Pomarza 1,0 mg/2,0 mg/3,0 mg/4,0 mg Capsules

• POMARZA in combination with bortezomib and dexamethasone (PBd) is indicated in the treatment of adult patients with multiple myeloma who have received at least one prior treatment regimen including lenalidomide.
• POMARZA in combination with dexamethasone (Pd) is indicated in the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least two prior treatment regimens, including both lenalidomide and a proteasome inhibitor (e.g., bortezomib), and have demonstrated disease progression on the last therapy.

Posology Treatment must be initiated and monitored under the supervision of a medical practitioner experienced in the management of multiple myeloma.

In combination with Bortezomib and Dexamethasone (PBd) u2013 patients with relapsed or refractory multiple myeloma after at least one prior therapy including lenalidomide:

Recommended dosage: The recommended starting dose of POMARZA is 4 mg orally once daily on days 1 - 14 for each 21 - day cycle. The recommended dose of bortezomib is:

• For cycles 1 - 8: 1.3mg/m2 on Days 1, 4, 8 and 11 of a 21 - day cycle.
• From cycle 9 onwards: 1.3mg/m2 on Days 1 and 8 of a 21 - day cycle.

The recommended dose of dexamethasone is:

• For cycles 1 - 8: 20 mg orally once daily on days 1, 2, 4, 5, 8, 9, 11, and 12 of a 21 - day cycle.
• From cycle 9 onwards: 20 mg orally once daily on days 1, 2, 8, and 9 of a 21 - day cycle.

For patients greater than 75 years of age, see section Special populations below. Dosing is to be continued or modified based upon clinical and laboratory findings. It is recommended that treatment be discontinued upon progression of disease.

In combination with Dexamethasone (Pd) u2013 patients with relapsed and refractory multiple myeloma after at least two prior therapies including lenalidomide and a proteasome inhibitor:

Recommended dosage: The recommended starting dose of is 4 mg/day taken orally on Days 1 - 21 of repeated 28 - day cycles (21/28 days) until disease progression. The recommended dose of dexamethasone is 40 mg/day on Days 1, 8, 15 and 22 of each 28 - day treatment cycle.

Dosing is continued or modified based upon clinical and laboratory findings.

Dose modification or interruption: Instructions for dose interruptions and reductions for POMARZA related to haematologic adverse reactions are outlined in the table below:

Dose modification instructions for POMARZA for haematologic toxicities:

Toxicity Dose modification

• Neutropenia u2022 ANC < 500/u03bcL or febrile neutropenia (fever u2265 38,5 u00b0C and ANC < 1000/u03bcL) u2022 Interrupt POMARZA treatment, follow CBC weekly. Add G - CSF (at the discretion of the treating doctor) u2022 Pd regimen: ANC return to u2265 500/u03bcL u2022 Resume POMARZA at 3 mg daily u2022 PBd regimen: ANC return to u2265 1000/u03bcL u2022 For each subsequent drop < 500/u03bcL u2022 Interrupt POMARZA treatment u2022 Pd regimen: Return to u2265 500/u03bcL u2022 Resume POMARZA at 1 mg less than the previous dose u2022 PBd regimen: Return to u2265 1000/u03bcL
• Thrombocytopenia u2022 Platelets 50 000/u03bcL u2022 Resume POMARZA treatment at 3 mg daily u2022 For each subsequent drop < 25 000/u03bcL u2022 Interrupt POMARZA treatment u2022 Return to u2265 50 000/u03bcL u2022 Resume POMARZA at 1 mg less than previous dose.

ANC = Absolute neutrophil count CBC = complete blood count PBd regimen: To initiate a new cycle of POMARZA, the neutrophil count must be u2265 1000/u03bcL, and the platelet count must be u2265 50 000/u03bcL. Pd regimen: To initiate a new cycle of POMARZA, the neutrophil count must be u2265 500/u03bcL, the platelet count must be u2265 50 000/u03bcL. For other Grade 3/4 toxicities judged to be related to POMARZA, stop treatment and restart treatment at 1 mg less than the previous dose when toxicity has resolved to u2264 Grade 2 at the medical practitioneru2019s discretion. If toxicities occur after dose reductions to 1 mg, then the medicine should be discontinued.

Dose Adjustment for Co - Administration of CYP1A2 Inhibitors: If strong inhibitors of CYP1A2 (e.g., fluvoxamine, ciprofloxacin) are co - administered with POMARZA, reduce the recommended starting POMARZA dose to 2 mg (a 50 % reduction for patients with multiple myeloma) (see section below).

PBd regimen: For dose adjustments due to toxicity with bortezomib, refer to the product professional information.

Dexamethasone dose modification instructions:

Toxicity Dose modification

• Dyspepsia = Grade 1 - 2 Maintain dose and treat with histamine (H 2 ) blockers or equivalent. Decrease by one dose level if symptoms persist.
• Dyspepsia u2265 Grade 3 Interrupt dose until symptoms are controlled. Add H 2 blocker or equivalent and decrease one dose level when dose restarted.
• Oedema u2265 Grade 3 Use diuretics as needed and decrease dose by one dose level.
• Confusion or mood alteration u2265 Grade 2 Interrupt dose until symptoms resolve. When dose restarted decrease dose by one dose level.
• Muscle weakness u2265 Grade 2 Interrupt dose until muscle weakness u2264 Grade 1. Restart with dose decreased by one level.
• Hyperglycaemia u2265 Grade 3 Decrease dose by one dose level. Treat with insulin or oral hypoglycaemic medicines as needed.
• Acute pancreatitis Discontinue patient from dexamethasone treatment regimen.
• Other u2265 Grade 3 dexamethasone - related adverse events Stop dexamethasone dosing until adverse event resolves to u2264 Grade 2. Resume with dose reduced by one level.

Discontinuation of POMARZA POMARZA interruption or discontinuation should be considered for Grade 2 - 3 skin rash. POMARZA must be discontinued for angioedema, anaphylaxis, Grade 4 rash, exfoliative or bullous rash, or if Stevens - Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) or medicine reaction with eosinophilia and systemic symptoms (DRESS) is suspected, and should not be resumed following discontinuation for these reactions.

Special populations Elderly population No dose adjustment is required for POMARZA. Pd regimen after at least 2 prior therapies: For patients > 75 years of age, the starting dose of dexamethasone is 20 mg once daily on Days 1, 8, 15 and 22 of each 28 - day treatment cycle. PBd regimen after at least one prior therapy: For patients > than 75 years of age, the dose of dexamethasone is: Cycles 1 - 8: 10 mg once daily on days 1, 2, 4, 5, 8, 9, 11, and 12 of a 21 - day cycle. From cycle 9 onwards: 10 mg once daily on days 1, 2, 8, and 9 of a 21 - day cycle.

Renal impairment No dose adjustment of POMARZA is required for patients with renal impairment. On haemodialysis days, patients should take their POMARZA dose following haemodialysis.

Hepatic impairment Hepatic impairment has a modest effect on the pharmacokinetics of pomalidomide (see section 5.2). No adjustment of the starting 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 and interruption of POMARZA should be carried out as needed.

Paediatric population The safety and effectiveness of pomalidomide have not been established in paediatric patients with recurrent or progressive brain tumours.

Method of administration POMARZA should be taken orally at the same time each day. The capsules should not be opened, broken or chewed and should be swallowed whole, preferably with water, with or without food.

• hypersensitivity to pomalidomide or to any of the excipients listed in section 6.1.
• pregnancy and lactation (see section 4.6).
• females of childbearing potential, unless all the conditions of the pregnancy prevention programme are met (see section 4.4).
• male patients unable to follow or comply with the required contraceptive measures (see section 4.4).

General Pregnancy warning Pomalidomide is a thalidomide analogue. Thalidomide is a known human teratogenic active substance that causes severe life - threatening birth defects. If POMARZA is taken during pregnancy, a teratogenic effect of pomalidomide in humans is expected. The conditions of the RISK MANAGEMENT PROGRAMME must be fulfilled for all patients unless there is reliable evidence that the patient does not have childbearing potential.

Criteria for females of non - childbearing potential A female patient or a female partner of a male patient is considered to have childbearing potential unless she meets at least one of the following criteria:

• Age u2265 50 years and naturally amenorrhoeic for u2265 2 + years.
• Premature ovarian failure confirmed by a specialist gynaecologist.
• Previous bilateral salping o - oophorectomy, or hysterectomy.
• XY genotype, Turner syndrome, uterine agenesis.

*Amenorrhoea following cancer therapy or during breast - feeding does not rule out childbearing potential.

Counselling For females of childbearing potential, POMARZA 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, 4 weeks before starting treatment, throughout the entire duration of treatment including dose interruptions, and for 4 weeks after the end of treatment.
• Even if a female 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 POMARZA is dispensed following a negative pregnancy test.
• She understands the need and accepts to undergo pregnancy testing every 4 weeks except in case of confirmed tubal sterilization.
• She acknowledges that she understands the hazards and necessary precautions associated with the use of POMARZA.

The prescriber must ensure that for females of childbearing potential:

• The patient complies with the conditions of the RISK MANAGEMENT PROGRAMME, including confirmation that she has an adequate level of understanding.
• The patient has acknowledged the aforementioned conditions.

For male patients taking POMARZA, pharmacokinetic data has demonstrated that pomalidomide is present in human semen. As a precaution, all male patients taking POMARZA must meet the following conditions:

• He understands the expected teratogenic risk if engaged in sexual activity with a pregnant female or a female of childbearing potential.
• He understands the need for the use of a condom if engaged in sexual activity with a pregnant female or a female of childbearing potential not using effective contraception, during treatment and for 4 weeks after dose interruptions and/or cessation of treatment. Vasectomised males should wear a condom if engaged in sexual activity with a pregnant female as seminal fluid may still contain pomalidomide in the absence of spermatozoa.
• He understands that if his female partner becomes pregnant whilst he is taking POMARZA or for 4 weeks after he has stopped taking POMARZA, he should inform his treating medical practitioner immediately and that it is recommended to refer the female partner to a medical practitioner specialised or experienced in teratology for evaluation and advice.

Contraception Females of childbearing potential must use two reliable methods of contraception for 4 weeks before therapy, during therapy including dose interruptions, and until 4 weeks after POMARZA therapy 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 to be examples of suitable methods of contraception:

Highly effective methods

• Intra Uterine Device (IUD)
• Hormonal (hormonal implants, levonorgestrel - releasing intrauterine system (IUS)), medroxyprogesterone acetate depot injections, ovulation inhibitory progesterone - only pills (e.g., desogestrel)
• Tubal ligation
• Partneru2019s vasectomy

Effective methods

• Male condom
• Diaphragm
• Cervical cap

Because there is an increased risk of venous thromboembolism (VTE) in patients taking combined oral contraceptive pills, medical practitioners should discuss the risk/benefit of contraceptive methods with their patients. If a patient is currently using combined oral contraception the patient should switch to one of the effective methods listed above. The risk of venous thromboembolism continues for 4 - 6 weeks after discontinuing combined oral contraception. The efficacy of contraceptive steroids may be reduced during co - treatment with dexamethasone (see section 4.5).

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.

Pregnancy testing Medically supervised pregnancy tests with a minimum sensitivity of 25 mIU/ml must be performed for females of childbearing potential as outlined below. This requirement includes females of childbearing potential who practice absolute and continuous abstinence. Ideally, pregnancy testing, issuing a prescription and dispensing should occur on the same day. Dispensing of POMARZA to females of childbearing potential should occur within 7 days of the last pregnancy test.

Prior to starting treatment A medically supervised pregnancy test should be performed within 7 days prior to the patient starting POMARZA once the patient had been using effective contraception for at least 4 weeks. The test should ensure the patient is not pregnant when she starts treatment with POMARZA.

Follow - up and end of treatment A medically supervised pregnancy test should be repeated every 4 weeks, including 4 weeks after the end of treatment, except in the case of confirmed tubal sterilisation. These pregnancy tests should be performed on the day of the prescribing visit or within the 7 days prior to the visit to the prescriber.

Men Pomalidomide is present in human semen during treatment. As a precaution, and taking into account special populations with potentially prolonged elimination time such as renal impairment, all male patients taking POMARZA, including those who have had a vasectomy, should use condoms throughout treatment duration, during dose interruption and for 4 weeks after cessation of treatment if their partner is pregnant or of childbearing potential and has no contraception. Male patients should not donate semen or sperm during treatment (including during dose interruptions) and for 4 weeks following discontinuation of POMARZA.

Additional precautions Patients should be instructed never to give POMARZA to another person and to return any unused capsules to their pharmacist at the end of treatment. Patients should not donate blood during therapy including dose interruptions and for 4 weeks following discontinuation of POMARZA. Healthcare professionals and caregivers should wear disposable gloves when handling the blister or capsule. Women who are pregnant or suspect they may be pregnant should not handle the blister or capsule (see section 6.6).

Educational materials Full patient information about the expected teratogenic risk and the strict pregnancy prevention measures as specified in the RISK MANAGEMENT PROGRAMME should be given by the medical practitioner to females of childbearing potential and, as appropriate, to male patients.

Haematological events Neutropenia was the most frequently reported Grade 3/4 haematologic adverse reaction (AR) during treatment for relapsed/refractory multiple myeloma, followed by anaemia and thrombocytopenia. Monitor patients for haematologic toxicities, especially neutropenia. Patients should be advised to report febrile episodes promptly. Medical practitioners should observe patients for signs of bleeding including epistaxes, especially with use of concomitant medicines known to increase the risk of bleeding (see section 4.8). Monitor complete blood counts at baseline, weekly for the first 8 weeks and monthly thereafter. A dose modification may be required. Patients may require use of blood product support and/or growth factors.

Thromboembolic events Patients receiving POMARZA have commonly developed venous thromboembolic events (VTE) (predominantly deep vein thrombosis and pulmonary embolism) and arterial thrombotic events (myocardial infarction and cerebrovascular accident). Patients with known risk factors for thromboembolism u2013 including prior thrombosis u2013 should be closely monitored. Action should be taken to try to minimise all modifiable risk factors (e.g., smoking, hypertension, and hyperlipidaemia). Patients and medical practitioners are advised to be observant for the signs and symptoms of thromboembolism. Patients should be instructed to seek medical care if they develop symptoms such as shortness of breath, chest pain, arm or leg swelling. Anti - coagulation therapy (unless contraindicated) is recommended, (such as acetylsalicylic acid, warfarin, heparin or clopidogrel), especially in patients with additional thrombotic risk factors. A decision to take prophylactic measures should be made after a careful assessment of the individual patientu2019s underlying risk factors. In clinical studies, patients received prophylactic acetylsalicylic acid or alternative antithrombotic therapy. The use of erythropoietic agents carries a risk of thrombotic events including thromboembolism. Therefore, erythropoietic medicines may increase the risk of thromboembolic events and should be used with caution.

Thyroid disorders Cases of hypothyroidism have been reported. Optimal control of co - morbid conditions influencing thyroid function is recommended before start of treatment. Baseline and ongoing monitoring of thyroid function is recommended.

Peripheral neuropathy Appropriate caution should be exercised when considering the treatment of patients with ongoing u2265 Grade 2 peripheral neuropathy with POMARZA.

Significant cardiac dysfunction Cardiac events, including congestive cardiac failure, pulmonary oedema and atrial fibrillation (see section 4.8), have been reported, mainly in patients with pre - existing cardiac disease or cardiac risk factors. Appropriate caution should be exercised when considering the treatment of such patients with POMARZA, including periodic monitoring for signs or symptoms of cardiac events.

Tumour lysis syndrome The patients at greatest risk of tumour lysis syndrome are those with high tumour burden prior to treatment. These patients should be monitored closely and appropriate precautions taken.

Second Primary Malignancies Second primary malignancies, such as non - melanoma skin cancer, have been reported in patients receiving POMARZA (see section 4.8). Medical practitioners should carefully evaluate patients before and during treatment using standard cancer screening for occurrence of second primary malignancies and institute treatment as indicated.

Allergic reactions and Serious Skin Reactions u2022 Angioedema, anaphylaxis and severe dermatologic reactions including Stevens - Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported. DRESS may present with a cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, fever, and/or lymphadenopathy with systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, and/or pericarditis. These events can be fatal. u2022 Patients with a prior history of serious allergic reactions associated with thalidomide or lenalidomide may be at a higher risk of hypersensitivity and should not receive POMARZA. POMARZA interruption or discontinuation should be considered for Grade 2 - 3 skin rash. POMARZA must be discontinued for angioedema, anaphylaxis, Grade 4 rash, exfoliative or bullous rash or if SJS, TEN or DRESS is suspected, and should not be resumed following discontinuation for these reactions.

Dizziness and confusion Confusion, fatigue, depressed level of consciousness and dizziness have been reported with the use of POMARZA. Patients must avoid situations where dizziness or confusion may be a problem and not to take other medicines that may cause dizziness or confusion without first seeking medical advice.

Interstitial lung disease (ILD) ILD and related events, including cases of pneumonitis, have been observed with pomalidomide. Careful assessment of patients with an acute onset or unexplained worsening of pulmonary symptoms should be performed to exclude ILD. POMARZA should be interrupted pending investigation of these symptoms and if ILD is confirmed, appropriate treatment should be should only be resumed after a thorough evaluation of the benefits and the risks.

Hepatic Disorders Markedly elevated levels of alanine aminotransferase and bilirubin have been observed in patients treated with pomalidomide (see section 4.8). There have also been cases of hepatitis that resulted in discontinuation of POMARZA. Regular monitoring of liver function is recommended for the first 6 months of treatment with pomalidomide and as clinically indicated thereafter.

Infection Reactivation of hepatitis B has been reported in patients receiving POMARZA in combination with dexamethasone who have previously been infected with the hepatitis B virus (HBV). Some of these cases have progressed to acute hepatic failure, resulting in discontinuation of POMARZA. Hepatitis B virus status should be established before initiating treatment with pomalidomide. For patients who test positive for HBV infection, consultation with a physician with expertise in the treatment of hepatitis B is recommended. Caution should be exercised when pomalidomide in combination with dexamethasone is used in patients previously infected with HBV, including patients who are anti - HBc positive but HBsAg negative. These patients should be closely monitored for signs and symptoms of active HBV infection throughout therapy.

Progressive multifocal leukoencephalopathy (PML) Cases of progressive multifocal leukoencephalopathy, including fatal cases, have been reported with pomalidomide. PML was reported several months to several years after starting the treatment with pomalidomide. Cases have generally been reported in patients taking concomitant dexamethasone or prior treatment with other immunosuppressive chemotherapy. Physicians should monitor patients at regular intervals and should consider PML in the differential diagnosis in patients with new or worsening neurological symptoms, cognitive or behavioural signs or symptoms. Patients should also be advised to inform their partner or caregivers about their treatment, since they may notice symptoms that the patient is not aware of. The evaluation for PML should be based on neurological examination, magnetic resonance imaging of the brain, and cerebrospinal fluid analysis for JC virus (JCV) DNA by polymerase chain reaction (PCR) or a brain biopsy with testing for JCV. A negative JCV PCR does not exclude PML. Additional follow - up and evaluation may be warranted if no alternative diagnosis can be established. If PML is suspected, further dosing must be suspended until PML has been excluded. If PML is confirmed, pomalidomide must be permanently discontinued.

POMARZA contains lactose Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose - galactose malabsorption should not take this medicine.

Effect of POMARZA on other medicines POMARZA does not cause clinically relevant enzyme inhibition or induction or transporter inhibition when co - administered with substrates of these enzymes or transporters. The potential for such interactions, including the potential impact of POMARZA on exposure of oral contraceptives, has not been evaluated clinically.

Effect of other medicines on POMARZA Pomalidomide is partly metabolised by CYP1A2 and CYP3A4/5. It is also a substrate for P - glycoprotein. Co - administration of pomalidomide with the strong CYP3A4/5 and P - gp inhibitor ketoconazole, or the strong CYP3A4/5 inducer carbamazepine, had no clinically relevant effect on exposure to pomalidomide. Co - administration of the strong CYP1A2 inhibitor fluvoxamine with pomalidomide in the presence of ketoconazole, increased exposure to pomalidomide by 104 % with a 90 % confidence interval [88 % to 122 %] compared to pomalidomide plus ketoconazole. During evaluation of the contribution of a CYP1A2 inhibitor alone to metabolism changes, co - administration of fluvoxamine alone with pomalidomide increased mean exposure to pomalidomide by 125 % with a 90 % confidence interval [98 % to 156 %] compared to pomalidomide alone. If strong inhibitors of CYP1A2 are co - administered with pomalidomide, reduce the pomalidomide dose by 50 % for patients with multiple myeloma (based on the recommended starting doses) (see section 4.2).

Dexamethasone Co - administration of multiple doses of 4 mg POMARZA with 20 mg to 40 mg dexamethasone (a weak to moderate inducer of several CYP enzymes including CYP3A) to patients with multiple myeloma had no effect on the pharmacokinetics of pomalidomide compared with pomalidomide administered alone. Dexamethasone is a weak to moderate enzyme inducer and its effect on warfarin is unknown. Close monitoring of warfarin concentration is advised during treatment.

Women of childbearing potential / Contraception in males and females Females of childbearing potential should use two effective methods of contraception. If pregnancy occurs in a female treated with POMARZA, treatment must be stopped and the patient should be referred to a medical practitioner specialised or experienced in teratology for evaluation and advice. If pregnancy occurs in a partner of a male patient taking POMARZA, it is recommended to refer the female partner to a medical practitioner specialised or experienced in teratology for evaluation and advice.

Pomalidomide is present in human semen. As a precaution, all male patients taking POMARZA should use condoms throughout treatment duration, during dose interruption and for 4 weeks after cessation of treatment if their partner is pregnant or of childbearing potential and has no contraception (see section 4.4).

Pregnancy POMARZA is contraindicated during pregnancy and in women of childbearing potential (see section 4.3).

Breastfeeding Breastfeeding of infants is contraindicated in mothers taking POMARZA (see section 4.3).

POMARZA may cause confusion, fatigue, depressed level of consciousness and dizziness and affect mental and/or physical abilities to perform or execute tasks or activities requiring mental alertness, judgment and/or sound coordination and vision. If affected, patients should be instructed not to drive cars, use machines or perform hazardous tasks while being treated with pomalidomide.

PBd Treatment Regimen u2013 for relapsed and refractory multiple myeloma after at least one prior therapy including lenalidomide:

Table 1: Tabulated summary of adverse reactions

System Organ Class Frequency Adverse effect

Infections and infestations Frequent Upper respiratory tract infection, pneumonia, bronchitis, viral upper respiratory infection, influenza, urinary tract infection, respiratory tract infection, lower respiratory tract infection, sepsis, septic shock, Clostridium difficile colitis, lung infection, bronchiolitis

Neoplasms benign, malignant and unspecified (including cysts and polyps) Frequent Basal cell carcinoma

Blood and lymphatic system disorders Frequent Neutropenia, thrombocytopenia, anaemia, leukopenia, lymphopenia, febrile neutropenia

Metabolism and nutrition disorders Frequent Hypokalemia, hyperglycemia, hypomagnesemia, hypocalcemia, hypophosphatemia, hyperkalemia, hypercalcemia

Psychiatric disorders Frequent Insomnia, depression

Nervous system disorders Frequent Peripheral sensory neuropathy, dizziness, tremor, dysgeusia, syncope, peripheral sensorimotor neuropathy, paresthesia

Eye disorders Frequent Cataract

Cardiac disorders Frequent Atrial fibrillation

Vascular disorders Frequent Hypotension, hypertension, deep vein thrombosis

Respiratory, thoracic and mediastinal disorders Frequent Cough, dyspnoea, pulmonary embolism

Gastro - intestinal disorders Frequent Constipation, diarrhoea, nausea, vomiting, abdominal pain, abdominal pain upper, stomatitis, dry mouth, abdominal distension

Skin and sub - cutaneous tissue disorders Frequent Rash

Musculo - skeletal and connective tissue disorders Frequent Back pain, muscular weakness, muscle spasms, bone pain

Renal and urinary disorders Frequent Acute kidney injury, chronic kidney disease, urinary retention

General disorders and administration site conditions Frequent Fatigue, oedema peripheral, pyrexia, non - cardiac chest pain, oedema

Investigations Frequent Weight decreased, alanine aminotransferase increased

Injury, poisoning and procedural complications Frequent Fall

Pd Treatment Regimen u2013 in relapsed and refractory multiple myeloma after at least two prior therapies including lenalidomide and a proteasome inhibitor:

Table 2: Tabulated summary of adverse reactions

System Organ Class Frequency Adverse effect

Infections and infestations Frequent Pneumonia (bacterial, viral and fungal infections, including opportunistic infections), neutropenic sepsis, bronchopneumonia, bronchitis, respiratory tract infection, upper respiratory tract infection, nasopharyngitis, herpes zoster

Frequency unknown Hepatitis B reactivation

Neoplasms benign, malignant and unspecified (including cysts and polyps) Less frequent Basal cell carcinoma, squamous cell carcinoma of the skin

Blood and lymphatic system disorders Frequent Neutropenia, thrombocytopenia, anaemia, leukopenia, febrile neutropenia, pancytopenia

Metabolism and nutrition disorders Frequent Decreased appetite, hyperkalemia, hyponatraemia, hyperuricaemia

Less frequent Tumour lysis syndrome

Psychiatric disorders Frequent Confusional state

Nervous system disorders Frequent Depressed level of consciousness, peripheral sensory neuropathy, dizziness, tremor, intracranial haemorrhage

Less frequent Cerebrovascular accident

Ear and labyrinth disorders Frequent Vertigo

Cardiac disorders Frequent Cardiac failure, atrial fibrillation, myocardial infarction

Vascular disorders Frequent Deep vein thrombosis

Immune system disorders Frequent Angioedema, urticaria

Respiratory, thoracic and mediastinal disorders Frequent Dyspnoea, cough, pulmonary embolism, epistaxis, interstitial lung disease

Gastro - intestinal disorders Frequent Diarrhoea, nausea, constipation, vomiting, gastrointestinal haemorrhage

Hepatobiliary disorders Less frequent Hyperbilirubinaemia, hepatitis

Skin and sub - cutaneous tissue disorders Frequent Rash, pruritus

Musculo - skeletal and connective tissue disorders Frequent Bone pain, muscle spasms

Renal and urinary disorders Frequent Renal failure, urinary retention

Reproductive system and breast disorders Frequent Pelvic pain

General disorders and administration site conditions Frequent Fatigue, pyrexia, oedema peripheral

Investigations Frequent Decreased neutrophil count, decreased white blood cell count, decreased platelet count, increased alanine aminotransferase, increased blood uric acid increased

Post - marketing data: Blood and Lymphatic System Disorders: Pancytopenia Endocrine Disorders: Hypothyroidism Gastrointestinal Disorders: Gastrointestinal haemorrhage Hepatobiliary Disorders: Hepatitis, increased liver function tests Immune System Disorders: Allergic reactions (e.g., angioedema, anaphylaxis, urticaria) Infections and Infestations: Viral reactivation (such as hepatitis B virus and herpes zoster), progressive multifocal leukoencephalopathy (PML) Neoplasms benign, malignant and unspecified (incl cysts and polyps): Tumour lysis syndrome, basal cell carcinoma, and squamous cell carcinoma of the skin Respiratory, Thoracic and Mediastinal Disorders: Interstitial lung disease (ILD), pneumonitis Skin and Subcutaneous Tissue Disorders: Stevens - Johnson Syndrome, toxic epidermal necrolysis, medicine reaction with eosinophilia and systemic symptoms (DRESS)

Description of selected adverse reactions: Teratogenicity: POMARZA is structurally related to thalidomide. Thalidomide is a known human teratogenic active substance that causes severe life - threatening birth defects. If POMARZA is taken during pregnancy, a teratogenic effect of pomalidomide in humans is expected (see section 4.4 and section 4.6). Neutropenia and thrombocytopenia: Neutropenia occurred in patients who received pomalidomide plus low dose dexamethasone (Pom + LD - Dex), and in patients who received high dose dexamethasone (HD - Dex). Neutropenia was Grade 3 or 4 in patients who received Pom + LD - Dex, compared with patients who received HD - Dex. In Pom + LD - Dex treated patients neutropenia was infrequently serious, and did not lead to treatment discontinuation, and was associated with treatment interruption and with dose reduction. Febrile neutropenia (FN) was experienced in patients who received Pom + LD - Dex, and in no patients who received HD - Dex. All were reported to be Grade 3 or 4. FN was reported to be serious. FN was associated with dose interruption, dose reduction and with no treatment discontinuations. Thrombocytopenia occurred in patients who received Pom + LD - Dex, and patients who received HD - Dex. Thrombocytopenia was Grade 3 or 4 in patients who received Pom + LD - Dex and who received HD - Dex. In Pom + LD - Dex treated patients, thrombocytopenia was serious, and led to dose reduction, to dose interruption and to treatment discontinuation (see section 4.4 and section 4.6). Infection Infection was the most common non haematological toxicity; it occurred in patients who received Pom + LD - Dex, and patients who received HD - Dex. Approximately half of those infections were Grade 3 or 4; in Pom + LD - Dex - treated patients and in patients who received HD - Dex. In Pom + LD - Dex treated patients pneumonia and upper respiratory tract infections were the most commonly reported infections with reported infections being serious and fatal infections (Grade 5) occurring in treated patients. In Pom + LD - Dex treated patients infections led to dose discontinuation, to treatment interruption, and to a dose reduction. Thromboembolic events: Venous embolic or thrombotic events (VTE) occurred in patients who received Pom + LD - Dex, and patients who received HD - Dex. Grade 3 or 4 reactions occurred in patients who received Pom + LD - Dex, and no patients who received HD - Dex. In Pom + LD - Dex treated patients, VTE was reported as serious in patients, no fatal reactions were reported in clinical studies, and VTE was not associated with dose discontinuation. Anticoagulation therapy (unless contraindicated) is recommended (see section 4.2). Peripheral neuropathy: Patients with ongoing peripheral neuropathy u2265 Grade 2 were excluded from clinical studies. Peripheral neuropathy, mostly Grade 1 or 2 occurred in patients who received Pom + LD - Dex, and patients who received HD - Dex. Grade 3 or 4 reactions occurred in patients who received Pom + LD - Dex and in patients who received HD - Dex. In patients treated with Pom + LD - Dex, no peripheral neuropathy reactions were reported to have been serious in clinical trials and peripheral neuropathy led to dose discontinuation (see section 4.4 and section 4.6). Haemorrhage: Haemorrhagic disorders have been reported with POMARZA, especially in patients with risk factors such as concomitant medicines that increase susceptibility to bleeding. Haemorrhagic events have included epistaxis, intracranial haemorrhage and gastrointestinal haemorrhage.

Adverse events will be an exaggeration of the side effects (see section 4.8). Treatment should be symptomatic and supportive. It is unknown whether pomalidomide or its metabolites are dialysable.