Thalidomide is one of the most commonly used drugs for multiple myeloma and is known under the trade name “Response Stop”. Thalidomide has anti-angiogenic and immunomodulatory effects, and has unique anti-myeloma effects. Although thalidomide is widely used, there is a lack of detailed description of adverse reactions to the drug, including the simple instructions for Thalidomide. In order to help patients better use thalidomide, reduce toxic side effects and improve the quality of life, this article combines literature reports and our clinical experience, hoping to provide patients with medication reference and treatment guidance.
The common side effects of thalidomide include drowsiness, fatigue, constipation, peripheral neuropathy, rash, etc. Less common side effects include dry mouth, deep vein thrombosis, tremor of hands, menstrual disorders, lower limb edema, bradycardia, granulocytopenia, etc. Neonatal teratogenicity is the most dangerous side effect of thalidomide. Both male and female patients of childbearing age must use strict contraception while taking the drug, and even a single dose in early pregnancy is enough to cause fetal malformation. Fortunately, this serious side effect can be avoided with strict contraception, and in the United States, patients must receive adequate safety education involving clinicians and pharmacists before taking thalidomide.
The incidence of thalidomide adverse reactions is related to the dose taken. The incidence of adverse reactions is low at doses below 200 mg per day, but some sensitive patients can experience significant adverse reactions at 50 mg per day. The incidence of peripheral neuropathy increases significantly with prolonged thalidomide administration for more than 6 months. Only by properly dealing with adverse reactions during thalidomide administration can we ensure uninterrupted dosing and adequate dosage to achieve a satisfactory treatment effect. So what are the tips and tricks, and listen to me one by one.
1, drowsiness and fatigue
Most patients often feel drowsy, weak, weak, inattentive, mood change, the incidence of serious reactions does not exceed 10%. To reduce daytime discomfort, we recommend that patients take the drug at night before bedtime. The first dose is recommended to start with a small dose, such as 50mg per night, and increase the dose in a week or so until the target dose is reached. If drowsiness and weakness still occur in the morning, the dose can also be divided into 2 doses a day in the morning and evening, and some patients can also improve. If the degree is more serious, the drug can be temporarily stopped, and then the dose is halved and restarted after the symptoms improve.
2.Peripheral neuropathy
Patients experience numbness, dullness, tingling, inflexible fingers, unstable holding or walking at the end of the limbs. If serious peripheral neuropathy occurs, such as severe numbness, tingling, or interference with daily life, the best way to deal with it is to stop the drug immediately and start it again after the side effects have recovered significantly, when the dose is reduced by half. If 50mg per day is still not tolerated, it is recommended to discontinue the drug. Neurotrophic drugs such as methylcobalamin have a more limited effect, and gabapentin or pregabalin (Lerica) is preferred for better pain relief when accompanied by significant tingling. If these drugs are not available, tramadol or carbamazepine (Deloitte) may also be chosen. After peripheral neuropathy occurs, most patients can recover as long as the dose is promptly reduced and stopped, but the symptoms do not improve immediately after stopping the drug and will continue for some time.
3.Constipation
Constipation is the most common adverse effect of thalidomide, especially in elderly patients or those with a previous history of constipation. It is not difficult to solve the problem of constipation, and the most important thing is to change your lifestyle. Drinking a glass of warm water in the morning on an empty stomach, eating more fresh vegetables and fruits, walking more after meals, and having regular bowel movements will help. For some bedridden patients you can do lower limb flexion and extension exercises in bed or increase abdominal massage, all of which are good for bowel movement. We recommend that patients start taking thalidomide along with a laxative, such as rhubarb soda tablets and paregoric capsules. Long-term use of opiates may be harmful. Thalidomide is usually not discontinued because of constipation.
4. Skin rash
About 10-20% of patients will have a rash of varying degrees, manifested as maculopapular rash, erythema with scratching, herpes and desquamation. It often occurs in the hairline, neck and forehead, and appears within 2 weeks of taking the drug. Once a large rash appears, thalidomide use should be discontinued and a prompt visit to the dermatologist should be made to give anti-allergy medication, most of which can be controlled. A small percentage of patients develop widespread exfoliative dermatitis, i.e., severe drug rash, which must be treated immediately with medical attention and hospital admission. Some patients have no other choice of medication than thalidomide, so it is important to weigh the pros and cons. Our experience is that you can start with one tablet and increase it by one tablet per week, which is called “desensitization” therapy, and it does work for some patients who have had a rash. Of course, this does not apply to patients with severe drug rashes, and it is recommended that the medication be administered under medical follow-up to prevent severe drug rashes. Zhang Chunyang, Department of Hematology, Shanghai Long March Hospital
5.Deep vein thrombosis
This is a more troublesome and dangerous side effect that may lead to pulmonary embolism. Patients often present with significant swelling of one limb, and vascular ultrasound can help diagnose it. But in fact the incidence of deep vein thrombosis is only 1-3% with thalidomide alone, only when combined with dexamethasone or other chemotherapy drugs does it rise significantly to more than 10%, when anticoagulant therapy is also emphasized for prevention such as bye aspirin. Warfarin or low molecular heparin anticoagulation may be considered for patients who have had previous venous thrombosis or are prone to venous thrombosis. However, our clinical experience shows that the incidence of thrombosis in domestic patients is significantly lower than that reported abroad, which may be related to ethnic differences. Patients with advanced myeloma who start treatment should pay special attention to the prevention of deep vein thrombosis. In addition to the anticoagulation therapy mentioned earlier, it is very important to improve symptoms as soon as possible with effective chemotherapy, reduce bed rest time and increase lower limb activity.
6.Neutropenia
The incidence of neutropenia caused by thalidomide is 10%-20%, and most of them are mild. Therefore, thalidomide is a very good drug of choice for myeloma patients with low blood cells. Close monitoring of blood routine is still required during treatment. If granulocytes are significantly reduced, granulocyte colony-stimulating factor therapy is recommended and the dosage of thalidomide should be adjusted.
7.Sinus bradycardia
A small number of patients may experience significant bradycardia, with heart rate below 50 beats per minute, and patients often feel weak, dizzy, or even black and faint during the course of drug administration. Therefore, it is recommended that patients learn to count their pulses and can monitor themselves to prevent accidents caused by severe bradycardia. This situation should be temporarily discontinued and the thalidomide dosage should be reduced by 50% when the heart rate recovers.
8.Postural hypotension
Patients should be alerted to postural hypotension if they experience significant dizziness when getting up after taking the drug or when they change their position after squatting. An effective preventive measure is to sit still for a few minutes when getting up before getting out of bed, which can avoid the occurrence.
9. Lower limb edema
The incidence of mild edema is about 15%, and the incidence of severe edema is less than 3%. Patients with combined renal insufficiency, congestive heart failure or amyloidosis are prone to it, and it is related to water and sodium retention, and diuretic drugs can be added.
In conclusion, thalidomide is a very effective drug for the treatment of multiple myeloma. Familiarity with the common adverse reactions and treatment countermeasures of thalidomide can help us to better apply the drug, and we welcome you to exchange medication experience and help each other to improve the quality of life together.