PREVYMIS FILM COATED TABLET 240MG [SIN15757P]

Product Info

PREVYMIS FILM COATED TABLET 240MG

[SIN15757P]

1. INDICATIONS AND USAGE

PREVYMIS is indicated for the prophylaxis of cytomegalovirus (CMV) infection and disease in adult CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant (HSCT).

PREVYMIS is indicated for prophylaxis of CMV disease in CMV-seronegative adults who have received a kidney transplant from a CMV-seropositive donor [D+/R-].

2. DOSAGE AND ADMINISTRATION

2.1 General
PREVYMIS Tablets

• Administer with or without food.

• Swallow tablets whole. Do not divide, crush or chew.

PREVYMIS Concentrate for Solution for Infusion

• PREVYMIS injection must be administered 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 over approximately 60 minutes.

• Do not administer as an intravenous bolus injection.

PREVYMIS tablet and concentrate for solution for infusion may be used interchangeably at the discretion of the physician, and no dose adjustment is necessary.

Missed Dose
Instruct patients that if they miss a dose of PREVYMIS, they should take it as soon as they remember. If they do not remember until it is time for the next dose, instruct them to skip the missed dose and go back to the regular schedule. Instruct patients not to double their next dose or take more than the prescribed dose.

2.2 Recommended Dosage in Adults
The recommended dosage of PREVYMIS is 480 mg administered once daily.

HSCT
PREVYMIS should be started after HSCT. PREVYMIS may be started on the day of transplant and no later than 28 days post-HSCT. PREVYMIS may be started before or after engraftment. Continue PREVYMIS through 100 days post-HSCT.

Prolonged PREVYMIS prophylaxis beyond 100 days post-HSCT may be of benefit in some patients at high risk for late CMV reactivation [see section 9 CLINICAL STUDIES – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information]. The safety and efficacy of PREVYMIS use for more than 200 days has not been studied in clinical trials.

Kidney transplant
PREVYMIS should be started on the day of transplant and no later than 7 days post-kidney transplant and continued through 200 days post-transplant.

2.3 Dosage Adjustment in Adults
If PREVYMIS is co-administered with cyclosporine, the dosage of PREVYMIS should be decreased to 240 mg once daily [see Table 1 in 5 DRUG INTERACTIONS AND OTHER FORMS OF INTERACTIONS, 5.3 Established and Other Potential Drug Interactions – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information].

• If cyclosporine is initiated after starting PREVYMIS, the next dose of PREVYMIS should be decreased to 240 mg once daily.

• If cyclosporine is discontinued after starting PREVYMIS, the next dose of PREVYMIS should be increased to 480 mg once daily.

• If cyclosporine dosing is temporarily interrupted due to high cyclosporine levels, no dose adjustment of PREVYMIS is needed.

2.4 Pediatric Patients
Safety and efficacy of PREVYMIS have not been established in pediatric patients less than 18 years of age.

2.5 Geriatric Patients
No dose adjustment of PREVYMIS is required based on age [see 6 USE IN SPECIFIC POPULATIONS, 6.5 Geriatric Use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information].

2.6 Renal Impairment
No dose adjustment of PREVYMIS is required based on renal impairment [see 2 DOSAGE AND ADMINISTRATION, 2.7 Hepatic Impairment, and 6 USE IN SPECIFIC POPULATIONS, 6.6 Renal Impairment – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information].

2.7 Hepatic Impairment
No dose adjustment of PREVYMIS is required based on mild (Child-Pugh Class A) to moderate (Child-Pugh Class B) hepatic impairment. PREVYMIS is not recommended for patients with severe (Child-Pugh Class C) hepatic impairment.

PREVYMIS is not recommended in patients with moderate hepatic impairment combined with moderate or severe renal impairment [see 6 USE IN SPECIFIC POPULATIONS, 6.7 Hepatic Impairment – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information].

2.8 Preparation and Administration of Intravenous Solution
PREVYMIS concentrate for solution for infusion is supplied in 30 mL single-dose vials containing either 240 mg (12 mL per vial) or 480 mg (24 mL per vial). The preparation and administration instructions are the same for either dose.

PREVYMIS vials are for single use only. Discard any unused portion.

Preparation

• PREVYMIS must be diluted prior to intravenous (IV) use.

• Inspect vial contents for discoloration and particulate matter prior to dilution. PREVYMIS concentrate for solution for infusion 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.

• Do not use PREVYMIS injection with IV bags and infusion set materials containing polyurethane or the plasticizer diethylhexyl phthalate (DEHP). Materials that are phthalate-free are also DEHP-free.

• Do not shake PREVYMIS vial.

• Add one single-dose vial of PREVYMIS concentrate for solution for infusion to a 250 mL pre-filled IV bag containing either 0.9% sodium chloride or 5% dextrose and mix bag gently. Do not shake.

• 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. The diluted solution 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 Diluted Solution

• The diluted solution can be stored 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.

Administration

• The diluted solution must be administered through a sterile 0.2 micron or 0.22 micron PES in-line filter.

• Do not administer the diluted solution through a filter other than a sterile 0.2 micron or 0.22 micron PES in-line filter.

• Administer as an intravenous infusion only. Do not administer as an intravenous push or bolus.

• After dilution, administer PREVYMIS via intravenous infusion via peripheral or central venous catheter using a total time of approximately 60 minutes. Administer the entire contents of the IV bag.

2.9 Compatible Diluents, Drug Products, and Other Materials Used for Intravenous Administration
Compatible Diluents
PREVYMIS concentrate for solution for infusion is compatible with 0.9% sodium chloride and 5% dextrose solutions.

Compatible Drug Products
A study was conducted to evaluate physical compatibility of PREVYMIS concentrate for solution for infusion with injectable drug products. Compatibility was determined through visual observations, turbidity, and measurement of particulate matter. Compatible drug products are listed below.

PREVYMIS should not be co-administered through the same intravenous line (or cannula) with other drug products and diluent combinations except those listed below.

The following compatible drug products may be co-administered with PREVYMIS for injection when both drug products are in 0.9% Sodium Chloride via Y tubing only, as per the approved instructions of the respective drug products.

• Ampicillin sodium

• Ampicillin sodium/Sulbactam sodium

• Anti-thymocyte globulin

• Caspofungin

• Daptomycin

• Fentanyl citrate

• Fluconazole

• Furosemide

• Human insulin

• Magnesium sulfate

• Methotrexate

• Micafungin

The following compatible drug products may be co-administered with PREVYMIS for injection when both drug products are in 5% Dextrose via Y tubing only, as per the approved instructions of the respective drug products.

• Amphotericin B (lipid complex)*

• 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

* Amphotericin B (lipid complex) is compatible with PREVYMIS. However, Amphotericin B (liposomal) is incompatible [see 2 DOSAGE AND ADMINISTRATION, 2.10 Incompatible Diluents, Drug Products, and Other Materials Used for Intravenous Administration – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information].

Compatible IV Bags and Infusion Set Materials
PREVYMIS is compatible with the following IV bags and infusion set materials. Any IV bags or infusion set materials not listed below should not be used.

IV Bag Materials
Polyvinyl chloride (PVC), ethylene vinyl acetate (EVA) and polyolefin (polypropylene and polyethylene)

Infusion Set 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), butyl benzyl phthalate (BBP)

Catheters
Radiopaque polyurethane

2.10 Incompatible Diluents, Drug Products, and Other Materials Used for Intravenous Administration
Incompatible Drug Products
PREVYMIS concentrate for solution for infusion is physically incompatible with amiodarone hydrochloride, amphotericin B (liposomal), aztreonam, cefepime hydrochloride, ciprofloxacin, cyclosporine, diltiazem hydrochloride, filgrastim, gentamicin sulfate, levofloxacin, linezolid, lorazepam, midazolam HCl, mycophenolate mofetil hydrochloride, ondansetron, palonosetron.

Incompatible IV Bags and Infusion Set Materials
PREVYMIS concentrate for solution for infusion is incompatible with diethylhexyl phthalate (DEHP) plasticizers and polyurethane-containing IV administration set tubing.

3. CONTRAINDICATIONS

PREVYMIS is contraindicated in patients with hypersensitivity to letermovir or any of its inactive ingredients.

Pimozide
Concomitant administration of PREVYMIS may result in increased concentrations of pimozide due to inhibition of cytochrome P450 (CYP3A) by letermovir, leading to QT prolongation and torsades de pointes [see 4 WARNINGS AND PRECAUTIONS, 4.1 Risk of Adverse Reactions or Reduced Therapeutic Effect Due to Drug Interactions, and 5 DRUG INTERACTIONS AND OTHER FORMS OF INTERACTIONS, 5.2 Effects of PREVYMIS on Other Drugs – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information].

Ergot alkaloids
Concomitant administration of PREVYMIS may result in increased concentrations of ergot alkaloids (ergotamine and dihydroergotamine) due to inhibition of CYP3A by letermovir, which may lead to ergotism [see 4 WARNINGS AND PRECAUTIONS, 4.1 Risk of Adverse Reactions or Reduced Therapeutic Effect Due to Drug Interactions, and 5 DRUG INTERACTIONS AND OTHER FORMS OF INTERACTIONS, 5.2 Effects of PREVYMIS on Other Drugs – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information].

Cyclosporine with pitavastatin or simvastatin
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 4 WARNINGS AND PRECAUTIONS, 4.1, Risk of Adverse Reactions or Reduced Therapeutic Effect Due to Drug Interactions, and 5 DRUG INTERACTIONS AND OTHER FORMS OF INTERACTIONS, 5.2 Effects of PREVYMIS on Other Drugs – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information].