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Drug Interactions between Agamree and thalidomide

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

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Interactions between your drugs

Major

thalidomide vamorolone

Applies to: thalidomide and Agamree (vamorolone)

MONITOR CLOSELY: Coadministration of thalidomide with glucocorticoids and/or antineoplastic agents in the treatment of malignancy may potentiate the risk of thromboembolism. The exact mechanism is unknown but likely multifactorial. Thalidomide alone has been associated with the development of deep-vein thrombosis (DVT), and malignancy itself is also a common cause. In a study of 100 patients receiving induction chemotherapy (combinations of dexamethasone, vincristine, doxorubicin, cyclophosphamide, etoposide, and cisplatin) for multiple myeloma, the addition of thalidomide was associated with an increased incidence of DVT compared to chemotherapy without thalidomide (28% vs. 4%). Administration of thalidomide was safely resumed in 75% of patients after initiation of appropriate anticoagulation therapy. In another study, 9 of 21 (43%) patients with metastatic renal cell carcinoma (RCC) receiving gemcitabine, 5-FU, and thalidomide developed venous thromboembolism, including one case of fatal cardiac arrest. This rate is substantially higher than the 3% rate observed in a group of 125 patients previously treated at the same institution with similar regimens of gemcitabine and 5-FU but without thalidomide. It is also higher than the 9% rate (12 of 140 patients) the investigators found in a review of published data from five RCC trials that used thalidomide therapy without concomitant cytotoxic therapy. Another study found a significant association of DVT with exposure to doxorubicin in patients receiving thalidomide. Specifically, 31 of 192 (16%) multiple myeloma patients treated with DT-PACE (a regimen of dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide) developed DVT, while only 1 of 40 (2.5%) did so on DCEP-T (similar to DT-PACE but without doxorubicin). The time to DVT was also significantly decreased with doxorubicin exposure. In a pooled analysis of 39 prospectively monitored clinical trials involving 1784 thalidomide-treated patients, the incidence of thromboembolism was 5% when thalidomide was used as a single agent, 13% when combined with corticosteroids (8% to 26% has been reported in individual studies with dexamethasone), and 17% when combined with chemotherapy. Among thalidomide-treated patients with multiple myeloma, thromboembolism rates ranged from a low of 1/30 among those treated with concomitant cyclophosphamide, etoposide, and cisplatin to a high of about 1/3 in those treated with doxorubicin-containing regimens.

MANAGEMENT: Close monitoring for DVT or pulmonary embolism is recommended in patients who require thalidomide therapy in combination with glucocorticoids and/or cytotoxic agents. Patients should be advised to seek medical attention if they develop potential signs and symptoms of thromboembolism such as chest pain, shortness of breath, and pain or swelling in the arms or legs. Prophylaxis with anticoagulants such as low-molecular weight heparins or warfarin may be appropriate, but the decision to take thromboprophylactic measures should be made after careful assessment of underlying risk factors. If a thromboembolic event occurs during therapy with thalidomide, treatment must be discontinued and standard anticoagulation therapy started. Once anticoagulation is stabilized and complications of the thromboembolic event under control, thalidomide may be restarted at the original dose if benefit is deemed to outweigh the risks. Anticoagulation therapy should be continued during the remaining course of thalidomide treatment.

References (16)
  1. (2001) "Product Information. Thalomid (thalidomide)." Celgene Corporation
  2. Zangari M, Anaissie E, Barlogie B, et al. (2001) "Increased risk of deep-vein thrombosis in patients with multiple myeloma receiving thalidomide and chemotherapy." Blood, 98, p. 1614-5
  3. Figg WD, Arlen P, Gulley J, et al. (2001) "A randomized phase II trial of docetaxel (taxotere) plus thalidomide in androgen-independent prostate cancer." Semin Oncol, 28(4 Suppl 15), p. 62-6
  4. Escudier B, Lassau N, Leborgne S, Angevin E, Laplanche A (2002) "Thalidomide and venous thrombosis." Ann Intern Med, 136, p. 711
  5. Urbauer E, Kaufmann H, Nosslinger T, Raderer M, Drach J (2002) "Thromboembolic events during treatment with thalidomide." Blood, 99, p. 4247-8
  6. Zangari M, Siegel E, Barlogie B, et al. (2002) "Thrombogenic activity of doxorubicin in myeloma patients receiving thalidomide: implications for therapy." Blood, 100, p. 1168-71
  7. Cavo M, Zamagni E, Cellini C, et al. (2002) "Deep-vein thrombosis in patients with multiple myeloma receiving first-line thalidomide-dexamethasone therapy." Blood, 100, p. 2272-3
  8. Desai AA, Vogelzang NJ, Rini BI, Ansari R, Krauss S, Stadler WM (2002) "A high rate of venous thromboembolism in a multi-institutional Phase II trial of weekly intravenous gemcitabine with continuous infusion fluorouracil and daily thalidomide in patients with metastatic renal cell carcinoma." Cancer, 95, p. 1629-36
  9. Rajkumar SV, Hayman S, Gertz MA, et al. (2002) "Combination therapy with thalidomide plus dexamethasone for newly diagnosed myeloma." J Clin Oncol, 20, p. 4319-23
  10. Bennett CL, Schumock GT, Desai AA, et al. (2002) "Thalidomide-associated deep vein thrombosis and pulmonary embolism." Am J Med, 113, p. 603-6
  11. Weber D, Rankin K, Gavino M, Delasalle K, Alexanian R (2003) "Thalidomide alone or with dexamethasone for previously untreated multiple myeloma." J Clin Oncol, 21, p. 16-9
  12. Fine HA, Wen PY, Maher EA, et al. (2003) "Phase II Trial of Thalidomide and Carmustine for Patients With Recurrent High-Grade Gliomas." J Clin Oncol, 21, p. 2299-304
  13. Lee CK, Barlogie B, Munshi N, et al. (2003) "DTPACE: an effective, novel combination chemotherapy with thalidomide for previously treated patients with myeloma." J Clin Oncol, 21, p. 2732-9
  14. Zangari M, Barlogie B, Anaissie E, et al. (2004) "Deep vein thrombosis in patients with mutiple myeloma treated with thalidomide and chemotherapy: effects of prophylactic and therapeutic anticoagulation." Br J Haematol, 126, p. 715-21
  15. Osman K, Comenzo R, Rajkumar SV (2001) "Deep venous thrombosis and thalidomide therapy for multiple myeloma." N Engl J Med, 344, p. 1951-2
  16. Bennett CL, Nebeker JR, Samore MH, et al. (2005) "The Research on Adverse Drug Events and Reports (RADAR) project." JAMA, 293, p. 2131-40

Drug and food interactions

Moderate

thalidomide food

Applies to: thalidomide

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References (4)
  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
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 (30)
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  3. Ulrich B, Frey FJ, Speck RF, Frey BM (1992) "Pharmacokinetics/pharmacodynamics of ketoconazole-prednisolone interaction." J Pharmacol Exp Ther, 260, p. 487-90
  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
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  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
  15. Couturier J, Steele M, Hussey L, Pawliuk G (2001) "Steroid-induced mania in an adolescent: risk factors and management." Can J Clin Pharmacol, 8, p. 109-12
  16. Gupta SK, Dube MP (2002) "Exogenous Cushing syndrome mimicking human immunodeficiency virus lipodystrophy." Clin Infect Dis, 35, E69-71
  17. Raaska K, Niemi M, Neuvonen M, Neuvonen PJ, Kivisto KT (2002) "Plasma concentrations of inhaled budesonide and its effects on plasma cortisol are increased by the cytochrome P4503A4 inhibitor itraconazole." Clin Pharmacol Ther, 72, p. 362-369
  18. Main KM, Skov M, Sillesen IB, et al. (2002) "Cushing's syndrome due to pharmacological interaction in a cystic fibrosis patient." Acta Paediatr, 91, p. 1008-11
  19. Skov M, Main KM, Sillesen IB, Muller J, Koch C, Lanng S (2002) "Iatrogenic adrenal insufficiency as a side-effect of combined treatment of itraconazole and budesonide." Eur Respir J, 20, p. 127-33
  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
  21. Bolland MJ, Bagg W, Thomas MG, Lucas JA, Ticehurst R, Black PN (2004) "Cushing's syndrome due to interaction between inhaled corticosteroids and itraconazole." Ann Pharmacother, 38, p. 46-9
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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)

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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