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Drug Interactions between Aldex G and ozanimod

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

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Moderate

phenylephrine ozanimod

Applies to: Aldex G (guaifenesin / phenylephrine) 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

  1. Pettinger WA, Soyangco FG, Oates JA "Inhibition of monoamine oxidase in man by furazolidone." Clin Pharmacol Ther 9 (1968): 442-7
  2. Schulz R, Antonin KH, Hoffmann E, et al. "Tyramine kinetics and pressor sensitivity during monoamine oxidase inhibition by selegiline." Clin Pharmacol Ther 46 (1989): 528-36
  3. Krisko I, Lewis E, Johnson JE "Severe hyperpyrexia due to tranylcypromine-amphetamine toxicity." Ann Intern Med 70 (1969): 559-64
  4. Elis J, Laurence DR, Mattie H, Prichard BN "Modification by monoamine oxidase inhibitors of the effect of some sympathomimetics on blood pressure." Br Med J 2 (1967): 75-8
  5. Davies B, Bannister R, Sever P "Pressor amines and monoamine-oxidase inhibitors for treatment of postural hypotension in autonomic failure: limitations and hazards." Lancet 1 (1978): 172-5
  6. Goldberg LI "Monoamine oxidase inhibitors: adverse reactions and possible mechanisms." JAMA 190 (1964): 456-62
  7. Horler AR, Wynne NA "Hypertensive crisis due to pargyline and metaraminol." Br Med J 5459 (1965): 460-1
  8. Sjoqvist F "Psychotropic drugs (2) interaction between monoamine oxidase (MAO) inhibitors and other substances." Proc R Soc Med 58 (1965): 967-78
  9. Harrison WM, McGrath PJ, Stewart JW, Quitkin F "MAOIs and hypertensive crises: the role of OTC drugs." J Clin Psychiatry 50 (1989): 64-5
  10. Cuthbert MF, Greenberg MP, Morley SW "Cough and cold remedies: a potential danger to patients on monoamine oxidase inhibitors." Br Med J 1 (1969): 404-6
  11. Humberstone PM "Hypertension from cold remedies." Br Med J 1 (1969): 846
  12. Wright SP "Hazards with monoamine-oxidase inhibitors: a persistent problem." Lancet 1 (1978): 284-5
  13. Boakes AJ, Laurence DR, Teoh PC, Barar FS, Benedikter LT, Pritchard BN "Interactions between sympathomimetic amines and antidepressant agents in man." Br Med J 1 (1973): 311-5
  14. Dally PJ "Fatal reaction associated with tranylcypromine and methylamphetamine." Lancet 1 (1962): 1235-6
  15. Schildkraut JJ, Klerman GL, Friend DG, Greenblatt M "Biochemical and pressor effects of oral d,l-dihydroxyphenylalanine in patients pretreated with antidepressant drugs." Ann N Y Acad Sci 107 (1963): 1005-15
  16. Sharpe J, Marquez-Julio A, Ashby P "Idiopathic orthostatic hypotension treated with levodopa and MAO inhibitor: a preliminary report." Can Med Assoc J 107 (1972): 296-300
  17. Teychenne PF, Calne DB, Lewis PJ, Findley LJ "Interactions of levodopa with inhibitors of monoamine oxidase and L-aromatic amino acid decarboxylase." Clin Pharmacol Ther 18 (1975): 273-7
  18. Smookler S, Bermudez AJ "Hypertensive crisis resulting from an MAO inhibitor and an over-the-counter appetite suppressant." Ann Intern Med 11 (1982): 482-4
  19. "Product Information. Aldomet (methyldopa)." Merck & Co., Inc PROD (2001):
  20. Paykel ES "Hallucinosis on combined methyldopa and pargyline." Br Med J 1 (1966): 803
  21. van Rossum JM, Hurkmans JA "Reversal of the effect of a-Methyldopa by monamine oxidase inhibitors." J Pharm Pharmacol 15 (1963): 493-9
  22. van Rossum JM "Potential danger of monoamineoxidase inhibitors and a-methyldopa." Lancet 1 (1963): 950-1
  23. Mason AM, Buckle RM ""Cold" cures and monoamine-oxidase inhibitors." Br Med J 1 (1969): 845-6
  24. Boakes AJ, Laurence DR, Teoh PC, Barar FS, Benedikter LT, Prichard BN "Interactions between sympathomimetic amines and antidepressant agents in man." Br Med J 1 (1973): 311-5
  25. Goulet JP, Perusse R, Turcotte JY "Contraindications to vasoconstrictors in dentistry: Part III. Pharmacologic interactions." Oral Surg Oral Med Oral Pathol 74 (1992): 692-7
  26. Sjoerdsma A "Catecholamine-drug interactions in man." Pharmacol Rev 18 (1966): 673-83
  27. Ban TA "Drug interactions with psychoactive drugs." Dis Nerv Syst 36 (1975): 164-6
  28. King MH, Richards DW "Near syncope and chest tightness after administration of apraclonidine before argon laser iridotomy." Am J Ophthalmol 110 (1990): 308-9
  29. Coleman AL, Robin AL, Pollack IP, Rudikoff MT, Enger C, Mayer PR "Cardiovascular and intraocular pressure effects and plasma concentrations of apraclonidine." Arch Ophthalmol 108 (1990): 1264-7
  30. "Product Information. Iopidine (apraclonidine ophthalmic)." Alcon Laboratories Inc PROD
  31. "Product Information. Tyzine Nasal (tetrahydrozoline nasal)." Kenwood Laboratories PROD
  32. Lefebvre H, Noblet C, Morre N, Wolf LM "Pseudo-phaeochromocytoma after multiple drug interactions involving the selective monoamine oxidase inhibitor selegiline." Clin Endocrinol (Oxf) 42 (1995): 95-8
  33. Darcy PF, Griffin JP "Interactions with drugs used in the treatment of depressive illness." Adverse Drug React Toxicol Rev 14 (1995): 211-31
  34. De Vita VT, Hahn MA, Oliverio VT "Monoamine oxidase inhibition by a new carcinostatic agent, n-isopropyl-a-(2-methylhydrazino)-p-toluamide (MIH). (30590)." Proc Soc Exp Biol Med 120 (1965): 561-5
  35. Hunter KR, Boakes AJ, Laurence DR, Stern GM "Monoamine oxidase inhibitors and L-dopa." Br Med J 3 (1970): 388
  36. Kraft KE, Dore FH "Computerized drug interaction programs: how reliable?." JAMA 275 (1996): 1087
  37. Kronig MH, Roose SP, Walsh BT, Woodring S, Glassman AH "Blood pressure effects of phenelzine." J Clin Psychopharmacol 3 (1983): 307-10
  38. Nordlund JR, Pasquale LR, Robin AL, Rudikoff MT, Ordman J, Chen KS, Walt J "The cardiovascular, pulmonary, and ocular hypotensive effects of 0.2% brimonidine." Arch Ophthalmol 113 (1995): 77-83
  39. "Product Information. Alphagan (brimonidine ophthalmic)." Allergan Inc PROD (2001):
  40. "Product Information. Sinemet (carbidopa-levodopa)." DuPont Pharmaceuticals PROD (2001):
  41. "Product Information. Ritalin (methylphenidate)." Novartis Pharmaceuticals PROD (2001):
  42. "Product Information. Dexedrine (dextroamphetamine)." SmithKline Beecham PROD (2001):
  43. "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc PROD (2001):
  44. Markowitz JS, Patrick KS "Pharmacokinetic and pharmacodynamic drug interactions in the treatment of attention-deficit hyperactivity disorder." Clin Pharmacokinet 40 (2001): 753-72
  45. "Product Information. Focalin (dexmethylphenidate)." Mikart Inc (2001):
  46. "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company (2002):
  47. "Product Information. Stalevo 50 (carbidopa/entacapone/levodopa)." Novartis Pharmaceuticals (2003):
  48. "Product Information. Parcopa (carbidopa-levodopa)." Schwarz Pharma (2004):
  49. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  50. "Product Information. Vyvanse (lisdexamfetamine)." Shire US Inc (2007):
  51. Pekdemir M, Yanturali S, Karakus G "More than just an ocular solution." Emerg Med J 22 (2005): 753-4
  52. Cerner Multum, Inc. "Australian Product Information." O 0
  53. "Product Information. Mirvaso (brimonidine topical)." Galderma Laboratories Inc (2013):
  54. "Product Information. Zeposia (ozanimod)." Celgene Corporation (2020):
View all 54 references

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Drug and food interactions

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

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Moderate

phenylephrine food

Applies to: Aldex G (guaifenesin / phenylephrine)

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