Rizatriptan (Maxalt) Interactions
- Amphetamine
- Buspirone
- Cocaine
- Dexfenfluramine
- Dextroamphetamine
- Dextromethorphan
Ergot Alkaloids
- Fenfluramine
- Feverfew, Tanacetum parthenium
- Lithium
- Meperidine
- Mirtazapine
Monoamine oxidase inhibitors (MAOIs)
- Nefazodone
Oral contraceptives
- Propranolol
Selective serotonin reuptake inhibitors (SSRIs)
Serotonin norepinephrine reuptake inhibitors
Serotonin-Receptor Agonists
- Sibutramine
- St. John’s Wort, Hypericum perforatum
- Trazodone
Tricyclic antidepressants
- Tryptophan, 5-Hydroxytryptophan
Rizatriptan (Maxalt) Interactions
Rizatriptan should not be administered within 24 hours of other 5HT1 serotonin-receptor agonists (e.g., almotriptan, eletriptan, frovatriptan, naratriptan, sumatriptan, or zolmitriptan).
Ergot alkaloids may cause prolonged or additive vasospastic effects when administered with 5-HT agonists. Rizatriptan should not be used within 24 hours of treatment with any ergotamine-containing or ergot-type medication (e.g., dihydroergotamine, methysergide).
The administration of rizatriptan to patients currently receiving MAOIs or within 2 weeks of discontinuation of MAOIs is contraindicated. Rizatriptan is principally metabolized by monoamine oxidase A (MAO-A). MAOIs which selectively inhibit MAO-A such as moclobemide or nonselective MAOIs increase plasma concentrations of rizatriptan 41% and increase the concentration of the active N-monodesmethyl metabolite more than 400%. Selegiline, a nonselective MAO-B inhibitor, may interact with rizatriptan at higher doses (> 20 mg); the manufacturer does not recommend concomitant use. Patients receiving concomitant administration of other antimigraine agents (e.g., calcium channel blockers, valproic acid, opiate analgesics, oral contraceptives/estrogen replacement) with rizatriptan had similar adverse reaction rates as compared to those who did not receive these medications concomitantly.
Concurrent administration of propranolol 240 mg/day and a single dose of rizatriptan 10 mg resulted in a 70% increase in the mean rizatriptan AUC. The AUC of the active N-monodesmethyl metabolite was not affected by propranolol. This interaction is most likely due to first-pass metabolic interaction between rizatriptan and propranolol. Based on in vitro data, no pharmacokinetic interaction is expected with timolol or atenolol. This interaction requires a dose adjustment of rizatriptan when it is given concurrently with propranolol. The recommended dose of rizatriptan 5 mg up to a maximum of 15 mg in 24 hours when given with propranolol. Patients receiving concomitant administration of other antimigraine agents (e.g., beta-blockers including propranolol) with rizatriptan had similar adverse reaction rates as compared to those who did not receive these medications concomitantly.
Tricyclic antidepressants (TCAs) inhibit serotonin uptake and rarely cause serotonin syndrome when used alone; cases of this complication usually have involved the combination of TCAs with other serotonergic therapies. However, TCAs should be used cautiously with drugs that augment serotonin, like the serotonin-receptor agonists (’triptans’) used for the treatment of migraine. Serotonin syndrome from the use of ‘triptan’-class drugs is a rare entity with monotherapy. If it is required that ‘triptans’ be given to patients receiving a drug with potential serotonergic effects, appropriate observation of the patient is recommended; serotonin excess may be possible. In clinical trials, patients receiving concomitant administration of other antimigraine agents (e.g., TCAs) with rizatriptan had similar adverse reaction rates as compared to those who did not receive these medications concomitantly.
Although unlikely to occur with serotonin-receptor agonists (’triptans’ used for migraine headache) when given alone, combining medications that potentiate serotonin neurotransmission could result in serotonin syndrome. Pharmacologically, buspirone is a serotonin agonist, and use in conjunction with other serotonin agonists could result in serotonin syndrome. Patients receiving serotonin-receptor agonists and buspirone should be informed of the signs and symptoms of serotonin syndrome; although rare, serotonin excess is possible with concurrent use.
Serotonin syndrome has been reported during concurrent use of serotonin norepinephrine reuptake inhibitors (SNRIs) or selective serotonin reuptake inhibitors (SSRIs) with serotonin-receptor agonists (e.g., almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan). Of the 27 cases reviewed by the FDA, 2 were considered life-threatening and 13 required hospitalization. Some patients had used the combination previously without incident. Eight of 27 cases involved a recent dose increase or addition of another serotonergic drug to the regimen, with a median onset of 1 day (range: 10 minutes to 6 days). It is thought that the interaction between SNRIs or SSRIs and serotonin-receptor agonists is the result of increased serotonergic activity by each of the drug classes. Serotonin syndrome consists of symptoms such as mental status changes (e.g., agitation, confusion, hallucinations), diaphoresis, hyperreflexia, hypertension, diarrhea, fever, tremor, and, in some instances, respiratory failure. At least 6 patients taking an SSRI antidepressant are known to have received sumatriptan for migraine where no apparent adverse effects were seen. In another case report, the addition of fluoxetine lead to loss of migraine control with sumatriptan. Careful monitoring is recommended if combination therapy is required.
Although unlikely to occur with 5HT1 agonists when given alone, combining medications that potentiate serotonin neurotransmission could result in serotonin syndrome. Serotonin syndrome, while uncommon, can be serious and consists of symptoms such as mental status changes, diaphoresis, tremor, myoclonus, hyperreflexia, and fever. Various medications potentiate the effects of serotonin through different mechanisms such as increasing serotonin synthesis (L-tryptophan), decreasing serotonin metabolism (MAOIs), primarily by increasing serotonin release (amphetamine, cocaine, fenfluramine and dexfenfluramine, dextroamphetamine), inhibiting serotonin uptake (cocaine, dextromethorphan, duloxetine, meperidine, nefazodone, St. John’s wort, Hypericum perforatum, trazodone, TCAs), direct action at serotonin receptors (buspirone), or otherwise increasing serotonin neurotransmission (lithium, mirtazapine, dopamine agonists).
Sibutramine is a serotonin reuptake inhibitor. Concomitant use of two serotonin-augmenting drugs has been associated with serotonin syndrome. Serotonin syndrome may be possible with the concomitant use of serotonin-receptor agonists (’triptan’ class medications). Because sibutramine inhibits serotonin reuptake, in general, it should not be administered with other serotonergic agents. However, if such a combination is clinically indicated, appropriate observation of the patient is warranted.
No studies have systematically evaluated the concurrent use of feverfew, Tanacetum parthenium with common medications used to abort acute migraine attacks (e.g., ergot-alkaloids like dihydroergotamine and ergotamine or the serotonin-receptor agonists). Due to the pharmacology of feverfew (e.g., inhibits 5HT release from platelets, decreases prostaglandin synthesis) and the similar pharmacology of traditional migraine treatments, there seems to be a theoretical basis to avoid concurrent use.
[ Last revised: 6/26/2007 1:51:00 PM ]
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