Lenalidomide

Registered South African indications:

• Myelodysplastic syndromes
• Multiple myeloma

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy
• Women of childbearing potential, except when all of the conditions for pregnancy prevention have been met
• Breastfeeding 

Cautions

• Moderate to severe renal impairment
• Hepatic impairment
• Elderly
• Blood donation
• Risk factors for myocardial infarction
• Risk factors for thromboembolism
• Thyroid dysfunction
• High tumour burden
• Risk factors for infections 
• History of severe rash associated with thalidomide treatment
• Galactose intolerance
• Lapp lactase deficiency 
• Glucose-galactose malabsorption
• May impair ability to drive and operate machinery

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

Used for the treatment of

Myelodysplastic syndromes
- Transfusion-dependent anaemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with a deletion 5q cytogenetic abnormality with or without other cytogenetic abnormalities
Multiple myeloma (additional agent required)
- Who have received at least one prior therapy

Consult specialist for dosages and regimens

Not established for use in children below 18 years

Pregnancy 

• Contraindicated 
• Lenalidomide is structurally related to thalidomide. Thalidomide is a known human teratogenic active substance that causes severe life-threatening birth defects
• Lenalidomide induced malformation in monkeys similar to those described with thalidomide, therefore, a teratogenic effect of lenalidomide is expected and lenalidomide is contraindicated during pregnancy
• Women of childbearing potential should use an effective method of contraception
• If pregnancy occurs in a woman treated with lenalidomide, treatment must be stopped and the patient should be referred to a physician specialised or experienced in teratology for evaluation and advice
• If pregnancy occurs in a partner of a male patient taking lenalidomide, it is recommended to refer the female partner to a physician specialised or experienced in teratology for evaluation and advice

Breastfeeding 

• Contraindicated
• It is not known whether lenalidomide is excreted in breast milk. Therefore, breastfeeding should be discontinued during therapy with lenalidomide

Fertility

• A fertility study in rats with lenalidomide doses up to 500 mg/kg (approximately 200 to 500 times the human doses of 25 mg and 10 mg, respectively, based on body surface area) produced no adverse effects on fertility and no parental toxicity
• Lenalidomide is present in human semen at extremely low levels during treatment and is undetectable in human semen 3 days after stopping the substance in the healthy subject. As a precaution, and taking into account special populations with prolonged elimination time such as renal impairment, all male patients taking lenalidomide should use condoms throughout treatment duration, during dose interruption and for 1 week after stopping treatment if their partner is pregnant or of childbearing potential and has no contraception

Renal Impairment

• Moderate to severe: Caution; dose adjustment recommended

Hepatic Impairment

• Caution; no information available

Elderly            

• Caution; no dose adjustment recommended

Porphyria Information

• Probably no porphyrinogenic (PNP)

Central Nervous System Disorders

• Paraesthesia
• Peripheral neuropathy
• Headache
• Fatigue

Cardiovascular Disorders

• Pulmonary embolism
• Deep vein thrombosis

Respiratory Disorders

• Cough
• Dyspnoea
• Rhinorrhoea
• Sinusitis
• Nasopharyngitis
• Rhinitis
• Pneumonias
• Upper respiratory tract infection
• Bronchitis
• Lower respiratory tract infection
• Lung infection

Gastrointestinal Disorders

• Diarrhoea
• Constipation
• Abdominal pain
• Nausea and vomiting
• Gastroenteritis

Hepatobiliary Disorders

• Abnormal hepatic function tests

Genitourinary Disorders

• Urinary tract infection

Endocrine and Metabolic Disorders

• Hypokalaemia
• Dehydration

Musculoskeletal Disorders

• Muscle spasms
• Myalgia
• Musculoskeletal pain

Skin and Subcutaneous Tissue Disorders

• Rash
• Dry skin
• Pruritus

Immune, Blood and Lymphatic System Disorders

• Neutropenia
• Febrile neutropenia
• Thrombocytopenia
• Anemia
• Leucopenia
• Lymphopenia
• Pancytopenia
• Myelodysplastic syndrome
• Pyrexia
• Sepsis
• Bacteraemia
• Herpes zoster
• Neutropenic infection
• Influenza
• Infection

• Erythropoietic agents
• Agents that may increase the risk of thrombosis
• Digoxin
• Statins 

• Full blood count with differential
• Renal function
• Hepatic function
• Thyroid function

Specific cases may require

• ECG
• Pregnancy test

Contraception

• Women of childbearing potential must use at least one effective method of contraception for at least 4 weeks before therapy, during therapy, and until at least 4 weeks after lenalidomide therapy and even in the case of dose interruption unless the patient commits to absolute and continuous abstinence confirmed on a monthly basis. If not established on effective contraception, the patient must be referred to an appropriately trained health care professional for contraceptive advice in order that contraception can be initiated
• The following can be considered examples of suitable methods of contraception:
  • Implant
  • Levonorgestrel-releasing intrauterine system (IUS)
  • Medroxyprogesterone acetate depot
  • Tubal sterilisation
  • Sexual intercourse with a vasectomied male partner only; vasectomy must be confirmed by two negative semen analyses
  • Ovulation inhibitory progesterone-only pills (i.e. desogestrel)

Lenalidomide is structurally related to thalidomide.  It has anti-neoplastic, anti-angiogenic, pro-erythropoietic, and immunomodulatory properties. It inhibits proliferation of certain haematopoietic tumour cells (including MM plasma tumour cells and those with deletions of chromosome 5), enhances T cell- and Natural Killer (NK) cell-mediated immunity and increases the number of NK T cells, inhibits angiogenesis by blocking the migration and adhesion of endothelial cells and the formation of microvessels, augments foetal haemoglobin production by CD34+ haematopoietic stem cells, and inhibits production of pro-inflammatory cytokines (e.g., TNF-α and IL-6) by monocytes.

Capsule 5mg

• Eurolen 5 (Eurolab)
• Lenalidomide Cipla 5 (Cipla Medpro)
• Lenalidomide DRL 5 (Dr Reddy's Laboratories)
• Revlimid (Key Oncologics) originator

Capsule 10mg

• Eurolen 10 (Eurolab)
• Mylomid 10 (Forrester Pharma)
• Lenalidomide Cipla 10 (Cipla Medpro)
• Lenalidomide DRL 10 (Dr Reddy's Laboratories)
• Revlimid (Key Oncologics) originator

Capsule 15mg

• Eurolen 15 (Eurolab)
• Lenalidomide Cipla 15 (Cipla Medpro)
• Lenalidomide DRL 15 (Dr Reddy's Laboratories)
• Revlimid (Key Oncologics) originator

Capsule 25mg

• Eurolen 25 (Eurolab)
• Mylomid 25 (Forrester Pharma)
• Lenalidomide Cipla 25 (Cipla Medpro)
• Lenalidomide DRL 25 (Dr Reddy's Laboratories)
• Revlimid (Key Oncologics) originator