Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
SUMATRIPTAN vs ACTIQ
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Selective 5-HT1B/1D receptor agonist; causes vasoconstriction of cranial arteries and inhibits trigeminal nerve transmission.
Opioid agonist; binds to mu-opioid receptors in the CNS, altering pain perception and response.
Acute treatment of migraine with or without aura,Acute treatment of cluster headache episodes
Management of breakthrough pain in cancer patients aged 16 and older who are already receiving and tolerant to opioid therapy for their underlying persistent cancer pain
Sumatriptan is available as oral tablets (25 mg, 50 mg, 100 mg), subcutaneous injection (6 mg/0.5 m L), and nasal spray (5 mg, 20 mg). For acute migraine: oral: 50-100 mg at onset, may repeat after 2 hours (max 200 mg/day). Subcutaneous: 6 mg at onset, may repeat after 1 hour (max 12 mg/24h). Nasal spray: 20 mg in one nostril at onset, may repeat after 2 hours (max 40 mg/day).
200 mcg transmucosally, titrated upward as needed; initial dose for opioid-tolerant patients is 200 mcg, with additional doses possible after 15 minutes if needed. Maximum 4 doses per episode. At least 4 hours between episodes.
2.5 hours (range 1–4 h); clinically relevant for redosing interval of ≥2 h.
Terminal half-life 0.83–2 hours (mean 1.3 h) in adults; note that context: transmucosal absorption leads to rapid onset but short duration; half-life is not correlated with clinical effect due to oral transmucosal route and rapid redistribution.
Primarily via monoamine oxidase A (MAO-A); minor via cytochrome P450 (CYP) enzymes.
Primarily hepatic via CYP3A4 to inactive metabolites (norfentanyl, despropionylfentanyl, hydroxyfentanyl) and other metabolites; <7% excreted unchanged in urine.
60% renal (as indole acetic acid metabolite), 40% fecal; <3% unchanged in urine.
Primarily renal as metabolites (about 75% as metabolites, <10% unchanged). Fecal excretion accounts for <9%. Biliary excretion is minor.
14–21%, primarily to albumin and alpha-1-acid glycoprotein.
Fentanyl is 80–85% bound to plasma proteins (primarily albumin and α1-acid glycoprotein).
2.0–3.3 L/kg; indicates extensive tissue distribution.
Approximately 4 L/kg (range 3–6 L/kg); large Vd indicates extensive tissue distribution and redistribution contributing to short duration.
Oral: 15% (due to first-pass metabolism); subcutaneous: 97%; intranasal: 17% (with variability).
Oral transmucosal: 50% (range 47–54%) relative to IV; variable and enhanced by rapid absorption through buccal mucosa.
No specific dose adjustment is recommended for renal impairment. However, sumatriptan and its metabolites are excreted renally, and caution is advised in severe renal impairment (Cr Cl <15 m L/min). No specific GFR-based guidelines are established.
No specific GFR-based dose adjustment recommended; use with caution in severe renal impairment (Cr Cl < 30 m L/min) and consider dose reduction due to potential accumulation.
Contraindicated in severe hepatic impairment (Child-Pugh C). For mild to moderate hepatic impairment (Child-Pugh A or B): oral maximum dose is 50 mg; nasal spray: 5 mg single dose; subcutaneous: no specific adjustment, but caution advised due to reduced clearance.
Child-Pugh Class A/B: No adjustment. Child-Pugh Class C: Reduce initial dose to 100 mcg and titrate slowly; monitor closely for prolonged effects.
Not approved for pediatric use <18 years. However, off-label: adolescent (12-17 years): oral 25-100 mg at onset, may repeat after 2 hours (max 200 mg/day). Subcutaneous: 3-6 mg at onset (based on weight, e.g., 0.06 mg/kg). Nasal spray: 5-20 mg at onset.
Not approved for pediatric use; safety and efficacy not established in patients under 16 years.
Limited data in elderly. Start with the lowest effective dose (e.g., oral 25 mg, subcutaneous 3 mg, nasal spray 5 mg). Caution due to potential for cardiovascular risk, hypertension, and reduced hepatic/renal function. Avoid in patients with uncontrolled hypertension or ischemic heart disease.
Initiate at 100 mcg transmucosally; titrate slowly due to increased sensitivity and risk of respiratory depression. Monitor for adverse effects.
Not recommended for use in patients with risk factors for coronary artery disease (e.g., hypertension, diabetes, smoking) unless a cardiovascular evaluation confirms absence of coronary artery disease.
Risk of respiratory depression, addiction, abuse, and misuse; accidental ingestion can be fatal; concomitant use with benzodiazepines or CNS depressants may cause profound sedation, respiratory depression, coma, and death; not for use in opioid non-tolerant patients; risk of neonatal opioid withdrawal syndrome with prolonged use during pregnancy; serious, life-threatening, or fatal respiratory depression may occur even at recommended doses.
Risk of myocardial ischemia, infarction, and Prinzmetal's angina,Life-threatening serotonin syndrome with concomitant serotonergic drugs,Elevations in blood pressure,Increased risk of cerebrovascular events,Overuse headache with frequent use
Risk of respiratory depression; addiction, abuse, and misuse; interactions with CNS depressants; serotonin syndrome; adrenal insufficiency; severe hypotension; seizures; withdrawal; use in patients with head injuries, increased intracranial pressure, biliary tract disease, pancreatitis; risk of choking with lozenge; oral mucosal irritation; dental caries; hypokalemia; hyponatremia; use in elderly, cachectic, or debilitated patients.
Ischemic heart disease,History of myocardial infarction,Uncontrolled hypertension,Hemiplegic or basilar migraine,Concomitant use of MAO-A inhibitors or within 2 weeks of discontinuation,Severe hepatic impairment,Hypersensitivity to sumatriptan
Significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or without resuscitative equipment; known or suspected paralytic ileus; hypersensitivity to fentanyl or any component; opioid non-tolerant patients; management of acute or postoperative pain including headache/migraine, dental pain, or emergency department use.
No significant food interactions. Avoid alcohol during migraine attacks as it can worsen headaches. May be taken with or without food.
No significant food interactions. Grapefruit juice may increase fentanyl levels, but specific studies with ACTIQ are lacking. Avoid alcohol, as it may increase sedation and respiratory depression risk.
FDA Pregnancy Category C. In first trimester, no increased risk of major congenital malformations from available data; however, animal studies show embryo lethality and increased malformations at high doses. Second and third trimester risks include potential for uterine hypertonus and fetal hypoxia during maternal use for migraine attacks; avoid during third trimester due to risk of premature uterine contractions.
FDA Pregnancy Category C. First trimester: limited human data; animal studies show increased resorptions and fetal growth restriction. Second/third trimester: chronic use may cause neonatal opioid withdrawal syndrome; avoid use during labor due to risk of neonatal respiratory depression.
Sumatriptan is excreted into human breast milk with a relative infant dose of 3.5% of maternal weight-adjusted dose (M/P ratio approximately 0.6-4.3). Clinical studies show no adverse effects in breastfed infants; however, wait at least 12 hours after injection or 24 hours after oral dose to breastfeed to minimize exposure.
Excreted in breast milk; M/P ratio not established. Limited data suggest low levels, but risk of infant sedation and respiratory depression. Avoid use while breastfeeding unless potential benefit outweighs risk.
No specific dose adjustments required for pregnancy based on pharmacokinetic changes; however, lower starting doses may be considered due to increased sensitivity to vascular effects. Avoid use in preeclampsia or uncontrolled hypertension.
Due to increased plasma volume and hepatic metabolism in pregnancy, dose requirements may increase; adjust based on clinical response and tolerance. Avoid use during labor and delivery due to risk of neonatal respiratory depression; short-term use preferred.
Sumatriptan is a 5-HT1B/1D receptor agonist used for acute migraine. It is available in oral, nasal, subcutaneous, and rectal formulations. Onset of action is fastest with subcutaneous injection (10-15 minutes). Avoid use within 24 hours of other triptans or ergot alkaloids. Contraindicated in patients with ischemic heart disease, cerebrovascular disease, uncontrolled hypertension, or hemiplegic/basilar migraine. Monitor for serotonin syndrome when combined with SSRIs/SNRIs.
ACTIQ is a transmucosal immediate-release fentanyl formulation indicated for breakthrough cancer pain in opioid-tolerant patients. Initiate with the lowest strength (200 mcg) and titrate upward. Avoid use in opioid-naive patients due to risk of fatal respiratory depression. Place the unit between cheek and lower gum, not sublingually. Instruct patient not to bite or suck the unit. Monitor for sedation and respiratory depression. Multiple units may be used per episode if needed, but wait at least 4 hours before next episode. Dispose of partially used units by flushing down toilet.
Take sumatriptan at the first sign of migraine headache for best results.,Do not exceed the recommended dose: maximum 100 mg orally or 20 mg intranasally per single dose, with a maximum of 200 mg daily for oral formulations.,Seek emergency medical attention if you experience chest pain, shortness of breath, irregular heartbeat, or signs of stroke.,Avoid driving or operating machinery until you know how sumatriptan affects you, as it may cause dizziness or drowsiness.,Inform your doctor if you have heart disease, high blood pressure, or are pregnant or breastfeeding.
Only use ACTIQ if you are already taking regular around-the-clock opioid pain medicine and are tolerant to opioids.,Do not use ACTIQ for short-term pain like after surgery, headache, or dental pain.,Place the unit in your cheek pouch, not under your tongue. Do not chew or suck it.,If you need more than 4 units per day, contact your doctor as your dose may need adjustment.,Store ACTIQ in a safe place away from children, as accidental ingestion can be fatal.,Dispose of unused or partially used units by flushing them down the toilet.
"Concurrent use of sumatriptan, a serotonin 5-HT1B/1D receptor agonist, and rasagiline, a selective monoamine oxidase B (MAO-B) inhibitor, can lead to serotonin syndrome due to excessive serotonergic activity in the central nervous system. Rasagiline inhibits the metabolism of serotonin, while sumatriptan indirectly increases serotonin release; their combination may result in life-threatening neuromuscular excitation, autonomic instability, and altered mental status. Symptoms may include hyperthermia, rigidity, myoclonus, and rapid fluctuations in vital signs, requiring immediate medical intervention."
"Sumatriptan, a 5-HT1B/1D receptor agonist used for migraine, and sulpiride, a dopamine D2 receptor antagonist with atypical antipsychotic properties, may exhibit additive or synergistic effects on the central nervous system. This combination can potentially increase the risk of serotonin syndrome (due to sumatriptan's serotonergic activity) and may also lead to enhanced extrapyramidal symptoms or neuroleptic malignant syndrome via combined dopaminergic antagonism. Clinical outcomes may include hyperthermia, rigidity, altered mental status, and autonomic instability."
"The combination of sumatriptan (a 5-HT1B/1D receptor agonist) and paroxetine (a selective serotonin reuptake inhibitor) increases the risk of serotonin syndrome, a potentially life-threatening condition characterized by neuromuscular excitation, autonomic instability, and altered mental status. This interaction is due to additive serotonergic effects, as both drugs enhance serotonin activity in the central nervous system. Clinical outcomes range from mild symptoms (tremor, hyperreflexia, diaphoresis) to severe manifestations (hyperthermia, rigidity, seizures) and require immediate medical attention."
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about SUMATRIPTAN vs ACTIQ, answered by our medical review team.
SUMATRIPTAN is a 5-HT1 Agonist that works by Selective 5-HT1B/1D receptor agonist; causes vasoconstriction of cranial arteries and inhibits trigeminal nerve transmission.. ACTIQ is a Opioid Analgesic that works by Opioid agonist; binds to mu-opioid receptors in the CNS, altering pain perception and response.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between SUMATRIPTAN and ACTIQ depend on the specific clinical indication. These are agents from distinct pharmacological classes and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of SUMATRIPTAN is: Sumatriptan is available as oral tablets (25 mg, 50 mg, 100 mg), subcutaneous injection (6 mg/0.5 m L), and nasal spray (5 mg, 20 mg). For acute migraine: oral: 50-100 mg at onset, may repeat after 2 hours (max 200 mg/day). Subcutaneous: 6 mg at onset, may repeat after 1 hour (max 12 mg/24h). Nasal spray: 20 mg in one nostril at onset, may repeat after 2 hours (max 40 mg/day).. The standard adult dose of ACTIQ is: 200 mcg transmucosally, titrated upward as needed; initial dose for opioid-tolerant patients is 200 mcg, with additional doses possible after 15 minutes if needed. Maximum 4 doses per episode. At least 4 hours between episodes.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
No direct drug-drug interaction has been formally documented between SUMATRIPTAN and ACTIQ in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.
The maternal-fetal safety profiles differ. SUMATRIPTAN is classified as Category D/X. FDA Pregnancy Category C. In first trimester, no increased risk of major congenital malformations from available data; however, animal studies show embryo lethality and increased m. ACTIQ is classified as Category C. FDA Pregnancy Category C. First trimester: limited human data; animal studies show increased resorptions and fetal growth restriction. Second/third trimester: chronic use may cause. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.