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Active ingredient: Thalidomide - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

  • Angiogenesis Inhibitors
  • Immunosuppressive Agents
  • Leprostatic Agents
  • Teratogens

Dosage Forms

  • Tablets for oral administration (50 mg)
  • Capsules for oral administration (50 mg, 100 mg and 200 mg)

Brands / Synonyms

Algosediv; alpha-phthalimidoglutarimide ; Asidon 3; Asmadion; Asmaval; Bonbrain; Bonbrrin; Calmore; Calmorex; Contergan; Corronarobetin; Distaval; Distaxal; Distoval; Ectiluran; Enterosediv; Gastrinide; Glupan; Glutanon; Grippex; Hippuzon; Imida-Lab; Imidan; Imidene; Isomin; Kedavon; Kevadon; Lulamin; N-Phthalimidoglutamic acid imide; N-Phthaloylglutamimide; N-Phthalylglutamic acid imide; Neaufatin; Neo; Neosedyn; Neosydyn; Nerosedyn; Neufatin; Neurodyn; Neurosedin; Neurosedym; Neurosedyn; Nevrodyn; Nibrol; Noctosediv; Noxodyn; Pangul; Pantosediv; Poly-Giron; Polygripan; Predni-Sediv; Pro-ban M; Profarmil; Psycholiquid; Psychotablets; Quetimid; Quietoplex; Sandormin; Sedalis; Sedalis sedi-lab; Sedimide; Sedin; Sedisperil; Sedoval; Shin-naito S; Shinnibrol; Sleepan; Slipro; Softenil; Softenon; Talargan; Talimol; Talismol; Telagan; Telargan; Telargean; Tensival; Thalidomide 99%; Thalidomine USP26; Thalin; Thalinette; Thalomid; Theophilcholine; Ulcerfen; Valgis; Valgraine; Yodomin

Indications

For the acute treatment of the cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL). Also for use as maintenance therapy for prevention and suppression of the cutaneous manifestations of ENL recurrence.

Pharmacology

Thalidomide is an immunomodulatory agent with a spectrum of activity that is not fully characterized. Thalidomide is racemic — it contains both left and right handed isomers in equal amounts: one enantiomer is effective against morning sickness, and the other is teratogenic. The enantiomers are converted to each other in vivo. That is, if a human is given D-thalidomide or L-thalidomide, both isomers can be found in the serum. Hence, administering only one enantiomer will not prevent the teratogenic effect in humans.

Mechanism of Action

In patients with erythema nodosum leprosum (ENL) the mechanism of action is not fully understood. Available data from in vitro studies and preliminary clinical trials suggest that the immunologic effects of this compound can vary substantially under different conditions, but may be related to suppression of excessive tumor necrosis factor-alpha (TNF-a) production and down-modulation of selected cell surface adhesion molecules involved in leukocyte migration. For example, administration of thalidomide has been reported to decrease circulating levels of TNF-a in patients with ENL, however, it has also been shown to increase plasma TNF-a levels in HIV-seropositive patients.

Absorption

The absolute bioavailability has not yet been characterized in human subjects due to its poor aqueous solubility. In studies of both healthy volunteers and subjects with Hansen’s disease, the mean time to peak plasma concentrations (Tmax) ranged from 2.9 to 5.7 hours indicating that thalidomide is slowly absorbed from the gastrointestinal tract.

Toxicity

The R-configuration and the S-configuration are more toxic individually than the racemic mixture. The LD50 could not be established in mice for racemic thalidomide, whereas LD50 values for the R and S configurations are reported to be 0.4 to 0.7 g/kg and 0.5 to 1.5 g/kg, respectively.

Biotrnasformation / Drug Metabolism

Thalidomide itself does not appear to be hepatically metabolized to any large extent, but appears to undergo non-enzymatic hydrolysis in plasma to multiple metabolites. Thalidomide may be metabolized hepatically by enzymes of the cytochrome P450 enzyme system. The end product of metabolism, phthalic acid, is excreted as a glycine conjugate.

Contraindications

Pregnancy: Category X

Due to its known human teratogenicity, even following a single dose, thalidomide is contraindicated in pregnant women and women capable of becoming pregnant. When there is no alternative treatment, women of childbearing potential may be treated with thalidomide provided adequate precautions are taken to avoid pregnancy. Women must commit either to abstain continuously from heterosexual sexual contact or to use two methods of reliable birth control, including at least one highly effective method (e.g., IUD, hormonal contraception, tubal ligation, or partner's vasectomy) and one additional effective method (e.g., latex condom, diaphragm, or cervical cap), beginning 4 weeks prior to initiating treatment with thalidomide, during therapy with thalidomide, and continuing for 4 weeks following discontinuation of thalidomide therapy. If hormonal or IUD contraception is medically contraindicated, two other effective or highly effective methods may be used.

Women of childbearing potential being treated with thalidomide should have a pregnancy test (sensitivity of at least 50 mIU/mL). The test should be performed within the 24 hours prior to beginning thalidomide therapy and then weekly during the first 4 weeks of thalidomide therapy, then at 4 week intervals in women with regular menstrual cycles or every 2 weeks in women with irregular menstrual cycles. Pregnancy testing and counseling should be performed if a patient misses her period or if there is any abnormality in menstrual bleeding. If pregnancy occurs during thalidomide treatment, thalidomide must be discontinued immediately. Under these conditions, the patient should be referred to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling.

Because thalidomide is present in the semen of patients receiving the drug, males receiving thalidomide must always use a latex condom during any sexual contact with women of childbearing potential. The risk to the fetus from the semen of male patients taking thalidomide is unknown.

THALOMIDÒ (thalidomide) is contraindicated in patients who have demonstrated hypersensitivity to the drug and its components.

Drug Interactions

Thalidomide has been reported to enhance the sedative activity of barbiturates, alcohol, chlorpromazine, and reserpine.

Peripheral Neuropathy: Medications known to be associated with peripheral neuropathy should be used with caution in patients receiving thalidomide.

Oral Contraceptives: In 10 healthy women, the pharmacokinetic profiles of norethindrone and ethinyl estradiol following administration of a single dose containing 1.0 mg of norethindrone acetate and 75 µg of ethinyl estradiol were studied. The results were similar with and without coadministration of thalidomide 200 mg/day to steady-state levels.

Important Non-Thalidomide Drug Interactions

Drugs That Interfere with Hormonal Contraceptives: Concomitant use of HIV-protease inhibitors, griseofulvin, modafinil, penicillins, rifampin, rifabutin, phenytoin, carbamazepine, or certain herbal supplements such as St. John's Wort with hormonal contraceptive agents may reduce the effectiveness of the contraception and up to one month after discontinuation of these concomitant therapies. Therefore, women requiring treatment with one or more of these drugs must use two OTHER effective or highly effective methods of contraception or abstain from heterosexual sexual contact while taking thalidomide.

 

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