PANRETIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PANRETIN (PANRETIN).

How it works

Alitretinoin is a naturally occurring endogenous retinoid that binds to and activates all known intracellular retinoid receptors (RARα, RARβ, RARγ, RXRα, RXRβ, RXRγ). It modulates cell growth, differentiation, and apoptosis in both normal and malignant cells. In Kaposi sarcoma, it inhibits tumor cell proliferation and induces differentiation.

What the body does with it

Metabolism	Metabolized primarily by CYP2C9, CYP3A4, and CYP2C8 to major metabolites (e.g., 4-oxo-alitretinoin, 9-cis-retinoic acid). Glucuronidation also contributes.
Excretion	Primarily hepatic metabolism; less than 1% excreted unchanged in urine.
Half-life	Mean terminal half-life of approximately 5-10 hours; clinical context: supports twice-daily topical application.
Protein binding	>99% bound to plasma proteins, primarily albumin and lipoproteins.
Volume of Distribution	Not applicable for topical administration; systemic absorption is minimal with no established Vd.
Bioavailability	Systemic bioavailability after topical application is <1% of applied dose.
Onset of Action	Clinical improvement in cutaneous Kaposi sarcoma lesions typically seen within 2-4 weeks of twice-daily topical application.
Duration of Action	Duration of effect is continuous with regular application; response is sustained with continued use.

Classification & Brands

Dosing & administration

Apply 0.1% gel topically to lesions twice daily.

Dosage form	GEL
Renal impairment	No dose adjustment required for renal impairment.
Liver impairment	No dose adjustment recommended for hepatic impairment.
Pediatric use	Not indicated for pediatric patients below 18 years of age.
Geriatric use	No specific dose adjustment; use with caution due to potential for increased skin sensitivity.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PANRETIN (PANRETIN).

Breastfeeding

No data on excretion in human milk. Retinoids are known to be excreted in animal milk. Because of potential for serious adverse reactions in nursing infants (teratogenicity, retinoid toxicity), breastfeeding is contraindicated during therapy and for at least 1 month after last dose.

Teratogenic Risk

PANRETIN (alitretinoin) is a retinoid and is contraindicated in pregnancy. Category X: Animal studies have demonstrated teratogenic effects (craniofacial, cardiovascular, CNS abnormalities). First trimester exposure carries highest risk. Second and third trimester: risk of fetal retinoid syndrome (craniofacial dysmorphism, CNS anomalies, cardiovascular malformations). Effective contraception must be used.

Warnings & precautions

■ FDA Black Box Warning

Not applicable for topical formulation. Oral alitretinoin (not marketed in US) carries a boxed warning for teratogenicity and must not be used during pregnancy.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to alitretinoin or any component of the formulation","Pregnancy (topical: use only if no safer alternative; oral: absolutely contraindicated)"]

Clinical Precautions

Precautions

["Teratogenicity: Avoid use during pregnancy; effective contraception required","Photosensitivity: Avoid excessive sun exposure","Local skin reactions: erythema, edema, peeling at application site","Hyperlipidemia: Monitor lipids in prolonged use","Pancreatitis: Risk in patients with hypertriglyceridemia","Hepatotoxicity: Monitor liver function tests","Pseudotumor cerebri: Discontinue if signs of intracranial hypertension"]

Clinical Tips & Counseling

Drug interactions

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PANRETIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PANRETIN (PANRETIN).

How it works

What the body does with it

Metabolism	Metabolized primarily by CYP2C9, CYP3A4, and CYP2C8 to major metabolites (e.g., 4-oxo-alitretinoin, 9-cis-retinoic acid). Glucuronidation also contributes.
Excretion	Primarily hepatic metabolism; less than 1% excreted unchanged in urine.
Half-life	Mean terminal half-life of approximately 5-10 hours; clinical context: supports twice-daily topical application.
Protein binding	>99% bound to plasma proteins, primarily albumin and lipoproteins.
Volume of Distribution	Not applicable for topical administration; systemic absorption is minimal with no established Vd.
Bioavailability	Systemic bioavailability after topical application is <1% of applied dose.
Onset of Action	Clinical improvement in cutaneous Kaposi sarcoma lesions typically seen within 2-4 weeks of twice-daily topical application.
Duration of Action	Duration of effect is continuous with regular application; response is sustained with continued use.

Classification & Brands

Dosing & administration

Apply 0.1% gel topically to lesions twice daily.

Dosage form	GEL
Renal impairment	No dose adjustment required for renal impairment.
Liver impairment	No dose adjustment recommended for hepatic impairment.
Pediatric use	Not indicated for pediatric patients below 18 years of age.
Geriatric use	No specific dose adjustment; use with caution due to potential for increased skin sensitivity.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PANRETIN (PANRETIN).

Breastfeeding

Teratogenic Risk

Warnings & precautions

■ FDA Black Box Warning

Not applicable for topical formulation. Oral alitretinoin (not marketed in US) carries a boxed warning for teratogenicity and must not be used during pregnancy.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to alitretinoin or any component of the formulation","Pregnancy (topical: use only if no safer alternative; oral: absolutely contraindicated)"]