Videx Information
Videx (Didanosine) Indications And Usage
Videx (Didanosine) (didanosine, USP), also known as ddI, in combination with other antiretroviral agents is indicated for the treatment of human immunodeficiency virus (HIV)-1 infection [].
Videx (Didanosine) Dosage And Administration
Videx (Didanosine) should be administered on an empty stomach, at least 30 minutes before or 2 hours after eating.
The preferred dosing frequency of Videx (Didanosine) is twice daily because there is more evidence to support the effectiveness of this dosing regimen. Once-daily dosing should be considered only for patients whose management requires once-daily dosing of Videx (Didanosine) []. The recommended adult total daily dose is based on body weight (kg) (see ).
Pediatric Patients (2 weeks old to 18 years old):
Dosing recommendations 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 (Didanosine) in pediatric patients.
Videx (Didanosine) Dosage Forms And Strengths
Videx (Didanosine) (didanosine, USP) Pediatric Powder for Oral Solution is supplied in 4- and 8-ounce glass bottles containing 2 g or 4 g of Videx (Didanosine) , respectively.
Videx (Didanosine) Contraindications
These recommendations are based on either drug interaction studies or observed clinical toxicities.
Videx (Didanosine) Warnings And Precautions
Fatal and nonfatal pancreatitis has occurred during therapy with Videx (Didanosine) used alone or in combination regimens in both treatment-naive and treatment-experienced patients, regardless of degree of immunosuppression. Videx (Didanosine) should be suspended in patients with signs or symptoms of pancreatitis and discontinued in patients with confirmed pancreatitis. Patients treated with Videx (Didanosine) in combination with stavudine may be at increased risk for pancreatitis.
When treatment with life-sustaining drugs known to cause pancreatic toxicity is required, suspension of Videx (Didanosine) therapy is recommended. In patients with risk factors for pancreatitis, Videx (Didanosine) should be used with extreme caution and only if clearly indicated. Patients with advanced HIV-1 infection, especially the elderly, are at increased risk of pancreatitis and should be followed closely. Patients with renal impairment may be at greater risk for pancreatitis if treated without dose adjustment. The frequency of pancreatitis is dose related. [.]
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including didanosine and other antiretrovirals.
see Use in Specific Populations
The safety and efficacy of Videx (Didanosine) have not been established in HIV-infected patients with significant underlying liver disease. During combination antiretroviral therapy, patients with preexisting liver dysfunction, including chronic active hepatitis, have an increased frequency of liver function abnormalities, including severe and potentially fatal hepatic adverse events, and should be monitored according to standard practice. If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment must be considered.
Hepatotoxicity and hepatic failure resulting in death were reported during postmarketing surveillance in HIV-infected patients treated with hydroxyurea and other antiretroviral agents. Fatal hepatic events were reported most often in patients treated with the combination of hydroxyurea, didanosine, and stavudine. This combination should be avoided. [.]
Postmarketing cases of non-cirrhotic portal hypertension have been reported, including cases leading to liver transplantation or death. Cases of didanosine-associated non-cirrhotic portal hypertension were confirmed by liver biopsy in patients with no evidence of viral hepatitis. Onset of signs and symptoms ranged from months to years after start of didanosine therapy. Common presenting features included elevated liver enzymes, esophageal varices, hematemesis, ascites, and splenomegaly.
Patients receiving Videx (Didanosine) should be monitored for early signs of portal hypertension (eg, thrombocytopenia and splenomegaly) during routine medical visits. Appropriate laboratory testing including liver enzymes, serum bilirubin, albumin, complete blood count, and international normalized ratio (INR) and ultrasonography should be considered. Videx (Didanosine) should be discontinued in patients with evidence of non-cirrhotic portal hypertension.
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including Videx (Didanosine) . During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as infection, cytomegalovirus, pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.
Autoimmune disorders (such as Graves’ disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment.
Videx (Didanosine) Adverse Reactions
The following adverse reactions are discussed in greater detail in other sections:
Videx (Didanosine) Drug Interactions
Clinical recommendations based on the results of drug interaction studies are listed in . Pharmacokinetic results of drug interaction studies are shown in and [].
Exposure to didanosine is increased when coadministered with tenofovir disoproxil fumarate [ and ]. Increased exposure may cause or worsen didanosine-related clinical toxicities, including pancreatitis, symptomatic hyperlactatemia/lactic acidosis, and peripheral neuropathy. Coadministration of tenofovir disoproxil fumarate with Videx (Didanosine) should be undertaken with caution, and patients should be monitored closely for didanosine-related toxicities and clinical response. Videx (Didanosine) should be suspended if signs or symptoms of pancreatitis, symptomatic hyperlactatemia, or lactic acidosis develop []. Suppression of CD4 cell counts has been observed in patients receiving tenofovir disoproxil fumarate with didanosine at a dose of 400 mg daily.
Videx (Didanosine) Use In Specific Populations
The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV.
mothers should be instructed not to breastfeed if they are receiving didanosine
Videx (Didanosine) Overdosage
There is no known antidote for Videx (Didanosine) overdosage. In phase 1 studies, in which Videx (Didanosine) was initially administered at doses ten times the currently recommended dose, toxicities included: pancreatitis, peripheral neuropathy, diarrhea, hyperuricemia, and hepatic dysfunction. Didanosine is not dialyzable by peritoneal dialysis, although there is some clearance by hemodialysis [].
Videx (Didanosine) Nonclinical Toxicology
Lifetime carcinogenicity studies were conducted in mice and rats for 22 and 24 months, respectively. In the mouse study, initial doses of 120, 800, and 1200 mg/kg/day for each sex were lowered after 8 months to 120, 210, and 210 mg/kg/day for females and 120, 300, and 600 mg/kg/day for males. The two higher doses exceeded the maximally tolerated dose in females and the high dose exceeded the maximally tolerated dose in males. The low dose in females represented 0.68-fold maximum human exposure and the intermediate dose in males represented 1.7-fold maximum human exposure based on relative AUC comparisons. In the rat study, initial doses were 100, 250, and 1000 mg/kg/day, and the high dose was lowered to 500 mg/kg/day after 18 months. The upper dose in male and female rats represented 3-fold maximum human exposure.
Didanosine induced no significant increase in neoplastic lesions in mice or rats at maximally tolerated doses.
Didanosine was positive in the following genetic toxicology assays: 1) the tester strain WP2 uvrA bacterial mutagenicity assay; 2) the L5178Y/TK +/- mouse lymphoma mammalian cell gene mutation assay; 3) the chromosomal aberrations assay in cultured human peripheral lymphocytes; 4) the chromosomal aberrations assay in Chinese Hamster Lung cells; and 5) the BALB/c 3T3 transformation assay. No evidence of mutagenicity was observed in an Ames bacterial mutagenicity assay or in rat and mouse micronucleus assays.
Videx (Didanosine) Clinical Studies
Videx (Didanosine) How Supplied/storage And Handling
Videx (Didanosine) (didanosine, USP) Pediatric Powder for Oral Solution is supplied as shown in :
Prior to dispensing, the pharmacist must reconstitute 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:
Videx (Didanosine) Patient Counseling Information
See .
Patients should be informed that when Videx (Didanosine) is used in combination with other agents with similar toxicities, the incidence of adverse events may be higher than when Videx (Didanosine) is used alone. These patients should be followed closely.
Patients should be cautioned about the use of medications or other substances, including alcohol, which may exacerbate Videx (Didanosine) toxicities.
Videx (Didanosine) is not a cure for HIV-1 infection, and patients may continue to experience illnesses associated with HIV-1 infection, including opportunistic infections. Therefore, patients should remain under the care of a physician when using Videx (Didanosine) .
Patients should be advised to avoid doing things that can spread HIV-1 infection to others.
Patients should be informed that the preferred dosing frequency of Videx (Didanosine) is twice daily because there is more evidence to support the effectiveness of this dosing frequency. Once-daily dosing should be considered only for patients whose management requires once-daily dosing of Videx (Didanosine) .
Patients should be instructed to not miss a dose but if they do, patients should take Videx (Didanosine) as soon as possible. Patients should be told that if it is almost time for the next dose, they should skip the missed dose and continue with the regular dosing schedule.
Patients should be instructed to contact a poison control center or emergency room right away in case of an overdose.
Videx (Didanosine)
Videx (Didanosine)
Videx (Didanosine)
