Pomide 4 mg

INDICATIONS

Multiple Myeloma: Pomalidomide, in combination with dexamethasone, is indicated for adult patients with multiple myeloma (MM) 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 ... Read moreMultiple Myeloma: Pomalidomide, in combination with dexamethasone, is indicated for adult patients with multiple myeloma (MM) 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. Kaposi Sarcoma: Pomalidomide is indicated for the treatment of:

Adult patients with AIDS-related Kaposi sarcoma (KS) after failure of highly active antiretroviral therapy (HAART)
Kaposi sarcoma (KS) in adult patients who are HIV-negative

PHARMACOLOGY

Pomalidomide is an analogue of thalidomide with immunomodulatory, antiangiogenic, and antineoplastic properties. Cellular activities of pomalidomide are mediated through its target cereblon, a component of a cullin ring E3 ubiquitin ligase enzyme complex. In vitro, in the presence of drug, substrate proteins (including Aiolos and Ikaros) are targeted for ubiquitination and subsequent degradation leading to direct cytotoxic and immunomodulatory effects. In in vitro cellular assays, pomalidomide inhibited proliferation and induced apoptosis of hematopoietic tumor cells. Additionally, pomalidomide inhibited the proliferation of lenalidomideresistant multiple myeloma (MM) cell lines and synergized with dexamethasone in both lenalidomide-sensitive and lenalidomide-resistant cell lines to induce tumor cell apoptosis. Pomalidomide enhanced T cell- and natural killer (NK) cell-mediated immunity and inhibited production of pro-inflammatory cytokines (e.g., TNF-α and IL-6) by monocytes. Pomalidomide demonstrated anti-angiogenic activity in a mouse tumor model and in the in vitro umbilical cord model.Pharmacodynamics: Pomalidomide exposure-response analyses showed that there was no relationship between systemic Pomalidomide exposure level and efficacy or safety following Pomalidomide dose of 4 mg.Pharmacokinetics: In patients with MM who received Pomalidomide 4 mg daily alone or in combination with dexamethasone, Pomalidomide steady-state drug exposure was characterized by AUC (CV%) of 860 (37%) ng-h/mL and Cmax (CV%) of 75 (32%) ng/mL. In patients with Kaposi sarcoma (KS) who received Pomalidomide 5 mg daily, Pomalidomide steady-state drug exposure was characterized by AUC of 462.3 ng-h/mL (82%) and Cmax of 53.1 ng/mL (50%).Absorption: Following administration of single oral doses of Pomalidomide, the maximum plasma concentration (Cmax) for Pomalidomide occurs at 2 to 3 hours postdose in patients with MM or KS.Distribution: Pomalidomide has a mean apparent volume of distribution (Vd/F) between 62 and 138 L at steady state in patients with MM or KS. Pomalidomide is distributed in semen of healthy subjects at a concentration of approximately 67% of plasma level at 4 hours postdose (~Tmax) after 4 days of 2 mg once-daily dosing. Fluman plasma protein binding of Pomalidomide ranges from12% to 44% and is not concentration dependent. Pomalidomide is a substrate for P-gp.Metabolism: Pomalidomide is primarily metabolized in the liver by CYP1A2 and CYP3A4. Minor contributions from CYP2C19 and CYP2D6 were also observed in vitro.Elimination: Pomalidomide has a mean total body clearance (CL/F) of 7-10 L/h in patients with MM or KS. Pomalidomide is eliminated with a median plasma half-life of 9.5 hours in healthy subjects and 7.5 hours in patients with MM or KS. Excretion: Following a single oral administration of 14C-Pomalidomide to healthy subjects, approximately 73% and 15% of the  radioactive dose was eliminated in urine and feces, respectively, with approximately 2% and 8% of the radiolabeled dose eliminated unchanged as Pomalidomide in urine and feces.

DOSAGE & ADMINISTRATION

Pregnancy Testing Prior to Administration: Females of reproductive potential must have negative pregnancy testing and use contraception methods before initiating Pomalidomide.Recommended Dosage for Multiple Myeloma: The recommended dosage of Pomalidomide is 4 mg once daily orally with or without food on Days 1 through 21 of each 28-day cycle until disease progression. Give Pomalidomide in combination with dexamethasone.Recommended Dosage for Kaposi Sarcoma: The recommended dosage of Pomalidomide is 5 mg once daily taken orally with or without food on Days 1 through 21 of each 28-day cycle until disease progression or unacceptable toxicity. Continue HAART as HIV treatment in patients with AIDS-related Kaposi sarcoma (KS).Dosage Modifications for Hematologic Adverse Reactions-Multiple Myeloma: Dosage Modifications for Hematologic Adverse Reactions: Initiate a new cycle of Pomalidomide in patients with multiple myeloma (MM) when the neutrophil count is at least 500 per mcL and the platelet count is at least 50,000 per mcL.Kaposi Sarcoma: Dosage Modifications for Hematologic Adverse Reactions Initiate a new cycle of Pomalidomide in patients with KS when the neutrophil count is at least 1000 per mcL and the platelet count is at least 75,000 per mcL.Dosage Modifications for Non-Hematologic Adverse Reactions: Permanently discontinue Pomalidomide for angioedema, anaphylaxis, Grade 4 rash, 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.Dosage Modifications for Strong CYP1A2 Inhibitors: Avoid concomitant use of Pomalidomide with strong CYP1A2 inhibitors. If concomitant use of a strong CYP1A2 inhibitor is unavoidable, reduce Pomalidomide dose to 2 mg.Pediatric Use: The safety and effectiveness of POMALYST have not been established in pediatric patients.

INTERACTION

Strong CYP1A2 Inhibitors: Avoid concomitant use of strong CYP1A2 inhibitors. If concomitant use of a strong CYP1A2 inhibitor is unavoidable, reduce Pomalidomide dose to 2 mg.

SIDE EFFECTS

Multiple Myeloma: Most common adverse reactions (>30%) included fatigue and asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper-respiratory tract infections, back pain, and pyrexia.Kaposi Sarcoma: Most common adverse reactions including laboratory abnormalities (>30%) are decreased absolute neutrophil count or white blood cells, elevated creatinine or glucose, rash, constipation, fatigue, decreased hemoglobin, platelets, phosphate, albumin, or calcium, increased ALT, nausea, and diarrhea.

PREGNANCY & LACTATION

Pregnancy: Pomalidomide is contraindicated in females who are pregnant. Pomalidomide can cause fetal harm when administered to a pregnant female. Pomalidomide is a thalidomide analogue and is teratogenic in both rats and rabbits when administered during the period of organogenesis. If the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to a fetus.Lactation: There is no information regarding the presence of pomalidomide in human milk, the effects of Pomalidomide on the breastfed child, or the effects of Pomalidomide on milk production. Pomalidomide was excreted in the milk of lactating rats (see Data). Because many drugs are excreted in human milk and because of the potential for adverse reactions in a breastfed child from Pomalidomide, advise women not to breastfeed during treatment with Pomalidomide.

PRECAUTIONS & WARNINGS

Increased Mortality: Observed in patients with MM when pembrolizumab was added to dexamethasone and a thalidomide analogue
Hematologic Toxicity: Neutropenia was the most frequently reported Grade 3/4 adverse event. Monitor patients for hematologic toxicities, especially neutropenia
Hepatotoxicity: Hepatic failure including fatalities; monitor liver function tests monthly
Severe Cutaneous Reactions: Discontinue Pomalidomide for severe reactions
Tumor Lysis Syndrome (TLS): Monitor patients at risk of TLS (i.e., those with high tumor burden) and take appropriate precautions
Hypersensitivity: Monitor patients for potential hypersensitivity. Discontinue Pomalidomide for angioedema and anaphylaxis.

STORAGE CONDITIONS

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.