Letermovir
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From MedlinePlus, U.S. National Library of Medicine
Cytomegalovirus DNA Terminase Complex Inhibitor
Dosing in kidney impairment
Recommended Dosage for Adult and Pediatric Patients 12 Years of Age and Older Who Are HSCT or Kidney Transplant Recipients HSCT: Adult and Pediatric Patients 12 Years of Age and Older and Weighing at least 30 kg The recommended dosage of PREVYMIS is 480 mg administered orally or intravenously once daily. When PREVYMIS is administered orally, the recommended dosage is one 480 mg tablet once daily or two 240 mg tablets once daily.
Four 120 mg packets of oral pellets once daily can be used for patients who cannot swallow tablets [see Dosage and Administration ] . For preparation and administration instructions of intravenous dosing refer to instructions in subsection 2.10 [see Dosage and Administration ]. For pediatric patients less than 12 years of age or weighing less than 30 kg, refer to weight-based dosing in Table 1 and Table 2 [see Dosage and Administration ] .
Initiate PREVYMIS between Day 0 and Day 28 post-HSCT (before or after engraftment) and continue through Day 100 post-HSCT. In patients at risk for late CMV infection and disease, PREVYMIS may be continued through Day 200 post-HSCT [see Clinical Studies ] . Dosage of PREVYMIS should be adjusted when co-administered with cyclosporine [see Dosage and Administration ] .
Kidney Transplant: Adult and Pediatric Patients 12 Years of Age and Older and Weighing at least 40 kg The recommended dosage of PREVYMIS is 480 mg administered orally or intravenously once daily. When PREVYMIS is administered orally, the recommended dosage is one 480 mg tablet once daily or two 240 mg tablets once daily.
Four 120 mg packets of oral pellets once daily can be used for patients who cannot swallow tablets [see Dosage and Administration ] . For preparation and administration instructions of intravenous dosing refer to instructions in subsection 2.10 [see Dosage and Administration ]. Initiate PREVYMIS between Day 0 and Day 7 post-transplant and continue through Day 200 post-transplant.
Dosage of PREVYMIS should be adjusted when co-administered with cyclosporine [see Dosage and Administration ] .
Use in Patients with Renal Impairment For adult patients with creatinine clearance (CLcr) greater than 10 mL/min and pediatric patients with a similar degree of renal impairment (based on age-appropriate assessment of renal function), no dosage adjustment of PREVYMIS is required based on renal impairment [see Use in Specific Populations , and Clinical Pharmacology ] .
There are insufficient data in adult patients with CLcr 10 mL/min or less or in patients on dialysis or in pediatric patients with a similar degree of renal impairment (based on age-appropriate assessment of renal function) to make PREVYMIS dosing recommendations. In adult patients with CLcr less than 50 mL/min and in pediatric patients with a similar degree of renal impairment (based on age-appropriate assessment of renal function) receiving PREVYMIS injection, accumulation of the intravenous vehicle, hydroxypropyl betadex, may occur.
Closely monitor serum creatinine levels in these patients [see Warnings and Precautions ] .
Dosing in liver impairment
Use in Patients with Hepatic Impairment No dosage adjustment of PREVYMIS is required for patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment. PREVYMIS is not recommended for patients with severe (Child-Pugh Class C) hepatic impairment [see Use in Specific Populations ] .
Preparation and administration
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Important Dosing and Administration Information PREVYMIS is available in 3 dosage forms: PREVYMIS Tablets - Administer orally with or without food. - Swallow tablets whole. PREVYMIS Oral Pellets - Administer orally mixed with soft food or via nasogastric tube (NG tube) or gastric tube (G tube) [see Dosage and Administration ] . - Do not crush or chew.
PREVYMIS Injection - PREVYMIS injection must be diluted prior to administration. - Administer PREVYMIS through a sterile 0.2 micron or 0.22 micron polyethersulfone (PES) in-line filter. - Administer by intravenous infusion via a peripheral catheter or central venous line at a constant rate over 1 hour. - Do not administer as an intravenous bolus injection. - PREVYMIS injection, which contains hydroxypropyl betadex, should be used only in patients unable to take oral therapy.
Patients should be switched to oral PREVYMIS as soon as they are able to take oral medications. If possible, intravenous administration should not exceed 4 weeks [see Warnings and Precautions ] . No dosage adjustment is necessary when switching formulations in adult and pediatric patients 12 years of age and older [see Dosage and Administration ] .
Dosage adjustment may be necessary for pediatric patients less than 12 years of age when switching between oral and intravenous formulations (see Table 1 and Table 2 ) [see Dosage and Administration ] .
Preparation and Administration of Oral Pellets PREVYMIS oral pellets can be administered: orally after mixing with soft food or via NG tube or G tube. Preparation and Administration Mixed with Soft Food See Instructions for Use for details on the preparation and administration of PREVYMIS oral pellets mixed with soft food.
Do not crush or chew PREVYMIS oral pellets. Mix PREVYMIS oral pellets with 1 to 3 teaspoons of soft food (such as applesauce, yogurt, or pudding) that is at or below room temperature. Do not use hot food. Administer entire mixture within 10 minutes of mixing PREVYMIS oral pellets with the soft food. Preparation and Administration via NG Tube or G Tube See Instructions for Use , Table 4 (NG tube) and Table 5 (G tube) for details on the preparation and administration of PREVYMIS oral pellets via NG tube or G tube.
Pour PREVYMIS oral pellets into a medicine cup containing room temperature water (see Initial Volume in Table 4 and Table 5). Do not mix PREVYMIS oral pellets with hot or cold (refrigerated) water. Wait 10 minutes. Do not shake or swirl the medicine cup. PREVYMIS oral pellets will not dissolve but will become loose or broken up.
The entire mixture should be administered (see steps 3 and 4) within 2 hours. Stir the mixture with the syringe and administer entire mixture right away using the syringe and NG tube or G tube. Add room temperature water (see Rinse Volume in Table 4 and Table 5) to the medicine cup for rinsing, stir with a syringe and administer the entire rinse mixture using the syringe and NG tube or G tube.
Flush the NG tube or G tube with the volume of water recommended by the NG or G tube manufacturer. [See table below.] 0 mg to 480 mg Any ≥ 8 Fr NG tube Appropriately sized ENFit or catheter-tipped syringe Medicine Cup 15 15 40 mg to 80 mg 5 Fr PUR NG tube or Any ≥ 6 Fr NG tube 3 2 [See table below.] 0 mg to 480 mg Any G tube Appropriately sized ENFit or catheter-tipped syringe Medicine Cup 15 15 40 mg to 80 mg Any 12 Fr G tube 3 2
Preparation and Administration of Intravenous Solution PREVYMIS injection is supplied in 30 mL single-dose vials containing either 240 mg/12 mL per vial (20 mg/mL) or 480 mg/24 mL per vial (20 mg/mL). PREVYMIS vials are for single use only. Discard any unused portion. Preparation Instructions PREVYMIS must be diluted prior to intravenous (IV) use.
Only 0.9% Sodium Chloride and 5% Dextrose are chemically and physically compatible with PREVYMIS injection. Do not shake PREVYMIS vial. Inspect vial contents for discoloration and particulate matter prior to dilution. PREVYMIS injection is a clear colorless solution and may contain a few product-related small translucent or white particles.
Do not use the vial if the solution is cloudy, discolored, or contains matter other than a few small translucent or white particles. Once diluted, the solution of PREVYMIS is clear, and ranges from colorless to yellow. Variations of color within this range do not affect the quality of the product. Do not use PREVYMIS injection with IV bags and infusion set materials containing the plasticizer diethylhexyl phthalate (DEHP).
Use only with IV bags and infusion set materials that are DEHP-free. Materials that are phthalate-free are also DEHP-free. Use compatible IV bags and infusion set materials. PREVYMIS injection is compatible with the following IV bags and infusion set materials. PREVYMIS injection is not recommended with any IV bags or infusion set materials not listed below (note that PREVYMIS injection is not recommended for use with polyurethane-containing IV administration set tubing).
IV Bags Materials: Polyvinyl chloride (PVC), ethylene vinyl acetate (EVA) and polyolefin (polypropylene and polyethylene) Infusion Sets Materials: PVC, polyethylene (PE), polybutadiene (PBD), silicone rubber (SR), styrene–butadiene copolymer (SBC), styrene-butadiene-styrene copolymer (SBS), polystyrene (PS) Plasticizers: Tris (2-ethylhexyl) trimellitate (TOTM), benzyl butyl phthalate (BBP) Catheters: Radiopaque polyurethane For the 480 mg or 240 mg dose , add PREVYMIS injection (see Table 6 ) into a 250 mL pre-filled IV bag containing either 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP and mix bag gently.
Do not shake. For the 120 mg or 60 mg dose , add PREVYMIS injection into a pre-filled IV bag containing either 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP (see Table 6 ) and mix bag gently. Do not shake. [See table below.] 240 mg 12 mL 250 mL 120 mg 6 mL 100 mL 60 mg 3 mL 50 mL For the 40 mg dose , prepare a dilution of PREVYMIS injection according to Table 7 in either 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP and mix bag gently.
Transfer 20 mL from the prepared dilution into an appropriately sized IV bag or syringe. Do not shake. [See table below.] Administration Instructions Administer the entire contents of the intravenous bag or syringe by intravenous infusion via a peripheral catheter or central venous line at a constant rate over 1 hour [see Dosage and Administration ] .
The diluted solution must be administered through a sterile 0.2 micron or 0.22 micron polyethersulfone (PES) in-line filter. Do not administer through a filter other than a sterile 0.2 micron or 0.22 micron PES in-line filter. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.
Discard if the diluted solution is cloudy, discolored, or contains matter other than a few small translucent or white particles.
Storage of the Diluted Solution The diluted solutions (as prepared in Table 6 or Table 7) are stable for up to 24 hours at room temperature or up to 48 hours under refrigeration at 2°C to 8°C (36°F to 46°F) (this time includes storage of the diluted solution in the intravenous bag through the duration of infusion).
Compatible Drug Products Used for Intravenous Administration Compatible Drug Products The physical compatibility of PREVYMIS injection with selected injectable drug products was evaluated in two commonly available diluents. PREVYMIS should not be co-administered through the same intravenous line (or cannula) with other drug products and diluent combinations except those listed below.
Refer to the respective prescribing information of the co-administered drug(s) to confirm compatibility of simultaneous co-administration. List of Compatible Drug Products when PREVYMIS and Drug Products are Prepared in 0.9% Sodium Chloride Injection, USP: Ampicillin sodium, ampicillin sodium/sulbactam sodium, anti-thymocyte globulin, caspofungin, daptomycin, fentanyl citrate, fluconazole, furosemide, human insulin, magnesium sulfate, methotrexate, micafungin.
List of Compatible Drug Products when PREVYMIS and Drug Products are Prepared in 5% Dextrose Injection, USP: Amphotericin B (lipid complex) Amphotericin B (lipid complex) is compatible with PREVYMIS. However, Amphotericin B (liposomal) is incompatible [see Dosage and Administration ] . , anidulafungin, cefazolin sodium, ceftaroline, ceftriaxone sodium, doripenem, famotidine, folic acid, ganciclovir sodium, hydrocortisone sodium succinate, morphine sulfate, norepinephrine bitartrate, pantoprazole sodium, potassium chloride, potassium phosphate, tacrolimus, telavancin, tigecycline.
| Dosage | NG TubeFr = French; PUR = polyurethane | Syringe TypeWith ENFit syringe, a medicine straw (large bore) is needed to aid withdrawal of the mixture from the medicine cup. | Mixing Container | Initial Volume (mL) | Rinse Volume (mL) |
|---|---|---|---|---|---|
| 120 mg to 480 mg | Any ≥ 8 Fr NG tube | Appropriately sized ENFit or catheter-tipped syringe | Medicine Cup | 15 | 15 |
| 40 mg to 80 mg | 5 Fr PUR NG tube or Any ≥ 6 Fr NG tube | 3 | 2 |
| Dosage | G TubeFr = French; PUR = polyurethane | Syringe TypeWith ENFit syringe, a medicine straw (large bore) is needed to aid withdrawal of the mixture from the medicine cup. | Mixing Container | Initial Volume (mL) | Rinse Volume (mL) |
|---|---|---|---|---|---|
| 120 mg to 480 mg | Any G tube | Appropriately sized ENFit or catheter-tipped syringe | Medicine Cup | 15 | 15 |
| 40 mg to 80 mg | Any 12 Fr G tube | 3 | 2 |
| PREVYMIS Dose | Volume of PREVYMIS 20 mg/mL to be Withdrawn from Vial | Volume of Diluent |
|---|---|---|
| 480 mg | 24 mL | 250 mL |
| 240 mg | 12 mL | 250 mL |
| 120 mg | 6 mL | 100 mL |
| 60 mg | 3 mL | 50 mL |
Drug interactions
Check letermovir against a medication listLabel text (15 paragraphs)
Dosage Adjustment: If PREVYMIS is co-administered with cyclosporine, the dosage of PREVYMIS should be decreased to 240 mg once daily in adult and pediatric patients 12 years of age and older. ( 2.4 ) If PREVYMIS is co-administered with cyclosporine in pediatric patients less than 12 years of age, dose adjustment may be required. ( 2.6 ) Co-administration of PREVYMIS may alter the plasma concentrations of other drugs and other drugs may alter the plasma concentrations of PREVYMIS. Consult the full prescribing information prior to and during treatment for potential drug interactions. ( 2.4 , 2.6 , 4 , 5.1 , 7.1 , 7.2 , 7.3 , 7.4 , 12.3 )
7.1 Potential for Other Drugs to Affect PREVYMIS Letermovir is a substrate of organic anion-transporting polypeptide 1B1/3 (OATP1B1/3) and P-glycoprotein (P-gp) transporters and UDP-glucuronosyltransferase 1A1/3 (UGT1A1/3) enzymes. Co-administration of PREVYMIS with drugs that are inhibitors of OATP1B1/3 transporters may result in increases in letermovir plasma concentrations (Table 11). Co-administration of PREVYMIS with inducers of transporters (e.g., P-gp) and/or enzymes (e.g., UGTs) is not recommended due to the potential for a decrease in letermovir plasma concentrations (see Table 11 ) .
7.2 Potential for PREVYMIS to Affect Other Drugs Co-administration of PREVYMIS with midazolam results in increased midazolam plasma concentrations, indicating that letermovir is a moderate inhibitor of CYP3A [see Clinical Pharmacology (12.3) ] . Co-administration of PREVYMIS with drugs that are CYP3A substrates may result in clinically relevant increases in the plasma concentrations of co-administered CYP3A substrates (Table 11) [see Contraindications (4) and Warnings and Precautions (5.1) ] . Letermovir is an inhibitor of OATP1B1/3 transporters.
Co-administration of PREVYMIS with drugs that are substrates of OATP1B1/3 transporters may result in a clinically relevant increase in plasma concentrations of co-administered OATP1B1/3 substrates (Table 11). The magnitude of CYP3A- and OATP1B1/3-mediated drug interactions on co-administered drugs may be different when PREVYMIS is co-administered with cyclosporine. See the prescribing information for cyclosporine for information on drug interactions with cyclosporine.
7.3 Established and Other Potentially Significant Drug Interactions If dose adjustments of concomitant medications are made due to treatment with PREVYMIS, doses should be readjusted after treatment with PREVYMIS is completed. Table 11 provides a listing of established or potentially clinically significant drug interactions. The drug interactions described are based on adult studies conducted with PREVYMIS or are predicted drug interactions that may occur with PREVYMIS [see Contraindications (4) , Warnings and Precautions (5.1) , and Clinical Pharmacology (12.3) ] .
Table 11: Potentially Significant Drug Interactions: Alteration in Dose May Be Recommended Based on Results from Adult Drug Interaction Studies or Predicted Interactions This table is not all inclusive. (Information in the Table Applies to Co-administration of PREVYMIS and the Concomitant Drug without Cyclosporine, Unless Otherwise Indicated) Concomitant Drug Class and/or Clearance Pathway: Drug Name Effect on Concentration ↓ =decrease, ↑ =increase Clinical Comments Anti-arrhythmic Agents amiodarone ↑ amiodarone Close clinical monitoring for adverse events related to amiodarone is recommended during co-administration.
Frequently monitor amiodarone concentrations when amiodarone is co-administered with PREVYMIS. Antibiotics nafcillin ↓ letermovir Co-administration of PREVYMIS and nafcillin is not recommended due to potential for loss of efficacy of PREVYMIS. Anticoagulants warfarin ↓ warfarin When PREVYMIS is co-administered with warfarin, frequently monitor International Normalized Ratio (INR) Refer to the respective prescribing information. . Anticonvulsants carbamazepine ↓ letermovir Co-administration of PREVYMIS and carbamazepine is not recommended due to potential for loss of efficacy of PREVYMIS.
phenobarbital ↓ letermovir Co-administration of PREVYMIS and phenobarbital is not recommended due to potential for loss of efficacy of PREVYMIS. phenytoin ↓ letermovir ↓ phenytoin Co-administration of PREVYMIS and phenytoin is not recommended due to potential for loss of efficacy of PREVYMIS. Antidiabetic Agents Examples: glyburide, repaglinide, rosiglitazone ↑ glyburide ↑ repaglinide ↑ rosiglitazone When PREVYMIS is co-administered with glyburide, repaglinide, or rosiglitazone, frequently monitor glucose concentrations . When PREVYMIS is co-administered with cyclosporine, use of repaglinide is not recommended.
Antifungals voriconazole These interactions have been studied [see Clinical Pharmacology (12.3) ] . ↓ voriconazole If concomitant administration of voriconazole is necessary, closely monitor for reduced effectiveness of voriconazole . Antimycobacterials rifabutin ↓ letermovir Co-administration of PREVYMIS and rifabutin is not recommended due to potential for loss of efficacy of PREVYMIS. rifampin ↓ letermovir Co-administration of PREVYMIS and rifampin is not recommended due to potential for loss of efficacy of PREVYMIS. Antipsychotics pimozide ↑ pimozide Co-administration is contraindicated due to risk of QT prolongation and torsades de pointes [see Contraindications (4) ] .
thioridazine ↓ letermovir Co-administration of PREVYMIS and thioridazine is not recommended due to potential for loss of efficacy of PREVYMIS. Endothelin Antagonists bosentan ↓ letermovir Co-administration of PREVYMIS and bosentan is not recommended due to potential for loss of efficacy of PREVYMIS. Ergot Alkaloids ergotamine, dihydroergotamine ↑ ergotamine, dihydroergotamine Co-administration is contraindicated due to risk of ergotism [see Contraindications (4) ] . Herbal Products St. John's wort ( Hypericum perforatum ) ↓ letermovir Co-administration of PREVYMIS and St. John's wort is not recommended due to potential for loss of efficacy of PREVYMIS.
HIV Medications efavirenz ↓ letermovir Co-administration of PREVYMIS and efavirenz is not recommended due to potential for loss of efficacy of PREVYMIS. etravirine ↓ letermovir Co-administration of PREVYMIS and etravirine is not recommended due to potential for loss of efficacy of PREVYMIS. nevirapine ↓ letermovir Co-administration of PREVYMIS and nevirapine is not recommended due to potential for loss of efficacy of PREVYMIS. HMG-CoA Reductase Inhibitors atorvastatin ↑ atorvastatin When PREVYMIS is co-administered with atorvastatin, do not exceed an atorvastatin dosage of 20 mg daily . Closely monitor patients for myopathy and rhabdomyolysis.
When PREVYMIS is co-administered with cyclosporine, use of atorvastatin is not recommended. pitavastatin, simvastatin ↑ HMG-CoA reductase inhibitors Co-administration of PREVYMIS and pitavastatin or simvastatin is not recommended. When PREVYMIS is co-administered with cyclosporine, use of either pitavastatin or simvastatin is contraindicated due to significantly increased pitavastatin or simvastatin concentrations and risk of myopathy or rhabdomyolysis [see Contraindications (4) ] . fluvastatin, lovastatin, pravastatin, rosuvastatin ↑ HMG-CoA reductase inhibitors When PREVYMIS is co-administered with these statins, a statin dosage reduction may be necessary .
Closely monitor patients for myopathy and rhabdomyolysis. When PREVYMIS is co-administered with cyclosporine, use of lovastatin is not recommended. When PREVYMIS is co-administered with cyclosporine, refer to the statin prescribing information for specific statin dosing recommendations. Immunosuppressants cyclosporine ↑ cyclosporine ↑ letermovir Decrease the dosage of PREVYMIS to 240 mg once daily in adult and pediatric patients 12 years of age and older [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3) ] . Dose adjustment may be required in pediatric patients less than 12 years of age [see Dosage and Administration (2.6) and Clinical Pharmacology (12.3) ] .
Frequently monitor cyclosporine whole blood concentrations during treatment and after discontinuation of PREVYMIS and adjust the dose of cyclosporine accordingly . sirolimus ↑ sirolimus When PREVYMIS is co-administered with sirolimus, frequently monitor sirolimus whole blood concentrations during treatment and after discontinuation of PREVYMIS and adjust the dose of sirolimus accordingly . When PREVYMIS is co-administered with cyclosporine and sirolimus, refer to the sirolimus prescribing information for specific sirolimus dosing recommendations .
tacrolimus ↑ tacrolimus Frequently monitor tacrolimus whole blood concentrations during treatment and after discontinuation of PREVYMIS and adjust the dose of tacrolimus accordingly . Proton Pump Inhibitors omeprazole ↓ omeprazole Clinical monitoring and dose adjustment may be needed. pantoprazole ↓ pantoprazole Clinical monitoring and dose adjustment may be needed. Wakefulness-Promoting Agents modafinil ↓…
Contraindications
4 CONTRAINDICATIONS PREVYMIS is contraindicated in patients receiving pimozide or ergot alkaloids: Pimozide: Concomitant administration of PREVYMIS in patients receiving pimozide may result in increased concentrations of pimozide due to inhibition of cytochrome P450 3A (CYP3A) by letermovir, which may lead to QT prolongation and torsades de pointes [see Warnings and Precautions (5.1) and Drug Interactions (7.2 , 7.3) ] .
Ergot alkaloids: Concomitant administration of PREVYMIS in patients receiving ergot alkaloids may result in increased concentrations of ergot alkaloids (ergotamine and dihydroergotamine) due to inhibition of CYP3A by letermovir, which may lead to ergotism [see Warnings and Precautions (5.1) and Drug Interactions (7.2 , 7.3) ] . PREVYMIS is contraindicated with pitavastatin and simvastatin when co-administered with cyclosporine.
Concomitant administration of PREVYMIS in combination with cyclosporine may result in significantly increased pitavastatin or simvastatin concentrations, which may lead to myopathy or rhabdomyolysis [see Warnings and Precautions (5.1) and Drug Interactions (7.2 , 7.3) ] . PREVYMIS is contraindicated with: Pimozide. ( 4 ) Ergot Alkaloids. ( 4 ) Pitavastatin and simvastatin when co-administered with cyclosporine. ( 4 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
ELikelihood score E: Unlikely cause of clinically apparent liver injury.
Letermovir is an antiviral agent which targets the DNA terminal transferase complex of the cytomegalovirus (CMV) and which is used to prevent CMV reactivation in immunocompromised patients. Letermovir has been associated with mild-to-moderate serum aminotransferase elevations during therapy but has not been linked to cases of clinically apparent acute liver injury.
ABCDEA: well known cause; E: unlikely cause. [HD]: high doses only.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary No adequate human data are available to establish whether PREVYMIS poses a risk to pregnancy outcomes. 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).
In a rat pre/post-natal development study, total litter loss was observed at maternal letermovir exposures approximately 2 times higher than human exposure at the RHD (see Data ) . The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Letermovir was administered orally to pregnant rats at 0, 10, 50 or 250 mg/kg/day from gestation days 6 to 17.
Developmental toxicities, including skeletal malformations and umbilical cord shortening, were observed at 250 mg/kg/day (approximately 11 times higher than human exposure at the RHD). In addition, decreased fetal body weight and skeletal variations (due to maternal toxicity) were observed at this dose. No embryo-fetal toxicities were observed at 50 mg/kg/day (approximately 3 times higher than human exposure at the RHD). Letermovir was administered orally to pregnant rabbits at 0, 25, 75 or 225 mg/kg/day from gestation days 6 to 20.
Developmental toxicities, including spontaneous abortion, increased post-implantation loss, and skeletal variations, were observed at a maternally toxic dose (225 mg/kg/day; approximately 2 times higher than human exposure at the RHD). No embryo-fetal toxicities were observed at 75 mg/kg/day (less than human exposure at the RHD). In the pre/post-natal development study, letermovir was administered orally to pregnant rats at 0, 10, 45 or 180 mg/kg/day from gestation day 6 to lactation day 22.
At 180 mg/kg/day (approximately 2 times higher than human exposure at the RHD), total litter loss due to stillbirth or possible maternal neglect was observed in 5 of 23 pregnant females by post-partum/lactation day 4. In surviving offspring, slight developmental delays in vaginal opening and pinna unfolding were accompanied by reduced body weight gain at this dose. No toxicities were observed at 45 mg/kg/day…
Breastfeeding (LactMed)
No information is available on the use of letermovir during breastfeeding. Because letermovir is 99% bound to plasma proteins, the amount in milk is likely to be very low. However, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
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