Acitretin Capsules - Dosage, Indications, Contraindications, Side Effects

Overview

Acitretin is a retinoid with similar properties and activity to vitamin A. Vitamin A promotes cell growth, differentiation, and proliferation and regulates the immune system. It also helps in embryonic development, has anti-inflammatory effects, inhibits tumor growth, and induces apoptosis.

Acitretin is an FDA (Food and Drug Administration) approved drug for the treatment of psoriasis, combination therapy with PUVA (psoralen + ultraviolet light A), UVB (ultraviolet B), Cyclosporine, and biological therapies. However, Acitretin is the only FDA-approved drug that is effective as monotherapy for the treatment of psoriasis.

Acitretin is available in a gelatin capsule for oral administration. It contains a yellow to greenish-yellow powder with a molecular weight of about 326.44 g/mol.

What Are the Uses of Acitretin?

• Acitretin is used to treat serious skin disorders like psoriasis. The drug works by letting the normal development and growth of the skin.

• The drug treats other skin conditions, such as non-melanoma skin cancers and inflammatory and hyperkeratotic (thickening of the outer layer of skin) dermatoses (skin lesions).

Use in Specific Populations

Renal Impairment: In patients with end-stage renal disease, a 53 percent reduction of Acitretin plasma concentration was seen in patients. The drug could not be removed by hemodialysis in patients with renal impairment.

Hepatic Impairment: No specific dose adjustment has been given by the manufacturer for patients with hepatic impairment. However, Acitretin is contraindicated in patients with severe hepatic disease.

Pregnancy: Acitretin can cause significant developmental abnormalities in the fetus. Therefore, the drug should not be prescribed to pregnant people or those planning to conceive during treatment or at least three years after stopping the Acitretin medication.

Breastfeeding Women: Acitretin should not be prescribed to breastfeeding mothers as it can be present in human milk and thus cause fetal abnormalities.

Pediatric Use: The safety and efficacy of Acitretin are not yet established in pediatric patients.

Geriatric Use: In clinical trials, Acitretin has shown a significant increase (almost double) in plasma concentration in geriatric patients.

For Patients:

What Is Psoriasis?

Psoriasis is a skin condition causing itchy, dry, and scaly patches on the skin due to an abnormal build-up of skin cells. The condition is usually caused due to cold, stress, and infections in the body die to weak immune response.

Why Is Acitretin Prescribed to Patients?

Acitretin is used to treat patients with severe skin conditions, such as psoriasis, which is an abnormal skin growth that causes scaly, thickened, and red skin.

How Should the Person Use Acitretin?

Acitretin capsule is taken along with a meal once every day at the same time. The drug should be taken as directed by the doctor. A person should not take more or fewer drug doses than the doctor prescribes. The doctor usually starts the Acitretin in small doses, gradually increasing the dose as per the patient's condition.

What Special Precautions Need To Be Taken for Acitretin?

• A person should inform the doctor if they have any allergic reactions, such as itching, breathing and swallowing difficulties, hives, and swelling on the tongue, throat, eyes, and lips caused by Acitretin and other retinoids or any ingredients in the drug. The doctor may ask the patient to stop using this drug.

• Inform the doctor about all the prescription, non-prescription, nutritional supplements, vitamins, and herbal supplements a person takes. This helps the doctor to prescribe or change the dosage of Acitretin and monitor the patient carefully for any side effects.

• People should inform their doctor about any past or present medical condition. They should tell the doctor if they are alcoholic, have depression, diabetes, stroke, spinal problems, heart, bone, or joint disease.

• A person prescribed Acitretin should also inform their doctor if they ever had high triglyceride levels or high cholesterol and any family history of kidney disease or high cholesterol levels.

• If a person has to receive phototherapy, they must inform the doctor that they are taking Acitretin.

• Inform the doctor if a person is taking medications, such as tetracycline antibiotics, Methotrexate, etc. A doctor may ask a person to stop using Acitretin if they take these medications.

• Acitretin causes dry eyes and sometimes makes it difficult for a person to wear contact lenses. They should inform the doctor if this happens and remove the lenses immediately.

• Women should not take this medication if breastfeeding and if it has been stopped recently.

What Are the Side Effects of Acitretin?

Side effects of Acitretin include

• Dry, blistered, peeling, itchy, cracked, or infected skin.

• Dandruff.

• Sunburn.

• Hair loss.

• Dry eyes.

• Excessive saliva.

• Abnormal skin odor.

• Swollen or chapped lips.

• Weak or brittle nails.

• Excessive sweating.

• Diarrhea.

• Dry nose.

• Sinus infection.

• Flushing or hot flashes.

• Nosebleed.

• Stomach pain.

• Changes in hair texture.

• Joint pain.

• Changes in taste.

• Increased appetite.

• Runny nose.

• Loss of eyelashes and eyebrows.

• Mouth blisters or swelling.

• Tight muscles.

• Change in hair texture.

Some serious side effects include

• Depression.

• Headache.

• Swelling and redness in one leg only.

• Bone, back, and muscle pain.

• Loss of muscle tone.

• Sensitivity to light.

• Rapid heartbeat.

• Dizziness.

• Shortness of breath, nausea, dry mouth, vomiting, decreased consciousness.

• Blurred vision, frequent urination, excessive thirst, weakness, extreme hunger.

• Irregular or slow heartbeat.

• Slow speech.

• Tinnitus or ringing in the ears.

• Loss of senses in hands and feet.

• Pale, cold, or gray skin.

• Pain in the eyes.

• Swelling in feet, hands, lower legs, or ankles.

A person should inform the doctor immediately if they experience these symptoms while taking Acitretin.

Overdose:

Inform the local poison control department if someone overdoses Acitretin and contact the emergency healthcare service on 911 if a victim has trouble breathing, collapses, or seizures.

Missed Dose:

If a person misses a dose of Acitretin, skip the missed dose and continue taking the regular dose. Do not take a double dose of the medication to compensate for the missed dose.

Drug Storage and Disposal:

The drug should be stored at room temperature, away from moisture and excess heat. It should be kept in an airtight container with its packaging and away from children’s reach.

The drug should be disposed of by the FDA (Food and Drug Administration) safety rules for safe drug disposal or can be returned to the pharmacy through a take-back of drugs program by talking to any nearest pharmacy.

For Doctors:

Clinical Pharmacology

Mechanism of Action

The mechanism of action of Acitretin still needs to be discovered.

Pharmacodynamics

Acitretin is a retinoid having a structure similar to vitamin A that initiates normal skin growth cells. The drugs work by inhibiting keratinization (skin cell thickening process due to protein deposition) and excessive cell growth in psoriasis. Therefore, Acitretin reduces plaque formation, skin thickening, and scaling.

Pharmacokinetics

Absorption

Oral absorption of Acitretin is optimal along with food. The linear and proportional dosage increases from 25 to 100 milligrams. In a clinical trial, 50 mg of Acitretin administered to 12 healthy subjects was absorbed by approximately 72 percent.

Distribution

More than 99.9 percent of Acitretin is bound to plasma protein, mainly albumin.

Elimination

The conjugates and chain-shortened metabolites of Acitretin are excreted 16 to 53 percent in urine and 34 to 54 percent in feces. The elimination half-life of Acitretin is 49 hours, followed by multiple doses of drug administration. Also, the accumulation ratio of Ascitretin is 1:2.

Ingredients

Active Ingredients: Acitretin

Inactive Ingredients: Microcrystalline cellulose, sodium ascorbate, crospovidone, poloxamer, sodium lauryl sulfate, and povidone.

Dose Form and Strength

Form: Capsule (gelatin)

Strength: Acitretin is available in three strengths: 10 mg, 17.5 mg, and 25 mg.

Administration of the Drug

The initial dose of Acitretin is oral administration of 25 to 50 mg daily with the main meal. The dose is maintained after the patient’s initial response to the treatment and also depends on the clinical tolerability and efficacy of the drug.

Dose Maintenance: The psoriasis treatment is initiated at 25 mg orally daily. The potential improvements in the patient’s condition can be seen in approximately four to six months. The drug is then often reduced to 10 mg orally once a day or 25 mg every other day as per the drug maintenance protocol.

Consideration of the Administration

In case a patient is planning for phototherapy, the recommended dose of Acitretin is 25 mg orally once daily at least two weeks before the phototherapy. The initial dose of UV (ultraviolet) light is also reduced. Further, the dose of UV light is reduced by 30 to 50 percent in case a person is already on a stable dose of light and is going to start taking Acitretin.

What Are the Drug Warnings and Precautions?

The doctor should advise females of reproductive age not to take this medication if they are pregnant or planning to conceive. The females should be counseled about taking proper contraceptive measures during the therapy with Acitretin. In addition, they should also be informed not to consume any beverage containing ethanol while taking Acitretin and after two months of stopping the drug.

The drug has been associated with major fetal abnormalities, such as facial dysmorphia, malformations of the hips, forearms, and ankles, decreased cranial volume, alterations in the cervical vertebrae and skull, absences of terminal flanges, multiple synostoses, a high palate, and syndactyly (malformed or united toes and fingers, partly or wholly).

Therefore, doctors should advise the woman of childbearing age about the risk associated with Acitretin and the methods of contraception to prevent pregnancy for at least two to three years after stopping Acitretin.

Also, doctors should only be prescribed to such women if they have severe psoriasis and other treatment options are ineffective in treating the condition.

What Are the Contraindications of Acitretin Capsules?

• Nursing mothers.

• Pregnant women or those who are planning to conceive.

• Non-compliance with pregnancy contraception, the drug should be stopped immediately, and a doctor should be consulted.

• Patients with severely impaired hepatic and renal function.

What Are the Adverse Effects of Acitretin Capsules?

The adverse effects caused by Acitretin resemble hypervitaminosis A syndrome. Other adverse effects of Acitretin capsule include:

• Psychiatric: Insomnia, depression, aggression, and suicidal thoughts caused by Acitretin have been reported.

• Cardiovascular: Acute myocardial infarction, stroke, flushing, thromboembolism.

• Reproductive: Vulvovaginitis caused by Candida albicans.

• Nervous System: Myopathy, headache, rigors, and pain may occur after stopping Acitretin medicine.

• Immune System Disorder: Hypersensitivity reactions, such as urticaria and angioedema.

• Vascular Disorder: Capillary leak syndrome.

• Skin and Appendages: Xeroderma (dry skin), skin thinning, pruritus (itching), nail disease, exfoliation of the skin, nail fragility, exfoliative dermatitis, and erythematous rash on soles and palms.

• Laboratory Abnormality: Increased liver enzymes, hyperglycemia and hypoglycemia (high or low blood sugar levels), liver or hepatotoxicity, increased creatinine phosphokinase, hypercholesterolemia, and hypertriglyceridemia.

• Miscellaneous: Tinnitus, rhinitis, xerophthalmia (dryness of cornea or conjunctiva of an eye), cheilitis (chapped or inflamed lips), visual problems, and hepatitis.

Drug Interactions

Acitretin should not be taken along with other medications as it can cause a serious drug interaction leading to severe consequences. These drugs include

• Oral Retinoids or Vitamin A: Acitretin is taken along with retinoids, and vitamin A can lead to hypervitaminosis A in the patient. There this combination is contraindicated.

• Phenytoin: The protein binding of Phenytoin can get reduced if taken with Acitretin.

• Tetracycline: Acitretine and Tetracycline can cause increased intracranial pressure. There it is contraindicated to be taken along with Acitretin.

• Methotrexate: Acitretine, in combination with Methotrexate, can cause hepatitis. Hence, the drug is contraindicated in combination treatment.

• Progestin-only Contraceptive: There is no specific evidence showing any interaction of Acitretin with oral contraceptives. But the drug can affect the action of micro-dosed progestin preparations. Also, it is unknown whether other contraceptive methods, such as injectables and implants, are effective during Acitretin therapy.

Drug Toxicity

Carcinogenesis: In a clinical trial on rats, a dose of Acitretin of two mg per kg per day for 104 weeks showed no evidence of a neoplastic lesion.

Mutagenesis: Ames test conducted to evaluate the mutagenic potential of Acitretin using human fibroblasts and rat hepatocytes showed no evidence of mutagenicity related to the treatment with Acitretin.

Impairment of Fertility: The study on rats for fertility effects caused by three mg per kg per day of Acitretin showed no effects; chronic toxicity was seen in dogs treated with a higher dosage group (50 then 30 mg per kg per day), causing testicular changes. In a study on 31 men, including six healthy volunteers, 17 psoriatic patients, and eight patients with keratinization disorders, no changes were seen in sperm count, sperm motility, and concentration at the Acitretin dose of 30 to 50 mg daily for 12 weeks. In addition, these men were not found to have any effects on testosterone production, follicle-stimulating hormone (FSH), or luteinizing hormone (LH) levels. Also, no effects were observed on the hypothalamic-pituitary axis.