Acitretine

Generic name
Acitretine
Brand name
ATC Code
D05BB02
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Acitretine

Dosages
Side effects in children
Warnings & precautions in children
Contra-indications in children

Interactions
PK
Renal impairment
References

Pharmacokinetics in children

Pharmacokinetic properties have not been investigated in children.

dose recommendation of formulary compared to licensed use (on-label versus off-label)

No information is present at this moment.

Available formulations

No information is present at this moment.

Dosages

CAVE: PREGNANCY PREVENTION PROGRAMM FOR THIS DRUG
  • Route of administration not applicable
    • 9 years up to 18 years

      • See warnings and precautions section.
Psoriasis, keratinisation disorders
  • Oral
    • 1 month up to 18 years
      • Initial dose (during 2-4 weeks): 0.5 mg/kg/day in 1 dose. Max: 30 mg/day. Maintenance dose: adjust to the lowest effective dosage possible on the basis of the effect and side-effects .
      • Directions for administration:

        Preferably with meals or milk

      • Treatment by or after consultation with a (paediatric) dermatologist experienced in the use of acitretin.
Severe collodion / harlequin ichthyosis in neonates
  • Oral
    • Premature neonates Gestational age < 37 weeks
      • Initial dose: 0.5 mg/kg/day in 1 dose during 2-4 weeks. Maintenance dose: adjust to the lowest effective dosage possible on the basis of the effect and side-effects .
      • Directions for administration:

        Preferably with meals or milk

      • Treatment by or after consultation with a (paediatric) dermatologist experienced in the use of acitretin.

    • Term neonate
      • Initial dose: 0.5 mg/kg/day in 1 dose during 2-4 weeks. Maintenance dose: adjust to the lowest effective dosage possible on the basis of the effect and side-effects .
      • Directions for administration:

        Preferably with meals or milk

      • Treatment by or after consultation with a (paediatric) dermatologist experienced in the use of acitretin.

Renal impaiment in children > 3 months

GFR ≥10 ml/min/1.73m2: Dose adjustment not required.

GFR <10 ml/min/1.73m2: A general recommendation on dose adjustment cannot be provided.

The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects in children

Dry mucous membranes, (worsening of) itching, fragile skin, cheilitis, dry skin, skin irritation and rash. [Lacour 1996][Zhang 2008][DiLernia 2016][Chen 2018][Cave 2020].

The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here

Contra-indications

No information available on specific contra indications in children.

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions in children

Because there have been occasional reports of bone changes in children, including premature epiphyseal closure, skeletal hyperostosis and extraosseous calcification after long-term treatment with etretinate, these effects can be expected with the active metabolite acitretin. Growth parameters and bone development should be closely monitored in children. [SmPC]

Treatment of adolescent females is strongly discouraged due to the teratogenic potency of acitretin. [NVDV] Acitretin is teratogenic and can be converted to the also teratogenic etretinate. Use of acitretin in humans carries a high risk of severe birth defects (craniofacial, central nervous system, cardiovascular, skeletal and thymus) in the child and spontaneous abortion, regardless of the duration of treatment or the dose used.

Monitor liver function and lipids [Cave 2020].

Do not consume alcohol (in drinks, food or medicines) during and for 2 months after discontinuing therapy with acitretin, as it may increase the conversion of acitretin to the (also teratogenic) etretinate.

PREGNANCY PREVENTION PROGRAMM
Advice: Caution! Use is absolutely contraindicated in pregnant women. When treating fertile women, a protocol-based pregnancy prevention programme (ZPP) should be applied. Therefore, effective contraception should be ensured at least 1 month before, during, and for at least 3 years after discontinuation of therapy with acitretin. At least one highly effective contraceptive method (i.e. user-independent method), or two complementary user-dependent contraceptive methods (including a barrier method) should be used, even in women with amenorrhoea. Do not use low-dose progesterone pills ('minipill'), as the contraceptive effect may be insufficient. Exclude pregnancy before treatment begins, monthly during treatment, and every 1-3 months for 3 years after treatment is stopped. Start treatment on the second or third day of the next menstrual cycle. Follow-up consultations should take place every 28 days. During each follow-up consultation, perform a pregnancy test (minimum sensitivity 25 mIU/ml) to exclude pregnancy. Pregnancy test, prescription (maximum 30 days) and delivery should preferably take place on the same day; delivery by pharmacy should take place within 7 days after prescription.  Click here for additional risk minimisation material (INCLUDE LINK TO NATIONAL INFORMATION SOURCE)

Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

ANTIPSORIATICS FOR SYSTEMIC USE

This pages provides a list of drugs from the same ATC class for comparison. This does not necessarily mean that these drugs are interchangeable.

References

  1. Nederlandse Vereniging voor Dermatologie en Venerelogie, Richtlijn Psoriasis , 30-11-2018
  2. Lacour M., et al., An appraisal of acitretin therapy in children with inherited disorders of keratinization, Br J Dermatol, 1996, 134 (6), 1023-9.
  3. Aurobindo Pharma B.V., SmPC Neotigason (RVG 13103 – 13104) 15-02-2021, www.geneesmiddeleninformatiebank.nl
  4. Zhang X. B., et al., Clinical investigation of acitretin in children with severe inherited keratinization disorders in China, J Dermatolog Treat, 2008, 19 (4), 221-8
  5. Di Lernia V., et al., Effectiveness and Safety of Acitretin in Children with Plaque Psoriasis: A Multicenter Retrospective Analysis, Pediatr Dermatol, 2016, 33 (5), 530-5
  6. Ergun T., et al., Efficacy, safety and drug survival of conventional agents in pediatric psoriasis: A multicenter, cohort study., J Dermatol, 2017, 44 (6), 630-4
  7. Chen P., et al., Efficacy and safety of acitretin monotherapy in children with pustular psoriasis: results from 15 cases and a literature review., J Dermatolog Treat, 2018, 29 (4), 353-63
  8. Cave A., et al., The adverse effect profile of acitretin in a pediatric dermatology population-Longitudinal cohort study and recommendations for monitoring., J Am Acad Dermatol, 2020, 83 (6), 1779-81
  9. Saraçoğlu Z. N., et al., Oral acitretin treatment in severe congenital ichthyosis of the neonate., Turk J Pediatr, 2002, 44 (1), 61-4
  10. Harvey H. B., et al., Perinatal management of harlequin ichthyosis: a case report and literature review., J Perinatol, 2010, 30 (1), 66-72
  11. Arjona-Aguilera C., et al., Treatment of Harlequin Ichthyosis With Acitretin., Actas Dermosifiliogr, 2015, 106 (9), 759
  12. Patro N., et al., Congenital ichthyosiform erythroderma: A rare neonatal dermatoses responding to acitretin., Indian J Pharmacol, 2019, 51 (5), 343-345
  13. Kainth D., et al., Successful Treatment of Collodion Baby with Acitretin: A Report of Two Cases, Indian J Pediatr, 2021, 88 (1), 95-6
  14. Singh S., et al., Successful treatment of harlequin ichthyosis with acitretin, Int J Dermatol, 2001, 40 (7), 472-3
  15. Cakmak A., et al., Treatment of congenital ichthyosis with acitretin: a case report., Minerva Pediatr, 2010, 62 (6), 599-603
  16. Loo B. K. G., et al ., Compound heterozygous mutations with novel missense ABCA12 mutation in harlequin ichthyosis., BMJ Case Rep, 2018
  17. Nederlandse Vereniging voor Dermatologie en Venerelogie, Richtlijn Psoriasis, 30-11-2018
  18. Aurobindo Pharma B.V., SmPC Neotigason (RVG 13103 – 13104) 15-02-2021, www.geneesmiddeleninformatiebank.nl

Changes

Therapeutic Drug Monitoring


Overdose