Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
PROTOPIC 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, a calcineurin inhibitor, binds to FKBP-12 and inhibits calcineurin, thereby blocking dephosphorylation and nuclear translocation of NFAT, reducing transcription of pro-inflammatory cytokines (e.g., IL-2, IFN-γ) in T-cells.
Opioid agonist; binds to mu-opioid receptors in the CNS, altering pain perception and response.
Moderate to severe atopic dermatitis in non-immunocompromised patients where conventional therapy is inadvisable or ineffective,Prophylaxis of organ rejection in kidney or liver transplantation (systemic use, not topical),Off-label: Treatment of vitiligo, psoriasis, eczema of the face and neck (short-term)
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
Apply a thin layer of 0.03% or 0.1% ointment to affected areas twice daily. Discontinue when lesions resolve. For adults, use 0.03% or 0.1%; 0.1% is not indicated for children.
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 half-life ranges from 6–20 hours in pediatric atopic dermatitis patients; prolonged in hepatic impairment (mean 8–35 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 CYP3A4; also metabolized by CYP3A5. Topical absorption results in minimal systemic exposure, but systemic metabolism follows oral route.
Primarily hepatic via CYP3A4 to inactive metabolites (norfentanyl, despropionylfentanyl, hydroxyfentanyl) and other metabolites; <7% excreted unchanged in urine.
Primarily fecal (biliary) elimination of metabolites; <1% of parent drug excreted unchanged in urine.
Primarily renal as metabolites (about 75% as metabolites, <10% unchanged). Fecal excretion accounts for <9%. Biliary excretion is minor.
99% bound primarily to albumin and alpha-1-acid glycoprotein.
Fentanyl is 80–85% bound to plasma proteins (primarily albumin and α1-acid glycoprotein).
Vd/F ~ 30–50 L/kg after oral administration, indicating extensive tissue distribution; topical absorption negligible.
Approximately 4 L/kg (range 3–6 L/kg); large Vd indicates extensive tissue distribution and redistribution contributing to short duration.
Systemic bioavailability after topical application is <0.5% in adults with intact skin; increases in compromised skin barrier.
Oral transmucosal: 50% (range 47–54%) relative to IV; variable and enhanced by rapid absorption through buccal mucosa.
No dose adjustment required. Tacrolimus is not significantly renally excreted and systemic absorption is minimal.
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 specific dose adjustment for Child-Pugh class A or B. For severe hepatic impairment (Child-Pugh C), use with caution; consider starting at lower concentration (0.03%) due to potential increased systemic exposure.
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.
Children (2-15 years): Apply 0.03% ointment twice daily. Do not use 0.1% in this age group. For children 2 years and older.
Not approved for pediatric use; safety and efficacy not established in patients under 16 years.
No specific dose adjustment required. Use minimum effective amount; monitor for cutaneous infections.
Initiate at 100 mcg transmucosally; titrate slowly due to increased sensitivity and risk of respiratory depression. Monitor for adverse effects.
Long-term safety of topical calcineurin inhibitors has not been established. Although a causal relationship has not been established, rare cases of malignancy (e.g., lymphoma, skin cancer) have been reported in patients treated with topical calcineurin inhibitors. Therefore, continuous long-term use should be avoided, and application should be limited to areas of involvement.
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 infections (including herpes simplex, eczema herpeticum); avoid use on malignant or premalignant skin conditions; use with caution in patients with netherton syndrome; may cause photosensitivity; avoid concurrent UV exposure; monitor for lymphadenopathy; not for use in children <2 years (safety not established).
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; use in patients with known or suspected malignancy at the application site; use in immunocompromised patients (relative).
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 known food interactions with topical PROTOPIC. However, if absorbed systemically (rare), grapefruit juice may increase tacrolimus levels; avoid excessive consumption of grapefruit juice while using PROTOPIC.
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.
Pregnancy Category C. Animal studies have shown embryotoxicity and teratogenicity at systemic exposures below human therapeutic levels. No adequate human studies in pregnant women. Risk cannot be ruled out; use only if potential benefit justifies potential risk to fetus. First trimester: avoid if possible. Second and third trimesters: limited data; systemic absorption minimal with topical use, but theoretical risk remains.
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.
Not known if tacrolimus is excreted in human milk after topical administration. Systemic absorption is minimal (<0.5%), but caution is advised due to potential for infant immunosuppression. M/P ratio: not available. Consider benefit of breast-feeding vs risk of infant 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 recommended for topical use due to minimal systemic absorption. However, limit application to smallest area and shortest duration needed. Avoid use on large areas, broken skin, or under occlusion to reduce systemic exposure.
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.
PROTOPIC (tacrolimus) is a topical calcineurin inhibitor used for atopic dermatitis. It is steroid-sparing, thus avoiding skin atrophy and tachyphylaxis. Apply as a thin layer to affected areas. Avoid occlusive dressings. Can be used on face, neck, and intertriginous areas where topical steroids are riskier. Monitor for burning/stinging upon application, which often improves with continued use. Warn patients about rare risk of lymphoma and skin malignancy; use only as second-line therapy for short-term and intermittent treatment. Do not use in immunocompromised patients or those with active skin infections.
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.
Apply PROTOPIC exactly as prescribed; do not use more than directed.,Wash hands after application unless treating hands.,Do not cover treated area with bandages or dressings unless instructed.,Expect mild burning or stinging especially in the first few days; this usually resolves with continued use.,Avoid sun exposure and use sunscreen; protect treated areas from natural and artificial sunlight.,Do not use on infected skin; tell your doctor if you have an infection.,PROTOPIC is for external use only; do not get in eyes, mouth, or nose.,Inform your doctor if you are pregnant, planning to become pregnant, or breastfeeding.,Store at room temperature away from moisture and heat.,Report any signs of skin infection, rash, or swollen lymph nodes to your doctor 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.
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 PROTOPIC vs ACTIQ, answered by our medical review team.
PROTOPIC is a Topical Calcineurin Inhibitor that works by Tacrolimus, a calcineurin inhibitor, binds to FKBP-12 and inhibits calcineurin, thereby blocking dephosphorylation and nuclear translocation of NFAT, reducing transcription of pro-inflammatory cytokines (e.g., IL-2, IFN-γ) in T-cells.. 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 PROTOPIC 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 PROTOPIC is: Apply a thin layer of 0.03% or 0.1% ointment to affected areas twice daily. Discontinue when lesions resolve. For adults, use 0.03% or 0.1%; 0.1% is not indicated for children.. 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 PROTOPIC 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. PROTOPIC is classified as Category C. Pregnancy Category C. Animal studies have shown embryotoxicity and teratogenicity at systemic exposures below human therapeutic levels. No adequate human studies in pregnant women.. 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.