Mulpleta Drug Information
Generic name: LUSUTROMBOPAG
Uses of Mulpleta
is indicated for the treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure. MULPLETA is a thrombopoietin receptor agonist indicated for the treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure.
Dosage & Administration of Mulpleta
Recommended Dosage Begin
MULPLETA dosing 8-14 days prior to a scheduled procedure. Patients should undergo their procedure 2-8 days after the last dose. The recommended dosage of MULPLETA is 3 mg taken orally once daily with or without food for 7 days.
In the case of a missed dose of MULPLETA, patients should take the missed dose as soon as possible on the same day and return to the normal schedule the following day. MULPLETA has been investigated only as a single 7-day once daily dosing regimen in clinical trials in patients with chronic liver disease . MULPLETA should not be administered to patients with chronic liver disease in an attempt to normalize platelet counts.
Monitoring Obtain a platelet count prior to initiation of
MULPLETA therapy and not more than 2 days before the procedure.
Side Effects of Mulpleta
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of MULPLETA was evaluated in 3 randomized, double-blind, placebo-controlled trials, L-PLUS 1, L-PLUS 2, and M0626, in which patients with chronic liver disease and thrombocytopenia were treated with MULPLETA (N=171) or placebo (N=170) at a dose of 3 mg daily for up to 7 days prior to a scheduled procedure. The majority of patients were males (59%), and median age was 61 years (range 19-88). The racial and ethnic distribution was White (50%), Asian (47%), Black (<1%), and Other (3%). The most common adverse reactions (those occurring in at least 3%) in the MULPLETA-treated group across the pooled data from the three trials are summarized in table 1. Table 1. Adverse Reactions with a Frequency ≥3% in Patients Treated with MULPLETA (Pooled Data (L-PLUS 1, L-PLUS 2, and M0626)) Adverse Reaction Includes treatment-emergent adverse reactions occurring at a rate higher than placebo.
MULPLETA 3 mg (N=171) % Placebo (N=170) % Headache 5 4 The incidence of serious adverse events was 5% (9 of 171 patients) in the MULPLETA group and 7% (12 of 170 patients) in the placebo group. The most common serious adverse reaction reported with MULPLETA was portal vein thrombosis . No adverse reactions resulted in discontinuation of MULPLETA.
Warnings & Cautions for Mulpleta
Thrombotic/Thromboembolic Complications
MULPLETA is a thrombopoietin (TPO) receptor agonist, and TPO receptor agonists have been associated with thrombotic and thromboembolic complications in patients with chronic liver disease. Portal vein thrombosis has been reported in patients with chronic liver disease treated with TPO receptor agonists. Portal vein thrombosis was reported in 1% (2 of 171) of MULPLETA-treated patients and 1% (2 of 170) of placebo-treated patients in 3 randomized, double-blind trials and was identified post-procedure in protocol-specified imaging.
The thromboses were not associated with a marked increase in platelet count. Consider the potential increased thrombotic risk when administering MULPLETA to patients with known risk factors for thromboembolism, including genetic pro-thrombotic conditions (Factor V Leiden, Prothrombin 20210A, Antithrombin deficiency, or Protein C or S deficiency). In patients with ongoing or prior thrombosis or absence of hepatopetal blood flow, MULPLETA should only be used if the potential benefit to the patient justifies the potential risk. MULPLETA should not be administered to patients with chronic liver disease in an attempt to normalize platelet counts.
Pregnancy Safety for Mulpleta
Pregnancy Risk Summary There are no available data on MULPLETA in pregnant women to inform the drug-associated risk. In animal reproduction studies, oral administration of lusutrombopag to pregnant rats during organogenesis and the lactation period resulted in adverse developmental outcomes. These findings were observed at exposures based on AUC that were substantially higher than the AUC observed in patients (approximately 89 times) at the recommended clinical dose of 3 mg once daily.
Advise pregnant women of the potential risk to a fetus (see Data ). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the general population in the United States, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data Animal Data In an embryo-fetal development study in rats, lusutrombopag was orally administered during organogenesis at doses of 4, 12.5, 40, and 80 mg/kg/day. Low body weight and a decrease in the number of ossified sternebrae were noted in fetuses at 80 mg/kg/day (approximately 251 times the AUC observed in patients at the recommended clinical dose of 3 mg once daily). Minor skeletal variations (supernumerary ribs) were observed at doses of 4 mg/kg/day (approximately 23 times the AUC observed in patients at the recommended clinical dose of 3 mg once daily). In an embryo-fetal development study in rabbits following oral administration of lusutrombopag at doses up to 1000 mg/kg/day, no effect of lusutrombopag was observed on any parameter of embryo-fetal development. In a pre- and postnatal development study in rats at oral doses of 1, 4, 12.5, and 40 mg/kg/day, there were adverse effects of lusutrombopag on postnatal development at 40 mg/kg/day (approximately 230 times the AUC observed in patients at the recommended clinical dose of 3 mg once daily). The effects included prolongation of the gestation period in dams, low viability before weaning, delayed postnatal growth (delayed negative geotaxis, delayed eyelid opening, or low pup body weight), abnormal clinical signs (prominent annular rings on the tail after weaning), low fertility index, a low number of corpora lutea or implantations, and increased pre-implantation loss.
The incidence of short thoracolumbar supernumerary ribs on postnatal Day 4 of F1 pups was high at doses of 12.5 mg/kg/day or more (approximately 89 times the AUC observed in patients at the recommended clinical dose of 3 mg once daily).
Pediatric Use of Mulpleta
Pediatric Use Safety and effectiveness in pediatric patients have not been established.
Overdosage Information for Mulpleta
No antidote for MULPLETA overdose is known. In the event of overdose, platelet count may increase excessively and result in thrombotic or thromboembolic complications. Closely monitor the patient and platelet count.
Treat thrombotic complications in accordance with standard of care. Hemodialysis is not expected to enhance the elimination of MULPLETA because lusutrombopag is highly bound to protein in plasma .
Clinical Studies of Mulpleta
The efficacy of MULPLETA for the treatment of thrombocytopenia in patients with chronic liver disease who are scheduled to undergo a procedure was evaluated in 2 randomized, double-blind, placebo-controlled trials (L-PLUS 1 (N=97) and L-PLUS 2 (N=215; NCT02389621)). Patients with chronic liver disease who were undergoing an invasive procedure and had a platelet count less than 50 × 10 9 /L were eligible to participate. Patients undergoing laparotomy, thoracotomy, open-heart surgery, craniotomy, or organ resection were excluded. Patients with a history of splenectomy, partial splenic embolization, or thrombosis and those with Child-Pugh class C liver disease, absence of hepatopetal blood flow, or a prothrombotic condition other than chronic liver disease were not allowed to participate.
The patient populations were similar between the MULPLETA and placebo arms and consisted of 60% male and 40% female; median age was 60 years (range 19-88). The racial and ethnic distribution was White (55%), Asian (41%), and Other (4%). Patients were randomized 1:1 to receive 3 mg of MULPLETA or placebo once daily for up to 7 days. Randomization was stratified by liver ablation/coagulation or other procedures and the platelet count at screening/baseline. In L-PLUS 1, 57% of patients underwent procedures other than liver ablation/coagulation and 43% underwent liver ablation/coagulation (RFA/MCT). In L-PLUS 2, 98% of patients underwent procedures other than liver ablation/coagulation and 2% underwent liver ablation/coagulation (RFA/MCT). Procedures other than liver ablation/coagulation (RFA/MCT) included liver-related procedures (transcatheter arterial chemoembolization, liver biopsy, and others), upper and lower gastrointestinal endoscopy-related procedures (endoscopic variceal ligation, endoscopic injection sclerotherapy, polypectomy, and biopsy), and other procedures (dental extraction, diagnostic paracentesis or laparocentesis, septoplasty, embolization of splenic artery aneurysm, bone marrow biopsy, removal of cervical polyp, and inguinal hernia repair (non-laparotomy based)). In L-PLUS 1, the major efficacy outcome was the proportion of patients who require no platelet transfusion prior to the primary invasive procedure.
In L-PLUS 2, the major efficacy outcome was the proportion of patients who require no platelet transfusion prior to the primary invasive procedure and no rescue therapy for bleeding (i.e., platelet preparations, other blood preparations, including red blood cells and plasma, volume expanders) from randomization through 7 days after the primary invasive procedure. In both trials, additional efficacy outcomes included the proportion of patients who require no platelet transfusion during the study, proportion of responders, duration of the increase in platelet count defined as the number of days during which the platelet count was maintained as ≥50 × 10 9 /L, and the time course of platelet counts. In both the L-PLUS 1 and L-PLUS 2 trials, responders were defined as patients who had a platelet count of ≥50 × 10 9 /L with an increase of ≥20 × 10 9 /L from baseline.
Table 2. L-PLUS 1 Trial: Proportion of Patients Not Requiring Platelet Transfusion Prior to Invasive Procedure and Proportion of Responders Endpoint Proportion (n/N) Exact 95% Confidence Interval Treatment Difference (95% Confidence Interval) p value MULPLETA (N=49) Placebo (N=48) Not requiring platelet transfusion prior to invasive procedure A platelet transfusion was required if the platelet count was less than 50 × 10 9/L. 78% (38/49) 13% (6/48) 64 <0.0001 Cochran-Mantel-Haenszel test with baseline platelet count as stratum; p value and confidence interval calculated using Wald method. Responder Platelet count reached at least 50 × 10 9/L and increased at least 20 × 10 9/L from baseline. during study 76% (37/49) 6% (3/48) 68 <0.0001 Table 3. L-PLUS 2 Trial: Proportion of Patients Not Requiring Platelet Transfusion Prior to Invasive Procedure or Rescue Therapy for Bleeding Through 7 Days After Invasive Procedure and Proportion of Responders Endpoint Proportion (n/N) Exact 95% Confidence Interval Treatment Difference (95% Confidence Interval) p value MULPLETA (N=108) Placebo (N=107) Not requiring platelet transfusion prior to invasive procedure A platelet transfusion was required if the platelet count was less than 50 × 10 9/L. or rescue therapy for bleeding from randomization through 7 days after invasive procedure 65% (70/108) 29% (31/107) 37 <0.0001 Cochran-Mantel-Haenszel test with baseline platelet count as stratum; p value and confidence interval calculated using Wald method. Responder Platelet count reached at least 50 × 10 9/L and increased at least 20 × 10 9/L from baseline. during study 65% (70/108) 13% (14/107) 52 <0.0001 The median (Q1, Q3) duration of platelet count increase to at least 50 × 10 9 /L was 22 days in MULPLETA-treated patients without platelet transfusion and 1.8 days in placebo-treated patients with platelet transfusion in L-PLUS 1 and 19 days in MULPLETA-treated patients without platelet transfusion and 0.0 days in placebo-treated patients with platelet transfusion in L-PLUS 2.
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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