[8] Thalidomide is a known human teratogen and carries an extremely high risk of severe, life-threatening birth defects if administered or taken during pregnancy.

[8][13] Thalidomide is used as a first-line treatment for multiple myeloma in combination with dexamethasone or with melphalan and prednisone to treat acute episodes of erythema nodosum leprosum, as well as for maintenance therapy.

Thalidomide may be helpful in some cases where standard TB drugs and corticosteroids are not sufficient to resolve severe inflammation in the brain.

[18] It is recommended only as a third line treatment in graft-versus-host-disease in adults because of lack of efficacy and side effects observed in clinical trials.

[14][15] In addition, very common (reported in more than 10% of people) adverse effects include tremor, dizziness, tingling, numbness, constipation, and peripheral edema.

[14][15] Common adverse effects (reported by 1–10% of people) include confusion, depressed mood, reduced coordination, heart failure, difficulty breathing, interstitial lung disease, lung inflammation, vomiting, dry mouth, rashes, dry skin, fever, weakness, and a sense of unwellness.

[24] The risk of venous thromboembolisms with thalidomide seems to be increased when patients are treated with oral contraceptives or other cytotoxic agents (including doxorubicin and melphalan) concurrently.

[37] Celgene Corporation originally synthesized thalidomide using a three-step sequence starting with L-glutamic acid treatment, but this has since been reformed by the use of L-glutamine.

[citation needed] In 2023, it is reported that phthalic anhydride and L-glutamine under suitable conditions can react directly to form thalidomide.

[40] The German company had been established as a soap maker after World War II ended, to address the urgent market need for antibiotics.

[41] Heinrich Mückter[42] was appointed to head the discovery program based on his experience working with the German army's antiviral research.

While preparing reagents for the work, Mueckter's assistant Wilhelm Kunz isolated a by-product that was recognized by pharmacologist Herbert Keller as an analog of glutethimide, a sedative.

In late 1959, it was noticed that peripheral neuritis developed in patients who took the drug over a period of time, and it was only after this point that thalidomide ceased to be provided over the counter.

[49] While initially considered safe, the drug was responsible for teratogenic deformities in children born after their mothers used it during pregnancies, prior to the third trimester.

[citation needed] In the US, representatives from Chemie Grünenthal approached Smith, Kline & French (SKF), now GlaxoSmithKline, with a request to market and distribute the drug in North America.

A memorandum, rediscovered in 2010 in the archives of the FDA, shows that in 1956–57, as part of its in-licensing approach, Smith, Kline and French conducted animal tests and ran a clinical trial of the drug in the US involving 875 people, including pregnant women.

[citation needed] When administered at doses 50 to 650 times larger than that claimed by Chemie Grünenthal to be "sleep-inducing", the researchers could still not achieve the hypnotic effect in animals that it had on humans.

In 1958, Chemie Grünenthal reached an agreement with the William S. Merrell Company in Cincinnati, Ohio (later Richardson-Merrell, now part of Sanofi), to market and distribute thalidomide throughout the US.

However, the drug was distributed in large quantities for testing purposes, after the American distributor and manufacturer Richardson-Merrell had applied for its approval in September 1960.

[citation needed] The official in charge of the FDA review, Frances Oldham Kelsey, did not rely on information from the company, which did not include any test results.

The treatment was attempted despite the ban on thalidomide's use, and the results were favourable: the patient slept for hours and was able to get out of bed without aid upon awakening.

[62] 5.8 million thalidomide pills were distributed throughout Brazil in this time period, largely to poor Brazilians in areas with little access to healthcare, and these cases have occurred despite the controls.

The conditions required under the program include limiting prescription and dispensing rights to authorized prescribers and pharmacies only, keeping a registry of all patients prescribed thalidomide, providing extensive patient education about the risks associated with the drug, and providing periodic pregnancy tests for women who take the drug.

[65] Judah Folkman pioneered studies into the role of angiogenesis (the proliferation and growth of blood vessels) in the development of cancer, and in the early 1970s had shown that solid tumors could not expand without it.

[71] Around that time, the wife of a man who was dying of multiple myeloma and whom standard treatments had failed, called Folkman asking him about his anti-angiogenesis ideas.

[67][72] After further work was done by Celgene and others, in 2006 the US Food and Drug Administration granted accelerated approval for thalidomide in combination with dexamethasone for the treatment of newly diagnosed multiple myeloma patients.

[57][77] The disaster prompted many countries to introduce tougher rules for the testing and licensing of drugs, such as the 1962 Kefauver Harris Amendment[85] (US), 1965 Directive 65/65/EEC1 (EU),[86] and the Medicines Act 1968 (UK).

[87][88] In the United States, the new regulations strengthened the FDA, among other ways, by requiring applicants to prove efficacy and to disclose all side effects encountered in testing.

[94][95] Celgene has sponsored numerous clinical trials with analogues to thalidomide, such as lenalidomide, that are substantially more powerful and have fewer side effects — except for greater myelosuppression.

[99] It received a similar approval from the European Commission in August 2013, and is expected to be marketed in Europe under the brand name Imnovid.