REZUROCK- belumosudil tablet

Land: USA

Sprog: engelsk

Kilde: NLM (National Library of Medicine)

Aktiv bestanddel:

BELUMOSUDIL (UNII: 834YJF89WO) (BELUMOSUDIL - UNII:834YJF89WO)

Tilgængelig fra:

Kadmon Pharmaceuticals, LLC

Indgivelsesvej:

ORAL

Recept type:

PRESCRIPTION DRUG

Terapeutiske indikationer:

REZUROCK is indicated for the treatment of adult and pediatric patients 12 years and older with chronic graft-versus-host disease (chronic GVHD) after failure of at least two prior lines of systemic therapy. None. Risk Summary Based on findings from animal studies and the mechanism of action [see Clinical Pharmacology (12.1)] , REZUROCK can cause fetal harm when administered to pregnant women. There are no available human data on REZUROCK use in pregnant women to evaluate for a drug-associated risk. In animal reproduction studies, administration of belumosudil to pregnant rats and rabbits during the period of organogenesis resulted in adverse developmental outcomes, including alterations to growth, embryo-fetal mortality, and embryo-fetal malformations at maternal exposures (AUC) approximately ≥3- (rat) and ≥0.07 (rabbit) times the human exposure (AUC) at the recommended dose (see Data) . Advise pregnant women and females of reproductive potential of the potential risk to the fetus. In the U.S. general population, 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 Embryo-fetal development studies were conducted in rats with administration of belumosudil to pregnant animals during the period of organogenesis at oral doses of 25, 50, 150, and 300 mg/kg/day in a pilot study and doses of 15, 50, and 150 mg/kg/day in a pivotal study. In the pilot study, maternal toxicity and embryo-fetal developmental effects were observed. Maternal toxicity (reduced body weight gain) occurred at 150 and 300 mg/kg/day doses. Increased post-implantation loss occurred at 50 and 300 mg/kg/day. Fetal-malformations were observed at ≥50 mg/kg/day and included absence of anus and tail, omphalocele, and dome shaped head. The exposure (AUC) at 50 mg/kg/day in rats is approximately 3 times the human exposure at the recommended dose of 200 mg. In an embryo-fetal developmental study in rabbits, pregnant animals administered oral doses of belumosudil at 50, 125, and 225 mg/kg/day during the period of organogenesis resulted in maternal toxicity and embryo-fetal developmental effects. Maternal toxicity (body weight loss and mortality) was observed at doses ≥125 mg/kg/day. Embryo-fetal effects were observed at doses ≥50 mg/kg/day and included spontaneous abortion, increased post-implantation loss, decreased percentage of live fetuses, malformations, and decreased fetal body weight. Malformations included those in the tail (short), ribs (branched, fused or deformed), sternebrae (fused), and neural arches (fused, misaligned, and deformed). The exposure (AUC) at 50 mg/kg/day in rabbits is approximately 0.07 times the human exposure at the recommended dose of 200 mg. Risk Summary There are no data available on the presence of belumosudil or its metabolites in human milk or the effects on the breastfed child, or milk production. Because of the potential for serious adverse reactions from belumosudil in the breastfed child, advise lactating women not to breastfeed during treatment with REZUROCK and for one week after the last dose. REZUROCK can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)] . Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to initiating treatment with REZUROCK. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with REZUROCK and for one week after the last dose of REZUROCK. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be informed of the potential hazard to a fetus. Males Advise males with female partners of reproductive potential to use effective contraception during treatment with REZUROCK and for one week after the last dose of REZUROCK. Infertility Females Based on findings from rats, REZUROCK may impair female fertility. The effect on fertility is reversible [see Nonclinical Toxicology (13.1)]. Males Based on findings from rats and dogs, REZUROCK may impair male fertility. The effects on fertility are reversible [see Nonclinical Toxicology (13.1)] . The safety and effectiveness of REZUROCK have been established in pediatric patients 12 years and older. Use of REZUROCK in this age group is supported by evidence from adequate and well-controlled studies of REZUROCK in adults with additional population pharmacokinetic data demonstrating that age and body weight had no clinically meaningful effect on the pharmacokinetics of drug substance, that the exposure of drug substance is expected to be similar between adults and pediatric patients age 12 years and older, and that the course of disease is sufficiently similar in adult and pediatric patients to allow extrapolation of data in adults to pediatric patients. The safety and effectiveness of REZUROCK in pediatric patients less than 12 years old have not been established. Of the 186 patients with chronic GVHD in clinical studies of REZUROCK, 26% were 65 years and older. No clinically meaningful differences in safety or effectiveness of REZUROCK were observed in comparison to younger patients. Treatment with REZUROCK has not been studied in patients with pre-existing severe renal impairment. For patients with pre-existing severe renal impairment, consider the risks and potential benefits before initiating treatment with REZUROCK [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3)] . Avoid use in patients with moderate hepatic impairment (Child-Pugh B) or severe hepatic impairment (Child-Pugh C) without liver GVHD [see Dosage and Administration (2.4), Clinical Pharmacology (12.3)] . No dosage adjustment is recommended for patients with mild hepatic impairment (Child-Pugh A) [see Dosage and Administration (2.4), Clinical Pharmacology (12.3)] .

Produkt oversigt:

REZUROCK 200 mg tablets are supplied as pale yellow film-coated oblong tablets containing 200 mg of belumosudil (equivalent to 242.5 mg belumosudil mesylate). Each tablet is debossed with "KDM" on one side and "200" on the other side and is packaged as follows: Store at room temperature, 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Dispense to patient in original container only. Store in original container to protect from moisture. Replace cap securely each time after opening. Do not discard desiccant.

Autorisation status:

New Drug Application

Produktets egenskaber

REZUROCK- BELUMOSUDIL TABLET
KADMON PHARMACEUTICALS, LLC
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
REZUROCK SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR REZUROCK.
REZUROCK (BELUMOSUDIL) TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2021
RECENT MAJOR CHANGES
Dosage and Administration (2.1, 2.4)
11/2023
INDICATIONS AND USAGE
REZUROCK is a kinase inhibitor indicated for the treatment of adult
and pediatric patients 12 years and
older with chronic graft-versus-host disease (chronic GVHD) after
failure of at least two prior lines of
systemic therapy. (1)
DOSAGE AND ADMINISTRATION
Recommended Dosage: 200 mg taken orally once daily with food. (2.1)
DOSAGE FORMS AND STRENGTHS
Tablet: 200 mg. (3)
CONTRAINDICATIONS
None. (4)
WARNINGS AND PRECAUTIONS
Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of
reproductive potential of the potential risk
to a fetus and to use effective contraception. (5.1, 8.1, 8.3)
ADVERSE REACTIONS
The most common (≥20%) adverse reactions, including laboratory
abnormalities, are infections, asthenia,
nausea, diarrhea, dyspnea, cough, edema, hemorrhage, abdominal pain,
musculoskeletal pain, headache,
phosphate decreased, gamma glutamyl transferase increased, lymphocytes
decreased, and
hypertension. (6.1)
TO REPORT SUSPECTED ADVERSE REACTIONS, CONTACT KADMON PHARMACEUTICALS,
LLC AT 1-
800-633-1610 OR FDA AT 1-800-FDA-1088 OR WWW.FDA.GOV/MEDWATCH.
DRUG INTERACTIONS
Strong CYP3A Inducers: Increase REZUROCK dosage to 200 mg twice daily.
(7.1, 2.3)
Proton Pump Inhibitors: Increase REZUROCK dosage to 200 mg twice
daily. (7.1, 2.3)
Certain P-gp, OATP1B1, BCRP, and UGT1A1 substrates: Avoid concomitant
use with these substrates
for which minimal concentration changes may lead to serious
toxicities. If coadministration cannot be
avoided, decrease the substrates dosage(s) in accordance with the
respective Prescribing Information.
(7.2)
USE IN SPECIFIC POPULATIONS
Lactation: Advise not to breastfeed. (8.2)
Mode