VALGANCICLOVIR — valganciclovir hydrochloride tablet
Ajanta Pharma USA Inc.
WARNING: HEMATOLOGIC TOXICITY, IMPAIRMENT OF FERTILITY, FETAL TOXICITY, MUTAGENESIS AND CARCINOGENESIS
- Hematologic Toxicity: Severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, and bone marrow failure including aplastic anemia have been reported in patients treated with valganciclovir [see Warnings and Precautions (5.1)].
- Impairment of Fertility: Based on animal data and limited human data, valganciclovir may cause temporary or permanent inhibition of spermatogenesis in males and suppression of fertility in females [see Warnings and Precautions (5.3)].
- Fetal Toxicity: Based on animal data, valganciclovir has the potential to cause birth defects in humans [see Warnings and Precautions (5.4)].
- Mutagenesis and Carcinogenesis: Based on animal data, valganciclovir has the potential to cause cancers in humans [see Warnings and Precautions (5.5)].
1 INDICATIONS AND USAGE
1.1 Adult 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)].
1.2 Pediatric Patients
Prevention of CMV Disease: Valganciclovir tablets, USP 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)].
2 DOSAGE AND ADMINISTRATION
2.1 General 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)].
2.2 Recommended 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.
2.3 Recommended Dosage in Pediatric Patients
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 (7 x 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.
Table 1: k Values According to Pediatric Patient Age*
|*The k values provided are based on the Jaffe method of measuring serum creatinine, and may require correction when enzymatic methods are used1.|
|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 year to less than 2 years|
|0.55||Boys aged 2 years to less than 13 years Girls aged 2 years to less than 16 years|
|0.7||Boys aged 13 years 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 25 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.
2.5 Dosage Recommendation for Adult Patients with Renal Impairment
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)].
Table 2: Dosage Recommendations for Adult Patients with Impaired Renal Function
|*An estimated creatinine clearance in adults is calculated from serum creatinine by the following formulas: (140 – age [years]) x (body weight [kg])For males = —————————————— (72) x (serum creatinine [mg/dL]) For females = 0.85 x male value|
|Valganciclovir 450 mg Tablets|
|CrCl* (mL/min)||Induction Dose||Maintenance/ Prevention Dose|
|≥ 60||900 mg twice daily||900 mg once daily|
|40 – 59||450 mg twice daily||450 mg once daily|
|25 – 39||450 mg once daily||450 mg every 2 days|
|10 – 24||450 mg every 2 days||450 mg twice weekly|
|< 10 (on hemodialysis)||not recommended||not recommended|
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)].
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