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Drug Interactions between ozanimod and Tussi-Organidin-S NR

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

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Interactions between your drugs

Moderate

codeine ozanimod

Applies to: Tussi-Organidin-S NR (codeine / guaifenesin) and ozanimod

GENERALLY AVOID: Coadministration of opioid analgesics with drugs that possess monoamine oxidase inhibition (MAOI) activity, including selective MAO-B inhibitors, has been associated with rare reports of severe and sometimes fatal adverse reactions. Because an active metabolite of ozanimod inhibits MAO-B in vitro, the interaction may theoretically occur with ozanimod. There appear to be two types of interaction, an excitatory and a depressive one. Symptoms of the excitatory reaction may include agitation, headache, diaphoresis, hyperpyrexia, flushing, shivering, myoclonus, rigidity, tremor, diarrhea, hypertension, tachycardia, seizures, and coma. Death has occurred in some cases. In contrast, symptoms of the depressive reaction probably stem from potentiation of CNS effects by MAOIs and include respiratory depression, cyanosis, hypotension, and coma. There have also been reports of serotonin syndrome, which is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A and 2A receptors, with symptoms similar to the excitatory reaction described above. Some opioids such as fentanyl, meperidine, methadone, tapentadol, and tramadol can inhibit serotonin reuptake and are more likely to cause serotonin syndrome. However, serotonin syndrome has also occurred with other opioids.

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

References

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  3. Pettinger WA, Soyangco FG, Oates JA (1968) "Inhibition of monoamine oxidase in man by furazolidone." Clin Pharmacol Ther, 9, p. 442-7
  4. 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
  5. Evans-Prosser CD (1968) "The use of pethidine and morphine in the presence of monoamine oxidase inhibitors." Br J Anaesth, 40, p. 279-82
  6. Goldberg LI (1964) "Monoamine oxidase inhibitors: adverse reactions and possible mechanisms." JAMA, 190, p. 456-62
  7. Vigran IM (1964) "Dangerous potentiation of meperidine hydrochloride by pargyline hydrochloride." JAMA, 187, p. 953-4
  8. Nierenberg DW, Semprebon M (1993) "The central nervous system serotonin syndrome." Clin Pharmacol Ther, 53, p. 84-8
  9. (2002) "Product Information. Demerol (meperidine)." Sanofi Winthrop Pharmaceuticals
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  11. (2001) "Product Information. Roxicodone (oxycodone)." Roxane Laboratories Inc
  12. Sternbach H (1991) "The serotonin syndrome." Am J Psychiatry, 148, p. 705-13
  13. Starr C (1991) "Interaction between pethidine and selegiline." Lancet, 337, p. 554
  14. (2001) "Product Information. Levo-Dromoran (levorphanol)." Roche Laboratories
  15. Youssef MS, Wilkinson PA (1988) "Epidural fentanyl and monoamine oxidase inhibitors." Anaesthesia, 43, p. 210-2
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  19. Garbutt JC (1987) "Potentiation of propoxyphene by phenelzine." Am J Psychiatry, 144, p. 251-2
  20. Zornberg GL, Hegarty JD (1993) "Adverse interaction between propoxyphene and phenelzine." Am J Psychiatry, 150, p. 1270-1
  21. (2001) "Product Information. Tylenol with Codeine (acetaminophen-codeine)." Janssen Pharmaceuticals
  22. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  23. (2001) "Product Information. Ultram (tramadol)." McNeil Pharmaceutical
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  28. Fischer P (1995) "Serotonin syndrome in the elderly after antidepressive monotherapy." J Clin Psychopharmacol, 15, p. 440-2
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  30. Michaels I, Serrins M, Shier NQ, Barash PG (1984) "Anesthesia for cardiac surgery in patients receiving monoamine oxidase inhibitors." Anesth Analg, 63, p. 1041-4
  31. Staufenberg EF, Tantam D (1989) "Malignant hyperpyrexia syndrome in combined treatment." Br J Psychiatry, 154, p. 577-8
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  35. (2001) "Product Information. Actiq (fentanyl)." Abbott Pharmaceutical
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  37. (2001) "Product Information. Nubain (nalbuphine)." Endo Laboratories LLC
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  56. (2009) "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals
  57. (2012) "Product Information. Methylene Blue (methylene blue)." American Regent Laboratories Inc
  58. (2020) "Product Information. Zeposia (ozanimod)." Celgene Corporation
View all 58 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. (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

codeine food

Applies to: Tussi-Organidin-S NR (codeine / guaifenesin)

GENERALLY AVOID: Ethanol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

MANAGEMENT: Concomitant use of opioid analgesics with ethanol should be avoided.

References

  1. Linnoila M, Hakkinen S (1974) "Effects of diazepam and codeine, alone and in combination with alcohol, on simulated driving." Clin Pharmacol Ther, 15, p. 368-73
  2. Sturner WQ, Garriott JC (1973) "Deaths involving propoxyphene: a study of 41 cases over a two-year period." JAMA, 223, p. 1125-30
  3. Girre C, Hirschhorn M, Bertaux L, et al. (1991) "Enhancement of propoxyphene bioavailability by ethanol: relation to psychomotor and cognitive function in healthy volunteers." Eur J Clin Pharmacol, 41, p. 147-52
  4. Levine B, Saady J, Fierro M, Valentour J (1984) "A hydromorphone and ethanol fatality." J Forensic Sci, 29, p. 655-9
  5. Sellers EM, Hamilton CA, Kaplan HL, Degani NC, Foltz RL (1985) "Pharmacokinetic interaction of propoxyphene with ethanol." Br J Clin Pharmacol, 19, p. 398-401
  6. Carson DJ (1977) "Fatal dextropropoxyphene poisoning in Northern Ireland. Review of 30 cases." Lancet, 1, p. 894-7
  7. Rosser WW (1980) "The interaction of propoxyphene with other drugs." Can Med Assoc J, 122, p. 149-50
  8. Edwards C, Gard PR, Handley SL, Hunter M, Whittington RM (1982) "Distalgesic and ethanol-impaired function." Lancet, 2, p. 384
  9. Kiplinger GF, Sokol G, Rodda BE (1974) "Effect of combined alcohol and propoxyphene on human performance." Arch Int Pharmacodyn Ther, 212, p. 175-80
View all 9 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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