PROMACTA- eltrombopag olamine tablet, film coated PROMACTA- eltrombopag olamine powder, for suspension

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

ELTROMBOPAG OLAMINE (UNII: 4U07F515LG) (ELTROMBOPAG - UNII:S56D65XJ9G)

Available from:

Novartis Pharmaceuticals Corporation

INN (International Name):

ELTROMBOPAG OLAMINE

Composition:

ELTROMBOPAG 12.5 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

PROMACTA is indicated for the treatment of thrombocytopenia in adult and pediatric patients 1 year and older with persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. PROMACTA should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding. PROMACTA is indicated for the treatment of thrombocytopenia in patients with chronic hepatitis C to allow the initiation and maintenance of interferon-based therapy. PROMACTA should be used only in patients with chronic hepatitis C whose degree of thrombocytopenia prevents the initiation of interferon-based therapy or limits the ability to maintain interferon-based therapy. - PROMACTA is indicated in combination with standard immunosuppressive therapy (IST) for the first-line treatment of adult and pediatric patients 2 years and older with severe aplastic anemia. - PROMACTA is indicated for the treatment of patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy. - PROMACTA is not indicated for the treatment of patients with myelodysplastic syndromes (MDS) [see Warnings and Precautions (5.3)] . - Safety and efficacy have not been established in combination with direct-acting antiviral agents used without interferon for treatment of chronic hepatitis C infection. None. Risk Summary Available data from a small number of published case reports and postmarketing experience with PROMACTA use in pregnant women are insufficient to assess any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction and developmental toxicity studies, oral administration of eltrombopag to pregnant rats during organogenesis resulted in embryolethality and reduced fetal weights at maternally toxic doses. These effects were observed at doses resulting in exposures that were six times the human clinical exposure based on area under the curve (AUC) in patients with persistent or chronic ITP at 75 mg/day, and three times the AUC in patients with chronic hepatitis C at 100 mg/day (see Data). The estimated 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 U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an early embryonic development study, female rats received oral eltrombopag at doses of 10, 20, or 60 mg/kg/day (0.8, 2, and 6 times, respectively, the human clinical exposure based on AUC in patients with ITP at 75 mg/day and 0.3, 1, and 3 times, respectively, the human clinical exposure based on AUC in patients with chronic hepatitis C at 100 mg/day). Increased pre- and post-implantation loss and reduced fetal weight were observed at the highest dose which also caused maternal toxicity. In an embryo-fetal development study eltrombopag was administered orally to pregnant rats during the period of organogenesis at doses of 10, 20, or 60 mg/kg/day (0.8, 2, and 6 times, respectively, the human clinical exposure based on AUC in patients with ITP at 75 mg/day and 0.3, 1, and 3 times, respectively, the human clinical exposure based on AUC in patients with chronic hepatitis C at 100 mg/day). Decreased fetal weights (6% to 7%) and a slight increase in the presence of cervical ribs were observed at the highest dose which also caused maternal toxicity. However, no evidence of major structural malformations was observed. In an embryo-fetal development study eltrombopag was administered orally to pregnant rabbits during the period of organogenesis at doses of 30, 80, or 150 mg/kg/day (0.04, 0.3, and 0.5 times, respectively, the human clinical exposure based on AUC in patients with ITP at 75 mg/day and 0.02, 0.1, and 0.3 times, respectively, the human clinical exposure based on AUC in patients with chronic hepatitis C at 100 mg/day). No evidence of fetotoxicity, embryolethality, or teratogenicity was observed. In a pre- and post-natal developmental toxicity study in pregnant rats (F0), oral eltrombopag was administered from gestation Day 6 through lactation Day 20. No adverse effects on maternal reproductive function or on the development of the offspring (F1) were observed at doses up to 20 mg/kg/day (2 times the human clinical exposure based on AUC in patients with ITP at 75 mg/day and similar to the human clinical exposure based on AUC in patients with chronic hepatitis C at 100 mg/day). Eltrombopag was detected in the plasma of offspring (F1). The plasma concentrations in pups increased with dose following administration of drug to the F0 dams. Risk Summary There are no data regarding the presence of eltrombopag or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. However, eltrombopag was detected in the pups of lactating rats 10 days postpartum suggesting the potential for transfer during lactation. Due to the potential for serious adverse reactions in a breastfed child from PROMACTA, breastfeeding is not recommended during treatment. Contraception Based on animal reproduction studies, PROMACTA can cause fetal harm when administered to a pregnant woman. Sexually-active females of reproductive potential should use effective contraception (methods that result in less than 1% pregnancy rates) when using PROMACTA during treatment and for at least 7 days after stopping treatment with PROMACTA. The safety and efficacy of PROMACTA have been established in pediatric patients 1 year and older with persistent or chronic ITP and in pediatric patients 2 years and older with IST-naïve severe aplastic anemia (in combination with h-ATG and cyclosporine). Safety and efficacy in pediatric patients below the age of 1 year with ITP have not been established. Safety and efficacy in pediatric patients with thrombocytopenia associated with chronic hepatitis C and refractory severe aplastic anemia have not been established. The safety and efficacy of PROMACTA in pediatric patients 1 year and older with persistent or chronic ITP were evaluated in two double-blind, placebo-controlled trials [see Adverse Reactions (6.1), Clinical Studies (14.1)] . The pharmacokinetics of eltrombopag have been evaluated in 168 pediatric patients 1 year and older with ITP dosed once daily [see Clinical Pharmacology (12.3)] . See Dosage and Administration (2.1) for dosing recommendations for pediatric patients 1 year and older. The safety and efficacy of PROMACTA in combination with h-ATG and cyclosporine for the first-line treatment of severe aplastic anemia in pediatric patients 2 years and older were evaluated in a single-arm, open-label trial [see Adverse Reactions (6.1), Clinical Studies (14.3)] . A total of 26 pediatric patients (ages 2 to < 17 years) were evaluated; 12 children (aged 2 to < 12 years) and 14 adolescents (aged 12 to < 17). See Dosage and Administration (2.3) for dosing recommendations for pediatric patients 2 years and older. The safety and efficacy of PROMACTA in combination with h-ATG and cyclosporine in pediatric patients younger than 2 years for the first-line treatment of severe aplastic anemia have not yet been established. In patients 2 to 16 years of age, 69% of patients experienced serious adverse events compared to 42% in patients 17 years and older. Among the 12 patients who were 2 to 11 years of age in the PROMACTA D1-M6 cohort and reached the 6-month assessment or withdrew earlier, the complete response rate at Month 6 was 8% versus 46% in patients age 12 to 16 years and 50% in patients 17 years of age and older. Of the 106 patients in two randomized clinical trials of PROMACTA 50 mg in persistent or chronic ITP, 22% were 65 years of age and over, while 9% were 75 years of age and over. Of the 1439 patients in two randomized clinical trials of PROMACTA in patients with chronic hepatitis C and thrombocytopenia, 7% were 65 years of age and over, while < 1% were 75 years of age and over. Of the 196 patients who received PROMACTA for the treatment of severe aplastic anemia, 18% were 65 years of age and over, while 3% were 75 years of age and over. No overall differences in safety or effectiveness were observed between these patients and younger patients. Patients With Persistent or Chronic ITP and Severe Aplastic Anemia Reduce the initial dose of PROMACTA in patients with persistent or chronic ITP (adult and pediatric patients 6 years and older only) or refractory severe aplastic anemia who also have hepatic impairment (Child-Pugh class A, B, C) [see Dosage and Administration (2.1, 2.3), Warnings and Precautions (5.2), Clinical Pharmacology (12.3)] . In a clinical trial in patients with severe aplastic anemia who had not received prior definitive immunosuppressive therapy, patients with baseline ALT or AST > 5 x ULN were ineligible to participate. If a patient with hepatic impairment (Child-Pugh class A, B, C) initiates therapy with PROMACTA for the first-line treatment of severe aplastic anemia, reduce the initial dose [see Dosage and Administration (2.3), Warnings and Precautions (5.2), Clinical Pharmacology (12.3)] . Patients With Chronic Hepatitis C No dosage adjustment is recommended in patients with chronic hepatitis C and hepatic impairment [see Clinical Pharmacology (12.3)] . Reduce the initial dose of PROMACTA for patients of East-/Southeast-Asian ancestry with ITP (adult and pediatric patients 6 years and older only) or severe aplastic anemia [see Dosage and Administration (2.1, 2.3), Clinical Pharmacology (12.3)] . No reduction in the initial dose of PROMACTA is recommended in patients of East-/Southeast-Asian ancestry with chronic hepatitis C [see Clinical Pharmacology (12.3)] .

Product summary:

Store at room temperature between 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Dispense in original bottle. Each kit (NDC 0078-0972-61) contains 30 packets: NDC 0078-0972-19 Each kit (NDC 0078-0697-61) contains 30 packets: NDC 0078-0697-19 Store at room temperature between 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Following reconstitution, the product should be administered immediately but may be stored for a maximum period of 30 minutes between 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Throw away (discard) the mixture if not used within 30 minutes.

Authorization status:

New Drug Application

Patient Information leaflet

PROMACTA- ELTROMBOPAG OLAMINE POWDER, FOR SUSPENSION
Novartis Pharmaceuticals Corporation
----------
This Medication Guide has been approved by the
U.S. Food and Drug Administration
Revised: March 2023
MEDICATION GUIDE
PROMACTA® (pro-MAC-ta)
(eltrombopag)
tablets
PROMACTA® (pro-MAC-ta)
(eltrombopag)
for oral suspension
What is the most important information I should know about PROMACTA?
PROMACTA can cause serious side effects, including:
Liver problems:
•
If you have chronic hepatitis C virus and take PROMACTA with
interferon and ribavirin
treatment, PROMACTA may increase your risk of liver problems. If your
healthcare provider
tells you to stop your treatment with interferon and ribavirin, you
will also need to stop taking
PROMACTA.
•
PROMACTA may increase your risk of liver problems that may be severe
and possibly life
threatening. Your healthcare provider will do blood tests to check
your liver function before you
start taking PROMACTA and during your treatment. Your healthcare
provider may stop your
treatment with PROMACTA if you have changes in your liver function
blood tests.
Tell your healthcare provider right away if you have any of these
signs and symptoms of liver problems:
•
yellowing of the skin or the whites of the
eyes (jaundice)
•
unusual darkening of the urine
•
unusual tiredness
•
right upper stomach area (abdomen) pain
•
confusion
•
swelling of the stomach area (abdomen)
See “What are the possible side effects of PROMACTA?” for other
side effects of PROMACTA.
What is PROMACTA?
PROMACTA is a prescription medicine used to treat adults and children
1 year of age and older with
low blood platelet counts due to persistent or chronic immune
thrombocytopenia (ITP), when other
medicines to treat ITP or surgery to remove the spleen have not worked
well enough.
PROMACTA is also used to treat people with:
•
low blood platelet counts due to chronic hepatitis C virus (HCV)
infection before and during
treatment with interferon.
•
severe aplastic anemia (SAA) in combination with other

Summary of Product characteristics

PROMACTA- ELTROMBOPAG OLAMINE TABLET, FILM COATED
PROMACTA- ELTROMBOPAG OLAMINE POWDER, FOR SUSPENSION
NOVARTIS PHARMACEUTICALS CORPORATION
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
PROMACTA SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR PROMACTA.
PROMACTA (ELTROMBOPAG) TABLETS, FOR ORAL USE
PROMACTA (ELTROMBOPAG) FOR ORAL SUSPENSION
INITIAL U.S. APPROVAL: 2008
WARNING: RISK FOR HEPATIC DECOMPENSATION IN PATIENTS WITH CHRONIC
HEPATITIS C AND RISK OF HEPATOTOXICITY
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
IN PATIENTS WITH CHRONIC HEPATITIS C, PROMACTA IN COMBINATION WITH
INTERFERON AND
RIBAVIRIN MAY INCREASE THE RISK OF HEPATIC DECOMPENSATION. (5.1)
PROMACTA MAY INCREASE THE RISK OF SEVERE AND POTENTIALLY
LIFE-THREATENING
HEPATOTOXICITY. MONITOR HEPATIC FUNCTION AND DISCONTINUE DOSING AS
RECOMMENDED.
(5.2)
INDICATIONS AND USAGE
PROMACTA is a thrombopoietin receptor agonist indicated:
for the treatment of thrombocytopenia in adult and pediatric patients
1 year and older with persistent
or chronic immune thrombocytopenia (ITP) who have had an insufficient
response to corticosteroids,
immunoglobulins, or splenectomy. PROMACTA should be used only in
patients with ITP whose degree of
thrombocytopenia and clinical condition increase the risk for
bleeding. (1.1)
for the treatment of thrombocytopenia in patients with chronic
hepatitis C to allow the initiation and
maintenance of interferon-based therapy. PROMACTA should be used only
in patients with chronic
hepatitis C whose degree of thrombocytopenia prevents the initiation
of interferon-based therapy or
limits the ability to maintain interferon-based therapy. (1.2)
in combination with standard immunosuppressive therapy for the
first-line treatment of adult and
pediatric patients 2 years and older with severe aplastic anemia.
(1.3)
for the treatment of patients with severe aplastic anemia who have had
an insufficient response to
immunosuppressive therapy. (1.3)
Li