LYNKUET

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE LYNKUET is indicated for the treatment of moderate to severe vasomotor symptoms (VMS) due to menopause. LYNKUET is a neurokinin 1 (NK1) and neurokinin 3 (NK3) receptor antagonist indicated for the treatment of moderate to severe vasomotor symptoms due to menopause. ( 1 ) Dosage and administration 2 DOSAGE AND ADMINISTRATION The recommended dosage is 120 mg (two 60 mg capsules) orally once daily at bedtime with or without food. ( 2.2 ) Swallow capsules whole. Do not cut, crush, or chew capsules. ( 2.2 ) See full prescribing information for LYNKUET dosage modification due to drug interactions. ( 2.3 ) 2.1 Recommended Evaluation and Testing Before Initiation of LYNKUET Exclude pregnancy in females of reproductive potential [see Contraindications (4) ], Warnings and Precautions (5.3) , and Use in Specific Populations (8.3) ]. Perform baseline hepatic laboratory tests to evaluate for hepatic function and injury [including serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), serum alkaline phosphatase (ALP), and serum bilirubin (total and direct)] before initiating treatment with LYNKUET. Do not start LYNKUET if ALT or AST is ≥ 2 times upper limit of normal (ULN) or if the total bilirubin is ≥ 2 times ULN [ see Warnings and Precautions (5.2) and Use in Specific Populations (8.7) ]. 2.2 Recommended Dosage The recommended dosage of LYNKUET is 120 mg (two 60 mg capsules) orally once daily at bedtime at about the same time each day. If a dose is missed at bedtime, take the next dose as scheduled on the following day. Do not take two doses on the same day to make up for a missed dose. Take LYNKUET with or without food. Take LYNKUET with water and swallow capsules whole. Do not cut, crush or chew capsules. 2.3 Dosage Modifications for Drug Interactions Dosage modifications for concomitant use with specific drugs are provided in Table 1 [see Drug Interactions (7.1) ]. Table 1. Dosage Modifications for Drug Interactions Concomitant Drug LYNKUET Dosage Strong CYP3A4 inhibitors and grapefruit (juice) Avoid concomitant use Moderate CYP3A4 inhibitors 60 mg (one capsule) orally once daily at bedtime [see Storage and Handling (16.2) ]. After discontinuation of the moderate CYP3A4 inhibitor (after 3 to 5 half-lives of the inhibitor), LYNKUET should be used at the usual dosage of 120 mg once daily. Strong and Moderate CYP3A4 inducers Avoid concomitant use Warnings and cautions 5 WARNINGS AND PRECAUTIONS CNS Depressant Effect and Daytime Impairment: Advise patients about the potential for somnolence and other nervous system effects. Advise patients who experience these effects to refrain from driving or engaging in hazardous occupations or activities until the effects have resolved ( 5.1 ) Hepatic Transaminase Elevations: Perform bloodwork prior to initiation of LYNKUET to evaluate for hepatic function and injury. Do not start therapy if serum transaminase concentration is equal to or exceeds two times the upper limit of normal (ULN). Perform follow-up evaluations of hepatic transaminase concentration 3 months after initiation. Do not start therapy if serum transaminase concentration is equal to or exceeds two times the ULN or if the total bilirubin is equal to or exceeds two times the ULN. Advise patients to discontinue LYNKUET immediately in case of signs or symptoms suggesting liver injury. ( 5.2 ) Risk of pregnancy loss: May cause pregnancy loss or stillbirth when administered during pregnancy. Exclude pregnancy in females of reproductive potential prior to initiating LYNKUET. Discontinue if pregnancy is confirmed ( 5.3 ) Risk of seizures in patients with a history of seizures ( 5.4 ) 5.1 Central Nervous System (CNS) Depressant Effect and Daytime Impairment In the three OASIS trials, nervous system effects (including somnolence, fatigue, vertigo, dizziness and presyncope) occurred in 11.9% of patients on LYNKUET compared to 3.5% on placebo. [see also Adverse Reactions (6.1) ]. Advise patients about the potential for somnolence and other nervous system effects. Advise patients who experience these effects to refrain from driving or engaging in hazardous occupations or activities until the effects have resolved [see Clinical Studies (14.3) ]. 5.2 Hepatic Transaminase Elevations Elevations in serum transaminase (ALT and/or AST) concentrations equal to or greater than three times the ULN occurred in 0.6% of patients receiving LYNKUET and 0.4% of patients receiving placebo up to 12 weeks in three clinical trials. Perform baseline bloodwork (including ALT, AST, alkaline phosphatase, and total and direct bilirubin) prior to initiation of LYNKUET to evaluate for hepatic function and injury. Do not start therapy if serum transaminase concentration is equal to or exceeds two times the ULN or if the total bilirubin is equal to or exceeds two times the ULN. Perform follow-up evaluations of hepatic transaminase concentration 3 months after initiation of therapy. Advi