Acitretin

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Mechanism of action

  • Modulation of epidermal proliferation.
  • Induction of orthokeratosis.
  • Comedolysis.
  • Inhibition of inflammation.
  • Inhibition of sebum secretion.
  • Anticarcinogenic effects.

Indications

  • Severe psoriasis that cannot be managed by topical treatments or photo(chemo)therapy
  • Monotherapy is indicated for erythrodermic or pustular psoriasis.
  • Combination therapy is indicated for chronic plaque psoriasis .
  • Lichen planus : 30 mg/day for 8 weeks.
  • Morphea.
  • Macular or lichen amyloidosis : 0.5 mg/kg/day.
  • Lipoid proteinosis : 0.5 mg/kg/day for 6 months.
  • Collodion baby.
  • Harlequin ichthyosis : 1 mg/kg/day.
  • Erythrokeratoderma.
  • Keratoderma.
  • Ichthyoses : 1 mg/kg /day.
  • Lupus erythematosus  : 50 mg daily + hydroxychloroquine 400 mg daily for 8 weeks.
  • Darier disease : 10-25 mg /day.
  •  Nail psoriasis: 0.2–0.3 mg/kg/day.
  • Perforating diseases.
  • Chronic hand eczema.
  • Chemoprevention of skin cancer : 0.2–0.4 mg/kg/day.

Dosage

  • Start with 10 mg/day increase up to 25–50 mg/day.

Monitoring

Baseline

  • History to exclude contraindications.
  • Pregnancy test (when indicated).
  • Complete blood count.
  • Liver function tests (AST, ALT, GGT, alkaline phosphatase, bilirubin).
  • Fasting Serum triglycerides, cholesterol.
  • Fasting glucose.
  • Serum creatinine.
  • Consider spinal X-ray (often initially performed during the first 3 months of therapy if long-term treatment is anticipated).

Follow up

  • Monitor mucocutaneous side effects.
  • liver function tests and  fasting cholesterol & triglycerides every 4 weeks for the first 2 months of then every 3 -6 months.
  • Serum creatinine (elderly patients or patients with mild to moderate renal dysfunction).
  • Monitor for development of hyperostosis by history (twice yearly) and by X-ray of spine (e.g. once yearly or every other year in patients receiving  long-term treatment).

Side effects

  • Teratogenic.
  • Cheilitis, dryness of the oral and nasal mucosa,  xerosis, pruritus and skin fragility.
  • Delayed wound healing.
  • Formation of excessive granulation tissue
  • Hypertriglyceridemia
  • Hyperostosis ( Long-term treatment ).
  • Myalgias, Arthralgia.
  • Back pain.
  • Vulvovaginitis.
  • Paronychia.
  • Increased insulin sensitivity.
  • Elevation of serum creatine kinase levels.
  • Eyes : Blepharitis, conjunctivitis, xerophthalmia, night blindness.
  • Liver: occasionally elevated transaminases.

Drug interactions

  • Tetracycline, doxycycline, minocycline : may increase intracranial pressure (Pseudotumor cerebri).
  • Alcohol : increased conversion of acitretin to etretinate and hepatotoxicity.
  • Methotrexate : synergistic liver toxicity with retinoids; however, combination may be used with caution in patients with PRP or severe psoriasis.
  •  vitamin A supplements : risk of hypervitaminosis A.
  • Retinoid drug levels and resultant potential for toxicity may increase with CYP3A4 inhibitors such as azoles and macrolides.
  • Antituberculosis drugs (rifampin) and anticonvulsants (phenytoin and carbamazepine) may decrease the drug levels of retinoids via CYP3A4  induction.
  • Retinoids may also increase the drug levels of cyclosporine.
  • Progesterone pills (minipill) preparations : Acitretin decreases the antiovulatory effect of the progestin only pill (mini-pill) but has no effect on the combined preparations.
  • Antidiabetic agents : Alterations in blood glucose may occur
  • Corticosteroids : Hyperlipidemia, pseudotumor cerebri.

Pregnancy and lactation

  • Category X.
  • Mothers receiving acitretin should not breast-feed.

Precautions

  • When acitretin is added to UV, light dose should be reduced by 30-50%.
  • In children on long-term therapy growth charting and annual screening radiography is advisable.
  • Patients should not donate blood during treatment or for at least 6 months after stoppage. 
  • pregnancy should be avoided for the duration of therapy and for 3 years after.

Drug info

  • Its bioavailability is increased by intake with fatty food.
  • Alcohol indirectly increases the conversion of acitretin to etretinate by acting as a catalyst for hepatic enzymes.
  • It can be used for psoriasis associated with human immunodeficiency virus (HIV) infection.


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