complex, and is administered orally or by intravenous infusion.PREVYMIS is available as 240 mg and 480 mg tablets. PREVYMIS tablets contain either 240 mg or 480 mg of letermovir and the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, povidone 25, and film-coated with a coating material containing the following inactive ingredients: hypromellose 2910, iron oxide red (only for 480 mg tablets), iron oxide yellow, lactose monohydrate, titanium dioxide, and triacetin, Carnauba wax is added as a polishing agent.PREVYMIS is also available as 240 mg and 480 mg injection for intravenous infusion. PREVYMIS injection is a clear, preservative-free sterile solution in single-dose vials of either 240 mg or 480 mg per vial. Each 1 mL of solution contains 20 mg letermovir, hydroxypropyl betadex (150 mg), sodium chloride (3.1 mg), sodium hydroxide (1.2 mg), and Water for Injection, USP. The amount of sodium hydroxide may be adjusted to achieve a pH of approximately 7.5.Letermovir has a molecular formula of C29H28F4N4O4 and a molecular weight of 572.55. The chemical name for letermovir is (4S)-2-{8-Fluoro-2-[4-(3- methoxyphenyl)piperazin-1-yl]-3-[2-methoxy-5- (trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl}acetic acid. Letermovir is very slightly soluble in water.The chemical structure of letermovir is:
12.1 Mechanism Of Action
PREVYMIS is an antiviral drug against CMV [see Microbiology (12.4)].
12.3 Pharmacokinetics
The pharmacokinetic properties of letermovir are displayed in Table 4.Table 4: Absorption, Distribution, Metabolism, Elimination (ADME), and Pharmacokinetic Properties of PREVYMISValues were obtained in studies of healthy subjects unless otherwise indicated.Pharmacokinetics in HSCT RecipientsTreatment RegimenSteady-state median (90% prediction interval) AUC (ng∙hr/mL) of PREVYMIS 480 mg oral once daily, no cyclosporine34,400 (16,900, 73,700) 480 mg IV once daily, no cyclosporine100,000 (65,300, 148,000) 240 mg oral once daily, with cyclosporine60,800 (28,700, 122,000) 240 mg IV once daily, with cyclosporine70,300 (46,200, 106,000)Pharmacokinetics in Healthy SubjectsTreatment RegimenSteady-state geometric mean AUC and Cmax of PREVYMIS 480 mg oral once dailyCmax: 13,000 ng/mLAUC: 71,500 ng∙hr/mLDose proportionalityGreater than proportional following single and multiple oral or IV doses of PREVYMIS 240 mg and 480 mgAccumulation ratioBased on geometric mean data.Cmax: 1.03AUC: 1.22Time to steady-state 9-10 daysAbsorptionBioavailabilityHealthy subjects administered PREVYMIS without cyclosporine: 94% at an oral dose range of 240 mg to 480 mgHSCT recipients administered PREVYMIS without cyclosporine: 35% with 480 mg oral once dailyHSCT recipients administered PREVYMIS with cyclosporine: 85% with 240 mg oral once dailyMedian Tmax (hr)45 min to 2.25 hrEffect of food (relative to fasting) Values refer to geometric mean ratio [fed/fasted] percentage and 90% confidence interval back transformed from linear mixed-effects model performed on natural log-transformed values. The meal administered was a standard high fat and high calorie meal (33 grams protein, 65 grams carbohydrates, 58 grams fat; 920 total calories).AUC: 99.63% [84.27% - 117.80%]Cmax: 129.82% [104.35% -161.50%]DistributionMean steady-state volume of distribution45.5 L following IV administration in HSCT recip |
