METICORTEN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for METICORTEN (METICORTEN).
Prednisone is a prodrug that is converted to prednisolone, which binds to the glucocorticoid receptor, modulating gene expression and suppressing inflammation, immune response, and adrenal function.
| Metabolism | Prednisone is converted to active prednisolone via 11-beta-hydroxysteroid dehydrogenase; both are metabolized by CYP3A4 and other enzymes. |
| Excretion | Primarily renal: approximately 80% as inactive metabolites (conjugated and oxidized forms) and <5% as unchanged prednisolone. Biliary/fecal excretion accounts for about 10-15% of the dose. |
| Half-life | Following oral or IV administration, the terminal elimination half-life of total prednisolone (active form) is 2.1–3.5 hours in adults with normal hepatic function. In hepatic impairment, half-life may be prolonged (up to 6–8 hours), necessitating dose adjustment. |
| Protein binding | Approximately 90–95% bound to serum proteins, primarily corticosteroid-binding globulin (CBG, transcorrin) and albumin. Binding is saturable; at high doses, the free fraction increases, enhancing tissue penetration. |
| Volume of Distribution | The apparent volume of distribution (Vd) is 0.6–1.0 L/kg, reflecting extensive distribution into tissues and body water compartments. In obesity, Vd may increase due to higher adipose tissue affinity. |
| Bioavailability | Oral bioavailability of prednisone (prodrug) is approximately 80%, with extensive first-pass hepatic conversion to prednisolone (active form). Sublingual and rectal routes have lower and more variable bioavailability (50–70%). |
| Onset of Action | Oral (tablet): Anti-inflammatory and immunosuppressive effects begin within 2–4 hours, with peak clinical response seen within 24–48 hours. IV (if applicable): Onset is more rapid, within 1–2 hours. |
| Duration of Action | The clinical duration of action for a single dose is 18–36 hours, sustained by the prolonged presence of active metabolites. Prednisolone's biological half-life (duration of ACTH suppression) is 18–36 hours, supporting once-daily dosing in chronic conditions. |
| Molecular Weight | 358.43 |
5-60 mg orally once daily, depending on condition; for acute exacerbations, up to 250 mg IV every 4-6 hours.
| Dosage form | TABLET |
| Renal impairment | No adjustment necessary for mild to moderate renal impairment; for severe renal impairment (GFR < 30 mL/min), consider prolonging dosing interval to every 12-24 hours. |
| Liver impairment | For Child-Pugh class A: no adjustment; class B: reduce dose by 50%; class C: reduce dose by 75% or avoid use. |
| Pediatric use | 0.14-2 mg/kg/day orally in divided doses every 6-12 hours, not to exceed 60 mg/day. |
| Geriatric use | Initiate at 5-10 mg/day orally, titrate slowly due to increased risk of osteoporosis, glucose intolerance, and immune suppression. |
| 1st trimester | Corticosteroids including prednisone have been associated with increased risk of cleft palate and intrauterine growth restriction. Use only if clearly needed and benefit outweighs risk. |
| 2nd trimester | May cause fetal adrenal suppression and growth restriction. Monitor fetal growth with serial ultrasound if prolonged therapy. |
| 3rd trimester | Risk of neonatal adrenal suppression if used near term. Withdrawal symptoms possible in newborn. Use lowest effective dose for shortest duration. |
Clinical note
Comprehensive clinical and safety monograph for METICORTEN (METICORTEN).
| Placental transfer | Prednisone is metabolized to prednisolone; about 10-12% of maternal dose crosses the placenta. The placenta expresses 11-beta-hydroxysteroid dehydrogenase type 2 which inactivates prednisolone but some active drug still reaches fetal circulation. |
| Breastfeeding | Prednisone is excreted into breast milk in low concentrations. Doses up to 50 mg/day are considered compatible with breastfeeding; however, monitor infant for potential growth suppression and adrenal suppression. Avoid high-dose or prolonged therapy. Ideally time feeding at least 4 hours after dose. |
■ FDA Black Box Warning
None.
| Serious Effects |
Systemic fungal infectionsHypersensitivity to prednisone or any componentAdministration of live or live-attenuated vaccines
| Precautions | Immunosuppression and increased infection risk; dose-dependent adrenal suppression; osteoporosis with prolonged use; gastrointestinal perforation risk; psychiatric disturbances; masking of infections; Kaposi sarcoma have been reported. |
| Food/Dietary | Avoid excessive grapefruit juice as it may increase prednisone levels. Limit high-sodium and high-sugar foods to minimize fluid retention and hyperglycemia. Increase calcium and vitamin D intake to counteract bone loss. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Increased risk of oral clefts (odds ratio ~1.5-3.0). Second/third trimester: Fetal adrenal suppression, growth restriction, preterm birth. Chronic use: Risk of neonatal adrenal insufficiency. |
| Fetal Monitoring | Maternal: Blood pressure, blood glucose, signs of infection, adrenal suppression. Fetal: Ultrasound for growth restriction, amniotic fluid volume; neonatal monitoring for adrenal insufficiency if used late in pregnancy. |
| Fertility Effects | May suppress hypothalamic-pituitary-adrenal axis; no direct effect on fertility but may alter menstrual cycles. Animal studies show no impaired fertility at therapeutic doses. |
| Clinical Pearls |
| Prednisone (METICORTEN) is a prodrug converted to prednisolone; use with caution in hepatic impairment as conversion may be reduced. Taper doses to avoid adrenal insufficiency. Monitor for hyperglycemia, osteoporosis, and immunosuppression. Do not abruptly discontinue after prolonged use. |
| Patient Advice | Take exactly as prescribed; do not stop suddenly without doctor's guidance. · Take with food or milk to reduce stomach upset. · Report any signs of infection (fever, sore throat) or unusual bruising/bleeding. · Avoid live vaccines while on this medication. · Carry a steroid warning card if on long-term therapy. |