Videx Ec 250mg & 400mg Capsule

VIDEX EC should be used in combination with other antiretroviral agents for the palliative treatment of adults with advanced HIV infection. This indication is based on increases in CD4 counts observed in patients during therapy with VIDEX EC. Increases in CD4 counts are considered markers of anti-viral activity and have been linked to clinical benefit in previous AIDS therapy trials.

DUE TO THE REDUCED ABSORPTION IN THE PRESENCE OF FOOD, VIDEX EC SHOULD BE TAKEN ON AN EMPTY STOMACH at least one hour before or two hours after a meal.

Recommended dosage: The recommended total daily dose is based on body weight (kg) and is administered as one capsule given on a once daily schedule as outlined in the table below.

VIDEX EC capsules should be swallowed intact (not chewed or opened).

TABLE 2: Recommended VIDEX EC Dosage

Patient Baseline Weight Dosage Weight (kg) Total daily dose at least 60 kg 400 mg Less than 60 kg 250 mg

Dose adjustment in patients with renal impairment Adults: In adult patients with impaired renal function, the dose of VIDEX EC should be adjusted to compensate for the lower rate of elimination. The recommended reductions in dose and/or dosage interval are as follows, based on creatinine clearance:

TABLE 3: Creatinine clearance (ml/min/1,73 m P 2 P ) Patient Weight u2265 60 kg Patient Weight < 60 kg u2265 60 (normal dose) 400 mg once daily 250 mg once daily VIDEX EC is not suitable for patient with creatinine clearance <60 ml/min. For patients undergoing dialysis, the daily dose of VIDEX EC should be administered after dialysis. It is not necessary to administer a supplemental dose of VIDEX EC following dialysis.

VIDEX EC is contraindicated in patients with hypersensitivity to didanosine or to any of the components of the formulation. Safety and efficacy of VIDEX EC in children have not been established. There are insufficient data to recommend the use of VIDEX EC in patients with impaired hepatic function.

Pancreatitis: Fatal and non-fatal pancreatitis has occurred during therapy with VIDEX EC used alone or in combination regimens in both treatment-nau00efve and treatment-experienced patients, regardless of degree of immunosuppression. Patients treated with VIDEX EC in combination with stavudine with or without hydroxyurea may be at increased risk for pancreatitis. VIDEX EC should be suspended in patients with signs and symptoms of pancreatitis and discontinued in patients with confirmed pancreatitis. Suspension should also be considered when biochemical markers of pancreatitis have increased to clinically significant levels even in the absence of symptoms and in patients with clinical symptoms suggestive of pancreatitis (e.g. abdominal pain, nausea, vomiting) until pancreatitis is excluded by appropriate laboratory and imaging techniques.

Lactic acidosis: 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. A majority of these cases have been in women. Obesity and prolonged nucleoside exposure may be risk factors. Treatment with VIDEX EC should be suspended in the setting of rapidly elevating aminotransferase levels, raised blood levels of bilirubin, progressive hepatomegaly, or metabolic/lactic acidosis of unknown aetiology. Caution should be exercised when administering VIDEX EC to any patient, particularly obese women with hepatomegaly, hepatitis, or other known risk factors for liver disease. These patients should be followed carefully while on therapy with VIDEX EC.

Peripheral neuropathy: Peripheral neuropathy, which was severe in some cases, has been reported in HIV-infected patients receiving hydroxyurea in combination with antiretroviral agents, including VIDEX EC, with or without stavudine (see SIDE EFFECTS). Patients on VIDEX EC may develop toxic peripheral neuropathy, usually characterised by bilateral symmetrical distal numbness, tingling and pain in feet and hands. Whenever warranted by clinical conditions, VIDEX EC therapy should be suspended until resolution of symptoms. Many patients tolerate a reduced dose after resolution of symptoms.

Liver failure: Liver failure of unknown aetiology has occurred. Patients should be observed for liver enzyme elevations and VIDEX EC should be suspended if enzymes rise to a clinically significant level above the upper limit of normal. In the event of rapidly elevating aminotransferase levels, consideration should be given to discontinuation of all nucleoside analogue therapy.

Non-cirrhotic portal hypertension: Post-marketing 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 VIDEX therapy. Common presenting features included elevated liver enzymes, oesophageal varices, haematemesis, ascites, and splenomegaly. Patients receiving VIDEX EC should be monitored for early signs of portal hypertension (e.g. thrombocytopenia and splenomegaly) during routine medical visits. Appropriate laboratory testing including liver enzymes, serum bilirubin, albumin, complete blood count, and international normalised ratio (INR) and ultrasonography should be considered. VIDEX EC should be discontinued in patients with evidence of non-cirrhotic portal hypertension.

Co-administration of VIDEX EC with medicines that are known to cause peripheral neuropathy or pancreatitis may increase the risk of these toxicities (see WARNINGS AND SPECIAL PRECAUTIONS). Specific interaction studies have been conducted with VIDEX chewable/dispersible tablets and loperamide, metoclopramide, ranitidine, zidovudine, stavudine, rifabutin, foscamet, trimethoprim, sulfamethoxazole and dapsone without evidence of interaction. Specific interaction studies with ciprofloxacin, ketoconazole and indinavir, showed no evidence of significant interaction. Therefore, VIDEX EC capsules can be prescribed concomitantly with these medicines.

Allopurinol: When VIDEX tablets were co-administered with allopurinol in 2 patients with renal impairment (creatinine clearance of 15 to 18 ml/min), the AUC of didanosine increased approximately 4-fold. In 14 healthy volunteers, the mean AUC of didanosine increased approximately 2-fold when VIDEX tablets were given with allopurinol. Thus the risk of dose-related toxicities, such as pancreatitis (see WARNINGS AND SPECIAL PRECAUTIONS, Pancreatitis), may be increased if VIDEX EC and allopurinol are administered together. It is recommended that these two medicines not be administered together.

Ribavirin increases the intracellular triphosphate levels of didanosine. Fatal hepatic failure, as well as peripheral neuropathy, pancreatitis, and symptomatic hyperlactataemia/lactic acidosis have been reported in patients receiving didanosine and ribavirin with or without stavudine. The administration of VIDEX EC and ribavirin should be avoided.

Safe use in pregnancy has not been established. Fatal lactic acidosis has been reported in pregnant women who received the combination of VIDEX EC and stavudine with other antiretroviral agents. It is not known whether VIDEX EC is excreted in human milk. It is recommended that women taking VIDEX EC do not breastfeed because of the potential for serious adverse reactions from VIDEX EC in breastfeeding infants.

Not stated in the provided text.

Adults: Pancreatitis: Fatal and nonfatal pancreatitis has occurred during therapy with VIDEX EC used alone or in combination regimens in both treatment-nau00efve and treatment-experienced patients, regardless of degree of immunosuppression. VIDEX EC should be suspended in patients with signs or symptoms of pancreatitis and discontinued in patients with confirmed pancreatitis. Other important toxicities include lactic acidosis and severe hepatomegaly with steatosis, retinal changes and optical neuritis (see WARNINGS AND SPECIAL PRECAUTIONS) and peripheral neuropathy (see WARNING AND SPECIAL PRECAUTIONS, DOSAGE AND DIRECTIONS FOR USE).

Adverse events: The following undesirable effects which occurred at a frequency of u2265 2 %, were reported. Frequency is defined as very common (u2265 1/10 or u2265 10 %); common (u2265 1/100, < 1/10 or u2265 1 % and < 10 %); uncommon (u2265 1/1000, < 1/100 or u2265 0,1 % and < 1 %), rare (u2265 1/1000 0, < 1/1000 or u2265 0,01 % and < 0,1 %) or very rare (< 1/10000 or < 0,01 %).

Nervous system disorders: Common: peripheral neurologic symptoms (including neuropathy), headache. Gastrointestinal: Very common: diarrhoea. Common: nausea, vomiting, abdominal pain. Skin and subcutaneous tissue disorder: Common: rash/pruritus. General disorders: Common: fatigue.

There is no known antidote for VIDEX EC overdosage. Early studies in which didanosine was initially administered at doses ten times the recommended doses indicate that the anticipated complications of chronic overdosage would be hyperuricaemia, pancreatitis, peripheral neuropathy and hepatic dysfunction. Didanosine is not dialysable by peritoneal dialysis, although there is some clearance by haemodialysis. The fractional removal of didanosine during an average haemodialysis session of 3 to 4 hours is approximately 20 to 35 % of the amount present in the body at the start of dialysis.