Pomalid Special Precautions

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. Pomalidomide was found to be teratogenic in both rats and rabbits when administered during the period of major organogenesis (see Pharmacology: Pharmacodynamics under Actions). 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; 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.
The prescriber must ensure that for women of childbearing potential: The patient complies with the conditions of the Pregnancy Prevention Programme, including confirmation that she has an adequate level of understanding.
The patient has acknowledged the aforementioned conditions.
For male patients taking pomalidomide, pharmacokinetic data has demonstrated that pomalidomide is present in human semen during treatment. As a precaution, and taking into account special populations with potentially prolonged elimination time such as hepatic impairment, all male patients taking pomalidomide must meet the following conditions: He understands the expected teratogenic risk if engaged in sexual activity with a pregnant woman or a woman of childbearing potential.
He understands the need for the use of a condom if engaged in sexual activity with a pregnant woman or a woman of childbearing potential not using effective contraception, throughout treatment duration, during dose interruption and for 7 days after dose interruptions and/or cessation of treatment. This includes vasectomised males who should wear a condom if engaged in sexual activity with a pregnant woman or a woman of childbearing potential 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 pomalidomide or 7 days after he has stopped taking pomalidomide, he should inform his treating physician immediately and that it is recommended to refer the female partner to a physician specialised or experienced in teratology for evaluation and advice.
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 pomalidomide therapy and even in 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 to be examples of suitable methods of contraception: Implant; Levonorgestrel-releasing intrauterine system; Medroxyprogesterone acetate depot; Tubal sterilisation; Sexual intercourse with a vasectomised male partner only; vasectomy must be confirmed by two negative semen analyses; Ovulation inhibitory progesterone-only pills (i.e. desogestrel).
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 Interactions). If a patient is currently using combined oral contraception the patient should switch to one of the effective methods listed previously. 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 (see Interactions).
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 25 mIU/mL must be performed for women of childbearing potential as outlined as follows. This requirement includes women 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 pomalidomide to women of childbearing potential should occur within 7 days of the prescription.
Prior to starting treatment: A medically supervised pregnancy test should be performed during the consultation, when pomalidomide is prescribed, or in the 3 days prior to the visit to the prescriber 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 pomalidomide.
Follow-up and end of treatment: A medically supervised pregnancy test should be repeated at least every 4 weeks, including at least 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 in the 3 days prior to the visit to the prescriber.
Additional precautions: Patients should be instructed never to give this medicinal product to another person and to return any unused capsules to their pharmacist at the end of treatment.
Patients should not donate blood, semen or sperm during treatment (including during dose interruptions) and for 7 days following discontinuation of pomalidomide.
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.
Educational materials, prescribing and dispensing restrictions: In order to assist patients in avoiding foetal exposure to pomalidomide, the Marketing Authorisation Holder will provide educational material to health care professionals to reinforce the warnings about the expected teratogenicity of pomalidomide, to provide advice on contraception before therapy is started, and to provide guidance on the need for pregnancy testing. The prescriber must inform the patient about the expected teratogenic risk and the strict pregnancy prevention measures as specified in the Pregnancy Prevention Programme and provide patients with appropriate patient educational brochure, patient card and/or equivalent tool in accordance with the national implemented patient card system. 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 4 weeks, 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 or 4 haematological adverse reaction in patients with relapsed/refractory multiple myeloma, followed by anaemia and thrombocytopenia. Patients should be monitored for haematological adverse reactions, especially neutropenia. Patients should be advised to report febrile episodes promptly. Physicians should observe patients for signs of bleeding including epistaxes, especially with use of concomitant medicinal products known to increase the risk of bleeding (see Adverse Reactions). Complete blood counts should be monitored at baseline, weekly for the first 8 weeks and monthly thereafter. A dose modification may be required (see Dosage & Administration). Patients may require use of blood product support and/or growth factors.
Thromboembolic events: Patients receiving pomalidomide either in combination with bortezomib and dexamethasone or in combination with dexamethasone have developed venous thromboembolic events (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 physicians 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 patient's underlying risk factors. In clinical studies, patients received prophylactic acetylsalicylic acid or alternative anti-thrombotic therapy. The use of erythropoietic agents carries a risk of thrombotic events including thromboembolism. Therefore, erythropoietic agents, as well as other agents that may increase the risk of thromboembolic events, should be used with caution.
Peripheral neuropathy: Patients with ongoing ≥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 III 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 Adverse Reactions), 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: 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 pomalidomide (see Adverse Reactions). Physicians 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 and severe dermatologic reactions including SJS, TEN and DRESS have been reported with the use of pomalidomide (see Adverse Reactions). 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. Pomalidomide 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 lenalidomide were excluded from clinical studies. Such patients may be at higher risk of hypersensitivity reactions and should not receive pomalidomide. Pomalidomide interruption or discontinuation should be considered for Grade 2-3 skin rash. Pomalidomide must be discontinued permanently for angioedema and anaphylactic reaction.
Dizziness and confusion: Dizziness and confusional state have been reported with pomalidomide. Patients must avoid situations where dizziness or confusion may be a problem and not to take other medicinal products 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. Pomalidomide should be interrupted pending investigation of these symptoms and if ILD is confirmed, appropriate treatment should be initiated. Pomalidomide 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 Adverse Reactions). 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 pomalidomide and as clinically indicated thereafter.
Infections: Reactivation of hepatitis B has been reported rarely 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 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.
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.
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.
Sodium content: This medicinal product contains less than 1 mmol sodium (23 mg) per capsule, i.e. essentially 'sodium-free'.
For information on other medicinal products given in combination with Pomalid, refer to the respective current leaflet/brochure.
Effects on ability to drive and use machines: Pomalidomide has minor or moderate influence on the ability to drive and use machines. Fatigue, depressed level of consciousness, confusion, and dizziness have been reported with the use of pomalidomide. If affected, patients should be instructed not to drive cars, use machines or perform hazardous tasks while being treated with pomalidomide.