Axert

Selective Serotonin 1B/1D Receptor Agonists (Triptans)

Avoid or use with caution with other serotonergic drugs to prevent serotonin syndrome (see Drug Interactions).

Oral Administration Oral Solid Formulations

May be administered without regard to meals.

Severe

serotonin syndrome / Delayed / 0-1.0
laryngospasm / Rapid / 0.1-1.0
bowel ischemia / Delayed / Incidence not known
seizures / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
anaphylactic shock / Rapid / Incidence not known
coronary vasospasm / Early / Incidence not known
ventricular fibrillation / Early / Incidence not known
ventricular tachycardia / Early / Incidence not known
myocardial infarction / Delayed / Incidence not known
stroke / Early / Incidence not known
intracranial bleeding / Delayed / Incidence not known
visual impairment / Early / Incidence not known
corneal opacification / Delayed / Incidence not known

Moderate

dyspnea / Early / 0.1-1.0
sinus tachycardia / Rapid / 0.1-1.0
palpitations / Early / 0.1-1.0
chest pain (unspecified) / Early / 0.1-1.0
hyperglycemia / Delayed / 0.1-1.0
colitis / Delayed / 0-0.1
gastritis / Delayed / 0-0.1
euphoria / Early / 0-0.1
depression / Delayed / 0-0.1
hypertonia / Delayed / 0-0.1
nystagmus / Delayed / 0-0.1
hyperreflexia / Delayed / 0-0.1
erythema / Early / 0-0.1
myopathy / Delayed / 0-0.1
myasthenia / Delayed / 0-0.1
hypertension / Early / 0-0.1
hypercholesterolemia / Delayed / 0-0.1
conjunctivitis / Delayed / 0-0.1
scotomata / Delayed / 0-0.1
hyperacusis / Delayed / 0-0.1
glossitis / Early / Incidence not known
medication overuse headache / Delayed / Incidence not known
withdrawal / Early / Incidence not known
confusion / Early / Incidence not known
peripheral vasoconstriction / Rapid / Incidence not known
angina / Early / Incidence not known
chest pressure syndrome / Rapid / Incidence not known
blepharospasm / Early / Incidence not known
blurred vision / Early / Incidence not known

Mild

drowsiness / Early / 0-5.0
dizziness / Early / 3.0-4.0
nausea / Early / 1.0-3.0
vomiting / Early / 0-2.0
headache / Early / 1.0-2.0
polydipsia / Early / 0.1-1.0
diarrhea / Early / 0.1-1.0
xerostomia / Early / 1.0-1.0
abdominal pain / Early / 0.1-1.0
dyspepsia / Early / 0.1-1.0
restlessness / Early / 0.1-1.0
fatigue / Early / 0.1-1.0
anxiety / Delayed / 0.1-1.0
paresthesias / Delayed / 0-1.0
vertigo / Early / 0.1-1.0
asthenia / Delayed / 0.1-1.0
hypoesthesia / Delayed / 0.1-1.0
tremor / Early / 0.1-1.0
pruritus / Rapid / 0.1-1.0
diaphoresis / Early / 0.1-1.0
rash / Early / 0.1-1.0
sinusitis / Delayed / 0.1-1.0
rhinitis / Early / 0.1-1.0
pharyngitis / Delayed / 0.1-1.0
myalgia / Early / 0.1-1.0
back pain / Delayed / 0.1-1.0
flushing / Rapid / 0.1-1.0
dysmenorrhea / Delayed / 0.1-1.0
otalgia / Early / 0.1-1.0
tinnitus / Delayed / 0.1-1.0
chills / Rapid / 0.1-1.0
gastroesophageal reflux / Delayed / 0-0.1
hypersalivation / Early / 0-0.1
nightmares / Early / 0-0.1
insomnia / Early / 0-0.1
photosensitivity / Delayed / 0-0.1
epistaxis / Delayed / 0-0.1
laryngitis / Delayed / 0-0.1
sneezing / Early / 0-0.1
hyperventilation / Early / 0-0.1
arthralgia / Delayed / 0-0.1
syncope / Early / 0-0.1
ocular irritation / Rapid / 0-0.1
xerophthalmia / Early / 0-0.1
dysgeusia / Early / 0-0.1
ocular pain / Early / 0-0.1
diplopia / Early / 0-0.1
parosmia / Delayed / 0-0.1
fever / Early / 0-0.1
hyperhidrosis / Delayed / Incidence not known
mastalgia / Delayed / Incidence not known
malaise / Early / Incidence not known

Axert

Rx

Oral serotonin agonist for migraine; similar to sumatriptan, but with a higher patient acceptability rating regarding ADRs; FDA approved in adults and pediatrics 12—17 years of age.

For the acute treatment of migraine attacks in patients with a history of migraine with or without aura .
NOTE: Use almotriptan only when a clear diagnosis of migraine is established. If a patient does not respond to almotriptan for the first migraine attack, re-evaluate the diagnosis of migraine prior to subsequent use. Almotriptan is not indicated for migraine prophylaxis or for the treatment of hemiplegic or basilar migraines or cluster headaches.
For the acute treatment of migraine headache pain in pediatric patients with a history of migraine attacks with or without aura usually lasting 4 hours or more (when untreated). Oral dosage Children and Adolescents 12 to 17 years

6.25 or 12.5 mg PO once. May repeat dose after 2 hours if the headache returns. Max: 25 mg/day. The efficacy on migraine-associated symptoms (i.e., nausea, photophobia, and phonophobia) and the safety of treating more than 4 headaches in a 30-day period have not been established. Guidelines recommend almotriptan for acute treatment of migraine in adolescents; however, those receiving almotriptan are possibly no more likely that those receiving placebo to be headache-free at 2 hours.

For the acute treatment of migraine attacks in adults with a history of migraine with or without aura. Oral dosage Adults

6.25 or 12.5 mg PO once, with 12.5 mg tending to be a more effective dose. May repeat dose after 2 hours if the headache returns. Max: 25 mg/day. Controlled trials have not adequately established the effectiveness of a second dose if the initial dose is ineffective. Single doses more than 12.5 mg do not improve efficacy. The safety of treating more than 4 headaches in a 30-day period has not been established. Guidelines classify almotriptan as having established efficacy for the treatment of acute migraine.[64551]

Hepatic Impairment

The recommended initial dose is 6.25 mg PO; the maximum dosage is 12.5 mg/day.

Renal Impairment

CrCl > 30 ml/min: No dosage adjustment is needed.
CrCl 10—30 ml/min: Initial dose is 6.25 mg PO; maximum dosage is 12.5 mg/day.
 
Intermittent hemodialysis
See dosage for renal impairment. It is not known whether hemodialysis removes almotriptan from plasma.
 
Peritoneal dialysis
The effects of peritoneal dialysis on plasma concentrations of almotriptan are unknown.

Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dihydrocodeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Acetaminophen; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Acetaminophen; Dextromethorphan: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Acetaminophen; Hydrocodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Acetaminophen; Oxycodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering oxycodone with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Adagrasib: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with adagrasib is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and adagrasib should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased almotriptan exposure by approximately 60%.
Alfentanil: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with almotriptan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Amitriptyline: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant serotonin-receptor agonist and tricyclic antidepressant use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with clarithromycin is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and clarithromycin should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Amphetamine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant serotonin-receptor agonist and amphetamine; dextroamphetamine use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Amphetamine; Dextroamphetamine Salts: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant serotonin-receptor agonist and amphetamine; dextroamphetamine use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Amphetamine; Dextroamphetamine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant serotonin-receptor agonist and amphetamine; dextroamphetamine use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Aprepitant, Fosaprepitant: (Moderate) Use caution if almotriptan and aprepitant, fosaprepitant are used concurrently and monitor for an increase in almotriptan-related adverse effects for several days after administration of a multi-day aprepitant regimen. Almotriptan is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of almotriptan. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Aspirin, ASA; Oxycodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering oxycodone with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Atazanavir: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with atazanavir is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and atazanavir should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Atazanavir; Cobicistat: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with atazanavir is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and atazanavir should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%. (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with cobicistat is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and cobicistat should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4; cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Benzhydrocodone; Acetaminophen: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering benzhydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Theoretically, concurrent use of methylene blue and serotonin-receptor agonists may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and serotonin-receptor agonists increase central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
Benzphetamine: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and serotonin-receptor agonists. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Bromocriptine: (Major) There are limited clinical trial data supporting the safety of giving a serotonin-receptor agonist ("triptan") with bromocriptine, an ergot derivative. The concomitant use of these agents with bromocriptine should be avoided. There is concern that prolonged vasospastic reactions, hypertension, tachycardia, or other side effects may occur.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Buprenorphine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering buprenorphine with serotonergic-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Buprenorphine; Naloxone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering buprenorphine with serotonergic-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Buspirone: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant buspirone and serotonin-receptor agonist use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Cabergoline: (Major) When possible, avoid concomitant use of serotonin-receptor agonists (triptans) within 24 hours of cabergoline administration to minimize the risk for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. The risk for vasospastic adverse reactions may be less with cabergoline, a semisynthetic ergot alkaloid derivative, than with other ergot alkaloids as cabergoline is a relatively selective dopamine agonist. In select patients, the combination of cabergoline and "triptans" has been utilized in the management of some headache types, but more data are needed regarding safety and efficacy.
Capsaicin; Metaxalone: (Moderate) Concomitant use of serotonin-receptor agonists ("triptans") and metaxalone may increase the risk for serotonin syndrome. Monitor patients for serotonin syndrome if concomitant use is necessary.
Celecoxib; Tramadol: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tramadol with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Ceritinib: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with ceritinib is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and ceritinib should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Chloramphenicol: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with chloramphenicol is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and chloramphenicol should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Chlordiazepoxide; Amitriptyline: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant serotonin-receptor agonist and tricyclic antidepressant use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Chlorpheniramine; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Chlorpheniramine; Dextromethorphan: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dihydrocodeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Chlorpheniramine; Hydrocodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Citalopram: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering almotriptan with citalopram. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and selective serotonin reuptake inhibitors (SSRIs). Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase of the SSRI or the addition of other serotonergic medications to an existing SSRI regimen. Discontinue citalopram and almotriptan and initiate symptomatic treatment if serotonin syndrome occurs.
Clarithromycin: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with clarithromycin is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and clarithromycin should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Clomipramine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant serotonin-receptor agonist and tricyclic antidepressant use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Cobicistat: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with cobicistat is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and cobicistat should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4; cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Cocaine: (Moderate) Concomitant use of cocaine with other drugs that have CNS serotonergic properties, such as serotonin-receptor agonists, could potentiate serotonin neurotransmission, and result in serotonergic side effects or rarely, serotonin syndrome. The actions of cocaine are presumed to include inhibition of presynaptic reuptake of serotonin. In most medical use cases, cocaine would be administered topically, and this interaction would not be of concern, as serotonin-agonists for migraine are used mostly "as needed". Illicit use of cocaine is of potential concern for interactions.
Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Codeine; Guaifenesin: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Codeine; Phenylephrine; Promethazine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Codeine; Promethazine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Dalfopristin; Quinupristin: (Major) Dalfopristin; quinupristin may increase the systemic exposure of almotriptan. If coadministered, the recommended starting dose of almotriptan is 6.25 mg; do not exceed 12.5 mg within a 24-hour period. Avoid coadministration in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and quinupristin is a potent CYP3A4 inhibitor. In a drug interaction study, coadministration of almotriptan and ketoconazole, another potent CYP3A4 inhibitor, resulted in an approximately 60% increase in almotriptan exposure.
Darunavir: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with darunavir is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and darunavir should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Darunavir; Cobicistat: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with cobicistat is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and cobicistat should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4; cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%. (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with darunavir is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and darunavir should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with cobicistat is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and cobicistat should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4; cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%. (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with darunavir is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and darunavir should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Delavirdine: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with delavirdine is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and delavirdine should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and delavirdine is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Desipramine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant serotonin-receptor agonist and tricyclic antidepressant use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Desvenlafaxine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering desvenlafaxine with other drugs that have serotonergic properties such as serotonin-receptor agonists (e.g., almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and serotonin norepinephrine reuptake inhibitors. Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose increases. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Dextroamphetamine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant serotonin-receptor agonist and amphetamine; dextroamphetamine use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Dextromethorphan: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Dextromethorphan; Bupropion: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Dextromethorphan; Guaifenesin: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Dextromethorphan; Quinidine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Doxepin: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant serotonin-receptor agonist and tricyclic antidepressant use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Droxidopa: (Major) Coadministration of droxidopa with other agents that increase blood pressure, such as serotonin-receptor agonists, would be expected to increase the risk for supine hypertension. Monitor supine blood pressure. Reduce or discontinue droxidopa if supine hypertension persists. If supine hypertension is not well-managed, droxidopa may increase the risk of cardiovascular events.
Duloxetine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant duloxetine and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Elbasvir; Grazoprevir: (Moderate) Administering almotriptan with elbasvir; grazoprevir may result in elevated almotriptan plasma concentrations. Almotriptan is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Eletriptan: (Contraindicated) Almotriptan is contraindicated for use within 24 hours of treatment with eletriptan due to the risk for additive vasospastic reactions. Additive serotonergic effects, including serotonin syndrome, may also occur.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with cobicistat is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and cobicistat should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4; cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with cobicistat is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and cobicistat should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4; cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Ergot alkaloids: (Contraindicated) Serotonin-receptor agonists (triptans) are contraindicated for use within 24 hours of treatment with ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications to avoid the potential for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. Additionally, ergot alkaloids are serotonergic agents whose effects on serotonin may be additive to those of the serotonin-receptor agonists.
Escitalopram: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering almotriptan with escitalopram. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and selective serotonin reuptake inhibitors (SSRIs). Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase of the SSRI or the addition of other serotonergic medications to an existing SSRI regimen. Discontinue escitalopram and almotriptan and initiate symptomatic treatment if serotonin syndrome occurs.
Fenfluramine: (Moderate) Use fenfluramine and serotonin receptor agonists with caution due to an increased risk of serotonin syndrome. Monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Fentanyl: (Moderate) If concomitant use of fentanyl and almotriptan is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Fluoxetine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering almotriptan with fluoxetine. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and selective serotonin reuptake inhibitors (SSRIs). Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase of the SSRI or the addition of other serotonergic medications to an existing SSRI regimen. Discontinue fluoxetine and almotriptan and initiate symptomatic treatment if serotonin syndrome occurs.
Fluvoxamine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering almotriptan with fluvoxamine. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and selective serotonin reuptake inhibitors (SSRIs). Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase of the SSRI or the addition of other serotonergic medications to an existing SSRI regimen. Discontinue fluvoxamine and almotriptan and initiate symptomatic treatment if serotonin syndrome occurs.
Fosamprenavir: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with fosamprenavir is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and fosamprenavir should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and fosamprenavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Frovatriptan: (Contraindicated) Almotriptan is contraindicated for use within 24 hours of treatment with frovatriptan due to the risk for additive vasospastic reactions. Additive serotonergic effects, including serotonin syndrome, may also occur.
Grapefruit juice: (Major) Avoid grapefruit and grapefruit juice while taking almotriptan, as coadministration may increase the systemic exposure of almotriptan. If coadministered, the recommended starting dose of almotriptan is 6.25 mg; do not exceed 12.5 mg within a 24-hour period. Avoid coadministration in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and grapefruit is a potent CYP3A4 inhibitor. In a drug interaction study, coadministration of almotriptan and ketoconazole, another potent CYP3A4 inhibitor, resulted in an approximately 60% increase in almotriptan exposure.
Guaifenesin; Hydrocodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Homatropine; Hydrocodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Hydrocodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Hydrocodone; Ibuprofen: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Hydrocodone; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Hydromorphone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydromorphone with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Theoretically, concurrent use of methylene blue and serotonin-receptor agonists may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and serotonin-receptor agonists increase central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
Ibuprofen; Oxycodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering oxycodone with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Idelalisib: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with idelalisib is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and idelalisib should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Imipramine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant serotonin-receptor agonist and tricyclic antidepressant use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Indinavir: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with indinavir is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and indinavir should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and indinavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with almotriptan may result in increased serum concentrations of almotriptan. Almotriptan is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Isocarboxazid: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering almotriptan with isocarboxazid. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and monoamine oxidase inhibitors (MAOIs). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue almotriptan and isocarboxazid and initiate symptomatic treatment if serotonin syndrome occurs.
Itraconazole: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with itraconazole is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and itraconazole should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and itraconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Ketoconazole: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with ketoconazole is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and ketoconazole should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor. Coadministration with ketoconazole increased almotriptan exposure by approximately 60%.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with clarithromycin is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and clarithromycin should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Lasmiditan: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Letermovir: (Moderate) No dosage adjustment is required in patients receiving letermovir with almotriptan who are not also receiving cyclosporine. The recommended starting dose of almotriptan is 6.25 mg (not to exceed 12.5 mg within a 24-hour period) in patients receiving letermovir with cyclosporine. Avoid almotriptan in combination with letermovir and cyclosporine in patients with renal or hepatic impairment. When cyclosporine is added to letermovir the magnitude of drug interactions may be increased. Almotriptan is a substrate of CYP3A4. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. Concurrent use with another moderate CYP3A4 inhibitor increased the maximum plasma concentration and exposure of almotriptan by 24% and 20%, respectively. Neither of these changes was considered clinically significant and did not require dose adjustment. However, concurrent administration with a strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Levoketoconazole: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with ketoconazole is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and ketoconazole should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor. Coadministration with ketoconazole increased almotriptan exposure by approximately 60%.
Levomilnacipran: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering levomilnacipran with other drugs that have serotonergic properties such as serotonin-receptor agonists (e.g., almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and serotonin norepinephrine reuptake inhibitors. Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose increases. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Levorphanol: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering levorphanol with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Linezolid: (Major) Linezolid is an antibiotic that is also a reversible, non-selective inhibitor of MAO and should not be administered with serotonin-receptor agonists. The monoamine oxidase type A enzyme metabolizes serotonin. Non-selective MAO inhibitors increase the plasma concentrations of these drugs and some of their active metabolites, thus increasing levels of serotonin. This interaction could lead to serotonin syndrome. The manufacturers of serotonin agonists contraindicate the administration of their drugs to patients receiving non-selective MAO inhibitors like linezolid or within 2 weeks of discontinuation of a MAO inhibitor.
Lisdexamfetamine: (Major) Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation or dosage increase, during concomitant lisdexamfetamine and serotonin-receptor agonist use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk of serotonin syndrome.
Lithium: (Major) If concurrent use is necessary, monitor for the emergence of serotonin syndrome and inform patients of the increased risk. If serotonin syndrome is suspected, serotonergic agents should be discontinued and appropriate medical treatment should be implemented. There is an increased risk of serotonin syndrome during concurrent use of drugs with central serotonergic properties such as lithium and serotonin-receptor agonists. Signs and symptoms of serotonin syndrome include autonomic instability (e.g., labile blood pressure, tachycardia, diaphoresis, dizziness, hyperthermia), mental status changes (e.g., delirium, confusion, coma), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), gastrointestinal effects (e.g., nausea, vomiting, diarrhea), seizures, and in rare cases, death.
Lonafarnib: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with lonafarnib is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and lonafarnib should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and lonafarnib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Lopinavir; Ritonavir: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with ritonavir is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and ritonavir should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Lorcaserin: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, serotonin-receptor agonists. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.
Lumacaftor; Ivacaftor: (Minor) Lumacaftor; ivacaftor may reduce the efficacy of almotriptan by decreasing its systemic exposure. If used together, monitor the patient for appropriate clinical effects. Almotriptan is partially metabolized by CYP3A4. Lumacaftor is a strong CYP3A inducer.
Meperidine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering meperidine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Metaxalone: (Moderate) Concomitant use of serotonin-receptor agonists ("triptans") and metaxalone may increase the risk for serotonin syndrome. Monitor patients for serotonin syndrome if concomitant use is necessary.
Methadone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering methadone with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Methamphetamine: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as methamphetamine and serotonin-receptor agonists. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Theoretically, concurrent use of methylene blue and serotonin-receptor agonists may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and serotonin-receptor agonists increase central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions o

f methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
Methylene Blue: (Major) Theoretically, concurrent use of methylene blue and serotonin-receptor agonists may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and serotonin-receptor agonists increase central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
Mifepristone: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with chronic mifepristone therapy is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and mifepristone should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Milnacipran: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering milnacipran with other drugs that have serotonergic properties such as serotonin-receptor agonists (e.g., almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and serotonin norepinephrine reuptake inhibitors. Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose increases. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Mirtazapine: (Major) The coadministration of serotonergic antidepressants with serotonin-agonists has sometimes resulted in serotonin syndrome. Careful observation of the patient is advised, particularly during treatment initiation and dose increases. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, and hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, and diarrhea). Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome, which includes hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs, and mental status changes. Discontinue the serotonergic agents immediately if serotonin syndrome reactions occur and initiate supportive symptomatic treatment.
Mitotane: (Moderate) Use caution if mitotane and almotriptan are used concomitantly, and monitor for decreased efficacy of almotriptan and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and almotriptan is a CYP3A4 substrate (approximately 12%); coadministration may result in decreased plasma concentrations of almotriptan.
Morphine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering morphine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Morphine; Naltrexone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering morphine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Nalbuphine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering nalbuphine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Naratriptan: (Contraindicated) Almotriptan is contraindicated for use within 24 hours of treatment with naratriptan due to the risk for additive vasospastic reactions. Additive serotonergic effects, including serotonin syndrome, may also occur.
Nefazodone: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with nefazodone is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and nefazodone should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and nefazodone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Nelfinavir: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with nelfinavir is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and nelfinavir should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and nelfinavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Nirmatrelvir; Ritonavir: (Major) Consider withholding almotriptan, if clinically appropriate, during receipt of ritonavir-boosted nirmatrelvir. If this is not feasible, consider using an alternative COVID-19 therapy or reducing the almotriptan dose. If coadministered, the recommended starting dose of almotriptan is 6.25 mg; do not exceed 12.5 mg within a 24-hour period. Avoid coadministration in patients with renal or hepatic impairment. Coadministration may increase almotriptan exposure resulting in increased toxicity. Almotriptan is a CYP3A substrate and nirmatrelvir is a CYP3A inhibitor. (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with ritonavir is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and ritonavir should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Nortriptyline: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant serotonin-receptor agonist and tricyclic antidepressant use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Olanzapine; Fluoxetine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering almotriptan with fluoxetine. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and selective serotonin reuptake inhibitors (SSRIs). Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase of the SSRI or the addition of other serotonergic medications to an existing SSRI regimen. Discontinue fluoxetine and almotriptan and initiate symptomatic treatment if serotonin syndrome occurs.
Oliceridine: (Moderate) If concomitant use of oliceridine and serotonin-receptor agonists is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Oxycodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering oxycodone with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Oxymorphone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering oxymorphone with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Ozanimod: (Major) Coadministration of ozanimod with serotonin receptor agonists "triptans" is not recommended due to the potential for hypertensive crisis or serotonin syndrome. If coadministration is necessary, closely monitor patients for hypertension and serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis or serotonin syndrome. Serotonin receptor agonists may increase blood pressure by increasing serotonin concentrations.
Paroxetine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering almotriptan with paroxetine. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and selective serotonin reuptake inhibitors (SSRIs). Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase of the SSRI or the addition of other serotonergic medications to an existing SSRI regimen. Discontinue paroxetine and almotriptan and initiate symptomatic treatment if serotonin syndrome occurs.
Pazopanib: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and almotriptan, a CYP3A4 substrate, may cause an increase in systemic concentrations of almotriptan. Use caution when administering these drugs concomitantly.
Perphenazine; Amitriptyline: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant serotonin-receptor agonist and tricyclic antidepressant use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Phenelzine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering almotriptan with phenelzine. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and monoamine oxidase inhibitors (MAOIs). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue almotriptan and phenelzine and initiate symptomatic treatment if serotonin syndrome occurs.
Posaconazole: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with posaconazole is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and posaconazole should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Promethazine; Dextromethorphan: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Protriptyline: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant serotonin-receptor agonist and tricyclic antidepressant use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Rasagiline: (Moderate) Use together with caution. Serotonin syndrome has been reported during administration of serotonin-receptor agonists ("triptans") and non-selective monoamine oxidase inhibitors (MAOIs). Since rasagiline selectively inhibits MAO-B at recommended doses, no interaction with almotriptan would be expected with normal prescription use. However, there is a decline in MAO-B selectivity with increasing rasagiline doses. Monitor for potential serotonin-related side effects. If serotonin syndrome occurs, discontinue all serotonergic agents and institute appropriate treatment.
Remifentanil: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering remifentanil with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Ribociclib: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with ribociclib is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and ribociclib should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Ribociclib; Letrozole: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with ribociclib is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and ribociclib should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Ritonavir: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with ritonavir is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and ritonavir should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Rizatriptan: (Contraindicated) Almotriptan is contraindicated for use within 24 hours of treatment with rizatriptan due to the risk for additive vasospastic reactions. Additive serotonergic effects, including serotonin syndrome, may also occur.
Safinamide: (Moderate) Safinamide and serotonin-receptor agonists, also known as triptans, should be used together with caution. Serotonin syndrome has been reported during administration of serotonin-receptor agonists and non-selective monoamine oxidase inhibitors (MAOIs). Since safinamide selectively inhibits MAO-B at recommended doses, no interaction with serotonin-receptor agonists would be expected with normal prescription use. However, monitoring for serotonin-related side effects is advisable since the potential for serotonin syndrome exists. If serotonin syndrome occurs, discontinue all serotonergic agents and institute appropriate treatment.
Saquinavir: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with saquinavir is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and saquinavir should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and saquinavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Selegiline: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant almotriptan and selegiline use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Sertraline: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering almotriptan with sertraline. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and selective serotonin reuptake inhibitors (SSRIs). Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase of the SSRI or the addition of other serotonergic medications to an existing SSRI regimen. Discontinue sertraline and almotriptan and initiate symptomatic treatment if serotonin syndrome occurs.
St. John's Wort, Hypericum perforatum: (Moderate) Although unlikely to occur during monotherapy with serotonin-receptor agonists ("triptans"), coadministration with serotonergic agents like St. John's Wort may increase the risk for serotonin syndrome. Inform the patient of the increased risk and monitor for the emergence of serotonin syndrome.
Streptogramins: (Major) Dalfopristin; quinupristin may increase the systemic exposure of almotriptan. If coadministered, the recommended starting dose of almotriptan is 6.25 mg; do not exceed 12.5 mg within a 24-hour period. Avoid coadministration in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and quinupristin is a potent CYP3A4 inhibitor. In a drug interaction study, coadministration of almotriptan and ketoconazole, another potent CYP3A4 inhibitor, resulted in an approximately 60% increase in almotriptan exposure.
Sufentanil: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Sumatriptan: (Contraindicated) Almotriptan is contraindicated for use within 24 hours of treatment with sumatriptan due to the risk for additive vasospastic reactions. Additive serotonergic effects, including serotonin syndrome, may also occur.
Sumatriptan; Naproxen: (Contraindicated) Almotriptan is contraindicated for use within 24 hours of treatment with sumatriptan due to the risk for additive vasospastic reactions. Additive serotonergic effects, including serotonin syndrome, may also occur.
Tapentadol: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tapentadol with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Tedizolid: (Minor) Caution is warranted with the concurrent use of tedizolid and serotonin-receptor agonists such as almotriptan. Tedizolid is an antibiotic that is also a weak reversible, non-selective inhibitor of MAO. The monoamine oxidase (MAO) type A enzyme metabolizes serotonin. Non-selective traditional MAO inhibitors increase the plasma concentrations of these drugs and some of their active metabolites, thus increasing levels of serotonin. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid, which is structurally similar to tedizolid, and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity. This interaction could lead to 'serotonin syndrome' (presenting as agitation, restlessness, aggressive behavior, insomnia, poor concentration, headache, paresthesia, incoordination, worsening of obsessive thoughts or compulsive behavior, nausea, abdominal cramps, diarrhea, palpitations, or chills). The manufacturers of serotonin agonists contraindicate the administration of their drugs to patients receiving non-selective MAO inhibitors or within 2 weeks of discontinuation of a MAO inhibitor.
Tipranavir: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with tipranavir is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and tipranavir should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and tipranavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Tramadol: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tramadol with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Tramadol; Acetaminophen: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tramadol with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Trandolapril; Verapamil: (Minor) Verapamil, a moderate CYP3A4 inhibitor, increases AUC and peak plasma concentrations of almotriptan by 20% and 24%, respectively; however, per the manufacturer, the changes are not clinically significant and no dosage adjustment of almotriptan is needed. Some patients might rarely have an increase in common side effects of almotriptan, such as dizziness, nausea or drowsiness.
Tranylcypromine: (Contraindicated) Due to the risk of serotonin syndrome, tranylcypromine is contraindicated for use with almotriptan. Tranylcypromine should not be used within 4 to 5 half-lives of discontinuing treatment with almotriptan.
Trazodone: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant trazodone and serotonin-receptor agonist use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Tricyclic antidepressants: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant serotonin-receptor agonist and tricyclic antidepressant use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Trimipramine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant serotonin-receptor agonist and tricyclic antidepressant use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Tryptophan, 5-Hydroxytryptophan: (Contraindicated) Combining medications that potentiate serotonin neurotransmission, such as serotonin-receptor agonists and tryptophan, 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.
Tucatinib: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with tucatinib is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and tucatinib should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Venlafaxine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant venlafaxine and serotonin-receptor agonist use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Verapamil: (Minor) Verapamil, a moderate CYP3A4 inhibitor, increases AUC and peak plasma concentrations of almotriptan by 20% and 24%, respectively; however, per the manufacturer, the changes are not clinically significant and no dosage adjustment of almotriptan is needed. Some patients might rarely have an increase in common side effects of almotriptan, such as dizziness, nausea or drowsiness.
Vilazodone: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering vilazodone with other drugs that have serotonergic properties such as serotonin-receptor agonists (e.g., almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan). Serotonin syndrome has been reported during concurrent use of serotonin norepinephrine reuptake inhibitors (SNRIs) or selective serotonin reuptake inhibitors (SSRIs) with serotonin-receptor agonists. 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. Patients receiving vilazodone and a serotonin-receptor agonist should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. Vilazodone and the serotonin-receptor agonist should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated.
Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with clarithromycin is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and clarithromycin should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Voriconazole: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with voriconazole is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and voriconazole should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and voriconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Vortioxetine: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering vortioxetine with other drugs that have serotonergic properties such as serotonin-receptor agonists (e.g., almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan). Serotonin syndrome has been reported during concurrent use of serotonergic antidepressants with the serotonin-receptor agonists. Some patients had used the combination previously without incident when serotonin syndrome occurred. Some cases have involved hospitalization. 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. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Careful monitoring for serotonin syndrome is recommended if combination therapy with is required. Risk factors can include a recent dose increase of the sertonergic antidepressant or the addition of other serotonergic medications to an existing antidepressant regimen.
Zolmitriptan: (Contraindicated) Almotriptan is contraindicated for use within 24 hours of treatment with zolmitriptan due to the risk for additive vasospastic reactions. Additive serotonergic effects, including serotonin syndrome, may also occur.

Almotriptan/Almotriptan Malate/Axert Oral Tab: 6.25mg, 12.5mg

Adults

25 mg/day PO.

Elderly

25 mg/day PO.

Adolescents

25 mg/day PO.

Children

>= 12 years: 25 mg/day PO.
< 12 years: Safety and efficacy have not been established.

Mechanism of Action: Almotriptan acts therapeutically as an agonist at central serotonin 5-HT1 type B and D receptors. Almotriptan binds with high affinity to 5-HT1D, 5-HT1B, and 5-HT1F receptors. The pathophysiology of migraine is not completely understood, and therefore the action of the serotonin-agonists (i.e., 'triptans' ) in treating migraine is not completely certain. Multiple pharmacological actions have been derived that appear important for antimigraine effects.. 'Triptans' stimulate presynaptic 5-HT1D receptors, an action that inhibits both dural vasodilation and inflammation. They directly inhibit trigeminal nuclei cell nociceptive neurotransmission via 5-HT1B/D receptor agonism within the trigeminocervical complex of the brainstem and upper spinal cord. In addition, vascular 5-HT1B receptor agonism results in vasoconstriction of painfully dilated intracranial extracerebral vessels.. Like other 5-HT1B/D receptor agonists, almotriptan has a high affinity for 5-HT1F; however, the pharmacological effects of this serotonin receptor subtype have not been determined.

Almotriptan is administered orally. Almotriptan is minimally protein bound (about 35%) with a mean Vd of approximately 180 to 200 L. One minor and two major pathways contribute to the metabolism of almotriptan. Monoamine oxidase (MAO)-mediated oxidative deamination (about 27% of the dose) and cytochrome P450-mediated oxidation (about 12% of the dose) are the major routes of metabolism, while flavin monooxygenase is the minor route. MAO-A is responsible for the formation of the indoleacetic acid metabolite, whereas cytochrome P450 (CYP3A4 and CYP2D6) catalyzes the hydroxylation of the pyrrolidine ring to an intermediate that is further oxidized by aldehyde dehydrogenase to the gamma-amino-butyric acid derivative; both metabolites are inactive. Renal clearance exceeds the glomerular filtration rate by 3-fold, indicating an active process. The mean elimination half-life of almotriptan is 3 to 4 hours. Almotriptan is primarily eliminated by the kidney (about 75%), with approximately 40% of the dose excreted unchanged in the urine. Approximately 13% of the administered dose is excreted in the feces.
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4 and CYP2D6
Cytochrome P450-mediated oxidation (about 12% of the dose) is one of the major routes of almotriptan metabolism. CYP3A4 and CYP2D6 catalyze the hydroxylation of the pyrrolidine ring to an intermediate that is further oxidized by aldehyde dehydrogenase to the gamma-amino-butyric acid derivative. Concomitant use of almotriptan and potent CYP3A4 inhibitors is expected to increase almotriptan exposure.

Oral Route

Almotriptan is well absorbed and has a bioavailability of 70%. Peak plasma levels of almotriptan occur 1 to 3 hours after oral administration; food does not affect its pharmacokinetics.

Pregnancy

Almotriptan is classified as FDA pregnancy risk category C. There have been no adequate and well controlled studies in pregnant women; therefore, almotriptan should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known if almotriptan crosses the placenta, but the low molecular weight and minimal protein binding of the drug suggest that placental transfer in humans is likely. In animal studies, almotriptan produced developmental toxicity (increased embryolethality, fetal skeletal variations (decreased ossification), and decreased offspring body weight) at doses greater than those used clinically. During administration to rats throughout gestation and lactation, gestation length was increased and litter size and offspring body weight were decreased at the highest dose. The decrease in pup weight persisted throughout lactation. Patients should be instructed to notify their physician if they become pregnant or intend to become pregnant during treatment with almotriptan. The effects of almotriptan during labor and delivery are unknown.

Use caution when administering almotriptan to a breast-feeding woman. Almotriptan is excreted into the breast milk of lactating rats, however, it is not known if almotriptan is distributed into human breast milk. In rats, concentrations of almotriptan were up to 7 times higher in breast milk compared to plasma. During administration of almotriptan to rats throughout gestation and lactation, pup weight was decreased at the highest dose, and the decrease in weight persisted throughout lactation. Low molecular weight and low protein binding suggest the drug will be excreted into human breast milk. Pumping or expressing breast milk and discarding it after a dose would help to avoid maximum infant exposure to almotriptan. Additionally, almotriptan is typically given as a 1 or 2 time dose, which may lessen infant risk. Sumatriptan is classified as compatible with breast-feeding by the American Academy of Pediatrics and may be considered as an alternative to almotriptan for the acute treatment of migraines in breast-feeding mothers.