Pomalidomide Zentiva

Treatment must be initiated and monitored under the supervision of physicians experienced in the management of multiple myeloma. 4). Posology Pomalidomide in combination with bortezomib and dexamethasone The recommended starting dose of pomalidomide is 4 mg taken orally once daily on Days 1 to 14 of repeated 21- day cycles.

Pomalidomide is administered in combination with bortezomib and dexamethasone, as shown in table 1. 3 mg/m2 intravenous or subcutaneous once daily, on the days shown in table 1. The recommended dose of dexamethasone is 20 mg taken orally once daily, on the days shown in table 1.

Treatment with pomalidomide combined with bortezomib and dexamethasone should be given until disease progression or until unacceptable toxicity occurs. Table 1. 3 mg/m2) • • 4 Dexamethasone (20 mg)* • • • • * For patients > 75 years of age, see Special populations.

Pomalidomide dose modification or interruption To initiate a new cycle of pomalidomide, the neutrophil count must be ≥ 1 x 109/l and the platelet count must be ≥ 50 x 109/l. Instructions on dose interruptions or reductions for pomalidomide related adverse reactions are outlined in the table 2 and dose levels are defined in table 3 below: Table 2.

5 °C and ANC < 1 x 109 /l) Interrupt pomalidomide treatment for remainder of cycle. Follow CBC*** weekly. ANC return to ≥ 1 x 109 /l Resume pomalidomide treatment at one dose level lower than previous dose. 5 x 109 /l Interrupt pomalidomide treatment.

ANC return to ≥ 1 x 109 /l Resume pomalidomide treatment at one dose level lower than the previous dose. Thrombocytopenia Platelet count < 25 x 109 /l Interrupt pomalidomide treatment for remainder of cycle. Follow CBC*** weekly. Platelet count return to ≥ 50 x 109 /l Resume pomalidomide treatment at one dose level lower than previous dose.

For each subsequent drop < 25 x 109 /l Interrupt pomalidomide treatment. Platelet count return to ≥ 50 x 109 /l Resume pomalidomide treatment at one dose level lower than the previous dose. Rash Rash = Grade 2-3 Consider dose interruption or discontinuation of pomalidomide treatment.

4). Other Other ≥ Grade 3 pomalidomide-related adverse events Interrupt pomalidomide treatment for remainder of cycle. Resume at one dose level lower than previous dose at next cycle (adverse event must be resolved or improved to ≤ Grade 2 before restarting dosing).

0%). 3%). 1%). 2%). 9%). 7%). 3% of patients. 3%). 3%). 7 %). Adverse reactions tended to occur more frequently within the first 2 cycles of treatment with pomalidomide. Tabulated list of adverse reactions The adverse reactions observed in patients treated with pomalidomide in combination with bortezomib and dexamethasone, pomalidomide in combination with dexamethasone and from post-marketing surveillance are listed in table 7 by system organ class (SOC) and frequency for all adverse reactions and for Grade 3 or 4 adverse reactions.

Frequencies are defined in accordance with current guidance, as: very common (≥1/10), common (≥1/100 to <1/10) and uncommon (≥1/1,000 to <1/100) and not known (frequency cannot be determined). Table 7. Adverse reactions (ADRs) reported in clinical trials and post-market settings Combination of treatment Pomalidomide/ bortezomib/dexamethasone Pomalidomide/ dexamethasone System Organ Class /Preferred term All ADRs Grade 3−4 ADRs All ADRs Grade 3−4 ADRs Infections and infestations Pneumonia Very common Very common Pneumonia (bacterial, viral and fungal infections, Very common Common 15 Combination of treatment Pomalidomide/ bortezomib/dexamethasone Pomalidomide/ dexamethasone System Organ Class /Preferred term All ADRs Grade 3−4 ADRs All ADRs Grade 3−4 ADRs including opportunistic infections) Bronchitis Very common Common Common Uncommon Upper respiratory tract infection Very common Common Common Common Viral upper respiratory tract infection Very common Sepsis Common Common Septic shock Common Common Neutropenic sepsis Common Common Clostridium difficile colitis Common Common Bronchopneumonia Common Common Respiratory tract infection Common Common Common Common Lower respiratory tract infection Common Common Lung infection Common Uncommon Influenza Very common Common Bronchiolitis Common Common Urinary tract infection Very common Common Nasopharyngitis Common Herpes zoster Common Uncommon Hepatitis B reactivation Not known* Not known* Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma Common Uncommon Basal cell carcinoma of the skin Uncommon Uncommon Squamous cell carcinoma of the skin Uncommon Uncommon Blood and lymphatic system disorders Neutropenia Very common Very common Very common Very common Thrombocytopenia Very common Very common Very common Very common Leucopenia Very common Common Very common Common Anaemia Very common Very common Very common Very common Febrile neutropenia Common Common Common Common Lymphopenia Common Common Pancytopenia Common* Common* Immune system disorders Angioedema Common* Uncommon* Urticaria Common* Uncommon* Anaphylactic reaction Not known* Not known* Solid organ transplant rejection Not known* Endocrine disorders 16 Combination of treatment Pomalidomide/ bortezomib/dexamethasone Pomalidomide/ dexamethasone System Organ Class /Preferred term All ADRs Grade 3−4 ADRs All ADRs Grade 3−4 ADRs Hypothyroidism Uncommon* Metabolism and nutrition disorders Hypokalaemia Very common Common Hyperglycaemia Very common Common Hypomagnesaemia Common Common Hypocalcaemia Common Common Hypophosphataemia Common Common Hyperkalaemia Common Common Common Common Hypercalcaemia Common Common Hyponatraemia Common Common Decreased appetite Very common Uncommon Hyperuricaemia Common* Common* Tumour lysis syndrome Uncommon* Uncommon* Psychiatric disorders Insomnia Very common Common Depression Common Common Confusional state Common Common Nervous system disorders Peripheral sensory neuropathy Very common Common Common Uncommon Dizziness Very common Uncommon Common Uncommon Tremor Very common Uncommon Common Uncommon Syncope Common Common Peripheral sensorimotor neuropathy Common Common Paraesthesia Common Dysgeusia Common Depressed level of consciousness Common Common Intracranial haemorrhage Common* Uncommon* Cerebrovascular accident Uncommon* Uncommon* Eye disorders Cataract Common Common Ear and labyrinth disorders Vertigo Common Common […]

Teratogenicity Pomalidomide must not be taken during pregnancy, since a teratogenic effect is expected. Pomalidomide is structurally related to thalidomide. Thalidomide is a known human teratogen that causes severe life-threatening birth defects.

3). The conditions of the Pregnancy Prevention Programme must be fulfilled for all patients unless there is reliable evidence that the patient does not have childbearing potential. Criteria for women of non-childbearing potential A female patient or a female partner of a male patient is considered of non-childbearing potential if she meets at least one of the following criteria: • Age ≥ 50 years and naturally amenorrhoeic for ≥ 1 year (amenorrhoea following cancer therapy or during breast-feeding does not rule out childbearing potential) • Premature ovarian failure confirmed by a specialist gynaecologist • Previous bilateral salpingo-oophorectomy, or hysterectomy 8 • XY genotype, Turner syndrome, uterine agenesis.

Counselling For women of childbearing potential, pomalidomide is contraindicated unless all of the following are met: • She understands the expected teratogenic risk to the unborn child • She understands the need for effective contraception, without interruption, at least 4 weeks before starting treatment, throughout the entire duration of treatment, and at least 4 weeks after the end of treatment • Even if a woman of childbearing potential has amenorrhoea she must follow all the advice on effective contraception • She should be capable of complying with effective contraceptive measures • She is informed and understands the potential consequences of pregnancy and the need to rapidly consult if there is a risk of pregnancy • She understands the need to commence the treatment as soon as pomalidomide is dispensed following a negative pregnancy test • She understands the need and accepts to undergo pregnancy testing at least every 4 weeks except in case of confirmed tubal sterilisation • She acknowledges that she understands the hazards and necessary precautions associated with the use of pomalidomide.

• Pregnancy. 6). 4). 1.