Pomalidomide

Registered South African indications:

• Relapsed and refractory multiple myeloma

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy
• Women of reproductive potential (unless all the conditions of the pregnancy prevention programme are met)
• Male patients unable to follow or comply with the required contraceptive measures

Cautions

• Breastfeeding
• Hepatic impairment
• Blood, semen or sperm donation within 7 days of pomalodomide therapy
• Handling blister pack or cap (Healthcare professionals)
• Known risk factors for thromboembolism
• Prior thrombosis
• Smoking
• Hypertension
• Hyperlipidaemia
• Co-morbid conditions influencing thyroid function
• Ongoing ≥Grade 2 peripheral neuropathy
• Pre-existing cardiac disease
• Significant cardiac dysfunction
  - Congestive heart failure (NY Heart Association Class III or IV)
  - Myocardial infarction within the last 12 months
  - Unstable or poorly controlled angina pectoris
• Cardiac risk factors
• High tumour burden prior to treatment
• Second primary malignancies
• Prior history of serious allergic reactions associated with thalidomide or lenalidomide
• Hepatitis B virus infection 
• Previously infected with Hepatitis B virus
• Pre-existing > Grade 2 peripheral neuropathy
• 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 agents required)
  - In combination with bortezomib and dexamethasone in patients who have received at least one prior treatment regimen including lenalidomide
• Relapsed and refractory multiple myeloma (additional agents required)
  - In patients who have received at least two prior treatment regimens, including both lenalidomide and bortezomib, and have demonstrated disease progression on the last therapy

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Consult specialist for dosages and regimens

Not established for use in children below 18 years

Pregnancy

• Contraindicated
• A teratogenic effect of pomalidomide in humans is expected. Pomalidomide is structurally related to thalidomide. Thalidomide is a known human teratogen that causes severe life-threatening birth defects. Pomalidomide was found to be teratogenic in both rats and rabbits when administered during the period of major organogenesis. Pomalidomide is contraindicated during pregnancy and in women of childbearing potential, except when all the conditions for pregnancy prevention have been met
• Women of childbearing potential should use effective method of contraception. If pregnancy occurs in a woman treated with pomalidomide, 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 pomalidomide, it is recommended to refer the female partner to a physician specialised or experienced in teratology for evaluation and advice. Pomalidomide is present in human semen (see additional prescribing points)
• As a precaution, all male patients taking pomalidomide should use condoms throughout treatment duration, during dose interruption and for 7 days after cessation of treatment if their partner is pregnant or of childbearing potential and has no contraception 

Breastfeeding

• Caution; not recommended
• It is unknown whether pomalidomide is excreted in human milk. Pomalidomide was detected in milk of lactating rats following administration to the mother. Because of the potential for adverse reactions in breastfed infants from pomalidomide, a decision must be made whether to discontinue breastfeeding or to discontinue the medicinal product, taking into account the benefit of breastfeeding for the child and the benefit of the therapy for the woman

Fertility

• Pomalidomide was found to impact negatively on fertility and be teratogenic in animals. Pomalidomide crossed the placenta and was detected in foetal blood following administration to pregnant rabbits

Renal impairment

• No dose adjustment recommended
  On haemodialysis days, patients should take their pomalidomide dose following haemodialysis

Hepatic impairment

• Caution; no dose adjustment recommended
  No adjustment of the initoal dose of pomalidomide is required for patients with hepatic impairment as defined by the Child-Pugh criteria. However, patients with hepatic impairment should be carefully monitored for adverse reactions and dose reduction or interruption of pomalidomide should be used as needed

Elderly

• No dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)
  Immunosupressive therapy increases the risk of infections which in turn, have the potential to trigger acute porphyric attacks, therefore, it is important to monitor for signs and symptoms of infection and/or symptoms of a possible porphyric attack. Diarrhea, constipation, nausea and vomiting may potentially be porphyrinogenic through a reduction in carbohydrate intake

Drugs in Sport

• Permitted - No warnings

Adverse reactions reported in pomalidomide, bortezomib and dexamethasone combination therapy

Central Nervous System Disorders

• Depression
• Insomnia
• Peripheral sensory neuropathy
• Dizziness
• Tremor
• Syncope
• Peripheral sensorimotor neuropathy
• Paraesthesia
• Fatigue

Cardiovascular Disorders

• Atrial fibrillation
• Deep vein thrombosis
• Hypotension
• Hypertension
• Peripheral oedema
• Oedema
• Non-cardiac chest pain

Respiratory Disorders

• Pneumonia
• Bronchitis
• Viral upper respiratory tract infection
• Respiratory tract infection (upper and lower)
• Lung infection
• Influenza
• Bronchiolitis
• Dyspnoea
• Cough
• Pulmonary embolism
• Non-cardiac chest pain

Gastrointestinal Disorders

• Diarrhoea
• Nausea and vomiting
• Constipation
• Abdominal pain (including upper)
• Stomatitis
• Dry mouth
• Abdominal distension

Hepatobiliary Disorders

• Increased alanine aminotransferase

Genitourinary Disorders

• Urinary tract infection
• Acute kidney injury
• Chronic kidney injury
• Urinary retention

Endocrine and Metabolic Disorders

• Hypokalaemia
• Hyperglycaemia
• Hypomagnesaemia
• Hypocalcaemia
• Hypophosphataemia
• Hyperkalaemia
• Hypercalcaemia
• Decreased weight

Musculoskeletal Disorders

• Muscular weakness
• Back pain
• Muscle spasms
• Bone pain

Skin and Subcutaneous Tissue Disorders

• Rash
• Basal cell carcinoma

Immune, Blood and Lymphatic System Disorders

• Sepsis
• Septic shock
• Clostridium difficile colitis
• Neutropenia
• Thrombocytopenia
• Leucopenia
• Anaemia
• Febrile neutropenia
• Lymphopenia
• Fever

Sensory Disorders

• Dysgeusia
• Cataract

Others

• Fall

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Adverse reactions reported in pomalidomide & dexamethasone combination therapy

Central Nervous System Disorders

• Confusional state
• Depressed level of consciousness
• Peripheral sensory neuropathy
• Dizziness
• Tremor
• Fatigue

Cardiovascular Disorders

• Peripheral oedema
• Deep vein thrombosis

Respiratory Disorders

• Pneumonia (bacterial, viral and fungal infections, including opportunistic infections)
• Bronchopneumonia
• Bronchitis
• Respiratory tract infection (including upper)
• Nasopharyngitis
• Dyspnoea
• Cough
• Pulmonary embolism

Gastrointestinal Disorders

• Diarrhoea
• Nausea and vomiting
• Constipation
• Gastrointestinal haemorrhage

Hepatobiliary Disorders

• Hyperbilirubinaemia
• Increased alanine aminotransferase

Genitourinary Disorders

• Renal failure
• Urinary retention
• Pelvic pain

Endocrine and Metabolic Disorders

• Decreased appetite
• Hyperkalaemia
• Hyponatraemia

Musculoskeletal Disorders

• Bone pain
• Muscle spasms

Skin and Subcutaneous Tissue Disorders

• Basal cell carcinoma
• Squamous cell carcinoma
• Rash
• Pruritus

Immune, Blood and Lymphatic System Disorders

• Neutropenic sepsis
• Herpes zoster
• Neutropenia
• Thrombocytopenia
• Leucopenia
• Anaemia
• Febrile neutropenia
• Decreased neutrophil count
• Decreased white blood cell count
• Decreased platelet count
• Fever

Sensory Disorders

• Vertigo

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ADRs reported in post-marketing use in patients treated with pomalidomide

Central Nervous System Disorders

• Cerebrovascular accident
• Intracranial haemorrhage

Cardiovascular Disorders

• Cardiac failure
• Atrial fibrillation
• Myocardial infarction

Respiratory Disorders

• Epistaxis
• Interstitial lung disease

Hepatobiliary Disorders

• Hepatitis B reactivation
• Hepatitis

Endocrine and Metabolic Disorders

• Hypothyroidism
• Hyperuricaemia
• Tumour lysis syndrome

Skin and Subcutaneous Tissue Disorders

• Urticaria
• Drug reaction with eosinophilia and systemic symptoms
• Toxic epidermal necrolysis
• Stevens-Johnson Syndrome

Immune, Blood and Lymphatic System Disorders

• Pancytopenia
• Angioedema
• Anaphylactic reaction
• Increased blood uric acid

• Strong CYP1A2 inhibitor
• Ciprofloxacin
• Enoxacin
• Fluvoxamine
• Agents known to increase the risk of bleeding
• Erythropoietic agents
• Agents that may increase the risk of thromboembolic events
• Warfarin (dexamethasone combination therapy)

• Full blood count with differential and platelets
• Renal function
• Hepatic function
• Thyroid function
• Pregnancy status

Contraception concerns in women

Combined oral contraceptives

• Because of the increased risk of venous thromboembolism in patients with multiple myeloma taking pomalidomide and dexamethasone, combined oral contraceptive pills are not recommended. If a patient is currently using combined oral contraception, the patient should switch to one of the effective methods listed below:
  - Implant
  - Levonorgestrel-releasing intrauterine system
  - Medroxyprogesterone acetate depot
  - Tubal sterilisation
  - Sexual intercourse with a vasectomised male partner only; vasectomy must be confirmed by 2 negative semen analysis
  - Ovulation inhibitory progesterone-only pills (i.e. desogestrel)
• The risk of venous thromboembolism continues for 4-6 weeks after discontinuing combined oral contraception
• The efficacy of contraceptive steroids may be reduced during cotreatment with dexamethasone

Implants and intrauterine systems

• Implants and levonorgestrel-releasing intrauterine systems are associated with an increased risk of infection at the time of insertion and irregular vaginal bleeding. Prophylactic antibiotics should be considered particularly in patients with neutropenia
• Insertion of copper-releasing intrauterine devices is not recommended due to the potential risks of infection at the time of insertion and menstrual blood loss which may compromise patients with severe neutropenia or severe thrombocytopenia

Pomalidomide has direct anti-myeloma tumoricidal activity, immunomodulatory activities and inhibits stromal cell support for multiple myeloma tumour cell growth. Specifically, pomalidomide inhibits proliferation and induces apoptosis of haematopoietic tumour cells. Additionally, pomalidomide inhibits the proliferation of lenalidomide-resistant multiple myeloma cell lines and synergises with dexamethasone in both lenalidomide-sensitive and lenalidomide-resistant cell lines to induce tumour cell apoptosis. Pomalidomide enhances T cell- and natural killer (NK) cell-mediated immunity and inhibits production of pro-inflammatory cytokines (e.g., TNF-α and IL-6) by monocytes. Pomalidomide also inhibits angiogenesis by blocking the migration and adhesion of endothelial cells. Pomalidomide binds directly to the protein cereblon (CRBN), which is part of an E3 ligase complex that includes deoxyribonucleic acid (DNA) damage-binding protein 1(DDB1), cullin 4 (CUL4), and regulator of cullins-1 (Roc1), and can inhibit the auto-ubiquitination of CRBN within the complex. E3 ubiquitin ligases are responsible for the poly-ubiquitination of a variety of substrate proteins, and may partially explain the pleiotropic cellular effects observed with pomalidomide treatment.

Capsule 1mg

• Imnovid ( Key Oncologics) originator

Capsule 2mg

• Imnovid (Key Oncologics) originator

Capsule 3mg

• Imnovid (Key Oncologics) originator

Capsule 4mg

• Imnovid (Key Oncologics) originator