VALGANCICLOVIR tablet, film coated

국가: 미국

언어: 영어

출처: NLM (National Library of Medicine)

유효 성분:

VALGANCICLOVIR HYDROCHLORIDE (UNII: 4P3T9QF9NZ) (GANCICLOVIR - UNII:P9G3CKZ4P5)

제공처:

AvPAK

INN (International Name):

VALGANCICLOVIR HYDROCHLORIDE

구성:

VALGANCICLOVIR 450 mg

관리 경로:

ORAL

처방전 유형:

PRESCRIPTION DRUG

치료 징후:

Treatment of Cytomegalovirus (CMV) Retinitis : Valganciclovir tablets, USP are indicated for the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS) [see Clinical Studies ( 14.1)]. Prevention of CMV Disease : Valganciclovir tablets, USP are 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 tablets, USP are indicated for the prevention of CMV disease in heart transplant patients (4 month to 16 years of age) at high risk [see Clinical Studies ( 14.2)]. Pediatric use information for pediatric kidney transplant patients ages 4 months to 16 years and for pediatric heart transplant patients ages 1 to less than 4 months is approved for Roche Palo Alto LLC' s VALCYTE (valganciclovir hydrochloride) tablets. However, due to Roche Palo Alto LLC' s marketing exclusivity rights, this drug product is not labeled with that pediatric information. Valganciclovir tablets are 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)]. Teratogenic Effects Risk Summary After oral administration, valganciclovir (prodrug) is converted to ganciclovir (active drug) and, therefore, valganciclovir tablets are 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 tablets 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. Advice 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       At doses resulting in two-times the human exposure of ganciclovir (all dose comparisons presented are based on the human AUC following a single intravenous infusion of 5 mg per kg of ganciclovir) resulted in maternal and embryofetal 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 embryofetal 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 embryofetal 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. 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 tablets 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, 5.2,5.3,5.4), Nonclinical Toxicology ( 13.1)]. Pregnancy Testing      Females of reproductive potential should undergo pregnancy testing before initiation of valganciclovir tablets [see Use in Specific Populations ( 8.1)]. Contraception Females       Because of the mutagenic and teratogenic potential of valganciclovir tablets, females of reproductive potential should be advised to use effective contraception during treatment and for at least 30 days following treatment with valganciclovir tablets [see Dosage and Administration (2.6), Warnings and Precautions ( 5.3, 5.4), Nonclinical Toxicology ( 13.1)]. Males      Because of its mutagenic potential, males should be advised to practice barrier contraception during and for at least 90 days following, treatment with valganciclovir tablets [see Dosage and Administration (2.6), Warnings and Precautions (5.3), Nonclinical Toxicology ( 13.1)]. Infertility        Valganciclovir tablets at the recommended doses may cause temporary or permanent female and male infertility [see Warnings and Precautions ( 5.2), Nonclinical Toxicology ( 13.1)]. Valganciclovir tablets are indicated for the prevention of CMV disease in pediatric heart transplant patients 4 month to 16 years of age at risk for developing CMV disease [see Indications and Usage ( 1.2), Dosage and Administration ( 2.3)]. Study 1 was a safety and pharmacokinetic study in pediatric solid organ transplant patients (kidney, liver, heart, and kidney/pancreas). Valganciclovir tablets were administered once daily within 10 days of transplantation for a maximum of 100 days post-transplantation. The use of valganciclovir tablets for the prevention of CMV disease in pediatric heart transplant patients 4 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)] . Study 3 was a pharmacokinetic and safety study of valganciclovir tablets in pediatric heart transplant patients less than 4 months of age who received a single dose of valganciclovir 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 tablets is not indicated for prophylaxis in this age group. The safety and efficacy of valganciclovir 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 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 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 for oral solution provided ganciclovir systemic exposures (median AUC 0 to 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 (AUC 0 to12h = 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 tablets twice daily. However, the efficacy and safety of intravenous ganciclovir and of valganciclovir 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. Pediatric use information for pediatric kidney transplant patients ages 4 months to 16 years and for pediatric heart transplant patients ages 1 to less than 4 months is approved for Roche Palo Alto LLC' s VALCYTE (valganciclovir hydrochloride) tablets. However, due to Roche Palo Alto LLC' s marketing exclusivity rights, this drug product is not labeled with that pediatric information. Studies of valganciclovir tablets have not been conducted in adults older than 65 years of age. Clinical studies of valganciclovir tablets 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 tablets are 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 elderly patients are more likely to have decreased renal function, care should be taken in dose selection. In addition, renal function should be monitored and dosage adjustments should be made accordingly [see Dosage and Administration ( 2.5), Warnings and Precautions ( 5.5), Use in Specific Populations ( 8.6), Clinical Pharmacology ( 12.3)]. Dose reduction is recommended when administering valganciclovir tablets to patients with renal impairment [see Dosage and Administration ( 2.5), Warnings and Precautions ( 5.5), Clinical Pharmacology ( 12.3)]. For adult patients on hemodialysis (CrCl less than 10 mL/min) valganciclovir 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 tablets have not been studied in patients with hepatic impairment.

제품 요약:

Valganciclovir tablets USP, 450 mg are pink, oval, biconvex, film-coated tablets, debossed with "J" on one side and "156"  on the other side. Each film-coated tablet contains 496.3 mg of valganciclovir hydrochloride, USP equivalent to 450 mg of valganciclovir. Valganciclovir tablets are supplied as: NDC 50268-787-12    5 tablets per card, 4 cards per carton. Store at 25 o C; excursions permitted between 15 o and 30 o C (59 o and 86 o F). [See USP Controlled Room Temperature.] Dispensed in Unit Dose Material. For Institutional Use Only.

승인 상태:

Abbreviated New Drug Application

제품 특성 요약

VALGANCICLOVIR- VALGANCICLOVIR TABLET, FILM COATED
AVPAK
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HIGHLIGHTS OF PRESCRIBING INFORMATION
VALGANCICLOVIR TABLET, USP
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
VALGANCICLOVIR
TABLETS SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
VALGANCICLOVIR
TABLETS.
VALGANCICLOVIR TABLETS USP, FOR ORAL USE
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, BONE MARROW APLASIA AND APLASTIC ANEMIA HAVE BEEN
REPORTED IN
PATIENTS TREATED WITH VALGANCICLOVIR TABLETS ( 5.1).
• IMPAIRMENT OF FERTILITY: BASED ON ANIMAL DATA, VALGANCICLOVIR
TABLETS MAY CAUSE
TEMPORARY OR PERMANENT INHIBITION OF SPERMATOGENESIS ( 5.2).
• FETAL TOXICITY: BASED ON ANIMAL DATA, VALGANCICLOVIR TABLETS HAVE
THE POTENTIAL TO
CAUSE BIRTH DEFECTS IN HUMANS ( 5.3).
• MUTAGENESIS AND CARCINOGENESIS: BASED ON ANIMAL DATA,
VALGANCICLOVIR TABLETS HAVE
THE POTENTIAL TO CAUSE CANCERS IN HUMANS ( 5.4).
RECENT MAJOR CHANGES
Indications and Usage, Pediatric Patients ( 1.2) 04/2015
Dosage and Administration, Pediatric Patients ( 2.3) 04/2015
INDICATIONS AND USAGE
Valganciclovir tablets, USP are a cytomegalovirus (CMV) nucleoside
analogue 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 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