VALGANCICLOVIR- valganciclovir tablet, film coated
Safecor Health, LLC
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, 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.
RECENT MAJOR CHANGES
Boxed Warning 08/2018
Warnings and Precautions (5.3) 08/2018
INDICATIONS AND USAGE
Valganciclovir tablet is a deoxynucleoside analogue cytomegalovirus (CMV) DNA polymerase inhibitor indicated for:
DOSAGE AND ADMINISTRATION
DOSAGE FORMS AND STRENGTHS
Hypersensitivity to valganciclovir or ganciclovir. (4)
WARNINGS AND PRECAUTIONS
USE IN SPECIFIC POPULATIONS
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
FULL PRESCRIBING INFORMATION: CONTENTS*
WARNING: HEMATOLOGIC TOXICITY, IMPAIRMENT OF FERTILITY, FETAL TOXICITY, MUTAGENESIS AND CARCINOGENESIS
WARNING: HEMATOLOGIC TOXICITY, IMPAIRMENT OF FERTILITY, FETAL TOXICITY, MUTAGENESIS AND CARCINOGENESIS
Treatment of Cytomegalovirus (CMV) Retinitis:
Valganciclovir tablets 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 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 are 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)].
For dosage recommendations in adult patients with renal impairment [see Dosage and Administration (2.5)].
Treatment of CMV Retinitis:
Prevention of CMV Disease:
Prevention of CMV Disease in Pediatric Kidney Transplant Patients: For pediatric kidney transplant patients 4 months to 16 years of age, the recommended once daily mg dose (7 x BSA x CrCL) should start within 10 days of post-transplantation until 200 days post-transplantation.
Prevention of CMV Disease in Pediatric Heart Transplant Patients: For pediatric heart transplant patients 1 month to 16 years of age, the recommended once daily mg dose (7x BSA x CrCl) should start within 10 days of transplantation until 100 days post-transplantation.
The recommended once daily dosage of valganciclovir tablets is based on body surface area (BSA) and creatinine clearance (CrCl) derived from a modified Schwartz formula, and is calculated using the equation below:
Pediatric Dose (mg) = 7 x BSA x CrCl (calculated using a modified Schwartz formula). If the calculated Schwartz creatinine clearance exceeds 150 mL/min/1.73m2, then a maximum value of 150 mL/min/1.73m2 should be used in the equation. The k values used in the modified Schwartz formula are based on pediatric patient age, as shown in Table 1.
|k value||Pediatric Patient Age|
|0.33||Infants less than 1 year of age with low birth weight for gestational age|
|0.45||Infants less than 1 year of age with birth weight appropriate for gestational age|
|0.45||Children aged 1 to less than 2 years|
|0.55||Boys aged 2 to less than 13 yearsGirls aged 2 to less than 16 years|
|0.7||Boys aged 13 to 16 years|
Monitor serum creatinine levels regularly and consider changes in height and body weight and adapt the dose as appropriate during prophylaxis period.
All calculated doses should be rounded to the nearest 10 mg increment for the actual deliverable dose. If the calculated dose exceeds 900 mg, a maximum dose of 900 mg should be administered.
Valganciclovir for oral solution is the preferred formulation since it provides the ability to administer a dose calculated according to the formula above; however, valganciclovir tablets may be used if the calculated doses are within 10% of available tablet strength (450 mg). For example, if the calculated dose is between 405 mg and 495 mg, one 450 mg tablet may be taken. Before prescribing valganciclovir tablets, pediatric patients should be assessed for the ability to swallow tablets.
Serum creatinine levels or estimated creatinine clearance should be monitored regularly during treatment. Dosage recommendations for adult patients with reduced renal function are provided in Table 2. For adult patients on hemodialysis (CrCl less than 10 mL/min), a dose recommendation for valganciclovir tablets cannot be given [see Use in Specific Populations (8.5, 8.6), Clinical Pharmacology (12.3)].
|Valganciclovir 450 mg Tablets|
|CrCl*(mL/min)||Induction Dose||Maintenance/ Prevention Dose|
|≥ 60||900 mg twice daily||900 mg once daily|
|40 to 59||450 mg twice daily||450 mg once daily|
|25 to 39||450 mg once daily||450 mg every 2 days|
|10 to 24||450 mg every 2 days||450 mg twice weekly|
|< 10 (on hemodialysis)||not recommended||not recommended|
For males= (140 – age [years]) x (body weight [kg])
(72) x (serum creatinine [mg/dL])
For females= 0.85 x male value
Dosing in pediatric patients with renal impairment can be done using the recommended equations because CrCl is a component in the calculation [see Dosage and Administration (2.3)].
Caution should be exercised in the handling of valganciclovir tablets USP. Tablets should not be broken or crushed. Because valganciclovir is considered a potential teratogen and carcinogen in humans, caution should be observed in handling broken tablets, [see Warnings and Precautions (5.4, 5.5)].
Avoid direct contact with broken or crushed tablets with skin or mucous membranes. If such contact occurs, wash thoroughly with soap and water, and rinse eyes thoroughly with plain water.
Handle and dispose valganciclovir tablets according to guidelines for antineoplastic drugs because ganciclovir shares some of the properties of antitumor agents (i.e., carcinogenicity and mutagenicity)2 .
Valganciclovir tablets, 450 mg are pink colored, oval shaped, film coated tablets debossed with ‘RDY’ on one side and ‘762’ on other side.
Valganciclovir 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)].
Severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, and bone marrow failure including aplastic anemia have been reported in patients treated with valganciclovir or ganciclovir. Valganciclovir should be avoided if the absolute neutrophil count is less than 500 cells/μL, the platelet count is less than 25,000/μL, or the hemoglobin is less than 8 g/dL. Valganciclovir should also be used with caution in patients with pre-existing cytopenias and in patients receiving myelosuppressive drugs or irradiation. Cytopenia may occur at any time during treatment and may worsen with continued dosing. Cell counts usually begin to recover within 3 to 7 days after discontinuing drug. In patients with severe leukopenia, neutropenia, anemia and/or thrombocytopenia, treatment with hematopoietic growth factors may be considered.
Due to the frequency of neutropenia, anemia, and thrombocytopenia in patients receiving valganciclovir [see Adverse Reactions (6.1)], complete blood counts with differential and platelet counts should be performed frequently, especially in infants, in patients with renal impairment and in patients in whom ganciclovir or other nucleoside analogues have previously resulted in leukopenia, or in whom neutrophil counts are less than 1000 cells/μL at the beginning of treatment. Increased monitoring for cytopenias may be warranted if therapy with oral ganciclovir is changed to valganciclovir , because of increased plasma concentrations of ganciclovir after valganciclovir administration [see Clinical Pharmacology (12.3)].
Acute renal failure may occur in:
Based on animal data and limited human data, with ganciclovir, valganciclovir at the recommended human doses may cause temporary or permanent inhibition of spermatogenesis in males, and may cause suppression of fertility in females. Advise patients that fertility may be impaired with use of valganciclovir [see Use in Specific Populations (8.1, 8.3), Nonclinical Toxicology (13.1)].
Ganciclovir may cause fetal toxicity when administered to pregnant women based on findings in animal studies. When given to pregnant rabbits at dosages resulting in 2 times the human exposure (based on AUC), ganciclovir caused malformations in multiple organs of the fetuses. Maternal and fetal toxicity were also observed in pregnant mice and rabbits. Therefore, valganciclovir has the potential to cause birth defects. Pregnancy should be avoided in female patients taking valganciclovir and in females with male partners taking valganciclovir. Females of reproductive potential should be advised to use effective contraception during treatment and for at least 30 days following treatment with valganciclovir because of the potential risk to the fetus. Similarly, males should be advised to use condoms during and for at least 90 days following treatment with valganciclovir [see Dosage and Administration (2.6), Use in Specific Populations (8.1, 8.3), Nonclinical Toxicology (13.1)].
In vivo drug-drug interaction studies were not conducted with valganciclovir. However, because valganciclovir is rapidly and extensively converted to ganciclovir, drug-drug interactions associated with ganciclovir will be expected for valganciclovir. Drug-drug interaction studies with ganciclovir were conducted in patients with normal renal function. Following concomitant administration of valganciclovir and other renally excreted drugs, patients with impaired renal function may have increased concentrations of ganciclovir and the coadministered drug. Therefore, these patients should be closely monitored for toxicity of ganciclovir and the coadministered drug.
Established and other potentially significant drug interactions conducted with ganciclovir are listed in Table 9.
|Name of the Concomitant Drug||Change in the Concentration of Ganciclovir or Concomitant Drug||Clinical Comment|
|Imipenem-cilastatin||Unknown||Coadministration with imipenem-cilastatin is not recommended because generalized seizures have been reported in patients who received ganciclovir and imipenem-cilastatin.|
|Cyclosporine or amphotericin B||Unknown||Monitor renal function when valganciclovir is coadministered with cyclosporine or amphotericin B because of potential increase in serum creatinine [see Warnings and Precautions (5.2)].|
|Mycophenolate mofetil (MMF)||↔ Ganciclovir (in patients with normal renal function)|
↔ MMF (in patients with normal renal function)
|Based on increased risk, patients should be monitored for hematological and renal toxicity.|
|Other drugs associated with myelosuppresion or nephrotoxicity (e.g., adriamycin, dapsone, doxorubicin, flucytosine, hydroxyurea, pentamidine, tacrolimus, trimethoprim/ sulfamethoxazole, vinblastine, vincristine, and zidovudine)||Unknown||Because of potential for higher toxicity, coadministration with valganciclovir should be considered only if the potential benefits are judged to outweigh the risks.|
|Patients should be closely monitored for didanosine toxicity (e.g., pancreatitis)|
|Probenecid||↑ Ganciclovir||Valganciclovir dose may need to be reduced. Monitor for evidence of ganciclovir toxicity.|
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)].
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.
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.
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)].
Females of reproductive potential should undergo pregnancy testing before initiation of valganciclovir [see Use in Specific Populations (8.1)].
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)].
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)].
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 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 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 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 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 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)]. Study 3 was a pharmacokinetic and safety study of valganciclovir 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 is not indicated for prophylaxis in this age group.
The safety and efficacy of valganciclovir 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 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 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 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.
Studies of valganciclovir 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 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 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)].
For adult patients on hemodialysis (CrCl less than10 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 and ganciclovir capsules complete product information section on DOSAGE AND ADMINISTRATION: Renal Impairment [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3)].
Experience with Valganciclovir Tablets: An overdose of valganciclovir could also possibly result in increased renal toxicity [see Dosage and Administration (2.5), Use in Specific Populations (8.6)]. Because ganciclovir is dialyzable, dialysis may be useful in reducing serum concentrations in patients who have received an overdose of valganciclovir [see Clinical Pharmacology (12.3)].
Reports of adverse reactions after overdoses with valganciclovir, some with fatal outcomes, have been received from clinical trials and during postmarketing experience. The majority of patients experienced one or more of the following adverse events:
Hematological toxicity: myelosuppression including pancytopenia, bone marrow failure, leukopenia, neutropenia, granulocytopenia
Hepatotoxicity: hepatitis, liver function disorder
Renal toxicity: worsening of hematuria in a patient with pre-existing renal impairment, acute kidney injury, elevated creatinine
Gastrointestinal toxicity: abdominal pain, diarrhea, vomiting
Neurotoxicity: generalized tremor, seizure
Valganciclovir tablets USP contains valganciclovir hydrochloride USP, a hydrochloride salt of the L-valyl ester of ganciclovir that exists as a mixture of two diastereomers. Ganciclovir is a synthetic guanine derivative active against CMV.
Valganciclovir hydrochloride USP is available as a 450 mg tablet for oral administration. Each tablet contains 496.3 mg of valganciclovir hydrochloride USP (corresponding to 450 mg of valganciclovir), and the inactive ingredients crospovidone, magnesium stearate, microcrystalline cellulose and povidone. The film-coat applied to the tablets contains hypromellose, iron oxide red, polyethylene glycol, polysorbate and titanium dioxide.
Valganciclovir hydrochloride USP is a white to almost white powder with a molecular formula of C14H22N6O5·HCl and a molecular weight of 390.71. The chemical name for valganciclovir hydrochloride USP is L-Valine, 2[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]-3-hydroxypropyl ester, monohydrochloride. Valganciclovir hydrochloride USP is a polar hydrophilic compound with a saturation solubility of 6029 mg/mL in water at 25°C and an n-octanol/water partition coefficient of 0.00701 at pH 5.1. The pKa for valganciclovir hydrochloride USP is 7.2.
The chemical structure of valganciclovir hydrochloride USP is:
All doses in this insert are specified in terms of valganciclovir.
Long-term carcinogenicity studies have not been conducted with valganciclovir . However, upon oral administration, valganciclovir is rapidly and extensively converted to ganciclovir. Therefore, like ganciclovir, valganciclovir is a potential carcinogen.
Ganciclovir was carcinogenic in the mouse at oral doses that produced exposures approximately 0.1x and 1.4x, respectively, the mean drug exposure in humans following the recommended intravenous dose of 5 mg/kg, based on area under the plasma concentration curve (AUC) comparisons. At the higher dose, there was a significant increase in the incidence of tumors of the preputial gland in males, forestomach (nonglandular mucosa) in males and females, and reproductive tissues (ovaries, uterus, mammary gland, clitoral gland and vagina) and liver in females. At the lower dose, a slightly increased incidence of tumors was noted in the preputial and harderian glands in males, forestomach in males and females, and liver in females. Ganciclovir should be considered a potential carcinogen in humans.
Valganciclovir increases mutations in mouse lymphoma cells. In the mouse micronucleus assay, valganciclovir was clastogenic. Valganciclovir was not mutagenic in the Ames Salmonella assay. Ganciclovir increased mutations in mouse lymphoma cells and DNA damage in human lymphocytes in vitro. In the mouse micronucleus assay, ganciclovir was clastogenic. Ganciclovir was not mutagenic in the Ames Salmonella assay.
Valganciclovir is converted to ganciclovir and therefore is expected to have similar reproductive toxicity effects as ganciclovir [see Warnings and Precautions (5.3)]. Ganciclovir caused decreased mating behavior, decreased fertility, and an increased incidence of embryolethality in female mice following intravenous doses that produced an exposure approximately 1.7x the mean drug exposure in humans following the dose of 5 mg per kg, based on AUC comparisons. Ganciclovir caused decreased fertility in male mice and hypospermatogenesis in mice and dogs following daily oral or intravenous administration. Systemic drug exposure (AUC) at the lowest dose showing toxicity in each species ranged from 0.03 to 0.1x the AUC of the recommended human intravenous dose. Valganciclovir caused similar effects on spermatogenesis in mice, rats, and dogs. These effects were reversible at lower doses but irreversible at higher doses. It is considered likely that ganciclovir (and valganciclovir) could cause temporary or permanent inhibition of human spermatogenesis.
1. Brion, L.P., Fleischman, A.R., McCarton, C., Schwartz, G.J. A simple estimate of glomerular filtration rate in low birth weight infants during the first year of life: noninvasive assessment of body composition and growth. J of Ped 1986: 109(4): 698-707.
2. NIOSH . NIOSH list of antineoplastic and other hazardous drugs in healthcare settings. By Connor TH, MacKenzie B.A., DeBord D.G., Trout D.B., O’Callaghan J.P., Cincinnati, O.H.: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2014-138 (Supersedes 2012-150).
Valganciclovir Tablets USP, 450 mg are pink colored, oval shaped, film coated tablets debossed with ‘RDY’ on one side and ‘762’ on other side, and are supplied in unit dose package of 100’s (10 x 10).
Unit Dose Blister (NDC 48433-124-01)
Box of 100 Unit Dose (NDC 48433-124-10)
Store at 20°C-25°C (68°F-77°F) [See USP Controlled Room Temperature].
Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).
Serious Adverse Reactions
Inform patients that valganciclovir may cause granulocytopenia (neutropenia), anemia, thrombocytopenia and elevated creatinine levels and that dose modification or discontinuation of dosing may be required. Complete blood counts, platelet counts, and creatinine levels should be monitored frequently during treatment [see Warnings and Precautions (5.1)].
Pregnancy and Contraception
Inform females of reproductive potential that valganciclovir causes birth defects in animals. Advise them to use effective contraception during and for at least 30 days following treatment with valganciclovir. Similarly, advise males to use condoms during and for at least 90 days following treatment with valganciclovir [see Use in Specific Populations (8.1, 8.3)].
Advise patients that valganciclovir is considered a potential carcinogen [see Nonclinical Toxicity (13.1)].
Advise mothers not to breast-feed if they are receiving valganciclovir because of the potential for hematologic toxicity and cancer in nursing infants, and because HIV can be passed to the baby in breast milk [see Use in Specific Populations (8.2)].
Impairment of Cognitive Ability
Inform patients that tasks requiring alertness may be affected including the patient’s ability to drive and operate machinery as seizures, dizziness, and/or confusion have been reported with the use of valganciclovir [see Adverse Reactions (6.1)].
Use in Patients with CMV Retinitis
Inform patients that valganciclovir is not a cure for CMV retinitis, and they may continue to experience progression of retinitis during or following treatment. Advise patients to have ophthalmologic follow-up examinations at a minimum of every 4 to 6 weeks while being treated with valganciclovir. Some patients will require more frequent follow-up.
Inform adult patients that they should use valganciclovir tablets, not valganciclovir for oral solution [see Dosage and Administration (2.1)].
Inform patients to take valganciclovir with food to maximize bioavailability.
For more information, call 1-888-375-3784.
Valganciclovir Tablets USP
(val'' gan sye' kloe vir)
What is the most important information I should know about valganciclovir? Valganciclovir can cause serious side effects, including:
• Blood and bone marrow problems. Valganciclovir can affect the bone marrow lowering the amount of your white blood cells, red blood cells, and platelets and may cause serious and life-threatening problems.
• Kidney failure. Kidney failure may happen in people who are elderly, people who take valganciclovir with certain other medicines, or people who are not adequately hydrated.
• Fertility problems. Valganciclovir may lower sperm count in males and cause fertility problems. Valganciclovir may also cause fertility problems in women. Talk to your healthcare provider if this is a concern for you.
• Birth defects. Valganciclovir causes birth defects in animals. It is not known if valganciclovir causes birth defects in people. If you are a female who can become pregnant, you should use effective birth control during treatment with valganciclovir and for at least 30 days after treatment. If you are pregnant, talk to your healthcare provider before starting treatment with valganciclovir. If you are a female who can become pregnant, you should have a pregnancy test done before starting valganciclovir.
o Tell your healthcare provider right away if you become pregnant during treatment with valganciclovir.
o Males should use condoms during treatment with valganciclovir, and for at least 90 days after treatment, if their female sexual partner can become pregnant. Talk to your healthcare provider if you have questions about birth control.
• Cancer. Valganciclovir causes cancer in animals and may potentially cause cancer in people.
Your healthcare provider will do regular blood test during treatment with valganciclovir to check you for side effects. Your healthcare provider may change your dose or stop treatment with valganciclovir if you have serious side effects.
What is valganciclovir?
Valganciclovir is a prescription antiviral medicine.
In adults, valganciclovir tablets are used:
Valganciclovir does not cure CMV retinitis. You may still get retinitis or worsening of retinitis during or after treatment with valganciclovir. It is important to stay under a healthcare provider’s care and have your eyes checked at least every 4 to 6 weeks during treatment with valganciclovir.
In children, valganciclovir tablets or oral solution are used:
Do not take valganciclovir if you have had a serious allergic reaction to valganciclovir, ganciclovir or any of the ingredients of valganciclovir. See the end of this leaflet for a list of the ingredients in valganciclovir.
Before you take valganciclovir, tell your healthcare provider about all of your medical conditions, including if you:
• have low blood cell counts
• have kidney problems
• are receiving hemodialysis
• are receiving radiation treatment
• are pregnant or plan to become pregnant. See “What is the most important information I should know about valganciclovir?”
• are breastfeeding or plan to breastfeed. It is not known if valganciclovir passes into your milk. You should not breastfeed if you take valganciclovir.
• You should not breastfeed if you have Human Immunodeficiency Virus (HIV-1) because of the risk of passing HIV-1 to your baby.
• Talk to your healthcare provider about the best way to feed your baby.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements.
Valganciclovir and other medicines may affect each other and cause serious side effects. Keep a list of your medicines to show your healthcare provider and pharmacist.
How should I take valganciclovir?
What should I avoid during treatment with valganciclovir?
Valganciclovir can cause seizures, dizziness, and confusion. You should not drive a car or operate machinery until you know how valganciclovir affects you.
What are the possible side effects of valganciclovir?
Valganciclovir may cause serious side effects, including: See “What is the most important information I should know about valganciclovir?”
The most common side effects of valganciclovir in adults include:
|• diarrhea||• low white cell, red cell and platelet cell counts in blood tests|
|• fever||• headache|
|• fatigue||• sleeplessness|
|• nausea||• urinary tract infection|
|• shaky movement (tremors)||• vomiting|
The most common side effects of in children include:
|• diarrhea||• vomiting|
|• fever||• low white blood cell counts in blood test|
|• upper respiratory tract infection||• headache|
|• urinary tract infection|
These are not all the possible side effects of valganciclovir
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store valganciclovir tablets?
Keep valganciclovir tablets and all medicines out of the reach of children.
General information about the safe and effective use of valganciclovir
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use valganciclovir for a condition for which it was not prescribed. Do not give valganciclovir to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about valganciclovir that is written for health professionals.
What are the ingredients in valganciclovir tablets?
Active Ingredient: valganciclovir hydrochloride
Inactive Ingredients for Tablets: crospovidone, magnesium stearate, microcrystalline cellulose and povidone. The film-coating applied to the tablets contains hypromellose, iron oxide red, polyethylene glycol, polysorbate and titanium dioxide.
This Patient Information has been approved by the U.S. Food and Drug Administration.
For more information, call 1-888-375-3784.
Safecor Health, LLC
4060 Business Park Drive
Columbus, OH 43204
Dr. Reddy’s Laboratories Limited
Bachupally – 500 090 INDIA
Revised: 03/2019 PN5645
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PKG BY: Safecor Health
valganciclovir tablet, film coated
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