TAVALISSE- fostamatinib tablet

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

FOSTAMATINIB (UNII: SQ8A3S5101) (FOSTAMATINIB - UNII:SQ8A3S5101)

Available from:

Rigel Pharmaceuticals, Inc.

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

TAVALISSE is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. None. Risk Summary Based on findings from animal studies and the mechanism of action, TAVALISSE can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)]. There are no available data in pregnant women to inform the drug-associated risk. In animal reproduction studies, administration of fostamatinib to pregnant rats and rabbits during organogenesis caused adverse developmental outcomes that were directly attributed to exposure in utero to the major fostamatinib metabolite (R406) at maternal exposures (AUC) as low as 0.3 and 10 times the exposure in patients at the maximum recommended human dose (MRHD), respectively (see Data). Advise pregnant women of the potential risk to a fetus. 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 miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. An estimated background risk of major birth defects and miscarriage for the chronic ITP population is 8% and 4-11%, respectively. Data Animal Data In a fertility and early embryonic development study in female rats, fostamatinib was administered orally for 15 days before mating to Day 7 of pregnancy, which caused a slight decrease in pregnancy rates and an increase in post-implantation loss were seen at maternal doses approximately 4.2 times the dose in patients at the MRHD. In embryo-fetal development studies, pregnant animals were orally administered fostamatinib during the period of organogenesis at doses up to 25 and 50 mg/kg/day in rats and rabbits, respectively. The adverse developmental outcomes included an increase in embryo-fetal mortality (post-implantation loss), alterations to growth (lower fetal weights), and structural abnormalities (variations and malformations). These effects occurred at maternal exposures (AUCs) of 3,763 ng.h/mL in rats and 111,105 ng.h/mL in rabbits that were approximately 0.3 and 10 times the human exposure at the MRHD in rats and rabbits, respectively. In a peri and postnatal development study in rats, fostamatinib was orally administered at doses of 2.5, 12.5, and 25 mg/kg/day from gestation day 7 until lactation day 20. The dose of 25 mg/kg/day was associated with maternal toxicity, including decreased body weights, body weight gains, and food consumption. At doses as low as 12.5 mg/kg/day fostamatinib caused increases in newborn mortality (neonatal mortality), alterations in growth and/or development (lower neonatal weights into post-weaning and structural abnormalities [malformations]). Functional impairment (delayed sexual maturation) was observed at 25 mg/kg/day. There was no evidence of neurobehavioral defects (maze learning and shuttle box avoidance) or immunological compromise (influenza host resistance challenge) in the F1 generation or latent untoward effects in the F2 generation. The maternal doses were approximately 2.1 and 4.2 times the MHRD in patients. Risk Summary There are no data on the presence of fostamatinib and/or its metabolites in human milk, the effects on the breastfed child, or on milk production. In rodents, R406 (the major active metabolite) was detected in maternal milk in concentrations 5- to 10-fold higher than in maternal plasma. Because of the potential for serious adverse reactions in a breastfed child from TAVALISSE, advise a lactating woman not to breastfeed during treatment with TAVALISSE and for at least 1 month after the last dose. Pregnancy Testing Based on animal studies, TAVALISSE can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)] . For females of reproductive potential, verify pregnancy status prior to initiating TAVALISSE. Contraception Females Based on animal studies, TAVALISSE can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)] . Advise females of reproductive potential to use effective contraception during treatment with TAVALISSE and for at least 1 month after the last dose. Infertility There are no data on the effect of TAVALISSE on human fertility. Based on the finding of reduced pregnancy rates in animal studies, TAVALISSE may affect female fertility [see Use in Specific Populations (8.1)] . Safety and effectiveness in pediatric patients have not been established. TAVALISSE is not recommended for use in patients less than 18 years of age because adverse effects on actively growing bones were observed in nonclinical studies. In subchronic, chronic, and carcinogenicity studies of TAVALISSE, chondrodystrophy of the femoral head was seen in rodents. In a study in juvenile rabbits, growth plate dysplasia was observed in the proximal femur and femoro-tibial joint, and bone marrow cellularity was reduced in the femur and sternum. Of the 102 patients with ITP who received TAVALISSE, 28 (27%) were 65 years of age and older, while 11 (11%) were 75 years of age and older. In patients 65 years of age and older, 6 (21%) patients experienced serious adverse events and 5 (18%) experienced adverse events leading to treatment withdrawal while in patients under 65 years of age, 7 (9%) and 5 (7%) experienced serious adverse events and adverse events leading to treatment withdrawal, respectively. In patients 65 years of age and older who received TAVALISSE, 11 (39%) patients experienced hypertension versus 2 (18%) placebo compared to 17 (23%) in patients under 65 of age versus 4 (11%) placebo. No overall differences in effectiveness were observed in these patients compared to younger patients.

Product summary:

TAVALISSE 100 mg tablets are round, biconvex, orange, film-coated tablets debossed with "100" on one side and "R" on the reverse side. TAVALISSE 150 mg tablets are oval, biconvex, orange, film-coated tablets debossed with "150" on one side and "R" on the reverse side. Store at room temperature, 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Do not remove desiccants.

Authorization status:

New Drug Application

Summary of Product characteristics

TAVALISSE- FOSTAMATINIB TABLET
RIGEL PHARMACEUTICALS, INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
TAVALISSE SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR TAVALISSE.
TAVALISSE (FOSTAMATINIB DISODIUM HEXAHYDRATE) TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2018
INDICATIONS AND USAGE
TAVALISSE is a kinase inhibitor indicated for the treatment of
thrombocytopenia in adult patients with
chronic immune thrombocytopenia (ITP) who have had an insufficient
response to a previous treatment.
(1)
DOSAGE AND ADMINISTRATION
Initiate TAVALISSE at 100 mg orally twice daily with or without food.
After 4 weeks, increase to 150 mg
twice daily, if needed, to achieve platelet counts of at least 50 ×
10 /L as necessary to reduce the risk
of bleeding. (2.1)
Manage adverse reactions using dose reduction, interruption of
treatment, or discontinuation. (2.3)
Discontinue TAVALISSE after 12 weeks of treatment if the platelet
count does not increase to a level
sufficient to avoid clinically important bleeding. (2.5)
DOSAGE FORMS AND STRENGTHS
Tablets: 100 mg, 150 mg (3)
CONTRAINDICATIONS
None. (4)
WARNINGS AND PRECAUTIONS
Hypertension: Monitor blood pressure every 2 weeks until stable, then
monthly. Manage hypertension
using standard antihypertensive treatment and, if needed, interrupt,
reduce or discontinue TAVALISSE.
(5.1)
Hepatotoxicity: Monitor LFTs monthly. If LFT levels are elevated,
interrupt, reduce or discontinue
TAVALISSE. (5.2)
Diarrhea: Manage diarrhea with supportive measures. If diarrhea
becomes severe, interrupt, reduce or
discontinue TAVALISSE. (5.3)
Neutropenia: Monitor ANC monthly, and for infection. If neutrophil
count decreases below 1.0 × 10 /L,
interrupt, reduce or discontinue TAVALISSE. (5.4)
Embryo-Fetal Toxicity: TAVALISSE can cause fetal harm. Advise patients
of potential risk to a fetus and
to use effective contraception. (5.5_)_
ADVERSE REACTIONS
The most common adverse reactions (≥5% and more than placebo) are
diarrhea