Valganciclovir 450 mg Tablet, Film Coated
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Cytomegalovirus Nucleoside Analog DNA Polymerase Inhibitor class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
Valganciclovir is used to treat cytomegalovirus (CMV) retinitis (eye infection that can cause blindness) in people who have acquired immunodeficiency syndrome (AIDS). Valganciclovir is also used to prevent cytomegalovirus (CMV) disease in people who have received a heart, kidney, or kidney-pancreas transplant and who have a chance of getting CMV disease. Valganciclovir is in a class of medications called antivirals. It works by preventing the spread of CMV disease or slowing the growth of CMV.
Read the full MedlinePlus article ↗- Valganciclovir is used for two main purposes. First, it treats a serious viral eye infection called CMV retinitis in adults living with AIDS. Second, it prevents a virus called CMV...
- You really do need to take valganciclovir with food — it's not just a suggestion. Eating a meal when you take it increases the amount of active drug your body absorbs by a meaningf...
- Do I have to take this with food, or can I take it on an empty stomach?
- The most common ones are diarrhea, nausea, vomiting, fever, headache, and feeling tired. Shakiness (tremor) and trouble sleeping also happen fairly often. The ones your doctor real...
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Valganciclovir — tap one for details:
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
💊 What it looks like
Where does this data come from?
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
-
UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
-
UNII 68401960MK
Crospovidone is a synthetic polymer made from polyvinylpyrrolidone. It acts as a disintegrant, helping tablets break apart quickly in the stomach so the medicine dissolves and absorbs into the body.
-
UNII 1K09F3G675
Ferric oxide red is an inorganic iron compound used as a colorant in medicines. It gives tablets, capsules, or other dosage forms a red or reddish tint for identification and appearance.
-
UNII 3NXW29V3WO
Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
-
UNII 3WJQ0SDW1A
Polyethylene glycol is a synthetic liquid or solid polymer used in medicines as a solvent, lubricant, and humectant. It helps dissolve active ingredients, reduces friction during manufacturing, and retains moisture in the final product.
-
UNII 6OZP39ZG8H
Polysorbate 80 is a synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together in medications and improves how the product disperses in the body.
-
UNII FZ989GH94E
Povidone is a synthetic polymer made from a plastic-like material. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in your stomach so the medicine can be absorbed.
-
UNII 4ELV7Z65AP
Stearic acid is a fatty acid derived from plant or animal sources. It acts as a binder and lubricant in tablets and capsules, helping them hold together and flow smoothly during manufacturing.
-
UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
9 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $2.015 | $40.30 / 20 tablet |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $3.50 | $69.99 / 20 tablet |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Valganciclovir 450 mg 00904-6796-04 | Major | 1 tablet | $2.015 | AB | Availability likely | — |
| Valganciclovir 450 mg 27241-0158-60 | Ajanta | 60 tablets | $2.015 | AB | Availability likely | — |
| Valganciclovir 450 mgthis 50268-0787-12 | AvPAK | 1 tablet | $2.015 | AB | Availability likely | — |
| Valganciclovir 450 mg 64380-0153-01 | Strides | 60 tablets | $2.015 | AB | Availability likely | — |
| Valganciclovir 450 mg 64380-0161-01 | Strides | 60 tablets | $2.015 | AB | Availability likely | — |
| Valganciclovir 450 mg 68084-0965-25 | American | 1 tablet | $2.015 | AB | Availability likely | — |
| Valganciclovir Hydrochloride 450 mg 72603-0750-01 | NorthStar | 60 tablets | $2.015 | AB | Availability likely | — |
| Valganciclovir 450 mg 31722-0832-31 | Camber | 10 tablets | — | AB | FDA listed | — |
| Valganciclovir 450 mg 42291-0973-60 | AvKARE | 60 tablets | — | AB | FDA listed | — |
| valganciclovir hydrochloride 450 mg 43598-0356-30 | Dr. | 30 tablets | — | AB | FDA listed | — |
| Valganciclovir 450 mg 55111-0762-05 | Dr. | 500 tablets | — | AB | FDA listed | — |
| Valganciclovir 450 mg 60429-0846-60 | Golden | 60 tablets | — | AB | Discontinued | — |
| Valcyte 450 mg 61269-0480-60 | H2-Pharma, | 60 tablets | — | AB | FDA listed | — |
| Valganciclovir Hydrochloride 450 mg 65862-0753-01 | Aurobindo | 100 tablets | — | AB | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
Where does this data come from?
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 50268-0787-12 You're viewing this | 20 BLISTER PACK in 1 BOX, UNIT-DOSE (50268-787-12) / 1 TABLET, FILM COATED in 1 BLISTER PACK (50268-787-11) | 2016-07-27 | Active |
📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
BOXED WARNING WARNING: HEMATOLOGIC TOXICITY, IMPAIRMENT OF FERTILITY, FETAL TOXICITY, MUTAGENESIS AND CARCINOGENESIS • Hematologic Toxicity: Severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, bone marrow aplasia and aplastic anemia have been reported in patients treated with valganciclovir tablets [see Warnings and Precautions ( 5.1 )]. • Impairment of Fertility: Based on animal data, valganciclovir tablets may cause temporary or permanent inhibition of spermatogenesis [see Warnings and Precautions ( 5.2 )]. • Fetal Toxicity: Based on animal data, valganciclovir tablets have the potential to cause birth defects in humans [see Warnings and Precautions ( 5.3 )]. • Mutagenesis and Carcinogenesis: Based on animal data, valganciclovir tablets have the potential to cause cancers in humans [see Warnings and Precautions ( 5.4 )].
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 ).
🎯 Indications and Usage ▾
1 INDICATIONS & 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.
1.1Adult Patients 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 )].
1.2Pediatric Patients 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.
⏱️ Dosage and Administration ▾
2 DOSAGE & 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 transplantation until 100 days post-transplantation Prevention of CMV disease in kidney transplant patients 900 mg (two 450 mg tablets) once a day within 10 days of transplantation until 200 days post-transplantation Pediatric Dosage (2.3) Prevention of CMV disease in heart transplant patients 4 months to 16 years of age Dose once a day within 10 days of transplantation until 100 days post-transplantation according to dosage algorithm (note the calculation of creatinine clearance using a modified Schwartz formula in children) • Valganciclovir tablets should be taken with food ( 2.1 , 12.3 ). • Valganciclovir tablets should not be broken or crushed ( 2.6 ). • Adult patients should use valganciclovir tablets, not valganciclovir for oral solution ( 2.1 ). • Adults with renal impairment: Adjust dose based on creatinine clearance.
For adult patients receiving hemodialysis a dose recommendation cannot be given ( 2.5 , 8.6, 12.3 ).
2.1General Dosing Information • Adult patients should use valganciclovir tablets, not valganciclovir for oral solution. • Valganciclovir tablets should be taken with food [see Clinical Pharmacology ( 12.3 )].
2.2Recommended Dosage in Adult Patients with Normal Renal Function For dosage recommendations in adult patients with renal impairment [see Dosage and Administration ( 2.5 )]. Treatment of CMV Retinitis: • Induction: The recommended dosage is 900 mg (two 450 mg tablets) taken orally twice a day for 21 days. • Maintenance: Following induction treatment, or in adult patients with inactive CMV retinitis, the recommended dosage is 900 mg (two 450 mg tablets) taken orally once a day. Prevention of CMV Disease: • For adult patients who have received a heart or kidney-pancreas transplant, the recommended dosage is 900 mg (two 450 mg tablets) taken orally once a day starting within 10 days of transplantation until 100 days post-transplantation. • For adult patients who have received a kidney transplant, the recommended dosage is 900 mg (two 450 mg tablets) taken orally once a day starting within 10 days of transplantation until 200 days post-transplantation.
2.3Recommended Dosage in Pediatric Patients Prevention of CMV Disease in Pediatric Heart Transplant Patients : For pediatric heart transplant patients 4 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 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/1.73m 2 , then a maximum value of 150 mL/min/1.73m 2 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. Mosteller BSA (m 2 ) = √ Height (cm) x weight (kg) 3600 Schwartz Creatinine Clearance (mL/min/1.73m 2 ) = K x Height (cm) Serum Creatinine (mg/dL) Table 1. k Values According to Pediatric Patient Age* 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 years Girls aged 2 to less than 16 years
0.7Boys aged 13 to 16 years * The k values provided are based on the Jaffe method of measuring serum creatinine, and may require correction when enzymatic methods are used 1 Monitor serum…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS & STRENGTHS 450 mg, pink, oval, biconvex, film-coated tablets, debossed with "J" on one side and "156" on the other side. • Tablets: 450 mg ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS 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 )]. Hypersensitivity to valganciclovir or ganciclovir ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Hematologic toxicity: Severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, bone marrow depression, and aplastic anemia have occurred with the use of valganciclovir tablets or ganciclovir. Avoid valganciclovir tablets use if absolute neutrophil count is less than 500 cells/µL, platelet count is less than 25,000/µL, or hemoglobin is less than 8 g/dL. Use with caution in pre-existing cytopenias and when receiving myelosuppressive drugs or irradiation.
Monitor with frequent testing of platelet and complete blood counts ( 5.1 ). • Impairment of fertility: Based on animal studies, valganciclovir tablets may cause temporary or permanent inhibition of spermatogenesis ( 5.2 ). • Fetal toxicity: Based on animal studies, valganciclovir tablets may cause fetal harm. Females of reproductive potential should use effective contraception during and following treatment and males should practice barrier contraception during and following treatment (5.3 ). • Mutagenicity and carcinogenicity: Based on animal studies, valganciclovir tablets are potentially mutagenic and carcinogenic ( 5.4 ). • Acute renal failure: Acute renal failure may occur in elderly patients (with or without reduced renal function), patients who receive concomitant nephrotoxic drugs, or inadequately hydrated patients.
Use with caution in elderly patients or those taking nephrotoxic drugs, reduce dosage in patients with renal impairment, and monitor renal function ( 2.5 , 5.5 , 8.5 , 8.6 , 12.3 ). 5.1Hematologic Toxicity Severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, bone marrow aplasia, and aplastic anemia have been reported in patients treated with valganciclovir tablets or ganciclovir. Valganciclovir tablets 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 tablets should also be used with caution in patients with pre-existing cytopenias, or who have received or who are 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.
Due to the frequency of neutropenia, anemia, and thrombocytopenia in patients receiving valganciclovir tablets [see Adverse Reactions ( 6.1 )], complete blood counts with differential and platelet counts should be performed frequently, especially 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 tablets, because of increased plasma concentrations of ganciclovir after valganciclovir tablets administration [see Clinical Pharmacology ( 12.3 )].
5.2Impairment of Fertility Based on animal data with ganciclovir, valganciclovir tablets 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 tablets [see Use in Specific Populations ( 8.1, 8.3 ), Nonclinical Toxicology ( 13.1 )].
5.3Fetal Toxicity 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 tablets and in females with male partners taking valganciclovir tablets. Females of reproductive potential shou…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following serious adverse events are discussed in greater detail in other sections of the labeling: • Hematologic toxicity [see Boxed Warning, Warnings and Precautions ( 5.1 )]. • Acute renal failure [see Warnings and Precautions ( 5.5 )]. The most common adverse events and laboratory abnormalities reported in at least one indication by greater than or equal to 20% of adult patients treated with valganciclovir tablets are diarrhea, pyrexia, nausea, tremor, neutropenia, anemia, graft rejection, thrombocytopenia, and vomiting.
The most common reported adverse events and laboratory abnormalities reported in greater than or equal to 20% of pediatric solid organ transplant recipients treated with valganciclovir tablets are diarrhea, pyrexia, hypertension, upper respiratory tract infection, urinary tract infection, vomiting, neutropenia, leukopenia, and head ache. • Adult patients: Most common adverse events and laboratory abnormalities (reported in at least one indication by greater than or equal to 20% of patients) are diarrhea, pyrexia, nausea, tremor, neutropenia, anemia, graft rejection, thrombocytopenia, and vomiting ( 6.1 ). • Pediatric patients: Most common adverse events and laboratory abnormalities (reported in greater than or equal to 20% of pediatric solid organ transplant recipients) are diarrhea, pyrexia, hypertension, upper respiratory tract infection, urinary tract infection, vomiting, neutropenia, leukopenia, and headache ( 6.1 ).
To report SUSPECTED ADVERSE REACTIONS, contact AvKARE, Inc. at 1-855-361-3993 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse event rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect rates observed in practice. Valganciclovir, a prodrug of ganciclovir, is rapidly converted to ganciclovir after oral administration. Adverse events known to be associated with ganciclovir usage can therefore be expected to occur with valganciclovir tablets.
Adverse Events in Adults: Treatment of CMV Retinitis in AIDS Patients : In a clinical study for the treatment of CMV retinitis in HIV-infected patients, the adverse events reported by patients receiving valganciclovir tablets (n=79) or intravenous ganciclovir (n=79) for 28 days of randomized therapy (21 days induction dose and 7 days maintenance dose), respectively, included diarrhea (16%, 10%), nausea (8%, 14%), headache (9%, 5%), and catheter-related infections (3%, 11%). The incidence of adverse events was similar between the group who received valganciclovir tablets and the group who received intravenous ganciclovir, with the exception of catheter-related infections, which occurred with greater frequency in patients randomized to receive intravenous ganciclovir.
The frequencies of neutropenia (ANC less than 500/μL) were 11% for patients receiving valganciclovir tablets compared with 13% for patients receiving intravenous ganciclovir. Anemia (Hgb less than 8 g/dL) occurred in 8% of patients in each group. Other laboratory abnormalities occurred with similar frequencies in the two groups.
Adverse events and abnormal laboratory values data are available for 370 patients who received maintenance therapy with valganciclovir tablets 900 mg once daily in two open-label clinical trials. Approximately 252 (68%) of these patients received valganciclovir tablets for more than nine months (maximum duration was 36 months). Table 3 and Table 4 show the pooled adverse event data and abnormal laboratory values from these patients.
Table 3 Pooled Selected Adverse Events Reported in greater than or equal to 5% of Patients who Received Valganciclovir Tablets Maintenance Therapy for CMV Retinitis Patients with CMV Retinitis Adverse Events According to Body System Valganciclovir Tablets (N=370) % Gastrointestinal system Diarrhea 41 Nausea 30 Vomiti…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS 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 tablets. Established and other potentially significant drug interactions conducted with ganciclovir are listed in Table 9.
Table 9 Established and Other Potentially Significant Drug Interactions with Ganciclovir Name of the Concomitant Drug Change in the Concentration of Ganciclovir or Concomitant Drug Clinical Comment Zidovudine ↓ Ganciclovir ↑ Zidovudine Zidovudine and valganciclovir tablets each have the potential to cause neutropenia and anemia Probenicid ↑ Ganciclovir Patients taking probenicid and valganciclovir tablets should be monitored for evidence of ganciclovir toxicity Mycophenolate Mofetil (MMF) ↔ Ganciclovir (in patients with normal renal function) ↔ MMF (in patients with normal renal function) Patients with renal impairment should be monitored carefully as levels of MMF metabolites and ganciclovir may increase Didanosine ↓ Ganciclovir ↑ Didanosine Patients should be closely monitored for didanosine toxicity • Zidovudine: Potential to cause neutropenia and anemia.
Monitor with frequent tests of white blood cell counts with differential and hemoglobin levels (7 ). • Probenecid: May increase ganciclovir levels. Monitor for evidence of ganciclovir toxicity (7 ). • Mycophenolate mofetil (MMF): May increase ganciclovir concentrations and levels of MMF metabolites in patients with renal impairment. Monitor for ganciclovir and MMF toxicity ( 7 ). • Didanosine: May increase didanosine concentrations.
Monitor for didanosine toxicity ( 7 ).
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS • Lactation: Breastfeeding is not recommended with use of valganciclovir tablets (8.2 ) See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling 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.
8.1Pregnancy 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.
8.2 Lacta…
🤰 Pregnancy ▾
8.1Pregnancy 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.
🧒 Pediatric Use ▾
8.4Pediatric Use 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.
🧓 Geriatric Use ▾
8.5Geriatric Use 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 )].
🆘 Overdosage ▾
10 OVERDOSAGE Experience With Valganciclovir Tablets: One adult developed fatal bone marrow depression (medullary aplasia) after several days of dosing that was at least 10-fold greater than recommended for the patient’s estimated degree of renal impairment. An overdose of valganciclovir tablets 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 tablets [see Clinical Pharmacology ( 12.3 )].
Adequate hydration should be maintained. The use of hematopoietic growth factors should be considered [see Clinical Pharmacology ( 12.3 )]. Experience with Intravenous Ganciclovir: Reports of overdoses with intravenous ganciclovir 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: pancytopenia, bone marrow depression, medullary aplasia, leukopenia, neutropenia, granulocytopenia Hepatotoxicity: hepatitis, liver function disorder Renal toxicity: worsening of hematuria in a patient with pre-existing renal impairment, acute renal failure, elevated creatinine Gastrointestinal toxicity: abdominal pain, diarrhea, vomiting Neurotoxicity: generalized tremor, convulsion
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Valganciclovir is an antiviral drug [see Microbiology ( 12.4 )].
12.3Pharmacokinetics Because the major elimination pathway for ganciclovir is renal, dosage reductions according to creatinine clearance are required for valganciclovir tablets [see Dosage and Administration ( 2.5 )]. Pharmacokinetics in Adults: The pharmacokinetics of valganciclovir and ganciclovir after administration of valganciclovir tablets have been evaluated in HIV- and CMV-seropositive patients, patients with AIDS and CMV retinitis, and in solid organ transplant patients. The ganciclovir pharmacokinetic parameters following administration of 900 mg valganciclovir tablets and 5 mg per kg intravenous ganciclovir and 1000 mg three times daily oral ganciclovir in HIV-positive/CMV-positive patients are summarized in Table 10 .
Table 10 Mean Ganciclovir Pharmacokinetic* Measures in Healthy Volunteers and HIV-positive/CMV-positive Adults at Maintenance Dosage Formulation Valganciclovir Tablets Intravenous Ganciclovir Ganciclovir Capsules Dosage 900 mg once daily with food 5 mg/kg once daily 1000 mg three times daily with food AUC 0-24h (mcg · h/mL) 29.1 ± 9.7 (3 studies, n=57) 26.5 ± 5.9 (4 studies, n=68) Range of means 12.3 to 19.2 (6 studies, n=94) C max (mcg/mL) 5.61 ± 1.52 (3 studies, n=58) 9.46 ± 2.02 (4 studies, n=68) Range of means 0.955 to 1.40 (6 studies, n=94) Absolute oral bioavailability (%) 59.4 ± 6.1 (2 studies, n=32) Not Applicable Range of means 6.22 ± 1.29 to 8.53 ± 1.53 (2 studies, n=32) Elimination half-life (hr) 4.08 ± 0.76 (4 studies, n=73) 3.81 ± 0.71 (4 studies, n=69) Range of means 3.86 to 5.03 (4 studies, n=61) Renal clearance (mL/min/kg) 3.21 ± 0.75 (1 study, n=20) 2.99 ± 0.67 (1 study, n=16) Range of means 2.67 to 3.98 (3 studies, n=30) *Data were obtained from single and multiple dose studies in healthy volunteers, HIV-positive patients, and HIV-positive/CMV-positive patients with and without retinitis.
Patients with CMV retinitis tended to have higher ganciclovir plasma concentrations than patients without CMV retinitis. The area under the plasma concentration-time curve (AUC) of ganciclovir administered as valganciclovir tablets (900 mg once daily) is comparable to the AUC of ganciclovir after administration of intravenous ganciclovir (5 mg per kg once daily). The C max of ganciclovir following valganciclovir tablets administration is 40% lower than the C max following intravenous ganciclovir administration.
During maintenance dosing, ganciclovir AUC 0 to 24h and C max following oral ganciclovir administration (1000 mg three times daily) are lower relative to valganciclovir tablets and intravenous ganciclovir. The ganciclovir C min following intravenous ganciclovir and valganciclovir tablets administration are less than the ganciclovir C min following oral ganciclovir administration. The clinical significance of the differences in ganciclovir pharmacokinetics after administration of valganciclovir tablets, ganciclovir capsules, and intravenous ganciclovir is unknown.
Figure 1 Ganciclovir Plasma Concentration Time Profiles in HIV-positive/CMV-positive Patients* *Plasma concentration-time profiles for ganciclovir (GCV) from valganciclovir (VGCV) and intravenous ganciclovir were obtained from a multiple dose study (n=21 and n=18, respectively) in HIV-positive/CMV-positive patients with CMV retinitis. The plasma concentration-time profile for oral ganciclovir was obtained from a multiple dose study (n=24) in HIV-positive/CMV-positive patients without CMV retinitis. In solid organ transplant recipients, the mean systemic exposure to ganciclovir was 1.7x higher following administration of 900 mg valganciclovir tablets once daily versus 1000 mg ganciclovir capsules three times daily, when both drugs were administered according to their renal function dosing algorithms.
The systemic ganciclovir exposures attained were comparable across kidney, heart and liver transplant recipients based on…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Valganciclovir is an antiviral drug [see Microbiology ( 12.4 )].
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING 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.
📋 Description ▾
11 DESCRIPTION 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 tablets, USP are available as a 450 mg tablet for oral administration.
Each film coated tablet contains 496.3 mg of valganciclovir hydrochloride, USP (corresponding to 450 mg of valganciclovir), and the inactive ingredients crospovidone, microcrystalline cellulose, povidone and stearic acid. The tablets are coated with Opadry Pink which contains hypromellose, iron oxide red, polyethylene glycol, polysorbate 80 and titanium dioxide. Valganciclovir hydrochloride, USP is a white to off-white powder, slightly hygroscopic with a molecular formula of C 14 H 22 N 6 O 5 •HCl and a molecular weight of 390.82.
The chemical name for valganciclovir hydrochloride, USP is L-Valine, 2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]-3-hydroxypropylester, monohydrochloride. Valganciclovir hydrochloride, USP is a polar hydrophilic compound with a solubility of 70 mg/mL in water at 25°C at a pH of 7 and an n-octanol/water partition coefficient of 0.0095 at pH 7. The pKa for valganciclovir hydrochloride, USP is 7.5.
The chemical structure of valganciclovir hydrochloride, USP is: All doses in this insert are specified in terms of valganciclovir. valganciclovirstructure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Serious Adverse Reactions Inform patients that valganciclovir tablets 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 performed frequently during treatment [see Warnings and Precautions ( 5.1 )].
Pregnancy and Contraception Inform females of reproductive potential that valganciclovir tablets causes birth defects in animals. Advise them to use effective contraception during and for at least 30 days following treatment with valganciclovir tablets. Similarly, advise males to practice barrier contraception during and for at least 90 days following treatment with valganciclovir tablets [see Use in Specific Populations ( 8.1 , 8.3 )].
Carcinogenicity Advise patients that valganciclovir is considered a potential carcinogen [see Nonclinical Toxicity ( 13.1 )]. Lactation Advise mothers not to breast-feed if they are receiving valganciclovir tablets 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 )]. Infertility Advise patients that valganciclovir tablets may cause temporary or permanent female and male infertility [see Warnings and Precautions ( 5.2 ), Use in Specific Populations ( 8.3 )].
Impairment of Cognitive Ability Inform patients that tasks requiring alertness may be affected including the patient’s ability to drive and operate machinery as convulsions, sedation, dizziness, ataxia and/or confusion have been reported with the use of valganciclovir tablets [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 tablets.
Some patients will require more frequent follow-up. Administration 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 tablets with food to maximize bioavailability.
Manufactured for: AvKARE Pulaski, TN 38478 Mfg. Rev. 03/16 AV Rev.
02/24 (M) AvPAK