What are the primary uses of Acitretin. How does Acitretin affect pregnancy and liver function. What precautions should be taken when using Acitretin. How long should birth control be used after stopping Acitretin treatment. Why is alcohol consumption prohibited while taking Acitretin.

Understanding Acitretin: A Powerful Treatment for Severe Psoriasis

Acitretin, marketed under the brand name SORIATANE®, is a potent oral medication primarily used to treat severe psoriasis. This retinoid drug, derived from vitamin A, has proven effective in managing stubborn cases of psoriasis that have not responded to other treatments. However, its use comes with significant risks and stringent precautions that both patients and healthcare providers must carefully consider.

What is Acitretin used for?

Acitretin is primarily prescribed for:

• Severe psoriasis that has not responded to other treatments
• Cases where other psoriasis medications cannot be used

It works by slowing down the rapid growth of skin cells characteristic of psoriasis, helping to reduce scaling, redness, and inflammation.

Critical Safety Information: Pregnancy and Birth Defects

The most crucial aspect of Acitretin usage is its potential to cause severe birth defects. This risk is so significant that the medication is subject to strict regulations and guidelines for use in women of childbearing age.

Can Acitretin be used during pregnancy?

Absolutely not. Acitretin is strictly contraindicated in pregnant women or those who may become pregnant during treatment or within three years after discontinuing the medication. The risk of severe birth defects is extremely high and long-lasting.

What birth control measures are required?

Women of childbearing potential must adhere to the following contraceptive requirements:

1. Use two effective forms of birth control simultaneously
2. Start birth control at least one month before beginning Acitretin
3. Continue using birth control during treatment
4. Maintain contraception for at least three years after stopping Acitretin

It’s important to note that progestin-only birth control pills (“minipills”) may not be effective while taking Acitretin.

Liver Function and Acitretin: Monitoring and Precautions

Another significant concern with Acitretin use is its potential impact on liver function. Regular monitoring is essential to ensure patient safety.

How does Acitretin affect the liver?

Acitretin can cause liver problems, including abnormal liver function tests and inflammation (hepatitis). To mitigate these risks, healthcare providers should:

• Conduct blood tests before initiating Acitretin treatment
• Perform regular liver function tests during treatment
• Monitor patients for signs of liver problems

What are the signs of liver problems to watch for?

Patients should be aware of the following symptoms that may indicate liver issues:

• Yellowing of the skin or whites of the eyes (jaundice)
• Nausea and vomiting
• Loss of appetite
• Dark urine

If any of these symptoms occur, patients should stop taking Acitretin immediately and contact their healthcare provider.

Alcohol and Acitretin: A Dangerous Combination

The interaction between Acitretin and alcohol is a critical concern that requires strict adherence to guidelines.

Why is alcohol prohibited while taking Acitretin?

Alcohol consumption is strictly forbidden during Acitretin treatment and for two months after discontinuation. This is because alcohol can alter Acitretin into a compound that may remain in the body for longer than three years, potentially extending the risk period for birth defects.

This prohibition extends to:

• Alcoholic beverages
• Foods containing alcohol
• Over-the-counter products with alcohol content
• Medicines containing alcohol

Pregnancy Testing and Monitoring During Acitretin Treatment

To ensure the safety of women of childbearing potential, a rigorous pregnancy testing regimen is required before, during, and after Acitretin treatment.

What is the pregnancy testing schedule for Acitretin users?

The pregnancy testing schedule is as follows:

1. Two negative pregnancy tests before starting treatment
2. Monthly pregnancy tests during treatment
3. Pregnancy tests every three months for at least three years after stopping treatment

This extensive testing period is crucial due to the prolonged risk of birth defects associated with Acitretin.

Breastfeeding and Acitretin: Incompatible Choices

Women who are breastfeeding face a clear choice when it comes to Acitretin treatment.

Is it safe to breastfeed while taking Acitretin?

No, breastfeeding is not compatible with Acitretin use. The medication can pass into breast milk and potentially harm the nursing infant. Women must choose between breastfeeding and taking Acitretin; both cannot be done simultaneously.

Patient Education: The Do Your P.A.R.T. Program

To ensure that patients fully understand the risks and responsibilities associated with Acitretin use, a comprehensive education program has been developed.

What is the Do Your P.A.R.T. program?

The Do Your P.A.R.T. program is an educational initiative designed to inform patients about:

• Pregnancy prevention strategies
• Available birth control options
• Potential side effects of Acitretin
• The importance of avoiding alcohol-containing products

Patients should receive the Do Your P.A.R.T. brochure from their healthcare provider before starting Acitretin treatment.

Managing Acitretin Treatment: A Collaborative Effort

Successfully managing Acitretin treatment requires a strong partnership between patients and healthcare providers. Open communication, strict adherence to guidelines, and regular monitoring are essential components of safe and effective treatment.

How can patients ensure safe use of Acitretin?

To use Acitretin safely, patients should:

• Fully understand and comply with all safety precautions
• Attend all scheduled appointments and tests
• Report any concerning symptoms promptly
• Avoid alcohol and products containing alcohol
• Use effective contraception as directed
• Never share medication or skip doses without consulting their healthcare provider

By following these guidelines and maintaining open communication with their healthcare team, patients can maximize the benefits of Acitretin while minimizing potential risks.

Alternative Treatments for Severe Psoriasis

Given the significant risks associated with Acitretin, it’s important to consider alternative treatments for severe psoriasis when appropriate.

What other options are available for treating severe psoriasis?

Alternative treatments for severe psoriasis may include:

• Biologic drugs that target specific components of the immune system
• Systemic medications like methotrexate or cyclosporine
• Phototherapy using UVB or PUVA light treatments
• Topical treatments for milder cases or as adjunct therapy
• Lifestyle modifications, including stress reduction and dietary changes

The choice of treatment depends on various factors, including the severity of psoriasis, overall health, and individual patient preferences.

Long-term Considerations for Acitretin Users

Patients who have used Acitretin must be aware of long-term considerations that extend beyond the treatment period.

What long-term precautions should Acitretin users take?

Long-term considerations for Acitretin users include:

• Continued pregnancy prevention for at least three years after stopping treatment
• Regular follow-up appointments to monitor for any delayed side effects
• Awareness of potential long-term risks, such as bone changes or lipid abnormalities
• Maintaining a healthy lifestyle to support overall skin health

Healthcare providers should discuss these long-term considerations with patients and develop a plan for ongoing care and monitoring.

Acitretin in the Context of Psoriasis Management

While Acitretin is a powerful tool in the treatment of severe psoriasis, it’s important to view it as part of a comprehensive management strategy.

How does Acitretin fit into overall psoriasis management?

Acitretin can be an effective component of psoriasis management when:

• Other treatments have failed or are not suitable
• The benefits outweigh the potential risks for the individual patient
• The patient can comply with strict safety protocols
• It’s used in combination with other therapies for optimal results

A holistic approach to psoriasis management, including lifestyle modifications and psychological support, can enhance the effectiveness of Acitretin treatment.

Navigating Insurance and Cost Considerations for Acitretin

The cost of Acitretin can be a significant factor for many patients, and understanding insurance coverage and assistance programs is crucial.

How can patients manage the cost of Acitretin treatment?

To manage the cost of Acitretin treatment, patients can:

• Check with their insurance provider about coverage and copay amounts
• Inquire about patient assistance programs offered by the manufacturer
• Discuss generic options with their healthcare provider
• Explore pharmacy discount programs or coupons
• Consider working with a patient advocate to navigate financial options

Healthcare providers can often assist patients in finding the most cost-effective way to access necessary treatment.

The Future of Psoriasis Treatment: Beyond Acitretin

As medical research advances, new treatments for psoriasis continue to emerge, potentially offering alternatives to Acitretin with improved safety profiles or efficacy.

What new developments are on the horizon for psoriasis treatment?

Emerging treatments and areas of research in psoriasis management include:

• Novel biologic therapies targeting specific inflammatory pathways
• Gene therapy approaches to address underlying genetic factors
• Personalized medicine strategies based on individual genetic profiles
• Microbiome-based treatments targeting skin flora
• Advanced combination therapies for enhanced efficacy and reduced side effects

Patients and healthcare providers should stay informed about these developments, as they may offer new options for those who cannot use or do not respond to current treatments like Acitretin.

In conclusion, Acitretin remains a potent tool in the management of severe psoriasis, but its use requires careful consideration, strict adherence to safety protocols, and ongoing monitoring. By understanding the benefits, risks, and responsibilities associated with Acitretin treatment, patients and healthcare providers can work together to achieve optimal outcomes while minimizing potential hazards. As the field of dermatology continues to advance, it’s likely that new treatments will emerge, potentially offering safer or more effective alternatives for those struggling with severe psoriasis.

SORIATANE® (acitretin) Capsules

Important Safety Information for SORIATANE:

What is the most important information I should know about SORIATANE?

SORIATANE can cause serious side effects, including:

• Severe birth defects. If you are a female who can get pregnant, you should use SORIATANE only if:
• you are not pregnant now
• you can avoid becoming pregnant while taking SORIATANE and for at least 3 years after stopping SORIATANE and
• other medicines do not work for your severe psoriasis or you cannot use other psoriasis medicines

• Liver problems, including abnormal liver function tests and inflammation of your liver (hepatitis). Your prescriber should do blood tests to check how your liver is working before you start
  taking and during treatment with SORIATANE. Stop taking SORIATANE and call your prescriber right away if you have any of the following signs or symptoms of a serious liver problem:
• yellowing of your skin or the whites of your eyes
• nausea and vomiting
• loss of appetite
• dark urine

What are the important warnings and instructions about SORIATANE for women who can get pregnant?

• You must not take SORIATANE if you are pregnant or might become pregnant during treatment or at any time for at least 3 years after you stop treatment, because SORIATANE can cause severe birth defects.
• You must use 2 effective forms of birth control (contraception) at the same time while you are taking SORIATANE. You must use birth control for at least 1 month before you start taking SORIATANE, during treatment, and for at least 3 years after you stop treatment.
• Avoid progestin-only birth control pills (“minipills”). This type of birth control pill may not work while you take SORIATANE. Ask your prescriber if you are not sure what type of pills
  you are using.
• Do not take St. John’s wort while taking SORIATANE. St. John’s wort may interfere with some types of birth control.

• During treatment and for 2 months after you stop SORIATANE, you must avoid drinks, foods, and all medicines that contain alcohol. This includes over-the-counter products that contain alcohol. Avoiding alcohol is very important because alcohol changes SORIATANE into a drug that may take longer than 3 years to leave your body.
• You and your prescriber must be sure you are not pregnant before you start SORIATANE. Do not start SORIATANE until you have negative results from 2 pregnancy tests.
• After you start taking SORIATANE, you must have a pregnancy test repeated each month that you are on treatment. You must have a pregnancy test repeated every 3 months for at least 3 years after you stop
  taking SORIATANE to make sure that you are not pregnant.
• Stop taking SORIATANE right away and contact your prescriber if you get pregnant while taking SORIATANE or at any time for at least 3 years after you have stopped treatment. You need to discuss the possible effects on the unborn baby with your prescriber.
• Do not take SORIATANE if you are breastfeeding. SORIATANE can pass into your milk and may harm your baby. You will need to choose either to breastfeed or to take SORIATANE, but not both.
• You should receive the Do Your P.A.R.T. brochure from your prescriber. The brochure contains information about preventing pregnancy, birth control options, side effects, and the importance
  of avoiding products containing alcohol.

What are the important warnings and instructions about SORIATANE for male patients?

• Small amounts of SORIATANE are found in the semen of males taking SORIATANE. The amount of SORIATANE needed in semen to cause a birth defect is unknown.

What are the important warnings and instructions about SORIATANE for all patients?

• Do not donate blood while you are taking SORIATANE and for at least 3 years after stopping SORIATANE. SORIATANE in your blood can harm an unborn baby if your blood is given to a pregnant
  woman. SORIATANE does not affect your ability to receive a blood transfusion.

Who should not take SORIATANE?

• Do not take SORIATANE if you have severe liver or kidney disease.
• Do not take SORIATANE if you have repeated high blood lipids (fat in the blood).
• Do not take SORIATANE if you take methotrexate or tetracyclines. The use of these medicines with SORIATANE may cause serious side effects.
• Do not take SORIATANE if you have had an allergic reaction to SORIATANE, other medicines like SORIATANE, or to any other ingredient of SORIATANE.

What are other possible side effects of SORIATANE?

• 
  Stop taking SORIATANE and call your prescriber right away if you get the following signs or symptoms of possible serious side effects:
• aches or pains in your bones, joints, muscles, or back; trouble moving; loss of feeling in your hands or feet. These can be signs of abnormal changes to your bones or muscles.
• shortness of breath, dizziness, nausea, chest pain, weakness, trouble speaking, or swelling of a leg. These may be signs of a heart attack, blood clots, or stroke. SORIATANE can cause
  serious changes in blood fats (lipids). It is possible for these changes to cause blood vessel blockages that lead to heart attacks, strokes, or blood clots.
• vision problems. Decreased vision in the dark (night blindness). Since this can start suddenly, you should be very careful when driving at night. Stop taking SORIATANE and call your
  prescriber if you develop any vision problems or eye pain.
• abdominal pain, nausea, vomiting. These may be signs of pancreatitis (inflammation of the pancreas).
• bad headaches, nausea, vomiting, blurred vision. These can be signs of increased brain pressure that can lead to blindness or even death.
• depression and other mental health problems. There have been some reports of patients developing mental problems including a depressed mood, aggressive feelings, or thoughts of ending
  their own life (suicide). It is very important to stop taking SORIATANE and call your prescriber right away if you develop such problems.
• visual changes, frequent urination, great thirst, or hunger. These can be signs of high blood sugar.
• blood vessel problems. SORIATANE can cause fluid to leak out of your blood vessels into your body tissues. Call your prescriber right away if you have any of the following symptoms: sudden swelling in one part of your body or all over your body, weight gain, fever, lightheadedness or feeling faint, or muscle aches. If this happens, your prescriber will tell you to stop taking
  SORIATANE.
• serious allergic reactions. Call your prescriber right away if you get any of the following symptoms: hives, itching, swelling of your face, mouth, or tongue, or problems breathing.
  If this happens, stop taking SORIATANE and do not take it again.
• serious skin problems. SORIATANE can cause skin problems that can begin in a small area and then spread over large areas of your body. Call your prescriber right away if your skin becomes red and swollen (inflamed), you have peeling of your skin, or your skin becomes itchy and painful. You should stop SORIATANE if this happens.

• Common side effects. If you develop any of these side effects or any unusual reaction, contact your prescriber to see if you need to change the amount of SORIATANE you take:
• Chapped lips; peeling fingertips, palms, and soles; itching; scaly skin all over; weak nails; sticky or fragile (weak) skin; runny or dry nose, or nosebleeds. Your prescriber or pharmacist
  can recommend a lotion or cream to help treat drying or chapping.
• dry mouth
• joint pain
• tight muscles
• hair loss. Most patients have some hair loss, but this condition varies among patients. No one can tell if you will lose hair, how much hair you may lose, or if and when it may grow
  back. You may also lose your eyelashes.
• dry eyes. SORIATANE may dry your eyes. Wearing contact lenses may be uncomfortable during and after treatment with SORIATANE because of the dry feeling in your eyes. If this happens,
  remove your contact lenses and call your prescriber.
• rise in blood fats (lipids). SORIATANE can cause your blood fats (lipids) to rise. Most of the time this is not serious. But sometimes the increase can become a serious problem (see
  information under “Serious side effects”). You should have blood tests as directed by your prescriber.

Psoriasis gets worse for some patients when they first start treatment with SORIATANE. Some patients have more redness or itching. If this happens, tell your prescriber.

These are not all the possible side effects of SORIATANE. For more information, ask your prescriber or pharmacist.

What else should I avoid while taking SORIATANE?

• Avoid non-medical ultraviolet (UV) light. SORIATANE can make your skin more sensitive to UV light. Do not use sunlamps, and avoid sunlight as much as possible. If you are taking light
  treatment (phototherapy), your prescriber may need to change your light dosages to avoid burns.
• Avoid dietary supplements containing vitamin A. SORIATANE is related to vitamin A. Therefore, do not take supplements containing vitamin A because they may add to the unwanted effects
  of SORIATANE. Check with your prescriber or pharmacist if you have any questions about vitamin supplements.
• DO NOT SHARE SORIATANE with anyone else, even if they have the same symptoms. Your medicine may harm them or their unborn child.

What should I tell my doctor before taking SORIATANE?

Tell your prescriber if you have or ever had:

• liver problems
• alcoholism
• kidney problems
• high cholesterol or high triglycerides
  (fat in the blood)

• heart disease
• depression
• diabetes or high blood sugar
• an allergic reaction to a medication

Your prescriber needs this information to decide if SORIATANE is right for you and to know what dose is best for you.

Tell your prescriber about all the medicines you take, including prescription and non-prescription medicines, alcohol-containing medicines, vitamins, and herbal supplements. Some medicines
can cause serious side effects if taken while you also take SORIATANE. Some medicines may affect how SORIATANE works, or SORIATANE may affect how your other medicines work. Be especially sure to tell your prescriber if you are taking the following medicines:

• methotrexate
• tetracyclines
• glyburide
• phenytoin

• vitamin A supplements
• progestin-only oral contraceptives (“minipills”)
• St. John’s wort herbal supplement

Tell your prescriber if you are getting phototherapy treatment. Your doses of phototherapy may need to be changed to prevent a burn.

For more information about SORIATANE, please see the full Prescribing Information, including Boxed Warning,
and Medication Guide.

Acitretin – StatPearls – NCBI Bookshelf

Continuing Education Activity

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

Objectives:

• Identify the indications for acitretin.

• Describe the adverse effects/toxicity with acitretin use.

• Outline the monitoring necessary for patients on acitretin therapy.

• Review interprofessional team strategies for improving care coordination for patients undergoing acitretin therapy to improve patient outcomes.

Access free multiple choice questions on this topic.

Indications

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

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

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

FDA-approved Indication

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

Off-labeled Use

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

Mechanism of Action

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

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

Pharmacokinetics

Absorption: Generally administered with food and reaches peak plasma concentration in 2.7 hours (2-5 hours).

Plasma Protein Binding: 99.9%

Metabolism: The initial metabolism of acitretin involves isomerization; this differs from isotretinoin, where the initial metabolism is oxidation. Acitretin converts to isoacitretin. Acitretin is ultimately eliminated in the bile as beta-glucuronide derivatives or through the kidneys as soluble metabolites. Acitretin can undergo reverse metabolism to etretinate when acitretin is used in combination with alcohol.

Excretion:  Its metabolites, as well as conjugates of acitretin and cis-acitretin, are excreted in the feces (34% to 54%) and urine (16% to 53%).

Terminal Elimination Half-life: Following multiple-dose, acitretin has a half-life of 49 hours, and cis-acitretin has 63 hours.

Administration

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

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

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

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

Specific Patients Population 

• Patient with Hepatic Impairment: There is no dose adjustment guidance in the manufacturer label for patients with hepatic impairment. However, the use of acitretin is contraindicated in patients with severe hepatic impairment.

• Patient with Renal Impairment: A 53 % reduction of acitretin plasma concentrations was observed in patients with end-stage renal disease. The drug was not able to be removed by hemodialysis in these subjects.

• Pregnant Women: It is considered a pregnancy category X medicine. As per the box warning, acitretin must not be given to pregnant patients, patients who intend to become pregnant during therapy, or at least three years following discontinuation of treatment. Significant human fetal abnormalities have been reported with the administration of acitretin.

• Breastfeeding Women: Due to the potential for serious adverse reactions to infants, the manufacturer recommends avoiding acitretin in nursing mothers as the drug presents in breast milk.[7]

• Pediatric Patients: The safety and efficacy of acitretin are not established for pediatric patients.

• Geriatric Patients: In a multiple-dose trial, a 2-fold increase in acitretin plasma concentrations were observed in geriatric patients.

Adverse Effects

A high amount of vitamin A produces a wide spectrum of signs and symptoms primarily of the musculoskeletal, mucocutaneous, neuropsychiatric, central nervous systems, and hepatic systems. Many of the adverse reactions reported using acitretin capsules resemble those of the hypervitaminosis A syndrome. Following adverse reactions are reported in clinical trials and post-marketing experience.[8]

Cardiovascular: Flushing, acute myocardial infarction, thromboembolism, stroke

Immune System Disorders: Hypersensitivity, including angioedema and urticaria 

Nervous System: Headache, pain, rigors; myopathy with peripheral neuropathy which improved upon discontinuation of the acitretin.

Psychiatric: Aggressive feelings, depression, insomnia, self-injurious behavior, and/or suicidal thoughts have been reported. Since other factors may have contributed to psychiatric events, it is not known if they are related to acitretin.

Reproductive: Vulvo-vaginitis (due to Candida albicans)

Skin and Appendages: Thinning of the skin, exfoliation of the skin, xeroderma, nail disease, pruritus, erythematous rash, paronychia, particularly on the palms and soles; nail fragility, madarosis, alopecia, paresthesia, hyperesthesia, and exfoliative dermatitis

Vascular Disorders: Capillary leak syndrome

Miscellaneous: xerophthalmia, visual problems, cheilitis, rhinitis, pseudotumor cerebri, tinnitus, and epistaxis, hepatitis

Laboratory Abnormality: Hypercholesterolemia, increased liver enzymes, increased creatinine phosphokinase, hepatotoxicity, hypertriglyceridemia, hyperglycemia, hypoglycemia, reticulocytosis

Contraindications

Absolute Contraindications

• Pregnancy or woman who is likely to become pregnant

• Non-compliance with contraception

• Nursing mothers

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

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

United States Boxed Warning

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

Caution

• Concomitant administration with methotrexate increases the risk of hepatic adverse effects.

• Concomitant administration with cyclosporine increases the risk of hypertriglyceridemia.

• Acitretin can undergo reverse metabolism to etretinate with acitretin if used in combination with alcohol.[9]

• The use of other vitamin A compounds can lead to hypervitaminosis A-like toxicities.

• The combination of tetracyclines and retinoids can lead to pseudotumor cerebri and should be avoided.

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

Monitoring

• Lipid profile

• Liver function tests[10]

• Complete blood count (CBC)

• Blood glucose in patients with diabetes

• Evaluation of bone abnormalities and visual problems

• Serum pregnancy testing

Toxicity

Acitretin must be withdrawn all at once in case of acute overdosage. Overdose symptoms are similar to acute hypervitaminosis A (headache and vertigo). In both mice and rats, the acute oral toxicity (LD50) of acitretin was only observed at greater than 4,000 mg per kg dose. In one case report of an overdose, a 32-year old adult male patient with Darier’s disease took 525 mg single dose. Later, he has vomited for several hours; however, he did not experience any other ill effects. One case of fulminant hepatic failure following an intentional overdose of 600 mg of acitretin was reported where the patient demonstrated a rapid recovery and did not require liver transplantation. [11] If any female patients of childbearing potential take an overdose of acitretin, a pregnancy test is recommended at the time of overdose and needed to council patient as per box contraindication and warning related to potential birth defects. Also, need to encourage patients to use contraceptives for at least three years’ duration after the overdose.

Enhancing Healthcare Team Outcomes

Acitretin is frequently used to treat several skin disorders, including acne, psoriasis, lichen planus, and discoid lupus. While the drug is effective, it is crucial for interprofessional healthcare team members, including pharmacists, nurse practitioners, PAs, and primary care clinicians, to know its potential adverse effects. Clinicians should never prescribe the drug to a pregnant female because of the risk of teratogenicity. Also, the FDA has issued several boxed warnings about the risk of hepatitis when combining the agent with alcohol or methotrexate. When prescribing acitretin, the patient must understand the potential adverse effects and the importance of avoiding alcohol. [12][13]

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

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References

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Skillen LA, Corry A. Combination therapy of sirolimus and acitretin in solid organ transplant recipients: a new cutaneous adverse event. Clin Exp Dermatol. 2019 Jan;44(1):62-63. [PubMed: 30430627]

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Mehrtens SH, de la Hera I, Shankar S. Case of keratoacanthoma centrifugum marginatum treated with acitretin. BMJ Case Rep. 2018 Nov 01;2018 [PMC free article: PMC6214385] [PubMed: 30389737]

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Kaushik SB, Lebwohl MG. Review of safety and efficacy of approved systemic psoriasis therapies. Int J Dermatol. 2019 Jun;58(6):649-658. [PubMed: 30246393]

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Chen W, Zhang X, Zhang W, Peng C, Zhu W, Chen X. Polymorphisms of SLCO1B1 rs4149056 and SLC22A1 rs2282143 are associated with responsiveness to acitretin in psoriasis patients. Sci Rep. 2018 Sep 04;8(1):13182. [PMC free article: PMC6123456] [PubMed: 30181619]

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Guenther LC, Kunynetz R, Lynde CW, Sibbald RG, Toole J, Vender R, Zip C. Acitretin Use in Dermatology. J Cutan Med Surg. 2017 Nov/Dec;21(3_suppl):2S-12S. [PubMed: 28952335]

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Sauder MB, Cheung L, Beecker J. Acitretin-induced hepatitis: when to monitor cholestatic enzymes. J Cutan Med Surg. 2015 Mar-Apr;19(2):115-20. [PubMed: 25775629]

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Leithead JA, Simpson KJ, MacGilchrist AJ. Fulminant hepatic failure following overdose of the vitamin A metabolite acitretin. Eur J Gastroenterol Hepatol. 2009 Feb;21(2):230-2. [PubMed: 19092674]

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Disclosure: Patrick Zito declares no relevant financial relationships with ineligible companies.

Disclosure: Thomas Mazzoni declares no relevant financial relationships with ineligible companies.

The Ministry of Health withdrew the registration of two drugs due to non-submission of documents » Pharmvestnik

The Ministry of Health canceled the registration of Nevirapine for the treatment of HIV infection and the painkiller Nebolin® Caps due to the fact that manufacturers did not submit documents confirming their safety. In total, the ministry canceled the registration of nine drugs.

The regulator’s decision to cancel the state registration of Nevirapine (nevirapine), 200 mg tablets, produced by JSC R-Pharm, has been placed in the state register of medicines. The reason is the non-confirmation of state registration based on the results of an examination of the ratio of the expected benefit of the drug to the possible risk of its use.

Experts of the Federal State Budgetary Institution “NTs ESMP” of the Ministry of Health of Russia identified defects in the documents submitted to confirm registration. Based on the results of pharmacovigilance, it was not possible to evaluate the efficacy and safety of the antiretroviral drug.

In addition, the drug has not been sold in Russia since the moment of its registration, follows from the conclusion attached to the letter of the agency.

The experts also noted shortcomings in the draft instructions for medical use. They made comments, including to the sections of the instructions on pharmacological properties, dosing regimen, drug interactions and contraindications.

R-Pharm received the initial registration of the antiretroviral drug Nevirapine on July 28, 2016, registration certificate LP-003760. As indicated on the official website of the manufacturer, the company’s product portfolio includes eight drugs for the treatment of HIV infection, including Nevirapine.

Due to the lack of circulation on the Russian market, the registration of the Indian analogue of ibuprofen, Nebolin® Caps, capsules 200 mg, 400 mg, was withdrawn, the owner of Markans Pharma Limited, India, registration certificate LP-003293 dated November 05, 2015

At the same time, changes were made to the drug dossier, including the change of the copyright holder, but they did not concern the drug safety assessment, follows from the expert opinion. The drug has not been imported to Russia since 2015, and data on its safety and use to renew the registration were also not provided.

The Ministry of Health withdrew the registration of seven other drugs at the request of the holders of registration certificates:

Para Plus, aerosol for external use, Omega Pharma Laboratories, France, RU P N011606/01 dated 14. 01.2011;

Fosavans® Forte (alendronic acid + cholecalciferol), tablets 70 mg + 140 mcg, Merck Sharp and Dome B.V., The Netherlands, RU LP-001839 dated 14.09.2012;

“Syndroxocin” (doxorubicin), lyophilisate for solution preparation for intravascular and intravesical administration 10 mg, 50 mg, Actavis Group PTS exf, Iceland, RU LS-002670 dated 12/29/2011;

“Neotigazon®” (acitretin), capsules 10 mg, 25 mg, Actavis Group PTS exf, Iceland, RU P N016163/01 of 08/23/2010;

“Galantamine-Teva” (galantamine), film-coated tablets 4 mg, 8 mg, Teva Pharmaceutical Enterprises Ltd, Israel, RU LP-001539 of 27.02.2012;

Oprah (citalopram), film-coated tablets, 20 mg, 40 mg, Actavis Group PTS echf, Iceland, RU LS-000866 of 10/21/2011;

“Desmopressin” (desmopressin), dosed nasal spray, 10 mcg/dose, Actavis Group AO, Iceland, RU LSR-004295/09 dated May 29, 2009

Systemic treatment
– NEO-Clinic Tyumen

For successful treatment, it is necessary to strictly follow all the doctor’s recommendations, do not change the treatment regimen on your own.

It may be necessary to discuss this or that type of treatment with the closest family members. It is important that they understand the treatment program and give you the support you need.

Psoriasis is treated with drugs that are applied directly to the skin (topical therapy) and drugs that are taken by mouth or given by injection (systemic therapy).

The most serious side effect is the effect on fetal development during pregnancy. Women of childbearing age during treatment with Neotigazon should use contraceptives (contraception), since one of the components of the drug is excreted from the body very slowly, then contraception should be carried out within two years after the completion of the course of treatment. On the function of the gonads in men, the drug does not have a negative effect.

Neotigazon (Acitretin).

Neotigazon is a drug containing acitretin used for the systemic treatment of psoriasis. It belongs to a group of drugs called retinoids, which are synthetic derivatives of vitamin A.

Acitretin normalizes the process of maturation of the surface layer of the skin (epidermis), which is disturbed in psoriasis. Neotigazon is taken in the form of capsules. It is especially effective in people with advanced psoriasis who are not helped by topical treatments. Neotigazon treatment is best combined with phototherapy.

Like all medicines, Neotigazon has a number of side effects. Most often, dryness of the mucous membrane of the lips and eyes occurs.

There may also be a slight increase in blood fat, however, this can be monitored by regular testing and corrected either by diet or by reducing the dose of the drug.

Neoral (Cyclosporin A, sandimmun).

Cyclosporin A was originally developed to prevent rejection in kidney transplant patients. The drug is known in Russia under the name Neoral. It has a pronounced effect on the immune system, and in this regard, it has proven effective in the treatment of psoriasis. Neoral in the treatment of psoriasis is used in much lower doses than in surgical practice and only in severe cases. Neoral is taken in the form of gelatin capsules and as a solution.

Patients receiving Neoral need special supervision, therefore the drug is prescribed mainly by those doctors who have extensive experience in its use. During treatment, a number of adverse reactions may occur, including a slight increase in blood pressure, impaired kidney function, and excessive hair growth.

It is necessary to constantly do blood tests, and if adverse reactions occur, other studies. Treatment usually takes several weeks. Neoral should not be used by people with impaired renal function, with hypertension and any form of malignant diseases.

Hofitol

Hofitol is a herbal preparation produced from artichoke leaves, the main constituents of which are caffeolic and quinic acids, flavonoids and sequiterpene lactone. The drug also contains vitamins and a number of important trace elements.

In patients with psoriasis, metabolic disorders are often found, and in particular, fat metabolism, which is most often manifested by an increase in cholesterol. The use of hofitol leads to a decrease in cholesterol levels, to an increase in bile secretion, binds toxic products, improves carbohydrate metabolism, has a diuretic effect and reduces the level of urea.

It is necessary to constantly do blood tests, and if adverse reactions occur, other studies. Treatment usually takes several weeks. Neoral should not be used by people with impaired renal function, with hypertension and any form of malignant diseases.

Hofitol is available as tablets, oral solution and intramuscular injection. It should be applied 2-3 times a day. The drug can be used without age restrictions and during pregnancy.

It has practically no side effects, has a positive multifaceted effect on the organs and tissues of the human body.

Methotrexate.

Methotrexate is only used to treat severe psoriasis. It is a powerful drug that inhibits cell division. It is administered orally in tablets or by injection. Methotrexate acts on all rapidly dividing cells, so it is necessary to conduct a regular blood test to prevent inhibition of bone marrow function.