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Drug Interactions between procarbazine and thalidomide

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

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Interactions between your drugs

Major

procarbazine thalidomide

Applies to: procarbazine and thalidomide

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

Major

procarbazine food

Applies to: procarbazine

CONTRAINDICATED: Foods that contain large amounts of tyramine may precipitate a hypertensive crisis in patients treated with monoamine oxidase inhibitors (MAOIs). The mechanism is inhibition of MAO-A, the enzyme responsible for metabolizing exogenous amines such as tyramine in the gut and preventing them from being absorbed intact. Once absorbed, tyramine is metabolized to octopamine, a substance that is believed to displace norepinephrine from storage granules.

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

MANAGEMENT: In general, patients treated with MAOIs or other agents that possess MAOI activity (e.g., furazolidone, linezolid, procarbazine) should avoid consumption of products that contain large amounts of amines and protein foods in which aging or breakdown of protein is used to increase flavor. These foods include cheese (particularly strong, aged or processed cheeses), sour cream, wine (particularly red wine), champagne, beer, pickled herring, anchovies, caviar, shrimp paste, liver (particularly chicken liver), dry sausage, salamis, figs, raisins, bananas, avocados, chocolate, soy sauce, bean curd, sauerkraut, yogurt, papaya products, meat tenderizers, fava bean pods, protein extracts, yeast extracts, and dietary supplements. Caffeine may also precipitate hypertensive crisis so its intake should be minimized as well. At least 14 days should elapse following discontinuation of MAOI therapy before these foods may be consumed. Specially designed reference materials and dietary consultation are recommended so that an appropriate and safe diet can be planned. Patients should be advised to promptly seek medical attention if they experience potential signs and symptoms of a hypertensive crisis such as severe headache, visual disturbances, difficulty thinking, stupor or coma, seizures, chest pain, unexplained nausea or vomiting, and stroke-like symptoms. Patients should also be counseled not to use MAOIs with alcohol, and to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them.

References (19)
  1. Pettinger WA, Soyangco FG, Oates JA (1968) "Inhibition of monoamine oxidase in man by furazolidone." Clin Pharmacol Ther, 9, p. 442-7
  2. Goldberg LI (1964) "Monoamine oxidase inhibitors: adverse reactions and possible mechanisms." JAMA, 190, p. 456-62
  3. Nuessle WF, Norman FC, Miller HE (1965) "Pickled herring and tranylcypromine reaction." JAMA, 192, p. 142-3
  4. Sweet RA, Liebowitz MR, Holt CS, Heimberg RG (1991) "Potential interactions between monoamine oxidase inhibitors and prescribed dietary supplements." J Clin Psychopharmacol, 11, p. 331-2
  5. Walker JI, Davidson J, Zung WWK (1984) "Patient compliance with MAO Inhibitor therapy." J Clin Psychiatry, 45, p. 78-80
  6. Ban TA (1975) "Drug interactions with psychoactive drugs." Dis Nerv Syst, 36, p. 164-6
  7. Darcy PF, Griffin JP (1995) "Interactions with drugs used in the treatment of depressive illness." Adverse Drug React Toxicol Rev, 14, p. 211-31
  8. Maxwell MB (1980) "Reexamining the dietary restrictions with procarbazine (an MAOI)." Cancer Nurs, 3, p. 451-7
  9. (2001) "Product Information. Matulane (procarbazine)." Roche Laboratories
  10. De Vita VT, Hahn MA, Oliverio VT (1965) "Monoamine oxidase inhibition by a new carcinostatic agent, n-isopropyl-a-(2-methylhydrazino)-p-toluamide (MIH). (30590)." Proc Soc Exp Biol Med, 120, p. 561-5
  11. Zetin M, Plon L, DeAntonio M (1987) "MAOI reaction with powdered protein dietary supplement." J Clin Psychiatry, 48, p. 499
  12. Domino EF, Selden EM (1984) "Red wine and reactions." J Clin Psychopharmacol, 4, p. 173-4
  13. Tailor SA, Shulman KI, Walker SE, Moss J, Gardner D (1994) "Hypertensive episode associated with phenelzine and tap beer--a reanalysis of the role of pressor amines in beer." J Clin Psychopharmacol, 14, p. 5-14
  14. Pohl R, Balon R, Berchou R (1988) "Reaction to chicken nuggets in a patient taking an MAOI." Am J Psychiatry, 145, p. 651
  15. (2001) "Product Information. Furoxone (furazolidone)." Roberts Pharmaceutical Corporation
  16. (2001) "Product Information. Nardil (phenelzine)." Parke-Davis
  17. (2001) "Product Information. Marplan (isocarboxazid)." Roche Laboratories
  18. (2001) "Product Information. Zyvox (linezolid)." Pharmacia and Upjohn
  19. Martin TG (1996) "Serotonin syndrome." Ann Emerg Med, 28, p. 520-6
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

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.

Further information

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