Acitretin is an orally administered retinoid approved for the treatment of severe psoriasis in non-pregnant adults who are unresponsive to or cannot use other therapies. Acitretin is the active metabolite of etretinate, which is no longer available in the US. Acitretin has a much shorter half-life (approximately 50 hours) than its parent etretinate (approximately 120 days); etretinate has been detected in serum up to 2.9 years after completing a course of therapy. Although acitretin, like etretinate, is also teratogenic, patients can conceive much earlier after discontinuing treatment with acitretin than after etretinate. Patients must avoid becoming pregnant for at least 3 years after stopping acitretin therapy. Ingestion of acitretin and alcohol has been associated with the formation of etretinate; therefore, patients of reproductive potential should avoid alcohol-containing products, including beverages and all medicines that contain alcohol, while taking acitretin and for 2 months after acitretin has been discontinued. The Do Your P.A.R.T. program (Pregnancy Prevention Actively Required During and After Treatment) has been developed to prevent females who are pregnant from receiving acitretin and to prevent pregnancies from occurring during and for 3 years after treatment with acitretin. A prescription for acitretin must not be given to any female of reproductive potential until pregnancy has been excluded by negative results from 2 pregnancy tests. Additionally, patients of reproductive potential must use 2 effective forms of contraception simultaneously for at least 1 month before, during, and for at least 3 years after treatment.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
NOTE: Acitretin should only be prescribed by healthcare providers who have special competence in the diagnosis and treatment of severe psoriasis, are experienced in the use of systemic retinoids, and understand the risk of teratogenicity with this drug.
-Patients of childbearing potential must have had 2 negative urine or serum pregnancy tests with a sensitivity of at least 25 million international units/mL before receiving the initial acitretin prescription. Pregnancy testing and contraception counseling should be repeated monthly during treatment, and every 3 months for at least 3 years after discontinuing therapy. To encourage compliance, it is recommended that a monthly supply of the drug be prescribed.
-Two effective forms of contraception must be used simultaneously for at least 1 month before beginning acitretin therapy, during therapy, and for at least 3 years following discontinuation of therapy. At least 1 of these should be a primary form of contraception (i.e., tubal ligation, partner's vasectomy, IUDs, oral contraceptives, and injectable/ implantable/ insertable/ topical hormonal contraceptive products), unless the chosen method is abstinence or the patient has had a hysterectomy or is postmenopausal.
-Patients must have signed a Patient Agreement/Informed Consent for Female Patients that contains warnings about the risks of acitretin therapy prior to receiving a prescription for acitretin.
-Pharmacists: A Soriatane Medication Guide must be given to the patient each time Soriatane is dispensed.
Hazardous Drugs Classification
-NIOSH 2016 List: Group 3
-NIOSH (Draft) 2020 List: Table 2
-Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
-Use gloves to handle. Cutting, crushing, or otherwise manipulating capsules will increase exposure and require additional protective equipment.
Route-Specific Administration
Oral Administration
-Administer orally with the main meal.
-When used with phototherapy, the prescriber should decrease the phototherapy dose, depending on the patient's individual response.
Hypervitaminosis A may occur during acitretin therapy or in overdose situations and produces a wide spectrum of signs and symptoms primarily of the mucocutaneous, musculoskeletal, hepatic, neuropsychiatric, and central nervous systems. Many adverse reactions to acitretin may resemble those of the hypervitaminosis A syndrome.
The most frequent adverse reactions reported with acitretin therapy involve the skin and mucous membranes; these adverse reactions were the primary reason patients prematurely stopped therapy during clinical trials. Exfoliative dermatitis or erythroderma has been reported in patients receiving acitretin. Discontinue acitretin if exfoliative dermatitis or erythroderma occurs during therapy. The most commonly reported skin and mucous membrane adverse reactions to acitretin during psoriasis clinical trials include cheilitis (more than 75%), alopecia (50% to 75%), skin peeling (50% to 75%), xerosis (25% to 50%), nail disorder (25% to 50%), pruritus (25% to 50%), erythematous rash (10% to 25%), epistaxis (10% to 25%), hyperesthesia (10% to 25%), paresthesias (10% to 25%), paronychia (10% to 25%), skin atrophy (10% to 25%), sticky skin (10% to 25%), and xerostomia (10% to 25%). Other less commonly (1% to 10%) reported reactions include abnormal skin odor, abnormal hair texture, bullous rash or eruption, cold and clammy skin, dermatitis, diaphoresis (increased sweating), flushing, gingival bleeding, gingivitis, hypersalivation, psoriaform rash, purpura, pyogenic granuloma, rash, seborrhea, skin fissures, skin ulcer, stomatitis, photosensitivity or sunburn, increased thirst, and ulcerative stomatitis. Thinning of the skin, skin fragility, and scaling may occur all over the body, particularly on the palms and soles; nail fragility is frequently observed.
Similar to etretinate, acitretin can cause teratogenesis if administered during pregnancy or within 3 years after discontinuation of therapy. Spontaneous fetal abortion has been reported in cases where conception occurred during or after therapy with acitretin in either partner. Major human fetal abnormalities associated with etretinate or acitretin administration include meningomyelocele, meningoencephalocele, multiple synostoses, facial dysmorphia, syndactylies, absence of terminal phalanges, malformations of hip, ankle and forearm, low set ears, high palate, decreased cranial volume, cardiovascular malformation, and alterations of the skull and cervical vertebrae.
Adverse reactions reported at an incidence of 1% to 10% during clinical trials of acitretin in psoriasis patients include appetite stimulation, abdominal pain, anorexia, diarrhea, dysgeusia (taste perversion), edema, fatigue, hot flashes, infection, nausea, and tongue disorder. The most frequent ocular adverse reactions associated with acitretin in clinical studies were brow and lash loss (5%), ocular irritation (9%), and xerophthalmia (23%). Ocular reactions occurring in 1% to 10% of patients during clinical trials for psoriasis include abnormal/blurred vision, blepharitis, conjunctivitis, corneal epithelial abnormality, decreased night vision or night blindness, ocular pain, and photophobia. Changes in vision may occur suddenly. Other ocular adverse reactions reported in less than 5% of patients included crusting of lids, cortical cataracts, cranial nerve palsies (specifically, Bell's palsy), nuclear cataracts, pannus, and posterior subcapsular cataracts. Abnormal lacrimation, chalazion (meibomian cyst), conjunctival/ocular hemorrhage, corneal ulcer, diplopia, ectropion, ocular pruritus including eyelids, papilledema, recurrent sties, and subepithelial corneal lesions have also been reported at an incidence of less than 1%. Any patient treated with acitretin who is experiencing visual difficulties should discontinue the drug and undergo ophthalmologic examination.
Acitretin has been associated with cases of clinical jaundice with hyperbilirubinemia and elevated hepatic enzymes and toxic hepatitis. Hepatic enzymes returned to normal following discontinuation of acitretin therapy. The potential for acitretin to cause hepatotoxicity was evaluated prospectively using liver biopsies. In 58% of patients, no change was noted, 21% improved, and 17% had worsening of their liver biopsy status. No correlation could be found between liver function test result abnormalities and the change in liver biopsy status, and no cumulative dose relationship was found. Elevations in AST (SGOT), ALT (SGPT), GGT (GGTP), or LDH have occurred in approximately 1 in 3 patients treated with acitretin. Of the patients treated in clinical trials, treatment was discontinued in 3.8% due to elevated hepatic enzymes. If hepatotoxicity is suspected during acitretin therapy, the drug should be discontinued and the etiology further investigated. In patients treated with etretinate, of which acitretin is the active metabolite, 1.5% of patients (10 of 652) had clinical or histologic hepatitis considered to be possibly or probably related to etretinate treatment. There have been reports of hepatitis-related deaths worldwide; a few of these patients had received etretinate for a month or less before presenting with hepatic symptoms.
Arthralgia and spinal hyperostosis (progression of existing lesions) were reported at an incidence of 10% to 25% in clinical trials. Other musculoskeletal reactions reported in 1% to 10% of patients treated with acitretin during clinical trials include arthritis, arthropathy, back pain, hypertonia, myalgia, bone pain, and peripheral joint hyperostosis (progression of existing lesions}. Of 380 patients treated with acitretin, 15% had preexisting abnormalities of the spine which showed new changes or progression of preexisting findings. Changes included degenerative bone spurs, anterior bridging of spinal vertebrae, diffuse idiopathic skeletal hyperostosis, ligament calcification and narrowing, and destruction of cervical disc space. De novo changes (formation of small spurs) were seen in 3 patients after 1.5 to 2.5 years of treatment. Six of 128 patients treated with acitretin showed abnormalities in the knees or ankles before treatment that progressed during treatment. In 5 patients, these changes involved formation of additional spurs or enlargement of existing spurs. The sixth patient had degenerative joint disease that worsened. None of these patients developed spurs de novo. Postmarketing cases of myopathy with peripheral neuropathy have been reported. Both conditions improve with discontinuation of the drug.
Hyperlipidemia (25% to 50%) is associated with acitretin therapy. During clinical trials, 66% and 33% of patients experienced hypertriglyceridemia and hypercholesterolemia, respectively. Decreased high density lipoproteins (HDL) occurred in 40% of patients. These effects of acitretin were reversible upon discontinuation of therapy. It is recommended that serum lipid monitoring be performed every 1 to 2 weeks until the lipid response to acitretin stabilizes, usually within 4 to 8 weeks; ongoing monitoring of serum lipids is recommended in high-risk patients and during long-term therapy. Although no casual relationship has been established, there have been postmarketing reports of acute myocardial infarction, stroke, or thromboembolism in patients receiving acitretin. Elevated serum triglycerides to greater than 800 mg/dL have been associated with fatal fulminant pancreatitis; although, there have been rare reports of pancreatitis during acitretin therapy in the absence of hypertriglyceridemia. Therefore, dietary modifications, acitretin dose reduction, or drug therapy, as appropriate, should be utilized to control significant elevations of triglycerides; acitretin discontinuation should be considered if hypertriglyceridemia and low HDL levels persist.
Depression, headache, insomnia, otalgia (ear pain or earache), somnolence, and tinnitus were reported in 1% to 10% of patients during clinical trials. Depression and other psychiatric symptoms such as aggressive feelings or suicidal ideation have been reported. These events have been reported in patients taking other systemically administered retinoids, as well as patients taking acitretin. Since other factors may have contributed to these events, it is not known if they are related to acitretin. Instruct patients to stop taking acitretin and notify their prescriber immediately if they experience psychiatric symptoms.
Some patients receiving retinoids, such as acitretin, have experienced problems with blood sugar control. Hyperglycemia (25% to 50%) and hypoglycemia (10% to 25%) were reported during clinical trials of acitretin. In addition, new cases of diabetes mellitus, including diabetic ketoacidosis, have been diagnosed during retinoid therapy. In diabetics, blood sugar levels should be carefully monitored.
Acitretin (less than 1%) and other retinoids administered orally have been associated with cases of pseudotumor cerebri (benign intracranial hypertension or increased intracranial pressure). Some of these events involved concomitant use of tetracyclines. The single case reported with acitretin use, however, was not associated with tetracycline use. Early signs and symptoms include papilledema, headache, nausea, vomiting, and visual impairment. Patients with these signs and symptoms should be examined for papilledema and, if present, should discontinue acitretin use immediately and be referred for neurological evaluation and care.
Capillary leak syndrome has been reported in patients receiving acitretin. Capillary leak syndrome is a potential manifestation of retinoic acid syndrome; features may include localized or generalized edema with secondary weight gain, fever, and hypotension. Rhabdomyolysis and myalgias have been reported in association with capillary leak syndrome. Laboratory tests may reveal neutrophilia, hypoalbuminemia, and an elevated hematocrit. Discontinue acitretin if capillary leak syndrome develops during therapy.
Hypersensitivity, including angioedema and urticaria, has been reported during postmarketing use of acitretin.
Vulvo-vaginitis due to Candida albicans has been reported during postmarketing use of acitretin.
Rhinitis (25% to 50%) and sinusitis (1% to 10%) were reported during clinical trials of acitretin.
Additional adverse event reported in less than 1% of acitretin recipients during clinical trials include alcohol intolerance, dizziness, influenza-like symptoms, malaise, moniliasis, muscle weakness, chest pain (unspecified), cyanosis, increase or prolonged bleeding time, intermittent claudication, peripheral ischemia, gait disturbance, migraine, neuritis, constipation, dyspepsia, esophagitis, gastritis, gastroenteritis, glossitis, hemorrhoids, melena, tenesmus, tongue ulceration, anal disorder, gum hyperplasia, hemorrhage, pharyngitis, olecranon bursitis, tendonitis, anxiety, dysphonia, libido decrease, nervousness, leukorrhea, cough, increased sputum, laryngitis, acne vulgaris, breast pain, cyst, eczema, fungal infection, furunculosis, hair discoloration, herpes simplex, hyperkeratosis, hypertrichosis, hypoesthesia, impaired wound healing, otitis media, otitis externa, psoriasis aggravation, scleroderma, skin nodule, skin hypertrophy, skin disorder, skin irritation, sweat gland disorder, verrucae, ceruminosis, deafness, taste loss or ageusia, abnormal urine, dysuria, and penial disorder. Although reported during clinical trials, some of the above reactions may bear no relationship to therapy.
Acitretin is teratogenic and is contraindicated in patients who are pregnant or who intend to become pregnant during therapy or within 3 years after therapy. Before initiating treatment in patients of childbearing potential, patients must be told clearly and in detail about the precautions to be taken, the risks involved, and the possible consequences should pregnancy occur during treatment or within 3 years of discontinuing therapy. A program called Do Your P.A.R.T (Pregnancy prevention Actively Required during and after Treatment) has been developed to educate women and their healthcare providers about the risks associated with acitretin therapy. Prescribers must have patients of childbearing potential sign a Patient Agreement/Informed Consent form that describes the warnings and requirements associated with acitretin therapy and pregnancy prior to beginning treatment. Acitretin is a metabolite of etretinate; major human fetal malformations have been associated with the maternal use of both drugs. Ethanol ingestion has been shown to be associated with the transesterification of acitretin to etretinate. Because the half-life of etretinate is significantly longer than acitretin, the duration of teratogenic potential would be increased; therefore, females should avoid ethanol ingestion during and for 2 months after discontinuing therapy. Adverse fetal outcomes associated with acitretin and etretinate use have included spontaneous abortion, absent hand/wrist, cardiac malformations, chromosomal disorders, decreased cranial volume, facial dysmorphia, GI malformations, limb malformations, meningomyelocele, placental disorder/death, premature birth, stillbirth, and other abnormalities. Further, it is not known whether residual acitretin in seminal fluid poses risk to a fetus while a male patient is taking the drug or after it is discontinued. Minimal concentrations (12.5 ng/mL) have been found in the seminal fluid of men receiving acitretin or etretinate and may cause male-mediated teratogenicity. It appears that residual acitretin in seminal fluid poses little, if any, risk to a fetus while a male patient is taking the drug, or after it is discontinued; however, the no-effect limit for teratogenicity is not known, and there is no registry for birth defects associated with acitretin. There have been 25 cases of reported conception when the male partner was taking acitretin. The pregnancy outcome is known in 13 of the cases. When acitretin therapy was ongoing at the time of conception, delivery of a healthy neonate occurred in 5 cases, spontaneous abortion occurred in 5 cases, and there was 1 case of induced abortion. In 1 case, a spontaneous abortion occurred when acitretin had been discontinued 6 to 8 months prior to conception. In another case where acitretin had been discontinued about 4 weeks prior to conception, abortion was induced; however, the fetal malformation pattern was not typical of retinoid embryopathy. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to acitretin; information about the registry can be obtained at www.tevagenerics.com/acitretin or by calling 1-855-850-2138.
Acitretin is teratogenic; therefore, before initiating therapy in patients of childbearing potential, patients must be told clearly and in detail about the precautions to be taken, the risks involved, and the possible consequences should pregnancy occur during treatment or within 3 years of discontinuing therapy. A program called Do Your P.A.R.T (Pregnancy prevention Actively Required during and after Treatment) has been developed to educate women and their healthcare providers about the serious risks associated with acitretin therapy. Prescribers must have patients of childbearing potential sign a Patient Agreement/Informed Consent form that describes the warnings and requirements associated with acitretin therapy and pregnancy prior to beginning treatment. Patients of childbearing potential must undergo pregnancy testing and have had 2 negative urine or serum pregnancy tests with a sensitivity of at least 25 million international units/mL before receiving the initial acitretin prescription. The first test is obtained by the prescriber when the decision is made to pursue acitretin therapy. The second test should be done during the first 5 days of the menstrual period immediately preceding the beginning of acitretin therapy. For patients with amenorrhea, the second test should be done at least 11 days after the last act of unprotected sexual intercourse (without using 2 effective forms of contraception simultaneously). If the second pregnancy test is negative, initiation of treatment should begin within 7 days of the specimen collection; limit to a monthly supply. Obtain a pregnancy test with a sensitivity of at least 25 million international units/mL monthly during treatment; after acitretin is discontinued, repeat pregnancy testing every 3 months for at least 3 years. Patients of childbearing potential are also required to use reliable contraception during and for at least 3 years after treatment. Counseling regarding these contraception requirements must be repeated by the prescriber monthly during therapy and every 3 months for at least 3 years after acitretin discontinuation. Effective contraception must be used for at least 1 month before beginning acitretin therapy, during therapy, and for at least 3 years after discontinuation even where there has been a history of infertility, unless due to hysterectomy or if the woman is clearly postmenopausal. Two reliable forms of contraception (primary and secondary forms) must be used simultaneously unless absolute abstinence is the chosen method. Primary forms of birth control include tubal ligation, partner's vasectomy, intrauterine devices, birth control pills, and non-oral hormonal birth control products while secondary forms include diaphragms, latex condoms, cervical caps, and vaginal sponges; each secondary form (except condoms) must be used with a spermicide. Acitretin interferes with the contraceptive effect of microdose progestin preparations; therefore, these preparations are not recommended for use with acitretin. In addition, prescribers must be cautious to avoid any potential drug interactions that may reduce the effectiveness of hormonal contraception in females who are using hormonal contraception as a primary form of birth. Counsel patients to avoid self-medicating with St. John's Wort, as it may decrease the effectiveness of hormonal contraceptives.
Blood donation should be avoided during and for 3 years following completion of acitretin therapy because women of childbearing potential must not receive blood products from patients being treated with acitretin.
According to the manufacturer, women who are nursing should not receive acitretin prior to or during breast-feeding because of the potential for serious adverse reactions in nursing infants. Studies in animals show that etretinate, a metabolite of acitretin, is excreted in the milk. There is 1 prospective case report where acitretin is reported to be excreted in human breast milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Acitretin is contraindicated in patients with severe renal impairment or renal failure. Plasma concentrations of acitretin after a 50 mg dose were significantly (59.3%) lower in end-stage renal failure patients (n = 6) when compared to age-matched controls. Acitretin was not removed by dialysis in these patients.
Acitretin is contraindicated in patients with hepatic disease resulting in severe hepatic dysfunction; use has resulted in hepatotoxicity, which has been fatal in some cases. Use caution in patients with mild-to-moderate hepatic disease. Evaluate hepatic function before acitretin initiation, every 1 to 2 weeks until stable, and then at intervals as clinically indicated thereafter. If hepatotoxicity is suspected, discontinue acitretin and investigate the etiology. Additionally, there have been reports of an increased risk of hepatotoxicity in patients treated with etretinate and methotrexate concomitantly; therefore, the concurrent use of acitretin and methotrexate is contraindicated.
In adults receiving long-term treatment with acitretin, appropriate examinations for possible ossification abnormalities (e.g., hyperostosis) should be performed periodically. Because the frequency and severity of iatrogenic bony abnormalities in adults is low, periodic radiography is only warranted in the presence of symptoms or long-term acitretin use. If such disorders arise, the continuation of therapy should be discussed with the patient based on the risks versus benefits.
Use acitretin with caution in patients with a preexisting visual disturbance. Visual adverse effects were reported during clinical trials. Any patient treated with acitretin who is experiencing visual difficulties should discontinue the drug and undergo ophthalmologic evaluation. Decreased night vision has been reported with acitretin therapy. Patients should be advised of this potential effect and warned to be cautious when driving or operating machinery at night. Patients may experience decreased tolerance to contact lenses during the treatment period and sometimes after treatment has stopped.
Acitretin should be avoided in patients with retinoid hypersensitivity, including hypersensitivity to vitamin A, tretinoin, and isotretinoin, due to the possibility of cross-sensitivity.
Use acitretin cautiously in patients with preexisting hypertriglyceridemia or hypercholesterolemia; acitretin is contraindicated in patients with chronic abnormally elevated blood lipid values. Blood lipid determinations, under fasting conditions, should be performed before acitretin is administered, at intervals of 1 to 2 weeks until the lipid response to the drug is established, usually within 4 to 8 weeks, and thereafter at regular intervals as clinically indicated. Hypertriglyceridemia and lowered HDL may increase a patient's cardiovascular risk status; therefore, use acitretin with caution in patients with cardiac disease. There have been postmarketing reports of acute myocardial infarction or thromboembolic events in patients receiving acitretin. Further, elevations of serum triglycerides to greater than 800 mg/dL have been associated with fatal fulminant pancreatitis. Dietary modifications, reduction in acitretin dose, or drug therapy should be employed to control significant elevations of triglycerides. If, despite these measures, hypertriglyceridemia and low HDL levels persist, the discontinuation of acitretin should be considered. Patients with an increased tendency to develop hypertriglyceridemia include those with diabetes mellitus, increased alcohol intake or alcoholism, obesity, or a familial history of these conditions. Additionally, patients with diabetes mellitus or hyperglycemia may experience loss of blood glucose control; instruct patients with diabetes to monitor their blood glucose carefully.
The safety and effectiveness of acitretin in neonates, infants, children and adolescents have not been established. Ossification of interosseous ligaments and tendons of the extremities, skeletal hyperostoses, decreases in bone mineral density, and premature epiphyseal closure have been reported in pediatric patients taking other systemic retinoids.
Patients should avoid the use of sun lamps and excessive sunlight (UV) exposure (non-medical UV exposure) during acitretin therapy. Patients receiving phototherapy in combination with acitretin will require a significant reduction in the phototherapy dose due to increased sensitivity and potential for serious burns. Appropriate protective clothing (e.g., hat) and sunscreen should be used if patients are in the sunlight for an extended period of time.
If patients develop feelings of depression or suicidal ideation, they should be counseled to stop taking acitretin and notify their health care provider immediately. Depression and other psychiatric symptoms such as aggressive behavior or thoughts of self-harm have been reported during acitretin therapy. Since other factors may have contributed to these events, it is not known if they are related to acitretin.
Acitretin and other retinoids administered orally have been associated with cases of pseudotumor cerebri (benign increased intracranial pressure). Some of these events involved concomitant use of isotretinoin and tetracyclines. The single case reported with acitretin use, however, was not associated with tetracycline use. Early signs and symptoms include headache, nausea, vomiting, visual disturbances, and papilledema. Patients with these signs and symptoms should be examined for papilledema, and if present, should discontinue acitretin immediately and be referred for neurologic evaluation.
Acitretin therapy requires an experienced clinician who has special competence in the diagnosis and treatment of severe psoriasis. Healthcare professionals should understand the risk of teratogenicity and have experience prescribing systemic retinoids, such as acitretin.
Due to the risk of developing hypervitaminosis A, concurrent administration of acitretin with vitamin A or other oral retinoids must be avoided.
For the treatment of severe psoriasis:
NOTE: Reserve treatment for non-pregnant patients who are unresponsive to other therapies or whose clinical condition contraindicates the use of other treatments.
NOTE: Most patients experience psoriasis relapse after discontinuing therapy. The efficacy of subsequent courses are similar to the initial course of therapy.
Oral dosage:
Adults: 10 to 50 mg PO once daily. The FDA-approved dosage is 25 to 50 mg PO once daily. Guidelines recommend the addition of calcipotriene to standard dose acitretin for the treatment of moderate to severe psoriasis.
Children* and Adolescents*: 0.1 to 1 mg/kg/dose PO once daily. Adult Max: 50 mg per day. Guidelines recommend acitretin as an effective, nonimmunosuppressive systemic therapy for children with extensive guttate or moderate to severe (ideally thin plaque) psoriasis vulgaris or pustular psoriasis. Acitretin combined with narrow band ultraviolet B (NB-UVB) therapy may be synergistic for plaque and pustular psoriasis in childhood and allows for a reduction in dosing of both agents. Acitretin may be combined with other systemic therapies such as methotrexate or cyclosporine, or biologics.
For the treatment of lichen planus*:
Oral dosage:
Adults: 30 mg PO once daily was effective for severe cases of lichen planus in a placebo-controlled, double-blind study. A significant number of placebo-treated patients who received acitretin in the open phase of the study also responded favorably. The drug has been recommended as a first-line treatment of cutaneous and mucosal lichen planus, as well as a second-line option for lichen planopilaris.
For the treatment of hyperkeratotic dermatitis of the palms (eczema* keratoticum):
Oral dosage:
Adults: In a single-blind, placebo-controlled study, 30 mg PO once daily resulted in a 51% reduction in all symptoms in patients as compared to a 9% reduction in the placebo-treated group after 4 weeks of therapy. No further improvement was seen over an additional 4-week period.
Maximum Dosage Limits:
-Adults
50 mg per day PO.
-Geriatric
50 mg per day PO.
-Adolescents
Safety and efficacy have not established.
-Children
Safety and efficacy have not established.
-Infants
Safety and efficacy have not established.
-Neonates
Safety and efficacy have not established.
Patients with Hepatic Impairment Dosing
Contraindicated for use in patients with severely impaired hepatic function.
Patients with Renal Impairment Dosing
Dosage should be modified depending on clinical response and degree of renal impairment, but no quantitative recommendations are available. Contraindicated for use in patients with severely impaired renal function.
*non-FDA-approved indication
Aminolevulinic Acid: (Moderate) Acitretin may increase the effects of photosensitizing agents used during photodynamic therapy; significantly lower doses of phototherapy are required when acitretin is used because acitretin-induced effects on the stratum corneum can increase the risk of erythema (burning).
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Contraindicated) The concomitant use of acitretin and systemic tetracyclines is contraindicated, due to the potential for increased cranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Pseudotumor cerebri has been reported with systemic retinoid use alone and early signs and symptoms include papilledema, headache, nausea, vomiting and visual disturbances.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Contraindicated) The concomitant use of acitretin and systemic tetracyclines is contraindicated, due to the potential for increased cranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Pseudotumor cerebri has been reported with systemic retinoid use alone and early signs and symptoms include papilledema, headache, nausea, vomiting and visual disturbances.
Conjugated Estrogens; Medroxyprogesterone: (Major) Acitretin interferes with the contraceptive effect of microdose progestins ('minipill' contraceptive preparations). It is not known if acitretin also interacts with other progestational contraceptives, such as medroxyprogesterone injectables, or if this method is an adequate method of contraception during acitretin therapy. However, female patients should be advised of the possibility that any contraceptive method can fail. Since Acitretin may cause serious birth defects, the patient should use 2 forms of reliable contraception at the same time for at least 1 month before beginning acitretin therapy, during acitretin therapy, and must continue to use them for at least 3 years after acitretin treatment has stopped. It is recommended that the patient either abstain from sexual intercourse or use 2 reliable kinds of birth control at the same time to prevent unwanted pregnancy.
Demeclocycline: (Contraindicated) The concomitant use of acitretin and systemic tetracyclines is contraindicated, due to the potential for increased cranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Pseudotumor cerebri has been reported with systemic retinoid use alone and early signs and symptoms include papilledema, headache, nausea, vomiting and visual disturbances.
Doxycycline: (Contraindicated) The concomitant use of acitretin and systemic tetracyclines is contraindicated, due to the potential for increased cranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Pseudotumor cerebri has been reported with systemic retinoid use alone and early signs and symptoms include papilledema, headache, nausea, vomiting and visual disturbances.
Elagolix; Estradiol; Norethindrone acetate: (Major) Acitretin reduces the efficacy of oral progestin only contraceptives. Since Acitretin may cause serious birth defects, the patient should use 2 forms of reliable contraception at the same time for at least 1 month before beginning acitretin therapy, during acitretin therapy, and must continue to use them for at least 3 years after acitretin treatment has stopped. It is recommended that the patient either abstain from sexual intercourse or use 2 reliable kinds of birth control at the same time to prevent unwanted pregnancy.
Eravacycline: (Contraindicated) The concomitant use of acitretin and eravacycline is contraindicated, due to the potential for increased cranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Pseudotumor cerebri has been reported with systemic retinoid use alone and early signs and symptoms include papilledema, headache, nausea, vomiting and visual disturbances.
Estradiol; Levonorgestrel: (Major) Acitretin interferes with the contraceptive effect of microdose progestins ('minipill' contraceptive preparations), and may possibly interfere with the effecitivenss of emergency contraceptives like levonorgestrel (e.g., Plan B, Plan B OneStep). It is not known if acitretin also interacts with other progestational contraceptives, such as levonorgestrel implants or IUDs or if these methods are adequate methods of contraception during acitretin therapy. However, female patients should be advised of the possibility that any contraceptive method can fail. Since Acitretin may cause serious birth defects, the patient should use 2 forms of reliable contraception at the same time for at least 1 month before beginning acitretin therapy, during acitretin therapy, and must continue to use them for at least 3 years after acitretin treatment has stopped. It is recommended that the patient either abstain from sexual intercourse or use 2 reliable kinds of birth control at the same time to prevent unwanted pregnancy.
Estradiol; Norethindrone: (Major) Acitretin reduces the efficacy of oral progestin only contraceptives. Since Acitretin may cause serious birth defects, the patient should use 2 forms of reliable contraception at the same time for at least 1 month before beginning acitretin therapy, during acitretin therapy, and must continue to use them for at least 3 years after acitretin treatment has stopped. It is recommended that the patient either abstain from sexual intercourse or use 2 reliable kinds of birth control at the same time to prevent unwanted pregnancy.
Ethanol: (Contraindicated) Advise patients who may become pregnant to avoid alcohol-containing beverages and medicines, including over-the-counter products, during and for 2 months after stopping therapy with acitretin. Concurrent ingestion of alcohol and acitretin results in the conversion of acitretin to etretinate. Etretinate has a significantly longer elimination half-life than acitretin and extends the duration of teratogenic potential for patients who may become pregnant beyond 3 years. (Contraindicated) Although the injection of alcohol used for therapeutic procedures is not expected to produce significant systemic effects of ethanol, avoid concomitant use of acitretin due to the unknown potential. Ethanol ingestion has been shown to be associated with the transesterification of acitretin to etretinate. Because the half-life of etretinate is significantly longer than acitretin, the duration of teratogenic potential would be increased; therefore, the product labeling recommends that females should avoid ethanol ingestion during and for 2 months after discontinuing acitretin therapy.
Ethinyl Estradiol; Norethindrone Acetate: (Major) Acitretin reduces the efficacy of oral progestin only contraceptives. Since Acitretin may cause serious birth defects, the patient should use 2 forms of reliable contraception at the same time for at least 1 month before beginning acitretin therapy, during acitretin therapy, and must continue to use them for at least 3 years after acitretin treatment has stopped. It is recommended that the patient either abstain from sexual intercourse or use 2 reliable kinds of birth control at the same time to prevent unwanted pregnancy.
Ethinyl Estradiol; Norgestrel: (Major) Acitretin reduces the efficacy of oral progestin only contraceptives. Since Acitretin may cause serious birth defects, the patient should use 2 forms of reliable contraception at the same time for at least 1 month before beginning acitretin therapy, during acitretin therapy, and must continue to use them for at least 3 years after acitretin treatment has stopped. It is recommended that the patient either abstain from sexual intercourse or use 2 reliable kinds of birth control at the same time to prevent unwanted pregnancy.
Etonogestrel: (Major) Acitretin interferes with the contraceptive effect of microdose progestins ('minipill' contraceptive preparations). It is not known if acitretin also interacts with other progestational contraceptives, such as etonogestrel implants, or if this method is an adequate method of contraception during acitretin therapy. However, female patients should be advised of the possibility that any contraceptive method can fail. Since Acitretin may cause serious birth defects, the patient should use 2 forms of reliable contraception at the same time for at least 1 month before beginning acitretin therapy, during acitretin therapy, and must continue to use them for at least 3 years after acitretin treatment has stopped. It is recommended that the patient either abstain from sexual intercourse or use 2 reliable kinds of birth control at the same time to prevent unwanted pregnancy.
Etonogestrel; Ethinyl Estradiol: (Major) Acitretin interferes with the contraceptive effect of microdose progestins ('minipill' contraceptive preparations). It is not known if acitretin also interacts with other progestational contraceptives, such as etonogestrel implants, or if this method is an adequate method of contraception during acitretin therapy. However, female patients should be advised of the possibility that any contraceptive method can fail. Since Acitretin may cause serious birth defects, the patient should use 2 forms of reliable contraception at the same time for at least 1 month before beginning acitretin therapy, during acitretin therapy, and must continue to use them for at least 3 years after acitretin treatment has stopped. It is recommended that the patient either abstain from sexual intercourse or use 2 reliable kinds of birth control at the same time to prevent unwanted pregnancy.
Fosphenytoin: (Moderate) Acitretin may reduce the protein binding of phenytoin. Free fosphenytoin concentrations may be useful for therapeutic monitoring if both acitretin and fosphenytoin are administered concurrently.
Glimepiride: (Moderate) Retinoids have been reported to cause changes in blood sugar control in diabetics. In a study of 7 healthy male volunteers, acitretin treatment potentiated the blood glucose lowering effect of glibenclamide (a sulfonylurea similar to chlorpropamide) in 3 of the 7 subjects. Repeating the study with 6 healthy male volunteers in the absence of glibenclamide did not detect an effect of acitretin on glucose tolerance. Careful supervision of diabetic patients under treatment with acitretin is recommended, especially those taking concomitant sulfonylureas. There appears to be no pharmacokinetic interaction between acitretin and glyburide.
Glipizide: (Moderate) Retinoids have been reported to cause changes in blood sugar control in diabetics. In a study of 7 healthy male volunteers, acitretin treatment potentiated the blood glucose lowering effect of glibenclamide (a sulfonylurea similar to chlorpropamide) in 3 of the 7 subjects. Repeating the study with 6 healthy male volunteers in the absence of glibenclamide did not detect an effect of acitretin on glucose tolerance. Careful supervision of diabetic patients under treatment with acitretin is recommended, especially those taking concomitant sulfonylureas. There appears to be no pharmacokinetic interaction between acitretin and glyburide.
Glipizide; Metformin: (Moderate) Retinoids have been reported to cause changes in blood sugar control in diabetics. In a study of 7 healthy male volunteers, acitretin treatment potentiated the blood glucose lowering effect of glibenclamide (a sulfonylurea similar to chlorpropamide) in 3 of the 7 subjects. Repeating the study with 6 healthy male volunteers in the absence of glibenclamide did not detect an effect of acitretin on glucose tolerance. Careful supervision of diabetic patients under treatment with acitretin is recommended, especially those taking concomitant sulfonylureas. There appears to be no pharmacokinetic interaction between acitretin and glyburide.
Glyburide: (Moderate) Retinoids have been reported to cause changes in blood sugar control in diabetics. In a study of 7 healthy male volunteers, acitretin treatment potentiated the blood glucose lowering effect of glibenclamide (a sulfonylurea similar to chlorpropamide) in 3 of the 7 subjects. Repeating the study with 6 healthy male volunteers in the absence of glibenclamide did not detect an effect of acitretin on glucose tolerance. Careful supervision of diabetic patients under treatment with acitretin is recommended, especially those taking concomitant sulfonylureas. There appears to be no pharmacokinetic interaction between acitretin and glyburide.
Glyburide; Metformin: (Moderate) Retinoids have been reported to cause changes in blood sugar control in diabetics. In a study of 7 healthy male volunteers, acitretin treatment potentiated the blood glucose lowering effect of glibenclamide (a sulfonylurea similar to chlorpropamide) in 3 of the 7 subjects. Repeating the study with 6 healthy male volunteers in the absence of glibenclamide did not detect an effect of acitretin on glucose tolerance. Careful supervision of diabetic patients under treatment with acitretin is recommended, especially those taking concomitant sulfonylureas. There appears to be no pharmacokinetic interaction between acitretin and glyburide.
Leuprolide; Norethindrone: (Major) Acitretin reduces the efficacy of oral progestin only contraceptives. Since Acitretin may cause serious birth defects, the patient should use 2 forms of reliable contraception at the same time for at least 1 month before beginning acitretin therapy, during acitretin therapy, and must continue to use them for at least 3 years after acitretin treatment has stopped. It is recommended that the patient either abstain from sexual intercourse or use 2 reliable kinds of birth control at the same time to prevent unwanted pregnancy.
Levonorgestrel: (Major) Acitretin interferes with the contraceptive effect of microdose progestins ('minipill' contraceptive preparations), and may possibly interfere with the effecitivenss of emergency contraceptives like levonorgestrel (e.g., Plan B, Plan B OneStep). It is not known if acitretin also interacts with other progestational contraceptives, such as levonorgestrel implants or IUDs or if these methods are adequate methods of contraception during acitretin therapy. However, female patients should be advised of the possibility that any contraceptive method can fail. Since Acitretin may cause serious birth defects, the patient should use 2 forms of reliable contraception at the same time for at least 1 month before beginning acitretin therapy, during acitretin therapy, and must continue to use them for at least 3 years after acitretin treatment has stopped. It is recommended that the patient either abstain from sexual intercourse or use 2 reliable kinds of birth control at the same time to prevent unwanted pregnancy.
Levonorgestrel; Ethinyl Estradiol: (Major) Acitretin interferes with the contraceptive effect of microdose progestins ('minipill' contraceptive preparations), and may possibly interfere with the effecitivenss of emergency contraceptives like levonorgestrel (e.g., Plan B, Plan B OneStep). It is not known if acitretin also interacts with other progestational contraceptives, such as levonorgestrel implants or IUDs or if these methods are adequate methods of contraception during acitretin therapy. However, female patients should be advised of the possibility that any contraceptive method can fail. Since Acitretin may cause serious birth defects, the patient should use 2 forms of reliable contraception at the same time for at least 1 month before beginning acitretin therapy, during acitretin therapy, and must continue to use them for at least 3 years after acitretin treatment has stopped. It is recommended that the patient either abstain from sexual intercourse or use 2 reliable kinds of birth control at the same time to prevent unwanted pregnancy.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Major) Acitretin interferes with the contraceptive effect of microdose progestins ('minipill' contraceptive preparations), and may possibly interfere with the effecitivenss of emergency contraceptives like levonorgestrel (e.g., Plan B, Plan B OneStep). It is not known if acitretin also interacts with other progestational contraceptives, such as levonorgestrel implants or IUDs or if these methods are adequate methods of contraception during acitretin therapy. However, female patients should be advised of the possibility that any contraceptive method can fail. Since Acitretin may cause serious birth defects, the patient should use 2 forms of reliable contraception at the same time for at least 1 month before beginning acitretin therapy, during acitretin therapy, and must continue to use them for at least 3 years after acitretin treatment has stopped. It is recommended that the patient either abstain from sexual intercourse or use 2 reliable kinds of birth control at the same time to prevent unwanted pregnancy.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Major) Acitretin interferes with the contraceptive effect of microdose progestins ('minipill' contraceptive preparations), and may possibly interfere with the effecitivenss of emergency contraceptives like levonorgestrel (e.g., Plan B, Plan B OneStep). It is not known if acitretin also interacts with other progestational contraceptives, such as levonorgestrel implants or IUDs or if these methods are adequate methods of contraception during acitretin therapy. However, female patients should be advised of the possibility that any contraceptive method can fail. Since Acitretin may cause serious birth defects, the patient should use 2 forms of reliable contraception at the same time for at least 1 month before beginning acitretin therapy, during acitretin therapy, and must continue to use them for at least 3 years after acitretin treatment has stopped. It is recommended that the patient either abstain from sexual intercourse or use 2 reliable kinds of birth control at the same time to prevent unwanted pregnancy.
Medroxyprogesterone: (Major) Acitretin interferes with the contraceptive effect of microdose progestins ('minipill' contraceptive preparations). It is not known if acitretin also interacts with other progestational contraceptives, such as medroxyprogesterone injectables, or if this method is an adequate method of contraception during acitretin therapy. However, female patients should be advised of the possibility that any contraceptive method can fail. Since Acitretin may cause serious birth defects, the patient should use 2 forms of reliable contraception at the same time for at least 1 month before beginning acitretin therapy, during acitretin therapy, and must continue to use them for at least 3 years after acitretin treatment has stopped. It is recommended that the patient either abstain from sexual intercourse or use 2 reliable kinds of birth control at the same time to prevent unwanted pregnancy.
Methotrexate: (Contraindicated) The combination of methotrexate and acitretin is contraindicated. An increased risk of hepatitis has been reported from the combined use of methotrexate and the retinoid etretinate. Acitretin is the principal active component of etretinate. Although no longer available commercially in the United States, etretinate has been shown to increase methotrexate serum concentrations and cases of hepatotoxicity (e.g., hepatitis) have also been reported in patients receiving etretinate and methotrexate concomitantly.
Methoxsalen: (Moderate) Use methoxsalen and retinoids together with caution; the risk of severe burns/phototoxicity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
Minocycline: (Contraindicated) The concomitant use of acitretin and systemic tetracyclines is contraindicated, due to the potential for increased cranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Pseudotumor cerebri has been reported with systemic retinoid use alone and early signs and symptoms include papilledema, headache, nausea, vomiting and visual disturbances.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Major) Acitretin reduces the efficacy of oral progestin only contraceptives. Since Acitretin may cause serious birth defects, the patient should use 2 forms of reliable contraception at the same time for at least 1 month before beginning acitretin therapy, during acitretin therapy, and must continue to use them for at least 3 years after acitretin treatment has stopped. It is recommended that the patient either abstain from sexual intercourse or use 2 reliable kinds of birth control at the same time to prevent unwanted pregnancy.
Norethindrone: (Major) Acitretin reduces the efficacy of oral progestin only contraceptives. Since Acitretin may cause serious birth defects, the patient should use 2 forms of reliable contraception at the same time for at least 1 month before beginning acitretin therapy, during acitretin therapy, and must continue to use them for at least 3 years after acitretin treatment has stopped. It is recommended that the patient either abstain from sexual intercourse or use 2 reliable kinds of birth control at the same time to prevent unwanted pregnancy.
Norethindrone; Ethinyl Estradiol: (Major) Acitretin reduces the efficacy of oral progestin only contraceptives. Since Acitretin may cause serious birth defects, the patient should use 2 forms of reliable contraception at the same time for at least 1 month before beginning acitretin therapy, during acitretin therapy, and must continue to use them for at least 3 years after acitretin treatment has stopped. It is recommended that the patient either abstain from sexual intercourse or use 2 reliable kinds of birth control at the same time to prevent unwanted pregnancy.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Major) Acitretin reduces the efficacy of oral progestin only contraceptives. Since Acitretin may cause serious birth defects, the patient should use 2 forms of reliable contraception at the same time for at least 1 month before beginning acitretin therapy, during acitretin therapy, and must continue to use them for at least 3 years after acitretin treatment has stopped. It is recommended that the patient either abstain from sexual intercourse or use 2 reliable kinds of birth control at the same time to prevent unwanted pregnancy.
Norgestrel: (Major) Acitretin reduces the efficacy of oral progestin only contraceptives. Since Acitretin may cause serious birth defects, the patient should use 2 forms of reliable contraception at the same time for at least 1 month before beginning acitretin therapy, during acitretin therapy, and must continue to use them for at least 3 years after acitretin treatment has stopped. It is recommended that the patient either abstain from sexual intercourse or use 2 reliable kinds of birth control at the same time to prevent unwanted pregnancy.
Omadacycline: (Contraindicated) The concomitant use of acitretin and systemic tetracyclines is contraindicated, due to the potential for increased cranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Pseudotumor cerebri has been reported with systemic retinoid use alone and early signs and symptoms include papilledema, headache, nausea, vomiting and visual disturbances.
Orlistat: (Moderate) Due the effect of orlistat on fat absorption and the lower serum levels of fat-soluble vitamins noted during clinical trials, the bioavailability of acitretin may be decreased. Close monitoring of patients receiving acitretin with orlistat is recommended.
Palovarotene: (Major) Avoid concomitant use of palovarotene and other retinoids, such as acitretin, due to the risk for hypervitaminosis A.
Phenytoin: (Moderate) Acitretin reduces the protein binding of phenytoin. Free phenytoin concentrations may be useful for therapeutic monitoring if both acitretin and phenytoin are administered concurrently.
Photosensitizing agents (topical): (Moderate) Acitretin may increase the effects of photosensitizing agents used during photodynamic therapy; significantly lower doses of phototherapy are required when acitretin is used because acitretin-induced effects on the stratum corneum can increase the risk of erythema (burning).
Pioglitazone; Glimepiride: (Moderate) Retinoids have been reported to cause changes in blood sugar control in diabetics. In a study of 7 healthy male volunteers, acitretin treatment potentiated the blood glucose lowering effect of glibenclamide (a sulfonylurea similar to chlorpropamide) in 3 of the 7 subjects. Repeating the study with 6 healthy male volunteers in the absence of glibenclamide did not detect an effect of acitretin on glucose tolerance. Careful supervision of diabetic patients under treatment with acitretin is recommended, especially those taking concomitant sulfonylureas. There appears to be no pharmacokinetic interaction between acitretin and glyburide.
Porfimer: (Major) Avoid coadministration of porfimer with retinoids due to the risk of increased photosensitivity. Porfimer is a light-activated drug used in photodynamic therapy; all patients treated with porfimer will be photosensitive. Concomitant use of other photosensitizing agents like retinoids may increase the risk of a photosensitivity reaction.
Relugolix; Estradiol; Norethindrone acetate: (Major) Acitretin reduces the efficacy of oral progestin only contraceptives. Since Acitretin may cause serious birth defects, the patient should use 2 forms of reliable contraception at the same time for at least 1 month before beginning acitretin therapy, during acitretin therapy, and must continue to use them for at least 3 years after acitretin treatment has stopped. It is recommended that the patient either abstain from sexual intercourse or use 2 reliable kinds of birth control at the same time to prevent unwanted pregnancy.
Salicylic Acid: (Moderate) Dryness of the skin and mucus membranes are common side effects of retinoid therapy. Simultaneous use of retinoids and topical drying agents, such as salicylic acid, can potentiate the drying effects of retinoids on the skin. Be alert for signs of skin irritation, the offending topical agents may need to be used less often or discontinued during retinoid therapy.
Sarecycline: (Contraindicated) The concomitant use of acitretin and systemic tetracyclines is contraindicated, due to the potential for increased cranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Pseudotumor cerebri has been reported with systemic retinoid use alone and early signs and symptoms include papilledema, headache, nausea, vomiting and visual disturbances.
Segesterone Acetate; Ethinyl Estradiol: (Major) Acitretin interferes with the contraceptive effect of microdose progestins ('minipill' contraceptive preparations). It is not known if acitretin also interacts with other progestational contraceptives, such as segesterone vaginal rings, or if this method is an adequate method of contraception during acitretin therapy. However, female patients should be advised of the possibility that any contraceptive method can fail. Since Acitretin may cause serious birth defects, the patient should use 2 forms of reliable contraception at the same time for at least 1 month before beginning acitretin therapy, during acitretin therapy, and must continue to use them for at least 3 years after acitretin treatment has stopped. It is recommended that the patient either abstain from sexual intercourse or use 2 reliable kinds of birth control at the same time to prevent unwanted pregnancy.
Sodium Thiosulfate; Salicylic Acid: (Moderate) Dryness of the skin and mucus membranes are common side effects of retinoid therapy. Simultaneous use of retinoids and topical drying agents, such as salicylic acid, can potentiate the drying effects of retinoids on the skin. Be alert for signs of skin irritation, the offending topical agents may need to be used less often or discontinued during retinoid therapy.
St. John's Wort, Hypericum perforatum: (Major) Because of the teratogenic potential of acitretin, the coadministration of St. John's wort, Hypericum perforatum and acitretin should be avoided in females who are using hormonal contraceptives as their primary form of birth control. St. John's wort, Hypericum perforatum appears to interact with estrogens and oral contraceptives. Breakthrough bleeding and pregnancies have been reported following coadministration of St. John's Wort and hormonal contraception. It is thought that St. John's wort induces hormone metabolism via induction of the hepatic CYP3A4 isoenzyme. It is possible that, as with other CYP3A4 inducers, St. John's wort could also reduce the therapeutic efficacy of non-oral combination contraceptives or progestin-only contraceptives (i.e., norgestrel, levonorgestrel, and medroxyprogesterone).
Sulfonylureas: (Moderate) Retinoids have been reported to cause changes in blood sugar control in diabetics. In a study of 7 healthy male volunteers, acitretin treatment potentiated the blood glucose lowering effect of glibenclamide (a sulfonylurea similar to chlorpropamide) in 3 of the 7 subjects. Repeating the study with 6 healthy male volunteers in the absence of glibenclamide did not detect an effect of acitretin on glucose tolerance. Careful supervision of diabetic patients under treatment with acitretin is recommended, especially those taking concomitant sulfonylureas. There appears to be no pharmacokinetic interaction between acitretin and glyburide.
Tetracycline: (Contraindicated) The concomitant use of acitretin and systemic tetracyclines is contraindicated, due to the potential for increased cranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Pseudotumor cerebri has been reported with systemic retinoid use alone and early signs and symptoms include papilledema, headache, nausea, vomiting and visual disturbances.
Tetracyclines: (Contraindicated) The concomitant use of acitretin and systemic tetracyclines is contraindicated, due to the potential for increased cranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Pseudotumor cerebri has been reported with systemic retinoid use alone and early signs and symptoms include papilledema, headache, nausea, vomiting and visual disturbances.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with retinoids is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use of other photosensitizing agents like retinoids may increase the risk of a photosensitivity reaction.
According to the manufacturer, the exact mechanism of action of acitretin is unknown; however, the drug is hypothesized to disrupt the psoriatic disease process through several mechanisms. First, acitretin may inhibit the cytokine-induced increase in retinoic acid formation. Second, acitretin may stimulate metabolism and buffering of cytokine-induced increases in retinoic acid by inducing increased cellular concentrations of cellular retinoic acid binding protein (CRABP 2). Third, the drug may alter the metabolism of endogenous retinoids at the level of degradation. These pharmacologic activities of synthetic retinoids are likely to be mediated through binding and activation of nuclear receptors that mediate retinoid activity. Retinoid receptors are divided into retinoid X receptors (RXRs) and retinoic acid receptors (RARs); both types can be further divided into 3 subtypes: alpha, beta, and gamma. Acitretin has been shown to be active at all 3 RAR subtypes without measurable receptor binding in vitro. Activation of these nuclear receptors modulates transcription of genes that code for various proteins involved in the pathogenesis of psoriasis. In hyperproliferative tissues, such as psoriasis plaques, acitretin produces an antiproliferative effect; which reduces desquamation, erythema, and overall thickness of the lesion.
Acitretin is administered orally. Once in the systemic circulation, the drug is more than 99.9% bound to plasma proteins, primarily to albumin. Acitretin undergoes extensive metabolism and interconversion by simple isomerization to its 13-cis form (cis-acitretin). The formation of cis-acitretin relative to parent compound is not altered by dose or fed/fast conditions. Both the parent compound and isomer are further metabolized into chain-shortened breakdown products and conjugates. Following multiple-dosing, steady-state concentrations of acitretin and cis-acitretin in plasma are achieved within approximately 3 weeks. The chain-shortened metabolites and conjugates are ultimately excreted in the feces (34% to 54%) and urine (16% to 53%). The terminal elimination half-life of acitretin following multiple-dosing is 49 hours (range 33 to 96 hours), and that of cis-acitretin under the same conditions is 63 hours (range 28 to 157 hours). Concurrent ingestion of ethanol with acitretin results in the conversion of acitretin to etretinate, which has a much longer half-life (approximately 120 days).
Affected cytochrome P450 isoenzymes: none
-Route-Specific Pharmacokinetics
Oral Route
Oral absorption of acitretin is linear and proportional with increasing doses from 25 mg to 100 mg. Absorption is optimal when administered with food; therefore, the drug was given with food during clinical studies. Following administration of a single 50 mg oral dose to 18 healthy subjects, maximum plasma concentrations ranged from 196 to 728 ng/mL (mean 416 ng/mL) and were achieved in 2 to 5 hours (mean 2.7 hours). Approximately 72% (range 47% to 109%) of the administered dose was absorbed after a single 50 mg dose of acitretin was given to 12 healthy subjects.
-Special Populations
Renal Impairment
Plasma concentrations of acitretin following a 50 mg dose were significantly (59.3%) lower in end-stage renal failure patients (n = 6) when compared to age-matched controls. Acitretin was not removed by dialysis in these patients.
Geriatric
Elderly patients may have up to a 2-fold increase in acitretin plasma concentrations with no change in elimination half-life.