Vitamin D Analogs

Information about Vitamin D analogs and their use in treating psoriasis.

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Analogs of vitamin D3 metabolites (not the nutritional vitamin itself) can be used to treat psoriasis. Probably the best-known analog is a drug called calcipotriol, which is sold under the brand name Dovonex®. The drugs work primarily by slowing the rate at which psoriatic skin cells mutliply, and by making newly-formed skin cells differentiate into their proper forms. How, precisely, they accomplish this is not yet fully known.

These drugs are usually well-tolerated, but the most-common side effect is skin irritation at the sites of application (these are topical drugs, available as ointments, creams, or scalp solution in the case of Dovonex®). Some studies have found that up to 20% of patients experience these typically mild side effects. The risk and severity of side effects can be dramatically increased by occluding (or covering) the drug, and so Dovonex® isn’t generally recommended for “skin fold” areas, where skin can occlude other skin (such as the groin or armpits). Dovonex® is also not generally recommended for use on the face, where the skin is particularly sensitive.

A much rarer side-effect is hypercalcemia, which is an increase in the levels of calcium in the body. Risk of hypercalcemia (which can have some devastating, but reversible, effects) can be reduced greatly by following the dosage instructions on the labels (typically, for Dovonex®, do not exceed 100 grams per week for an average adult — dosage limits vary based on total area of the skin). In those cases where this is impossible (perhaps due to widespread psoriasis), your doctor may insist on monitoring your calcium levels through periodic blood tests.

There are two vitamin-D analogs which are available commercially:

Calcipotriol or Calcipotriene: This is Dovonex®. It is called Daivonex® outside North America, and Psorcutan in Germany. It is typically applied twice a day.

Tacalcitol: This is known by the brand name Curatoderm®. It is used once a day, and fewer people experience side effects with its use than with calcipotriol (perhaps due to it only being used once a day). It is also, however, less effective, in general, than calcipotriol. It is available as an ointment.

Maxacalcitol (also known as OCT) is another vitamin D analog which appears to have gone through some testing, and may soon be available under the brand name Oxarol®, at least in Japan and/or Europe. Preliminary findings showed this analog to be ten times more active than calcipotriol, but that was in, I believe, a petri dish. In November of 1999, Schering-Plough was testing it in Europe in Phase-III clinical trials, according to this web pageBroken Link. Time will tell.

Calcitriol, by the way, is another term you may hear in discussions about these drugs. It is simply the chemical name of the biologically-active form of vitamin D. WebMD also refers to another vitamin D analog only by a code: SM-10193. A quick search of Medline reveals that it apparently has no chemical or trade name yet, and SM-10193 is simply an experimental label for the chemical 26,26,26,27,27,27-hexafluoro-1 alpha,23(S),25-trihydroxyvitamin D3, which is quite a mouthful, otherwise.

And speaking of code names, calcipotriol is also known as MC903. Two “side-chain” analogs of calcipotriol are called GS1500 and CB1093 (although the latter appears to be being studied as a cancer treatment, not for psoriasis). There are various other analogs with other code names. If they become relevant to psoriasis, they’ll be listed here.

The use of calcipotriol and other vitamin D analogs is increasing as time goes by. Researchers and doctors are also finding that using these drugs in combination with other therapies can be a “one-two punch” against psoriasis. Also, adding these drugs to a treatment regimen can reduce the amount of other, riskier, drugs (such as retinoids) needed to provide adequate clearing of psoriasis, thus reducing the risk of harmful side effects overall.

Along the combination-therapy line, a new product, Dovobet®, was launched in 2002. This combines calcipotriol with betamethasone, a steroid. According to the manufacturer, LEO Pharma A/S, the two drugs are incompatible, without carefully adjusting them for pH issues, as they’ve done in Dovobet®. This product is also called Daivobet®. This is also available in the United States as Talconex.

And while we’re talking about steroids, it is technically true that Dovonex is a steroid (due to its molecular structure, vitamin D and its analogs are technically steroid hormones), but these drugs aren’t among the classes of steroids people generally talk about when discussing psoriasis. There are lots of different kinds of steroids. We don’t, for example, use anabolic steroids (the kind that build muscles) to treat psoriasis. So in the popular sense of the word ‘steroid’ (popular among psoriatics, that is), the sentence “Dovonex® is not a steroid” is correct. But if you’re talking to a molecular biologist, it’s not quite correct (and possibly, depending on what you’re talking about, just plain wrong).

Finally, while calcipotriene and related drugs are vitamin-D analogs, derived from natural vitamin D, and it is known that dietary vitamin D can have the same antipsoriatic effects, the dietary vitamin is too toxic for use as a psoriasis treatment. As I understand it, the amount of vitamin D required to treat the disease nearly guarantees hypercalcemia (see above). Suggestions from naturopaths and other alternative-medicine promoters to supplement with vitamin D to treat psoriasis should be seen as dangerous and misguided.

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