Leprosy mailing list – December 10^th, 2005

Ccn:     all.

From:   G Penna, Brasilia, Brazil.

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Dear Dr. Noto,

 I have been involved in leprosy activities for the last 20 years, using and doing research on thalidomide. Therefore, I would like to add some topics in the THALIDOMIDE x SEMINAL FLUID x TERATOGENICITY discussion.

            Brazil has the largest use of thalidomide in public health service in the world. Moreover, Brazil is the only endemic country for leprosy that provides this drug. Despite its extensive use, there is no report of birth defects relating its uses in man. Among the 62 reported cases of teratogenicity involving thalidomide in Brazil, for the last 30 years, none of them was related to seminal fluid. In all cases, the mother was taken the medicine, even when the husband was a leprosy patient. .

In 2000, during a workshop on thalidomide which was held in U.S.A. and sponsored by FDA, NIH and CDC, thalidomide´s metabolites were demonstrated in rare patient’s seminal fluid. This information was available on FDA´s homepage until the publication of Teo SK et al in 2001.

It was well established that a single dosis of 100mg of thalidomide is enough to cause teratogenicity, if the drug is taken between the 27^th to the 50^th day of pregnancy.

Thalidomide has a half-life of 8,7 ±4,11h and urinary excretion. It was stressed that the drug is not detected in the urine 48h after its withdrawn.

Therefore, since those rare cases were reported, a consensus was published establishing that men should use one contraceptive method during the entire of treatment and until one month after the end of it. Women should use 2 contraceptive methods before, during and one month after the drug withdrawn.

I was involved, as a PI, in the CIlinical trial - Thalidomide in the treatment of erythema nodosum leprosum (ENL): systematic review of clinical trials and prospects of new investigations Penna GO, Martelli CMT, Stefani M.A, Macedo VO. Maroja MF and Chaul A) Published in Anais Bras. Dermatol. Vol80 N5 511-522 set-out 2005 Avaliable in English and Portuguese in www.anaisdedermatoligia.org.br This study was supported by Celgene Corporation and regulated by FDA.

Thalidomide is a teratogenic sedative first developed for the use as antiemetic drug for pregnancy. Once the disaster happened, a great development of world pharmacology took place

 The hypothesis that these metabolites found on seminal fluid of rare patients could cause teratogenicity is based only on anecdotal reports. Thalidomide cause 62 unpleased cases of birth defects, however, it avoided disabilities in thousands of patients.

 References:

 (1)

CDC / FDA / NIH - Thalidomide: Potential Benefits and Risks. An open Public Scientific Workshop Washington September 1997 - Site FDA / 2000

 (2) Peuckmannn, V. et al - Potential Novel Uses of Thalidomide Focus on Paliative Care, Drugs 2000

 (3) Neiger, L. Brad - The Re-emergence of Thalidomide: Results of a Scientific Conference - Teratology – 2000

 (4) Steve K. Teo et al – Thalodomide is distributed into human semen after oral dosing. Drugs Metabolism and Deposition, Vol 29 N0 19 1355-1357 2001

 

Sincerely yours,

Gerson Penna - MD PhD
Núcleo de Medicina Tropical 
Universidade de Brasilia
Brasília - DF