How thalidomide works
The first effect of thalidomide, which was discovered in the 1950s, is based on the imitation of a messenger substance in the brain (neurotransmitter). This neurotransmitter – known as GABA – is the most important inhibitory messenger substance in the brain. It reduces communication between nerve cells, which makes people sleepy.
Thalidomide mimics this effect and was therefore initially used as a sleeping pill. It was later discovered that the active ingredient also has an anti-nausea effect, including morning sickness in pregnant women. As a result, thalidomide was also advertised specifically for this application.
The drug laws at the time did not yet guarantee comprehensive drug safety. As a result, the researchers failed to realize that thalidomide also had an inhibitory effect on inflammation, tumours and the formation of new blood vessels. The latter effect in particular is fatal in pregnant women, as was shown around 1960:
Many women who had taken thalidomide during pregnancy gave birth to children with missing or insufficiently developed arms and legs (phocomelia). The name of the drug is still referred to today as the “thalidomide scandal”. After the serious side effects became known, the drug was withdrawn from the market worldwide.
Malignant tumors sometimes grow so quickly that they need to stimulate the formation of new blood vessels in order to enable a rapid and targeted supply of nutrients and oxygen. This is the only way to ensure the rapid growth of the tumor.
Thalidomide and similar, newer active substances such as lenalidomide impede this new blood vessel formation, which impairs the growth of the tumor. They are known as IMiD (immunomodulatory mide drugs).
Absorption, breakdown and excretion
After ingestion, thalidomide is absorbed into the blood via the intestine, where it reaches its highest levels after one to five hours. The active substance is broken down in the body and excreted mainly via the urine.
Approximately five to seven hours after ingestion, around half of the administered dose can still be found in the blood (half-life).
When is thalidomide used?
Thalidomide is approved in Germany for the treatment of untreated multiple myeloma (plasmacytoma) in patients over 65 years of age or who cannot tolerate high-dose chemotherapy. There are no preparations on the market in Austria and Switzerland.
However, the active substance may only be used in combination with prednisone (an anti-inflammatory corticosteroid) and melphalan (a cytostatic drug for cancer therapy). This application within the official approval is referred to as “in-label use”.
Treatment with Thalidomide is carried out in cycles, allowing the body to recover in the meantime. A maximum of twelve cycles with a duration of six weeks each are recommended.
How thalidomide is used
As thalidomide makes you tired, the daily dose of usually 200 milligrams should be taken at bedtime (25 to 100 milligrams of thalidomide were taken when it was first used as a sleeping pill). The medication is swallowed with a glass of water and independently of a meal.
In addition, the active ingredients prednisone and melphalan must be taken in the dosage prescribed by the doctor.
Women must take a pregnancy test before starting treatment and regularly during therapy. Contraception must also be used for the entire duration of treatment. Male patients must also use suitable contraception (e.g. a condom), as even the amount of thalidomide present in the ejaculate can have a fertility-damaging effect in women.
What are the side effects of thalidomide?
The side effects relate to the approved use of thalidomide together with prednisone and melphalan:
In one in ten to one hundred patients, thalidomide causes pneumonia, depression, confusion, coordination disorders, reduced cardiac performance, slowed heartbeat, blood clot formation, shortness of breath, vomiting, dry mouth, skin rash, dry skin, fever, weakness and/or malaise as side effects.
What should be considered when taking Thalidomide?
Contraindications
Thalidomide must not be taken…
- in case of hypersensitivity to the active substance or any of the other ingredients of the medicine
- during pregnancy
- by women of childbearing potential who do not meet the requirements of the pregnancy prevention program
- by men who are unable or unwilling to use the required contraceptive methods
Interactions
Taking thalidomide with other active substances that make you tired can increase tiredness. These include, for example, psychotropic drugs for anxiety, delusions and psychosis as well as sleeping pills, drugs for seizures and epilepsy, drugs for allergies (antihistamines), strong painkillers (opiates and opioids) and also alcohol.
During treatment with thalidomide, the effect of drugs that slow down the heartbeat may increase. Such medications include beta-blockers (used to treat high blood pressure, among other things).
Age restriction
There is no relevant benefit in children and adolescents in the approved indication “multiple myeloma”. This form of cancer is a disease of advanced age.
Pregnancy and breastfeeding
Pregnant and breastfeeding women must not be treated with thalidomide under any circumstances, as the active substance severely impairs the normal development of the child and can even lead to the child’s death in pregnant women.
How to obtain medication with thalidomide
According to the German Medicines Act, the prescription and dispensing of medicines containing thalidomide are subject to special requirements. The doctor may only prescribe such medication on a special white prescription – the so-called T-prescription (T for thalidomide).
The pink prescription (generally for prescription-only medicines) and the yellow prescription (for narcotics) cannot be used for this purpose. The T prescription is only issued to the doctor after further training in the treatment of patients with this specific active substance. He must also note on the prescription that the patient is not pregnant and whether the application is “in-label” or “off-label”.
No medicinal products containing the active substance thalidomide are registered in Austria and Switzerland.
Since when has thalidomide been known?
It has been approved for the treatment of leprosy in the USA since 1998 and for the treatment of cancer in Germany since 2008. The pharmaceutical company Celgene is the only company worldwide to market drugs containing the active ingredient thalidomide.
