letermovir

Action and Spectrum

Actions and Spectrum:   

letermovir is an antiviral medication used to prevent cytomegalovirus (CMV) infection in adult patients who have undergone hematopoietic stem cell transplantation. It works by inhibiting the DNA packaging process in the virus, which prevents the virus from replicating. 

The spectrum of letermovir is limited to preventing CMV infections in adult patients who have received stem cell transplants. It does not treat active CMV infections or other viral infections. 

The action of letermovir is to inhibit the DNA terminase complex of the cytomegalovirus, which is required to package viral DNA into the viral capsid. By inhibiting this process, letermovir prevents the formation of infectious virions and thus the spread of the virus. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Adults 

Peripheral edema (14%) 

Cough (14%) 

Headache (14%) 

Fatigue (13%) 

Abdominal pain (12%) 

Nausea (27%) 

Diarrhea (26%) 

Vomiting (19%) 

1-10% 

Atrial fibrillation (3%) 

Tachycardia (4%) 

Black Box Warning

Black Box Warning:  

The black box warning of letermovir is related to the risk of drug interactions with certain medications that are metabolized by the liver enzyme CYP3A4. Concomitant use of letermovir with certain medications that are CYP3A4 substrates may result in increased plasma concentrations of these drugs, which can increase the risk of adverse reactions, including QT interval prolongation, torsades de pointes, and potentially fatal cardiac arrhythmias. 

The black box warning advises healthcare providers to monitor patients for signs and symptoms of drug interactions and to adjust the dose of co-administered medications as necessary. Patients should also be advised to inform their healthcare provider of all medications they are taking, including prescription drugs, over-the-counter medications, and herbal supplements, before starting letermovir treatment. 

Contraindication / Caution

Contraindication/Caution:  

letermovir is contraindicated in patients with known hypersensitivity to letermovir or its components. It should not be used in patients who are allergic to the drug or have had an allergic reaction to it in the past. 

Additionally, letermovir is contraindicated in patients who are taking certain medications that are strong CYP3A4 inducers or inhibitors, as they may interact with letermovir and affect its effectiveness or increase the risk of adverse effects. Examples of strong CYP3A4 inducers include rifampin, carbamazepine, and phenytoin, while strong CYP3A4 inhibitors include ketoconazole, itraconazole, and clarithromycin. 

Patients with severe hepatic impairment should also avoid letermovir, as its safety and effectiveness have not been established in this population. letermovir is metabolized by the liver, and patients with impaired liver function may have difficulty processing the drug, leading to an increased risk of adverse effects. 

Finally, letermovir is not recommended for use during pregnancy or breastfeeding. Its safety in these populations has not been established, and it may harm the developing fetus or be excreted in breast milk. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excreted into human milk is unknown 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in the first or second trimester. 

Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.   

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.   

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology:

letermovir is an antiviral medication that belongs to a class of drugs known as viral DNA terminase complex inhibitors. It works by inhibiting the function of a protein called the viral terminase complex, which is essential for the replication of the cytomegalovirus (CMV) DNA. 

Pharmacodynamics: 

letermovir is an antiviral medication used to prevent cytomegalovirus (CMV) infection in certain patients who have received a stem cell transplant. Its pharmacodynamic mechanism involves targeting the viral terminase complex, which is essential for viral replication. 

MOA:  

letermovir is an antiviral medication that works by inhibiting the activity of the viral terminase complex, which is essential for the replication of cytomegalovirus (CMV). 

The terminase complex is responsible for cleaving and packaging viral DNA into virions during the late stage of viral replication. letermovir binds to the UL56 subunit of the terminase complex, which prevents the cleavage of viral DNA and the subsequent packaging of the DNA into virions.  

Pharmacokinetics: 

Absorption:  

letermovir is administered orally and has a bioavailability of approximately 37%. food does not significantly affect absorption, and it can be taken with or without food. 

Distribution: 

letermovir has a high protein binding capacity of approximately 99%. It has a large volume of distribution, suggesting that it distributes widely in the body. 

Metabolism:  

letermovir is mainly metabolized in the liver via the cytochrome P450 enzyme system. The primary metabolic pathway involves hydroxylation and oxidation, and the major metabolite is M8. 

Elimination and excretion: 

letermovir and its metabolites are primarily eliminated through feces, with approximately 74% of the dose excreted unchanged or as metabolites in the feces. A small amount of the drug and its metabolites (approximately 17%) is eliminated in the urine. The half-life of letermovir is approximately 12 hours. 

Adminstartion

Administration:  

letermovir is available as tablets and an injection for intravenous (IV) use. 

The recommended dose of letermovir is 480 mg once daily, taken orally or by IV infusion.  

letermovir tablets should be swallowed whole with water and can be taken with or without food.  

For patients who are unable to swallow tablets, letermovir injection may be given by a healthcare provider.  

letermovir should be started as soon as possible after HSCT and continued for as long as the patient is at risk of CMV infection, which is typically for up to 100 days post-transplant. 

letermovir should not be used in patients with severe liver impairment.  

letermovir may interact with certain medications, so it is important to inform the healthcare provider about all medications, supplements, and herbal products being taken.  

letermovir should be stored at room temperature, away from moisture and heat.  

In case of a missed dose, the patient should take the missed dose as soon as possible, but not double the next dose.  

It is important to follow the healthcare provider’s instructions and complete the full course of treatment with letermovir to achieve maximum benefit. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: letermovir 

Why do we use letermovir?  

letermovir is a medication that is used to prevent cytomegalovirus (CMV) infection and disease in certain patients. CMV is a virus that can cause serious infections in people with weakened immune systems, such as those who have had organ transplants or are undergoing chemotherapy. 

letermovir works by blocking a protein that is essential for the replication of the CMV virus. By inhibiting the replication of the virus, letermovir can help prevent CMV infection and disease in patients who are at risk. 

letermovir is typically used in combination with other medications to prevent CMV infection and disease.