Adult: Prophylaxis of CMV reactivation and disease in CMV-seropositive recipients [R+] of allogeneic HSCT: 480 mg once daily via infusion over 1 hour, start within 28 days post-transplant continue until 100 days post-transplantation.
Oral Cytomegaloviral infections
Adult: Prophylaxis of CMV reactivation and disease in CMV-seropositive [R+] recipients of allogeneic haematopoietic stem cell transplant (HSCT): 480 mg once daily, start within 28 days post-transplant continue until 100 days post-transplantation.
Special Patient Group
Patient taking ciclosporin: 240 mg once daily, may increase to 480 mg once daily if ciclosporin is discontinued.
Hepatic Impairment
Severe (Child-Pugh Class C): Not recommended.
Administration
film-coated tab: May be taken with or without food.
Reconstitution
IV infusion: Add contents of a vial containing 20 mg/mL solution to 250 mL infusion bag or bottle containing 5% dextrose or 0.9% NaCl solution and mix bag gently. Do not shake.
Incompatibility
IV: Incompatible with amphotericin B (liposomal), amiodarone, aztreonam, cefepime, ciprofloxacin, ciclosporin, diltiazem, filgrastim, gentamicin, levofloxacin, linezolid, lorazepam, midazolam, mycophenolate mofetil, ondansetron, and palonosetron.
Contraindications
Hypersensitivity. Concomitant use with pimozide, ergot alkaloids, St. John’s wort, dabigatran; admin with simvastatin, rosuvastatin, pitavastatin when co-administered with ciclosporin.
Special Precautions
Pregnancy and lactation. Renal and severe hepatic impairment.
Adverse Reactions
Gastrointestinal disorders: Nausea, diarrhoea, vomiting, abdominal pain. General disorders and admin site conditions: Fatigue. Metabolism and nutrition disorders: Peripheral oedema. Nervous system disorders: Headache. Respiratory, thoracic and mediastinal disorders: Cough.
Patient Counseling Information
This drug may cause fatigue and vertigo, if affected do not drive or operate machinery.
Monitoring Parameters
Monitor CMV DNA weekly until week 14 post-transplant then every 2 weeks until week 24. Monitor for CMV reactivation.
Drug Interactions
May increase serum concentration of ciclosporin, sirolimus, tacrolimus, amiodarone, glyburide. May decrease serum concentration of warfarin, phenytoin, voriconazole, omeprazole, pantoprazole. Decreased concentration with nafcillin, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampicin, thioridazine, bosentan, efavirenz, etravirine. Potentially Fatal: May increase serum concentrations of pimozide and ergot alkaloids (e.g. ergotamine, dihydroergotamine) leading to increased risk of tachycardia (e.g. QT interval prolongation, torsade de pointes) and ergotism, respectively. May increase serum concentrations of HMG-CoA reductase inhibitors (e.g. atorvastatin, simvastatin, rosuvastatin, pitavastatin) which may lead to myopathy or rhabdomyolysis. May decrease plasma concentrations and efficacy of medicines transported hepatically by P-gp (e.g. dabigatran).
Food Interaction
Decreased serum concentration and efficacy with St. John’s wort.
Action
Description: Mechanism of Action: Letermovir inhibits cytomegalovirus (CMV) DNA terminase complex (pUL51, pUL56, pUL89), which is important for viral DNA cleavage and packaging. It also affects production of proper unit length genomes and interferes with virion maturation. Pharmacokinetics: Absorption: Rapidly absorbed. Bioavailability: Approx 35%. Time to peak plasma concentration: 1.5-3 hours. Distribution: Volume of distribution: 45.5 L (IV). Plasma protein binding: 99%. Metabolism: Metabolised in the liver by UGT1A1/1A3 (minor). Excretion: Via faeces (93%; 70% as unchanged drug); urine (<2%). Elimination half-life: 12 hours.
Chemical Structure
Letermovir Source: National Center for Biotechnology Information. PubChem Database. Letermovir, CID=45138674, https://pubchem.ncbi.nlm.nih.gov/compound/Letermovir (accessed on Jan. 22, 2020)
Storage
Tab: Store below 30°C. Solution for inj: Store below 30°C. Protect from light. Reconstituted soln: Store between 2-8°C for 48 hours or 24 hours at room temp.
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