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Drug Interactions between itraconazole and vamorolone

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

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Interactions between your drugs

Moderate

itraconazole vamorolone

Applies to: itraconazole and vamorolone

Consumer information for this interaction is not currently available.

ADJUST DOSE: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations and effects of vamorolone. The proposed mechanism is inhibition of CYP450 3A4, one of the isoenzymes involved in the metabolic clearance of vamorolone. Drug interaction studies have shown the administration of vamorolone following multiple doses of the potent CYP450 3A4 inhibitor itraconazole increased the systemic exposure (AUC) and peak plasma concentration (Cmax) by 44% and 8%, respectively, compared to vamorolone administered alone. Increased plasma concentrations of vamorolone may increase the risk of corticosteroid-related adverse effects.

MANAGEMENT: If concomitant use of vamorolone with potent CYP450 3A4 inhibitors is required, the manufacturer advises that the maximum recommended daily dose of vamorolone in patients weighing at least 50 kg not exceed 4 mg/kg or 200 mg vamorolone. Patients should be monitored for signs and symptoms of corticosteroid-related adverse effects. Patients should also be monitored for corticosteroid-related adverse effects, including 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, and depression. In addition, if vamorolone therapy is to be discontinued, those who have received treatment lasting longer than one week should have their dose of vamorolone gradually decreased, due to the 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 an 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):
  30. "Product Information. Agamree (vamorolone)." Santhera Pharmaceuticals (US) (2023):
View all 30 references

Drug and food interactions

Moderate

itraconazole food

Applies to: itraconazole

Food increases the absorption of itraconazole capsules but decreases the absorption of itraconazole oral solution. Capsules should be taken immediately after a full meal and the solution be taken on an empty stomach to ensure best results.

Switch to professional interaction data

Moderate

vamorolone food

Applies to: vamorolone

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of vamorolone. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism in the gut wall by certain compounds present in grapefruit. The metabolism of vamorolone is mediated by the isoenzymes CYP450 3A4/5, and CYP450 2C8, and uridine diphosphate glucuronosyltransferases (UGT) 1A3, 2B7, and 2B17. In general, the effect of grapefruit juice is concentration-, dose-, and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased systemic exposure to vamorolone may increase the risk of corticosteroid adverse effects such as hypercorticism, hyperglycemia, adrenal suppression, immunosuppression, hypertension, salt and water retention, electrolyte abnormalities, behavioral and mood disturbances, posterior subcapsular cataracts, glaucoma, bone loss, and growth retardation in children and adolescents.

MANAGEMENT: Until further information is available, it may be advisable for patients to avoid the consumption of large amounts of grapefruit and grapefruit juice during vamorolone therapy unless otherwise directed by their doctor, as the interaction is unreliable and subject to a high degree of interpatient variation. If coadministration is considered necessary, patients should be closely monitored for signs and symptoms of corticosteroid adverse effects. Patients should also 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, and depression. 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 an inability to respond to stress (e.g., illness, infection, surgery, trauma). Consultation with product labeling for specific recommendations is advisable.

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):
  30. "Product Information. Agamree (vamorolone)." Santhera Pharmaceuticals (US) (2023):
View all 30 references

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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