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Amlodipine and Atorvastatin Tablets and Letermovir Injection

Determining the interaction of Amlodipine and Atorvastatin Tablets and Letermovir Injection and the possibility of their joint administration.

Check result:
Amlodipine and Atorvastatin Tablets <> Letermovir Injection
Relevance: 13.05.2023 Reviewer: Shkutko P.M., M.D., in

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Consumer:

Letermovir may significantly increase the blood levels of atorvastatin. This can increase the risk of side effects such as liver damage and a rare but serious condition called rhabdomyolysis that involves the breakdown of skeletal muscle tissue. In some cases, rhabdomyolysis can cause kidney damage and even death. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring to safely use both medications. Let your doctor know immediately if you have unexplained muscle pain, tenderness, or weakness during treatment with atorvastatin or similar medications, especially if these symptoms are accompanied by fever or dark colored urine. You should also seek immediate medical attention if you develop fever, chills, joint pain or swelling, unusual bleeding or bruising, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, dark colored urine, and/or yellowing of the skin or eyes, as these may be signs and symptoms of liver damage. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Professional:

ADJUST DOSE: Coadministration with letermovir may significantly increase the plasma concentrations of atorvastatin and its active metabolites. The proposed mechanism is letermovir inhibition of intestinal and hepatic CYP450 3A4, the isoenzyme responsible for the metabolic clearance of atorvastatin. In addition, atorvastatin and its metabolites are substrates of the hepatic uptake transporters, organic anion transporting polypeptide protein (OATP) 1B1 and 1B3, which are also inhibited by letermovir. According to the product labeling, atorvastatin peak plasma concentration (Cmax), systemic exposure (AUC) and concentration at 24 hours postdose (C24hr) increased by an average of 2.2-, 3.3- and 3.6-fold, respectively, when a single 20 mg dose of atorvastatin was coadministered with letermovir 480 mg orally once daily. Additional use of cyclosporine is likely to further increase the magnitude of interaction, since it is an inhibitor of CYP450 3A4 and a strong inhibitor of OATP 1B1 and 1B3. High levels of HMG-CoA reductase inhibitory activity in plasma is associated with an increased risk of musculoskeletal toxicity. Myopathy manifested as muscle pain and/or weakness associated with grossly elevated creatine kinase exceeding ten times the upper limit of normal has been reported occasionally. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death.

MANAGEMENT: The dosage of atorvastatin should not exceed 20 mg daily when used with letermovir. Concomitant use of atorvastatin is not recommended when letermovir is coadministered with cyclosporine. Fluvastatin or pravastatin may be suitable alternatives, although lower dosages of the statin are recommended in combination with letermovir and cyclosporine. Please refer to the statin prescribing information for specific statin dosing recommendations. All patients receiving statin therapy should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise, and/or dark colored urine. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.

References
  • "Product Information. Prevymis (letermovir)." Merck & Company Inc, Whitehouse Station, NJ.
Amlodipine and Atorvastatin Tablets

Generic Name: amlodipine / atorvastatin

Brand name: Caduet

Synonyms: Amlodipine and atorvastatin, Amlodipine and Atorvastatin

Letermovir Injection

Generic Name: letermovir

Brand name: Prevymis

Synonyms: Letermovir (oral/injection), Letermovir

In the course of checking the drug compatibility and interactions, data from the following reference sources was used: Drugs.com, Rxlist.com, Webmd.com, Medscape.com.