Letermovir

Letermovir is a prescription medication used for the prevention of cytomegalovirus infection.

• Letermovir is available under the following different brand names: Prevymis

Common side effects of Letermovir include:

• nausea,
• diarrhea,
• vomiting,
• swelling of the ankles or feet,
• cough, and
• headache

Serious side effects of Letermovir include:

• hives,
• difficulty breathing,
• swelling of the face, lips, tongue, or throat,
• fast or irregular heartbeat,
• rash,
• itching, and
• severe dizziness

Rare side effects of Letermovir include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 240 mg
• 480 mg

Solution for injection

• 20 mg/mL (vials contain 240 mg/12 mL or 480 mg/24 mL)
• Further dilution required

Cytomegalovirus Infection Prophylaxis

Adult dosage

• 480 mg PO/IV every day; initiate between Day 0 and Day 28 posttransplantation (before or after engraftment) and continue through Day 100

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Letermovir has severe interactions with the following drugs:
  • dihydroergotamine
  • dihydroergotamine inhaled
  • dihydroergotamine intranasal
  • ergotamine
  • lonafarnib
  • pimozide
  • pitavastatin
  • simvastatin
• Letermovir has serious interactions with at least 33 other drugs.
• Letermovir has moderate interactions with at least 206 other drugs.
• Letermovir has minor interactions with the following drugs:
  • entecavir
  • voclosporin

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Pimozide, ergot alkaloids (see Cautions)
• Pitavastatin or simvastatin when coadministered with cyclosporine (see Cautions)

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Letermovir?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Letermovir?”

Cautions

• Coadministration of letermovir with certain drugs may result in potentially significant drug interactions, some of which may lead to adverse reactions or reduced therapeutic effect of either drug (see Contraindications)
• Drug interaction overview
• Cyclosporine and letermovir may increase plasma concentrations of each other (see Dosage Modifications)
• Contraindicated drug interactions
  • Pimozide: Coadministration with pimozide may result in increased concentrations of pimozide, owing to an inhibition of CYP3A4 by letermovir, which may lead to QT prolongation and torsades de pointes
  • Ergot alkaloids: Coadministration with ergot alkaloids may result in increased concentrations of ergot alkaloids (ergotamine and dihydroergotamine), owing to an inhibition of CYP3A by letermovir, which may lead to ergotism
  • Pitavastatin or simvastatin when coadministered with cyclosporine: Coadministration of letermovir in combination with cyclosporine may result in significantly increased pitavastatin or simvastatin concentrations, which may lead to myopathy or rhabdomyolysis
• Potential for other drugs to affect letermovir
  • Letermovir is a substrate of CYP3A (minor), CYP2D6 (minor), UGT1A1, and UGT1A3, and transporters OATP1B1/3 and P-gp; oxidative metabolism is considered to be a minor elimination pathway based on in vivo human data
  • Coadministration of letermovir with inducers of P-gp and/or UGT 1A1/3 is not recommended owing to the potential for decreased letermovir plasma concentrations
  • Inhibitors of OATP1B1/3 may result in increases in letermovir plasma concentrations
  • Changes in letermovir plasma concentrations due to inhibition of P-gp or UGTs are not anticipated to be clinically relevant
  • Potential for letermovir to affect other drugs
  • Letermovir is a time-dependent inhibitor and inducer of CYP3A in vitro; drug interaction studies showed a net effect of letermovir on CYP3A is moderate inhibition
  • Letermovir is a reversible inhibitor of CYP2C8 in vitro; if coadministered, plasma concentrations of CYP2C8 substrates are predicted to increase
  • Letermovir induces CYP2C9 and CYP2C19; if coadministered, plasma concentrations of CYP2C9 and CYP2C19 substrates may decrease
  • Letermovir induces CYP2B6 in vitro; clinical relevance is unknown
  • Letermovir inhibits efflux transporters P-gp, breast cancer resistance protein (BCRP), bile salt export pump (BSEP), multidrug resistance-associated protein 2 (MRP2), OAT3, and hepatic uptake transporter OATP1B1/3 in vitro; coadministration with substrates of OATP1B1/3 transporters (eg, atorvastatin, a known substrate of CYP3A, OATP1B1/3, and potentially BCRP) may result in a clinically relevant increase in plasma concentrations of OATP1B1/3 substrates
  • Note: There were no clinically relevant changes in plasma concentrations of digoxin, a P-gp substrate, or acyclovir, an OAT3 substrate

Pregnancy and Lactation

• No data are available regarding use in pregnant women
• In animal reproduction studies, embryo-fetal developmental toxicity (including fetal malformations) was observed in rats during the period of organogenesis at letermovir exposures (AUC) 11 times higher than human exposure at the recommended human dose (RHD); in rabbits, no embryo-fetal developmental toxicity was noted at exposures that were not maternally toxic (up to letermovir exposures 2 times higher than human exposure at the RHD)
• Infertility: No data are available on the effect of letermovir on human fertility; decreased fertility due to testicular toxicity was observed in male rats
• Lactation
  • Unknown if present in human breast milk affects human milk production, or has effects on the breastfed child
  • When administered to lactating rats, letermovir was present in the milk of lactating rats as well as the blood of nursing pups
  • The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed child or from the underlying maternal condition