Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
ACTIQ vs UPTRAVI
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Opioid agonist; binds to mu-opioid receptors in the CNS, altering pain perception and response.
Uptravi (selexipag) is a prostacyclin receptor (IP receptor) agonist. Selexipag and its active metabolite, ACT-333679, selectively bind to the IP receptor, leading to vasodilation, inhibition of platelet aggregation, and antiproliferative effects on smooth muscle cells.
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
Treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression and reduce the risk of hospitalization,Off-label: None established
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.
Initial dose 200 mcg orally twice daily, titrated in increments of 200 mcg twice daily at weekly intervals to a maximum of 1600 mcg twice daily.
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.
Terminal elimination half-life is approximately 7–9 hours in healthy subjects, but prolonged in patients with hepatic impairment (Child-Pugh class A: ~11 hours; class B: ~16 hours). Steady-state is reached within 2–4 days of twice-daily dosing.
Primarily hepatic via CYP3A4 to inactive metabolites (norfentanyl, despropionylfentanyl, hydroxyfentanyl) and other metabolites; <7% excreted unchanged in urine.
Selexipag is hydrolyzed by carboxylesterases (mainly CES1 and CES2) to its active metabolite, ACT-333679. Both are further metabolized by CYP3A4 and CYP2C8. ACT-333679 is also a substrate for UGT1A3 and UGT2B7.
Primarily renal as metabolites (about 75% as metabolites, <10% unchanged). Fecal excretion accounts for <9%. Biliary excretion is minor.
Primarily hepatic metabolism; renal excretion of unchanged drug is <1%. Fecal excretion accounts for approximately 70% of total elimination, mainly as metabolites. Biliary excretion contributes to fecal elimination.
Fentanyl is 80–85% bound to plasma proteins (primarily albumin and α1-acid glycoprotein).
99% bound to plasma proteins, primarily to albumin and alpha-1-acid glycoprotein.
Approximately 4 L/kg (range 3–6 L/kg); large Vd indicates extensive tissue distribution and redistribution contributing to short duration.
Approximately 0.3 L/kg in healthy subjects, indicating distribution primarily within the vascular space and well-perfused tissues.
Oral transmucosal: 50% (range 47–54%) relative to IV; variable and enhanced by rapid absorption through buccal mucosa.
Oral bioavailability is approximately 50–60% due to first-pass metabolism. Food does not significantly affect absorption.
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.
No dose adjustment required for mild to moderate renal impairment (e GFR ≥15 m L/min/1.73 m²). Not studied in severe renal impairment (e GFR <15 m L/min/1.73 m²) or on dialysis; use caution.
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.
Mild hepatic impairment (Child-Pugh A): No dose adjustment. Moderate hepatic impairment (Child-Pugh B): Initial dose 200 mcg once daily, titrate cautiously. Severe hepatic impairment (Child-Pugh C): Not recommended.
Not approved for pediatric use; safety and efficacy not established in patients under 16 years.
Not indicated for pediatric patients; safety and efficacy not established in patients <18 years.
Initiate at 100 mcg transmucosally; titrate slowly due to increased sensitivity and risk of respiratory depression. Monitor for adverse effects.
No specific dose adjustment recommended; elderly patients may have increased sensitivity, monitor closely.
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.
None.
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.
Pulmonary edema may occur; consider the possibility of pulmonary veno-occlusive disease (PVOD) if symptoms develop,Hepatic impairment: Avoid use in severe hepatic impairment (Child-Pugh Class C),Concomitant use with strong CYP2C8 inhibitors (e.g., gemfibrozil) increases exposure; reduce dose or consider alternative,Concomitant use with strong CYP3A4 inducers (e.g., rifampin) may reduce efficacy; monitor for loss of effect
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.
Severe hepatic impairment (Child-Pugh Class C),Concomitant use with strong CYP2C8 inhibitors (e.g., gemfibrozil)
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.
Avoid grapefruit juice as it may increase systemic exposure to UPTRAVI. Take with or without food, but consistent timing with meals is recommended to maintain stable drug levels.
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.
In animal studies, UPTRAVI (selexipag) and its active metabolite showed developmental toxicity including reduced fetal weights and increased skeletal variations at maternal toxic doses. No adequate and well-controlled studies in pregnant women. Risk cannot be ruled out. First trimester: potential teratogenicity based on animal data. Second and third trimesters: may cause fetal harm due to pharmacological action (IP receptor agonist) potentially affecting uterine blood flow.
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 data on presence in human milk, effects on breastfed infant, or milk production. M/P ratio is unknown. The active metabolite is potentially excreted in animal milk. Due to potential for serious adverse reactions, breastfeeding is not recommended during treatment and for at least 2 days after final dose.
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.
No pharmacokinetic studies in pregnant women. Pregnancy may alter drug metabolism (e.g., increased clearance, Vd). No specific dose adjustment recommendations; use only if benefit outweighs risk. Close clinical monitoring for efficacy and tolerability.
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.
Titrate to maximum tolerated dose up to 1600 mg twice daily. Monitor for signs of pulmonary edema (PPH with veno-occlusive disease). Co-administration with strong CYP2C8 inhibitors (e.g., gemfibrozil) reduces UPTRAVI clearance; decrease dose by 50% during co-administration. Avoid abrupt discontinuation; taper if possible. May cause orthostatic hypotension; assess blood pressure regularly. UPTRAVI is a prodrug of the active metabolite ACT-333679, a selective prostacyclin receptor (IP receptor) agonist.
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.
Take exactly as prescribed; do not crush or split tablets.,Do not stop taking this medication suddenly; consult your doctor if you need to discontinue.,Avoid grapefruit juice as it may increase drug exposure.,Report any severe headaches, jaw pain, or flushing to your healthcare provider.,Use caution when driving or operating machinery until you know how this medication affects you.,Store at room temperature away from moisture and heat.
No interactions on record
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about ACTIQ vs UPTRAVI, answered by our medical review team.
ACTIQ is a Opioid Analgesic that works by Opioid agonist; binds to mu-opioid receptors in the CNS, altering pain perception and response.. UPTRAVI is a Prostacyclin Receptor Agonist that works by Uptravi (selexipag) is a prostacyclin receptor (IP receptor) agonist. Selexipag and its active metabolite, ACT-333679, selectively bind to the IP receptor, leading to vasodilation, inhibition of platelet aggregation, and antiproliferative effects on smooth muscle cells.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between ACTIQ and UPTRAVI 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 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.. The standard adult dose of UPTRAVI is: Initial dose 200 mcg orally twice daily, titrated in increments of 200 mcg twice daily at weekly intervals to a maximum of 1600 mcg twice daily.. 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 ACTIQ and UPTRAVI 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. 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. UPTRAVI is classified as Category C. In animal studies, UPTRAVI (selexipag) and its active metabolite showed developmental toxicity including reduced fetal weights and increased skeletal variations at maternal toxic d. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.