VALGANCICLOVIR HYDROCHLORIDE- valganciclovir for solution

Land: USA

Språk: engelsk

Kilde: NLM (National Library of Medicine)

Aktiv ingrediens:

VALGANCICLOVIR (UNII: GCU97FKN3R) (VALGANCICLOVIR - UNII:GCU97FKN3R)

Tilgjengelig fra:

Somerset Therapeutics, LLC

Administreringsrute:

ORAL

Resept typen:

PRESCRIPTION DRUG

Indikasjoner:

Treatment of Cytomegalovirus (CMV) Retinitis : Valganciclovir hydrochloride is indicated for the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS) [see Clinical Studies (14.1)] . Prevention of CMV Disease : Valganciclovir hydrochloride is indicated for the prevention of CMV disease in kidney, heart, and kidney- pancreas transplant patients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-]) [see Clinical Studies (14.1)] . Prevention of CMV Disease : Valganciclovir hydrochloride is indicated for the prevention of CMV disease in kidney transplant patients (4 months to 16 years of age) and heart transplant patients (1 month to 16 years of age) at high risk[see Clinical Studies (14.2)] . Valganciclovir hydrochloride is contraindicated in patients who have had a demonstrated clinically significant hypersensitivity reaction (e.g., anaphylaxis) to valganciclovir, ganciclovir, or any component of the formulation[see Adverse Reactions (6.1)] . Risk Summary After oral administration, valganciclovir (prodrug) is converted to ganciclovir (active drug) and, therefore, Valganciclovir is expected to have reproductive toxicity effects similar to ganciclovir. In animal studies, ganciclovir caused maternal and fetal toxicity and embryo-fetal mortality in pregnant mice and rabbits as well as teratogenicity in rabbits at exposures two- times the human exposure. There are no available human data on use of Valganciclovir or ganciclovir in pregnant women to establish the presence or absence of drug-associated risk. The background risk of major birth defects and miscarriage for the indicated populations is unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4% and the risk of miscarriage is    15 to 20% of clinically recognized pregnancies. Advise pregnant women of the potential risk to the fetus [see Warnings and Precautions (5.3),Use in Specific Populations (8.3)]. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Most maternal CMV infections are asymptomatic or they may be associated with a self-limited mononucleosis-like syndrome. However, in immunocompromised patients (i.e., transplant patients or patients with AIDS) CMV infections may be symptomatic and may result in significant maternal morbidity and mortality. The transmission of CMV to the fetus is a result of maternal viremia and transplacental infection. Perinatal infection can also occur from exposure of the neonate to CMV shedding in the genital tract. Approximately 10% of children with congenital CMV infection are symptomatic at birth. Mortality in these infants is about 10% and approximately 50 to 90% of symptomatic surviving newborns experience significant morbidity, including mental retardation, sensorineural hearing loss, microcephaly, seizures, and other medical problems. The risk of congenital CMV infection resulting from primary maternal CMV infection may be higher and of greater severity than that resulting from maternal reactivation of CMV infection. Data Animal Data Doses resulting in two-times the human exposure of ganciclovir (based on the human AUC following a single intravenous infusion of 5 mg per kg of ganciclovir) resulted in maternal and embryo-fetal toxicity in pregnant mice and rabbits as well as teratogenicity in the rabbits. Fetal resorptions were present in at least 85% of rabbits and mice. Rabbits showed increased embryo-fetal mortality, growth retardation of the fetuses and structural abnormalities of multiple organs of the fetuses including the palate (cleft palate), eyes (anophthalmia/microphthalmia), brain (hydrocephalus), jaw (brachygnathia), kidneys and pancreas (aplastic organs). Increased embryo-fetal mortality was also seen in mice. Daily intravenous doses of approximately 1.7 times the human exposure (based on AUC) administered to female mice prior to mating, during gestation, and during lactation caused hypoplasia of the testes and seminal vesicles in the male offspring, as well as pathologic changes in the nonglandular region of the stomach. Data from an ex-vivo human placental model showed that ganciclovir crosses the human placenta. The transfer occurred by passive diffusion and was not saturable over a concentration range of 1 to 10 mg/mL. Risk Summary No data are available regarding the presence of valganciclovir (prodrug) or ganciclovir (active drug) in human milk, the effects on the breastfed infant, or the effects on milk production. Animal data indicate that ganciclovir is excreted in the milk of lactating rats. The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV. Advise nursing mothers that breastfeeding is not recommended during treatment with valganciclovir because of the potential for serious adverse events in nursing infants and because of the potential for transmission of HIV [see Boxed Warning, Warnings and Precautions(5.1,5.3,5.4,5.5),Nonclinical Toxicology (13.1)] . Pregnancy Testing Females of reproductive potential should undergo pregnancy testing before initiation of valganciclovir[see Use in Specific Populations (8.1)]. Contraception Females Because of the mutagenic and teratogenic potential of valganciclovir, females of reproductive potential should be advised to use effective contraception during treatment and for at least 30 days following treatment with valganciclovir [see Dosage and Administration (2.6), Warnings and Precautions (5.4, 5.5), Nonclinical Toxicology (13.1)]. Males Because of its mutagenic potential, males should be advised to use condoms during and for at least 90 days following, treatment with valganciclovir [see Dosage and Administration (2.6), Warnings and Precautions (5.3, 5.5), Nonclinical Toxicology (13.1)]. Infertility Valganciclovir at the recommended doses may cause temporary or permanent female and male infertility [see Warnings and Precautions (5.3), Nonclinical Toxicology (13.1)]. Data Human Data In a small, open-label, non-randomized clinical study, adult male renal transplant patients receiving Valganciclovir for CMV prophylaxis for up to 200 days post-transplantation were compared to an untreated control group. Patients were followed-up for six months after valganciclovir discontinuation. Among 24 evaluable patients in the valganciclovir group, the mean sperm density at the end of treatment visit decreased by 11 million/mL from baseline; whereas, among 14 evaluable patients in the control group the mean sperm density increased by 33 million/mL. However, at the follow-up visit among 20 evaluable patients in the valganciclovir group the mean sperm density was comparable to that observed among 10 evaluable patients in the untreated control group (the mean sperm density at the end of follow-up visit increased by 41 million/mL from baseline in the valganciclovir group and by 43 million/mL in the untreated group). Valganciclovir hydrochloride for oral solution and tablets are indicated for the prevention of CMV disease in pediatric kidney transplant patients 4 months to 16 years of age and in pediatric heart transplant patients 1 month to 16 years of age at risk for developing CMV disease [see Indications and Usage (1.2),Dosage and Administration (2.3)]. The use of valganciclovir hydrochloride for oral solution and tablets for the prevention of CMV disease in pediatric kidney transplant patients 4 months to 16 years of age is based on two single-arm, open-label, non-comparative studies in patients 4 months to 16 years of age. Study 1 was a safety and pharmacokinetic study in pediatric solid organ transplant patients (kidney, liver, heart, and kidney/pancreas). Valganciclovir hydrochloride was administered once daily within 10 days of transplantation for a maximum of 100 days post-transplantation. Study 2 was a safety and tolerability study where valganciclovir hydrochloride was administered once daily within 10 days of transplantation for a maximum of 200 days post-transplantation in pediatric kidney transplant patients. The results of these studies were supported by previous demonstration of efficacy in adult patients [see Adverse Reactions (6.1),Clinical Pharmacology (12.3),Clinical Studies (14.2)]. The use of valganciclovir hydrochloride for oral solution and tablets for the prevention of CMV disease in pediatric heart transplant patients 1 month to 16 years of age is based on two studies (Study 1 described above and Study 3) and was supported by previous demonstration of efficacy in adult patients [see Clinical Pharmacology (12.3),Clinical Studies (14.2)]. S tudy 3 was a pharmacokinetic and safety study of valganciclovir hydrochloride in pediatric heart transplant patients less than 4 months of age who received a single dose of valganciclovir hydrochloride oral solution on each of two consecutive days. A physiologically based pharmacokinetic (PBPK) model was developed based on the available pharmacokinetic data from pediatric and adult patients to support dosing in heart transplant patients less than 1 month of age. However, due to uncertainty in model predictions for neonates, valganciclovir hydrochloride is not indicated for prophylaxis in this age group. The safety and efficacy of valganciclovir hydrochloride for oral solution and tablets have not been established in children for prevention of CMV disease in pediatric liver transplant patients, in kidney transplant patients less than 4 months of age, in heart transplant patients less than 1 month of age, in pediatric AIDS patients with CMV retinitis, and in infants with congenital CMV infection. A pharmacokinetic and pharmacodynamic evaluation of valganciclovir hydrochloride for oral solution was performed in 24 neonates with congenital CMV infection involving the central nervous system. All patients were treated for 6 weeks with a combination of intravenous ganciclovir 6 mg per kg twice daily or valganciclovir hydrochloride for oral solution at doses ranging from 14 mg per kg to 20 mg per kg twice daily. The pharmacokinetic results showed that in infants greater than 7 days to 3 months of age, a dose of 16 mg per kg twice daily of valganciclovir hydrochloride for oral solution provided ganciclovir systemic exposures (median AUC0-12h =23.6 [range 16.8 to 35.5] mcg∙h/mL; n=6) comparable to those obtained in infants up to 3 months of age from a 6 mg per kg dose of intravenous ganciclovir twice daily (AUC0-12h =25.3 [range 2.4 to 89.7] mcg∙h/mL; n=18) or to the ganciclovir systemic exposures obtained in adults from a 900 mg dose of valganciclovir hydrochloride tablets twice daily. However, the efficacy and safety of intravenous ganciclovir and of valganciclovir hydrochloride have not been established for the treatment of congenital CMV infection in infants and no similar disease occurs in adults; therefore, efficacy cannot be extrapolated from intravenous ganciclovir use in adults. Studies of valganciclovir hydrochloride for oral solution or tablets have not been conducted in adults older than 65 years of age. Clinical studies of valganciclovir did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Valganciclovir hydrochloride is known to be substantially excreted by the kidneys, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because renal clearance decreases with age, valganciclovir hydrochloride should be administered with consideration of their renal status. Renal function should be monitored and dosage adjustments should be made accordingly [see Dosage and Administration (2.5),Warnings and Precautions (5.2),Use in Specific Populations (8.6),Clinical Pharmacology (12.3)]. Dose reduction is recommended when administering valganciclovir to patients with renal impairment [see Dosage and Administration (2.5), Warnings and Precautions (5.2), Clinical Pharmacology (12.3)] . For adult patients on hemodialysis (CrCl less than 10 mL/min), valganciclovir hydrochloride tablets should not be used. Adult hemodialysis patients should use ganciclovir in accordance with the dose-reduction algorithm cited in the CYTOVENE® -IV complete product information section on DOSAGE AND ADMINISTRATION: Renal Impairment [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3)]. The safety and efficacy of valganciclovir hydrochloride have not been studied in patients with hepatic impairment. Valganciclovir (val-gan-SYE-kloe-ver) Hydrochloride for Oral Solution Be sure that you read, and that you understand and follow these instructions carefully to ensure proper dosing of the oral solution. Important: - Avoid contact with your skin or eyes. If you come in contact with the contents of the oral solution, wash your skin well with soap and water or rinse your eyes well with plain water. - Do not use valganciclovir hydrochloride for oral solution after the discard date on the bottle. - Always use the oral dispenser provided to give or take a dose of valganciclovir hydrochloride for oral solution. - Call your pharmacist if your oral dispenser is lost or damaged, and they will tell you how to continue to give or take a dose of valganciclovir hydrochloride for oral solution. - Ask your healthcare provider or pharmacist to show you how to measure your prescribed dose. To take a dose of valganciclovir hydrochloride for oral solution, you will need the bottle of medicine and an oral dispenser provided with the medicine (see Figure 1 ). Your pharmacist inserts the bottle adapter in the valganciclovirhydrochloride for oral solution bottle. - Place the tip of the oral dispenser in the mouth.  - Slowly push down the oral dispenser plunger until the oral dispenser is empty. - Remove the plunger from the oral dispenser barrel by pulling the plunger all the way out of the barrel.  - Rinse the oral dispenser barrel and plunger with water and let them air dry. - When the oral dispenser barrel and plunger are dry, put the plunger back into the oral dispenser barrel for the next use. How should I store valganciclovir hydrochloride for oral solution? - Store solution in the refrigerator at 36°to 46°F (2°to 8°C) for no longer than 49 days. - Do not freeze. This Patient Information and Instructions for Use have been approved by the U.S. Food and Drug Administration. Brands listed are the trademarks of their respective owners. Manufactured by:                                                                     Manufactured for: Granules Pharmaceuticals Inc.  Somerset Therapeutics, LLC Chantilly, VA 20151                                                                 Hollywood, FL 33024 Rev. 01/2022 For more information about valganciclovir hydrochloride, please contact Granules Pharmaceuticals Inc. at 1-877-770-3183.

Produkt oppsummering:

valganciclovir hydrochloride for oral solution: Supplied as a white to off-white powder blend for constitution, forming a colorless to brownish-yellow tutti-frutti flavored solution. Available in amber colored glass bottles containing approximately 100 mL of solution after constitution. Each bottle can deliver up to a total of 88 mL of solution. Each bottle is supplied with a bottle adapter and 2 oral dispensers (NDC 70069-810-01). Prior to dispensing to the patient, valganciclovir hydrochloride for oral solution must be prepared by the pharmacist [see Dosage and Administration (2.4)]. Store dry powder at 20° to 25°C (68° to 77°F) [see USP controlled room temperature]. Store constituted solution under refrigeration at 2° to 8°C (36° to 46°F) for no longer than 49 days. Do not freeze.

Autorisasjon status:

Abbreviated New Drug Application

Preparatomtale

VALGANCICLOVIR HYDROCHLORIDE- VALGANCICLOVIR FOR SOLUTION
SOMERSET THERAPEUTICS, LLC
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
VALGANCICLOVIR
HYDROCHLORIDE FOR ORAL SOLUTION SAFELY AND EFFECTIVELY. SEE FULL
PRESCRIBING
INFORMATION FOR VALGANCICLOVIR HYDROCHLORIDE FOR ORAL SOLUTION.
VALGANCICLOVIR HYDROCHLORIDE, FOR ORAL SOLUTION
INITIAL U.S. APPROVAL: 2001
WARNING: HEMATOLOGIC TOXICITY, IMPAIRMENT OF FERTILITY, FETAL
TOXICITY,
MUTAGENESIS AND CARCINOGENESIS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
HEMATOLOGIC TOXICITY: SEVERE LEUKOPENIA, NEUTROPENIA, ANEMIA,
THROMBOCYTOPENIA,
PANCYTOPENIA, AND BONE MARROW FAILURE INCLUDING APLASTIC ANEMIA HAVE
BEEN
REPORTED IN PATIENTS TREATED WITH VALGANCICLOVIR _(5.1)_
IMPAIRMENT OF FERTILITY: BASED ON ANIMAL DATA AND LIMITED HUMAN DATA,
VALGANCICLOVIR MAY CAUSE TEMPORARY OR PERMANENT INHIBITION OF
SPERMATOGENESIS IN
MALES AND SUPPRESSION OF FERTILITY IN FEMALES. _(5.3)_
FETAL TOXICITY: BASED ON ANIMAL DATA, VALGANCICLOVIR HAS THE POTENTIAL
TO CAUSE BIRTH
DEFECTS IN HUMANS. _(5.4)_
MUTAGENESIS AND CARCINOGENESIS: BASED ON ANIMAL DATA, VALGANCICLOVIR
HAS THE
POTENTIAL TO CAUSE CANCERS IN HUMANS. _(5.5)_
INDICATIONS AND USAGE
Valganciclovir hydrochloride is a deoxynucleoside analogue
cytomegalovirus (CMV) DNA polymerase
inhibitor indicated for:
Adult Patients _(1.1)_
• Treatment of CMV retinitis in patients with acquired
immunodeficiency syndrome (AIDS).
• Prevention of CMV disease in kidney, heart, and kidney-pancreas
transplant patients at high risk.
Pediatric Patients_(1.2)_
• Prevention of CMV disease in kidney and heart transplant patients
at high risk.
DOSAGE AND ADMINISTRATION
ADULT DOSAGE (2.2)
Treatment of CMV
retinitis
Induction: 900 mg (two 450 mg tablets) twice a
day for 21 days
Maintenance: 900 mg (two 450 mg tablets) once a day
Prevention of CMV
disease in heart or
kidney-pancreas
transplant patients
900 mg (two 450 mg tablets) once a day within
10 days of transplant