Alitretinoin

Action and Spectrum

Actions and Spectrum: 

Action: alitretinoin serves as a systemic medication primarily indicated for the management of severe chronic hand eczema. that has not responded to topical treatments. It belongs to the retinoid class of drugs and works by modifying the immune response and reducing inflammation in the skin. 

Spectrum: alitretinoin has a specific spectrum of action, primarily targeting the treatment of severe chronic hand eczema. Its use is limited to this dermatological condition and is not typically prescribed for other skin disorders or diseases. alitretinoin is available in oral capsule form and is generally prescribed under medical supervision when other treatments have failed to produce satisfactory results. 

Drug Interaction

Adverse Reaction

Frequency defined  

>10% 

Endocrine & metabolic: Increased LDL cholesterol (>10%) 

increased serum triglycerides (10 mg:17%,30 mg: 35%) 

Nervous system: Headache (11% to 22%) 

Hematologic & oncologic: Decreased monocytes (16% to 22%) 

1% to 10% 

Dermatologic: cheilitis (1% to 2%), erythema of skin (2% to 7%), Alopecia (2%), xeroderma (3%) 

Gastrointestinal: xerostomia (3%), upper abdominal pain (1%), Dyspepsia (1%), vomiting (1%) 

Infection: Influenza (2%)  

Cardiovascular: hypertension (1% to 2%), Flushing (2% to 6%) 

Nervous system: dizziness (2%), Depression (3%) 

Respiratory: pharyngitis (1%),Nasopharyngitis (6%) 

Hematologic & oncologic: Reticulocytopenia (1% to 5%) 

Ophthalmic: dry eye syndrome (2% to 3%) Abnormal sensation in eyes (≤1%), conjunctivitis (2%) 

Endocrine & metabolic: hypercholesterolemia (1%), Decreased HDL cholesterol (5% to 10%), high total iron binding capacity (1% to 5%), weight gain (1%) 

Neuromuscular & skeletal: increased creatine phosphokinase in blood specimen (2% to 3%), Arthralgia (2%), back pain (2%) 

Frequency not defined: 

Neuromuscular & skeletal: Myalgia 

Gastrointestinal: Ileitis 

Hematologic & oncologic: decreased red blood cells, Decreased hematocrit, decreased hemoglobin 

Black Box Warning

Black Box Warning:  

Teratogenicity: alitretinoin is a known human teratogen based on findings in animal studies and its structural similarity to other retinoids, which have been shown to cause developmental abnormalities.  

alitretinoin is contraindicated in pregnant womens. alitretinoin should only be prescribed by healthcare providers who are experienced in the use of systemic retinoids and are knowledgeable about the risk of teratogenicity. 

Contraindication / Caution

Contraindication/Caution:  

Pregnancy: alitretinoin is known to cause severe birth defects and should not be used during pregnancy. Women of childbearing age should use effective contraception before starting treatment, during treatment, and for at least one month after discontinuing the medication. 

Breastfeeding: alitretinoin may be excreted in breast milk and has the potential to harm the nursing infant. It is not recommended for use while breastfeeding. 

Hypersensitivity: Individuals with a known hypersensitivity or allergy to alitretinoin or any of its components should not use this medication. 

Severe liver disease: alitretinoin is metabolized in the liver, and individuals with severe liver impairment may experience increased toxicity from the drug. Its use is contraindicated in such cases. 

Elevated blood lipid levels: alitretinoin may cause an increase in blood lipid levels, including triglycerides and cholesterol. Individuals with pre-existing or uncontrolled high blood lipid levels should not use this medication. 

Vitamin A toxicity: alitretinoin is a retinoid, and its use is contraindicated in individuals with a history of vitamin A toxicity. 

Hypercalcemia: alitretinoin can cause an increase in blood calcium levels. It should be avoided in individuals with hypercalcemia (elevated blood calcium levels). 

Pancreatitis: alitretinoin has been associated with cases of pancreatitis. Individuals with a history of pancreatitis should not use this medication. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excreted into human milk is unknown 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 

Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.   

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.   

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology:  

alitretinoin serves as a systemic medication primarily indicated for the management of severe chronic hand eczema in adult patients who have not responded to potent topical corticosteroids. 

Pharmacodynamics:  

alitretinoin is a synthetic retinoid, which is a derivative of Vitamin A. It exerts its pharmacological effects by binding to specific nuclear receptors (retinoic acid receptors) within the cells. Once bound, these receptors act as transcription factors, leading to the regulation of target genes involved in cell differentiation and proliferation.   

Pharmacokinetics: 

Absorption 

alitretinoin is administered orally as a capsule. After ingestion, it is absorbed from the gastrointestinal tract into the bloodstream. The absorption of alitretinoin can be affected by food intake, as taking the medication with a high-fat meal can increase its bioavailability. 

Distribution 

Once absorbed into the bloodstream, alitretinoin circulates throughout the body and can distribute to various tissues, including the skin. It has a high affinity for binding to plasma proteins, such as albumin. 

Metabolism 

alitretinoin undergoes extensive metabolism in the liver. The primary pathway of metabolism is through the cytochrome P450 enzyme system, mainly CYP2C9 and CYP3A4. These enzymes convert alitretinoin into various metabolites, some of which are active and contribute to its pharmacological effects. 

Excretion and Elimination 

The elimination of alitretinoin and its metabolites primarily occurs through the feces (main route) and, to a lesser extent, in the urine. The elimination half-life of alitretinoin can vary between individuals but is generally around 0.5 to 2 days. 

Adminstartion

Administration:  

Dosing: The dosage of alitretinoin will vary depending on the individual’s condition, weight, and response to the treatment.  

Timing: alitretinoin is usually taken once daily with a meal to increase its absorption and reduce the risk of stomach upset. Taking it with a high-fat meal can also enhance its absorption. 

Duration: The duration of treatment with alitretinoin can vary, but it often lasts for several weeks to months. Follow your healthcare provider’s instructions regarding the duration of treatment. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: alitretinoin (systemic) 

Why do we use alitretinoin (systemic)?  

Treatment of Chronic Hand Eczema: alitretinoin is specifically indicated for severe cases of chronic hand eczema in adult patients. It is used when other treatments, such as topical steroids or immunosuppressive agents, have not been effective or are not suitable for various reasons. 

Improvement of Skin Symptoms: alitretinoin helps reduce inflammation, redness, and scaling of the skin, which are common symptoms of chronic hand eczema. By improving these symptoms, it can alleviate discomfort and pain associated with the condition. 

Restoration of Hand Function: Severe hand eczema can impair hand function, making it difficult for individuals to carry out everyday tasks and work-related activities. alitretinoin’s efficacy in treating the condition may help restore hand function and improve patients’ ability to use their hands without pain or discomfort. 

Disease Control and Management: alitretinoin is used to achieve disease control in chronic hand eczema patients, as it helps suppress inflammation and minimize flare-ups. Maintaining disease control is crucial for long-term management and preventing the condition from worsening. 

Oral Therapy Option: For individuals with severe chronic hand eczema that cannot be effectively managed with topical treatments alone, alitretinoin provides an oral therapy option to address the condition systemically.