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Drug Interactions between indinavir and Key-Pred SP

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

prednisoLONE indinavir

Applies to: Key-Pred SP (prednisolone) and indinavir

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations and pharmacologic effects of corticosteroids, which are primarily metabolized by the isoenzyme. The interaction has been reported with potent inhibitors such as clarithromycin, erythromycin, itraconazole, nefazodone, cobicistat, and ritonavir during concomitant use of various corticosteroids, including inhaled, nasal, and ophthalmic formulations. Systemic corticosteroid adverse effects may occur following intensive or long-term continuous ophthalmic corticosteroid therapy. Cushing's syndrome and adrenal insufficiency have been attributed to the interaction.

MANAGEMENT: The possibility of increased corticosteroid effects should be considered during coadministration with potent and moderate CYP450 3A4 inhibitors. Some authorities advise against concomitant use unless the potential benefit outweighs the risk. If the combination is considered necessary, a lower dosage of the corticosteroid may be required. When indicated for intranasal or inhalational use, alternative corticosteroids such as beclomethasone, which is less dependent on CYP450 3A4 metabolism, should be considered, particularly if long term treatment is required. Patients should be monitored for signs and symptoms of hypercorticism such as acne, striae, thinning of the skin, easy bruising, moon facies, dorsocervical "buffalo" hump, truncal obesity, increased appetite, acute weight gain, edema, hypertension, hirsutism, hyperhidrosis, proximal muscle wasting and weakness, glucose intolerance, exacerbation of preexisting diabetes, depression, and menstrual disorders. Other systemic glucocorticoid effects may include adrenal suppression, immunosuppression, posterior subcapsular cataracts, glaucoma, bone loss, and growth retardation in children and adolescents. Following extensive use with a potent CYP450 3A4 inhibitor, a progressive dosage reduction may be required over a longer period if the corticosteroid is to be withdrawn from therapy, as there may be a significant risk of adrenal suppression. Signs and symptoms of adrenal insufficiency include anorexia, hypoglycemia, nausea, vomiting, weight loss, muscle wasting, fatigue, weakness, dizziness, postural hypotension, depression, and adrenal crisis manifested as inability to respond to stress (e.g., illness, infection, surgery, trauma).

References

  1. Zurcher RM, Frey BM, Frey FJ "Impact of ketoconazole on the metabolism of prednisolone." Clin Pharmacol Ther 45 (1989): 366-72
  2. Yamashita SK, Ludwig EA, Middleton E Jr, Jusko WJ "Lack of pharmacokinetic and pharmacodynamic interactions between ketoconazole and prednisolone." Clin Pharmacol Ther 49 (1991): 558-70
  3. Ulrich B, Frey FJ, Speck RF, Frey BM "Pharmacokinetics/pharmacodynamics of ketoconazole-prednisolone interaction." J Pharmacol Exp Ther 260 (1992): 487-90
  4. Kandrotas RJ, Slaughter RL, Brass C, Jusko WJ "Ketoconazole effects on methylprednisolone disposition and their joint suppression of endogenous cortisol." Clin Pharmacol Ther 42 (1987): 465-70
  5. Glynn AM, Slaughter RL, Brass C, et al. "Effects of ketoconazole on methylprednisolone pharmacokinetics and cortisol secretion." Clin Pharmacol Ther 39 (1986): 654-9
  6. Itkin IH, Menzel ML "The use of macrolide antibiotic substances in the treatment of asthma." J Allergy Clin Immunol 45 (1970): 146-62
  7. LaForce CF, Szefler SJ, Miller MF, Ebling W, Brenner M "Inhibition of methylprednisolone elimination in the presence of erythromycin therapy." J Allergy Clin Immunol 72 (1983): 34-9
  8. Finkenbine RD, Frye MD "Case of psychosis due to prednisone-clarithromycin interaction." Gen Hosp Psychiat 20 (1998): 325-6
  9. Varis T, Kaukonen KM, Kivisto KT, Neuvonen PJ "Plasma concentrations and effects of oral methylprednisolone are considerably increased by itraconazole." Clin Pharmacol Ther 64 (1998): 363-8
  10. Hillebrand-Haverkort ME, Prummel MF, ten Veen JH "Ritonavir-induced Cushing's syndrome in a patient treated with nasal fluticasone." AIDS 13 (1999): 1803
  11. Varis T, Kivisto KT, Neuvonen PJ "The effect of itraconazole on the pharmacokinetics and pharmacodynamics of oral prednisolone." Eur J Clin Pharmacol 56 (2000): 57-60
  12. Varis T, Backman JT, Kivisto KT, Neuvonen PJ "Diltiazem and mibefradil increase the plasma concentrations and greatly enhance the adrenal-suppressant effect of oral methylprednisolone." Clin Pharmacol Ther 67 (2000): 215-21
  13. Garey KW, Rubinstein I, Gotfried MH, Khan IJ, Varma S, Danziger LH "Long-term clarithromycin decreases prednisone requirements in elderly patients with prednisone-dependent asthma." Chest 118 (2000): 1826-7
  14. Lebrun-Vignes B, Archer VC, Diquest B, et al. "Effect of itraconazole on the pharmacokinetics of prednisolone and methylprednisolone and cortisol secretion in healthy subjects." Br J Clin Pharmacol 51 (2001): 443-50
  15. Couturier J, Steele M, Hussey L, Pawliuk G "Steroid-induced mania in an adolescent: risk factors and management." Can J Clin Pharmacol 8 (2001): 109-12
  16. Gupta SK, Dube MP "Exogenous Cushing syndrome mimicking human immunodeficiency virus lipodystrophy." Clin Infect Dis 35 (2002): E69-71
  17. Raaska K, Niemi M, Neuvonen M, Neuvonen PJ, Kivisto KT "Plasma concentrations of inhaled budesonide and its effects on plasma cortisol are increased by the cytochrome P4503A4 inhibitor itraconazole." Clin Pharmacol Ther 72 (2002): 362-369
  18. Main KM, Skov M, Sillesen IB, et al. "Cushing's syndrome due to pharmacological interaction in a cystic fibrosis patient." Acta Paediatr 91 (2002): 1008-11
  19. Skov M, Main KM, Sillesen IB, Muller J, Koch C, Lanng S "Iatrogenic adrenal insufficiency as a side-effect of combined treatment of itraconazole and budesonide." Eur Respir J 20 (2002): 127-33
  20. Kotlyar M, Brewer ER, Golding M, Carson SW "Nefazodone inhibits methylprednisolone disposition and enhances its adrenal-suppressant effect." J Clin Psychopharmacol 23 (2003): 652-6
  21. Bolland MJ, Bagg W, Thomas MG, Lucas JA, Ticehurst R, Black PN "Cushing's syndrome due to interaction between inhaled corticosteroids and itraconazole." Ann Pharmacother 38 (2004): 46-9
  22. Edsbacker S, Andersson T "Pharmacokinetics of budesonide (Entocort EC) capsules for Crohn's disease." Clin Pharmacokinet 43 (2004): 803-21
  23. Samaras K, Pett S, Gowers A, McMurchie M, Cooper DA "Iatrogenic Cushing's syndrome with osteoporosis and secondary adrenal failure in HIV-infected patients receiving inhaled corticosteroids and ritonavir-boosted protease inhibitors: six cases." J Clin Endocrinol Metab 90 (2005): 4394-8
  24. Soldatos G, Sztal-Mazer S, Woolley I, Stockigt J "Exogenous glucocorticoid excess as a result of ritonavir-fluticasone interaction." Intern Med J 35 (2005): 67-8
  25. Penzak SR, Formentini E, Alfaro RM, Long M, Natarajan V, Kovacs J "Prednisolone pharmacokinetics in the presence and absence of ritonavir after oral prednisone administration to healthy volunteers." J Acquir Immune Defic Syndr 40 (2005): 573-80
  26. EMEA. European Medicines Agency "EPARs. European Union Public Assessment Reports. http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landingpage.jsp&mid" (2007):
  27. Bhumbra NA, Sahloff EG, Oehrtman SJ, Horner JM "Exogenous Cushing syndrome with inhaled fluticasone in a child receiving lopinavir/ritonavir." Ann Pharmacother 41 (2007): 1306-9
  28. Busse KH, Formentini E, Alfaro RM, Kovacs JA, Penzak SR "Influence of antiretroviral drugs on the pharmacokinetics of prednisolone in HIV-infected individuals." J Acquir Immune Defic Syndr 48 (2008): 561-6
  29. Agencia Española de Medicamentos y Productos Sanitarios Healthcare "Centro de información online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html" (2008):
View all 29 references

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Drug and food interactions

Moderate

indinavir food

Applies to: indinavir

ADJUST DOSING INTERVAL: According to the manufacturer, coadministration with a meal high in calories, fat, and protein reduces the absorption of indinavir. In ten patients given indinavir in this manner, the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of indinavir decreased by an average of 84% and 77%, respectively. In contrast, grapefruit juice may have only minor effects on the oral bioavailability of indinavir. The manufacturer's package labeling states that administration of a single 400 mg dose of indinavir with 8 oz. of grapefruit juice decreased indinavir AUC by an average of 26%. Likewise, a study consisting of 14 HIV-infected subjects found no uniform nor significant changes in steady-state indinavir AUC during administration with double-strength grapefruit juice compared to water. There was, however, a delay in absorption (Tmax) due to grapefruit juice that is unlikely to be of clinical significance.

MANAGEMENT: To ensure maximal oral absorption, indinavir should be administered without food but with water 1 hour before or 2 hours after a meal. Alternatively, indinavir may be administered with other liquids such as skim milk, juice, coffee, or tea, or with a light meal (e.g., dry toast with jelly, juice, and coffee with skim milk and sugar; corn flakes, skim milk and sugar).

References

  1. "Product Information. Crixivan (indinavir)." Merck & Co., Inc PROD (2001):
  2. Yeh KC, Deutsch PJ, Haddix H, Hesney M, Hoagland V, Ju WD, Justice SJ, Osborne B, Sterrett AT, Stone JA, Woolf E, Waldman S "Single-dose pharmacokinetics of indinavir and the effect of food." Antimicrob Agents Chemother 42 (1998): 332-8
  3. Shelton MJ, Wynn HE, Newitt RG, DiFrancesco R "Effects of grapefruit juice on pharmacokinetic exposure to indinavir in HIV-positive subjects." J Clin Pharmacol 41 (2001): 435-42

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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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.

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