Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
TACROLIMUS vs ACTIQ
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Tacrolimus is a calcineurin inhibitor. It binds to FK506-binding protein 12 (FKBP12), forming a complex that inhibits calcineurin phosphatase activity. This prevents dephosphorylation and nuclear translocation of nuclear factor of activated T-cells (NFAT), thereby inhibiting transcription of interleukin-2 (IL-2) and other cytokines, leading to suppressed T-cell activation and proliferation.
Opioid agonist; binds to mu-opioid receptors in the CNS, altering pain perception and response.
Prophylaxis of organ rejection in patients receiving allogeneic liver, kidney, or heart transplants,Treatment of rejection in liver, kidney, and heart transplants,Off-label: Treatment of moderate to severe atopic dermatitis (topical),Off-label: Graft-versus-host disease (GVHD) prophylaxis and treatment
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
0.1-0.2 mg/kg/day orally in two divided doses (immediate-release); 0.05-0.15 mg/kg/day orally once daily (extended-release); 0.01-0.05 mg/kg/day continuous IV infusion.
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.
Terminal elimination half-life is approximately 8.7-21.7 hours in healthy volunteers and 18-41 hours in liver transplant recipients. Prolonged half-life in hepatic impairment requires dose adjustments.
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 metabolized by cytochrome P450 3A4 (CYP3A4) and to a lesser extent by CYP3A5 in the liver and intestinal wall. It is a substrate of P-glycoprotein (ABCB1).
Primarily hepatic via CYP3A4 to inactive metabolites (norfentanyl, despropionylfentanyl, hydroxyfentanyl) and other metabolites; <7% excreted unchanged in urine.
Primarily fecal (approximately 93%), with renal excretion accounting for about 2.4% of the unchanged drug. Biliary excretion is a minor route for metabolites.
Primarily renal as metabolites (about 75% as metabolites, <10% unchanged). Fecal excretion accounts for <9%. Biliary excretion is minor.
Approximately 99% bound, primarily to albumin and alpha-1-acid glycoprotein.
Fentanyl is 80–85% bound to plasma proteins (primarily albumin and α1-acid glycoprotein).
Approximately 0.85-1.5 L/kg, reflecting extensive tissue distribution and binding to lymphocytes.
Approximately 4 L/kg (range 3–6 L/kg); large Vd indicates extensive tissue distribution and redistribution contributing to short duration.
Oral: about 17-25% (variable due to first-pass metabolism and food effects); topical: minimal systemic absorption (less than 5% in healthy skin).
Oral transmucosal: 50% (range 47–54%) relative to IV; variable and enhanced by rapid absorption through buccal mucosa.
No standard dose adjustment for renal impairment; monitor renal function closely and reduce dose if nephrotoxicity occurs. For GFR < 30 m L/min, consider dose reduction by 50% and close monitoring.
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; Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: reduce dose by 75%; monitor trough levels.
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.
0.15-0.3 mg/kg/day orally in two divided doses (immediate-release); 0.03-0.1 mg/kg/day continuous IV infusion; titrate to target trough levels.
Not approved for pediatric use; safety and efficacy not established in patients under 16 years.
Start at lower end of dosing range (0.05-0.1 mg/kg/day orally); monitor renal function and trough levels closely due to age-related decline in renal function.
Initiate at 100 mcg transmucosally; titrate slowly due to increased sensitivity and risk of respiratory depression. Monitor for adverse effects.
Increased susceptibility to infection and the possible development of lymphoma. Only physicians experienced in immunosuppressive therapy and management of transplant patients should prescribe tacrolimus. Patients receiving tacrolimus should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources.
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.
Increased risk of lymphomas and other malignancies, particularly skin cancer,Increased susceptibility to infections, including opportunistic infections and reactivation of latent viruses (e.g., BK virus, CMV, EBV),Nephrotoxicity: acute and chronic renal impairment, monitor renal function closely,Neurotoxicity: tremors, headache, seizures, posterior reversible encephalopathy syndrome (PRES),Hyperkalemia: monitor serum potassium levels,Hypertension: monitor blood pressure and manage accordingly,Post-transplant diabetes mellitus: monitor blood glucose levels,Anaphylactic reactions: risk with intravenous formulation due to castor oil derivative (polyoxyl 60 hydrogenated castor oil) in some formulations,QT prolongation: caution in patients with risk factors or with drugs that prolong QT interval
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.
Hypersensitivity to tacrolimus or any component of the formulation,Hypersensitivity to hydrogenated castor oil (present in some intravenous formulations)
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.
Grapefruit and grapefruit juice increase tacrolimus levels by inhibiting CYP3A4 and must be avoided. High-fat meals decrease absorption; consistent timing relative to meals recommended.
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.
First trimester: Increased risk of congenital malformations including cardiac anomalies. Second and third trimesters: Risk of fetal growth restriction, preterm delivery, and neonatal hyperkalemia. Tacrolimus crosses the placenta.
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.
Tacrolimus is excreted into breast milk. M/P ratio (concentration in milk:plasma) is approximately 0.3-0.9. It is recommended to use with caution; monitor infant for immunosuppression and tacrolimus trough levels.
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.
Increased dose requirements due to increased volume of distribution and clearance. Monitoring tacrolimus trough levels recommended every 1-2 weeks; dose adjustments to maintain therapeutic range (typically 5-15 ng/m L).
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.
Monitor trough levels 2-3 days after dose changes; target 5-15 ng/m L for most indications. Use with caution in renal impairment due to nephrotoxicity. Strong CYP3A4 interaction potential; avoid grapefruit and adjust azole antifungals. Hypomagnesemia common; supplement as needed.
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 consistently with or without food, but do not switch between.,Avoid grapefruit and grapefruit juice.,Report signs of infection, tremors, or kidney issues (swelling, decreased urine).,Do not take any new medications without consulting your doctor.,Use sun protection due to increased skin cancer risk.,Do not miss doses; if you do, take as soon as remembered unless near next dose.
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.
"Tacrolimus, a potent CYP3A4 inhibitor, significantly decreases the metabolism of citalopram, a CYP3A4 substrate, leading to elevated citalopram plasma concentrations. This pharmacokinetic interaction increases the risk of dose-dependent adverse effects such as QT prolongation, serotonin syndrome, and central nervous system toxicity. Clinical outcomes may include corrected QT (QTc) interval prolongation, increasing the risk of torsade de pointes, and enhanced serotonergic effects requiring careful monitoring."
"Tacrolimus, a calcineurin inhibitor, primarily induces nephrotoxicity through afferent arteriolar vasoconstriction and direct tubular injury. Etofenamate, a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX) enzymes, reduces prostaglandin synthesis, leading to decreased renal blood flow and glomerular filtration rate. Concomitant use synergistically impairs renal function, increasing the risk of acute kidney injury, hyperkalemia, and hypertension, particularly in patients with preexisting renal impairment or volume depletion."
"Tacrolimus, a calcineurin inhibitor and CYP3A4 substrate, may inhibit the metabolism of isoflurophate, a long-acting cholinesterase inhibitor used in glaucoma. This interaction can lead to increased systemic exposure of isoflurophate, potentially exacerbating cholinergic side effects such as bradycardia, hypersalivation, and bronchospasm. Clinically, patients may experience enhanced toxicity, including prolonged muscle weakness or respiratory depression, especially in those with compromised hepatic function."
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about TACROLIMUS vs ACTIQ, answered by our medical review team.
TACROLIMUS is a Calcineurin Inhibitor that works by Tacrolimus is a calcineurin inhibitor. It binds to FK506-binding protein 12 (FKBP12), forming a complex that inhibits calcineurin phosphatase activity. This prevents dephosphorylation and nuclear translocation of nuclear factor of activated T-cells (NFAT), thereby inhibiting transcription of interleukin-2 (IL-2) and other cytokines, leading to suppressed T-cell activation and proliferation.. 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 TACROLIMUS 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 TACROLIMUS is: 0.1-0.2 mg/kg/day orally in two divided doses (immediate-release); 0.05-0.15 mg/kg/day orally once daily (extended-release); 0.01-0.05 mg/kg/day continuous IV infusion.. 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 TACROLIMUS 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. TACROLIMUS is classified as Category D/X. First trimester: Increased risk of congenital malformations including cardiac anomalies. Second and third trimesters: Risk of fetal growth restriction, preterm delivery, and neonat. 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.