as flank pain, hematuria, dysuria, anuria, and urinary urgency. A brief interruption (e.g., 1 to 3 days) or discontinuation of therapy may be required.

References

  1. Guery B, Tubiana R, Martinez F, Jacquiaud C, Bochet M, Katlama C, Deray G "Renal tolerance of indinavir in HIV-positive patients." Nephron 82 (1999): 72
  2. Rich JD, Ramratnam B, Chiang M, Tashima KT "Management of indinavir associated nephrolithiasis." J Urol 158 (1997): 2228
  3. Reiter WJ, SchonPernerstorfer H, Dorfinger K, Hofbauer J, Marberger M "Frequency of urolithiasis in individuals seropositive for human immunodeficiency virus treated with indinavir is higher than previously assumed." J Urol 161 (1999): 1082-4
  4. Kohan AD, Armenakas NA, Fracchia JA "Indinavir urolithiasis: An emerging cause of renal colic in patients with human immunodeficiency virus." J Urol 161 (1999): 1765-8
  5. Sarcletti M, Petter A, Zangerle R "Indinavir and interstitial nephritis." Ann Intern Med 128 (1998): 320-1
  6. Gentle DL, Stoller ML, Jarrett TW, Ward JF, Geib KS, Wood AF "Protease inhibitor-induced urolithiasis." Urology 50 (1997): 508-11
  7. Grunke M, Valerius T, Manger B, Kalden JR, Harrer T "Renal dysfunction in a human immunodeficiency virus-infected patient who was treated with indinavir." Clin Infect Dis 25 (1997): 1270-1
  8. Padberg J, Fritsche L, Bergmann F, Schurmann D, Suttorp N "Nephropathy and renal colic in patients treated with indinavir, ritonavir plus indinavir or ritonavir plus saquinavir." AIDS 13 (1999): 2173-4
  9. Famularo G, Di Toro S, Moretti S, De Simone C "Symptomatic crystalluria associated with indinavir." Ann Pharmacother 34 (2000): 1414-8
  10. Dieleman JP, Gyssens IC, vanderEnde ME, deMarie S, Burger DM "Urological complaints in relation to indinavir plasma concentrations in HIV-infected patients." AIDS 13 (1999): 473-8
  11. Polhemus ME, Aronson NE "Persistent nephrolithiasis after discontinuation of indinavir therapy." Clin Infect Dis 27 (1998): 1536-7
  12. Kopp JB, Miller KD, Mican JA, et al. "Crystalluria and urinary tract abnormalities associated with indinavir." Ann Intern Med 127 (1997): 119-25
  13. Martinez E, Leguizamon M, Mallolas J, Miro JM, Gatell JM "Influence of environmental temperature on incidence of indinavir-related nephrolithiasis." Clin Infect Dis 29 (1999): 422-5
  14. Lerner LB, Cendron M, Rous SN "Nephrolithiasis from indinavir, a new human immunodeficiency virus drug." J Urol 159 (1998): 2074-5
  15. Sutherland SE, Reigle MD, Seftel AD, Resnick MI "Protease inhibitors and urolithiasis." J Urol 158 (1997): 31-3
  16. Ascher DP, Lucy MD "Indinavir sulfate renal toxicity in a pediatric hemophiliac with HIV infection." Ann Pharmacother 31 (1997): 1146-9
  17. Jaradat M, Phillips C, Yum MN, Cushing H, Moe S "Acute tubulointerstitial nephritis attributable to indinavir therapy." Am J Kidney Dis 35 (2000): e161-5
  18. Brodie SB, Keller MJ, Ewenstein BM, Sax PE "Variation in incidence of indinavir-associated nephrolithiasis among HIV-positive patients." AIDS 12 (1998): 2433-7
  19. Vigano A, Rombola G, diBelgioioso GB, Sala N, Principi N "Subtle occurrence of indinavir-induced acute renal insufficiency." AIDS 12 (1998): 954-5
  20. Boubaker K, Sudre P, Bally F, Vogel G, Meuwly JY, Glauser MP, Telenti A "Changes in renal function associated with indinavir." AIDS 12 (1998): f249-54
  21. Bruce RG, Munch LC, Hoven AD, Jerauld RS, Greenburg R, Porter WH, Rutter PW "Urolithiasis associated with the protease inhibitor indinavir." Urology 50 (1997): 513-8
  22. Bach MC, Godofsky EW "Indinavir nephrolithiasis in warm climates." J Acquir Immune Defic Syndr Hum Retrovirol 14 (1997): 296-7
  23. Marroni M, Gaburri M, Mecozzi F, Baldelli F "Acute interstitial nephritis secondary to the administration of indinavir." Ann Pharmacother 32 (1998): 843-4
  24. Perazella MA, Kashgarian M, Cooney E "Indinavir nephropathy in an AIDS patient with renal insufficiency and pyuria." Clin Nephrol 50 (1998): 194-6
  25. "Product Information. Crixivan (indinavir)." Merck & Co, Inc, West Point, PA.
  26. Berns JS, Cohen RM, Silverman M, Turner J "Acute renal failure due to indinavir crystalluria and nephrolithiasis: report of two cases." Am J Kidney Dis 30 (1997): 558-60
  27. Gagnon RF, Tsoukas CM, Watters AK "Light microscopy of indinavir urinary crystals." Ann Intern Med 128 (1998): 321
  28. Grabe DW, Eisele G, Miller C, Singh J, Stein D "Indinavir-induced nephropathy." Clin Nephrol 51 (1999): 181-3
  29. Tashima KT, Horowitz JD, Rosen S "Indinavir nephropathy." N Engl J Med 336 (1997): 138-40
  30. Antony SJ "Rapid development of indinavir-induced asymptomatic crystalluria in a human immunodeficiency virus-negative patient." Clin Infect Dis 27 (1998): 911-2
  31. Tsao JW, Kogan SC "Indinavir crystalluria." N Engl J Med 340 (1999): 1329
  32. Daudon M, Estepa L, Viard JP, Joly D, Jungers P "Urinary stones in HIV-1-positive patients treated with indinavir." Lancet 349 (1997): 129-45
  33. Noble CB, Klein LT, Staiman VR, Neu N, Hensle TW, Berdon WE "Ureteral obstruction secondary to indinavir in the pediatric HIV population." Pediatr Radiol 28 (1998): 627-9
  34. Salahuddin S, Hsu YS, Buchholz NP, Dieleman JP, Gyssens IC, Kok DJ "Is indinavir crystalluria an indicator for indinavir stone formation?." Aids 15 (2001): 1079-80
View all 34 references
Major

Pis (Includes Crixivan) ↔ Hemophilia

Severe Potential Hazard, Low plausibility

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

Indinavir (Includes Crixivan) ↔ Liver Disease

Moderate Potential Hazard, High plausibility

Applies to: Liver Disease

Indinavir is primarily metabolized by the liver. Patients with liver disease may be at greater risk for adverse effects from indinavir due to decreased drug clearance. Therapy with indinavir should be administered cautiously in patients with liver disease. A dosage reduction to 600 mg three times a day is recommended for patients with mild to moderate hepatic insufficiency due to cirrhosis.

References

  1. Chiba M, Hensleigh M, Nishime JA, Balani SK, Lin JH "Role of cytochrome P450 3A4 in human metabolism of MK-639, a potent human immunodeficiency virus protease inhibitor." Drug Metab Dispos 24 (1996): 307-14
  2. Balani SK, Woolf EJ, Hoagland VL, Sturgill MG, Deutsch PJ, Yeh KC, Lin JH "Disposition of indinavir, a potent HIV-1 protease inhibitor, after an oral dose in humans." Drug Metab Dispos 24 (1996): 1389-94
  3. Sommadossi JP "HIV protease inhibitors: pharmacologic and metabolic distinctions." AIDS 13 (1999): s29-40
  4. "Product Information. Crixivan (indinavir)." Merck & Co, Inc, West Point, PA.
View all 4 references
Moderate

Pis (Includes Crixivan) ↔ Hyperglycemia

Moderate Potential Hazard, Moderate plausibility

Applies to: Abnormal Glucose Tolerance, Diabetes Mellitus

New onset or exacerbation of preexisting diabetes mellitus, glucose intolerance, and hyperglycemia have been reported during postmarketing surveillance in HIV patients treated with protease inhibitors (PIs). 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 patients during treatment with potent antiretroviral regimens containing PIs. Patients with or predisposed to glucose disorders should be monitored during PI therapy. Dosage adjustments in insulin or oral hypoglycemic medications may be necessary in patients with diabetes. In some cases, glucose abnormalities persisted despite discontinuation of PI therapy.

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. "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline, Research Triangle Park, NC.
  4. "Product Information. Invirase (saquinavir)." Roche Laboratories, Nutley, NJ.
  5. 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
  6. "Product Information. Crixivan (indinavir)." Merck & Co, Inc, West Point, PA.
  7. 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
  8. Kaufman MB, Simionatto C "A review of protease inhibitor-induced hyperglycemia." Pharmacotherapy 19 (1999): 114-7
  9. "Product Information. Kaletra (lopinavir-ritonavir)" Abbott Pharmaceutical, Abbott Park, IL.
  10. 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
  11. Dube MP, Johnson DL, Currier JS, Leedom JM "Protease inhibitor-associated hyperglycaemia." Lancet 350 (1997): 713-4
  12. 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
  13. "Product Information. Agenerase (amprenavir)." Glaxo Wellcome, Research Triangle Pk, NC.
  14. Carr A "HIV protease inhibitor-related lipodystrophy syndrome." Clin Infect Dis 30 (2000): s135-42
  15. "Product Information. Fortovase (saquinavir)" Roche Laboratories, Nutley, NJ.
  16. 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
  17. Walli R, Demant T "Impaired glucose tolerance and protease inhibitors." Ann Intern Med 129 (1998): 837-8
  18. 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
  19. "Product Information. Aptivus (tipranavir)." Boehringer-Ingelheim, Ridgefield, CT.
  20. "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb, Princeton, NJ.
  21. Qaqish RB, Fisher E, Rublein J, Wohl DA "HIV-associated lipodystrophy syndrome." Pharmacotherapy 20 (2000): 13-22
  22. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical, Abbott Park, IL.
View all 22 references
Moderate

Pis (Includes Crixivan) ↔ Hyperlipidemia

Moderate Potential Hazard, High plausibility

Applies to: History - Myocardial Infarction, Hyperlipidemia, Ischemic Heart Disease

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, Nutley, NJ.
  2. "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline, Research Triangle Park, NC.
  3. "Product Information. Crixivan (indinavir)." Merck & Co, Inc, West Point, PA.
  4. "Product Information. Agenerase (amprenavir)." Glaxo Wellcome, Research Triangle Pk, NC.
  5. "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb, Princeton, NJ.
  6. 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
  7. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical, Abbott Park, IL.
  8. "Product Information. Fortovase (saquinavir)" Roche Laboratories, Nutley, NJ.
  9. 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
  10. "Product Information. Aptivus (tipranavir)." Boehringer-Ingelheim, Ridgefield, CT.
  11. Echevarria KL, Hardin TC, Smith JA "Hyperlipidemia associated with protease inhibitor therapy." Ann Pharmacother 33 (1999): 859-63
  12. Flynn TE, Bricker LA "Myocardial infarction in HIV-infected men receiving protease inhibitors." Ann Intern Med 131 (1999): 548
  13. 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
  14. Sullivan AK, Feher MD, Nelson MR, Gazzard BG "Marked hypertriglyceridaemia associated with ritonavir therapy." AIDS 12 (1998): 1393-4
  15. "Product Information. Kaletra (lopinavir-ritonavir)" Abbott Pharmaceutical, Abbott Park, IL.
  16. 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
  17. 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
  18. Segerer S, Bogner JR, Walli R, Loch O, Goebel FD "Hyperlipidemia under treatment with proteinase inhibitors." Infection 27 (1999): 77-81
  19. "Product Information. Viracept (nelfinavir)." Agouron Pharma Inc, La Jolla, CA.
View all 19 references

Crixivan (indinavir) drug Interactions

There are 576 drug interactions with Crixivan (indinavir)

Crixivan (indinavir) alcohol/food Interactions

There are 2 alcohol/food interactions with Crixivan (indinavir)

Drug Interaction Classification

The classifications below are a general guideline only. It is difficult to determine the relevance of a particular drug interaction to any individual given the large number of variables.
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 information available.

Do not stop taking any medications without consulting your healthcare provider.

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