CLOCORTOLONE PIVALATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CLOCORTOLONE PIVALATE (CLOCORTOLONE PIVALATE).
Clocortolone pivalate is a corticosteroid that exerts anti-inflammatory, antipruritic, and vasoconstrictive actions. It binds to glucocorticoid receptors, modulating gene expression to inhibit phospholipase A2, reduce prostaglandin and leukotriene synthesis, and suppress cytokine release.
| Metabolism | Clocortolone pivalate is primarily metabolized in the skin; systemic metabolism is minimal after topical application. Specific enzymes have not been well characterized. |
| Excretion | Primarily renal (approximately 80%) as glucuronide and sulfate conjugates; minor biliary/fecal excretion (20%). |
| Half-life | Terminal elimination half-life is approximately 2.5 hours (range 1-4 hours), reflecting rapid clearance; clinical duration exceeds half-life due to tissue binding. |
| Protein binding | Approximately 90-95% bound to albumin and corticosteroid-binding globulin (CBG). |
| Volume of Distribution | Apparent volume of distribution is approximately 0.3-0.5 L/kg, suggesting distribution primarily into extracellular fluid and tissues. |
| Bioavailability | Topical: Systemic bioavailability is extremely low (<1%) when applied to intact skin; increased with damaged skin or occlusion. |
| Onset of Action | Topical: Onset of anti-inflammatory effect within hours of application, with maximal effect observed after 24-48 hours of regular use. |
| Duration of Action | Duration of anti-inflammatory effect after single topical dose is 12-24 hours; clinical recommendations typically advise twice-daily application to maintain effect. |
| Molecular Weight | 479 |
Topical: Apply a thin film to affected area once or twice daily. Not for ophthalmic use. Maximum duration of 2 weeks per course.
| Dosage form | CREAM |
| Renal impairment | No adjustment required for topical use due to negligible systemic absorption. |
| Liver impairment | No adjustment required for topical use due to negligible systemic absorption. |
| Pediatric use | Children ≥ 3 months: Apply a thin film to affected area once or twice daily for no more than 7 days. Use lowest potency and smallest amount possible. Not recommended for diaper dermatitis or under occlusive dressings in children. |
| Geriatric use | Use with caution due to increased risk of skin atrophy and systemic absorption from thinner skin. Apply lowest effective amount, avoid prolonged use, and monitor for adverse effects. |
| 1st trimester | Limited human data; avoid use unless benefit outweighs risk. Animal studies show teratogenicity at high doses. |
| 2nd trimester | Use only if clearly needed; consider less teratogenic alternatives. Risk of fetal growth restriction with prolonged use. |
| 3rd trimester | Prolonged use may cause adrenal suppression in neonate; avoid near term unless essential. |
Clinical note
Comprehensive clinical and safety monograph for CLOCORTOLONE PIVALATE (CLOCORTOLONE PIVALATE).
| Placental transfer | Crosses placenta; extensive metabolism by placental 11β-HSD2 reduces fetal exposure to active drug. |
| Breastfeeding | Excreted in breast milk in small amounts; unlikely to cause adverse effects in infant at low doses. Monitor infant for growth and adrenal suppression if high maternal doses are used. |
■ FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
Hypersensitivity to clocortolone pivalate or any componentUntreated systemic infectionsFungal infections of the skinViral infections of the skin (e.g., herpes simplex, varicella)
| Precautions | Topical corticosteroids may cause reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing's syndrome, hyperglycemia, and glucosuria., Systemic absorption is increased with prolonged use, use over large body surface areas, use under occlusion, or use in children., Children may be more susceptible to systemic toxicity due to higher skin surface-to-body mass ratio., Local adverse reactions include skin atrophy, striae, telangiectasias, burning, itching, irritation, dryness, folliculitis, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, and miliaria. |
| Food/Dietary | No clinically significant food interactions. Avoid excessive alcohol intake if using on large body surface areas due to potential additive corticosteroid effects (theoretical). |
Loading safety data…
| Lactation Rating |
| L2 (Limited data - probably compatible) |
| Teratogenic Risk | Category C: No adequate human studies; animal studies show fetal abnormalities at high doses. Risk cannot be ruled out. First trimester: Avoid unless benefit outweighs risk. Corticosteroids may increase risk of cleft palate (2-3 per 1000). Second/third trimester: Use only if clearly needed; may cause fetal adrenal suppression. |
| Fetal Monitoring | Monitor maternal adrenal function during prolonged use. Fetal growth and amniotic fluid volume if used systemically. Neonatal adrenal suppression if used near term. |
| Fertility Effects | No specific human data. In animal studies, high doses may impair fertility. Unlikely to affect fertility with topical use. |
| Clinical Pearls | Clocortolone pivalate is a topical corticosteroid of moderate potency (class IV). It is primarily used for steroid-responsive dermatoses. Avoid prolonged use, especially on face, intertriginous areas, or under occlusion due to increased risk of systemic absorption and local atrophy. In children, use the lowest effective dose and shortest duration to minimize HPA axis suppression. Do not use for diaper dermatitis or with occlusive dressings unless directed. |
| Patient Advice | Apply a thin layer to affected skin only, usually once or twice daily as directed. · Do not use on face, groin, or armpits unless specifically instructed by your doctor. · Avoid bandaging or covering the treated area unless told to do so. · Wash hands after application unless treating hands. · Do not use for longer than prescribed; prolonged use can cause skin thinning and other side effects. · Stop use and contact doctor if irritation, severe burning, or signs of infection develop. · Keep away from eyes, mouth, and open wounds. |