Drug Interactions between Despec-Tab and ozanimod
This report displays the potential drug interactions for the following 2 drugs:
- Despec-Tab (guaifenesin/pseudoephedrine)
- ozanimod
Interactions between your drugs
pseudoephedrine ozanimod
Applies to: Despec-Tab (guaifenesin / pseudoephedrine) 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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- (2013) "Product Information. Mirvaso (brimonidine topical)." Galderma Laboratories Inc
- (2020) "Product Information. Zeposia (ozanimod)." Celgene Corporation
Drug and food interactions
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
- (2022) "Product Information. Zeposia (ozanimod)." Celgene Pty Ltd
- (2023) "Product Information. Zeposia (ozanimod)." Bristol-Myers Squibb
- (2023) "Product Information. Zeposia (ozanimod)." Bristol-Myers Squibb Canada Inc
- (2023) "Product Information. Zeposia (ozanimod)." Bristol-Myers Squibb Pharmaceuticals Ltd
- Choi DK, Rubin DT, Puangampai A, Cleveland N (2022) "Hypertensive emergency after initiating ozanimod: a case report." Inflamm Bowel Dis, 28, e114-5
pseudoephedrine food
Applies to: Despec-Tab (guaifenesin / pseudoephedrine)
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
- 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
- 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
- (2001) "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc
- (2001) "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals
- (2001) "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals
- (2001) "Product Information. Focalin (dexmethylphenidate)." Mikart Inc
- (2002) "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company
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.
See also
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
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. | |
No interaction information available. |
Further information
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