Dosing and uses of Pomalyst (pomalidomide)
Adult dosage forms and strengths
capsule
- 1mg
- 2mg
- 3mg
- 4mg
Multiple Myeloma
Thalidomide analogue, in combination with dexamethasone, is indicated for multiple myeloma in patients who have received at least 2 prior therapies (including lenalidomide and a proteasome inhibitor) and have disease progression on or within 60 days of completion of the last therapy
4 mg PO qDay on days 1-21 of repeated 28-day cycles until disease progression; give in combination with low-dose dexamethasone
Low-dose dexamethasone
- Give PO only on Days 1, 8, 15, and 22 of each 28-day cycle
- ≤75 years: 40 mg/day
- >75 years: 20 mg/day
Dosage modifications
Discontinue treatment if toxicities continue to occur after dose reductions to 1 mg
Neutropenia
- ANC <500/mcL or febrile neutropenia (ie, fever ≤38.5°C and ANC <1,000/mcL): Interrupt treatment and follow CBC weekly, may resume at 3 mg/day if ANC returns to ≥500/mcL
- For each subsequent drop <500/mcL: Interrupt treatment, may resume at 1 mg less than previous dose if ANC returns to ≥500/mcL
Thrombocytopenia
- Platelets <25,000/mcL: Interrupt treatment and follow CBC weekly, may resume at 3 mg/day if platelets returns to ≥50,000/mcL
- For each subsequent drop <25,000/mcL: Interrupt treatment, may resume at 1 mg less than previous dose if platelets returns to ≥50,000/mcL
Other
- Permanently discontinue for angioedema, skin exfoliation, bullae, or any other severe dermatologic reaction
- For other grade 3 or 4 toxicities, hold treatment and restart treatment at 1 mg less than the previous dose when toxicity has resolved to less than or equal to Grade 2 at the physician’s discretion
Renal & hepatic impairment
- Avoid use if serum creatinine >3 mg/dL
- Avoid use if serum bilirubin >2 mg/dL and AST/ALT >3x ULN
Dosing Considerations
Females of reproductive potential must have negative pregnancy testing and use contraception methods before initiating
To initiate a new cycle, the neutrophil count must be ≥500/mcL and the platelet count must be ≥50,000/mcL
Systemic Sclerosis (Orphan)
Orphan designation for treatment of systemic sclerosis
Orphan sponsor
- Celgene Corporation; 86 Morris Avenue; Summit, NJ 07901
Pediatric dosage forms and strengths
<18 years: Safety and efficacy not established
Pomalyst (pomalidomide) adverse (side) effects
>10%
Fatigue and asthenia (55-63%)
Neutropenia (47-52%)
Dyspnea (34-45%)
Anemia (38-39%)
Constipation (35-36%)
Nausea (22-36%)
Diarrhea (33-34%)
Back pain (30-32%)
Upper respiratory tract infection (25-32%)
Pyrexia (19-30%)
Pneumonia (23-29%)
Thrombocytopenia (23-25%)
Peripheral edema (16-23%)
Musculoskeletal chest pain (20-22%)
Decreased appetite (18-22%)
Rash (16-22%)
Cough (14-21%)
Hypercalcemia (12-21%)
Dizziness (17-20%)
Muscle spasms (19%)
Leukopenia (11-18%)
Arthralgia (15-16%)
Urinary tract infection (8-16%)
Hyperhidrosis (6-16%)
Hyperglycemia (12-15%)
Musculoskeletal pain (11-15%)
Epistaxis (11-15%)
Pruritus (11-15%)
Increased blood creatinine (11-15%)
Renal failure (10-15%)
Lymphopenia (4-15%)
Vomiting (13-14%)
Decreased weight (8-14%)
Insomnia (7-14%)
Pain in extremity (5-14%)
Hyponatremia (10-13%)
Confusional state (10-13%)
Tremor (9-13%)
Headache (8-13%)
Night sweats (5-13%)
Muscular weakness (12%)
Hypocalcemia (6-12%)
Bone pain (5-12%)
Hypokalemia (11%)
Dry skin (9-11%)
Chills (9-11%)
Anxiety (7-11%)
Increased weight (1-11%)
1-10%
Neuropathy, peripheral (7-10%)
Pain (5-6%)
Thromboembolism (3%)
Febrile neutropenia (3%)
Postmarketing reports
Tumor lysis syndrome
Hepatitis B virus reactivation
Herpes zoster
Gastrointestinal hemorrhage
Basal cell carcinoma
Squamous cell carcinoma of the skin
Warnings
Black box warnings
Only available from a restricted distribution program; 1-888-423-5436
Embryo-fetal toxicity
- Contraindicated in pregnancy
- Pomalidomide is a thalidomide analog and 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 initiating treatment
- Women of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after stopping pomalidomide
- Present in semen; males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking pomalidomide and for 4 weeks after stopping treatment
- Male patients must not donate sperm during and for 4 weeks after stopping drug
- Male and female patients must not donate blood during treatment and for 4 weeks after stopping drug
Venous and thromboembolism
- Deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke occur in patients with multiple myeloma treated with pomalidomide; antithrombotic prophylaxis recommended
- Prophylactic antithrombotic measures were employed in the clinical trials; thromboprophylaxis recommended, and the choice of regiment should be based on assessment of the individual patient’s underlying risk factors
Contraindications
Pregnancy
Cautions
Analog of known human teratogen, thalidomide, and is contraindicated during pregnancy in women, and during treatment and for 4 weeks after stopping therapy in both men and women (see Black box warnings and Contraindications)
Venous and arterial thromboembolic events reported as serious adverse reactions; patients with known risk factors, including prior thrombosis, may be at greater risk, and actions should be taken to minimize all modifiable factors (e.g., hyperlipidemia, hypertension, smoking); in the trial, all patients were required to receive prophylaxis or antithrombotic treatment (eg, aspirin, warfarin, heparin, clopidogrel) (see Black box warnings)
Hematologic toxicity reported, including neutropenia, anemia, and thrombocytopenia; monitor complete blood counts weekly for the first 8 weeks and monthly thereafter
Hepatic failure, including fatalities, have occurred; monitor LFTs monthly and discontinue drug if increased LFTs occur; after LFTs return to baseline values, treatment at a lower dose may be considered
Hypersensitivity and severe dermatologic reactions reported; discontinue for angioedema, skin exfoliation, bullae, or any other severe dermatologic reactions, and do not resume therapy
Dizziness or confusional state reported
Neuropathy reported
Tumor lysis syndrome may occur; risk is increased in patients with high tumor burden prior to treatment
Strong CYP1A2, CYP3A4, or P-gp inhibitors may increase pomalidomide exposure
Cigarette smoking and strong inducers of CYP1A2, CYP3A4, and P-gp may decrease pomalidomide exposure
Risk of second primary malignancies (ie, acute myelogenous leukemia) reported
Pregnancy and lactation
Pregnancy category: X
Lactation: Unknown whether distributed in human breast milk; a decision should be made whether to discontinue nursing or discontinue the drug
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Pomalyst (pomalidomide)
Mechanism of action
Thalidomide analog that elicits immunomodulatory and antineoplastic activity; it inhibits proliferation and induced apoptosis of hematopoietic tumor cells
Additionally, it enhances T-cell and natural killer cell-mediated immunity and suppresses production of TNF-alpha and interleukin-6; down-modulates cell surface adhesion molecules involved in leukocyte migration
Anticancer activity may be due to inhibition of angiogenesis
Absorption
Peak plasma time: 2-3 hr
Peak plasma concentration: 75 ng/mL
AUC: 400 ng•hr/mL
Distribution
Protein bound: 12-44%
Vd: 62-138 L
Semen concentration: 67% of plasma level at 4 hr post-dose
Metabolism
Metabolized in liver by CYP1A2 and CYP3A4 (primary enzymes involved the hydroxylation); minor contribution by CYP2C19 and CYP2D6
Elimination
Half-life: 7.5 hr
Total body clearance: 7-10 L/hr
Excretion: 73% urine (2% unchanged); 15% feces (8% unchanged)
Administration
Instructions
Swallow capsule whole with water; do not break, chew, or open the capsules
Take without food, at least 2 hr before or 2 hr after a meaL
Use procedures for proper handling and disposal according to anticancer drug guidelines
