LUPIN-LETERMOVIR

1 Dosing Considerations • Administer with or without food. • Swallow tablets whole. Do not divide, crush or chew. LUPIN-LETERMOVIR is only available as a tablet. The solution for injection of letermovir may be obtained from other authorized sources.

Letermovir tablets and injection may be used interchangeably at the discretion of the physician, and no dose adjustment is necessary. 2 Recommended Dose and Dosage Adjustment Adults: The recommended dosage of LUPIN-LETERMOVIR is 480 mg administered once daily.

If LUPIN-LETERMOVIR is co-administered with cyclosporine, the dosage of LUPIN-LETERMOVIR should be decreased to 240 mg once daily (see Dosage Adjustment in Adults section below). HSCT LUPIN-LETERMOVIR should be started after HSCT. LUPIN-LETERMOVIR may be started on the day of transplant and no later than 28 days post-HSCT.

LUPIN-LETERMOVIR may be started before or after engraftment. Continue LUPIN-LETERMOVIR through 100 days post-HSCT. Following completion of LUPIN-LETERMOVIR prophylaxis, monitoring for CMV reactivation in HSCT recipients is recommended.

Pediatrics (< 18 years of age):

Safety and efficacy of letermovir has not been established in pediatric patients less than 18 years of age. 3 Pharmacokinetics). 3 Pharmacokinetics). • If cyclosporine is initiated after starting LUPIN-LETERMOVIR, the next dose of LUPIN-LETERMOVIR should be decreased to 240 mg once daily.

• If cyclosporine is discontinued after starting LUPIN-LETERMOVIR, the next dose of LUPIN-LETERMOVIR should be increased to 480 mg once daily. • If cyclosporine dosing is temporarily interrupted due to high cyclosporine levels, no dose adjustment of LUPIN-LETERMOVIR is needed.

3 Pharmacokinetics). There are no data in patients with end-stage renal disease (CrCL less than 10 mL/min), including patients LUPIN-LETERMOVIR (letermovir tablets) Page 6 of 37 on dialysis. Hepatic Impairment No dose adjustment of LUPIN-LETERMOVIR is required based on mild (Child-Pugh Class A) to moderate (Child-Pugh Class B) hepatic impairment.

3 Pharmacokinetics). 3 Pharmacokinetics). 5 Missed Dose Instruct patients that if they miss a dose of LUPIN-LETERMOVIR, they should take it as soon as they remember. If they do not remember until it is time for the next dose, instruct them to skip the missed dose and go back to the regular schedule.

1 Adverse Reaction Overview The safety summary for letermovir in HSCT recipients was based on data from a randomized, placebo- controlled Phase 3 clinical trials (P001 and P040) in which CMV seropositive HSCT recipients received letermovir or placebo.

In P001, the most commonly reported adverse reactions in subjects treated with letermovir through Week 14 post-HSCT and followed for safety through Week 24 post-HSCT were nausea, diarrhea, and vomiting. In other clinical trial findings the following three adverse reactions have been reported: leukopenia, neutropenia, and white blood cell count decreased.

2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use. Adult CMV-seropositive Recipients [R+] of an Allogeneic HSCT Prophylaxis Through Week 14 (~100 days) Post-HSCT The safety of letermovir was evaluated in a Phase 3 randomized, double-blind, placebo-controlled trial (P001) through Week 14 post-HSCT and were followed for safety through Week 24 post-HSCT (see 14 CLINICAL TRIALS).

The most commonly reported adverse reactions occurring in at least 1% of subjects in the letermovir group through Week 24 post-HSCT and at a frequency greater than placebo were: nausea, diarrhea, and vomiting (see Table 2). 6%) in the placebo group.

The reported serious adverse reactions, which had a temporal association but no other plausible causal relationship to study treatment, were pancytopenia, thrombocytopenia, and delayed engraftment in the letermovir group and Bowen’s disease, mental status changes, and acute kidney injury in the placebo group.

2 Drug Interactions Overview). 2 Drug Interactions Overview). 2 Drug Interactions Overview). 2 Drug Interactions Overview). 1 Dosing Considerations • Administer with or without food. • Swallow tablets whole. Do not divide, crush or chew.

LUPIN-LETERMOVIR is only available as a tablet. The solution for injection of letermovir may be obtained from other authorized sources. Letermovir tablets and injection may be used interchangeably at the discretion of the physician, and no dose adjustment is necessary.

2 Recommended Dose and Dosage Adjustment Adults: The recommended dosage of LUPIN-LETERMOVIR is 480 mg administered once daily. If LUPIN-LETERMOVIR is co-administered with cyclosporine, the dosage of LUPIN-LETERMOVIR should be decreased to 240 mg once daily (see Dosage Adjustment in Adults section below).

HSCT LUPIN-LETERMOVIR should be started after HSCT. LUPIN-LETERMOVIR may be started on the day of transplant and no later than 28 days post-HSCT. LUPIN-LETERMOVIR may be started before or after engraftment. Continue LUPIN-LETERMOVIR through 100 days post-HSCT.

Following completion of LUPIN-LETERMOVIR prophylaxis, monitoring for CMV reactivation in HSCT recipients is recommended.

Pediatrics (< 18 years of age):

Safety and efficacy of letermovir has not been established in pediatric patients less than 18 years of age. 3 Pharmacokinetics). 3 Pharmacokinetics). • If cyclosporine is initiated after starting LUPIN-LETERMOVIR, the next dose of LUPIN-LETERMOVIR should be decreased to 240 mg once daily.

• If cyclosporine is discontinued after starting LUPIN-LETERMOVIR, the next dose of LUPIN-LETERMOVIR should be increased to 480 mg once daily. • If cyclosporine dosing is temporarily interrupted due to high cyclosporine levels, no dose adjustment of LUPIN-LETERMOVIR is needed.

LUPIN-LETERMOVIR is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.

2 Drug Interactions Overview). 2 Drug Interactions Overview). 2 Drug Interactions Overview). 2 Drug Interactions Overview).