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#15170 - 05/25/01 01:21 PM Waiting Period Before Pregnancy
Laura Phillips Offline


Member

Registered: 07/31/08
Posts: 12
Loc: Detroit, MI
Hi guys,

On another discussion here http://www.ichthyosis.com/ubb/Forum3/HTML/000013.html we talked about how long you needed to wait from when you stopped taking Accutane until you tried to get pregnant. It was interesting to me, to hear peoples' doctors telling them anywhere from 2 months to 3 years (or more). I just came across this article, which seems to explain the differing wait times (oh, and keep in mind that Soriatane is acitretin):

British Journal of Dermatology
December 2000 (Volume 143, Issue 6)



Acitretin is Converted to Etretinate Only During Concomitant Alcohol Intake
Larsen FG, Steinkjer B, Jakobsen P, Hjorter A, Brockhoff PB, Nielsen-Kudsk F
Br J Dermatol. 2000;143:1164-1169
Oral retinoids such as acitretin and etretinate are highly effective agents for the treatment of keratinizing disorders such as psoriasis. Unfortunately, these drugs are also well known teratogens, limiting their use in reproductive-aged females, especially those planning to have children within years of therapy. While acitretin is rapidly cleared from the body (half-life = 2 days), its ethyl ester etretinate is highly lipophilic, with a half-life of around 120 days, leading to detectable etretinate levels up to 3 years after discontinuation of therapy.[2,3] Unfortunately, acitretin can be metabolized to etretinate, prompting agencies such as the US Food and Drug Administration to recommend pregnancy avoidance for at least 3 years after discontinuation of all retinoids, including acitretin.[3]

Is this precaution necessary for patients taking acitretin, since the drug has a half-life of 2 days? To address this problem, Larsen and colleagues designed a study with the following aims:

<OL TYPE=1>

[*]To measure the plasma levels of etretinate in 86 patients using acitretin for an assortment of keratinizing disorders (psoriasis vulgaris, pustular psoriasis, chronic dermatitis, Darier's disease, basal cell carcinoma, ichthyosis, lupus erythematosus, and lichen planus).


[*]To assess the influence of alcohol consumption on the plasma etretinate level.

</OL>
Their second goal is especially pertinent, since data from both in vivo and in vitro studies suggest that acitretin is metabolized to its ethyl ester etretinate only in the presence of ethanol.[4,5]

Results

Eighty-six patients participated in the study, in which they received daily doses of acitretin (0.1 mg/kg to 1.3 mg/kg) for up to 6 years. To ensure that steady-state plasma concentrations were obtained, only patients on acitretin for at least 4 weeks were enrolled in the study. Furthermore, no patients had been on etretinate for at least 4 years prior to study initiation. Patient alcohol consumption during the study was estimated based on patient questionnaires. Concentrations of acitretin and its primary metabolites (etretinate and 13-cis-acitretin) were measured using a reverse-phase high-performance liquid chromatography technique.

Thirty of the 86 acitretin-treated patients showed measurable etretinate levels in their plasma (concentrations ranging from 2 ng/mL to 57 ng/mL). No etretinate was found in the serum of 20 patients who reported "never drinking" alcohol, while all 16 patients consuming an average of more than 200 g/week of ethanol had detectable levels. Furthermore, 14 out of 50 patients reporting "moderate" alcohol consumption (< 200 g/week) had detectable levels. A logistic regression analysis of these findings showed that 100 g of alcohol consumption per week conferred an estimated 10 times higher risk of etretinate formation.

Discussion

In agreement with previous data,[4,5] acitretin is metabolized to etretinate in the presence of ethanol in vivo. Therefore, fertile women taking this "rapidly metabolized" retinoid should be counseled on the need for strict alcohol avoidance during therapy. In cases of noncompliance, pregnancy avoidance should be recommended for at least 2 years after treatment. Unfortunately, it is not clear whether or not certain concurrent medications, dietary, or intrinsic factors could also influence the metabolism of acitretin to etretinate. Clearly, further data are needed to better define the true "time window" of teratogenic risk associated with acitretin and its cousins.

References


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[*]Ehmann CW, Voorhees JJ. International studies of the efficacy of etretinate in the treatment of psoriasis. J Am Acad Dermatol. 1982;6:692-696.

[*]Larsen FG, Jakobsen P, Larsen CG, et al. Pharmacokinetics of etretin and etretinate during long-term treatment of psoriasis patients. Pharmacol Toxicol. 1988;62:159-165.

[*]Wiegand UW, Chou RC. Pharmacokinetics of acitretin and etretinate. J Am Acad Dermatol. 1998;39(suppl):S25-33.

[*]Larsen FG, Jakobsen P, Knudsen J, et al. Conversion of acitretin to etretinate in psoriatic patients is influenced by ethanol. J Invest Dermatol. 1993;100:623-627.

[*]Laugier JP, de Sousa G, Bun H, et al. Acitretin biotransformation into etretinate: role of ethanol on in vitro hepatic metabolism. Dermatology. 1994;188:122-125.
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[This message has been edited by Laura Phillips (edited May 27, 2001).]

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#15171 - 05/26/01 03:29 AM Re: Waiting Period Before Pregnancy
Les Avakian Offline


Member

Registered: 08/13/00
Posts: 680
Loc: Fresno, Calif. USA 93705
Hello Laura, I think your last post was very informative and very interesting.Since I only take acid creams, I would like to know more about the difference between Accutane and Soritain/Neotigason.I think both are made by Roche, which one has fewer side affects?Is one specifically made for one type of ichthyosis such as lamellar, and the other is for EHK/CIE? As for pregnancy, is one less hard on the system as the other and is the waiting period the same for both medications.Many have posted the pros and cons, but would like to know the comparisons between the two. Also, is the waiting period for resting the body from Accutane and Soritain the same? It would be a good panel discussion at the Seattle conference. I bet we would have a multiple set of answers and disagreements from the doctors and derms, but would be a good interactive session as I see it.Take care all and thanks. Bye for now. Les
_________________________
Les Avakian

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#15172 - 10/28/03 06:50 PM Re: Waiting Period Before Pregnancy
Steven Flury Offline
Junior Member

Registered: 06/20/02
Posts: 4
Loc: Louisville, Kentucky USA
Quote:
Originally posted by Les Avakian:
Hello Laura, I think your last post was very informative and very interesting.Since I only take acid creams, I would like to know more about the difference between Accutane and Soritain/Neotigason.I think both are made by Roche, which one has fewer side affects?Is one specifically made for one type of ichthyosis such as lamellar, and the other is for EHK/CIE? As for pregnancy, is one less hard on the system as the other and is the waiting period the same for both medications.Many have posted the pros and cons, but would like to know the comparisons between the two. Also, is the waiting period for resting the body from Accutane and Soritain the same? It would be a good panel discussion at the Seattle conference. I bet we would have a multiple set of answers and disagreements from the doctors and derms, but would be a good interactive session as I see it.Take care all and thanks. Bye for now. Les


Dear Les,
I suffer from Lemellar Ichthyosis & Eczema and am currently in pretty bad shape. My dermatologist has once again pushed the issue for me to get on Accutaine. I am curious as to what Laura's response was to you about this discussion. I am going in on Friday (10/31) to speak to him about starting this treatment. Please let me know. Thanks.
Steven

[This message has been edited by Steven Flury (edited October 28, 2003).]
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Steven LI sufferer

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