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Drug Interactions between Agamree and ocrelizumab

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

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Interactions between your drugs

Moderate

ocrelizumab vamorolone

Applies to: ocrelizumab and Agamree (vamorolone)

MONITOR: The concomitant use of the CD20-directed cytolytic antibody ocrelizumab with other immune-modulating or immunosuppressive therapies, including immunosuppressant doses of corticosteroids, may result in an increased risk of immunosuppression. However, data is conflicting. Factors that appear to be associated with a risk of serious infections include higher doses of ocrelizumab than those recommended for multiple sclerosis (MS), other comorbidities, and concomitant use in patients on chronic immunosuppressants/corticosteroids. Ocrelizumab alone has been reported to increase the risk for respiratory tract infections and herpes-related infections in MS trials. In the postmarketing setting, hepatitis B reactivation, cases of progressive multifocal leukoencephalopathy (PML), and immune-mediated colitis have been reported. In relapsing MS (RMS) studies, 58% of ocrelizumab-treated patients experienced infections compared to 52% of interferon-treated patients. However, the proportion of patients reporting serious infection was higher in the interferon-treated group (2.9% versus 1.3%). On the other hand, when ocrelizumab is used concomitantly with immunosuppressants in other autoimmune conditions (e.g., rheumatoid arthritis) some studies have reported an increase in serious infections such as atypical pneumonia, pneumocystis jirovecii pneumonia, varicella pneumonia, tuberculosis, and histoplasmosis have been reported from some studies, including rare reports of fatalities.

MANAGEMENT: The increased risk of additive immunosuppression should be considered if co-administering ocrelizumab with other immunosuppressive therapy. Some authorities recommend avoiding concomitant use of other immunosuppressive therapies with ocrelizumab, except for the use of corticosteroids for symptomatic treatment of a MS relapse. Patients should be advised to notify their doctor if they develop signs or symptoms of infection, including upper or lower respiratory tract infection, skin infection, herpes related infection, or PML. If switching from a drug with prolonged immune effects (e.g., daclizumab, fingolimod, natalizumab, teriflunomide, mitoxantrone), the duration and mechanism of action should be considered prior to starting ocrelizumab therapy. The product labeling should be consulted for more specific recommendations.

References

  1. Emery P, Rigby W, tak pp, et al. (2023) Safety with ocrelizumab in rheumatoid arthritis: results from the ocrelizumab phase III program. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3911947/
  2. (2022) "Product Information. Ocrevus (ocrelizumab)." Roche Products Ltd
  3. (2023) "Product Information. Ocrevus (oCRELizumab)." Roche Products Pty Ltd
  4. (2023) "Product Information. Ocrevus (ocrelizumab)." Genentech
  5. (2017) "Product Information. Ocrevus (ocrelizumab)." Hoffmann-La Roche Limited
View all 5 references

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Drug and food interactions

Moderate

vamorolone food

Applies to: Agamree (vamorolone)

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

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  4. Kandrotas RJ, Slaughter RL, Brass C, Jusko WJ (1987) "Ketoconazole effects on methylprednisolone disposition and their joint suppression of endogenous cortisol." Clin Pharmacol Ther, 42, p. 465-70
  5. Glynn AM, Slaughter RL, Brass C, et al. (1986) "Effects of ketoconazole on methylprednisolone pharmacokinetics and cortisol secretion." Clin Pharmacol Ther, 39, p. 654-9
  6. Itkin IH, Menzel ML (1970) "The use of macrolide antibiotic substances in the treatment of asthma." J Allergy Clin Immunol, 45, p. 146-62
  7. LaForce CF, Szefler SJ, Miller MF, Ebling W, Brenner M (1983) "Inhibition of methylprednisolone elimination in the presence of erythromycin therapy." J Allergy Clin Immunol, 72, p. 34-9
  8. Finkenbine RD, Frye MD (1998) "Case of psychosis due to prednisone-clarithromycin interaction." Gen Hosp Psychiat, 20, p. 325-6
  9. Varis T, Kaukonen KM, Kivisto KT, Neuvonen PJ (1998) "Plasma concentrations and effects of oral methylprednisolone are considerably increased by itraconazole." Clin Pharmacol Ther, 64, p. 363-8
  10. Hillebrand-Haverkort ME, Prummel MF, ten Veen JH (1999) "Ritonavir-induced Cushing's syndrome in a patient treated with nasal fluticasone." AIDS, 13, p. 1803
  11. Varis T, Kivisto KT, Neuvonen PJ (2000) "The effect of itraconazole on the pharmacokinetics and pharmacodynamics of oral prednisolone." Eur J Clin Pharmacol, 56, p. 57-60
  12. Varis T, Backman JT, Kivisto KT, Neuvonen PJ (2000) "Diltiazem and mibefradil increase the plasma concentrations and greatly enhance the adrenal-suppressant effect of oral methylprednisolone." Clin Pharmacol Ther, 67, p. 215-21
  13. Garey KW, Rubinstein I, Gotfried MH, Khan IJ, Varma S, Danziger LH (2000) "Long-term clarithromycin decreases prednisone requirements in elderly patients with prednisone-dependent asthma." Chest, 118, p. 1826-7
  14. Lebrun-Vignes B, Archer VC, Diquest B, et al. (2001) "Effect of itraconazole on the pharmacokinetics of prednisolone and methylprednisolone and cortisol secretion in healthy subjects." Br J Clin Pharmacol, 51, p. 443-50
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  20. Kotlyar M, Brewer ER, Golding M, Carson SW (2003) "Nefazodone inhibits methylprednisolone disposition and enhances its adrenal-suppressant effect." J Clin Psychopharmacol, 23, p. 652-6
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  22. Edsbacker S, Andersson T (2004) "Pharmacokinetics of budesonide (Entocort EC) capsules for Crohn's disease." Clin Pharmacokinet, 43, p. 803-21
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  24. Soldatos G, Sztal-Mazer S, Woolley I, Stockigt J (2005) "Exogenous glucocorticoid excess as a result of ritonavir-fluticasone interaction." Intern Med J, 35, p. 67-8
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  30. (2023) "Product Information. Agamree (vamorolone)." Santhera Pharmaceuticals (US)
View all 30 references

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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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