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Drug Interactions between Or-Phen-Ade and ozanimod

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

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Interactions between your drugs

Moderate

phenylpropanolamine ozanimod

Applies to: Or-Phen-Ade (chlorpheniramine / phenylpropanolamine) and ozanimod

GENERALLY AVOID: Coadministration of sympathomimetic agents with drugs that possess monoamine oxidase inhibition (MAOI) activity may precipitate severe hypertensive reactions and hyperpyrexia. Death has occurred in some reported cases. The mechanism involves a synergistic sympathomimetic effect due to enhanced norepinephrine storage in adrenergic neurons secondary to MAOI activity. MAOIs also slow the metabolism of some sympathomimetics such as amphetamines, which may potentiate their effect on the release of norepinephrine and other monoamines from adrenergic nerve endings. Although the interaction has primarily involved nonselective MAOIs, hypertensive crisis has been reported with selective MAO-B inhibitors. Because an active metabolite of ozanimod inhibits MAO-B in vitro, the interaction may theoretically occur with ozanimod. In a placebo-controlled crossover study involving healthy subjects, coadministration of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure; however, ozanimod did increase the pseudoephedrine-induced heart rate response by approximately 3 beats per minute (bpm). In two clinical studies, ozanimod increased systolic pressure by an average of 1 to 2 mmHg over interferon beta-1a, but had no effect on diastolic pressure. The increase in systolic pressure was first detected after approximately 3 months of treatment and persisted throughout treatment. Hypertension was reported as an adverse reaction in 3.9% of patients treated with ozanimod 0.92 mg, compared to 2.1% of patients treated with interferon beta-1a. Two patients treated with ozanimod and one patient treated with interferon beta-1a in these studies experienced a hypertensive crisis.

MANAGEMENT: Until more information is available, concomitant use of ozanimod with sympathomimetic agents should be avoided when possible. Blood pressure and other vitals should be monitored if coadministration is required.

References

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  2. Schulz R, Antonin KH, Hoffmann E, et al. (1989) "Tyramine kinetics and pressor sensitivity during monoamine oxidase inhibition by selegiline." Clin Pharmacol Ther, 46, p. 528-36
  3. Krisko I, Lewis E, Johnson JE (1969) "Severe hyperpyrexia due to tranylcypromine-amphetamine toxicity." Ann Intern Med, 70, p. 559-64
  4. Elis J, Laurence DR, Mattie H, Prichard BN (1967) "Modification by monoamine oxidase inhibitors of the effect of some sympathomimetics on blood pressure." Br Med J, 2, p. 75-8
  5. Davies B, Bannister R, Sever P (1978) "Pressor amines and monoamine-oxidase inhibitors for treatment of postural hypotension in autonomic failure: limitations and hazards." Lancet, 1, p. 172-5
  6. Goldberg LI (1964) "Monoamine oxidase inhibitors: adverse reactions and possible mechanisms." JAMA, 190, p. 456-62
  7. Horler AR, Wynne NA (1965) "Hypertensive crisis due to pargyline and metaraminol." Br Med J, 5459, p. 460-1
  8. Sjoqvist F (1965) "Psychotropic drugs (2) interaction between monoamine oxidase (MAO) inhibitors and other substances." Proc R Soc Med, 58, p. 967-78
  9. Harrison WM, McGrath PJ, Stewart JW, Quitkin F (1989) "MAOIs and hypertensive crises: the role of OTC drugs." J Clin Psychiatry, 50, p. 64-5
  10. Cuthbert MF, Greenberg MP, Morley SW (1969) "Cough and cold remedies: a potential danger to patients on monoamine oxidase inhibitors." Br Med J, 1, p. 404-6
  11. Humberstone PM (1969) "Hypertension from cold remedies." Br Med J, 1, p. 846
  12. Wright SP (1978) "Hazards with monoamine-oxidase inhibitors: a persistent problem." Lancet, 1, p. 284-5
  13. Boakes AJ, Laurence DR, Teoh PC, Barar FS, Benedikter LT, Pritchard BN (1973) "Interactions between sympathomimetic amines and antidepressant agents in man." Br Med J, 1, p. 311-5
  14. Dally PJ (1962) "Fatal reaction associated with tranylcypromine and methylamphetamine." Lancet, 1, p. 1235-6
  15. Schildkraut JJ, Klerman GL, Friend DG, Greenblatt M (1963) "Biochemical and pressor effects of oral d,l-dihydroxyphenylalanine in patients pretreated with antidepressant drugs." Ann N Y Acad Sci, 107, p. 1005-15
  16. Sharpe J, Marquez-Julio A, Ashby P (1972) "Idiopathic orthostatic hypotension treated with levodopa and MAO inhibitor: a preliminary report." Can Med Assoc J, 107, p. 296-300
  17. Teychenne PF, Calne DB, Lewis PJ, Findley LJ (1975) "Interactions of levodopa with inhibitors of monoamine oxidase and L-aromatic amino acid decarboxylase." Clin Pharmacol Ther, 18, p. 273-7
  18. Smookler S, Bermudez AJ (1982) "Hypertensive crisis resulting from an MAO inhibitor and an over-the-counter appetite suppressant." Ann Intern Med, 11, p. 482-4
  19. (2001) "Product Information. Aldomet (methyldopa)." Merck & Co., Inc
  20. Paykel ES (1966) "Hallucinosis on combined methyldopa and pargyline." Br Med J, 1, p. 803
  21. van Rossum JM, Hurkmans JA (1963) "Reversal of the effect of a-Methyldopa by monamine oxidase inhibitors." J Pharm Pharmacol, 15, p. 493-9
  22. van Rossum JM (1963) "Potential danger of monoamineoxidase inhibitors and a-methyldopa." Lancet, 1, p. 950-1
  23. Mason AM, Buckle RM (1969) ""Cold" cures and monoamine-oxidase inhibitors." Br Med J, 1, p. 845-6
  24. Boakes AJ, Laurence DR, Teoh PC, Barar FS, Benedikter LT, Prichard BN (1973) "Interactions between sympathomimetic amines and antidepressant agents in man." Br Med J, 1, p. 311-5
  25. Goulet JP, Perusse R, Turcotte JY (1992) "Contraindications to vasoconstrictors in dentistry: Part III. Pharmacologic interactions." Oral Surg Oral Med Oral Pathol, 74, p. 692-7
  26. Sjoerdsma A (1966) "Catecholamine-drug interactions in man." Pharmacol Rev, 18, p. 673-83
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  28. King MH, Richards DW (1990) "Near syncope and chest tightness after administration of apraclonidine before argon laser iridotomy." Am J Ophthalmol, 110, p. 308-9
  29. Coleman AL, Robin AL, Pollack IP, Rudikoff MT, Enger C, Mayer PR (1990) "Cardiovascular and intraocular pressure effects and plasma concentrations of apraclonidine." Arch Ophthalmol, 108, p. 1264-7
  30. "Product Information. Iopidine (apraclonidine ophthalmic)." Alcon Laboratories Inc
  31. "Product Information. Tyzine Nasal (tetrahydrozoline nasal)." Kenwood Laboratories
  32. Lefebvre H, Noblet C, Morre N, Wolf LM (1995) "Pseudo-phaeochromocytoma after multiple drug interactions involving the selective monoamine oxidase inhibitor selegiline." Clin Endocrinol (Oxf), 42, p. 95-8
  33. Darcy PF, Griffin JP (1995) "Interactions with drugs used in the treatment of depressive illness." Adverse Drug React Toxicol Rev, 14, p. 211-31
  34. 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
  35. Hunter KR, Boakes AJ, Laurence DR, Stern GM (1970) "Monoamine oxidase inhibitors and L-dopa." Br Med J, 3, p. 388
  36. Kraft KE, Dore FH (1996) "Computerized drug interaction programs: how reliable?." JAMA, 275, p. 1087
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  38. Nordlund JR, Pasquale LR, Robin AL, Rudikoff MT, Ordman J, Chen KS, Walt J (1995) "The cardiovascular, pulmonary, and ocular hypotensive effects of 0.2% brimonidine." Arch Ophthalmol, 113, p. 77-83
  39. (2001) "Product Information. Alphagan (brimonidine ophthalmic)." Allergan Inc
  40. (2001) "Product Information. Sinemet (carbidopa-levodopa)." DuPont Pharmaceuticals
  41. (2001) "Product Information. Ritalin (methylphenidate)." Novartis Pharmaceuticals
  42. (2001) "Product Information. Dexedrine (dextroamphetamine)." SmithKline Beecham
  43. (2001) "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc
  44. Markowitz JS, Patrick KS (2001) "Pharmacokinetic and pharmacodynamic drug interactions in the treatment of attention-deficit hyperactivity disorder." Clin Pharmacokinet, 40, p. 753-72
  45. (2001) "Product Information. Focalin (dexmethylphenidate)." Mikart Inc
  46. (2002) "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company
  47. (2003) "Product Information. Stalevo 50 (carbidopa/entacapone/levodopa)." Novartis Pharmaceuticals
  48. (2004) "Product Information. Parcopa (carbidopa-levodopa)." Schwarz Pharma
  49. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  50. (2007) "Product Information. Vyvanse (lisdexamfetamine)." Shire US Inc
  51. Pekdemir M, Yanturali S, Karakus G (2005) "More than just an ocular solution." Emerg Med J, 22, p. 753-4
  52. Cerner Multum, Inc. "Australian Product Information."
  53. (2013) "Product Information. Mirvaso (brimonidine topical)." Galderma Laboratories Inc
  54. (2020) "Product Information. Zeposia (ozanimod)." Celgene Corporation
View all 54 references

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Drug and food interactions

Moderate

chlorpheniramine food

Applies to: Or-Phen-Ade (chlorpheniramine / phenylpropanolamine)

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

  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
View all 4 references

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Moderate

phenylpropanolamine food

Applies to: Or-Phen-Ade (chlorpheniramine / phenylpropanolamine)

GENERALLY AVOID: Alcohol may potentiate the central nervous system and cardiovascular effects of centrally-acting appetite suppressants. In one study, concurrent administration of methamphetamine (30 mg intravenously) and ethanol (1 gm/kg orally over 30 minutes) increased heart rate by 24 beats/minute compared to methamphetamine alone. This increases cardiac work and myocardial oxygen consumption, which may lead to more adverse cardiovascular effects than either agent alone. Subjective effects of ethanol were diminished in the eight study subjects, but those of methamphetamine were not affected. The pharmacokinetics of methamphetamine were also unaffected except for a decrease in the apparent volume of distribution at steady state.

MANAGEMENT: Concomitant use of centrally-acting appetite suppressants and alcohol should be avoided if possible, especially in patients with a history of cardiovascular disease. Patients should be counselled 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

  1. Mendelson J, Jones RT, Upton R, Jacob P 3rd (1995) "Methamphetamine and ethanol interactions in humans." Clin Pharmacol Ther, 57, p. 559-68
  2. (2001) "Product Information. Didrex (benzphetamine)." Pharmacia and Upjohn
  3. (2012) "Product Information. Suprenza (phentermine)." Akrimax Pharmaceuticals

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Moderate

ozanimod food

Applies to: ozanimod

GENERALLY AVOID: Foods that contain large amounts of tyramine may precipitate a hypertensive crisis in patients treated with ozanimod. The proposed mechanism involves potentiation of the tyramine pressor effect due to inhibition of monoamine oxidase (MAO) by the major active metabolites of ozanimod, CC112273 and CC1084037. Monoamine oxidase in the gastrointestinal tract and liver, primarily type A (MAO-A), is the enzyme responsible for metabolizing exogenous amines such as tyramine 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 causing a rise in blood pressure. In vitro, CC112273 and CC1084037 inhibited MAO-B (IC50 values of 5.72 nM and 58 nM, respectively) with more than 1000-fold selectivity over MAO-A (IC50 values >10000 nM). Because of this selectivity, as well as the fact that free plasma concentrations of CC112273 and CC1084037 are less than 8% of the in vitro IC50 values for MAO-B inhibition, ozanimod is expected to have a much lower propensity to cause hypertensive crises than nonselective MAO inhibitors. However, rare cases of hypertensive crisis have occurred during clinical trials for the treatment of multiple sclerosis (MS) and ulcerative colitis (UC) and in postmarketing use. In controlled clinical trials, hypertension and blood pressure increases were reported more frequently in patients treated with ozanimod (up to 4.6% in MS patients receiving ozanimod 0.92 mg/day) than in patients treated with interferon beta-1a (MS) or placebo (UC).

Administration of ozanimod with either a high-fat, high-calorie meal (1000 calories; 50% fat) or a low-fat, low-calorie meal (300 calories; 10% fat) had no effects on ozanimod peak plasma concentration (Cmax) and systemic exposure (AUC) compared to administration under fasted conditions.

MANAGEMENT: Dietary restriction is not ordinarily required during ozanimod treatment with respect to most foods and beverages that contain tyramine, which usually include aged, fermented, cured, smoked, or pickled foods (e.g., air-dried and fermented meats or fish, aged cheeses, most soybean products, yeast extracts, red wine, beer, sauerkraut). However, certain foods like some of the aged cheeses (e.g., Boursault, Liederkrantz, Mycella, Stilton) and pickled herring may contain very high amounts of tyramine and could potentially cause a hypertensive reaction in patients taking ozanimod, even at recommended dosages, due to increased sensitivity to tyramine. Patients should be advised to avoid the intake of very high levels of tyramine (e.g., greater than 150 mg) and to promptly seek medical attention if they experience potential signs and symptoms of a hypertensive crisis such as severe headache, visual disturbances, confusion, stupor, seizures, chest pain, unexplained nausea or vomiting, and stroke-like symptoms. Blood pressure should be regularly monitored and managed accordingly. Because of the long elimination half-lives of the major active metabolites, these precautions may need to be observed for up to 3 months following the last ozanimod dose. Ozanimod can be administered with or without food.

References

  1. (2022) "Product Information. Zeposia (ozanimod)." Celgene Pty Ltd
  2. (2023) "Product Information. Zeposia (ozanimod)." Bristol-Myers Squibb
  3. (2023) "Product Information. Zeposia (ozanimod)." Bristol-Myers Squibb Canada Inc
  4. (2023) "Product Information. Zeposia (ozanimod)." Bristol-Myers Squibb Pharmaceuticals Ltd
  5. Choi DK, Rubin DT, Puangampai A, Cleveland N (2022) "Hypertensive emergency after initiating ozanimod: a case report." Inflamm Bowel Dis, 28, e114-5
View all 5 references

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Moderate

phenylpropanolamine food

Applies to: Or-Phen-Ade (chlorpheniramine / phenylpropanolamine)

MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.

References

  1. Rosenblatt JE, Lake CR, van Kammen DP, Ziegler MG, Bunney WE Jr (1979) "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res, 1, p. 45-52
  2. Cavanaugh JH, Griffith JD, Oates JA (1970) "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther, 11, p. 656
  3. (2001) "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc
  4. (2001) "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals
  5. (2001) "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals
  6. (2001) "Product Information. Focalin (dexmethylphenidate)." Mikart Inc
  7. (2002) "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company
View all 7 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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