Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
LEVORPHANOL TARTRATE vs ACTIQ
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Levorphanol is a potent opioid analgesic that acts as a mu-opioid receptor agonist. It also has NMDA receptor antagonist activity, inhibits norepinephrine and serotonin reuptake, and acts as a sigma receptor agonist, contributing to its analgesic effects and reduced tolerance development.
Opioid agonist; binds to mu-opioid receptors in the CNS, altering pain perception and response.
Management of moderate to severe pain where opioid treatment is appropriate,Off-label: treatment-refractory neuropathic pain, chronic pain syndromes
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
2 mg orally every 6-8 hours as needed for pain; for opioid-tolerant patients, doses up to 4 mg orally every 6-8 hours may be used. Parenterally: 1-2 mg subcutaneously or intramuscularly every 6-8 hours; may be given intravenously at 0.5-1 mg every 6-8 hours.
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.
11-16 hours; extended in hepatic impairment (up to 30 hours).
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 hepatic via glucuronidation and N-demethylation; CYP450 involvement not fully characterized.
Primarily hepatic via CYP3A4 to inactive metabolites (norfentanyl, despropionylfentanyl, hydroxyfentanyl) and other metabolites; <7% excreted unchanged in urine.
Renal: approximately 30% as unchanged drug and 50% as glucuronide conjugates; fecal: 20% via biliary excretion.
Primarily renal as metabolites (about 75% as metabolites, <10% unchanged). Fecal excretion accounts for <9%. Biliary excretion is minor.
Approximately 50% bound to albumin.
Fentanyl is 80–85% bound to plasma proteins (primarily albumin and α1-acid glycoprotein).
10-15 L/kg; 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: 50-70% (first-pass effect); intravenous: 100%.
Oral transmucosal: 50% (range 47–54%) relative to IV; variable and enhanced by rapid absorption through buccal mucosa.
Cr Cl 10-50 m L/min: Administer 75% of usual dose at extended intervals (e.g., every 12 hours). Cr Cl <10 m L/min: Administer 50% of usual dose at extended intervals (e.g., every 12-24 hours). For patients on dialysis, use with caution and reduce dose; not well-studied.
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.
Child-Pugh Class A: No adjustment needed. Child-Pugh Class B: Reduce dose by 50% and administer at extended intervals (e.g., every 12 hours). Child-Pugh Class C: Avoid use; if necessary, reduce dose by 75% and monitor closely.
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 recommended for use in pediatric patients due to lack of safety and efficacy data; use in children under 18 years is generally avoided. For palliative care in older children, consult specialist.
Not approved for pediatric use; safety and efficacy not established in patients under 16 years.
Start at 50% of the usual adult dose (e.g., 1 mg orally every 6-8 hours) due to increased sensitivity and reduced clearance; titrate carefully with close monitoring for respiratory depression and constipation.
Initiate at 100 mcg transmucosally; titrate slowly due to increased sensitivity and risk of respiratory depression. Monitor for adverse effects.
Risk of addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants.
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.
Respiratory depression: potentially fatal, especially at initiation and dose escalation,Adrenal insufficiency,Severe hypotension,Seizures,Serotonin syndrome,Risks from concomitant CNS depressants,Impaired mental or physical abilities
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.
Significant respiratory depression,Acute or severe bronchial asthma,Known or suspected gastrointestinal obstruction,Concurrent use of MAOIs or within 14 days,Hypersensitivity to levorphanol
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.
Avoid grapefruit juice as it may increase levorphenol levels via CYP3A4 inhibition. High-fat meals may delay absorption but not overall extent. Alcohol must be avoided due to additive CNS depression.
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.
Levorphanol is an opioid agonist; limited data in pregnancy. First trimester: potential for neural tube defects based on animal studies; human risk unclear. Second/third trimesters: risk of fetal opioid dependence, preterm labor, and intrauterine growth restriction. Use only if benefit outweighs risk.
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.
Unknown if levorphanol is excreted in human milk; other opioids are present in breast milk. Consider benefits of breastfeeding vs. risk of infant opioid exposure (respiratory depression, withdrawal). M/P ratio not established.
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.
Pregnancy may alter opioid pharmacokinetics (increased clearance, volume of distribution). Dose adjustments may be needed to maintain analgesic efficacy; consider lower starting doses and titrate to effect. Avoid use during first and third trimesters; taper to avoid withdrawal if discontinuing. No specific dose adjustment guidelines are established; individualize based on response and risk.
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.
Levorphanol is a potent mu-opioid agonist with a long half-life (12-16 hours) and active metabolites; avoid use in opioid-naive patients due to risk of respiratory depression. It has NMDA antagonist activity, which may provide benefit in neuropathic pain but also contributes to psychotomimetic effects. Equianalgesic dose: 2 mg oral levorphenol ≈ 10 mg morphine. Accumulation occurs with repeated dosing; monitor for sedation and respiratory depression.
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 exactly as prescribed; do not increase dose or frequency without consulting your doctor.,Avoid alcohol and other CNS depressants (e.g., benzodiazepines, sedatives) as they increase risk of severe drowsiness and breathing problems.,Do not drive or operate heavy machinery until you know how levorphenol affects you.,Do not stop abruptly; withdrawal symptoms may occur. Taper under medical supervision.,Constipation is common; increase fluid and fiber intake, and consider stool softeners.,Store securely out of reach of others, as misuse can cause overdose and death.,Report any difficulty breathing, severe drowsiness, or confusion immediately.
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.
"The combination of Biperiden, an anticholinergic agent used for Parkinsonism, and Levorphanol, a potent opioid analgesic, can lead to additive central nervous system depression and increased anticholinergic side effects. Specifically, both drugs can cause sedation, confusion, and respiratory depression, particularly in elderly patients or those with compromised central nervous system function. Additionally, the anticholinergic effects of Biperiden (e.g., dry mouth, urinary retention, constipation) may be exacerbated by Levorphanol, which also has mild anticholinergic properties, leading to enhanced adverse effects."
"The combination of meprobamate, a carbamate anxiolytic with central nervous system (CNS) depressant properties, and levorphanol, a potent opioid analgesic, results in additive or synergistic CNS depression. This leads to increased risks of profound sedation, respiratory depression, coma, and death. Patients experience compounded impairment of cognitive and motor functions, necessitating cautious use or avoidance."
"Levorphanol, a potent mu-opioid receptor agonist, and Bromazepam, a benzodiazepine acting as a positive allosteric modulator of GABA-A receptors, synergistically depress the central nervous system (CNS), particularly affecting respiratory centers in the brainstem. This combination significantly increases the risk of severe respiratory depression, hypotension, profound sedation, coma, and death. Additive CNS depression can also impair cognitive and motor function, increasing fall risk and accidental injury."
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about LEVORPHANOL TARTRATE vs ACTIQ, answered by our medical review team.
LEVORPHANOL TARTRATE is a Opioid Analgesic that works by Levorphanol is a potent opioid analgesic that acts as a mu-opioid receptor agonist. It also has NMDA receptor antagonist activity, inhibits norepinephrine and serotonin reuptake, and acts as a sigma receptor agonist, contributing to its analgesic effects and reduced tolerance development.. 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 LEVORPHANOL TARTRATE and ACTIQ depend on the specific clinical indication. These are both Opioid Analgesic agents and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of LEVORPHANOL TARTRATE is: 2 mg orally every 6-8 hours as needed for pain; for opioid-tolerant patients, doses up to 4 mg orally every 6-8 hours may be used. Parenterally: 1-2 mg subcutaneously or intramuscularly every 6-8 hours; may be given intravenously at 0.5-1 mg every 6-8 hours.. 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 LEVORPHANOL TARTRATE 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. LEVORPHANOL TARTRATE is classified as Category C. Levorphanol is an opioid agonist; limited data in pregnancy. First trimester: potential for neural tube defects based on animal studies; human risk unclear. Second/third trimesters. 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.