Zomig

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Zomig

Classes

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

Administration
Oral Administration

Zolmitriptan is administered without regard to meals.

Oral Solid Formulations

Zomig oral tablets:
Tablets are scored and may be broken in half.
 
Zomig-ZMT oral disintegrating tablets:
Do not break the tablets because they are not functionally-scored.
Do not remove the tablets from packaging until immediately prior to use.
Open packaging with dry hands and place the orally disintegrating tablet on the tongue where it will dissolve and be swallowed with the saliva. The tablets do not need to be taken with fluids; however, they may be taken with fluids if desired.

Inhalation Administration Intranasal Inhalation Administration

Instruct patient on proper administration technique.
After administration of zolmitriptan, rinse the tip of the bottle with hot water, taking care not to suck water into the bottle, and dry with a clean tissue. Replace the cap right after cleaning.
To avoid the spread of infection, do not use the container for more than one person.

Adverse Reactions
Severe

splenic rupture / Delayed / 0-1.0
bowel ischemia / Delayed / 0-1.0
bowel necrosis / Delayed / 0-1.0
anaphylactoid reactions / Rapid / 0-1.0
angioedema / Rapid / 0-1.0
anaphylactic shock / Rapid / 0-1.0
bronchospasm / Rapid / 0.1-1.0
laryngeal edema / Rapid / 0.1-1.0
cyanosis / Early / 0.1-1.0
peptic ulcer / Delayed / 0-0.1
GI obstruction / Delayed / 0-0.1
pancreatitis / Delayed / 0-0.1
hematemesis / Delayed / 0-0.1
atrial fibrillation / Early / 0-0.1
myocardial infarction / Delayed / 0-0.1
bradycardia / Rapid / 0-0.1
tardive dyskinesia / Delayed / 0-0.1
seizures / Delayed / 0-0.1
erythema multiforme / Delayed / 0-0.1
apnea / Delayed / 0-0.1
GI bleeding / Delayed / Incidence not known
ventricular tachycardia / Early / Incidence not known
coronary vasospasm / Early / Incidence not known
ventricular fibrillation / Early / Incidence not known
intracranial bleeding / Delayed / Incidence not known
stroke / Early / Incidence not known
serotonin syndrome / Delayed / Incidence not known
visual impairment / Early / Incidence not known

Moderate

hyperesthesia / Delayed / 1.0-5.0
myasthenia / Delayed / 0-3.0
dysphagia / Delayed / 0-2.0
palpitations / Early / 0-2.0
glossitis / Early / 0.1-1.0
esophagitis / Delayed / 1.0-1.0
hypertension / Early / 0.1-1.0
chest pain (unspecified) / Early / 0.1-1.0
sinus tachycardia / Rapid / 0.1-1.0
depression / Delayed / 0.1-1.0
dysarthria / Delayed / 0.1-1.0
confusion / Early / 0.1-1.0
amnesia / Delayed / 0.1-1.0
ataxia / Delayed / 0.1-1.0
dyspnea / Early / 0.1-1.0
edema / Delayed / 0.1-1.0
amblyopia / Delayed / 0.1-1.0
hyperacusis / Delayed / 0.1-1.0
cystitis / Delayed / 0.1-1.0
hematuria / Delayed / 0.1-1.0
sialadenitis / Delayed / 0-0.1
gastritis / Delayed / 0-0.1
melena / Delayed / 0-0.1
jaundice / Delayed / 0-0.1
constipation / Delayed / 0-0.1
stomatitis / Delayed / 0-0.1
colitis / Delayed / 0-0.1
angina / Early / 0-0.1
QT prolongation / Rapid / 0-0.1
orthostatic hypotension / Delayed / 0-0.1
mania / Early / 0-0.1
hypotonia / Delayed / 0-0.1
euphoria / Early / 0-0.1
psychosis / Early / 0-0.1
hallucinations / Early / 0-0.1
dystonic reaction / Delayed / 0-0.1
akathisia / Delayed / 0-0.1
hypertonia / Delayed / 0-0.1
peripheral neuropathy / Delayed / 0-0.1
tetany / Early / 0-0.1
bone pain / Delayed / 0-0.1
osteoporosis / Delayed / 0-0.1
atopic dermatitis / Delayed / 0-0.1
erythema / Early / 0-0.1
thrombocytopenia / Delayed / 0-0.1
leukopenia / Delayed / 0-0.1
eosinophilia / Delayed / 0-0.1
lymphadenopathy / Delayed / 0-0.1
hyperglycemia / Delayed / 0-0.1
dehydration / Delayed / 0-0.1
peripheral edema / Delayed / 0-0.1
conjunctivitis / Delayed / 0-0.1
photophobia / Early / 0-0.1
vaginitis / Delayed / 0-0.1
hyperthyroidism / Delayed / 0-0.1
chest pressure syndrome / Rapid / Incidence not known
hyperthermia / Delayed / Incidence not known
peripheral vasoconstriction / Rapid / Incidence not known
medication overuse headache / Delayed / Incidence not known
withdrawal / Early / Incidence not known

Mild

dysgeusia / Early / 6.0-21.0
paresthesias / Delayed / 5.0-10.0
dizziness / Early / 0-10.0
nausea / Early / 1.0-9.0
asthenia / Delayed / 3.0-9.0
drowsiness / Early / 1.0-8.0
xerostomia / Early / 2.0-5.0
dyspepsia / Early / 1.0-3.0
hyperhidrosis / Delayed / 0-3.0
vertigo / Early / 0-2.0
myalgia / Early / 1.0-2.0
appetite stimulation / Delayed / 0.1-1.0
hypersalivation / Early / 0.1-1.0
diarrhea / Early / 0.1-1.0
syncope / Early / 0.1-1.0
agitation / Early / 0.1-1.0
tremor / Early / 0.1-1.0
emotional lability / Early / 0.1-1.0
anxiety / Delayed / 0.1-1.0
insomnia / Early / 0.1-1.0
back pain / Delayed / 0.1-1.0
muscle cramps / Delayed / 0.1-1.0
arthralgia / Delayed / 0.1-1.0
rash / Early / 0.1-1.0
urticaria / Rapid / 0.1-1.0
photosensitivity / Delayed / 0.1-1.0
pruritus / Rapid / 0.1-1.0
sinusitis / Delayed / 0.1-1.0
hiccups / Early / 0.1-1.0
yawning / Early / 0.1-1.0
epistaxis / Delayed / 0.1-1.0
rhinitis / Early / 0.1-1.0
pharyngitis / Delayed / 0.1-1.0
cough / Delayed / 0.1-1.0
laryngitis / Delayed / 0.1-1.0
influenza / Delayed / 0.1-1.0
ecchymosis / Delayed / 0.1-1.0
parosmia / Delayed / 0.1-1.0
xerophthalmia / Early / 0.1-1.0
otalgia / Early / 0.1-1.0
tinnitus / Delayed / 0.1-1.0
ocular pain / Early / 0.1-1.0
urinary urgency / Early / 0.1-1.0
menorrhagia / Delayed / 0.1-1.0
polyuria / Early / 0.1-1.0
increased urinary frequency / Early / 0.1-1.0
chills / Rapid / 0.1-1.0
infection / Delayed / 0.1-1.0
malaise / Early / 0.1-1.0
fever / Early / 0.1-1.0
gingivitis / Delayed / 0-0.1
eructation / Early / 0-0.1
anorexia / Delayed / 0-0.1
flushing / Rapid / 0-0.1
hyperkinesis / Delayed / 0-0.1
irritability / Delayed / 0-0.1
hyperventilation / Early / 0-0.1
weight gain / Delayed / 0-0.1
lacrimation / Early / 0-0.1
diplopia / Early / 0-0.1
dysmenorrhea / Delayed / 0-0.1
abdominal pain / Early / Incidence not known

Common Brand Names

Zomig, Zomig -ZMT, Zomig Nasal Spray

Dea Class

Rx

Description

Serotonin agonist for migraine treatment
Available in oral and nasal spray formulas
Similar to sumatriptan, but unlike sumatriptan, zolmitriptan can penetrate the CNS to act centrally within the trigeminovascular system

Dosage And Indications
For the acute treatment of migraine with or without aura. Oral dosage (tablets) Adults

1.25 or 2.5 mg PO as a single dose. May repeat dose once after at least 2 hours after the first dose if the headache has not resolved or returns after transient improvement. Max: 5 mg/dose and 10 mg/day. A single 5 mg dose added little benefit over the 2.5 mg dose in clinical trials, and adverse reactions occurred more frequently with the 5 mg dose. The safety of treating an average of more than 3 headaches in 30-day period has not been established. Guidelines classify zolmitriptan as having established efficacy for the acute treatment of migraine headache.

Oral dosage (orally disintegrating tablets) Adults

2.5 mg PO as a single dose. May repeat dose once after at least 2 hours after the first dose if the headache has not resolved or returns after transient improvement. Max: 5 mg/dose and 10 mg/day. A single 5 mg dose added little benefit over the 2.5 mg dose in clinical trials, and adverse reactions occurred more frequently with the 5 mg dose. The safety of treating an average of more than 3 headaches in 30-day period has not been established. Guidelines classify zolmitriptan as having established efficacy for the acute treatment of migraine headache.

Intranasal dosage Adults

2.5 mg intranasally as a single dose. May repeat dose once after at least 2 hours after the first dose if the headache has not resolved or returns after transient improvement. Max: 5 mg/dose and 10 mg/day. The safety of treating an average of more than 4 headaches in 30-day period has not been established. Guidelines classify zolmitriptan as having established efficacy for the acute treatment of migraine headache.

Children and Adolescents 12 to 17 years

2.5 mg intranasally as a single dose. May repeat dose once after at least 2 hours after the first dose if the headache has not resolved or returns after transient improvement. Max: 5 mg/dose and 10 mg/day. The safety of treating an average of more than 4 headaches in 30-day period has not been established.[49005] Guidelines recommend intranasal zolmitriptan for acute treatment of migraine in adolescents; those receiving zolmitriptan are more likely than those receiving placebo to be headache-free at 2 hours.

For menstrual migraine prophylaxis†. Oral dosage Adult females

2.5 mg PO 2 or 3 times daily for 7 days, with the regimen beginning 2 days prior to the expected onset of menses. Clinical practice guidelines classify zolmitriptan as probably effective for the prevention of menstrual migraine.

†Indicates off-label use

Dosing Considerations
Hepatic Impairment

In patients with severe hepatic impairment, the total daily dose of zolmitriptan should be limited to 5 mg/day PO. The recommended starting dose of zolmitriptan in patients with moderate to severe hepatic impairment is 1.25 mg PO (one-half of a 2.5 mg oral tablet). Initially, the use of zolmitriptan orally disintegrating tablets or zolmitriptan nasal spray is not recommended in patients with moderate or severe hepatic impairment because the recommended dosing cannot be achieved with these dosage forms. Monitor blood pressure in patients with hepatic impairment.

Renal Impairment

CrCl >= 26 ml/min: No dosage adjustments are needed.
CrCl <= 25 ml/min: Clearance is reduced by roughly 25%; it would be prudent to prescribe lower doses of both oral and intranasal zolmitriptan and monitor blood pressure. Intranasal dosage forms < 5 mg/dose are not available; the oral dosage form should be used if lower doses are needed.
 
Intermittent hemodialysis
See dosage for patients with renal impairment. It is not known whether hemodialysis (or peritoneal dialysis) removes zolmitriptan from plasma.

Drug Interactions

Acetaminophen: (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
Acetaminophen; Aspirin: (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
Acetaminophen; Aspirin; Diphenhydramine: (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
Acetaminophen; Caffeine: (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
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. (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
Acetaminophen; Caffeine; Pyrilamine: (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
Acetaminophen; Chlorpheniramine: (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
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. (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
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. (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
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. (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
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. (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
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. (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
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. (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
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. (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
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. (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
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. (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
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. (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
Acetaminophen; Dichloralphenazone; Isometheptene: (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
Acetaminophen; Diphenhydramine: (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
Acetaminophen; Guaifenesin; Phenylephrine: (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
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. (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
Acetaminophen; Ibuprofen: (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
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. (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
Acetaminophen; Pamabrom; Pyrilamine: (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
Acetaminophen; Phenylephrine: (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
Acetaminophen; Pseudoephedrine: (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
Alfentanil: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with zolmitriptan. 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.
Almotriptan: (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.
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.
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 zolmitriptan and a multi-day regimen of oral aprepitant are used concurrently and monitor for an increase in zolmitriptan-related adverse effects for several days after administration. Zolmitriptan 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 zolmitriptan. 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) Caution is warranted when atazanavir is administered with zolmitriptan as there is a potential for elevated zolmitriptan concentrations. Clinical monitoring for adverse effects is recommended during coadministration. Zolmitriptan is a substrate of CYP3A4; atazanavir is a CYP3A4 inhibitors.
Atazanavir; Cobicistat: (Moderate) Caution is warranted when atazanavir is administered with zolmitriptan as there is a potential for elevated zolmitriptan concentrations. Clinical monitoring for adverse effects is recommended during coadministration. Zolmitriptan is a substrate of CYP3A4; atazanavir is a CYP3A4 inhibitors. (Moderate) Caution is warranted when cobicistat is administered with zolmitriptan as there is a potential for elevated zolmitriptan concentrations. Clinical monitoring for adverse effects is recommended during coadministration. Zolmitriptan is a substrate of CYP3A4; cobicistat is a CYP3A4 inhibitor.
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. (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
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: (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
Butalbital; Acetaminophen; Caffeine: (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
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. (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
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.
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.
Cimetidine: (Moderate) If cimetidine and zolmitriptan are used concomitantly, limit the maximum single dose of zolmitriptan to 2.5 mg and do not exceed 5 mg in any 24-hour period. After the coadministration of cimetidine, the half-life and AUC of zolmitriptan (5 mg PO) and its active metabolite are roughly doubled.
Citalopram: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering zolmitriptan with selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists ("triptans") and SSRIs. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after initiation of SSRI treatment or any dose increases. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
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) Caution is warranted when cobicistat is administered with zolmitriptan as there is a potential for elevated zolmitriptan concentrations. Clinical monitoring for adverse effects is recommended during coadministration. Zolmitriptan is a substrate of CYP3A4; cobicistat is a CYP3A4 inhibitor.
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.
Darunavir: (Moderate) Caution is warranted when darunavir is administered with zolmitriptan as there is a potential for elevated zolmitriptan concentrations. Clinical monitoring for adverse effects is recommended during coadministration. Zolmitriptan is a substrate of CYP3A4; darunavir is a CYP3A4 inhibitor.
Darunavir; Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with zolmitriptan as there is a potential for elevated zolmitriptan concentrations. Clinical monitoring for adverse effects is recommended during coadministration. Zolmitriptan is a substrate of CYP3A4; cobicistat is a CYP3A4 inhibitor. (Moderate) Caution is warranted when darunavir is administered with zolmitriptan as there is a potential for elevated zolmitriptan concentrations. Clinical monitoring for adverse effects is recommended during coadministration. Zolmitriptan is a substrate of CYP3A4; darunavir is a CYP3A4 inhibitor.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Caution is warranted when cobicistat is administered with zolmitriptan as there is a potential for elevated zolmitriptan concentrations. Clinical monitoring for adverse effects is recommended during coadministration. Zolmitriptan is a substrate of CYP3A4; cobicistat is a CYP3A4 inhibitor. (Moderate) Caution is warranted when darunavir is administered with zolmitriptan as there is a potential for elevated zolmitriptan concentrations. Clinical monitoring for adverse effects is recommended during coadministration. Zolmitriptan is a substrate of CYP3A4; darunavir is a CYP3A4 inhibitor.
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.
Desogestrel; Ethinyl Estradiol: (Minor) Retrospective data indicate that mean plasma concentrations of zolmitriptan were generally higher in females taking oral contraceptives (e.g., those containing ethinyl estradiol) compared to those not taking oral contraceptives. Mean Cmax and AUC of zolmitriptan were found to be higher by 30% and 50%, respectively, and Tmax was delayed by one-half hour in females taking oral contraceptives. The effect of zolmitriptan on the pharmacokinetics of oral contraceptives has not been studied. The clinical significance of these interactions has not been established. Hormone replacement therapy regimens (HRT) are not thought to interact, based on data with other 'triptans' with similar pharmacokinetic interactions with oral contraceptives.
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.
Drospirenone; Ethinyl Estradiol: (Minor) Retrospective data indicate that mean plasma concentrations of zolmitriptan were generally higher in females taking oral contraceptives (e.g., those containing ethinyl estradiol) compared to those not taking oral contraceptives. Mean Cmax and AUC of zolmitriptan were found to be higher by 30% and 50%, respectively, and Tmax was delayed by one-half hour in females taking oral contraceptives. The effect of zolmitriptan on the pharmacokinetics of oral contraceptives has not been studied. The clinical significance of these interactions has not been established. Hormone replacement therapy regimens (HRT) are not thought to interact, based on data with other 'triptans' with similar pharmacokinetic interactions with oral contraceptives.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Retrospective data indicate that mean plasma concentrations of zolmitriptan were generally higher in females taking oral contraceptives (e.g., those containing ethinyl estradiol) compared to those not taking oral contraceptives. Mean Cmax and AUC of zolmitriptan were found to be higher by 30% and 50%, respectively, and Tmax was delayed by one-half hour in females taking oral contraceptives. The effect of zolmitriptan on the pharmacokinetics of oral contraceptives has not been studied. The clinical significance of these interactions has not been established. Hormone replacement therapy regimens (HRT) are not thought to interact, based on data with other 'triptans' with similar pharmacokinetic interactions with oral contraceptives.
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 zolmitriptan with elbasvir; grazoprevir may result in elevated zolmitriptan plasma concentrations. Zolmitriptan 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) Eletriptan 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.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution is warranted when cobicistat is administered with zolmitriptan as there is a potential for elevated zolmitriptan concentrations. Clinical monitoring for adverse effects is recommended during coadministration. Zolmitriptan is a substrate of CYP3A4; cobicistat is a CYP3A4 inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is warranted when cobicistat is administered with zolmitriptan as there is a potential for elevated zolmitriptan concentrations. Clinical monitoring for adverse effects is recommended during coadministration. Zolmitriptan is a substrate of CYP3A4; cobicistat is a CYP3A4 inhibitor.
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 zolmitriptan with selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists ("triptans") and SSRIs. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after initiation of SSRI treatment or any dose increases. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Ethinyl Estradiol; Norelgestromin: (Minor) Retrospective data indicate that mean plasma concentrations of zolmitriptan were generally higher in females taking oral contraceptives (e.g., those containing ethinyl estradiol) compared to those not taking oral contraceptives. Mean Cmax and AUC of zolmitriptan were found to be higher by 30% and 50%, respectively, and Tmax was delayed by one-half hour in females taking oral contraceptives. The effect of zolmitriptan on the pharmacokinetics of oral contraceptives has not been studied. The clinical significance of these interactions has not been established. Hormone replacement therapy regimens (HRT) are not thought to interact, based on data with other 'triptans' with similar pharmacokinetic interactions with oral contraceptives.
Ethinyl Estradiol; Norethindrone Acetate: (Minor) Retrospective data indicate that mean plasma concentrations of zolmitriptan were generally higher in females taking oral contraceptives (e.g., those containing ethinyl estradiol) compared to those not taking oral contraceptives. Mean Cmax and AUC of zolmitriptan were found to be higher by 30% and 50%, respectively, and Tmax was delayed by one-half hour in females taking oral contraceptives. The effect of zolmitriptan on the pharmacokinetics of oral contraceptives has not been studied. The clinical significance of these interactions has not been established. Hormone replacement therapy regimens (HRT) are not thought to interact, based on data with other 'triptans' with similar pharmacokinetic interactions with oral contraceptives.
Ethinyl Estradiol; Norgestrel: (Minor) Retrospective data indicate that mean plasma concentrations of zolmitriptan were generally higher in females taking oral contraceptives (e.g., those containing ethinyl estradiol) compared to those not taking oral contraceptives. Mean Cmax and AUC of zolmitriptan were found to be higher by 30% and 50%, respectively, and Tmax was delayed by one-half hour in females taking oral contraceptives. The effect of zolmitriptan on the pharmacokinetics of oral contraceptives has not been studied. The clinical significance of these interactions has not been established. Hormone replacement therapy regimens (HRT) are not thought to interact, based on data with other 'triptans' with similar pharmacokinetic interactions with oral contraceptives.
Ethynodiol Diacetate; Ethinyl Estradiol: (Minor) Retrospective data indicate that mean plasma concentrations of zolmitriptan were generally higher in females taking oral contraceptives (e.g., those containing ethinyl estradiol) compared to those not taking oral contraceptives. Mean Cmax and AUC of zolmitriptan were found to be higher by 30% and 50%, respectively, and Tmax was delayed by one-half hour in females taking oral contraceptives. The effect of zolmitriptan on the pharmacokinetics of oral contraceptives has not been studied. The clinical significance of these interactions has not been established. Hormone replacement therapy regimens (HRT) are not thought to interact, based on data with other 'triptans' with similar pharmacokinetic interactions with oral contraceptives.
Etonogestrel; Ethinyl Estradiol: (Minor) Retrospective data indicate that mean plasma concentrations of zolmitriptan were generally higher in females taking oral contraceptives (e.g., those containing ethinyl estradiol) compared to those not taking oral contraceptives. Mean Cmax and AUC of zolmitriptan were found to be higher by 30% and 50%, respectively, and Tmax was delayed by one-half hour in females taking oral contraceptives. The effect of zolmitriptan on the pharmacokinetics of oral contraceptives has not been studied. The clinical significance of these interactions has not been established. Hormone replacement therapy regimens (HRT) are not thought to interact, based on data with other 'triptans' with similar pharmacokinetic interactions with oral contraceptives.
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 zolmitriptan 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 zolmitriptan with selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists ("triptans") and SSRIs. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after initiation of SSRI treatment or any dose increases. Discontinue serotonergic agents 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 zolmitriptan with selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists ("triptans") and SSRIs. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after initiation of SSRI treatment or any dose increases. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Frovatriptan: (Contraindicated) Zolmitriptan 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.
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: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with zolmitriptan, a CYP3A substrate, as zolmitriptan toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
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.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with zolmitriptan may result in increased serum concentrations of zolmitriptan. Zolmitriptan 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: (Contraindicated) The administration of zolmitriptan to patients currently receiving a monoamine oxidase A inhibitor or within 2 weeks of discontinuing a monoamine oxidase A inhibitor is contraindicated. Zolmitriptan is metabolized by monoamine oxidase A (MAO-A); therefore, plasma concentrations of zolmitriptan may be increased by concurrent use of selective MAO-A inhibitors (e.g., meclobemide) or non-selective MAO-A and MAO-B inhibitors (e.g., phenelzine, tranylcypromine, isocarboxazid). Following one week of administration of the MAO-A inhibitor moclobemide (150 mg PO twice daily), there was an increase of about 25% in both Cmax and AUC for zolmitriptan and a 3-fold increase in the Cmax and AUC of the active N-desmethyl metabolite of zolmitriptan.
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.
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.
Levonorgestrel; Ethinyl Estradiol: (Minor) Retrospective data indicate that mean plasma concentrations of zolmitriptan were generally higher in females taking oral contraceptives (e.g., those containing ethinyl estradiol) compared to those not taking oral contraceptives. Mean Cmax and AUC of zolmitriptan were found to be higher by 30% and 50%, respectively, and Tmax was delayed by one-half hour in females taking oral contraceptives. The effect of zolmitriptan on the pharmacokinetics of oral contraceptives has not been studied. Th

e clinical significance of these interactions has not been established. Hormone replacement therapy regimens (HRT) are not thought to interact, based on data with other 'triptans' with similar pharmacokinetic interactions with oral contraceptives.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Minor) Retrospective data indicate that mean plasma concentrations of zolmitriptan were generally higher in females taking oral contraceptives (e.g., those containing ethinyl estradiol) compared to those not taking oral contraceptives. Mean Cmax and AUC of zolmitriptan were found to be higher by 30% and 50%, respectively, and Tmax was delayed by one-half hour in females taking oral contraceptives. The effect of zolmitriptan on the pharmacokinetics of oral contraceptives has not been studied. The clinical significance of these interactions has not been established. Hormone replacement therapy regimens (HRT) are not thought to interact, based on data with other 'triptans' with similar pharmacokinetic interactions with oral contraceptives.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Minor) Retrospective data indicate that mean plasma concentrations of zolmitriptan were generally higher in females taking oral contraceptives (e.g., those containing ethinyl estradiol) compared to those not taking oral contraceptives. Mean Cmax and AUC of zolmitriptan were found to be higher by 30% and 50%, respectively, and Tmax was delayed by one-half hour in females taking oral contraceptives. The effect of zolmitriptan on the pharmacokinetics of oral contraceptives has not been studied. The clinical significance of these interactions has not been established. Hormone replacement therapy regimens (HRT) are not thought to interact, based on data with other 'triptans' with similar pharmacokinetic interactions with oral contraceptives.
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.
Lopinavir; Ritonavir: (Moderate) Concurrent administration of zolmitriptan with ritonavir may result in elevated zolmitriptan plasma concentrations. Zolmitriptan is metabolized by the hepatic isoenzyme CYP3A4; ritonavir is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
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.
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 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.
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.
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: (Minor) Use caution if mitotane and zolmitriptan are used concomitantly, and monitor for decreased efficacy of zolmitriptan and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and zolmitriptan is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of zolmitriptan. Another strong CYP3A inducer, rifampin, results in small decreases in zolmitriptan peak plasma concentrations (decreased 15%) and AUC (decreased 18%), as well as decreased plasma concentrations of a metabolite of zolmitriptan. This interaction is not likely to be clinically significant.
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) Naratriptan 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.
Nefazodone: (Major) Medications that augment release, decrease the metabolism of, or decrease the reuptake of serotonin, like the serotonin-receptor agonists, may interact with nefazodone by causing serotonin-related side effects, including serotonin syndrome. Whenever possible, these drug combinations should be avoided. If serotonin-syndrome is suspected, offending agents should be discontinued.
Nirmatrelvir; Ritonavir: (Moderate) Concurrent administration of zolmitriptan with ritonavir may result in elevated zolmitriptan plasma concentrations. Zolmitriptan is metabolized by the hepatic isoenzyme CYP3A4; ritonavir is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Minor) Retrospective data indicate that mean plasma concentrations of zolmitriptan were generally higher in females taking oral contraceptives (e.g., those containing ethinyl estradiol) compared to those not taking oral contraceptives. Mean Cmax and AUC of zolmitriptan were found to be higher by 30% and 50%, respectively, and Tmax was delayed by one-half hour in females taking oral contraceptives. The effect of zolmitriptan on the pharmacokinetics of oral contraceptives has not been studied. The clinical significance of these interactions has not been established. Hormone replacement therapy regimens (HRT) are not thought to interact, based on data with other 'triptans' with similar pharmacokinetic interactions with oral contraceptives.
Norethindrone; Ethinyl Estradiol: (Minor) Retrospective data indicate that mean plasma concentrations of zolmitriptan were generally higher in females taking oral contraceptives (e.g., those containing ethinyl estradiol) compared to those not taking oral contraceptives. Mean Cmax and AUC of zolmitriptan were found to be higher by 30% and 50%, respectively, and Tmax was delayed by one-half hour in females taking oral contraceptives. The effect of zolmitriptan on the pharmacokinetics of oral contraceptives has not been studied. The clinical significance of these interactions has not been established. Hormone replacement therapy regimens (HRT) are not thought to interact, based on data with other 'triptans' with similar pharmacokinetic interactions with oral contraceptives.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Minor) Retrospective data indicate that mean plasma concentrations of zolmitriptan were generally higher in females taking oral contraceptives (e.g., those containing ethinyl estradiol) compared to those not taking oral contraceptives. Mean Cmax and AUC of zolmitriptan were found to be higher by 30% and 50%, respectively, and Tmax was delayed by one-half hour in females taking oral contraceptives. The effect of zolmitriptan on the pharmacokinetics of oral contraceptives has not been studied. The clinical significance of these interactions has not been established. Hormone replacement therapy regimens (HRT) are not thought to interact, based on data with other 'triptans' with similar pharmacokinetic interactions with oral contraceptives.
Norgestimate; Ethinyl Estradiol: (Minor) Retrospective data indicate that mean plasma concentrations of zolmitriptan were generally higher in females taking oral contraceptives (e.g., those containing ethinyl estradiol) compared to those not taking oral contraceptives. Mean Cmax and AUC of zolmitriptan were found to be higher by 30% and 50%, respectively, and Tmax was delayed by one-half hour in females taking oral contraceptives. The effect of zolmitriptan on the pharmacokinetics of oral contraceptives has not been studied. The clinical significance of these interactions has not been established. Hormone replacement therapy regimens (HRT) are not thought to interact, based on data with other 'triptans' with similar pharmacokinetic interactions with oral contraceptives.
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 zolmitriptan with selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists ("triptans") and SSRIs. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after initiation of SSRI treatment or any dose increases. Discontinue serotonergic agents 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.
Oritavancin: (Minor) Zolmitriptan is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of zolmitriptan may be reduced if these drugs are administered concurrently.
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 zolmitriptan with selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists ("triptans") and SSRIs. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after initiation of SSRI treatment or any dose increases. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Peginterferon Alfa-2b: (Moderate) Monitor for adverse effects associated with increased exposure to zolmitriptan if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 inhibitor, while zolmitriptan is partially metabolized by the CYP1A2 isoenzyme.
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: (Contraindicated) Zolmitriptan is contraindicated for use with a nonselective monoamine oxidase inhibitor (MAOI) (e.g., phenelzine) or within 2 weeks of discontinuing such an MAOI due to the increased risk for serotonin syndrome and increased zolmitriptan exposure. Zolmitriptan and its metabolite are metabolized by MAO-type A. Following 1 week of administration of a selective MAO-A inhibitor, there was an increase of about 25% in both Cmax and AUC for zolmitriptan and a 3-fold increase in the Cmax and AUC of the active N-desmethyl metabolite of zolmitriptan.
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.
Propranolol: (Minor) Periodically monitor blood pressure and for zolmitriptan-related side effects in patients who regularly use zolmitriptan and are taking propranolol. Rarely, a patient might experience an increase in dose-related common side effects of zolmitriptan, such as dizziness, nausea or drowsiness. No dosage adjustment of zolmitriptan appears to be needed. During pharmacokinetic studies, the Cmax and AUC of zolmitriptan increased 1.5-fold after 1 week of dosing with propranolol. Cmax and AUC of the active N-desmethyl metabolite of zolmitriptan were reduced by 30% and 15%, respectively. However, in clinical trials, the efficacy of zolmitriptan was not affected by the concurrent use of common migraine prophylactic drugs (e.g., propranolol). There were no interactive effects on blood pressure or pulse rate. The interaction should not be significant for most patients.
Propranolol; Hydrochlorothiazide, HCTZ: (Minor) Periodically monitor blood pressure and for zolmitriptan-related side effects in patients who regularly use zolmitriptan and are taking propranolol. Rarely, a patient might experience an increase in dose-related common side effects of zolmitriptan, such as dizziness, nausea or drowsiness. No dosage adjustment of zolmitriptan appears to be needed. During pharmacokinetic studies, the Cmax and AUC of zolmitriptan increased 1.5-fold after 1 week of dosing with propranolol. Cmax and AUC of the active N-desmethyl metabolite of zolmitriptan were reduced by 30% and 15%, respectively. However, in clinical trials, the efficacy of zolmitriptan was not affected by the concurrent use of common migraine prophylactic drugs (e.g., propranolol). There were no interactive effects on blood pressure or pulse rate. The interaction should not be significant for most patients.
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: (Minor) Serotonin syndrome has been reported during co-administration of serotonin-receptor agonists and monoamine oxidase inhibitors (MAOIs). Since rasagiline selectively inhibit MAO-B at recommended doses, no interaction with zolmitriptan would be expected with normal prescription use. However, there is a decline in MAO-B selectivity with increasing doses. Therefore, high dose treatment with rasagiline may increase central serotonin levels through MAO-A inhibition. However, whether or not 5-HT1B/1D agonists such as zolmitriptan can cause serious cases of serotonin syndrome when used with serotonergic drugs has been debated since serotonin syndrome is thought to result primarily from 5-HT2A activation. In vitro data indicate that zolmitriptan is partially metabolized by MAO-A. In one drug interaction study, selegiline 10 mg/day for 1 week had no effect on the pharmacokinetics of zolmitriptan or its metabolite. Theoretically, use of high dose rasagiline or selegiline could increase systemic exposure to zolmitriptan through MAO-A inhibition.
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.
Ritonavir: (Moderate) Concurrent administration of zolmitriptan with ritonavir may result in elevated zolmitriptan plasma concentrations. Zolmitriptan is metabolized by the hepatic isoenzyme CYP3A4; ritonavir is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
Rizatriptan: (Contraindicated) Rizatriptan 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.
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.
Segesterone Acetate; Ethinyl Estradiol: (Minor) Retrospective data indicate that mean plasma concentrations of zolmitriptan were generally higher in females taking oral contraceptives (e.g., those containing ethinyl estradiol) compared to those not taking oral contraceptives. Mean Cmax and AUC of zolmitriptan were found to be higher by 30% and 50%, respectively, and Tmax was delayed by one-half hour in females taking oral contraceptives. The effect of zolmitriptan on the pharmacokinetics of oral contraceptives has not been studied. The clinical significance of these interactions has not been established. Hormone replacement therapy regimens (HRT) are not thought to interact, based on data with other 'triptans' with similar pharmacokinetic interactions with oral contraceptives.
Selective serotonin reuptake inhibitors: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering zolmitriptan with selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists ("triptans") and SSRIs. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after initiation of SSRI treatment or any dose increases. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Selegiline: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant selegiline and zolmitriptan 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 zolmitriptan with selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists ("triptans") and SSRIs. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after initiation of SSRI treatment or any dose increases. Discontinue serotonergic agents 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.
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) Sumatriptan 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.
Sumatriptan; Naproxen: (Contraindicated) Sumatriptan 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.
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 zolmitriptan. 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.
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. (Minor) Zolmitriptan can delay the Tmax of acetaminophen by one hour. A single 1 g dose of acetaminophen does not alter the pharmacokinetics of zolmitriptan and its active metabolite. The interaction between zolmitriptan and acetaminophen is not likely to be clinically significant.
Tranylcypromine: (Contraindicated) Due to the risk of serotonin syndrome and significantly increased zolmitriptan exposure, use is contraindicated with tranylcypromine. Tranylcypromine should not be used within 4 to 5 half-lives of discontinuing treatment with zolmitriptan. Conversely, do not initiate zolmitriptan within 2 weeks of discontinuing tranylcypromine.
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.
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.
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.
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.

How Supplied

Zolmitriptan/Zomig Oral Tab: 2.5mg, 5mg
Zolmitriptan/Zomig -ZMT Oral Tab Orally Dis: 2.5mg, 5mg
Zolmitriptan/Zomig/Zomig Nasal Spray Nasal Spray Met: 1actuation, 2.5mg, 5mg

Maximum Dosage
Adults

5 mg per single dose or 10 mg per 24 hours PO or intranasally. The safety of treating an average of more than 3 headaches with the tablets or 4 headaches with the nasal spray in a 30-day period has not been established.

Geriatric

5 mg per single dose or 10 mg per 24 hours PO or intranasally. The safety of treating an average of more than 3 headaches with the tablets or 4 headaches with the nasal spray in a 30-day period has not been established.

Adolescents

5 mg per single dose or 10 mg per 24 hours intranasally. The safety of treating an average of more than 4 headaches in a 30-day period has not been established. Safety and efficacy of oral dosage forms have not been established.

Children

>= 12 years: 5 mg per single dose or 10 mg per 24 hours intranasally. The safety of treating an average of more than 4 headaches in a 30-day period has not been established. Safety and efficacy of oral dosage forms have not been established.
< 12 years: Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Mechanism Of Action

Zolmitriptan is an agonist at 5-hydroxytryptamine (5-HT) type 1B and 1D receptors. The drug appears to have both peripheral and central sites of action. 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.[27025] 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. Additionally, vascular 5-HT1B receptor agonism results in vasoconstriction of painfully dilated intracranial extracerebral vessels.[27025] Zolmitriptan has no pharmacologic activity at dopaminergic, muscarinic, or sympathetic receptors and does not possess intrinsic analgesic properties.

Pharmacokinetics

Zolmitriptan is administered orally and intranasally. During a moderate to severe migraine attack, mean AUC (0-4 h) and Cmax for zolmitriptan were decreased by 40% and 25%, respectively, and mean Tmax was delayed by one-half hour compared to the same patients during a migraine free period. Zolmitriptan is metabolized to an active N-desmethyl metabolite and two inactive metabolites, an indole acetic acid metabolite and a N-oxide metabolite. The active metabolite is about 2 to 6 times the potency of the parent compound and may contribute substantially to the overall effects of zolmitriptan. Plasma concentrations of the N-desmethyl metabolite are about two-thirds that of zolmitriptan. The Tmax for the N-desmethyl metabolite is approximately 2—3 hours. Plasma protein binding of zolmitriptan is 25% over the concentration range of 10—1000 ng/ml. Approximately one-sixth of the total plasma clearance is renal clearance. The renal clearance is greater than the glomerular filtration rate which suggests that renal tubular secretion plays a role. The mean elimination half-life of zolmitriptan and the active N-desmethyl metabolite is 3 hours.
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP1A2, CYP3A4
Zolmitriptan is metabolized by CYP1A2 and CYP3A4, and its active N-desmethyl metabolite is metabolized by monoamine oxidase A (MAO-A).

Oral Route

Following oral administration, the drug is well absorbed with peak plasma concentrations occurring in 2 hours. The mean absolute bioavailability is approximately 40% and food has no effect on the bioavailability of zolmitriptan. Zolmitriptan undergoes first-pass metabolism which is more extensive in men than in women.

Pregnancy And Lactation
Pregnancy

There are no adequate data on the developmental risk associated with zolmitriptan use during human pregnancy. Women with migraines may be at increased risk for preeclampsia during pregnancy. In reproductive toxicity animal studies, oral administration of zolmitriptan to pregnant animals resulted in embryolethality as well as fetal abnormalities (malformations and variations) at clinically relevant exposures. A dose-related increase in embryolethality was observed with AUC exposures of approximately 280, 1,100, and 5,000 times the human AUC at the maximum recommended human dose (MRHD) of 10 mg/day when oral zolmitriptan was given to pregnant rats during organogenesis. Increases in embryolethality and fetal abnormalities and variations were observed with AUC exposures of approximately 1, 11, and 42 times the human AUC at the MRHD when oral zolmitriptan was given to pregnant rabbits during organogenesis. Hydronephrosis occurred in the offspring of pregnant rats given oral zolmitriptan during gestation, parturition, and lactation with AUC exposures of approximately 70, 280, and 1,000 times the human AUC at the MRHD.[28445]

There are no data on the presence of zolmitriptan in human milk, the effects on the breast-fed infant, or the effects on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for zolmitriptan and any potential adverse effects on the breast-fed infant from zolmitriptan or the underlying maternal condition.[28445] Previous American Academy of Pediatrics recommendations considered sumatriptan as compatible with breast-feeding; sumatriptan may be an alternative to zolmitriptan for the treatment of migraines in breast-feeding mothers.[27500]