AVAGE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AVAGE (AVAGE).
Avage (tazarotene) is a retinoid prodrug that is converted to its active metabolite, tazarotenic acid, which binds to retinoic acid receptors (RAR-β, RAR-γ) with high affinity and modulates gene expression, leading to reduced keratinocyte proliferation, differentiation, and inflammation.
| Metabolism | Tazarotene is rapidly metabolized via ester hydrolysis to its active metabolite, tazarotenic acid. Tazarotenic acid is further metabolized via oxidation and conjugation (glucuronidation). The enzymes involved include esterases and possibly CYP450 isoforms; specific CYP450 enzymes are not well characterized. |
| Excretion | Primarily renal excretion (70-80% as unchanged drug) with 10-20% biliary/fecal elimination. |
| Half-life | Terminal elimination half-life is approximately 2-4 hours in patients with normal renal function; prolonged to 12-24 hours in severe renal impairment (CrCl <30 mL/min). |
| Protein binding | Approximately 90% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.3-0.5 L/kg, indicating distribution primarily into extracellular fluid. |
| Bioavailability | Oral: 60-70% due to first-pass metabolism; Intravenous: 100%. |
| Onset of Action | Intravenous: 5-10 minutes; Oral: 30-60 minutes. |
| Duration of Action | 4-6 hours for most indications; may be extended in hepatic impairment. |
Applied topically as a cream 0.05% to affected areas once daily at bedtime.
| Dosage form | CREAM |
| Renal impairment | No specific dose adjustment required for renal impairment. |
| Liver impairment | No specific dose adjustment required for hepatic impairment. |
| Pediatric use | Not recommended for use in pediatric patients due to lack of safety and efficacy data. |
| Geriatric use | No specific dose adjustment required; however, use with caution due to potential increased sensitivity and skin fragility in elderly patients. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AVAGE (AVAGE).
| Breastfeeding | Contraindicated in breastfeeding. Excreted into human milk; M/P ratio not established. Risk of serious adverse effects in nursing infant, including keratoderma-like skin changes and potential for growth impairment. |
| Teratogenic Risk | FDA Pregnancy Category X. First trimester: High risk of major congenital malformations including craniofacial defects (cleft lip/palate), cardiovascular abnormalities, and neural tube defects. Second and third trimesters: Risk of fetal growth restriction, oligohydramnios, and premature closure of the ductus arteriosus. Avoid use throughout pregnancy. |
■ FDA Black Box Warning
Avage is contraindicated in women who are or may become pregnant. Tazarotene is a teratogen, and fetal harm can occur when administered to a pregnant woman. If the drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
| Serious Effects |
["Pregnancy (FDA Pregnancy Category X)","Women of childbearing potential unless using effective contraception and have a negative pregnancy test within 2 weeks prior to therapy","Hypersensitivity to tazarotene or any component of the formulation"]
| Precautions | ["Avoid contact with eyes, mouth, and mucous membranes","Not for use on eczematous or sunburned skin","May cause severe local skin reactions (e.g., redness, peeling, burning, stinging)","Photosensitivity: patients should avoid or minimize exposure to sunlight and artificial UV sources","Concomitant use with other photosensitizing agents should be approached with caution"] |
| Food/Dietary | AVAGE should be taken with a meal containing fat (e.g., whole milk, peanut butter) to enhance absorption. Avoid excessive vitamin A supplements as they may add to toxic effects. Grapefruit juice may increase isotretinoin levels; consider avoidance. |
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| Fetal Monitoring |
| Before therapy: Negative pregnancy test (serum beta-hCG) within 1 week of start. Monthly pregnancy tests during treatment. Fetal ultrasound if pregnancy occurs during therapy. Monitor liver function tests and serum lipids monthly. Renal function (creatinine, BUN) every 3 months. |
| Fertility Effects | Reversible impairment of spermatogenesis in males (decreased sperm count, motility, and morphology) reported. In females, may disrupt menstrual cycle (irregular menses, anovulation) due to retinoid effects. Not formally studied for fertility restoration after cessation. |
| Clinical Pearls | AVAGE (isotretinoin) is highly teratogenic; confirm negative pregnancy test within 5 days before starting therapy and monthly thereafter. Monitor triglycerides, liver function, and CBC at baseline and monthly. Avoid blood donation during treatment and for 1 month after discontinuation. Use with caution in patients with depression; monitor for mood changes. Administer with food to increase absorption. |
| Patient Advice | AVAGE can cause severe birth defects; females must use two effective forms of contraception and have monthly pregnancy tests. · Do not donate blood while taking AVAGE and for 1 month after stopping. · Avoid exposure to sunlight or tanning beds; use sunscreen and protective clothing. · Report any signs of depression, mood changes, or thoughts of self-harm immediately. · Take each dose with a full meal to ensure proper absorption. · May cause dry skin, lips, eyes; use moisturizers and artificial tears as needed. · Avoid waxing or laser treatments during therapy and for 6 months after. |