Topical and Oral Retinoids to Treat Psoriasis

Retinoids are forms of Vitamin A delivered in topical and oral formulations that can slow the growth of skin cells in people with psoriasis. Since their introduction in 1971, retinoids have been used to treat a variety of skin concerns including fine wrinkles, flat warts, acne, and certain types of skin cancer.

In total, there are six topical and five oral retinoids approved for use in the United States. Of these, two are indicated for the treatment of psoriasis:

• Tazorac (tazarotene), applied topically as a cream, gel, or foam for mild to moderate psoriasis
• Soriatane (acitretin), taken orally in gelcap form for severe psoriasis only

Both are contraindicated for use in pregnancy.

How They Work

Psoriasis is an inflammatory autoimmune disease characterized by the hyperproduction of skin cells known as keratinocytes. Rather than turning over every 28 to 30 days as they are supposed to, keratinocytes divide at an incredibly accelerated rate—every three to five days—under the burden of chronic inflammation. This can lead to the formation of the dry, itchy skin plaques recognized as psoriasis.

Retinoids work by facilitating cell turnover. Rather than tempering inflammation like corticosteroids and disease-modifying antirheumatic drugs (DMARDs) do, retinoids penetrate skin cells and bind to the DNA receptors that regulate mitosis (cell division). By doing so, retinoid drugs can:

• Slow the hyperproduction of skin cells
• Reduce the size and thickness of skin plaques
• Promote the shedding of dead skin cells
• Reduce dryness and flaking
• Improve the overall skin appearance

Tazorac (Tazarotene)

Tazorac cream was the first retinoid formulation approved by the U.S. Food and Drug Administration (FDA) for the treatment of psoriasis. Generic versions of the drug have since been introduced under the brand names Avage, Fabior, Zorac, and others.

Uses

Tazorac is approved to treat mild to moderate plaque psoriasis covering less than 20% of the body in adults and children under the age of 12. Younger children should only use the product under the direction of a qualified dermatologist.

Topical corticosteroids, along with emollient moisturizers, are usually more effective at bringing symptoms under control than Tazorac. As such, Tazorac is generally used if topical corticosteroids fail to provide relief or cause serious side effects. It is rarely used on its own and may be combined with a topical steroid or vitamin D derivative to reap the benefits of both.

Tazorac is also effective as a maintenance therapy once the condition is brought under control as it has fewer long-term side effects. It is also known to increase light sensitivity and may enhance the benefits of phototherapy.

Tazorac can even be used to support the treatment of severe psoriasis when used in combination with stronger oral or injected drugs.

Contraindications

Tazorac carries a black box warning advising women to never use the drug during pregnancy, as studies have shown it can cause fetal harm. It should, therefore, only be considered when no other options are available.

Scientists aren’t sure if Tazorac can be passed to a baby through breastmilk, so speak with your healthcare provider to understand the benefits and risks of nursing while on treatment.

Tazorac should not be used in people with a known allergy to tazarotene or any of the other ingredients in the product.

Dosage

Tazorac is available in cream, gel, and foam formulations in 0.05% and 0.1% strengths. Comparatively speaking, the 0.1% formulation is more effective but is also more likely to cause side effects. Because of this, your dermatologist will likely prescribe a 0.05% formulation and switch you to the stronger 0.1% formulation if needed.

Unlike most corticosteroid creams, the 0.1% formulation is safe to use on the face. The foam version is especially useful for treating scalp psoriasis as it can better penetrate thick hair.

Application

Tazorac is used once daily and applied to the affected skin only. To prevent dryness, rub some light moisturizing cream onto the skin before applying a thin layer of Tazorac cream. You can do the same with the scalp, but avoid heavier scalp serums or oils that can block absorption.

Tazorac should never be used internally, including the mouth, vagina, or anus. It should also not be applied to the genitals unless your dermatologist tells you to. If you get some in your eyes, rinse thoroughly with water.

Side Effects

The most common side effects of Tazorac use (affecting 10% to 30% of users) are:

• Itching
• Burning
• Stinging
• Dryness and flaking
• Skin redness
• Skin pain

Many of these side effects will resolve as your body adapts to the medication; however, you may need to lower the dose or "pulse" treatment with on and off days until you are better able to tolerate it. Speak with your healthcare provider before adjusting your dosing.

In addition to the above, some people may experience a short-term worsening of psoriasis symptoms themselves.

Tazorac can also make your skin extremely sensitive to the sun. Because of this, you need to use sunscreen and wear protective clothing whenever outdoors. Unprotected skin is more likely to burn, which may, in turn, trigger a worsening of symptoms.

Interactions

If you take medications that increase photosensitivity, you will need to take extra precautions when outdoors or switch to another product.

Examples of drugs that can interact with Tazorac include:

• Thiazide drugs, like Diuril (chlorothiazide), used to treat high blood pressure
• Certain antibiotics, including tetracycline, doxycycline ciprofloxacin, and Bactrim (sulfamethoxazole/trimethoprim)

Advise your healthcare provider about any drugs you are taking before starting treatment, including over-the-counter medications, dietary supplements, herbal remedies, and recreational drugs. Never stop Tazorac without your healthcare provider's approval.

Soriatane (Acitretin)

Soriatane was approved for use by the FDA in 2003 for the treatment of severe psoriasis in adults. It is a second-generation retinoid developed from an earlier form of the drug known as Tegison (etretinate). Tegison was removed from the market in 1998 due to the high risk of side effects.

Uses

Soriatane is only used in adults with severe psoriasis who have not responded to first- and second-line drugs like hydrocortisone cream, methotrexate, or cyclosporine. Severe psoriasis is generally defined as having psoriatic plaques on more than 30% of the body or on large portions of the face, palms, or soles.

Soriatane is often used in combination with phototherapy or newer-generation biologic drugs like Humira (adalimumab) and Enbrel (etanercept).

Contraindications

Like Tazorac, Soriatane carries a black box warning indicating that the drug should never be used by pregnant women. Soriatane especially has been known to cause bone and facial malformations, structural heart and vascular defects, and meningomyelocele ("split spine") in a fetus.

Likewise, it is not known whether Soriatane can pass through breastmilk, so discuss use of the drug if you breastfeed or plan to do so.

Soriatane should not be used in people with a known allergy to acitretin or any other ingredient in the drug. Other contraindications include:

• Severe liver disease
• Severe kidney impairment
• Methotrexate, which increases the risk of liver toxicity
• Tetracycline antibiotics, which can cause abnormal intracranial pressure

Dosage

Soriatane is available as a gel cap in a 10-milligram (mg), 17.5-mg, or 25-mg strength. It is generally prescribed in a once-daily, 25-mg to 50-mg dose and taken with food for optimal absorption.

While effective, it can take up to three months before you feel the benefits of Soriatane treatment. During this time, you may experience a temporary worsening of symptoms. This is normal and is not an indication that the treatment is failing.

Side Effects

The side effects of Soriatane use are significant and sometimes severe. In fact, according to the FDA, 98% of users will experience side effects; no less than one in four users will discontinue treatment due to intolerability.

The most common side effects of Soriatane (occurring in at least 10% of users) include:

• Lip inflammation
• Hair loss
• Peeling skin
• Sneezing
• Runny nose and congestion
• Dry skin
• Nail changes
• Itchiness
• Chills and shaking
• Eye dryness
• Dry mouth
• Nose bleeds
• Joint pain
• Spinal stiffness
• Worsening of psoriasis symptoms
• Skin rash
• Abnormal skin sensations
• Skin atrophy (thinning)

Soriatane can affect other organ systems as well, including the heart, brain, liver, and circulatory system. This can result in less common but potentially more serious side effects.

Interactions

Soriatane can interact with other medications, often increasing or decreasing the blood concentration of one or both drugs. These include:

• Dilantin (phenytoin), decreasing the concentration of the epilepsy drug
• Ethanol (alcohol), which can convert acitretin to etretinate
• Glynase (glyburide), increasing the potency of the diabetes drug
• Progestin-based contraception, reducing the efficacy of birth control
• Vitamin A, which can lead to hypervitaminosis A (vitamin A toxicity)

Pregnancy Prevention

Given the risks these drugs pose to fetuses, it is recommended that women have a negative pregnancy test two weeks prior to starting treatment with Soriatane. Some healthcare providers will advise their female patients to start treatment during their period when they are definitely not pregnant.

Woman of child-bearing age who take Soriatane must use contraception consistently and take pregnancy tests every month. Women on Soriatane need to continue this for three years after treatment is stopped due to the persistence of the drug in the body.

If a positive pregnancy test result is returned, you will need to stop treatment immediately and call your healthcare provider. If you are unable to adhere to contraception, you may need to choose a form of treatment other than Soriatane.