What are the potential medication interactions with Rizatriptan (Maxalt)?

From the Guidelines

Rizatriptan should be used with caution due to potential medication interactions, particularly with MAO inhibitors, SSRIs, SNRIs, and propranolol, which can increase the risk of serotonin syndrome or affect rizatriptan blood levels. When considering medication interactions with rizatriptan, it is essential to prioritize caution to minimize the risk of adverse reactions. According to the most recent evidence 1, triptans, including rizatriptan, have theoretical concerns regarding drug-drug interactions with some commonly used perioperative medications.

Key Interactions to Consider

• Avoid combining rizatriptan with MAO inhibitors, as this can lead to serotonin syndrome, a potentially life-threatening condition 1.
• Use caution when combining rizatriptan with SSRIs and SNRIs, as this can increase the risk of serotonin syndrome 1.
• If taking propranolol, the rizatriptan dose may need to be reduced, as propranolol can increase rizatriptan blood levels.
• Inform your doctor if you take St. John's Wort, as it may interact with rizatriptan.

Clinical Guidance

The American College of Physicians guideline 2 recommends individualized decision-making when choosing a specific triptan, such as rizatriptan, considering patient preferences and factors like route of administration and cost. However, this guideline does not specifically address medication interactions with rizatriptan. Therefore, it is crucial to rely on the most recent and highest-quality study available 1 to inform clinical decisions regarding rizatriptan use and potential medication interactions.

From the FDA Drug Label

Drug Interactions [See also Drug Interactions (7).] Monoamine oxidase inhibitors: Rizatriptan is principally metabolized via monoamine oxidase, 'A' subtype (MAO-A). Plasma concentrations of rizatriptan may be increased by drugs that are selective MAO-A inhibitors (e.g., moclobemide) or nonselective MAO inhibitors [type A and B] (e.g., isocarboxazid, phenelzine, tranylcypromine, and pargyline). In a drug interaction study, when rizatriptan 10 mg was administered to subjects (n=12) receiving concomitant therapy with the selective, reversible MAO-A inhibitor, moclobemide 150 mg t.i.d., there were mean increases in rizatriptan AUC and Cmax of 119% and 41% respectively; and the AUC of the active N-monodesmethyl metabolite of rizatriptan was increased more than 400%. The interaction would be expected to be greater with irreversible MAO inhibitors No pharmacokinetic interaction is anticipated in patients receiving selective MAO-B inhibitors [see Contraindications (4) and Drug Interactions (7. 5)]. Propranolol: In a study of concurrent administration of propranolol 240 mg/day and a single dose of rizatriptan 10 mg in healthy adult subjects (n=11), mean plasma AUC for rizatriptan was increased by 70% during propranolol administration, and a four-fold increase was observed in one subject The AUC of the active N-monodesmethyl metabolite of rizatriptan was not affected by propranolol [see Dosage and Administration (2.4) and Drug Interactions (7. 1)]. Nadolol/Metoprolol: In a drug interactions study, effects of multiple doses of nadolol 80 mg or metoprolol 100 mg every 12 hours on the pharmacokinetics of a single dose of 10 mg rizatriptan were evaluated in healthy subjects (n=12). No pharmacokinetic interactions were observed Paroxetine: In a study of the interaction between the selective serotonin reuptake inhibitor (SSRI) paroxetine 20 mg/day for two weeks and a single dose of rizatriptan 10 mg in healthy subjects (n=12), neither the plasma concentrations of rizatriptan nor its safety profile were affected by paroxetine [see Warnings and Precautions (5.7), Drug Interactions (7. 4), and Patient Counseling Information (17)]. Oral contraceptives: In a study of concurrent administration of an oral contraceptive during 6 days of administration of rizatriptan benzoate (10 to 30 mg/day) in healthy female volunteers (n=18), rizatriptan did not affect plasma concentrations of ethinyl estradiol or norethindrone.

Medication Interactions with Rizatriptan:

• Monoamine Oxidase Inhibitors: may increase plasma concentrations of rizatriptan
• Propranolol: may increase plasma AUC for rizatriptan by 70%
• Nadolol/Metoprolol: no pharmacokinetic interactions observed
• Paroxetine: no effect on plasma concentrations of rizatriptan
• Oral Contraceptives: rizatriptan does not affect plasma concentrations of ethinyl estradiol or norethindrone 3

From the Research

Medication Interactions with Rizatriptan

• Rizatriptan is a serotonin 5-HT1 receptor agonist selective for the 5-HT(1B/1D) subtypes 4
• The efficacy of oral rizatriptan has been demonstrated in large comparative trials with placebo and oral sumatriptan 4
• However, there is limited information on the interactions between rizatriptan and other medications

Interactions with Serotonergic Agents

• The concomitant use of sumatriptan (a triptan similar to rizatriptan) with serotonin selective-reuptake inhibitors (SSRIs) or lithium has been reported to cause symptoms suggestive of serotonin syndrome 5
• However, clinical evidence supporting the strict contraindication of MAOIs, SSRIs, and lithium with triptans is limited 5
• The FDA has warned about the potential life-threatening risk of serotonin syndrome when triptans are used in combination with SSRIs or selective serotonin/norepinephrine reuptake inhibitors (SNRIs) 6

Interactions with Opioids

• The concomitant use of opioids with triptans or serotonergic antidepressants has been reported to increase the risk of serotonin syndrome 7
• However, the evidence for this interaction is limited, and further studies are needed to determine the risk of serotonin syndrome with the addition of a triptan to SSRIs/SNRIs or with triptan monotherapy 6

Clinical Implications

• Clinicians should be vigilant to serotonin toxicity symptoms and signs when prescribing rizatriptan with other serotonergic agents 6
• The currently available evidence does not support limiting the use of triptans with SSRIs or SNRIs, or the use of triptan monotherapy, due to concerns for serotonin syndrome 6, 8