ENSTILAR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ENSTILAR (ENSTILAR).
ENSTILAR is a combination of calcipotriene (a vitamin D analog) and betamethasone dipropionate (a corticosteroid). Calcipotriene binds to vitamin D receptors, modulating cell proliferation and differentiation. Betamethasone suppresses inflammation by inhibiting phospholipase A2, reducing prostaglandin and leukotriene synthesis.
| Metabolism | Calcipotriene undergoes hepatic metabolism; betamethasone dipropionate is metabolized via CYP3A4. |
| Excretion | Calcipotriol is primarily excreted via bile/feces (approximately 70% of absorbed dose). Betamethasone dipropionate is mainly excreted renally (60-70% as metabolites) and up to 20-30% via feces. For the combination, renal excretion of betamethasone metabolites predominates, with fecal excretion of calcipotriol. |
| Half-life | Calcipotriol: terminal half-life ~12 hours. Betamethasone dipropionate: terminal half-life ~16-22 hours. Clinically, this supports once-daily application. |
| Protein binding | Calcipotriol: ~94% bound to plasma proteins, primarily albumin. Betamethasone dipropionate: ~64% bound, mainly to albumin and corticosteroid-binding globulin. |
| Volume of Distribution | Calcipotriol: Vd ~1.6 L/kg, indicating extensive tissue distribution. Betamethasone dipropionate: Vd ~1.4 L/kg, also widely distributed. |
| Bioavailability | Topical: systemic absorption minimal (<1% for calcipotriol, ~5-7% for betamethasone dipropionate with occlusive use; otherwise <1% each). Oral data not applicable. |
| Onset of Action | Topical: noticeable improvement in plaque psoriasis within 1-2 weeks of daily application. |
| Duration of Action | Clinical effect persists with continued use; rebound may occur upon discontinuation. Once-daily application maintains efficacy. |
| Molecular Weight | 470.6 |
Apply to affected area once daily for up to 4 weeks. Maximum 100 g/day or 30 g/week. Not for use on face, axillae, or groin.
| Dosage form | AEROSOL, FOAM |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment; use with caution. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). Not studied in moderate impairment; avoid use. Caution in mild impairment. |
| Pediatric use | Safety and efficacy not established in patients under 18 years; not recommended. |
| Geriatric use | No specific adjustment; use caution due to higher risk of corticosteroids-related adverse effects (e.g., skin atrophy, HPA axis suppression) and potential for impaired renal function. |
| 1st trimester | Contraindicated due to risk of fetal anomalies (corticosteroid and vitamin D analogue). Avoid use. |
| 2nd trimester | Caution: use only if potential benefit justifies risk; limit to small areas, short duration. Corticosteroids may cause fetal growth restriction. |
| 3rd trimester | Caution: use only if potential benefit justifies risk; prolonged use may cause neonatal adrenal suppression. Avoid near term. |
Clinical note
Comprehensive clinical and safety monograph for ENSTILAR (ENSTILAR).
| Placental transfer | Betamethasone (corticosteroid) crosses placenta; calcipotriol (vitamin D analogue) may cross in limited amounts. Degree: moderate for betamethasone, low for calcipotriol. |
| Breastfeeding | Not recommended during breastfeeding. Excreted in milk; risk of infant adrenal suppression and hypercalcemia. If used, apply to small area, avoid nipple area, and monitor infant for irritability, feeding problems, or weight loss. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to betamethasone, calcipotriol, or excipientsPregnancy (first trimester)Facial, axillary, inguinal, or genital skin lesionsBacterial, fungal, viral, or parasitic skin infectionsSevere renal or hepatic impairmentHypercalcemia or vitamin D toxicity
| Precautions | Hypercalcemia and hypercalciuria due to calcipotriene, Hypothalamic-pituitary-adrenal (HPA) axis suppression from corticosteroid, Local adverse reactions including skin atrophy, striae, and telangiectasias, Photosensitivity reactions, Avoid use on face, groin, or axillae, Not recommended in patients with known or suspected disorders of calcium metabolism |
| Food/Dietary | No clinically significant food interactions. However, patients on calcium or vitamin D supplements should be monitored for hypercalcemia due to calcipotriene absorption, especially with extensive use. |
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| Lactation Rating | L4 - Possibly Hazardous |
| Teratogenic Risk | Enstilar (calcipotriene 0.005% and betamethasone dipropionate 0.064%) is classified as Pregnancy Category C. Topical corticosteroids have shown teratogenic effects in animal studies, but no adequate human studies exist. Calcipotriene is a vitamin D analogue; risks are theoretical due to low systemic absorption. First trimester: limited data, but avoid high doses. Second and third trimesters: minimal risk with topical use, but prolonged high-dose application may lead to fetal growth restriction or adrenal suppression. Systemic absorption is low (<1%) with recommended use. |
| Fetal Monitoring | Monitor for maternal adrenal suppression if used over large areas, under occlusion, or for prolonged periods. Assess fetal growth if used extensively. Evaluate for signs of hypercalcemia (calcipotriene component) if applied to >30% body surface area. No routine fetal monitoring required for standard use. |
| Fertility Effects | No known effects on human fertility. Animal studies with calcipotriene and betamethasone at high doses have not shown impaired fertility. Topical use at recommended doses is unlikely to impact reproductive function. |
| Clinical Pearls | ENSTILAR (calcipotriene 0.005% and betamethasone dipropionate 0.064%) topical foam is approved for plaque psoriasis. Avoid use on face, groin, axillae, or intertriginous areas due to risk of atrophy. Limit treatment to 4 weeks due to potential for adrenal suppression from corticosteroid component. Use only on up to 30% body surface area. Not recommended for patients with known disorders of calcium metabolism due to calcipotriene. |
| Patient Advice | Apply a thin layer once daily to affected areas only, avoiding healthy skin. · Do not use with occlusive dressings or bandages. · Wash hands after application unless treating hands. · Avoid contact with eyes, mouth, and mucous membranes. · Do not use more than 60 grams per week or for longer than 4 weeks without consulting your doctor. · Inform your doctor if you develop skin thinning, striae, or signs of infection. · Store at room temperature, do not refrigerate or freeze. · Keep away from open flame or heat; do not puncture or incinerate aerosol container. |