Introduction

Leniolisib phosphate is a kinase inhibitor.

Uses for Leniolisib

Leniolisib phosphate has the following uses:

Leniolisib phosphate is indicated for the treatment of activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) in adult and pediatric patients 12 years of age and older.

Leniolisib Dosage and Administration

General

Leniolisib phosphate is available in the following dosage form(s) and strength(s):

Tablets: 70 mg (of leniolisib)

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Verify pregnancy status in females of reproductive potential prior to initiating treatment.

Pediatric Patients

Dosage and Administration

• Recommended dosage in pediatric patients 12 years of age and older and weighing ≥45 kg: 70 mg administered orally twice daily approximately 12 hours apart, with or without food. There is no recommended dosage for patients weighing less than 45 kg.

Adults

Dosage and Administration

• Recommended dosage in adults weighing ≥45 kg: 70 mg administered orally twice daily approximately 12 hours apart, with or without food. There is no recommended dosage for patients weighing less than 45 kg.

Contraindications

• None.

Warnings/Precautions

Embryo-fetal Toxicity

Based on findings in animals, leniolisib may cause fetal harm when administered to a pregnant woman. Administration of leniolisib to rats and rabbits during the period of organogenesis caused embryo-fetal toxicity including malformations at exposures that were 2-6 times higher than the maximum recommended human dose (MRHD) in patients with phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) based on AUC comparisons.

Verify the pregnancy status of patients of reproductive potential prior to starting treatment. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use highly effective methods of contraception during treatment and for 1 week after the last dose.

Vaccinations

Live, attenuated vaccinations may be less effective if administered during leniolisib treatment.

Specific Populations

Pregnancy

Leniolisib can cause fetal harm based on findings from animal studies. There are no available data on leniolisib use in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.

In animal reproduction studies, oral administration of leniolisib to pregnant rats and rabbits during the period of organogenesis at exposures approximately 2-6 times the MRHD on an AUC basis, produced embryofetal toxicity including malformations. Advise pregnant women of the potential risk to a fetus.

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 miscarriage of clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Lactation

There are no data on the presence of leniolisib or its metabolites in human milk or the effects on the breastfed infant or milk production. Because of the potential for serious adverse reactions from leniolisib in the breastfed child, advise women not to breastfeed during treatment with the drug and for 1 week after the last dose.

Females and Males of Reproductive Potential

Based on findings from animal studies, leniolisib may cause fetal harm when administered to a pregnant woman.

Verify the pregnancy status in females of reproductive potential prior to initiating leniolisib phosphate.

Advise female patients of reproductive potential to use highly effective contraception during treatment with leniolisib and to continue contraception for 1 week after the last dose.

Pediatric Use

The safety and effectiveness of leniolisib for the treatment of activated phosphoinositide 3-kinase delta syndrome have been established in pediatric patients 12 years of age and older. Use of leniolisib for this indication is supported by evidence from an adequate and well-controlled study in adult and pediatric patients 12 years of age and older. There is no recommended dosage for pediatric patients 12 years of age and older who weigh less than 45 kg.

The safety and effectiveness of leniolisib phosphate have not been established in pediatric patients below the age of 12 years.

Geriatric Use

Because clinical studies of leniolisib did not include any patients 65 years of age and older, it cannot be determined whether they respond differently from younger adult patients.

Hepatic Impairment

Leniolisib is extensively (60%) metabolized by the liver. The effect of hepatic impairment on the pharmacokinetics of leniolisib has not been studied. The use of leniolisib in patients with moderate to severe hepatic impairment is not recommended.

Common Adverse Effects

Most common adverse reactions (incidence >10%) were headache, sinusitis, and atopic dermatitis.

General

Leniolisib phosphate is available in the following dosage form(s) and strength(s):

Tablets: 70 mg (of leniolisib)

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Verify pregnancy status in females of reproductive potential prior to initiating treatment.

Pediatric Patients

Dosage and Administration

• Recommended dosage in pediatric patients 12 years of age and older and weighing ≥45 kg: 70 mg administered orally twice daily approximately 12 hours apart, with or without food. There is no recommended dosage for patients weighing less than 45 kg.

Adults

Dosage and Administration

• Recommended dosage in adults weighing ≥45 kg: 70 mg administered orally twice daily approximately 12 hours apart, with or without food. There is no recommended dosage for patients weighing less than 45 kg.

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

• Strong CYP3A4 Inhibitors: Avoid concomitant use.

• Strong and Moderate CYP3A4 Inducers: Avoid concomitant use.

• CYP1A2 Metabolized Drugs with a Narrow Therapeutic Index (NTIs): Avoid concomitant use.

• BCRP, OATP1B1, and OATP1B3 Substrates: Avoid concomitant use.