What is an Acitretin capsule?
Acitretin capsules usp (acitretin) is a retinoid and is available in 25- or 10-mg gelatin capsules to be administered orally. Chemically, acitretin, usp, is (all-e)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoic acid. It's a derivative of etretinate that is related to both retinoic acid and retinol (vitamin A). It is a greenish or yellow crystallized powder that has a molecular weight of 326.44. The formula for structural properties is:
Each capsule is a combination of acitretin gelatin, edetate disodium maltodextrin, microcrystalline cellulose, poloxamer 407, red iron oxide ascorbate, sodium ascorbate, and titanium dioxide. The 25 mg capsules include black iron oxide as well as orange iron oxide.
Ink for imprinting black that is used for capsules of 10 mg includes black iron oxide, propylene glycol, potassium hydroxide shellac, and a strong ammonia solution.
The imprinting ink white used in the capsules of 25 mg includes propylene glycol, povidone, and shellac. It also contains sodium hydroxide and titanium dioxide.
Warnings
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The pregnancy process: acitretin capsules must not be used by women who are pregnant or are planning to get pregnant during therapy or for at least three years after the discontinuation of treatment. Acitretin capsules should not be taken by women who are not using an effective contraception method while receiving treatment for at least 3 years after stopping treatment. Acitretin is one of the metabolites of etretinate (tension), and significant human fetal anomalies have been identified with the use of acitretin as well as etretinate. It is possible that any fetus that is exposed could be affected. Evidence from clinical studies has demonstrated that consuming alcohol and acitretin is connected to the creation of etretinate. It has an extended elimination half-life compared to acitretin. Because the longer half-life for elimination of etretinate will extend the potential teratogenic effects when used in women, ethanol should not be consumed by females with pregnancy potential, either when they are receiving acitretin capsules or for two months after the end of treatment. This will allow for the elimination of acitretin and get rid of the substrate for transesterification into etretinate. The mechanism for the metabolic process involved in the conversion of acitretin into etretinate has not been thoroughly analyzed. It is unclear if substances other than ethanol are involved with transesterification. Acitretin has been found to be teratogenic, embryotoxic, and/or toxic in mice, rabbits, and rats in doses of 0.6, 3, and 15 mg per kilogram, respectively. The doses are about 0.2, 0.3, and three times the maximum dosage recommended for therapeutic use, respectively, in a mg-per-m2 comparison. Major human fetal abnormalities associated with acitretin and/or etretinate administration have been reported, including meningomyelocele, meningoencephalocele, multiple synostoses, facial dysmorphia, syndactyly, absence of terminal phalanges, malformations of the hip, ankle, and forearm, low-set ears, a high palate, decreased cranial volume, cardiovascular malformations, and alterations of the skull and cervical vertebrae. Acitretin capsules should only be prescribed by people who are experts in the treatment and diagnosis of severe psoriasis, have experience with the use of retinoids in the system, and are aware of the risks of teratogenicity. Details on dosageThere is a variation between subjects in the dosage, efficacy in clinical trials, and frequency of adverse reactions when taking the acitretin capsules. Some of the most frequent side effects are related to dose. The dosage must be adjusted to ensure sufficient therapeutic effects while minimizing any side effects. The treatment with acitretin capsules must begin with 25 to 50 mg daily, administered in one dose during the meal. Maintaining doses of 25–50 mg per day can be administered based on the individual's reaction to the initial treatment. Relapses can be treated in the same manner as described for the initial treatment. If acitretin capsules are taken in conjunction with phototherapy, the doctor must reduce the dosage of phototherapy in accordance with the individual patient's response. What happens if I overdose?In the event of an acute overdose, the acitretin capsules should be removed immediately. The symptoms of an overdose are similar to those of acute hypervitaminosis (e.g., headache, migraine, and vertigo). In the acute phase, or oral toxicity (ld50), for acitretin, both rats and mice had ld50s higher than 4,000 mg/kg. In an incident of overdose, a male of 32 with darier's disease took 21 capsules of 25 mg each (525 mg in one dose). He vomited for several hours afterward but did not experience any other side effects. |
Side effects of Acitretin capsule
Hypervitaminosis cause a broad range of symptoms and signs, mostly in the mucocutaneous, neuropsychiatric, hepatic, musculoskeletal, and central nervous systems. A large number of adverse reactions observed to date following treatment with acitretin capsules are similar to the hypervitaminosis-a syndrome.
Adverse side effects
Alongside the events mentioned in the tables of the clinical trials. These adverse events have been observed following the post-approval use of acitretin capsules. Because these adverse events occur voluntarily in a small sample of patients, it isn't always possible to determine their frequency or establish a causal connection to exposure to drugs.
The cardiovascular system: acute myocardial ischemia or a thromboembolismThe immune system: disorders of the hypersensitive, including angioedema, urticarial, and angioedema (see contraindications)
Neuromuscular system:
Myopathy that causes peripheral neuropathy was reported in the course of treatment with acitretin capsules. Both of these conditions improved after stopping the medication.
Psychiatric:
Aggression or suicidal thoughts have also been documented. These kinds of events, such as self-injurious behavior, were documented in patients who take other retinoids that are administered systemically and in patients who take capsules of acitretin. As other factors could be responsible for these incidents and are not fully understood, it isn't known whether or not they're connected to the capsules of acitretin.
Reproductive:
vaginitis due to candida albicans
The skin and the appendage's thinness on the face, skin damage, and scaling can occur throughout the body, with a particular focus on the soles of the hands and palms and the nails. Nail fragility is commonly noticed. Madarosis and exfoliative dermatitis/erythroderma have been reported.
Interaction with other drugs
Ethanol
Clinical evidence has demonstrated that etretinate is formed by consuming ethanol and acitretin (see the boxed warnings and contraindications as well as clinical pharmacokinetics).
Glyburide
In a study of seven healthy male participants, acitretin treatment enhanced the blood glucose-lowering effect of glyburide (a sulfonylurea that is similar to chlorpropamide) in three of the seven subjects. The same trial conducted with six healthy male participants without glyburide revealed no impact of acitretin treatment on reducing glucose tolerance. Be sure to supervise diabetic patients receiving treatment with capsules of acitretin, which is highly recommended
Hormonal contraceptives
It is not known whether there are any pharmacokinetic interactions between acitretin and combination oral contraceptives. However, it is now known that acitretin may interfere with the contraceptive effects of progestin-microdose "minipill" preparations. The micro-dosed "minipill" progestin preparations are not advised to be used with capsules of acitretin. (It is unclear if other contraceptives containing progestin, like implants or injectable, can be considered effective alternatives to contraception in the treatment with acitretin.
