letermovir: clinical use

Prescribing considerations

• Confirm transplant type, donor and recipient CMV serostatus, patient weight and formulation-specific licensed eligibility.
• Review CYP, UGT, P-gp, BCRP and OATP-mediated interactions, including when changing administration route.
• Letermovir is licensed for prophylaxis, not treatment of established CMV disease.
• Intravenous hydroxypropylbetadex may accumulate in renal impairment and young children.

Contraindications and cautions

• Hypersensitivity to letermovir or formulation excipients.
• Concomitant pimozide, ergot alkaloids or St John’s wort.
• With ciclosporin: dabigatran, atorvastatin, simvastatin, rosuvastatin and pitavastatin.
• Not recommended in severe hepatic impairment or combined moderate hepatic impairment with moderate or severe renal impairment; evidence is insufficient in end-stage renal disease.

Monitoring

• CMV DNA according to transplant protocol, with prompt assessment of breakthrough DNAemia or disease.
• Ciclosporin, tacrolimus and sirolimus concentrations when starting or stopping letermovir or changing route.
• INR for warfarin and therapeutic drug monitoring for voriconazole.
• Serum creatinine during intravenous use in moderate or severe renal impairment or very young children.
• Report suspected adverse reactions through the MHRA Yellow Card Scheme.

Clinical pharmacology

Letermovir inhibits the CMV terminase complex encoded by UL51, UL56 and UL89. Exposure is more than dose-proportional and is influenced by hepatic uptake transporters, glucuronidation, administration route and ciclosporin; elimination is predominantly biliary.

Formulation and product differences

• Film-coated tablets are swallowed whole and may be taken with or without food.
• The intravenous concentrate requires dilution, a specified polyethersulfone filter and compatible bags and tubing.
• The infusion contains sodium and hydroxypropylbetadex; renal accumulation of the latter requires consideration.
• Several medicines and administration materials are physically incompatible with the infusion and must not be mixed with it.

Solution for infusion

Route: Intravenous

Strengths: 240 mg

Tablet

Route: Oral

Strengths: 240 mg