Sumatriptan is a serotonin-receptor 1B and 1D agonist (triptan) indicated for the acute treatment of migraine with or without aura. Some formulations of subcutaneous sumatriptan are also indicated for the treatment of cluster headaches. Sumatriptan is not indicated for long-term migraine prophylaxis or for the management of hemiplegic or basilar migraine. Serious cardiac adverse effects may occur during sumatriptan administration and are more likely to occur in patients with risk factors for coronary artery disease, although some events have occurred in patients without known cardiac risk factors.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
-Sumatriptan injection is intended to be given subcutaneously, and intramuscular or intravascular delivery must be avoided.
-For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administering the first dose of sumatriptan injection in a medically supervised setting and performing an electrocardiogram (ECG) immediately after administration.
Subcutaneous Administration
Sumatriptan vials:
-Use injection sites with an adequate skin and subcutaneous thickness to accommodate the length of the needle.
-In patients receiving doses other than 4 or 6 mg, use the 6 mg single-dose vial.
Imitrex STATdose pen:
-Use injection sites with an adequate skin and subcutaneous thickness to accommodate the length of the needle. Change the injection site with each dose.
-Ensure the white priming rod is not sticking out beyond the end of the pen prior to loading syringe cartridge. If it is sticking out, put the pen back into the carrying case and press down firmly until it clicks.
-Load the pen by placing it within an open cartridge pack within the carrying case. Turn the pen clockwise until it will not turn anymore.
-Hold the loaded pen by the ridges and pull it straight out of the carrying case.
-To release the safety catch, press the loaded pen firmly against the skin so that the grey part of the barrel slides against the blue part until it cannot be pressed any further. The grey part of the barrel must stay in contact with the blue part during the injection.
-With the pen still pressed firmly against the skin, press the blue button to inject the dose subcutaneously. Hold the pen against the skin for a minimum of 5 seconds to ensure delivery of a complete dose.
Sumavel DosePro needle-free system:
-Use injection sites on the abdomen or thigh with an adequate skin and subcutaneous thickness. Change the injection site with each dose.
-Ensure the snap-off tip sits firmly on the end of the clear medication chamber; if the snap-off tip is tilted or broken, do not use the product.
-Remove the snap-off tip using a firm downward motion; do not twist or pull the snap-off tip. Prepare the dose by pressing the lavender or green lever down until it clicks and locks into the handle. Do not touch the end of the medication chamber; keep chamber pointed away from face and eyes.
-Pinch 2 inches of skin on the thigh or abdomen. Place medication chamber against skin and press device straight down until an audible click occurs to inject the dose subcutaneously. Do not hold Sumavel DosePro at an angle to the skin. Do not deliver into scars or moles, within 2 inches of the navel, or in the arm.
-Sumavel DosePro is provided as a single-use system; discard after use.
Zymbrace SymTouch autoinjector:
-Use injection sites with adequate skin and subcutaneous thickness to accommodate the length of the needle. Recommended injection sites are the lateral portion of the thigh or deltoid area.
-Hold the autoinjector in one hand, and pull the red cap straight off.
-Place the autoinjector at a 90-degree angle at the skin injection site with the yellow needle guard gently pressed against the skin.
-Press and hold the autoinjector down against the skin. Continue to hold the device down until 2 audible clicks occur. After the second click, wait 5 seconds before removing the autoinjector to ensure the full dose is delivered.
-Confirm that the red plunger rod has filled the medicine viewing window. This indicates a full dose has been delivered.
-The autoinjector is a prefilled, ready-to-use, single-dose device; discard after use.
Inhalation Administration
Intranasal Inhalation Administration
Imitrex nasal spray solution and generic equivalents:
-Instruct patient on proper administration technique.
-After administration, 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 1 person.
Tosymra nasal spray solution:
-Each spray delivers 10 mg of sumatriptan.
-Administer as single spray in 1 nostril.
-While sitting upright, gently blow nose to clear nostrils.
-Gently press 1 nostril with a finger to keep closed.
-Hold device upright and between thumb and first 2 fingers.
-Insert half of the spray nozzle into the open nostril and angle outward.
-While keeping the device in nose, tilt head back slightly.
-While slowly breathing through nose, firmly press plunger all the way up.
-Remove device from nostril, and gently breathe through nose and out through mouth for 10 to 20 seconds.
-Immediately discard the single-dose unit following administration.
-Separate doses by at least 1 hour. May also administer at least 1 hour after a dose of another sumatriptan product.
Onzetra Xsail nasal powder:
-Each nosepiece contains 1 dose of 11 mg of sumatriptan.
-Remove the clear device cap from the reusable delivery device.
-Remove a nosepiece from the foil pouch, and click the nosepiece into the device body.
-Fully press and then release the white piercing button on the device to pierce the capsule in the nosepiece. Only press the button once.
-Insert the nosepiece into the nostril and create a tight seal.
-Rotate the device to place the mouthpiece into the mouth. Blow forcefully into the mouthpiece to deliver the nasal powder into the nostril. Vibration may occur, which indicates that the patient is blowing forcefully as directed.
-Once the medication has been delivered, discard the nosepiece.
-Repeat the process to administer the drug into the other nostril.
Sumatriptan can cause serious cardiovascular and cerebrovascular events, including fatalities, due to vasospasm. These events seem to be rare and occur more commonly in patients with risk factors for coronary artery disease or patients who have received ergotamine within the previous 24 hours, although some events have occurred in patients with no known cardiac risk factors. Life-threatening arrhythmia exacerbation, including ventricular tachycardia and ventricular fibrillation leading to death, have been reported within a few hours following the administration of 5-HT1 agonists. Discontinue sumatriptan if these disturbances occur. Other serious cardiac events reported following sumatriptan include coronary vasospasm, abdominal aortic aneurysm (< 0.1%), angina (< 0.1%), transient myocardial ischemia (< 0.1%), myocardial infarction, and cardiac arrest. A myocardial infarction was reported in a 14 year old adolescent male following the use of oral sumatriptan; clinical signs occurred within 1 day of drug administration although causality cannot be definitively made. During pre-marketing evaluation of sumatriptan nasal spray, 1 patient experienced an asymptomatic subendocardial infarction possibly subsequent to a coronary vasospastic event. Cardiovascular, cerebrovascular, or peripheral vascular adverse effects associated with sumatriptan administration during clinical trial evaluation included decreased blood pressure (>= 1%), increased blood pressure (>= 1%), hypotension (<= 1%), hypertension (0.1 to 1%), syncope (>= 0.1%), palpitations ( >= 0.1%), pallor (<= 1%), phlebitis (< 0.1%), pulsating sensations (0.1 to 1%), abnormal pulse (< 0.1%), peripheral vasodilation (< 0.1%), Raynaud's syndrome (< 0.1%), peripheral cyanosis (< 0.1%), atherosclerosis (< 0.1%), cerebral ischemia (< 0.1%), cerebrovascular lesion (< 0.1%), increased intracranial pressure (< 0.1%), thrombosis (< 0.1%), heart block (AV block) (< 0.1%), sinus bradycardia (<= 1%), sinus tachycardia (0.1 to 1%), and transient ECG changes following parenteral use or nasal spray (e.g., ST-T wave changes, premature atrial contractions (PACs), premature ventricular contractions (PVCs), QT prolongation) (0.1 to 1%). Significant increases in blood pressure, including hypertensive crisis, have occurred rarely in patients with and without a history of hypertension. Chest pain (unspecified) and a chest pressure syndrome, which included sensations of chest pain, tightness and/or heaviness and jaw pain and tightness and regional pain and pressure have been reported immediately following sumatriptan administration and have been associated with cardiac events. During clinical trials of oral sumatriptan in the treatment of migraines, chest pain/tightness/pressure/heaviness occurred in 1 to 2% of patients receiving sumatriptan and 1% of patients receiving placebo. During clinical trials of subcutaneous sumatriptan for migraines, the following chest symptoms were reported in at least 2% of patients receiving sumatriptan and with an incidence higher than placebo: chest discomfort (5% vs. 1%), tightness in chest (3% vs. < 1%), and pressure in chest (2% vs. < 1%). Chest tightness, discomfort, and pressure/heaviness have also been associated with nasal spray administration (0.1 to 1%). Sumatriptan tablets and injection have been associated with cerebral vasospasm resulting in intracranial bleeding, subarachnoid hemorrhage, stroke, seizures, and other cerebrovascular events, some of which have lead to fatalities. The relationship with sumatriptan is unclear. In several cases, it appears that the cerebrovascular incident was the primary event and sumatriptan was given due to the incorrect assumption that these symptoms were due to a migraine. Sumatriptan should not be administered if the migraine symptoms are atypical for the patient. Cardiovascular and cerebrovascular effects reported during post-marketing use of sumatriptan include atrial fibrillation, cardiomyopathy, bowel ischemia, Prinzmetal variant angina, pulmonary embolism, shock, thrombophlebitis, vasculitis, stroke, subarachnoid hemorrhage, temporal arteritis, and cyanosis. In post-marketing reports, stroke has been rarely noted as a serious adverse event in adolescents. Death associated with sumatriptan has also been reported in adolescents; causality is not known.
During clinical trials of oral sumatriptan in the treatment of migraines, malaise or fatigue was reported in 2 to 3% of patients receiving sumatriptan and < 1% of those receiving placebo. Fever was observed in 0.1 to 1% of patients in association with oral and nasal administration of sumatriptan and rarely with subcutaneous administration (< 0.1%). Lymphadenopathy was reported rarely (< 0.1%).
During clinical trials of subcutaneous sumatriptan in the treatment of migraines, injection site reaction occurred in 30% to 59% of patients receiving sumatriptan vs. 13% to 24% of patients receiving placebo. Injection site reactions included bruising, erythema, hemorrhage, induration, skin irritation, pain, paresthesia, pruritus, swelling, and urticaria. Other dermatologic effects included hyperhidrosis (2% vs. 1%) and flushing (7% vs. 2%). Flushing, tingling, and/or a sensation of warmth, burning, or heat generation appear to be transient; the effects usually disappear within 10 to 30 minutes after subcutaneous administration. Hyperhidrosis was observed in 1% or more of patients in association with administration of sumatriptan tablets and in less than 0.1% of those receiving sumatriptan nasal spray. Infrequently reported events (0.1% to 1%) associated with the administration of any sumatriptan formulation included rash (unspecified), skin eruption, skin tenderness, and erythema. Rare events (less than 0.1%) included herpes, facial swelling, peeling of skin, skin tenderness, skin tightness, wrinkling of skin, atopic dermatitis, seborrhea, skin nodules, contusions, and xerosis. Hypersensitivity reactions were reported in 1% or less of patients during clinical trial evaluation. During postmarketing use, exacerbation of sunburn, photosensitivity, and hypersensitivity reactions (allergic vasculitis, erythema, pruritus, rash, shortness of breath, urticaria) have been reported. In addition, anaphylaxis or anaphylactoid reactions including angioedema have been reported in patients taking sumatriptan. Such reactions may be life-threatening or fatal and are more likely to occur in patients with a history of sensitivity to multiple allergens.
During clinical trials of subcutaneous sumatriptan in the treatment of migraines, the following centrally-mediated effects occurred in at least 2% of patients receiving sumatriptan and with an incidence greater than placebo: dizziness/vertigo (12% vs. 4%), drowsiness/sedation (3% vs. 2%), and headache (2% vs. less than 1%). Vertigo was reported more frequently in patients receiving oral sumatriptan 25 to 100 mg than placebo (2% or less vs. less than 1%) during clinical trials for migraines. Dizziness/vertigo occurred in 1% to 1.7% of those receiving nasal sumatriptan 5 to 20 mg vs. 0.9% of those receiving placebo. Centrally-mediated effects observed in at least 1% of patients in association with administration of any formulation of sumatriptan include anxiety, photophobia, and phonophobia. Infrequently reported events (0.1% to 1%) include agitation, anxiety, chills, confusion, depression, difficulty concentrating, drowsiness, dysarthria, euphoria, facial pain, heat sensitivity, incoordination, lacrimation, monoplegia, relaxation, sleep disturbance, tremor, and shivering. Rare events (less than 0.1%) include aggressiveness, agitation, anxiety, apathy, bradylogia, cluster headache, difficulty concentrating, depression, detachment, difficulty coordinating, disturbance of emotion, drug abuse, dysarthria, dystonic reaction, euphoria, facial pain, facial paralysis, hallucinations, transient hemiplegia, hunger, hyperesthesia, hysteria, globus hystericus, increased alertness, intoxication, lacrimation, myoclonia, monoplegia/diplegia, memory impairment, motor dysfunction, neuralgia, neurotic disorders, paralysis, personality change, phobia, psychomotor disorders, radiculopathy, reduced appetite, rigidity, secondary malignancy (pituitary), seizures, sleep disturbance, stress, suicide (suicidal ideation), twitching, voice/speech disturbances, and yawning. During postmarketing use, panic disorder and serotonin syndrome have been reported. Serotonin syndrome may occur with serotonin receptor agonists particularly during concurrent use of serotonergic agents such as SSRIs or SNRIs. Serotonin syndrome consists of symptoms such as mental status changes (e.g., agitation, confusion), diaphoresis, hyperreflexia, elevated blood pressure, hyperthermia, nauseousness, emesis, and diarrhea. Overuse of drugs for treating acute headaches, including triptans, may lead to medication overuse headache. Patients may experience migraine-like daily headaches or a significant increase in migraine attack frequency. Discontinuation of the overused drug and treatment of withdrawal symptoms (e.g., transient worsening of headache) may be necessary. Advise patients about the risks of medication overuse (e.g., use of sumatriptan or any combination of therapy for at least 10 days/month) and encourage them to keep a written record of headache frequency and drug use. Pediatric guidelines recommend no more than 9 days/month of triptans, 14 days/month of over-the-counter medication, and no more than 9 days/month of any combination of therapy to avoid medication overuse headache.
Unspecified vision alterations were observed in at least 1% of patients in association with administration of subcutaneous sumatriptan. Infrequently reported ophthalmic events (0.1 to 1%) occurring with any sumatriptan formulation included ocular irritation and visual disturbance (unspecified). Rare events (< 0.1%) included disorders of sclera, mydriasis, blindness and low vision, visual disturbances (unspecified), ocular swelling, ocular irritation and ocular pruritus, accomodation disorders, external ocular muscle disorders, ocular hemorrhage, ocular pain, keratitis, and conjunctivitis. Ophthalmic effects reported during post-marketing use include ischemic optic neuropathy, retinal artery occlusion, retinal thrombosis, and loss of vision. Visual impairment, including blurred vision, may be a part of any type of migraine headache; therefore, causality cannot be determined. Sumatriptan causes corneal opacities and defects in the corneal epithelium in dogs; there is the potential for these changes in humans.
During clinical trials of subcutaneous sumatriptan in the treatment of migraines, the following musculoskeletal effects occurred in at least 2% of patients receiving sumatriptan and with an incidence greater than placebo: myasthenia (5% vs. < 1%), neck pain/stiffness (5% vs. < 1%), and myalgia (2% vs. < 1%). Musculoskeletal effects observed in at least 1% of patients in association with administration of any formulation of sumatriptan include myalgia and muscle cramps. Infrequently reported events (0.1 to 1%) include arthritis, backache (back pain), joint symptoms (pain, stiffness, swelling, ache), myasthenia, and neck pain/stiffness. Rare events (< 0.1%) include acquired musculoskeletal deformity, arthralgia, articular rheumatitis, backache, intervertebral disc disorder, muscle atrophy, muscle cramps, muscle fatigue, muscle stiffness/tightness/rigidity, musculoskeletal inflammation, myasthenia, need to flex calf muscles, swelling of the extremities, and tetany. Serotonin receptor agonists may cause peripheral vasospastic reactions. Patients who experience signs or symptoms suggestive of peripheral vasoconstriction or decreased arterial flow, such as peripheral coldness or Raynaud's syndrome, should be further evaluated. Sumatriptan is contraindicated in patients with peripheral vascular disease.
During clinical trials of subcutaneous sumatriptan in the treatment of migraines, the following atypical sensations occurred in at least 2% of patients receiving sumatriptan and with an incidence greater than placebo: tingling (14% vs. 35%), warm/hot sensation (11% vs. 4%), burning sensation (7% vs. < 1%), feeling of heaviness (7% vs. 1%), pressure sensation (7% vs. 2%), feeling of tightness (5% vs. < 1%), numbness (5% vs. 2%), feeling strange (2% vs. < 1%), and tight feeling in head (2% vs. < 1%). Paresthesias were reported in 5% of patients receiving subcutaneous sumatriptan for cluster headache versus 0% of placebo-treated patients. Atypical sensations reported more frequently with oral sumatriptan 25 to 100 mg versus placebo included paresthesias (3 to 5% vs. 2%) and warm/cold sensations (2 to 3% vs. 2%). Burning sensation was reported in 0.4 to 1.4% of patients receiving nasal sumatriptan versus 0.1% of those receiving placebo. Atypical sensations observed in at least 1% of patients in association with administration of any formulation of sumatriptan included burning sensation and numbness. Infrequently reported events (0.1 to 1%) included tingling, warm/hot sensation, numbness, pressure sensation, feeling strange, feeling of heaviness, feeling of tightness, paresthesias, cold sensation, prickling sensations, stinging sensations, sensation of lightness, and tight feeling in head. Rare events (< 0.1%) included dysesthesia, simultaneous hot/cold sensations, tickling sensations, and prickling sensation.
During clinical trials of sumatriptan nasal spray in the treatment of migraines, dysgeusia occurred in 13.5% to 24.5% of patients treated with sumatriptan vs. 1.7% of patients who received placebo. Similarly, in clinical trials of sumatriptan nasal powder, dysgeusia occurred more frequently in sumatriptan-treated patients vs. placebo (20% vs. 3%). Nausea and vomiting were reported in 4% of patients receiving subcutaneous sumatriptan for cluster headache vs. 0% of placebo-treated patients; with oral or nasal therapy, nausea and vomiting often occurred at rates similar to placebo or just slightly higher than placebo but were reported in more than 1% of patients. For example, during clinical trials of nasal sumatriptan in the treatment of migraines, the incidence of nausea and/or vomiting was 11% to 13.5% vs. 11.3% for placebo. GI effects observed in at least 1% of patients in association with administration of any formulation of sumatriptan include abdominal discomfort, diarrhea, dysphagia, and gastric symptoms (unspecified). Infrequently reported events (0.1% to 1%) include abdominal discomfort, constipation, diarrhea, dysgeusia, dysphagia, and gastroesophageal reflux. Rare events (less than 0.1%) include colitis, constipation, GI bleeding or hemorrhage, intestinal GI obstruction, hematemesis, melena, peptic ulcer, GI pain, dyspeptic symptoms, dental pain, dysgeusia, feelings of GI pressure, flatulence/eructation, gallstones, gastroesophageal reflux, gastritis, gastroenteritis, hypersalivation, abdominal distention, oral itching and irritation, pancreatitis, retching, salivary gland swelling, and swallowing disorders. Use of sumatriptan nasal spray has been associated with disorders of the mouth and tongue (e.g., burning of tongue, numbness of tongue, and xerostomia) in 0.1% to 1% of patients. Xerostomia, dysphagia, and ischemic colitis with rectal bleeding have been reported during postmarketing use. Abdominal pain, bloody diarrhea, and cramping have been associated with ischemic colitis after sumatriptan administration.
During clinical trials of subcutaneous sumatriptan in the treatment of migraines, the following adverse reactions involving the ear, nose, throat, and related structures occurred in at least 2% of patients receiving sumatriptan and with an incidence greater than placebo: throat discomfort (3% vs. less than 1%), nasal cavity/sinus discomfort (2% vs. less than 1%), and jaw discomfort (2% vs. 0%). Neck/throat/jaw pain/tightness/pressure was reported more frequently in patients receiving oral sumatriptan 25 to 100 mg than placebo (3% or less vs. less than 1%) during clinical trials for migraines. During clinical trials of nasal sumatriptan spray 5 to 20 mg, the following effects occurred in at least 1% of patients receiving sumatriptan and with an incidence greater than placebo: disorder/discomfort of nasal cavity/sinuses or rhinalgia (2.5% to 3.8% vs. 2.4%) and throat discomfort (0.8% to 2.4% vs. 0.9%). Local irritative symptoms including application site reactions such as burning sensation in the nose (36%) and throat irritation (5%) were observed over 6 months in an open-label trial of sumatriptan nasal spray. During clinical trials of nasal sumatriptan powder, the following effects occurred in at least 2% of patients receiving sumatriptan and with an incidence greater than placebo: nasal discomfort (11% vs. 1%), rhinorrhea (5% vs. 2%), and rhinitis (2% vs. 0%). Adverse reactions observed in at least 1% of patients in association with administration of any formulation of sumatriptan included sinusitis, tinnitus, allergic rhinitis, upper respiratory inflammation, ear, nose (epistaxis), and throat bleeding (hemorrhage), external otitis, hearing loss, nasal inflammation, and sensitivity to noise (hyperacusis). Infrequently reported events (0.1% to 1%) included hearing disturbances, ear infection, parosmia, and otalgia. Rare events (less than 0.1%) included a feeling of fullness in the ear, otalgia, parosmia, and Meniere's disease. Deafness has been reported during postmarketing use.
Thirst was observed in 0.1 to 1% of patients in association with sumatriptan administration during clinical trial evaluation. Rare endocrine events (< 0.1%) included elevated thyrotropin stimulating hormone levels, dehydration, galactorrhea, hyperglycemia, hypoglycemia, hypothyroidism, polydipsia, weight gain, weight loss, endocrine cysts, lumps, and masses, and fluid disturbances.
Renal effects observed in 0.1 to 1% of patients in association with sumatriptan administration during clinical trial evaluation included dysuria and increased urinary frequency. Rare renal events (< 0.1%) included bladder inflammation (cystitis), dysuria, hematuria, increased urinary frequency, micturition disorders, urethritis, urinary infections, and renal calculus (nephrolithiasis). During post-marketing use, acute renal failure (unspecified) has been reported.
Dyspnea was observed in at least 1% of patients in association with oral sumatriptan administration during clinical trial evaluation. Bronchospasm was reported in 1% of patients receiving subcutaneous sumatriptan for cluster headache versus 0% of placebo-treated patients. Respiratory effects observed in 0.1 to 1% of patients receiving any sumatriptan formulation included asthma (bronchospasm), dyspnea, cough, and lower respiratory tract infection. Rare respiratory events (< 0.1%) included asthma (bronchospasm), hiccups, breathing disorders (unspecified), cough, influenza, lower respiratory tract disease (unspecified), and bronchitis. During post-marketing use, bronchospasm in patients with and without a history of asthma has been reported.
Anemia was observed in < 0.1% of patients in association with oral administration of sumatriptan. Hematologic effects reported during post-marketing use of sumatriptan include hemolytic anemia, pancytopenia, and thrombocytopenia.
Disturbances in liver function tests were reported infrequently (0.1 to 1%) during clinical study of sumatriptan. Elevated hepatic enzymes have been reported during post-marketing use of the drug.
During clinical trials of oral sumatriptan in the treatment of migraines, pain occurred in 1 to 2% of patients receiving sumatriptan and 1% of patients receiving placebo. Non-chest related pressure/tightness/heaviness sensations were reported in 1 to 3% of sumatriptan-treated patients and 2% of placebo-treated patients. Other general effects observed in 0.1 to 1% of patients in association with administration of any formulation of sumatriptan and not listed elsewhere included edema, fluid retention, and overdose. Rare events (< 0.1%) included edema and difficulty walking.
Reproductive and breast disorders observed in 0.1 to 1% of patients in association with administration of one or more sumatriptan formulations during clinical trial evaluation included intermenstrual bleeding, dysmenorrhea, unspecified breast disorders, and breast tenderness. Rare events (less than 0.1%) included spontaneous fetal abortion, dysmenorrhea, endometriosis (endometrial hyperplasia), unspecified menstruation symptoms, abnormal menstrual cycle (menstrual irregularity), nipple or breast discharge, breast swelling, breast cysts, lumps, and masses, primary malignant breast neoplasm, and inflammation of fallopian tubes.
Allergic contact dermatitis (ACD) was reported at a rate of 4% in two long-term open-label studies of the sumatriptan iontophoretic transdermal system (TDS). Discontinue the sumatriptan TDS if ACD is suspected. Erythema is commonly seen with use of the sumatriptan TDS and is not by itself an indication of sensitization. Following sensitization with the sumatriptan TDS, erythematous plaque and/or erythemato-vesicular or erythemato-bullous eruptions may develop. Clinical course is characterized by crescendo phenomenon of worsening pruritus and appearance over time with slower resolution to normal of affected skin areas. Patients sensitized from use of the sumatriptan TDS, as evidenced by development of ACD, may develop systemic sensitization or other systemic reactions if sumatriptan-containing products are taken via other routes, e.g., orally or subcutaneously. It is possible that some patients who developed ACD with sumatriptan by exposure to the sumatriptan TDS, and who have developed systemic sensitization, may not be able to take sumatriptan in any form. Patients who develop ACD with the sumatriptan TDS and require treatment with sumatriptan via other routes should receive their first subsequent dose under close medical supervision.
The sumatriptan iontophoretic transdermal system (TDS) should not be applied in areas near or over electrically-active implantable or body-worn medical devices (e.g., implantable cardiac pacemaker, body-worn insulin pump, implantable deep brain stimulator).
Sumatriptan is contraindicated in patients with sumatriptan hypersensitivity or any components of the commercially available products. In general, anaphylactic reactions are more likely to occur in individuals with a history of sensitivity to multiple allergens. Use sumatriptan cautiously in patients who have experienced allergic contact dermatitis (ACD) with the iontophoretic transdermal system (TDS). Patients sensitized from use of the sumatriptan TDS, as evidenced by development of ACD, may develop systemic sensitization or other systemic reactions if sumatriptan-containing products are taken via other routes, e.g., orally or subcutaneously. It is possible that some patients who developed ACD with sumatriptan by exposure to the sumatriptan TDS, and who have developed systemic sensitization, may not be able to take sumatriptan in any form. Patients who develop ACD with the sumatriptan TDS and require treatment with sumatriptan via other routes should receive their first subsequent dose under close medical supervision. The needle shield of the Imitrex Statdose prefilled syringe contains dry natural rubber (a latex derivative) and may cause allergic reactions in patients with latex hypersensitivity.
Rare, but serious adverse cardiac effects, including heart attacks, life-threatening disturbances of cardiac rhythm, and death have been reported within a few hours of receiving 5-HT1 agonists. Many of these patients had concurrent cardiovascular risk factors; therefore, it is difficult to assess causality. Sumatriptan and other 5-HT agonists may cause coronary vasospasm, and therefore are contraindicated in patients with known or suspected coronary artery disease (CAD), angina pectoris, vasospastic angina such as Prinzmetal's variant angina, arteriosclerosis, silent myocardial ischemia, acute myocardial infarction, history of myocardial infarction, or other significant cardiac disease. Patients with CAD risk factors (e.g., high blood pressure, diabetes mellitus, hypercholesterolemia, obesity, tobacco smoking, family history of CAD, female with surgical or physiological menopause, or male > 40 years old) should not be given sumatriptan unless a cardiac evaluation determines they are reasonably free of CAD, myocardial ischemia or other significant cardiac disease. Patients who are long-term users of sumatriptan and who have or acquire risk factors predictive of CAD should undergo periodic cardiac evaluation. For patients with risk factors predictive of CAD who are determined to have a satisfactory cardiac evaluation, the first dose of sumatriptan should be given in a controlled setting such as a clinic or physician's office. ECG monitoring is strongly encouraged due to the possibility of asymptomatic cardiac ischemia during the time immediately following sumatriptan administration in patients with risk factors. Inappropriate concomitant use of eletriptan and sumatriptan may have contributed to a fatal myocardial infarction in a patient with known cardiovascular risk factors; however, causality was not definitively determined. In addition, patients with cardiac arrhythmias should not receive sumatriptan as rhythm disturbances have been reported with the use of 5-HT1 agonists. Sumatriptan is contraindicated in patients with Wolff-Parkinson-White syndrome or cardiac arrhythmias associated with other cardiac accessory conduction pathway disorders.
Sumatriptan is contraindicated in patients with uncontrolled hypertension. Sumatriptan can produce a significant increase in blood pressure in patients with and without a history of hypertension. Patients with controlled hypertension may experience mild and transient elevations in blood pressure.
Sumatriptan is contraindicated in patients with cerebrovascular disease (i.e., stroke or transient ischemic attacks) and should be avoided in the presence of intracranial bleeding due to the vasospastic effects of 5-HT agonists. While stroke, cerebral hemorrhage, and related fatalities have been reported following administration of 5-HT1 agonists, these events may have been present prior to administration of the drug, and the drug was mistakenly given in response to the cerebrovascular symptoms. However, patients with migraines may be at an increased risk for cerebrovascular events (e.g., stroke, hemorrhage).
Sumatriptan is contraindicated in basilar/hemiplegic migraine because safety and efficacy have not been established. Safety and efficacy have not been established in cluster headaches. Sumatriptan should not be administered if the headache is atypical for the patient. Sumatriptan is not recommended for long-term prophylaxis of migraine headaches.
Intravenous administration of sumatriptan should be avoided because of the potential to cause coronary vasospasm.
A consistent pattern of birth defects among pregnant women exposed to sumatriptan has not been observed. The sumatriptan prospective pregnancy registry collected pregnancy outcomes of 528 infants and fetuses with earliest sumatriptan exposure during the first trimester, 78 during the second trimester, and 16 during the third trimester. The incidence of major birth defects during first trimester exposure was 4.2% (20/478 [95% CI 2.6% to 6.5%]) and during any trimester exposure was 4.2% (24/576 [95% CI 2.7% to 6.2%]). Birth defects reported for more than 2 infants after first trimester exposure included ventricular septal defects (n = 4) and pyloric stenosis (n = 3). Fetal deaths, spontaneous abortions, and elective abortions without reported defects were excluded from analysis. An analysis of data from the Swedish Medical Birth Register reported a relative risk of malformations of 0.99 (107/2,257 [95% CI 0.91 to 1.21]) among live births with first trimester exposure to sumatriptan. A study of the Norwegian birth registry and prescription data reported congenital malformations in 15 infants of 415 women who redeemed prescriptions for sumatriptan during the first trimester of pregnancy, and in 20 infants of 364 women who redeemed prescriptions for sumatriptan before, but not during, pregnancy. Compared to a general population group, the odds ratio for congenital malformation was 1.16 (95% CI 0.69 to 1.94) among women who redeemed prescriptions for sumatriptan during the first trimester and 1.83 (95% CI 1.17 to 2.88) for those who redeemed prescriptions for sumatriptan before pregnancy. During animal reproductive studies, intravenous administration of sumatriptan to rabbits during organogenesis resulted in an increased incidence of embryolethality with a no-effect dose of 0.75 mg/kg/day, which is approximately one tenth of the maximum single oral dose of 100 mg based on body surface area. In rats and rabbits, oral treatment with sumatriptan was associated with fetal abnormalities and pup mortality at doses higher than the maximum single recommended human oral dose based on body surface area.
Sumatriptan is excreted into the breast milk of humans. Previous American Academy of Pediatrics recommendations considered sumatriptan to be compatible with breast-feeding. Infant exposure to sumatriptan can be minimized by avoiding breast-feeding for 12 hours after treatment. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for sumatriptan and any potential adverse effects on the breast-fed infant from sumatriptan or the underlying maternal condition. In 1 trial, 5 women who had been lactating for an average of 22 weeks received a single 6 mg subcutaneous dose of sumatriptan. Drug concentrations were measured in milk and plasma over an 8 hour period after drug administration. The mean milk:plasma ratio of sumatriptan was 4.9 (95% CI 4.1 to 5.7), indicating a significant transfer of sumatriptan into the milk compartment. However, only 0.24% (14 mcg; CI 6.1 to 22.7 mcg) of the 6 mg sumatriptan dose was recovered in the milk, which corresponds to a weight-adjusted mean exposure of 3.5% (95% CI 0.3% to 6.7%) of the maternal dose. Assuming oral bioavailability of sumatriptan in infants is similar to adults (mean 14%), the weight-adjusted infant dose is roughly 0.49%. Allowance for reduced clearance in the infant predicts an infant exposure varying from 4.9% in the very premature neonate to 0.7% in a 30 week old infant (mean 3.5%). The authors of this study concluded that expressing breast milk and discarding it up to 8 hours after a dose would help to avoid any potential infant exposure to sumatriptan.
All formulations of sumatriptan are contraindicated in patients with severe hepatic disease or impairment. Sumatriptan is metabolized significantly by the liver. The bioavailability and peak serum concentrations can increase markedly in patients with hepatic disease. The oral formulation should be used cautiously in those with mild to moderate hepatic impairment; dosage adjustments are recommended if treatment with the oral formulation is deemed necessary.
Sumatriptan is renally excreted; therefore, renal impairment may contribute to an increase in bioavailability. Sumatriptan should be used with caution in patients with renal impairment, including renal disease or renal failure.
Sumatriptan is not approved in children under 18 years for the treatment of migraine and the manufacturer does not recommend its use. However, there are studies of sumatriptan for the treatment of migraine in children. Serious post-marketing adverse events have been reported in the pediatric population after use of subcutaneous, oral, and/or intranasal sumatriptan.
A cardiovascular evaluation is recommended for geriatric patients who have other cardiovascular risk factors (e.g., diabetes, hypertension, smoking, obesity, strong family history of CAD). Generally, dose selection should be cautious, starting at the lower end of the dosing range, reflecting greater frequency of decreased hepatic, renal, or cardiovascular function and of concomitant disease or drug therapy.
Patients should be warned about the possibility of sedation while taking sumatriptan and to use caution when driving or operating machinery.
Sumatriptan is contraindicated in patients with peripheral vascular disease including ischemic bowel disease (ischemic colitis) and Raynaud's phenomenon. Sumatriptan may cause vasospastic reactions leading to vascular and colonic ischemia with abdominal pain and bloody diarrhea.
There have been rare reports of seizure following administration of sumatriptan. Sumatriptan should be used with caution in patients with a history of seizures (seizure disorder) or structural brain lesions that lower their seizure threshold.
Rare reports of transient and permanent blindness, including significant partial vision loss have been reported with the use of sumatriptan. Visual disturbance may be a part of any type of migraine headache; therefore, causality cannot be determined.
Sumatriptan is contraindicated in patients concurrently or recently (i.e., within 2 weeks) receiving MAOI therapy (i.e., MAO-A inhibitors).
The sumatriptan iontophoretic transdermal system (TDS) contains metal parts. The TDS must be removed before a magnetic resonance imaging (MRI) procedure to prevent injury during the procedure.
For the acute treatment of migraine attacks with or without aura:
NOTE: Sumatriptan is not indicated for hemiplegic or basilar migraine.
Subcutaneous dosage (Alsuma, Sumavel DosePro, Imitrex, and generic equivalents):
Adults: 6 mg subcutaneously as a single dose. May repeat dose once after at least 1 hour after first dose if needed. Max: 12 mg/day. If side effects are limiting, a lower dose may be used. Controlled clinical trials have failed to show that clear benefit is associated with the administration of a second 6 mg dose in patients who have failed to respond to first injection. Guidelines classify sumatriptan as having established efficacy for the acute treatment of migraine headache.
Subcutaneous dosage (Zembrace SymTouch):
Adults: 3 mg subcutaneously as a single dose. May repeat dose after at least 1 hour between doses. Max: 12 mg/day. Guidelines classify sumatriptan as having established efficacy for the acute treatment of migraine headache.
Oral dosage:
Adults: 25, 50, or 100 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: 200 mg/day. If headache returns after initial treatment with sumatriptan injection, may give up to 100 mg/day PO with intervals of at least 2 hours between oral doses. Doses of 50 or 100 mg may provide a greater effect than 25 mg; however, 100 mg may not provide a greater effect than 50 mg. Guidelines classify sumatriptan as having established efficacy for the acute treatment of migraine headache.
Intranasal dosage (Imitrex nasal spray and generic equivalents):
Adults: 5, 10, or 20 mg into 1 nostril 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: 40 mg/day. In controlled clinical trials, a greater proportion of patients had headache response after a 20 mg dose than 5 or 10 mg doses. Guidelines classify sumatriptan as having established efficacy for the acute treatment of migraine headache.
Children and Adolescents 12 to 17 years*: 20 mg into 1 nostril as a single dose. May repeat dose once after at least 2 hours after the first dose. Max: 40 mg/day. Guidelines recommend sumatriptan nasal spray for acute treatment of migraine in adolescents; those receiving sumatriptan 20 mg intranasally are probably more likely that those receiving placebo to be headache-free at 2 hours.
Intranasal dosage (Tosymra nasal spray):
Adults: 10 mg into 1 nostril as a single dose. May repeat dose as needed with at least 1 hour between doses. Max: 30 mg/day. Guidelines classify sumatriptan as having established efficacy for the acute treatment of migraine headache.
Intranasal dosage (Onzetra Xsail nasal powder):
Adults: 22 mg (2 nosepieces with 11 mg into each nostril) nasally 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: 44 mg/day (4 nosepieces/day) or 1 dose/day of nasal powder and 1 dose/day of another sumatriptan product. Guidelines classify sumatriptan as having established efficacy for the acute treatment of migraine headache.
For the acute treatment of cluster headache:
Subcutaneous dosage (Alsuma, Sumavel DosePro, Imitrex, and generic equivalents):
Adults: Initially, 6 mg subcutaneously. If headache symptoms return, a second 6 mg dose may be given with a minimum 1-hour interval between doses. Consider giving a second dose only if some response to the first dose was observed. The maximum dose within 24 to 48 hours is two 6 mg injections. A cardiovascular evaluation is recommended for geriatric patients who have other cardiovascular risk factors (e.g., diabetes, hypertension, smoking, obesity, strong family history of coronary artery disease).
Maximum Dosage Limits:
-Adults
6 mg/dose or 12 mg/day subcutaneously (Alsuma, Sumavel DosePro, Imitrex, and generic equivalents); 3 mg/dose or 12 mg/day subcutaneously (Zembrace SymTouch); 100 mg/dose PO or 200 mg/day PO; 40 mg/day intranasally (Imitrex nasal spray and generic equivalents); 30 mg/day intranasally (Tosymra nasal spray); or 44 mg/day intranasally (nasal powder). The safety of treating more than 4 headaches in a 30-day period has not been established.
-Geriatric
6 mg/dose or 12 mg/day subcutaneously (Alsuma, Sumavel DosePro, Imitrex, and generic equivalents); 3 mg/dose or 12 mg/day subcutaneously (Zembrace SymTouch); 100 mg/dose PO or 200 mg/day PO; 40 mg/day intranasally (Imitrex nasal spray and generic equivalents); 30 mg/day intranasally (Tosymra nasal spray); or 44 mg/day intranasally (nasal powder). The safety of treating more than 4 headaches in a 30 day period has not been established.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Hepatic impairment may cause unpredictable increases in the bioavailability of orally administered sumatriptan. Do not exceed 50 mg/dose PO. Hepatic impairment does not significantly affect intranasal or subcutaneous sumatriptan. All formulations are contraindicated for use in patients with severe hepatic impairment.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
Intermittent hemodialysis
It is not known whether hemodialysis removes sumatriptan from plasma.
Peritoneal dialysis
It is not known whether peritoneal dialysis removes sumatriptan from plasma.
*non-FDA-approved indication
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dihydrocodeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Acetaminophen; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Acetaminophen; Dextromethorphan: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Acetaminophen; Hydrocodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Acetaminophen; Oxycodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering oxycodone with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Alfentanil: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with sumatriptan. 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 sumatriptan 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.
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.
Benzhydrocodone; Acetaminophen: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering benzhydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Theoretically, concurrent use of methylene blue and serotonin-receptor agonists may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and serotonin-receptor agonists increase central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
Benzphetamine: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and serotonin-receptor agonists. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Bromocriptine: (Major) There are limited clinical trial data supporting the safety of giving a serotonin-receptor agonist ("triptan") with bromocriptine, an ergot derivative. The concomitant use of these agents with bromocriptine should be avoided. There is concern that prolonged vasospastic reactions, hypertension, tachycardia, or other side effects may occur.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Buprenorphine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering buprenorphine with serotonergic-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Buprenorphine; Naloxone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering buprenorphine with serotonergic-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Buspirone: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant buspirone and serotonin-receptor agonist use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Butorphanol: (Moderate) The safety of using intranasal butorphanol and sumatriptan nasal spray during the same episode of migraine has not been established; however, it should be noted that both products are capable of producing transient increases in blood pressure. Theoretically, the effect of intranasal butorphanol may be increased by intranasal sumatriptan. To reduce the likelihood of this interaction, allow 30 minutes between the administration of each drug. In healthy volunteers, the pharmacokinetics of butorphanol intranasal (1 mg) were not affected by the coadministration of a single dose of sumatriptan SC 6 mg. However, in another study, the pharmacokinetics of butorphanol were significantly altered (29% decrease in AUC and 38% decrease in Cmax) when butorphanol intranasal (1 mg) was administered 1 minute after a 20-mg dose of sumatriptan nasal spray (in opposite nostrils); however, if patients wait 30 minutes between administrations any interaction effect should be minimal. Butorphanol intranasal administration does not affect the pharmacokinetics of sumatriptan when given intranasally.
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; Hydrocodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Citalopram: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sumatriptan 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.
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.
Desipramine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant serotonin-receptor agonist and tricyclic antidepressant use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Desvenlafaxine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering desvenlafaxine with other drugs that have serotonergic properties such as serotonin-receptor agonists (e.g., almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and serotonin norepinephrine reuptake inhibitors. Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose increases. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Dextroamphetamine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant serotonin-receptor agonist and amphetamine; dextroamphetamine use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Dextromethorphan: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Dextromethorphan; Bupropion: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Dextromethorphan; Guaifenesin: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Dextromethorphan; Guaifenesin; 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.
Dihydroergotamine: (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.
Doxepin: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant serotonin-receptor agonist and tricyclic antidepressant use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Droxidopa: (Major) Coadministration of droxidopa with other agents that increase blood pressure, such as serotonin-receptor agonists, would be expected to increase the risk for supine hypertension. Monitor supine blood pressure. Reduce or discontinue droxidopa if supine hypertension persists. If supine hypertension is not well-managed, droxidopa may increase the risk of cardiovascular events.
Duloxetine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant duloxetine and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Eletriptan: (Contraindicated) Eletriptan is contraindicated for use within 24 hours of treatment with sumatriptan due to the risk for additive vasospastic reactions. Additive serotonergic effects, including serotonin syndrome, may also occur.
Ergoloid Mesylates: (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.
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.
Ergotamine: (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.
Ergotamine; Caffeine: (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 sumatriptan 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.
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 sumatriptan 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 sumatriptan 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 sumatriptan 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) Sumatriptan 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.
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.
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.
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.
Isocarboxazid: (Contraindicated) Concurrent administration of MAO-A inhibitors or use of sumatriptan within 2 weeks of discontinuation of MAO-A inhibitor therapy is contraindicated. Sumatriptan appears to metabolized by monoamine oxidase (MAO), predominantly MAO-type A; therefore, plasma concentrations of sumatriptan 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). Because oral sumatriptan usually undergoes first-pass metabolism, the increase of AUC after coadministration of an MAO-A inhibitor is greater than the interaction with subcutaneous sumatriptan combined with an MAO-A inhibitor. The effects of an MAOI on the AUC after intranasal sumatriptan use would be expected to be greater than the effect after sumatriptan SC but smaller than the effect after sumatriptan PO. In a study of healthy female volunteers (n = 14), pretreatment with an MAO-A inhibitor (moclobemide) decreased the clearance of subcutaneous sumatriptan resulting in a 2-fold increase in sumatriptan AUC and a 40% increase in elimination half-life. In a similar study of oral sumatriptan, pretreatment with an MAO-A inhibitor followed by 25-mg PO of sumatriptan resulted in an approximately 7-fold increase in sumatriptan AUC.
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.
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.
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.
Methylergonovine: (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.
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.
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 sumatriptan 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.
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 sumatriptan 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.
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 sumatriptan 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.
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) Concurrent administration of sumatriptan and a non-selective monoamine oxidase inhibitor (MAOI) (e.g., phenelzine) or use of sumatriptan within 2 weeks of discontinuation of such an MAOI is contraindicated due to an increased risk for serotonin syndrome and increased sumatriptan concentrations. Sumatriptan appears to be predominantly metabolized by MAO-type A. In a study of healthy female volunteers, pretreatment with an MAO-type A inhibitor resulted in a 2-fold increase in sumatriptan AUC and a 40% increase in elimination half-life. In a similar study of oral sumatriptan, pretreatment with an MAO-A inhibitor followed by 25-mg PO of sumatriptan resulted in an approximately 7-fold increase in sumatriptan AUC.
Promethazine; Dextromethorphan: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Protriptyline: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant serotonin-receptor agonist and tricyclic antidepressant use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Rasagiline: (Moderate) Use together with caution. Serotonin syndrome has been reported during administration of serotonin-receptor agonists ("triptans") and non-selective monoamine oxidase inhibitors (MAOIs). Since rasagiline selectively inhibits MAO-B at recommended doses, no interaction with sumatriptan would be expected with normal prescription use. However, there is a decline in MAO-B selectivity with increasing rasagiline doses. Monitor for potential serotonin-related side effects. If serotonin syndrome occurs, discontinue all serotonergic agents and institute appropriate treatment.
Remifentanil: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering remifentanil with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Rizatriptan: (Contraindicated) Rizatriptan is contraindicated for use within 24 hours of treatment with sumatriptan due to the risk for additive vasospastic reactions. Additive serotonergic effects, including serotonin syndrome, may also occur.
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.
Selective serotonin reuptake inhibitors: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sumatriptan 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) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sumatriptan with transdermal selegiline, orally disintegrating selegiline tablets, and high doses of oral selegiline capsules and tablets. Since selegiline oral tablets and capsules selectively inhibit MAO-B at recommended doses, no interaction with sumatriptan would be expected with normal prescription use. However, MAO-B selectivity decreases with increasing doses, therefore, an interaction may occur with high dose treatment. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and monoamine oxidase inhibitors (MAOIs). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue sumatriptan and selegiline and initiate symptomatic treatment if serotonin syndrome occurs.
Sertraline: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sumatriptan 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.
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 sumatriptan. 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.
Tranylcypromine: (Contraindicated) Due to the risk of serotonin syndrome and significantly increased sumatriptan exposure, tranylcypromine is contraindicated for use with sumatriptan. Tranylcypromine should not be used within 4 to 5 half-lives of discontinuing treatment with sumatriptan. Conversely, do not initiate sumatriptan 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.
Zolmitriptan: (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 stimulates presynaptic 5-HT1D receptors, an action that inhibits both dural vasodilation and inflammation. It directly inhibits 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. Sumatriptan has no pharmacologic activity at dopaminergic, muscarinic, or sympathetic receptors and does not possess intrinsic analgesic properties.
Sumatriptan is administered orally, subcutaneously, or intranasally. Sumatriptan is widely distributed throughout the body. Protein binding ranges from 14% to 21%. Approximately 80% of a dose is hepatically metabolized. Metabolism produces an inactive metabolite and its glucuronide conjugate. Renal clearance is believed to be by tubular secretion as well as glomerular filtration. The elimination half-life of sumatriptan is approximately 2 hours.
Affected cytochrome P450 isoenzymes and drug transporters: none
-Route-Specific Pharmacokinetics
Oral Route
Oral absorption of sumatriptan, though influenced by variable gastric emptying and small-bowel transit, is rapid. The onset of relief of migraine-associated symptoms is approximately 60 minutes. Peak concentration is achieved within 2 hours; in clinical study, peak relief occurred in about 2 hours for 54% of patients and 4 hours for an additional 17%. Bioavailability is about 15% with oral administration. Poor bioavailability after oral administration results from incomplete absorption and first-pass hepatic metabolism. After oral administration, about 60% is excreted renally primarily as the IAA metabolite with approximately 3% as unchanged drug; the remaining 40% is excreted in the feces.
Subcutaneous Route
Subcutaneous absorption of sumatriptan has been shown to give more consistent blood plasma peak concentrations than are achieved from administration by other routes. Peak concentration is achieved within 5 to 20 minutes via the subcutaneous route. Onset of pain relief after subcutaneous injection can occur within 10 minutes, and as many as 80% of patients experience relief within 60 minutes. The onset of relief of migraine-associated symptoms is approximately 20 minutes. The time to peak relief for subcutaneous injection is 1 hour in 68% of patients and 2 hours in an additional 13% of patients. Bioavailability after subcutaneous injection is about 97%; distribution half-life is about 13 minutes. After subcutaneous administration, about 22% of a sumatriptan dose is excreted unchanged in the urine and 38% as the indole acetic acid (IAA) metabolite, with a small amount of excretion occurring in the feces. A single 3 mg subcutaneous dose of Zembrace SymTouch is bioequivalent to Imitrex subcutaneous injection.
Other Route(s)
Intranasal Route
Imitrex and Generic Equivalents Nasal Spray
Intranasal absorption of Imitrex nasal spray and generic equivalents is rapid with a peak concentration of sumatriptan achieved within 1 to 1.75 hours. Only 3% of the dose is renally eliminated as unchanged drug, with 42% eliminated as the major metabolite. Administration of two 5 mg doses, 1 in each nostril, is equivalent to administration of a single 10 mg dose in 1 nostril.
Tosymra Nasal Spray
A median Tmax of 10 minutes (range 5 to 23 minutes) occurred after a single 10 mg dose in 73 healthy subjects; mean Cmax was 51.8 ng/mL, and the mean AUC was 60.7 ng x hour/mL. Relative bioavailabilities after the single dose were approximately 87% (90% CI, 82% to 94%) and 58% (90% CI, 55% to 62%) of those obtained after subcutaneous injections of 4 and 6 mg, respectively.
Nasal Powder
Peak plasma concentration occurred on average at 45 minutes after administration. The relative bioavailability compared to subcutaneous injection is approximately 19%.