By Frangiska Mylona,
Back in 1954, a German pharmaceutical manufacturing company named Grünenthal, synthesized Thalidomide as a by-product of glutamic acid. It was not until later that the drug was issued in Germany under the brand name “Contergan”. Nevertheless,this drug was found to be catastrophic against pregnant women and their embryos.
It is crucial to remember that the procedures to test the effectiveness, reliability, and adverse reactions of drugs during these times, were not as advanced as they are today. In addition, there were no guidelines for developing, producing, and marketing pharmaceuticals, as they are today, in most countries. However, this is not something that can justify the following incidents and their severity. The ”Thalidomide tragedy” was one the most traumatic, pharmaceutical events that led to the establishment of today’s procedures regarding drug authorization and monitoring.
Later, in 1957, the drug was made available worldwide and shipped internationally. Thalidomide became very popular not only in Germany but also in Australia, Japan, and Europe, and especially among pregnant women.
Thalidomide drug was first advertised and used as a sedative drug because it could induce a state of deep sleep while reducing the risk of drug dependency. However, its popularity grew due to its anti-emetic properties that helped pregnant women overcome their morning sickness.
However, in 1959 its first adverse effects appeared. It was first suspected of causing polyneuritis, meaning multiple nerve damage, in patients treated with it. At the same time, towards the end of the 1950s, the number of children born with deformities increased. In fact, because Thalidomide has the ability to bind to and inactivate Cereblon, a protein important in limb formation, fetuses were born with amelia (absence of limbs), phocomelia (a rare congenital anomaly where the proximal aspect of an extremity is absent with the hand or foot attached directly to the trunk), external ear and ocular deformities as well as internal organ damage and congenital heart defects. The adverse effects of Thalidomide affected around 10.000 children worldwide and resulted in the death of fifty percent of them. Furthermore , pregnant women taking the drug had a marked increase in the chances of miscarriage.
These teratogenic effects were mostly observed by two doctors; Widukind Lenz in Hamburg and William McBride in Australia, that worked independently and concluded the same results. Their conclusions led Grünenthal to withdraw its Thalidomide-containing medicines from the German market and inform its international distribution and licensed partners to do the same.
The trial was called the “Thalidomide trial” and went against nine senior Grünenthal employees. The trial began in May of 1986 in Alsdorf and was concluded two and a half years later, in December of 1970. It has long been considered the most complex criminal proceeding in German legal history where dozens of witnesses and medical experts were heard.
However, since Thalidomide has unique and significant immunomodulatory and anti-angiogenic effects, it is still used for a few specific indications. Specifically, back in 2006, it started to be used to treat patients with multiple myeloma since it can prevent metastasis, growth, and hypervascularity of tumors. However, it was also associated with an increased risk of deep vein thrombosis and pulmonary embolus in patients taking this drug. Also, it has undergone clinical trials to treat patients with other illnesses like Crohn’s disease.
Moreover, in Brazil, Thalidomide was used to treat Erythema Nodosum Leprosum, a complication of leprosy that manifests with fever, painful skin nodules, arthralgia, and peripheral neuritis where Thalidomide proved to be pretty effective against it. In 2013, it is was again suspected and accused in Brazil for causing birth defects.
Thalidomide is strongly contraindicated during pregnancy, as it should be. It is included in the Category X drug’s list meaning that it can cause fetal abnormalities ,and therefore, its adverse effects outweigh any potential therapeutic benefits in pregnant women. The drug is also contraindicated for women who are or may become pregnant. If a woman is of childbearing age and has to take Thalidomide, she needs to follow the steps below.
The first step is to take a pregnancy test within 24 hours before the beginning of Thalidomide therapy. A prescription for Thalidomide must not be issued until a written report of a negative pregnancy test is obtained from the practitioner. Also, effective contraception must be used for at least 4 weeks prior to starting Thalidomide therapy, during Thalidomide therapy, and for 4 weeks after discontinuing Thalidomide therapy. Effective and reliable contraception must be used even if there is a history of infertility , with some minor exceptions, for example if the woman has undergo hysterectomy or if the patient is in a postmenopausal state for at least two years.
Lastly, once Thalidomide treatment begins, pregnancy testing should occur weekly during the first 4 weeks of use. It should be repeated once every 4 weeks for women with regular menstrual cycles. If menstrual cycles are irregular, pregnancy testing should be done every 2 weeks.
Pregnancy testing and counseling should be performed on any patient that misses her period or has any abnormal menstrual bleeding.
Male patients should also take precautions when they are needed to use Thalidomide because it is present in their semen. Latex condoms are imperative during any sexual contact with women of childbearing potential, even if the male has undergone a successful vasectomy.
In conclusion, many people were affected directly or indirectly by Thalidomide’s adverse effects. As a result of their children’s misfortune, many parents had to see themselves as the cause and blame themselves even if it was not their fault. It is not uncommon to see tragedies after drug use, even in our days.Therefore,it is crucial to conduct more rigorous and meticulous tests prior to a drug’s release.The center of medicine and pharmacology has always been and remains as to improve human life and provide therapy to the ones in need, so this should be protected by any means. It is always essential to determine if a drug is a “silent killer” regardless of whether its therapeutic effects seem ideal.
References
- Thalidomide. tmedweb.tulane.edu. Available here
- History of Thalidomide. news-medical.net. Available here
