Neotigason (Acitretin)

Acitretin is used in the management of severe keratinization disorders, primarily within the psoriasis disease spectrum, and is reserved for patients who have not responded adequately to topical agents.

• Severe psoriasis: decreases hyperproliferation of keratinocytes, leading to reduced plaque thickness and improved skin appearance.
• Psoriatic erythroderma: mitigates extensive erythema and scaling by normalizing epidermal turnover across large body areas.
• Other severe keratinization disorders: restores normal epidermal cell differentiation in rare conditions such as congenital ichthyosis, providing clinical improvement.

• Acitretin binds to nuclear retinoic acid receptors (RARα, RARβ, and RARγ) and retinoid X receptors, forming heterodimers that regulate gene transcription. This interaction modulates keratinocyte differentiation and reduces epidermal proliferation, leading to normalization of skin cell turnover. The altered transcription also influences inflammatory pathways, contributing to its therapeutic effect in psoriasis and related disorders. Additionally, acitretin decreases expression of keratin 16 and other markers of abnormal epidermal growth, further supporting clinical improvement.

Acitretin may cause a range of adverse reactions, varying from mild to serious.

Common Side Effects

• Dry skin: pronounced xerosis leading to scaling and itching, often requiring moisturizers.
• Cheilitis: inflammation, cracking and painful lips that may interfere with oral intake.
• Elevated triglycerides: measurable rise in serum triglyceride levels, sometimes necessitating dietary modification.
• Hair loss: temporary alopecia or diffuse thinning of scalp hair during therapy.
• Headache: mild to moderate cephalic pain that may be intermittent.

Serious or Rare Side Effects

• Hepatotoxicity: significant elevation of liver transaminases or clinical hepatitis requiring discontinuation.
• Severe hyperlipidemia: marked increase in total cholesterol and triglycerides, increasing cardiovascular risk.
• Pseudotumor cerebri: intracranial hypertension presenting with headache, visual disturbances and papilledema.
• Bone toxicity: premature epiphyseal closure or growth plate disturbance, particularly in skeletally immature patients.
• Depression or mood changes: emergence of depressive symptoms, anxiety or suicidal ideation during treatment.

When prescribing acitretin, several safety considerations and monitoring requirements should be observed.

• Pregnancy contraindication: teratogenic risk mandates effective contraception for women of childbearing potential.
• Liver function: baseline and periodic liver enzyme testing is recommended.
• Lipid profile: monitor serum cholesterol and triglycerides before and during therapy.
• Skeletal growth: avoid use in children and adolescents due to risk of premature epiphyseal closure.
• Vitamin A excess: assess for signs of hypervitaminosis A, especially with concurrent retinoid use.
• Store at ambient temperature: keep below 25 °C in the original packaging, protect from moisture and light.

Acitretin can interact with several medicines, altering its efficacy or safety profile.

Major Interactions (Avoid)

• Tetracyclines: increased risk of intracranial hypertension when combined.
• Vitamin A supplements: additive toxicity leading to hypervitaminosis A.
• Oral contraceptives: reduced effectiveness, raising teratogenic risk.

Moderate Interactions (Monitor Closely)

• Methotrexate: potential for enhanced hepatotoxicity; liver function should be closely followed.
• Lipid‑lowering agents (e.g., fibrates): may require dose adjustment of acitretin due to lipid changes.
• Antifungal azoles (e.g., ketoconazole): can increase acitretin plasma levels.