Pomylo 1 Mg/2 Mg/3 Mg/4 Mg Capsules

POMYLO in combination with dexamethasone is indicated for 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 medical practitioner experienced in the management of multiple myeloma.

Dosage: The recommended starting dose of POMYLO 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.

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

Dose modification instructions for POMYLO for haematologic toxicities:

• Toxicity Dose modification Neutropenia u2022 ANC < 500/u03bcL or Febrile neutropenia (fever u2265 38,5. u00b0C and ANC <1 ,000/u03bcL) u2022 ANC return to u2265 500/u03bcL u2022 For each subsequent drop < 500/u03bcL u2022 Return to u2265 500/u03bcL Interrupt POMYLO treatment, follow CBC weekly. Add G-CSF (at the discretion of the treating medical practitioner). Resume POMYLO at 3 mg daily. Interrupt POMYLO treatment. Resume POMYLO at 1 mg less than the previous dose.
• Thrombocytopenia u2022 Platelets 50 000/u03bcL u2022 For each subsequent drop < 25 000/u03bcL u2022 Return to u2265 50 000/u03bcL Interrupt POMYLO treatment, follow CBC weekly. Resume POMYLO treatment at 3 mg daily. Interrupt POMYLO treatment. Resume POMYLO at 1 mg less than the previous dose.

*ANC u2013 Absolute Neutrophil Count; ** CBC u2013 Complete Blood Count

To initiate a new cycle of POMYLO 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 POMYLO, stop treatment and restart treatment at 1 mg less than the previous dose when toxicity has resolved to u2264 Grade 2 at the medical practitioner's discretion. If toxicities occur after dose reductions to 1 mg, then the medicine should be discontinued.

Dexamethasone dose modification instructions: Dexamethasone dose reduction levels:

Toxicity Dose modification Dyspepsia = Grade 1-2 Maintain dose and treat with histamine (H2) blockers or equivalent. Decrease by one dose level if symptoms persist. Dyspepsia u2265 Grade 3 Interrupt dose until symptoms are controlled. Add H2 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 agents 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.

Dose reduction levels (u2264 75 years of age): Starting dose 40 mg; dose level -1 20 mg; dose level -2 10 mg on Days 1, 8, 15 and 22 of each 28-day treatment cycle. Dose reduction levels (> 75 years of age): Starting dose 20 mg; dose level -1 12 mg; dose level -2 8 mg on Days 1, 8, 15 and 22 of each 28-day treatment cycle. If recovery from toxicities is prolonged beyond 14 days, then the dose of dexamethasone will be decreased by one dose level.

Special populations Elderly population No dose adjustment is required for POMYLO. 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. Renal impairment A study in subjects with renal impairment has not been conducted with POMYLO. Patients with moderate or severe renal impairment (creatinine clearance < 45 mL/min) were excluded from clinical studies. Patients with renal impairment should be carefully monitored for adverse reactions. POMYLO should be avoided in patients with severe renal impairment (creatinine clearance 2,0 mg/dL were excluded from clinical studies. POMYLO should be avoided in patients with serum bilirubin greater than 2,0 mg/dL and AST or ALT greater than 3,0 mg/dL x ULN. Paediatric population: No data are available on administration of POMYLO to paediatric or adolescent subjects (< 18 years of age).

Method of administration: Oral use. POMYLO should be taken at the same time each day. The capsules should not be opened, broken or chewed. This medicine should be swallowed, preferably with water, with or without food.

• Hypersensitivity to POMYLO (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. Pomalidomide was found to be teratogenic in both rats and rabbits when administered during the period of major organogenesis. If POMYLO is taken during pregnancy, a teratogenic effect of pomalidomide in humans is expected. The conditions of the Active Risk Management Program 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 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 1 year*.
• Premature ovarian failure confirmed by a specialist gynaecologist.
• Previous bilateral salpingo-oophorectomy, or hysterectomy.
• XY genotype, Turner syndrome, uterine agenesis.

* Amenorrhoea following cancer therapy or during breastfeeding does not rule out childbearing potential.

Counselling: For women of childbearing potential, POMYLO is contraindicated unless all 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 amenorrhea 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 POMYLO 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 sterilisation.
• She acknowledges that she understands the hazards and necessary precautions associated with the use of POMYLO.

The prescriber must ensure that for females of childbearing potential:

• The patient complies with the conditions of the Active Risk Management Program, including confirmation that she has an adequate level of understanding.
• The patients has acknowledged the aforementioned conditions.

For male patients taking POMYLO, pharmacokinetic data has demonstrated that pomalidomide is present in human semen. As a precaution, all male patients taking POMYLO 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 POMYLO or for 4 weeks after he has stopped taking POMYLO, 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 POMYLO 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 of the increased risk of venous thromboembolism in patients with multiple myeloma taking pomalidomide and dexamethasone, combined oral contraceptive pills are not recommended (see also section 4.5). 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: According to local practice, medically supervised pregnancy tests with a minimum sensitivity of 50 IU/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 POMYLO 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 POMYLO 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 POMYLO.

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 POMYLO, 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 POMYLO.

Additional precautions: Patients should be instructed never to give POMYLO 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 POMYLO. 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: In order to assist patients in avoiding fetal exposure to pomalidomide, educational material will be provided to healthcare providers to reinforce the warnings about the expected teratogenicity of POMYLO, to provide advice on contraception before therapy is started, and to provide guidance on the need for pregnancy testing. Full patient information about the expected teratogenic risk and the strict pregnancy prevention measures as specified in the Active Risk Management Program should be given by the medical practitioner to females of childbearing potential and, as appropriate, to male patients. Ideally, pregnancy testing, issuing a prescription and dispensing should occur on the same day. Dispensing of pomalidomide to women of childbearing potential should occur within 7 days of the prescription and following a medically supervised negative pregnancy test result. Prescriptions for women of childbearing potential can be for a maximum duration of treatment of 4 weeks according to the approved indications dosing regimens (see section 4.2), and prescriptions for all other patients can be for a maximum duration of 12 weeks.

Haematological events: Neutropenia was the most frequently reported Grade 3/4 haematological adverse reaction (AR) in patients with relapsed/refractory multiple myeloma, followed by anaemia and thrombocytopenia. Monitor patients for haematological toxicities, especially neutropenia. Monitor complete blood counts 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 POMYLO 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 - including prior thrombosis - should be closely monitored. Action should be taken to try to minimise all modifiable risk factors (e.g. smoking, hypertension, and hyperlipidaemia). Patients and healthcare professionals 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 carefully after assessment of an individual patientu2019s underlying risk factors.

The use of erythropoietic medicines carries a risk of thrombotic events including thromboembolism. Therefore, erythropoietic medicines, as well as other medicines that may increase the risk of thromboembolic events, 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: Patients with ongoing u2265 Grade 2 peripheral neuropathy were excluded from clinical studies with pomalidomide. Appropriate caution should be exercised when considering the treatment of such patients with pomalidomide.

Significant cardiac dysfunction: Patients with significant cardiac dysfunction (congestive heart failure [NY Heart Association Class Ill or IV]; myocardial infarction within 12 months of starting study; unstable or poorly controlled angina pectoris) were excluded from clinical studies with pomalidomide. 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 pomalidomide, including periodic monitoring for signs or symptoms of cardiac events.

Tumour lysis syndrome: Tumour lysis syndrome may occur. 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 POMYLO (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 severe skin reactions: Angioedema, anaphylactic reaction and severe dermatologic reactions including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and Drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported with the use of pomalidomide (see section 4.8). Patients should be advised of the signs and symptoms of these reactions by their prescribers and should be told to seek medical attention immediately if they develop these symptoms. POMYLO must be discontinued for exfoliative or bullous rash, or if SJS, TEN or DRESS is suspected, and should not be resumed following discontinuation for these reactions. Patients with a prior history of serious allergic reactions associated with thalidomide or pomalidomide were excluded from clinical studies. Such patients may be at higher risk of hypersensitivity reactions and should not receive POMYLO. Pomalidomide interruption or discontinuation should be considered for Grade 2-3 skin rash. Pomalidomide must be discontinued permanently for angioedema and anaphylactic reaction.

Pulmonary hypertension: Cases of pulmonary hypertension, some fatal, have been reported in patients treated with pomalidomide. Patients should be evaluated for signs and symptoms of underlying cardiopulmonary disease prior to initiating and during pomalidomide therapy.

Dizziness and confusion: Confusion, fatigue, depressed level of consciousness and dizziness have been reported with the use of pomalidomide. Patients must avoid situations where dizziness or confusion may be a problem and should not 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. POMYLO should be interrupted pending investigation of these symptoms and if ILD is confirmed, appropriate treatment should be initiated. POMYLO 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 pomalidomide. Regular monitoring of liver function is recommended for the first 6 months of treatment with POMYLO and as clinically indicated thereafter.

Infections: Reactivation of hepatitis B has been reported in patients receiving pomalidomide 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 pomalidomide. Hepatitis B virus status should be established before initiating treatment with pomalidomide. For patients who test positive for HBV infection, consultation with a medical practitioner 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. Medical practitioners 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.

Excipient warning: POMYLO contains less than 1 mmol sodium (23 mg) per capsule, that is to say essentially u2018sodium - freeu2019.

Effect of POMYLO on other medicines: POMYLO 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 POMYLO on exposure of oral contraceptives, has not been evaluated clinically.

Effect of other medicines on POMYLO: Pomalidomide is partly metabolised by CYP1 A2 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. Co-administration of fluvoxamine alone with pomalidomide increased mean exposure to pomalidomide by 125 % with a 90% confidence interval [98 % to 157 %] compared to pomalidomide alone. If strong inhibitors of CYP1A2 (e.g. ciprofloxacin, enoxacin and fluvoxamine) are co-administered with POMYLO, patients should be closely monitored for the occurrence of side effects.

Dexamethasone: Co-administration of multiple doses of 4 mg POMYLO 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 POMYLO, 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 POMYLO, 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 POMYLO 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 sections 4.3 and 4.4).

Pregnancy: POMYLO is contraindicated during pregnancy and in women of childbearing potential (see section 4.3). Pomalidomide was found to be teratogenic in embryo-foetal development toxicity studies in rats and rabbits. Pomalidomide crosses the placenta and was detected in foetal blood following administration to pregnant rabbits.

Breastfeeding: Breastfeeding of infants is contraindicated in mothers taking POMYLO. Pomalidomide was detected in milk of lactating rats following administration to the mother.

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.

POMYLO 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.

a. Summary of the safety profile The frequently reported adverse reactions have been blood and lymphatic system disorders including anaemia, neutropenia and thrombocytopenia; in general disorders and administration site conditions including fatigue, pyrexia and peripheral oedema; and in infections and infestations including pneumonia. Peripheral neuropathy and venous embolic or thrombotic (VTE) adverse reactions were also reported. The frequently reported serious adverse reaction was pneumonia. Other serious adverse reactions reported included febrile neutropenia, neutropenia, thrombocytopenia and VTE adverse reactions.

System Organ Class: Frequency: Side effects Infections and Infestations Frequent Pneumonia (bacterial, viral and fungal infections, including opportunistic infections), neutropenic sepsis, septic shock, Frequency unknown Clostridium difficile colitis, influenza, bronchiolitis, urinary tract infection, bronchopneumonia, bronchitis respiratory tract infection, upper respiratory tract infections, nasopharyngitis, herpes zoster Hepatitis B reactivation Neoplasms benign, malignant and unspecified (including cysts and polyps) Less frequent Basal cell carcinoma of the skin, squamous cell carcinoma of the skin Blood and lymphatic system disorders Frequent Neutropenia, thrombocytopenia, leucopenia, anaemia, febrile neutropenia, pancytopenia* Immune system disorders Frequent Angioedema*, urticaria* Metabolism and nutrition disorders Frequent Less frequent Decreased appetite, hyperkalaemia, hyponatraemia, hyperuricaemia*, hypokalaemia, hyperglycaemia, hypomagnaesaemia, hypocalcaemia, hypophosphataemia, hypercalcaemia Tumour lysis syndrome* Psychiatric Frequent Confusional state, insomnia, disorders depression Nervous system disorders Frequent Less frequent Depressed level of consciousness, peripheral sensory neuropathy, dizziness, tremor, intracranial haemorrhage*, paraesthesia, dysgeusia, syncope Cerebrovascular accident* Ear and labyrinth disorders Frequent Vertigo Eye disorders Frequent Cataract Vascular disorders Frequent Deep vein thrombosis, hypotension, hypertension Cardiac disorders Frequent Cardia failure*, atrial fibrillation*, myocardial infarction* Respiratory, thoracic and mediastinal disorders Frequent Less frequent Dyspnoea, cough, pulmonary embolism, epistaxis*, interstitial lung disease* Pulmonary hypertension Gastrointestinal disorders Frequent Diarrhoea, nausea, constipation, vomiting, gastrointestinal haemorrhage, abdominal pain, stomatitis, dry mouth, abdominal distension Hepato-biliary disorders Less frequent Hyperbilirubinaemia, hepatitis* Skin and subcutaneous tissue disorders Frequent Rash, pruritus Frequency unknown Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), Toxic Epidermal Necrolysis, Stevens-Johnson Syndrome Musculoskeletal, and connective tissue disorders Frequent Bone pain, muscle spasms, muscular weakness, back pain Renal and urinary disorders Frequent Renal failure, urinary retention, acute kidney injury, chronic kidney injury Reproductive system and breast disorders Frequent Pelvic pain General disorders and administration site conditions Frequent Fatigue, pyrexia, peripheral oedema, non-cardiac chest pain Investigations Frequent Decreased neutrophil count, decreased white blood cell count, decreased platelet count, increased alanine aminotransferase, increased blood uric acid* Injury, poisoning and procedural complications Frequent Fall * Identified from post marketing data.

Reporting of suspected adverse reactions: Reporting of suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8.

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