TEGISON
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TEGISON (TEGISON).
Retinoid that binds to nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs), modulating gene transcription involved in cell differentiation, proliferation, and apoptosis. It reduces epidermal proliferation and promotes normal keratinization.
| Metabolism | Metabolized in the liver via isomerization and glucuronidation; undergoes enterohepatic circulation. Active metabolite: all-trans-retinoic acid and other isomers. Main enzyme: CYP2C8, CYP3A4. |
| Excretion | Primarily renal (60-80% as metabolites) and biliary/fecal (15-25% as unchanged drug and metabolites). |
| Half-life | Terminal elimination half-life is approximately 120-168 hours (5-7 days) due to extensive tissue storage; clinical effects persist for weeks after discontinuation. |
| Protein binding | ≥ 99.9% bound to albumin and lipoproteins. |
| Volume of Distribution | Approximately 1.5-2.0 L/kg, indicating extensive tissue distribution, particularly in adipose tissue and liver. |
| Bioavailability | Oral bioavailability is highly variable, approximately 60-70% when taken with food; absorption is enhanced by a high-fat meal. |
| Onset of Action | Peak plasma concentrations reached 3-5 hours after oral administration; clinical improvement in psoriasis typically noted after 2-4 weeks. |
| Duration of Action | Therapeutic effects can persist for 2-3 months after cessation due to slow elimination; adverse effects may resolve more slowly. |
| Molecular Weight | 326.43 |
Initial dose: 0.5-1 mg/kg/day orally, divided twice daily; maintenance dose: 0.3-0.5 mg/kg/day. Maximum dose: 1.5 mg/kg/day.
| Dosage form | CAPSULE |
| Renal impairment | eGFR >60 mL/min: no adjustment. eGFR 30-60: reduce dose by 25%. eGFR <30: use with caution, consider 50% dose reduction. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: contraindicated. |
| Pediatric use | 0.5-1 mg/kg/day orally, divided twice daily; not recommended for children <2 years due to risk of premature epiphyseal closure. |
| Geriatric use | Start at lower end of dosing range (0.5 mg/kg/day); monitor for renal function and adjust accordingly. |
| 1st trimester | Contraindicated due to high risk of major fetal malformations including CNS, cardiovascular, and craniofacial defects. |
| 2nd trimester | Contraindicated; continued risk of fetal harm due to teratogenicity. |
| 3rd trimester | Contraindicated; risk of fetal harm persists; may also cause premature epiphyseal closure. |
Clinical note
Comprehensive clinical and safety monograph for TEGISON (TEGISON).
| Placental transfer | Crosses placenta; documented in human studies with evidence of fetal exposure and teratogenicity. |
| Breastfeeding | Excreted in human milk; potential for serious adverse effects in nursing infant. Use is contraindicated during breastfeeding. |
| Lactation Rating |
■ FDA Black Box Warning
Contraindicated in women of childbearing potential unless they use effective contraception during and 3 years after therapy due to extremely high risk of severe birth defects (teratogenicity).
| Serious Effects |
PregnancyWomen of childbearing potential not using effective contraceptionBreastfeedingHypersensitivity to etretinate or any componentSevere hepatic impairmentHypervitaminosis A
| Precautions | Teratogenicity (must avoid pregnancy), hepatotoxicity (monitor LFTs), hyperlipidemia (monitor lipids), pseudotumor cerebri (risk with tetracyclines), skeletal hyperostosis, pancreatitis, mood changes/depression, photosensitivity, corneal opacities, decreased night vision. |
| Food/Dietary | Take with a full meal or with milk to enhance absorption. Avoid high-dose vitamin A supplements due to additive toxicity. Grapefruit juice may increase drug levels; limit consumption. |
Loading safety data…
| L5 (Contraindicated) |
| Teratogenic Risk | Tegison (etretinate) is a teratogen. Contraindicated in pregnancy. Fetal risk: major congenital malformations (CNS, cardiovascular, craniofacial) with any exposure. First trimester: highest risk; second/third trimester: also risk but less data. Pregnancy Category X. Must avoid pregnancy for at least 3 years after discontinuation due to prolonged elimination. |
| Fetal Monitoring | Pregnancy test (sensitive) before therapy, monthly during treatment, and every 3 months for 3 years after discontinuation. Discuss effective contraception. If pregnancy occurs, immediate discontinuation and referral for counseling. Monitor liver function tests, lipids, and skeletal changes (long bones). |
| Fertility Effects | Etretinate does not appear to impair fertility in males or females based on animal studies and limited human data. However, due to teratogenicity, strict contraception is mandatory. No evidence of persistent infertility. |
| Clinical Pearls | Tegison (etretinate) is a retinoid used for severe psoriasis. It has a very long half-life (up to 120 days) and can accumulate in adipose tissue, leading to prolonged teratogenic risk. Contraindicated in women of childbearing potential unless strict pregnancy prevention measures are followed for at least 3 years after discontinuation. Monitor liver enzymes and lipids regularly due to hepatotoxicity and hyperlipidemia risk. Avoid concurrent use with methotrexate due to increased hepatotoxicity. |
| Patient Advice | Do not become pregnant during treatment or for at least 3 years after stopping; use two effective forms of contraception. · Avoid alcohol consumption while taking this medication. · Report any signs of liver problems (yellowing eyes/skin, dark urine, abdominal pain) or vision changes immediately. · Do not donate blood during therapy or for 3 years after discontinuation. · Take with food to improve absorption and reduce gastrointestinal upset. · Avoid excessive sun exposure and use sunscreen as retinoids increase photosensitivity. |