Thalidomide

Registered South African indications:

• Multiple myeloma
• Erythema nodosum leprosum

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy
• Breastfeeding
• Women of childbearing potential who are not using, or not able to use adequate contraceptive measures to prevent pregnancy as outlined in the Thalidomide Risk Management Programme (TRMP)
• Sexually mature males who are not able or willing to comply with the contraceptive measures outlined in the Thalidomide Risk Management Programme (TRMP)
• Patients who, for whatever reasons, are unable to understand or comply with the instructions given in the Thalidomide Risk Management Programme (TRMP)

Cautions

• Renal impairment
• Hepatic impairment
• Elderly (>75 years)
• Men desiring fertility
• Men unable to follow or comply with the required contraceptive measures
• Donating blood or semen
• Amenorrhoea
• Risk factors for myocardial infarction
• Risk factors for thromboembolic events
• Peripheral neuropathy
• Underlying cardiopulmonary disease
• Pulmonary hypertension
• High tumour burden
• History of hepatitis B infection
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: cap

Used for the treatment of

Multiple myeloma (additional agent required)
- Untreated multiple myeloma
- Ineligible for high dose chemotherapy
Erythema nodosum leprosum - moderate to severe
- Acute treatment of the cutaneous manifestations
- Relapse after prior treatment 

Consult specialist for dosages and regimens

Not established for use in children below 12 years

Pregnancy

• Contraindicated
• Thalidomide is contraindicated during pregnancy and in women of childbearing potential unless all the conditions necessary precautions have been implemented
• Thalidomide is a powerful human teratogen, inducing a high frequency (about 30 %) of severe and life-threatening birth defects such as: ectromelia (amelia, phocomelia, hemimelia) of the upper and/or lower extremities, microtia with abnormality of the external acoustic meatus (blind or absent), middle and internal ear lesions (less frequent), ocular lesions (anophthalmia, microphthalmia), congenital heart disease, renal abnormalities. Other less frequent abnormalities have also been described
• Women of childbearing potential must use one effective method of contraception for 4 weeks before therapy, during therapy, and during 4 weeks after thalidomide therapy. If pregnancy occurs in a woman treated with thalidomide, treatment must be stopped immediately and the patient should be referred to a doctor specialised or experienced in teratology for evaluation and advice
• As thalidomide is found in semen, male patients must use condoms during treatment and for 1 week after dose interruption and/or cessation of treatment when having sexual intercourse with a pregnant woman or with a woman of childbearing potential who is not using effective contraception. This applies even if the man has had a vasectomy
• If pregnancy occurs in a partner of a male patient taking thalidomide, the female partner should be referred to a doctor specialised or experienced in teratology for evaluation and advice

Breastfeeding

• Contraindicated

Fertility

• A study in rabbits demonstrated no effect on fertility indices in males or females although testicular degeneration was observed in males

Renal Impairment

• Caution; no dose adjustment recommended

Hepatic Impairment

• Caution; no dose adjustment recommended

Elderly

• ≤75 years: No dose adjustment recommended
• > 75 years: Caution; dose adjustment recommended
  A low initial dose is recommended; Consult a specialist for doses

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Confusional state
• Depression
• Peripheral neuropathy
• Tremor
• Dizziness
• Paraesthesia
• Dysaesthesia
• Somnolence
• Abnormal coordination

Cardiovascular Disorders

• Cardiac failure
• Bradycardia
• Deep vein thrombosis

Respiratory Disorders

• Pneumonia
• Pulmonary embolism
• Interstitial lung disease
• Bronchopneumopathy
• Dyspnea

Gastrointestinal Disorders

• Constipation
• Vomiting
• Dry mouth

Genitourinary Disorders

• Amenorrhoea

Skin and Subcutaneous Tissue Disorders

• Toxic skin eruption
• Rash
• Dry skin
• Peripheral oedema

Immune, Blood and Lymphatic System Disorders

• Neutropenia
• Leukopenia
• Anaemia
• Lymphopenia
• Thrombocytopenia
• Pyrexia

• Anxiolytics
• Hypnotics
• Antipsychotics
• Anti-histamines
• Opiate derivatives
• Barbiturates 
• Alcohol
• Active substances known to induce torsade de pointes
• Beta blockers
• Anticholinesterase agents
• Medicinal products known to be associated with peripheral neuropathy
• Combined hormonal contraceptives
• Warfarin

• Full blood count with differential
• Thyroid function
• Hepatic function
• Pregnancy test
• Neurological examination

Specific cases may require

• Viral load
• Renal function

Thalidomide has a chiral centre and is used clinically as a racemate of (+)-(R)- and (-)- (S)-thalidomide. The spectrum of activity of thalidomide is not fully characterised. Thalidomide shows significant immunomodulatory, anti-inflammatory and potential anti-neoplastic activities. Data from in vitro studies and clinical trials suggest that the immunomodulatory, anti-inflammatory and anti-neoplastic effects of thalidomide may be related to suppression of excessive tumour necrosis factor-alpha (TNF-alpha) production, down-modulation of selected cell surface adhesion molecules involved in leukocyte migration and anti-angiogenic activity.

Capsule 50mg

• Thalidomide Celgene (Key Oncologics) originator