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Continuing Education Activity

Acitretin belongs to a group of drugs known as retinoids. Retinoids include natural and synthetic compounds that have similar activity to vitamin A. Vitamin A helps regulate the immune system, impacts cellular growth, differentiation, proliferation, and plays a role in embryonic development. Other effects of retinoids include immunologic anti-inflammatory effects, induction of apoptosis, and inhibition of tumor promotion. This activity reviews the indications, contraindications, and adverse events associated with acitretin so that interprofessional team members can work together to manage patients using the medication optimally.


  • Identify the indications for acitretin.
  • Describe the adverse effects/toxicity with acitretin use.
  • Outline the monitoring necessary for patients on acitretin therapy.
  • Review interprofessional team strategies for improving care coordination for patients undergoing acitretin therapy to improve patient outcomes.


Acitretin belongs to a group of drugs known as retinoids. Retinoids include natural and synthetic compounds that have similar activity to vitamin A. Vitamin A helps regulate the immune system, impacts cellular growth, differentiation, proliferation, and plays a role in embryonic development. Other effects of retinoids include immunologic anti-inflammatory effects, induction of apoptosis, and inhibition of tumor promotion.[1][2][3]

Vitamin A exists as retinol (vitamin A alcohol), retinal (vitamin A aldehyde), and retinoic acid (RA, vitamin A acid). The body cannot synthesize vitamin A; therefore, one must acquire it in the diet through foods such as eggs and milk. Carotenoids are precursors of vitamin A that are synthesized by plants. In the intestines, beta-carotene is converted to retinal then absorbed. Each molecule of beta-carotene converts into two molecules of retinal. Researchers have observed that animals with vitamin A deficiency have epidermal hyperkeratosis, squamous metaplasia of mucous membranes, and precancerous lesions. 

Currently, three generations of synthetic retinoids exist. First-generation retinoids include tretinoin (all-trans RA), isotretinoin (13-cis-retinoic acid), and alitretinoin (9-cis RA). Second-generation retinoids include etretinate and acitretin. Third-generation retinoids include adapalene, tazarotene, and bexarotene. In 1972, Bolag developed two aromatic retinoids: etretinate and acitretin. Acitretin is the retinoic acid metabolite of etretinate. Acitretin is relatively water-soluble in comparison and has a little deposition in adipose tissue. 

Acitretin is FDA-approved for psoriasis (severe plaque-type psoriasis, pustular psoriasis generalized, pustular psoriasis localized, combination therapy with ultraviolet B (UVB) or psoralen ultraviolet A (PUVA), combination therapy with cyclosporine, combination therapy with biologic therapies. Acitretin is the only systemic retinoid that is FDA-approved for psoriasis and effective as monotherapy. 

Acitretin has been used off-label in dermatology for other uses.  In those with solid organ transplants, acitretin has served as a chemoprevention measure for nonmelanoma skin cancers. Acitretin has also been used for Darier disease, pityriasis rubra pilaris (PRP), and ichthyoses such as lamellar ichthyosis. Additionally, acitretin has use in Grover disease (transient acantholytic dermatosis), lichen planus, and lupus erythematosus.[4]

Mechanism of Action

Retinoids bind cytosolic retinoic acid-binding protein (CRABP) that acts as the intracellular carrier transporting it to the nucleus. In the nucleus, retinoids impact transcription by binding two families of nuclear receptors: retinoic acid receptors (RARs) and retinoid X receptors (RXR). RAR and RXR families contain three receptor subtypes: alpha, beta, and gamma that are encoded by different genes. RAR can bind with RXR forming a heterodimer. RXR can bind with itself, forming a homodimer, or bind with other nuclear receptors such as thyroid hormone receptor, vitamin D3 receptor, and peripheral peroxidase-activated receptor (PPAR). Dimers of RAR/RXR or RXR/RXR bind to DNA regulatory sequences in the promoter region, retinoid acid response elements (RAREs). Once the ligand binds, it undergoes a conformational change to release co-repressors and recruit co-activators. The retinoid-receptor complex may antagonize the action of other transcription factors, thus working indirectly. Acitretin competes with RA for CRABP. Acitretin can activate but does not bind to multiple RARs.[5][6]

Acitretin has anti-inflammatory and anti-proliferative effects. It normalizes keratinocyte differentiation in the epithelium. It also hinders the expression of the proinflammatory cytokines like interleukin-6 (IL-6), migration inhibitory factor-related protein-8 (MRP-8), and interferon-gamma. The agent acts by binding and activating all nuclear subtypes of retinoid X-receptors and retinoic acid receptors.


The initial metabolism of acitretin involves isomerization; this differs from isotretinoin, where initial metabolism is oxidation. Acitretin converts to isoacitretin. Acitretin is ultimately eliminated in the bile as beta-glucuronide derivatives or through the kidneys as soluble metabolites.

Acitretin can undergo reverse metabolism to etretinate with acitretin is used in combination with alcohol.


Initial: Administer 25 to 50 mg orally daily as a single dose with the main meal.

Maintenance: Administer 25 to 50 mg orally daily after initial response to treatment. The maintenance dose should have its basis in clinical efficacy and tolerability.

In psoriasis treatment with acitretin, improvement is seen approximately at weeks 4 to 6. The maximum benefit may take between 3 to 4 months. Treatment dosing is initiated at 25 mg orally once daily. When the disease is stable, dosing is often reduced to 10 mg orally once daily or 25 mg orally every other day as a maintenance protocol. Treatment with acitretin leads to decreased plaque thickness, scaling, and pruritis. However, there is not much reduction in body surface area (BSA).

In combination with phototherapy, dosing is recommended at 25 mg orally once daily for two weeks before phototherapy, with a need to decrease the initial dose of ultraviolet (UV) light. If a patient is already on a stable dose of UV light and is starting acitretin, reduce the dose by 30% to 50% approximately seven days after initiation of acitretin.

Adverse Effects

Capillary leak syndrome, exfoliative dermatitis, hypercholesterolemia, increased liver enzymes, increased creatinine phosphokinase, hepatotoxicity, hyperesthesia, paresthesia, rigors, cheilitis, alopecia, exfoliation of the skin, xeroderma, nail disease, pruritus, erythematous rash, paronychia, hypertriglyceridemia, hyperglycemia, hypoglycemia, reticulocytosis, xerophthalmia, rhinitis, pseudotumor cerebri, tinnitus, and epistaxis.[7]

United States Boxed Warning



Absolute Contraindications

  • Pregnancy or woman who is likely to become pregnant
  • Non-compliance with contraception
  • Nursing mothers

Hypersensitivity to drug or components, pregnancy, intent to become pregnant within three years after treatment discontinuation, severe hepatic or renal dysfunction, chronic abnormally elevated blood lipid levels, or concomitant use with methotrexate or tetracyclines.

It is vital that clinicians who prescribe acitretin to women of childbearing age ensure that they do not get pregnant for at least three years after discontinuing the medication. 

United States Boxed Warning

Female patients should abstain from ethanol during therapy and for at least two months after discontinuing treatment.


  • Lipid profile
  • Liver function tests
  • Complete blood count (CBC)
  • Blood glucose in patients with diabetes
  • Evaluation of bone abnormalities
  • Serum pregnancy testing



  • Concomitant administration with methotrexate increases the risk of hepatic adverse effects.
  • Concomitant administration with cyclosporine increases the risk of hypertriglyceridemia.
  • Acitretin can undergo reverse metabolism to etretinate with acitretin if used in combination with alcohol.
  • The use of other vitamin A compounds can lead to hypervitaminosis A-like toxicities.
  • The combination of tetracyclines and retinoids can lead to pseudotumor cerebri and should be avoided.

Individuals prescribed acitretin should receive counsel against giving blood donations for at least three years. The drug is known to remain in the blood for a long time, and the risk of genetic defect is high.

Enhancing Healthcare Team Outcomes

Acitretin is frequently used to treat several skin disorders, including acne, psoriasis, lichen planus, and discoid lupus. While the drug is effective, it is crucial for interprofessional healthcare team members, including pharmacists, nurse practitioners, PAs, and primary care clinicians, to know its potential adverse effects. Clinicians should never prescribe the drug to a pregnant female because of the risk of teratogenicity. Also, the FDA has issued several boxed warnings about the risk of hepatitis when combining the agent with alcohol. When prescribing acitretin, the patient must understand the potential adverse effects and the importance of avoiding alcohol.[8][9]

Given the warnings, it is apparent that an interprofessional team is the best means to manage acitretin therapy. Once the prescriber has decided to give the patient the drug, nursing can counsel on the dosing and administration and the teratogenicity potential if the patient is female. The pharmacist will verify dosing and perform medication reconciliation, alerting the prescriber of any issues. Nursing can also chart the therapeutic progress of the condition treated, so the prescriber can make adjustments to therapy as needed. Through this interprofessional team paradigm, acitretin can deliver maximal benefit with minimal downside, resulting in better patient outcomes. [Level 5]

Article Details

Article Author

Patrick Zito

Article Editor:

Thomas Mazzoni


7/30/2021 10:22:21 PM

PubMed Link:




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