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Drug Interactions between safinamide and Wigraine

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

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Major

ergotamine safinamide

Applies to: Wigraine (caffeine / ergotamine) and safinamide

CONTRAINDICATED: By inhibiting serotonin metabolism, monoamine oxidase inhibitors (MAOIs) may potentiate the pharmacologic activity of serotonergic agents such as serotonin reuptake inhibitors, 5-HT1 receptor agonists, ergot alkaloids, buspirone, dextromethorphan, and most antidepressants. The result may be an increased risk 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. Symptoms of the serotonin syndrome may include mental status changes such as irritability, altered consciousness, confusion, hallucinations, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea.

MANAGEMENT: In general, serotonergic agents should not be used concurrently with MAOIs or other agents that possess MAOI activity (e.g., furazolidone, methylene blue, procarbazine). At least 14 days should elapse between discontinuation of MAOI therapy and initiation of treatment with serotonergic agents. A washout period of 5 to 14 days is usually recommended when switching from another antidepressant to an MAOI; however, the individual product labeling should be consulted.

References

  1. Pettinger WA, Soyangco FG, Oates JA (1968) "Inhibition of monoamine oxidase in man by furazolidone." Clin Pharmacol Ther, 9, p. 442-7
  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. Sternbach H (1988) "Danger of MAOI therapy after fluoxetine withdrawal." Lancet, 2, p. 850-1
  4. Sovner R, Wolfe J (1988) "Interaction between dextromethorphan and monoamine oxidase inhibitor therapy with isocarboxazid ." N Engl J Med, 319, p. 1671
  5. Bem JL, Peck R (1992) "Dextromethorphan. An overview of safety issues." Drug Saf, 7, p. 190-9
  6. Nierenberg DW, Semprebon M (1993) "The central nervous system serotonin syndrome." Clin Pharmacol Ther, 53, p. 84-8
  7. Graham PM, Potter JM, Paterson J (1982) "Combination monoamine oxidase inhibitor/tricyclic antidepressants interaction." Lancet, 2, p. 440
  8. Spiker DG, Pugh DD (1976) "Combining tricyclic and monoamine oxidase inhibitor antidepressants." Arch Gen Psychiatry, 33, p. 828-30
  9. White K, Pistole T, Boyd JL (1980) "Combined monoamine oxidase inhibitor-tricyclic antidepressant treatment: a pilot study." Am J Psychiatry, 137, p. 1422-5
  10. White K, Simpson G (1981) "Combined MAOI-tricyclic antidepressant treatment: a reevaluation." J Clin Psychopharmacol, 1, p. 264-82
  11. Rivers N, Horner B (1970) "Possible lethal reaction between nardil and dextromethorphan." Can Med Assoc J, 103, p. 85
  12. (2002) "Product Information. D.H.E. 45 (dihydroergotamine)." Sandoz Pharmaceuticals Corporation
  13. Sternbach H (1991) "The serotonin syndrome." Am J Psychiatry, 148, p. 705-13
  14. Feighner JP, Boyer WF, Tyler DL, Neborsky RJ (1990) "Adverse consequences of fluoxetine-MAOI combination therapy." J Clin Psychiatry, 51, p. 222-5
  15. Graham PM, Ilett KF (1988) "Danger of MAOI therapy after fluoxetine withdrawal." Lancet, 2, p. 1255-6
  16. Bhatara VS, Bandettini FC (1993) "Possible interaction between sertraline and tranylcypromine." Clin Pharm, 12, p. 222-5
  17. Suchowersky O, deVries JD (1990) "Interaction of fluoxetine and selegiline." Can J Psychiatry, 35, p. 571-2
  18. (2001) "Product Information. Effexor (venlafaxine)." Wyeth-Ayerst Laboratories
  19. Brannan SK, Talley BJ, Bowden CL (1994) "Sertraline and isocarboxazid cause a serotonin syndrome." J Clin Psychopharmacol, 14, p. 144-5
  20. Graber MA, Hoehns TB, Perry PJ (1994) "Sertraline-phenelzine drug interaction: a serotonin syndrome reaction." Ann Pharmacother, 28, p. 732-5
  21. Cetaruk EW, Aaron CK (1994) "Hazards of nonprescription medications." Emerg Med Clin North Am, 12, p. 483-510
  22. Diamond S (1995) "The use of sumatriptan in patients on monoamine oxidase inhibitors." Neurology, 45, p. 1039-40
  23. Phillips SD, Ringo P (1995) "Phenelzine and venlafaxine interaction." Am J Psychiatry, 152, p. 1400-1
  24. Klysner R, Larsen JK, Sorensen P, Hyllested M, Pedersen BD (1995) "Toxic interaction of venlafaxine and isocarboxazide." Lancet, 346, p. 1298-9
  25. Darcy PF, Griffin JP (1995) "Interactions with drugs used in the treatment of depressive illness." Adverse Drug React Toxicol Rev, 14, p. 211-31
  26. Heisler MA, Guidry JR, Arnecke B (1996) "Serotonin syndrome induced by administration of venlafaxine and phenelzine." Ann Pharmacother, 30, p. 84
  27. 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
  28. Fischer P (1995) "Serotonin syndrome in the elderly after antidepressive monotherapy." J Clin Psychopharmacol, 15, p. 440-2
  29. Corkeron MA (1995) "Serotonin syndrome - a potentially fatal complication of antidepressant therapy." Med J Aust, 163, p. 481-2
  30. Thomas JM, Rubin EH (1984) "Case report of a toxic reaction from a combination of tryptophan and phenelzine." Am J Psychiatry, 141, p. 281-3
  31. Pope HG Jr, Jonas JM, Hudson JI, Kafka MP (1985) "Toxic reactions to the combination of monoamine oxidase inhibitors and tryptophan." Am J Psychiatry, 142, p. 491-2
  32. Alvine G, Black DW, Tsuang D (1990) "Case of delirium secondary to phenelzine/L-tryptophan combination." J Clin Psychiatry, 51, p. 311
  33. Staufenberg EF, Tantam D (1989) "Malignant hyperpyrexia syndrome in combined treatment." Br J Psychiatry, 154, p. 577-8
  34. Levy AB, Bucher P, Votolato N (1985) "Myoclonus, hyperreflexia and diaphoresis in patients on phenelzine- tryptophan combination treatment." Can J Psychiatry, 30, p. 434-6
  35. Beasley CM Jr, Masica DN, Heiligenstein JH, Wheadon DE, Zerbe RL (1993) "Possible monoamine oxidase inhibitor-serotonin uptake inhibitor interaction: fluoxetine clinical data and preclinical findings." J Clin Psychopharmacol, 13, p. 312-20
  36. Mills KC (1997) "Serotonin syndrome: A clinical update." Crit Care Clin, 13, p. 763
  37. Gardner DM, Lynd LD (1998) "Sumatriptan contraindications and the serotonin syndrome." Ann Pharmacother, 32, p. 33-8
  38. Mathew NT, Tietjen GE, Lucker C (1996) "Serotonin syndrome complicating migraine pharmacotherapy." Cephalalgia, 16, p. 323-7
  39. Weiner LA, Smythe M, Cisek J (1998) "Serotonin syndrome secondary to phenelzine-venlafaxine interaction." Pharmacotherapy, 18, p. 399-403
  40. Diamond S, Pepper BJ, Diamond ML, Freitag FG, Urban GJ, Erdemoglu AK (1998) "Serotonin syndrome induced by transitioning from phenelzine to venlafaxine: four patient reports." Neurology, 51, p. 274-6
  41. Chan BSH, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG (1998) "Serotonin syndrome resulting from drug interactions." Med J Aust, 169, p. 523-5
  42. Brubacher JR, Hoffman RS, Lurin MJ (1996) "Serotonin syndrome from venlafaxine-tranylcypromine interaction." Vet Hum Toxicol, 38, p. 358-61
  43. Miller LG (1998) "Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions." Arch Intern Med, 158, p. 2200-11
  44. Martin TG (1996) "Serotonin syndrome." Ann Emerg Med, 28, p. 520-6
  45. Jacob JE, Wagner ML, Sage JI (2003) "Safety of selegiline with cold medications." Ann Pharmacother, 37, p. 438-41
  46. (2004) "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company
  47. (2005) "Product Information. Manerix (moclobemide)." Hoffmann-La Roche Limited
  48. Gillman PK (2005) "Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity." Br J Anaesth
  49. Bodner RA, Lynch T, Lewis L, Kahn D (1995) "Serotonin syndrome." Neurology, 45, p. 219-23
  50. Jimenez-Genchi A (2006) "Immediate switching from moclobemide to duloxetine may induce serotonin syndrome." J Clin Psychiatry, 67, p. 1821-1822
  51. (2008) "Product Information. Pristiq (desvenlafaxine)." Wyeth Laboratories
  52. (2009) "Product Information. Savella (milnacipran)." Forest Pharmaceuticals
  53. (2011) "Product Information. Viibryd (vilazodone)." Trovis Pharmaceuticals LLC
  54. (2013) "Product Information. Fetzima (levomilnacipran)." Forest Pharmaceuticals
View all 54 references

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Drug and food interactions

Moderate

ergotamine food

Applies to: Wigraine (caffeine / ergotamine)

MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of drugs that undergo significant presystemic metabolism by CYP450 3A4. Grapefruit and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact with these drugs.

References

  1. Edgar B, Bailey D, Bergstrand R, et al. (1992) "Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics on felodipine and its potential clinical relevance." Eur J Clin Pharmacol, 42, p. 313-7
  2. Jonkman JH, Sollie FA, Sauter R, Steinijans VW (1991) "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther, 49, p. 248-55
  3. Bailey DG, Arnold JM, Munoz C, Spence JD (1993) "Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin." Clin Pharmacol Ther, 53, p. 637-42
  4. Bailey DG, Arnold JMO, Spence JD (1994) "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet, 26, p. 91-8
  5. Sigusch H, Hippius M, Henschel L, Kaufmann K, Hoffmann A (1994) "Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation." Pharmazie, 49, p. 522-4
  6. Bailey DG, Arnold JM, Strong HA, Munoz C, Spence JD (1993) "Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics." Clin Pharmacol Ther, 54, p. 589-94
  7. Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG (1995) "Drug-food interactions in clinical practice." J Fam Pract, 40, p. 376-84
  8. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  9. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ (1995) "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther, 58, p. 127-31
  10. Min DI, Ku YM, Geraets DR, Lee HC (1996) "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol, 36, p. 469-76
  11. Majeed A, Kareem A (1996) "Effect of grapefruit juice on cyclosporine pharmacokinetics." Pediatr Nephrol, 10, p. 395
  12. Clifford CP, Adams DA, Murray S, Taylor GW, Wilkins MR, Boobis AR, Davies DS (1996) "Pharmacokinetic and cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice." Br J Clin Pharmacol, 42, p662
  13. Josefsson M, Zackrisson AL, Ahlner J (1996) "Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers." Eur J Clin Pharmacol, 51, p. 189-93
  14. Kantola T, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid." Clin Pharmacol Ther, 63, p. 397-402
  15. Ozdemir M, Aktan Y, Boydag BS, Cingi MI, Musmul A (1998) "Interaction between grapefruit juice and diazepam in humans." Eur J Drug Metab Pharmacokinet, 23, p. 55-9
  16. Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
  17. Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR (1998) "Grapefruit juice felodipine interaction: Effect of naringin and 6',7'-dihydroxybergamottin in humans." Clin Pharmacol Ther, 64, p. 248-56
  18. Garg SK, Kumar N, Bhargava VK, Prabhakar SK (1998) "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther, 64, p. 286-8
  19. Lilja JJ, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors." Clin Pharmacol Ther, 64, p. 477-83
  20. Fuhr U, Maier-Bruggemann A, Blume H, et al. (1998) "Grapefruit juice increases oral nimodipine bioavailability." Int J Clin Pharmacol Ther, 36, p. 126-32
  21. Lilja JJ, Kivisto KT, Neuvonen PJ (1999) "Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin." Clin Pharmacol Ther, 66, p. 118-27
  22. Eagling VA, Profit L, Back DJ (1999) "Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-I protease inhibitor saquinavir by grapefruit juice components." Br J Clin Pharmacol, 48, p. 543-52
  23. Damkier P, Hansen LL, Brosen K (1999) "Effect of diclofenac, disulfiram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine." Br J Clin Pharmacol, 48, p. 829-38
  24. Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BCC (1999) "The effects of grapefruit juice on sertraline metabolism: An in vitro and in vivo study." Clin Ther, 21, p. 1890-9
  25. Dresser GK, Spence JD, Bailey DG (2000) "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet, 38, p. 41-57
  26. Gunston GD, Mehta U (2000) "Potentially serious drug interactions with grapefruit juice." S Afr Med J, 90, p. 41
  27. Takanaga H, Ohnishi A, Maatsuo H, et al. (2000) "Pharmacokinetic analysis of felodipine-grapefruit juice interaction based on an irreversible enzyme inhibition model." Br J Clin Pharmacol, 49, p. 49-58
  28. Libersa CC, Brique SA, Motte KB, et al. (2000) "Dramatic inhibition of amiodarone metabolism induced by grapefruit juice." Br J Clin Pharmacol, 49, p. 373-8
  29. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
  30. Zaidenstein R, Soback S, Gips M, Avni B, Dishi V, Weissgarten Y, Golik A, Scapa E (2001) "Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite E3174 in healthy volunteers." Ther Drug Monit, 23, p. 369-73
  31. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K (1993) "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol, 44, p. 295-8
  32. Flanagan D (2005) "Understanding the grapefruit-drug interaction." Gen Dent, 53, 282-5; quiz 286
View all 32 references

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Moderate

safinamide food

Applies to: safinamide

GENERALLY AVOID: Foods that contain large amounts of tyramine may precipitate a hypertensive crisis in patients treated with safinamide. The proposed mechanism involves potentiation of the tyramine pressor effect due to inhibition of monoamine oxidase (MAO) by safinamide. 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, safinamide inhibits MAO-B with greater than 1000-fold selectivity over MAO-A, and neither safinamide nor its major metabolites inhibit MAO-A at clinically relevant concentrations. Results from an oral tyramine challenge study also suggest that safinamide is a selective inhibitor of MAO-B at the recommended dosages of 50 or 100 mg/day. However, this selectivity is not absolute and may diminish in a dose-related manner above the maximum recommended daily dosage. In clinical trials, the incidence of hypertension was 7% and 5% for safinamide 50 mg and 100 mg, respectively, versus 4% for placebo. There were no reported cases of hypertensive crisis.

Administration of safinamide following intake of a high-fat, high-caloric breakfast resulted in a slight delay in the absorption of safinamide, but had no effects on safinamide peak plasma concentration (Cmax) and systemic exposure (AUC) compared to administration under fasted conditions.

MANAGEMENT: Dietary restriction is not ordinarily required during safinamide 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 safinamide, 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. Medication adjustment may be necessary if blood pressure elevations are sustained or not adequately controlled. Safinamide should not be used at dosages exceeding 100 mg/day, or 50 mg/day in patients with moderate hepatic impairment (Child-Pugh B, 7-9), as it may increase the risk of hypertensive crisis and other adverse reactions associated with nonselective inhibition of MAO. Safinamide can be administered with or without food.

References

  1. (2023) "Product Information. Xadago (safinamide)." US WorldMeds LLC
  2. (2020) "Product Information. Onstryv (safinamide)." Valeo Pharma
  3. (2022) "Product Information. Xadago (safinamide)." Seqirus Pty Ltd
  4. (2021) "Product Information. Xadago (safinamide)." Zambon UK Ltd
View all 4 references

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Moderate

ergotamine food

Applies to: Wigraine (caffeine / ergotamine)

MONITOR: Nicotine may cause vasoconstriction in some patients and potentiate the ischemic response to ergot alkaloids.

MANAGEMENT: Caution may be advisable when ergot alkaloids are used in combination with nicotine products. Patients should be advised to seek immediate medical attention if they experience potential symptoms of ischemia such as coldness, pallor, cyanosis, numbness, tingling, or pain in the extremities; muscle weakness; severe or worsening headache; visual disturbances; severe abdominal pain; chest pain; and shortness of breath.

References

  1. (2001) "Product Information. Migranal (dihydroergotamine nasal)." Novartis Pharmaceuticals
  2. (2004) "Product Information. Cafergot (caffeine-ergotamine)." Novartis Pharmaceuticals
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  4. Cerner Multum, Inc. "Australian Product Information."
View all 4 references

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Minor

caffeine food

Applies to: Wigraine (caffeine / ergotamine)

The effect of grapefruit juice on the pharmacologic activity of caffeine is controversial. One report suggests that grapefruit juice increases the effect of caffeine. The proposed mechanism is inhibition of cytochrome P-450 metabolism of caffeine. However, a well-conducted pharmacokinetic/pharmacodynamic study did not demonstrate this effect. The clinical significance of this potential interaction is unknown.

References

  1. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  2. Maish WA, Hampton EM, Whitsett TL, Shepard JD, Lovallo WR (1996) "Influence of grapefruit juice on caffeine pharmacokinetics and pharmacodynamics." Pharmacotherapy, 16, p. 1046-52

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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.

Further information

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