Important Safety Info and Indication
WARNING: EMBRYO-FETAL TOXICITY and VENOUS AND ARTERIAL THROMBOEMBOLISM
Embryo-Fetal Toxicity
- POMALYST is contraindicated in pregnancy. POMALYST is a thalidomide analogue. Thalidomide is a known human
teratogen that causes severe birth defects or embryo-fetal death. In females of reproductive potential,
obtain 2 negative pregnancy tests before starting POMALYST treatment.
- Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual
sex during and for 4 weeks after stopping POMALYST treatment.
POMALYST is only available through a restricted distribution program called POMALYST REMS®.
Venous and Arterial Thromboembolism
- Deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke occur in patients
with multiple myeloma treated with POMALYST. Prophylactic antithrombotic measures were employed in clinical
trials. Thromboprophylaxis is recommended, and the choice of regimen should be based on assessment of the
patient’s underlying risk factors.
CONTRAINDICATIONS
- Pregnancy: POMALYST can cause fetal harm and is
contraindicated in females who are pregnant. If the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to a fetus.
- Hypersensitivity: POMALYST is contraindicated in
patients who have demonstrated severe hypersensitivity (e.g., angioedema, anaphylaxis) to pomalidomide or any
of the excipients.
WARNINGS AND PRECAUTIONS
- Embryo-Fetal Toxicity & Females of Reproductive Potential: See Boxed WARNINGS
- POMALYST REMS® Program: See Boxed WARNINGS
- Venous and Arterial Thromboembolism: See Boxed WARNINGS. Patients with
known risk factors, including prior thrombosis, may be at greater risk, and actions should be taken to try
to minimize all modifiable factors (e.g., hyperlipidemia, hypertension, smoking). Thromboprophylaxis is recommended,
and the choice of regimen should be based on assessment of the patient’s underlying risk factors.
- Increased Mortality With Pembrolizumab: In clinical
trials in patients with multiple myeloma, the addition of pembrolizumab to a thalidomide analogue plus dexamethasone
resulted in increased mortality. Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone
is not recommended outside of controlled clinical trials.
- Hematologic Toxicity: Neutropenia (46%) was the
most frequently reported Grade 3 or 4 adverse reaction in patients taking POMALYST in clinical trials, followed
by anemia and thrombocytopenia. Monitor complete blood counts weekly for the first 8 weeks and monthly thereafter.
Patients may require dose interruption and/or modification.
- Hepatotoxicity: Hepatic failure, including fatal
cases, has occurred in patients treated with POMALYST. Elevated levels of alanine aminotransferase and bilirubin
have also been observed in patients treated with POMALYST. Monitor liver function tests monthly. Stop POMALYST
upon elevation of liver enzymes. After return to baseline values, treatment at a lower dose may be considered.
- Severe Cutaneous Reactions:
Severe cutaneous reactions including Stevens-Johnson syndrome (SJS), 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 reactions can be fatal.
Consider POMALYST interruption or discontinuation for Grade 2 or 3 skin rash. Permanently discontinue POMALYST
for Grade 4 rash, exfoliative or bullous rash, or any other severe cutaneous reactions such as SJS, TEN or
DRESS.
- Dizziness and Confusional State: In patients taking
POMALYST in clinical trials, 14% experienced dizziness (1% Grade 3 or 4) and 7% a confusional state (3% Grade
3 or 4). Instruct patients to avoid situations where dizziness or confusional state may be a problem and not
to take other medications that may cause dizziness or confusional state without adequate medical advice.
- Neuropathy: In patients taking POMALYST in clinical
trials, 18% experienced neuropathy (2% Grade 3 in one trial) and 12% peripheral neuropathy.
- Second Primary Malignancies: Cases of acute myelogenous
leukemia have been reported in patients receiving POMALYST as an investigational therapy outside of multiple
myeloma.
- Tumor Lysis Syndrome (TLS): TLS may occur in patients
treated with POMALYST. Patients at risk are those with high tumor burden prior to treatment. These patients
should be monitored closely and appropriate precautions taken.
- Hypersensitivity: Hypersensitivity, including angioedema,
anaphylaxis, and anaphylactic reactions to POMALYST have been reported. Permanently discontinue POMALYST for
angioedema or anaphylaxis.
ADVERSE REACTIONS
The most common adverse reactions for POMALYST (≥30%) included fatigue and asthenia, neutropenia, anemia, constipation,
nausea, diarrhea, dyspnea, upper-respiratory tract infections, back pain, and pyrexia.
In the phase III trial, nearly all patients treated with POMALYST + low-dose dex experienced at least one adverse reaction (99%). Adverse reactions (≥15% in the POMALYST + low-dose dex arm and ≥2% higher than control) included neutropenia (51%), fatigue and asthenia (47%), upper respiratory tract infection (31%), thrombocytopenia (30%), pyrexia (27%), dyspnea (25%), diarrhea (22%), constipation (22%), back pain (20%), cough (20%), pneumonia (19%), bone pain (18%), edema peripheral (17%), peripheral neuropathy (17%), muscle spasms (15%), and nausea (15%). Grade 3 or 4 adverse reactions (≥15% in the POMALYST + low-dose dex arm and ≥1% higher than control) included neutropenia (48%), thrombocytopenia (22%), and pneumonia (16%).
DRUG INTERACTIONS
Avoid concomitant use of POMALYST with strong inhibitors of CYP1A2. If concomitant use of a strong CYP1A2 inhibitor is unavoidable, reduce POMALYST dose to 2 mg.
USE IN SPECIFIC POPULATIONS
- Pregnancy: See Boxed WARNINGS. If pregnancy does occur during treatment,
immediately discontinue the drug and refer patient to an obstetrician/gynecologist experienced in reproductive
toxicity for further evaluation and counseling. There is a POMALYST pregnancy exposure registry that monitors
pregnancy outcomes in females exposed to POMALYST during pregnancy as well as female partners of male patients
who are exposed to POMALYST. This registry is also used to understand the root cause for the pregnancy. Report
any suspected fetal exposure to POMALYST to the FDA via the MedWatch program at 1-800-FDA-1088 and also to
Celgene Corporation at 1-888-423-5436.
- Lactation: There is no information regarding the
presence of pomalidomide in human milk, the effects of POMALYST on the breastfed child, or the effects of POMALYST
on milk production. Pomalidomide was excreted in the milk of lactating rats. Because many drugs are excreted
in human milk and because of the potential for adverse reactions in a breastfed child from POMALYST, advise
women not to breastfeed during treatment with POMALYST.
- Pediatric Use: Safety and effectiveness have not
been established in pediatric patients.
- Geriatric Use: No dosage adjustment is required
for POMALYST based on age. Patients >65 years of age were more likely than patients ≤65 years of age to experience
pneumonia.
- Renal Impairment: For patients with severe renal impairment requiring dialysis, reduce the recommended dosage to 3 mg orally daily.
Take dose of POMALYST following hemodialysis on hemodialysis days.
- Hepatic Impairment: In patients with mild to moderate hepatic impairment, reduce POMALYST dosage to 3 mg orally daily and to 2 mg orally daily in patients with severe hepatic impairment.
- Smoking Tobacco: Advise patients that smoking
may reduce the efficacy of POMALYST. Cigarette smoking reduces pomalidomide AUC due to CYP1A2 induction.
Please see full Prescribing Information, including Boxed WARNINGS.
Indication
POMALYST® (pomalidomide) is a thalidomide analogue indicated, in combination with dexamethasone, for
adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome
inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy.
dex, dexamethasone; PI, proteasome inhibitor; RRMM, relapsed/refractory multiple myeloma.
Reference: 1. POMALYST [package insert]. Summit, NJ: Celgene Corp.