Generality
Thalidomide is an active ingredient currently used in the treatment of multiple myeloma .
More precisely, in the pharmacological therapy of the aforementioned malignant tumor, thalidomide is used in association with two other active ingredients: melphalan (an anticancer drug belonging to the class of alkylating agents) and prednisone (corticosteroid drug).
Thalidomide has a chiral center ; in fact, in the clinical setting, a mixture of enantiomers (R) - (+) - thalidomide and (S) - (-) - thalidomide is used.
In order to perform its action, thalidomide must be administered orally ; the drugs that contain it can be dispensed only upon presentation of a non-repeatable limitative prescription (drugs sold to the public on prescription from hospitals or specialists).
Among the contraindications of thalidomide, the use during pregnancy certainly stands out, absolutely forbidden because of the teratogenic effects it is able to induce. Paradoxically, thalidomide was marketed in the fifties with indications for the treatment of gravid nausea. The damage induced by taking the drug was considerable and led to the birth of thousands of children with congenital malformations of various types (in particular phocomelic newborns).
Examples of Specialties Medicines containing Thalidomide
- Thalidomide Celgene®
Therapeutic indications
When is the use of thalidomide indicated?
Thalidomide is currently used - in combination with melphalan and prednisone - in the treatment of multiple myeloma (a particular type of malignant tumor that affects certain types of cells in the immune system, the plasma cells).
Generally, thalidomide is used in the first-line treatment of patients who are 65 years of age or older. However, it can also be used in patients under the age of 65, but only if they cannot be treated with high-dose chemotherapy.
Did you know that ...
Before starting treatment with thalidomide, the doctor will give the patient all the necessary information, especially those related to side effects and use in pregnancy. In this regard, the doctor will provide patients with informational material, informing them of the existence of a particular program known as the " Pregnancy Prevention Program ". This program must be followed by women of childbearing age who must undergo therapy with thalidomide and women of childbearing age whose male partner must undergo the same drug therapy (in fact, thalidomide may be excreted in the seminal fluid).
Warnings
Warnings and Precautions for the use of Thalidomide
Before starting treatment with thalidomide, women of child- bearing age must necessarily adopt contraceptive measures within 4 weeks prior to treatment, for the duration of the treatment and for 4 weeks following the end of treatment. In this regard, the doctor will provide all the necessary information.
As a precautionary measure, male patients should also use adequate contraceptive measures (condoms) before, during and after thalidomide treatment. Indeed, thalidomide is excreted in the seminal fluid, therefore, it is necessary to use barrier contraceptive methods in order to avoid the possible onset of pregnancies.
In addition to the above, before starting thalidomide therapy, you must inform your doctor if you suffer - or have suffered in the past - of one or more of the following diseases and conditions:
- Heart attack and / or other heart conditions;
- Hypertension and / or other vascular diseases;
- Hypercholesterolemia;
- Neutropenia, thrombocytopenia and other blood cell disorders;
- Liver diseases and disorders;
- Diseases and disorders of the kidneys;
- Viral infections sustained by different types of viruses, such as that of varicella, that of hepatitis B, HIV, etc .;
- Stevens-Johnson syndrome or toxic epidermal necrolysis;
- Allergic reactions following a previous thalidomide intake.
In any case, before taking thalidomide-based medicines, it is always advisable to talk to your doctor about your health conditions and inform them of the possible presence of any type of disorder or illness, even if not listed in the above list.
Finally, it is recalled that the administration of thalidomide is not recommended in children and adolescents under the age of 18 years.
Please note
Thalidomide can cause side effects (dizziness, tiredness, drowsiness, etc.) that can alter the ability to drive and / or use machinery. Therefore, extreme caution is recommended.
Pharmacological Interactions
Interactions between Thalidomide and Other Drugs
Before starting thalidomide therapy, you need to tell your doctor if you are taking other medicines, such as:
- Sedatives or other drugs that can cause drowsiness;
- Drugs capable of reducing heart rate (for example, beta-blocker and anticholinesterase drugs);
- Digoxin or other drugs used to treat heart problems;
- Warfarin and other drugs that affect blood clotting;
- Drugs capable of causing neutropenia;
- Contraceptive drugs.
In any case, it is advisable to inform your doctor if you are taking - or if you have recently taken - drugs or products of any kind, including medicines without a prescription (SOP), over-the-counter drugs (OTC), herbal and herbal products and homeopathic products.
Please note
Alcohol consumption should be avoided during treatment with thalidomide.
Side effects
Side effects caused by thalidomide intake
Thalidomide can cause several side effects, although not all patients manifest them, or manifest them in the same way. In fact, each person responds in a subjective manner to the administration of the active ingredient in question. However, below are some of the main side effects that can occur during thalidomide treatment.
Blood and lymphatic system disorders
Treatment with thalidomide may cause:
- Neutropenia;
- Leukopenia;
- Anemia;
- lymphopenia;
- Thrombocytopenia;
- Febrile neutropenia;
- Pancytopenia.
Nervous system disorders
Thalidomide-based therapy can cause:
- dizziness;
- Tremors;
- paresthesia;
- dysesthesia;
- Peripheral neuropathy;
- Convulsions;
- Disorders of coordination;
- Reversible posterior encephalopathy syndrome (PRES);
- Worsening of the symptoms of Parkinson's disease.
Cardiac and vascular disorders
The use of thalidomide may give rise to:
- bradycardia;
- Heart failure;
- Deep venous thrombosis;
- Myocardial infarction;
- Atrial fibrillation;
- Atrioventricular block.
Gastrointestinal disorders
Oral administration of thalidomide can lead to the appearance of:
- Constipation;
- Dry mouth;
- He retched;
- Intestinal obstruction;
- Gastrointestinal perforation;
- Gastrointestinal hemorrhage.
Skin and subcutaneous tissue disorders
The treatment based on thalidomide could lead to the onset of:
- Skin eruptions;
- Dry skin;
- Stevens-Johmson syndrome or toxic epidermal necrolysis.
Lung and airway disorders
Thalidomide therapy may give rise to:
- Dyspnoea;
- Pulmonary;
- Pulmonary embolism and pulmonary infarction;
- Interstitial lung disease;
- Pulmonary hypertension.
Other side effects
Other side effects that could occur with thalidomide intake are:
- Allergic reactions, even serious, in sensitive individuals;
- Hypothyroidism;
- Confusion and depressive states;
- Hearing changes;
- Infections favored by the reduction of immune defenses;
- Hepatic disorders;
- Kidney failure;
- Temperature;
- Drowsiness;
- Malaise and tiredness;
- Sexual dysfunction and menstrual disorders.
Finally, treatment with thalidomide could also lead to the appearance of acute myeloid leukemia, myelodysplastic syndrome and tumor lysis syndrome.
Overdose
In the event of an overdose - ascertained or presumed - from thalidomide, it is necessary to contact the nearest emergency department bringing with them, if possible, the packaging of the medicinal product containing thalidomide that has been taken. There is no specific antidote against overdose with this active ingredient, therefore, the treatments put in place are generally symptomatic and supportive.
Action mechanism
How does Thalidomide work?
Thalidomide is used in association with other active ingredients in the treatment of multiple myeloma, a particular type of malignant tumor that affects certain cells of the immune system, the plasma cells.
More in detail, thalidomide is able to exert immunomodulatory, anti-inflammatory and antineoplastic activity . These activities seem to be related to the ability of the active principle to suppress the hyperproduction of tumor necrosis factor alpha (TNF-α) - involved in the proliferation of tumor cells - and to its ability to inhibit angiogenesis . Thanks to these activities, therefore, thalidomide is able to hinder the development of tumor cells and hinder the growth of blood vessels within the tumor (angiogenesis).
Finally, it should be remembered that thalidomide is also capable of exerting a sedative-hypnotic action at the central level.
Method of use and Posology
How to take thalidomide
Thalidomide is available as capsules for oral use . The capsules should be swallowed whole with a glass of water. Under no circumstances should the capsules be opened, broken or chewed.
Each capsule contains 50 mg of active ingredient. The usual recommended dose for patients over 75 years of age is 200 mg per day (4 capsules); while for patients under the age of 75, the usual recommended dose is 100 mg per day (2 capsules).
In any case, the exact dose of active ingredient to be taken will be established by the doctor on a strictly individual basis for each patient. Therefore, it is absolutely necessary to follow the instructions provided by it.
It is advisable to take the drug in the evening before going to bed.
Pregnancy and breastfeeding
Can thalidomide be taken during pregnancy and during breastfeeding?
The use of thalidomide during pregnancy is contraindicated . In fact, this active ingredient is able to exert a teratogenic effect and lead to the death of the fetus or the birth of children suffering from severe congenital malformations (phocomelia, eye malformations, heart malformations, etc.). Such malformations can sometimes prove fatal.
Studies have shown that even the intake of a single thalidomide capsule during the so-called "critical period" (estimated between 20 and 36 days after fertilization or between 34 and 50 days after the last menstrual period) is capable to cause congenital malformations in 50% of pregnancies.
Furthermore, women of child-bearing age must adopt appropriate contraceptive measures both before and during and after treatment with the active ingredient in question.
If pregnancy occurs during treatment with thalidomide, you should contact your doctor immediately, while taking the active ingredient should be stopped immediately.
It is not known whether thalidomide is excreted in breast milk. However, as a precautionary measure, breastfeeding during therapy with this active ingredient should be avoided .
Contraindications
When thalidomide should not be used
The use of thalidomide is contraindicated in the following cases:
- Known hypersensitivity to thalidomide itself and / or to any of the excipients contained in the medicinal product to be used;
- During pregnancy;
- In women of childbearing age who are planning a pregnancy;
- In women or men of child-bearing potential who are unable to follow or follow the recommended contraceptive measures during thalidomide treatment.
Thalidomide and Teratogenicity
Use of thalidomide and related teratogenic effects
As mentioned, the use of thalidomide is not indicated during pregnancy due to the teratogenic effect that the active ingredient in question is able to exercise.
Unfortunately, the teratogenicity of thalidomide was discovered only several years after it came on the market.
Thalidomide made its appearance on the pharmaceutical market in the fifties - first in Germany and then in many other countries, including Italy - in drugs used as sedative-hypnoitics and in drugs used against gravid nausea . The tests carried out in vivo before the marketing of the active ingredient were never carried out on pregnant animals, so that the correlation between teratogenicity and thalidomide intake during pregnancy was highlighted only in 1960, after the birth of many phocomelic newborns or those with other congenital mutations.
In 1961 the drugs containing thalidomide were withdrawn from the German market, while in Italy they were still on sale for some years, despite warnings from foreign health authorities.
Compensation for patients with congenital malformations caused by thalidomide
Currently, there are several people in Italy with congenital malformations whose mothers took thalidomide as an anti-nausea drug during gestation. In 2009, the Italian Ministry of Health recognized compensation for patients suffering from malformations caused by thalidomide born between 1959 and 1965. In 2017 the Ministry of Health extended the possibility of receiving compensation for those born between 1958 and 1966 and to patients born outside this time interval who present malformations compatible with what is defined as thalidomide syndrome (that is, a syndrome caused by the homonymous drug in the forms of amelia, hemimelia, phocomelia and micromelia ).
To obtain compensation, it is necessary to present a specific application that must be accompanied by the necessary documentation and sent to the Directorate General for Supervision of Bodies and Health Care in the Ministry of Health (more detailed information is available on the official website).
Did you know that ...
In Italy, there is an association of patients victims of thalidomide which, among the various activities carried out, aims to protect the rights and provide useful information to other patients suffering from congenital malformations caused by the active ingredient in question.
