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Videx (Didanosine) - Indications and Dosage

 
 



INDICATIONS AND USAGE

VIDEX (didanosine) in combination with other antiretroviral agents is indicated for the treatment of HIV-1 infection (see Clinical Studies).

Clinical Studies

Combination Therapy

START 2 was a multicenter, randomized, open-label study comparing VIDEX (200 mg twice daily)/stavudine/indinavir to zidovudine/lamivudine/indinavir in 205 treatment-naive patients. Both regimens resulted in a similar magnitude of suppression of HIV RNA levels and increases in CD4 cell counts through 48 weeks.

Study A1454-148 was a randomized, open-label, multicenter study comparing treatment with VIDEX (400 mg once daily) plus stavudine (40 mg twice daily) and nelfinavir (750 mg three times daily) versus zidovudine (300 mg twice daily) plus lamivudine (150 mg twice daily) and nelfinavir (750 mg three times daily) in 756 treatment-naive patients, with a median CD4 cell count of 340 cells/mm3 (range 80 to 1568 cells/mm3) and a median plasma HIV-1 RNA of 4.69 log10 copies/mL (range 2.6 to 5.9 log10 copies/mL) at baseline. Median CD4 cell count increases at 48 weeks were 188 cells/mm3 in both treatment groups. Treatment response and outcomes through 48 weeks are shown in Figure 1 and Table 5.

Table 5: Outcomes of Randomized Treatment Through Week 48, AI454-148
 Percent of Patients with HIV RNA <400 copies/mL (<50 copies/mL)
Week 48 StatusVIDEX/stavudine/nelfinavir
n=503
lamivudine/zidovudine/nelfinavir
n=253
* p <0.05 for the differences between treatment groups, by Cochran-Mantel-Haenszel test.
a Patients achieved virologic response [two consecutive viral loads <400 (<50) copies/mL] and maintained it to Week 48.
b Includes viral rebound and failing to achieve confirmed <400 (<50) copies/mL by Week 48.
c  Includes lost to follow-up, noncompliance, withdrawal, and pregnancy.
Respondera50* (34*)59 (47)
Virologic failureb36 (57)32 (48)
Death or disease progression<1 (<1)1 (<1)
Discontinued due to adverse events4 (2)2 (<1)
Discontinued due to other reasonsc6 (3)4 (2)
Never initiated treatment4 (4)2 (2)

Monotherapy

The efficacy of VIDEX was demonstrated in two randomized, double-blind studies comparing VIDEX, given on a twice-daily schedule, to zidovudine, given three times daily, in 617 (ACTG 116A, conducted 1989-1992) and 913 (ACTG 116B/117, conducted 1989-1991) patients with symptomatic HIV infection or AIDS who were treated for more than one year. In treatment-naive patients (ACTG 116A), the rate of HIV disease progression or death was similar between the treatment groups; mortality rates were 26% for patients receiving VIDEX and 21% for patients receiving zidovudine. Of the patients who had received previous zidovudine treatment (ACTG 116B/117), those treated with VIDEX had a lower rate of HIV disease progression or death (32%) compared to those treated with zidovudine (41%); however, survival rates were similar between the treatment groups.

Efficacy in pediatric patients was demonstrated in a randomized, double-blind, controlled study (ACTG 152, conducted 1991-1995) involving 831 patients 3 months to 18 years of age treated for more than 1.5 years with zidovudine (180 mg/m2 q6h), VIDEX (120 mg/m2 q12h), or zidovudine (120 mg/m2 q6h) plus VIDEX (90 mg/m2 q12h). Patients treated with VIDEX or VIDEX plus zidovudine had lower rates of HIV disease progression or death compared with those treated with zidovudine alone.

Studies have demonstrated that the clinical benefit of monotherapy with antiretrovirals, including VIDEX, was time limited.

DOSAGE AND ADMINISTRATION

Dosage

VIDEX should be administered on an empty stomach, at least 30 minutes before or 2 hours after eating.

Adults: The preferred dosing frequency of VIDEX is twice daily because there is more evidence to support the effectiveness of this dosing regimen. Once-daily dosing should be considered only for adult patients whose management requires once-daily dosing of VIDEX (see INDICATIONS AND USAGE: Clinical Studies). The daily dose in adult patients is dependent on weight as outlined in Table 13.

Table 13: Adult Dosing
 Recommended VIDEX Dose by Patient Weight
 ≥60 kg<60 kg
Preferred dosing 200 mg twice daily125 mg twice daily
Dosing for patients whose management
requires once-daily frequency
400 mg once daily250 mg once daily

Pediatric Patients: The recommended dose of VIDEX (didanosine) in pediatric patients between 2 weeks and 8 months of age is 100 mg/m2 twice daily, and the recommended VIDEX dose for pediatric patients older than 8 months is 120 mg/m2 twice daily.

Dosing recommendations for VIDEX in patients less than 2 weeks of age cannot be made because the pharmacokinetics of didanosine in these children are too variable to determine an appropriate dose. There are no data on once-daily dosing of VIDEX in pediatric patients.

Dose Adjustment

Clinical and laboratory signs suggestive of pancreatitis should prompt dose suspension and careful evaluation of the possibility of pancreatitis. VIDEX use should be discontinued in patients with confirmed pancreatitis (see WARNINGS and PRECAUTIONS: Drug Interactions).

Patients with symptoms of peripheral neuropathy may tolerate a reduced dose of VIDEX after resolution of the symptoms of peripheral neuropathy upon drug discontinuation. If neuropathy recurs after resumption of VIDEX, permanent discontinuation of VIDEX should be considered.

Concomitant Therapy: Tenofovir disoproxil fumarate. A dose reduction of VIDEX to 250 mg (adults weighing ≥60 kg with creatinine clearance ≥60 mL/min) or 200 mg (adults weighing<60 kg with creatinine clearance ≥60 mL/min) once daily is recommended. VIDEX and tenofovir may be taken together in the fasted state. Alternatively, if tenofovir is taken with food, VIDEX should be taken on an empty stomach (at least 30 minutes before food or 2 hours after food). The appropriate dose of VIDEX coadministered with tenofovir in patients with creatinine clearance<60 mL/min has not been established. [See CLINICAL PHARMACOLOGY: Drug Interactions and PRECAUTIONS: Drug Interactions ; see the complete prescribing information for VIDEX EC (enteric-coated formulation of didanosine) for results of drug interaction studies of tenofovir with reduced doses of the enteric-coated formulation of didanosine.]

Renal Impairment: In adult patients with impaired renal function, the dose of VIDEX should be adjusted to compensate for the slower rate of elimination. The recommended doses and dosing intervals of VIDEX in adult patients with renal insufficiency are presented in Table 14.

Table 14: Recommended Dosage of VIDEX in Renal Impairment
 Recommended VIDEX Dose by Patient Weight
Creatinine Clearance
(mL/min)
≥60 kg<60 kg
a 400 mg once daily (≥60 kg) or 250 mg once daily (<60 kg) for patients whose management requires once-daily frequency of administration.
≥60200 mg twice dailya125 twice dailya
30-59200 mg once daily
or 100 mg twice daily
150 mg once daily
or 75 mg twice daily
10-29150 mg once daily100 mg once daily
<10100 mg once daily75 mg once daily

Urinary excretion is also a major route of elimination of didanosine in pediatric patients; therefore, the clearance of didanosine may be altered in children with renal impairment. Although there are insufficient data to recommend a specific dose adjustment of VIDEX in this patient population, a reduction in the dose and/or an increase in the interval between doses should be considered.

Patients Requiring Continuous Ambulatory Peritoneal Dialysis (CAPD) or Hemodialysis: For patients requiring CAPD or hemodialysis, follow dosing recommendations for patients with creatinine clearance less than 10 mL/min, shown in Table 14. It is not necessary to administer a supplemental dose of VIDEX following hemodialysis.

Hepatic Impairment and Toxicity: See WARNINGS.

Method of Preparation

VIDEX Pediatric Powder for Oral Solution

Prior to dispensing, the pharmacist must constitute dry powder with Purified Water, USP, to an initial concentration of 20 mg/mL and immediately mix the resulting solution with antacid to a final concentration of 10 mg/mL as follows:

20 mg/mL Initial Solution: Constitute the product to 20 mg/mL by adding 100 mL or 200 mL of Purified Water, USP, to the 2 g or 4 g of VIDEX powder, respectively, in the product bottle.

10 mg/mL Final Admixture: 1. Immediately mix one part of the 20 mg/mL initial solution with one part of Maximum Strength Mylanta® Liquid for a final dispensing concentration of 10 mg VIDEX per mL. For patient home use, the admixture should be dispensed in appropriately sized, flint-glass or plastic (HDPE, PET, or PETG) bottles with child-resistant closures. This admixture is stable for 30 days under refrigeration, 36° to 46° F (2° to 8° C).

2. Instruct the patient to shake the admixture thoroughly prior to use and to store the tightly closed container in the refrigerator, 36° to 46° F (2° to 8° C), up to 30 days.

HOW SUPPLIED

VIDEX (didanosine) Pediatric Powder for Oral Solution is supplied in 4- and 8-ounce glass bottles containing 2 g or 4 g of VIDEX, respectively.

The bottles of powder should be stored at 59° to 86° F (15° to 30° C). The VIDEX admixture may be stored up to 30 days in a refrigerator, 36° to 46° F (2° to 8° C). Discard any unused portion after 30 days.

The NDC numbers for the previously described VIDEX products are:

Table 15
NDC NO.Packaging InformationProduct Strength
VIDEX® Pediatric Powder for Oral Solution
0087-6632-41One bottle per carton2 g/bottle
0087-6633-41One bottle per carton4 g/bottle

US Patent Nos: 4,861,759, 5,254,539, 5,616,566, and 5,880,106.

HANDLING AND DISPOSAL

Spill, Leak, and Disposal Procedure

Avoid generating dust during clean-up of powdered products; use wet mop or damp sponge. Clean surface with soap and water as necessary. Containerize larger spills.

There is no single preferred method of disposal of containerized waste. Disposal options include incineration, landfill, or sewer as dictated by specific circumstances and relevant national, state, and local regulations.

______________________

Mylanta® is a registered trademark of Johnson & Johnson-Merck Consumer Pharmaceuticals Company.

Bristol-Myers Squibb Company
Princeton, NJ 08543 USA
1196181A4
Revised January 2007




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