Videx

Nucleoside and Nucleotide Reverse Transcriptase Inhibitors (NRTI)s

The manufacturer recommend to administer on an empty stomach (i.e., at least 30 minutes before or 2 hours after eating). However, administration on an empty stomach may not be possible in frequently fed infants and it may decrease medication adherence. To improve adherence, some practitioners administer didanosine without regard to food administration. In a study comparing fed and fasting state administration of didanosine in children (n=106), overall systemic exposure (AUC) was similar between groups with slower absorption and prolonged elimination noted during the administration of food. Additionally, studies in adults suggest that didanosine may be given without regard to food.

Extended-release capsules:
Swallow whole. Do not crush, chew, or open.

Preparation of Pediatric powder for oral solution:
Prior to dispensing, reconstitute 2 or 4 gram bottle by adding 100 or 200 mL Purified Water, USP, respectively, to produce a solution containing 20 mg/mL. Immediately after reconstitution, the 20 mg/mL solution should be mixed with an equal amount of any commercially available antacid that contains as active ingredients aluminum hydroxide (400 mg/5 mL), magnesium hydroxide (400 mg/5 mL), and simethicone (40 mg/5 mL) to produce a final admixture concentration of 10 mg/mL.
Shake well prior to administering each dose.
Storage: Suspension is stable for 30 days when refrigerated at 2 to 8 degrees C (36 to 46 degrees F).

pancreatitis / Delayed / 1.0-13.0
lactic acidosis / Delayed / 0-1.0
hepatic failure / Delayed / 0-1.0
hematemesis / Delayed / 0-1.0
optic neuritis / Delayed / 0-1.0
anaphylactoid reactions / Rapid / 0-1.0
rhabdomyolysis / Delayed / 0-1.0
renal failure (unspecified) / Delayed / 0-1.0
hepatotoxicity / Delayed / Incidence not known

peripheral neuropathy / Delayed / 17.0-20.0
hyperamylasemia / Delayed / 15.0-17.0
elevated hepatic enzymes / Delayed / 1.0-9.0
hyperuricemia / Delayed / 2.0-3.0
ascites / Delayed / 0-1.0
hepatitis / Delayed / 0-1.0
steatosis / Delayed / 0-1.0
splenomegaly / Delayed / 0-1.0
thrombocytopenia / Delayed / 0-1.0
anemia / Delayed / 0-1.0
leukopenia / Delayed / 0-1.0
sialadenitis / Delayed / 0-1.0
hyperglycemia / Delayed / 0-1.0
hypoglycemia / Early / 0-1.0
diabetes mellitus / Delayed / 0-1.0
myopathy / Delayed / 0-1.0
hyperbilirubinemia / Delayed / 10.0
hepatomegaly / Delayed / Incidence not known
lipodystrophy / Delayed / Incidence not known

nausea / Early / 24.0-53.0
headache / Early / 21.0-46.0
vomiting / Early / 12.0-30.0
diarrhea / Early / 19.0-28.0
abdominal pain / Early / 7.0-13.0
pruritus / Rapid / 7.0-9.0
rash / Early / 7.0-9.0
flatulence / Early / 0-1.0
xerostomia / Early / 0-1.0
anorexia / Delayed / 0-1.0
dyspepsia / Early / 0-1.0
xerophthalmia / Early / 0-1.0
retinal pigment changes / Delayed / 0-1.0
alopecia / Delayed / 0-1.0
chills / Rapid / 0-1.0
asthenia / Delayed / 0-1.0
fever / Early / 0-1.0
arthralgia / Delayed / 0-1.0
myalgia / Early / 0-1.0

Didanosine should not be administered to patients with signs and symptoms of pancreatitis and should be discontinued in patients with confirmed pancreatitis. The incidence of didanosine-induced pancreatitis appears to be dose-related, and is higher in patients with advanced HIV-disease, a history of pancreatitis, alcoholism, or other risk factors for pancreatitis including cholelithiasis, endoscopic retrograde cholangiopancreatography (ERCP), hypertriglyceridemia, or morbid obesity. Medications that may increase the exposure to didanosine may also increase the risk of pancreatitis. Didanosine should be used with extreme caution, if at all, in these patients. If patients are treated with other drugs known to cause pancreatitis, it is recommended that didanosine therapy be discontinued.

Obesity and prolonged nucleoside exposure may be risk factors for hepatotoxicity or lactic acidosis during didanosine therapy. Fatalities associated with lactic acidosis and hepatomegaly have been reported with use of antiretroviral agents alone or in combination, including didanosine. A majority of these cases occurred in females. It is unknown if pregnant women are at increased risk; however, fatal cases of lactic acidosis, two with and one without pancreatitis, have occurred in women who were either pregnant or postpartum and whose antiretroviral therapy during gestation included stavudine and didanosine. Two of the infants of these women died. Clinicians need to be alert for early diagnosis of this syndrome. Pregnant women receiving nucleoside analogs should have LFTs and serum electrolytes assessed more frequently during the last trimester and any new symptoms should be evaluated thoroughly. Didanosine should be used with caution in patients with hepatic disease or in those with known risk factors for liver disease; however, cases have been reported in patients with no known risk factors. Treatment should be discontinued in any patient who develops clinical or laboratory findings suggestive of symptomatic hyperlactemia, hepatotoxicity or lactic acidosis which may include hepatomegaly and steatosis even in the absence of marked increases in transaminases. It is not known if hepatic impairment affects the pharmacokinetics of didanosine; therefore, these patients should be monitored closely. Postmarketing cases of non-cirrhotic portal hypertension, including cases leading to liver transplantation or death, have been reported with didanosine, ddI. Onset of signs and symptoms ranged from months to years after starting didanosine. Symptoms include elevated hepatic enzymes, esophageal varices, hematemesis, ascites, and splenomegaly. Monitor patients for early signs of portal hypertension, by obtaining routine hepatic enzymes, serum bilirubin, albumin, complete blood count (CBC), and INR. Ultrasonography should be considered. Discontinue didanosine in patients with evidence of non-cirrhotic portal hypertension.

Videx EC

Rx

Synthetic purine nucleoside reverse transcriptase inhibitor
Used for the treatment of HIV-1 infection in combination with other antiretroviral medications
Acid-labile drug and must be protected from stomach acids

NOTE: Patients must be able to swallow capsules whole; otherwise, use the oral solution.

400 mg PO once daily; if administered concurrently with tenofovir disoproxil fumarate, reduce dose to 250 mg PO once daily. HIV guidelines recommend against concurrent use of didanosine and tenofovir disoproxil fumarate.[28757] [46638]

250 mg PO once daily; if administered concurrently with tenofovir disoproxil fumarate, reduce dose to 200 mg PO once daily. HIV guidelines recommend against concurrent use of didanosine and tenofovir disoproxil fumarate.

400 mg PO once daily; if administered concurrently with tenofovir disoproxil fumarate, reduce dose to 250 mg PO once daily. HIV guidelines recommend against concurrent use of didanosine and tenofovir disoproxil fumarate.

250 mg PO once daily; if administered concurrently with tenofovir disoproxil fumarate, reduce dose to 200 mg PO once daily. HIV guidelines recommend against concurrent use of didanosine and tenofovir disoproxil fumarate.

200 mg PO once daily.

200 mg PO twice daily or 400 mg PO once daily; if administered concurrently with tenofovir disoproxil fumarate, reduce dose to 250 mg PO once daily. Twice daily dosing is supported by more efficacy data; thus, it is recommended to select the twice daily dosing regimen whenever possible. HIV guidelines recommend against concurrent use of didanosine and tenofovir disoproxil fumarate.

125 mg PO twice daily or 250 mg PO once daily; if administered concurrently with tenofovir disoproxil fumarate, reduce dose to 200 mg PO once daily. Twice daily dosing is supported by more efficacy data; thus, it is recommended to select the twice daily dosing regimen whenever possible. HIV guidelines recommend against concurrent use of didanosine and tenofovir disoproxil fumarate.

120 mg/m2/dose (range: 90 to 150 mg/m2/dose) PO every 12 hours (Max: 125 mg/dose for less than 60 kg; 200 mg/dose for 60 kg or more) for adolescents in early puberty. Once daily regimens (240 mg/m2/dose PO once daily [Max: 250 mg/dose for less than 60 kg; 400 mg/dose for 60 kg or more]) have been used with effective viral suppression; however, once-daily regimens are not FDA-approved for pediatric patients. For adolescents in late puberty (i.e., Sexual Maturity Rating (SMR) 4 or 5), refer to adult dosing schedules. Because of rapidly changing development during adolescence, monitor all patients for efficacy and toxicity.

120 mg/m2/dose (range: 90 to 150 mg/m2/dose) PO every 12 hours (Max: 125 mg/dose for less than 60 kg; 200 mg/dose for 60 kg or more). Once daily regimens (240 mg/m2/dose PO once daily [Max: 250 mg/dose for less than 60 kg; 400 mg/dose for 60 kg or more]) have been used with effective viral suppression in treatment-naive children older than 3 years; however, once-daily regimens are not FDA-approved for pediatric patients.

100 mg/m2/dose PO every 12 hours.

50 mg/m2/dose PO every 12 hours is recommended in the HIV clinical guidelines. Although the FDA-approved dosage is 100 mg/m2/dose PO twice daily, pharmacokinetic data suggest increased toxicity if this dosage is used in infants younger than 3 months.

The manufacturer states that no dosage adjustments are needed in patients with hepatic impairment as a similar range and distribution of AUC and Cmax values were observed when compared to healthy controls in a small study (n = 12). If didanosine is used, monitor patients closely for associated drug toxicities and further hepatic decompensation.

NOTE: Coadministration with tenofovir has not been established in patients with CrCl less than 60 mL/minute; HIV guidelines recommend against concurrent use of didanosine and tenofovir in all patients. The following guidelines are based on age and weight for patients with renal impairment who are not receiving tenofovir:
Adults weighing 60 kg or more:
CrCl 60 mL/minute or more: No dosage adjustment needed.
CrCl 30 to 59 mL/minute: reduce dose of oral solution to 100 mg PO every 12 hours or 200 mg PO every 24 hours; reduce the dose of extended-release capsules to 200 mg PO once daily.
CrCl 10 to 29 mL/minute: reduce dose of oral solution to 150 mg PO every 24 hours; reduce the dose of extended-release capsules to 125 mg PO once daily.
CrCl less than 10 mL/minute: reduce dose of oral solution to 100 mg PO every 24 hours; reduce the dose of extended release capsules to 125 mg PO once daily.
Adults weighing less than 60 kg:
CrCl 60 mL/minute or more: No dosage adjustment needed.
CrCl 30 to 59 mL/minute: reduce the dose of oral solution to 75 mg PO every 12 hours or to 150 mg PO every 24 hours; reduce the dose of extended-release capsules to 125 mg PO once daily.
CrCl 10 to 29 mL/minute: reduce dose of oral solution to 100 mg PO every 24 hours; reduce the dose of extended-release capsules to 125 mg PO once daily.
CrCl less than 10 mL/minute: reduce dose of oral solution to 75 mg PO every 24 hours; extended-release capsules are not recommended in these patients.
Pediatric patients
Oral solution
The following renal dose adjustments are based on a usual dose of 100 mg/m2/dose every 12 hours in infants (2 weeks to 8 months) and 120 mg/m2/dose every 12 hours in children.
CrCl 30 to 50 mL/minute/1.73 m2: 75 mg/m2/dose PO every 12 hours (Max: 75 mg/dose for those weighing less than 60 kg and 100 mg/dose for those weighing 60 kg or more).
CrCl 10 to 29 mL/minute/1.73 m2: 90 mg/m2/dose PO every 24 hours (Max: 100 mg/dose for those weighing less than 60 kg and 150 mg/dose for those weighing 60 kg or more ).
CrCl less than 10 mL/minute/1.73 m2: 75 mg/m2/dose PO every 24 hours (Max: 75 mg/dose for those weighing less than 60 kg and 100 mg/dose for those weighing 60 kg or more).
Extended-release capsules
Although the FDA-approved product labeling does not provide specific renal dosing guidelines in pediatric patients, the following adult renal dose adjustments may be considered for pediatric patients receiving the extended-release capsules.
Patients weighing less than 60 kg:
CrCl 30 to 59 mL/minute: 125 mg PO once daily.
CrCl 10 to 29 mL/minute: 125 mg PO once daily.
CrCl less than 10 mL/minute: delayed-release capsules are not recommended in these patients.
Patients weighing 60 kg or more:
CrCl 30 to 59 mL/minute: 200 mg PO once daily.
CrCl 10 to 29 mL/minute: 125 mg PO once daily.
CrCl less than 10 mL/minute: 125 mg PO once daily.
 
 
Intermittent hemodialysis
Dose reductions are required in patients receiving hemodialysis. For patients weighing 60 kg or more, administer 100 mg oral solution or 125 mg extended-release capsules PO every 24 hours. For patients weighing less than 60 kg, administer 75 mg oral solution PO every 24 hours, extended-release capsules are not recommended for patients weighing less than 60 kg. It is not necessary to administer a supplemental dose of didanosine following hemodialysis. In a study comparing 6 adults with normal renal function and 6 adults receiving hemodialysis, dialysis removed approximately 30% of didanosine from the body. The study stated that in an anuric patients with chronic renal failure, clearance is decreased approximately four-fold as compared to patients with normal renal function. To compensate for the decreased clearance, the study suggested administering approximately 25% of the total daily dose to these patients.
 
Continuous Ambulatory Peritoneal dialysis
Dose reductions are required in patients receiving CAPD. For patients weighing 60 kg or more, administer 100 mg oral solution or 125 mg extended-release capsules PO every 24 hours. For patients weighing less than 60 kg, administer 75 mg oral solution PO every 24 hours, extended-release capsules are not recommended for patients weighing less than 60 kg. In a study comparing 6 adults with normal renal function and 6 adults receiving CAPD, there was little effect on the removal didanosine from the body by CAPD. The study stated that in an anuric patients with chronic renal failure, the clearance of didanosine is decreased approximately four-fold as compared to patients with normal renal function. To compensate for the decreased clearance, the study suggested administering approximately 25% of the total daily dose to these patients.

Adefovir: (Major) Patients who are concurrently taking adefovir with antiretrovirals (i.e., anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs)) are at risk of developing lactic acidosis and severe hepatomegaly with steatosis. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with antiretrovirals. A majority of these cases have been in women; obesity and prolonged nucleoside exposure may also be risk factors. Particular caution should be exercised when administering nucleoside analogs to any patient with known risk factors for hepatic disease; however, cases have also been reported in patients with no known risk factors. Suspend adefovir in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).
Allopurinol: (Contraindicated) Concurrent use of allopurinol and didanosine, ddI is contraindicated. Coadministration may result in increased concentrations of didanosine and may increase the incidence of pancreatitis. In 14 healthy volunteers, the mean AUC of didanosine increased approximately 2-fold when given with allopurinol. This interaction was more pronounced in 2 patients with renal impairment, as coadministration resulted in elevated didanosine AUC and Cmax of 312% and 232%, respectively. The effects of allopurinol in patients with normal renal function is not known.
Aluminum Hydroxide: (Minor) The side effects associated with aluminum hydroxide may potentially be increased during concurrent use with didanosine, ddI because some ddI products also contain similar antacid ingredients.
Aluminum Hydroxide; Magnesium Carbonate: (Minor) The side effects associated with aluminum hydroxide may potentially be increased during concurrent use with didanosine, ddI because some ddI products also contain similar antacid ingredients. (Minor) The side effects associated with magnesium carbonate may potentially be increased during concurrent use with didanosine, ddI because some ddI products also contain similar antacid ingredients. Although this interaction should be of minor clinical significance for most patients, clinicians should be alert to a possible increased risk of side effects associated with taking an additional antacid product concurrently with ddI products.
Aluminum Hydroxide; Magnesium Hydroxide: (Minor) The side effects associated with aluminum hydroxide may potentially be increased during concurrent use with didanosine, ddI because some ddI products also contain similar antacid ingredients. (Minor) The side effects associated with magnesium hydroxide may potentially be increased during concurrent use with didanosine, ddI because some ddI products also contain similar antacid ingredients. Although this interaction should be of minor clinical significance for most patients, clinicians should be alert to a possible increased risk of side effects associated with taking an additional antacid product concurrently with ddI products.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Minor) The side effects associated with aluminum hydroxide may potentially be increased during concurrent use with didanosine, ddI because some ddI products also contain similar antacid ingredients. (Minor) The side effects associated with magnesium hydroxide may potentially be increased during concurrent use with didanosine, ddI because some ddI products also contain similar antacid ingredients. Although this interaction should be of minor clinical significance for most patients, clinicians should be alert to a possible increased risk of side effects associated with taking an additional antacid product concurrently with ddI products.
Aluminum Hydroxide; Magnesium Trisilicate: (Minor) The side effects associated with aluminum hydroxide may potentially be increased during concurrent use with didanosine, ddI because some ddI products also contain similar antacid ingredients.
Atazanavir: (Moderate) Separate the administration of atazanavir and didanosine, ddI by giving atazanavir 2 hours before or 1 hour after buffered didanosine. Atazanavir solubility decreases as gastric pH increases. Concomitant administration of atazanavir and buffered didanosine, ddI products resulted in a 4-fold decrease in the AUC of atazanavir. Didanosine chewable/dispersible buffered tablets contain calcium carbonate and magnesium hydroxide, and didanosine buffered powder for oral solution contains dibasic sodium phosphate, sodium citrate, and citric acid. No change in the AUC of enteric-coated didanosine occurred with concurrent use of atazanavir.
Atazanavir; Cobicistat: (Moderate) Separate the administration of atazanavir and didanosine, ddI by giving atazanavir 2 hours before or 1 hour after buffered didanosine. Atazanavir solubility decreases as gastric pH increases. Concomitant administration of atazanavir and buffered didanosine, ddI products resulted in a 4-fold decrease in the AUC of atazanavir. Didanosine chewable/dispersible buffered tablets contain calcium carbonate and magnesium hydroxide, and didanosine buffered powder for oral solution contains dibasic sodium phosphate, sodium citrate, and citric acid. No change in the AUC of enteric-coated didanosine occurred with concurrent use of atazanavir.
Bortezomib: (Minor) Monitor patients for the development of peripheral neuropathy when receiving bortezomib in combination with other drugs that can cause peripheral neuropathy like didanosine; the risk of peripheral neuropathy may be additive.
Cabotegravir; Rilpivirine: (Moderate) While no dosage adjustments are required, because didanosine, ddI is administered on an empty stomach and rilpivirine is given with food, do not give didanosine within at least two hours before or at least four hours after rilpivirine.
Cefpodoxime: (Moderate) Cefpodoxime proxetil requires a low gastric pH for dissolution; therefore, concurrent administration with medications that increase gastric pH, such as didanosine, ddI, may decrease the bioavailability of cefpodoxime. When cefpodoxime was administered with high doses of antacids and H2-blockers, peak plasma concentrations were reduced by 24% and 42% and the extent of absorption was reduced by 27% and 32%, respectively. The rate of absorption is not affected. This interaction is not expected with extended-release formulations of Didanosine.
Ciprofloxacin: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after didanosine tablets or powder for oral solution. Ciprofloxacin absorption may be reduced as it can chelate with the buffering agents contained in didanosine tablets and powder. The delayed-release didanosine capsules do not contain a buffering agent and would not be expected to interact with ciprofloxacin.
Dapsone: (Moderate) Dapsone clinical failures have been noted when dapsone was administered with didanosine. Despite a lack of a documented pharmacokinetic interaction, clinicians should be wary of possible dapsone clinical failure when dapsone is used with didanosine since this has been reported previously.
Darunavir: (Moderate) While a drug interaction between darunavir and didanosine, ddi is not known, because of the specific administration guidelines didanosine (administered on an empty stomach) should be administered 1 hour before or 2 hours after darunavir (administered with food).
Darunavir; Cobicistat: (Moderate) While a drug interaction between darunavir and didanosine, ddi is not known, because of the specific administration guidelines didanosine (administered on an empty stomach) should be administered 1 hour before or 2 hours after darunavir (administered with food).
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) While a drug interaction between darunavir and didanosine, ddi is not known, because of the specific administration guidelines didanosine (administered on an empty stomach) should be administered 1 hour before or 2 hours after darunavir (administered with food).
Delafloxacin: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after didanosine tablets or powder for oral solution. Delafloxacin absorption may be reduced as it can chelate with the buffering agents contained in didanosine tablets and powder. The delayed-release didanosine capsules do not contain a buffering agent and would not be expected to interact with delafloxacin.
Delavirdine: (Major) The administration of delavirdine concurrently with didanosine, ddI, tablets or oral solution results in a 20% decrease in systemic exposure of both drugs. Didanosine tablets and oral solutions contain buffers that increase gastric pH; therefore, administration of delavirdine and didanosine tablets and oral solution should be separated by at least one hour. Didanosine capsules do not contain buffers and would not be expected to interact with delavirdine.
Dolutegravir; Rilpivirine: (Moderate) While no dosage adjustments are required, because didanosine, ddI is administered on an empty stomach and rilpivirine is given with food, do not give didanosine within at least two hours before or at least four hours after rilpivirine.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Major) HIV guidelines recommend against concurrent use of tenofovir, PMPA and didanosine; however, these medications can be used together, if necessary, in patients with a creatinine clearance 60 mL/min or more if the didanosine dose is reduced; decrease the didanosine dose to 250 mg in patients weighing 60 kg or more and to 200 mg in patients weighing 25 to 59 kg. Concurrent administration of tenofovir, PMPA and didanosine, ddI increases the concentration of both didanosine and its active metabolite (dideoxyadenosine 5-triphosphate) which may cause or worsen didanosine-related clinical toxicities, including pancreatitis, symptomatic hyperlactatemia/lactic acidosis, and peripheral neuropathy. In addition, this combination has been associated with CD4 cell count decline despite viral suppression, high rates of early virologic failure, and rapid selection of resistance mutations. The mechanism of the interaction is not known, but the interaction occurs with both buffered and non-buffered didanosine formulations. When coadministered, tenofovir and didanosine EC may be taken under fasted conditions or with a light meal (under 400 kcal, containing 20% or less fat); coadministration of didanosine buffered tablet formulation with tenofovir should be under fasted conditions. Coadministration of tenofovir and didanosine should be undertaken with caution and patients receiving this combination should be monitored closely for didanosine-associated adverse events. Didanosine therapy should be suspended if signs or symptoms of pancreatitis, symptomatic hyperlactatemia, or lactic acidosis develop.
Echinacea: (Moderate) Use Echinacea sp. with caution in patients taking medications for human immunodeficiency virus (HIV) infection. Some experts have suggested that Echinacea's effects on the immune system might cause problems for patients with HIV infection, particularly with long-term use. There may be less risk with short-term use (less than 2 weeks). A few pharmacokinetic studies have shown reductions in blood levels of some antiretroviral medications when Echinacea was given, presumably due to CYP induction. However, more study is needed for various HIV treatment regimens. Of the agents studied, the interactions do not appear to be significant or to require dose adjustments at the time of use. Although no dose adjustments are required, monitoring drug concentrations may give reassurance during co-administration. Monitor viral load and other parameters carefully during therapy.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) HIV guidelines recommend against concurrent use of tenofovir, PMPA and didanosine; however, these medications can be used together, if necessary, in patients with a creatinine clearance 60 mL/min or more if the didanosine dose is reduced; decrease the didanosine dose to 250 mg in patients weighing 60 kg or more and to 200 mg in patients weighing 25 to 59 kg. Concurrent administration of tenofovir, PMPA and didanosine, ddI increases the concentration of both didanosine and its active metabolite (dideoxyadenosine 5-triphosphate) which may cause or worsen didanosine-related clinical toxicities, including pancreatitis, symptomatic hyperlactatemia/lactic acidosis, and peripheral neuropathy. In addition, this combination has been associated with CD4 cell count decline despite viral suppression, high rates of early virologic failure, and rapid selection of resistance mutations. The mechanism of the interaction is not known, but the interaction occurs with both buffered and non-buffered didanosine formulations. When coadministered, tenofovir and didanosine EC may be taken under fasted conditions or with a light meal (under 400 kcal, containing 20% or less fat); coadministration of didanosine buffered tablet formulation with tenofovir should be under fasted conditions. Coadministration of tenofovir and didanosine should be undertaken with caution and patients receiving this combination should be monitored closely for didanosine-associated adverse events. Didanosine therapy should be suspended if signs or symptoms of pancreatitis, symptomatic hyperlactatemia, or lactic acidosis develop.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) HIV guidelines recommend against concurrent use of tenofovir, PMPA and didanosine; however, these medications can be used together, if necessary, in patients with a creatinine clearance 60 mL/min or more if the didanosine dose is reduced; decrease the didanosine dose to 250 mg in patients weighing 60 kg or more and to 200 mg in patients weighing 25 to 59 kg. Concurrent administration of tenofovir, PMPA and didanosine, ddI increases the concentration of both didanosine and its active metabolite (dideoxyadenosine 5-triphosphate) which may cause or worsen didanosine-related clinical toxicities, including pancreatitis, symptomatic hyperlactatemia/lactic acidosis, and peripheral neuropathy. In addition, this combination has been associated with CD4 cell count decline despite viral suppression, high rates of early virologic failure, and rapid selection of resistance mutations. The mechanism of the interaction is not known, but the interaction occurs with both buffered and non-buffered didanosine formulations. When coadministered, tenofovir and didanosine EC may be taken under fasted conditions or with a light meal (under 400 kcal, containing 20% or less fat); coadministration of didanosine buffered tablet formulation with tenofovir should be under fasted conditions. Coadministration of tenofovir and didanosine should be undertaken with caution and patients receiving this combination should be monitored closely for didanosine-associated adverse events. Didanosine therapy should be suspended if signs or symptoms of pancreatitis, symptomatic hyperlactatemia, or lactic acidosis develop.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Elvitegravir must be taken with food; didanosine, ddI must be taken on an empty stomach. If these drug are administered together, give didanosine on an empty stomach at least 1 hour before or 2 hours after adminstering elvitegravir with food.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) HIV guidelines recommend against concurrent use of tenofovir, PMPA and didanosine; however, these medications can be used together, if necessary, in patients with a creatinine clearance 60 mL/min or more if the didanosine dose is reduced; decrease the didanosine dose to 250 mg in patients weighing 60 kg or more and to 200 mg in patients weighing 25 to 59 kg. Concurrent administration of tenofovir, PMPA and didanosine, ddI increases the concentration of both didanosine and its active metabolite (dideoxyadenosine 5-triphosphate) which may cause or worsen didanosine-related clinical toxicities, including pancreatitis, symptomatic hyperlactatemia/lactic acidosis, and peripheral neuropathy. In addition, this combination has been associated with CD4 cell count decline despite viral suppression, high rates of early virologic failure, and rapid selection of resistance mutations. The mechanism of the interaction is not known, but the interaction occurs with both buffered and non-buffered didanosine formulations. When coadministered, tenofovir and didanosine EC may be taken under fasted conditions or with a light meal (under 400 kcal, containing 20% or less fat); coadministration of didanosine buffered tablet formulation with tenofovir should be under fasted conditions. Coadministration of tenofovir and didanosine should be undertaken with caution and patients receiving this combination should be monitored closely for didanosine-associated adverse events. Didanosine therapy should be suspended if signs or symptoms of pancreatitis, symptomatic hyperlactatemia, or lactic acidosis develop. (Moderate) Elvitegravir must be taken with food; didanosine, ddI must be taken on an empty stomach. If these drug are administered together, give didanosine on an empty stomach at least 1 hour before or 2 hours after adminstering elvitegravir with food.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) While no dosage adjustments are required, because didanosine, ddI is administered on an empty stomach and rilpivirine is given with food, do not give didanosine within at least two hours before or at least four hours after rilpivirine.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) HIV guidelines recommend against concurrent use of tenofovir, PMPA and didanosine; however, these medications can be used together, if necessary, in patients with a creatinine clearance 60 mL/min or more if the didanosine dose is reduced; decrease the didanosine dose to 250 mg in patients weighing 60 kg or more and to 200 mg in patients weighing 25 to 59 kg. Concurrent administration of tenofovir, PMPA and didanosine, ddI increases the concentration of both didanosine and its active metabolite (dideoxyadenosine 5-triphosphate) which may cause or worsen didanosine-related clinical toxicities, including pancreatitis, symptomatic hyperlactatemia/lactic acidosis, and peripheral neuropathy. In addition, this combination has been associated with CD4 cell count decline despite viral suppression, high rates of early virologic failure, and rapid selection of resistance mutations. The mechanism of the interaction is not known, but the interaction occurs with both buffered and non-buffered didanosine formulations. When coadministered, tenofovir and didanosine EC may be taken under fasted conditions or with a light meal (under 400 kcal, containing 20% or less fat); coadministration of didanosine buffered tablet formulation with tenofovir should be under fasted conditions. Coadministration of tenofovir and didanosine should be undertaken with caution and patients receiving this combination should be monitored closely for didanosine-associated adverse events. Didanosine therapy should be suspended if signs or symptoms of pancreatitis, symptomatic hyperlactatemia, or lactic acidosis develop. (Moderate) While no dosage adjustments are required, because didanosine, ddI is administered on an empty stomach and rilpivirine is given with food, do not give didanosine within at least two hours before or at least four hours after rilpivirine.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) HIV guidelines recommend against concurrent use of tenofovir, PMPA and didanosine; however, these medications can be used together, if necessary, in patients with a creatinine clearance 60 mL/min or more if the didanosine dose is reduced; decrease the didanosine dose to 250 mg in patients weighing 60 kg or more and to 200 mg in patients weighing 25 to 59 kg. Concurrent administration of tenofovir, PMPA and didanosine, ddI increases the concentration of both didanosine and its active metabolite (dideoxyadenosine 5-triphosphate) which may cause or worsen didanosine-related clinical toxicities, including pancreatitis, symptomatic hyperlactatemia/lactic acidosis, and peripheral neuropathy. In addition, this combination has been associated with CD4 cell count decline despite viral suppression, high rates of early virologic failure, and rapid selection of resistance mutations. The mechanism of the interaction is not known, but the interaction occurs with both buffered and non-buffered didanosine formulations. When coadministered, tenofovir and didanosine EC may be taken under fasted conditions or with a light meal (under 400 kcal, containing 20% or less fat); coadministration of didanosine buffered tablet formulation with tenofovir should be under fasted conditions. Coadministration of tenofovir and didanosine should be undertaken with caution and patients receiving this combination should be monitored closely for didanosine-associated adverse events. Didanosine therapy should be suspended if signs or symptoms of pancreatitis, symptomatic hyperlactatemia, or lactic acidosis develop.
Food: (Major) Food interactions are possible with didanosine, ddI, and it should not be taken with food. Didanosine is acid-labile and susceptible to degradation by stomach acid. Absorption from the GI tract therefore varies among individuals and is also affected by the dosage form, presence of food, and gastric pH. The manufacturer recommends that all didanosine products be given on an empty stomach 30 minutes before or 2 hours after meals. Administration up to 2 hours after a meal reduces peak blood levels and AUC by 55%. To improve adherence, some practitioners administer didanosine without regard to food administration. In a study comparing fed and fasting state administration in children (n=106), overall systemic exposure (AUC) was similar between groups with slower absorption and prolonged elimination noted during the administration of food. Additionally, studies in adults suggest that it may be given without regard to food.
Fosamprenavir: (Moderate) It is recommended that the administration of fosamprenavir and buffered medications such as didanosine, ddI, be separated by at least 1 hour.
Ganciclovir: (Moderate) Ganciclovir can increase the AUC and Cmax of didanosine, ddI when given concurrently. Patients should be monitored closely for didanosine toxicity when receiving ganciclovir concurrently.
Gemifloxacin: (Major) Administer didanosine tablets or powder for oral solution at least 3 hours before or 2 hours after gemifloxacin. Gemifloxacin absorption may be reduced as it can chelate with the buffering agents contained in didanosine tablets and powder. The delayed-release didanosine capsules do not contain a buffering agent and would not be expected to interact with gemifloxacin.
Hydroxyurea: (Major) While there have been reports that the combined use of hydroxyurea and didanosine may result in an increased immune response for up to 1 year, the combined use of these drugs is associated with an increased incidence of didanosine-associated adverse effects, including pancreatitis and peripheral neuropathy. Additionally, there are post-marketing reports of hepatotoxicity and hepatic failure resulting in death with a treatment regimen of 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. Finally, it is recommended that hydroxyurea not be used in patients with HIV; reports of hydroxyurea's improvement of viral suppression are inconsistent and hydroxyurea is associated with decreased CD4 counts.
Indinavir: (Major) Concomitant use of indinavir and didanosine chewable tablets or powder for oral solution may decrease the serum concentratons of indinavir resulting in decreased efficacy. To avoid this interaction, administer indinavir 1 hour prior to didanosine chewable tablets or powder. No clinically significant pharmacokinetic interaction between didanosine capsules and indinavir have been reported.
Iron: (Moderate) Iron salts should not be administered simultaneously with didanosine, ddI chewable tablets or powder for oral solution. Oral absorption of iron supplements is reduced if given with antacids; the buffering agents contained in didanosine tablets and powder likewise reduce iron salt absorption. Administer oral doses of iron salts 1 hour before or 4 hours after didanosine tablet or powder administration. The delayed-release didanosine capsules do not contain a buffering agent and would not be expected to interact with iron salts.
Itraconazole: (Major) Administer itraconazole at least 2 hours before or several hours after didanosine chewable tablets and powder for oral solution. Didanosine chewable tablets and powder for oral solution contain acid buffers to enhance the bioavailability of didanosine. These buffers, however, may decrease the absorption of itraconazole, which requires an acid environment for absorption. The delayed-release didanosine capsules do not contain a buffering agent and would not be expected to interact with itraconazole.
Ketoconazole: (Major) Administer ketoconazole at least 2 hours before or several hours after didanosine chewable tablets and powder for oral solution. Didanosine chewable tablets and powder for oral solution contain acid buffers to enhance the bioavailability of didanosine. These buffers, however, may decrease the absorption of ketoconazole, which requires an acid environment for absorption. The delayed-release didanosine capsules do not contain a buffering agent and would not be expected to interact with ketoconazole.
Lamivudine; Tenofovir Disoproxil Fumarate: (Major) HIV guidelines recommend against concurrent use of tenofovir, PMPA and didanosine; however, these medications can be used together, if necessary, in patients with a creatinine clearance 60 mL/min or more if the didanosine dose is reduced; decrease the didanosine dose to 250 mg in patients weighing 60 kg or more and to 200 mg in patients weighing 25 to 59 kg. Concurrent administration of tenofovir, PMPA and didanosine, ddI increases the concentration of both didanosine and its active metabolite (dideoxyadenosine 5-triphosphate) which may cause or worsen didanosine-related clinical toxicities, including pancreatitis, symptomatic hyperlactatemia/lactic acidosis, and peripheral neuropathy. In addition, this combination has been associated with CD4 cell count decline despite viral suppression, high rates of early virologic failure, and rapid selection of resistance mutations. The mechanism of the interaction is not known, but the interaction occurs with both buffered and non-buffered didanosine formulations. When coadministered, tenofovir and didanosine EC may be taken under fasted conditions or with a light meal (under 400 kcal, containing 20% or less fat); coadministration of didanosine buffered tablet formulation with tenofovir should be under fasted conditions. Coadministration of tenofovir and didanosine should be undertaken with caution and patients receiving this combination should be monitored closely for didanosine-associated adverse events. Didanosine therapy should be suspended if signs or symptoms of pancreatitis, symptomatic hyperlactatemia, or lactic acidosis develop.
Lesinurad; Allopurinol: (Contraindicated) Concurrent use of allopurinol and didanosine, ddI is contraindicated. Coadministration may result in increased concentrations of didanosine and may increase the incidence of pancreatitis. In 14 healthy volunteers, the mean AUC of didanosine increased approximately 2-fold when given with allopurinol. This interaction was more pronounced in 2 patients with renal impairment, as coadministration resulted in elevated didanosine AUC and Cmax of 312% and 232%, respectively. The effects of allopurinol in patients with normal renal function is not known.
Levofloxacin: (Major) Administer didanosine tablets or powder for oral solution at least 2 hours before or 2 hours after orally administered levofloxacin. Levofloxacin absorption may be reduced as it can chelate with the buffering agents contained in didanosine tablets and powder. The delayed-release didanosine capsules do not contain a buffering agent and would not be expected to interact with levofloxacin.
Levoketoconazole: (Major) Administer ketoconazole at least 2 hours before or several hours after didanosine chewable tablets and powder for oral solution. Didanosine chewable tablets and powder for oral solution contain acid buffers to enhance the bioavailability of didanosine. These buffers, however, may decrease the absorption of ketoconazole, which requires an acid environment for absorption. The delayed-release didanosine capsules do not contain a buffering agent and would not be expected to interact with ketoconazole.
Levothyroxine: (Moderate) Oral thyroid hormones should be taken at least 2 hours before the administration of certain didanosine formulations to avoid an interaction. Certain didanosine, ddI formulations contain buffers (e.g., chewable/dispersible tablets and oral powder for solution) or are mixed with antacids (e.g., pediatric powder for oral solution). Thyroid hormones are susceptible to drug interactions with buffers/antacids containing aluminum, magnesium, or calcium, which may chelate thyroid hormones within the GI tract and decrease oral thyroid hormone absorption. Gastric acidity is also an essential requirement for adequate absorption of levothyroxine. Hypothyroidism may occur if doses are not separated. The delayed-release didanosine capsules (e.g., Videx EC) do not contain a buffering agent and are not expected to interact with thyroid hormones.
Levothyroxine; Liothyronine (Porcine): (Moderate) Oral thyroid hormones should be taken at least 2 hours before the administration of certain didanosine formulations to avoid an interaction. Certain didanosine, ddI formulations contain buffers (e.g., chewable/dispersible tablets and oral powder for solution) or are mixed with antacids (e.g., pediatric powder for oral solution). Thyroid hormones are susceptible to drug interactions with buffers/antacids containing aluminum, magnesium, or calcium, which may chelate thyroid hormones within the GI tract and decrease oral thyroid hormone absorption. Gastric acidity is also an essential requirement for adequate absorption of levothyroxine. Hypothyroidism may occur if doses are not separated. The delayed-release didanosine capsules (e.g., Videx EC) do not contain a buffering agent and are not expected to interact with thyroid hormones.
Levothyroxine; Liothyronine (Synthetic): (Moderate) Oral thyroid hormones should be taken at least 2 hours before the administration of certain didanosine formulations to avoid an interaction. Certain didanosine, ddI formulations contain buffers (e.g., chewable/dispersible tablets and oral powder for solution) or are mixed with antacids (e.g., pediatric powder for oral solution). Thyroid hormones are susceptible to drug interactions with buffers/antacids containing aluminum, magnesium, or calcium, which may chelate thyroid hormones within the GI tract and decrease oral thyroid hormone absorption. Gastric acidity is also an essential requirement for adequate absorption of levothyroxine. Hypothyroidism may occur if doses are not separated. The delayed-release didanosine capsules (e.g., Videx EC) do not contain a buffering agent and are not expected to interact with thyroid hormones.
Liothyronine: (Moderate) Oral thyroid hormones should be taken at least 2 hours before the administration of certain didanosine formulations to avoid an interaction. Certain didanosine, ddI formulations contain buffers (e.g., chewable/dispersible tablets and oral powder for solution) or are mixed with antacids (e.g., pediatric powder for oral solution). Thyroid hormones are susceptible to drug interactions with buffers/antacids containing aluminum, magnesium, or calcium, which may chelate thyroid hormones within the GI tract and decrease oral thyroid hormone absorption. Gastric acidity is also an essential requirement for adequate absorption of levothyroxine. Hypothyroidism may occur if doses are not separated. The delayed-release didanosine capsules (e.g., Videx EC) do not contain a buffering agent and are not expected to interact with thyroid hormones.
Magnesium Hydroxide: (Minor) The side effects associated with magnesium hydroxide may potentially be increased during concurrent use with didanosine, ddI because some ddI products also contain similar antacid ingredients. Although this interaction should be of minor clinical significance for most patients, clinicians should be alert to a possible increased risk of side effects associated with taking an additional antacid product concurrently with ddI products.
Methadone: (Major) Methadone decreases the AUC and Cmax of didanosine, ddI. Methadone may slow absorption, and increase first-pass metabolism of didanosine. Methadone decreased the AUC of didanosine tablets by 60% and the Cmax by 64% suggesting that increased doses of didanosine may be required in patients receiving methadone. Do not coadminister methadone with Videx pediatric powder due to significant decreases in didanosine concentrations. If coadministration of methadone and didanosine is necessary, the extended-release capsules are recommended (Videx EC). Patients should be closely monitored for adequate clinical response when the extended-release capsules are coadministered with methadone, including monitoring for changes in HIV RNA viral load.
Moxifloxacin: (Major) Administer oral moxifloxacin at least 4 hours before or 8 hours after didanosine tablets or powder for oral solution. Moxifloxacin absorption may be reduced as it can chelate with the buffering agents contained in didanosine tablets and powder. The delayed-release didanosine capsules do not contain a buffering agent and would not be expected to interact with moxifloxacin.
Nelfinavir: (Minor) When administered as a single 750-mg dose 1 hour after didanosine, ddI, nelfinavir's AUC was increased by 12%. Although this increase was found to be clinically insignificant, the manufacturer of nelfinavir recommends administering nelfinavir 1 hour after or 2 hours before didanosine.
Ofloxacin: (Major) Administer didanosine tablets or powder for oral solution at least 2 hours before or 2 hours after ofloxacin. Ofloxacin absorption may be reduced as it can chelate with the buffering agents contained in didanosine tablets and powder. The delayed-release didanosine capsules do not contain a buffering agent and would not be expected to interact with ofloxacin.
Orlistat: (Moderate) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
Pexidartinib: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with didanosine. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
Pretomanid: (Major) Avoid coadministration of pretomanid with didanosine, especially in patients with impaired hepatic function, due to increased risk for hepatotoxicity. Monitor for evidence of hepatotoxicity if coadministration is necessary. If new or worsening hepatic dysfunction occurs, discontinue hepatotoxic medications.
Ribavirin: (Contraindicated) Use of ribavirin in combination with didanosine, ddI is contraindicated. Concurrent administration increases blood concentrations of didanosine and its active metabolite, resulting in fatal hepatic failure and increased incidence of other didanosine-related clinical toxicities.
Rilpivirine: (Moderate) While no dosage adjustments are required, because didanosine, ddI is administered on an empty stomach and rilpivirine is given with food, do not give didanosine within at least two hours before or at least four hours after rilpivirine.
Riluzole: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and didanosine. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Stavudine, d4T: (Contraindicated) Concurrent administration of stavudine and didanosine is contraindicated. Use of these drugs together increases the risk for serious and life-threatening adverse events, including pancreatitis, lactic acidosis, hepatotoxicity, and peripheral neuropathy.
Tenofovir Disoproxil Fumarate: (Major) HIV guidelines recommend against concurrent use of tenofovir, PMPA and didanosine; however, these medications can be used together, if necessary, in patients with a creatinine clearance 60 mL/min or more if the didanosine dose is reduced; decrease the didanosine dose to 250 mg in patients weighing 60 kg or more and to 200 mg in patients weighing 25 to 59 kg. Concurrent administration of tenofovir, PMPA and didanosine, ddI increases the concentration of both didanosine and its active metabolite (dideoxyadenosine 5-triphosphate) which may cause or worsen didanosine-related clinical toxicities, including pancreatitis, symptomatic hyperlactatemia/lactic acidosis, and peripheral neuropathy. In addition, this combination has been associated with CD4 cell count decline despite viral suppression, high rates of early virologic failure, and rapid selection of resistance mutations. The mechanism of the interaction is not known, but the interaction occurs with both buffered and non-buffered didanosine formulations. When coadministered, tenofovir and didanosine EC may be taken under fasted conditions or with a light meal (under 400 kcal, containing 20% or less fat); coadministration of didanosine buffered tablet formulation with tenofovir should be under fasted conditions. Coadministration of tenofovir and didanosine should be undertaken with caution and patients receiving this combination should be monitored closely for didanosine-associated adverse events. Didanosine therapy should be suspended if signs or symptoms of pancreatitis, symptomatic hyperlactatemia, or lactic acidosis develop.
Tetracyclines: (Major) Tetracyclines should not be administered simultaneously with didanosine, ddI chewable tablets or powder for oral solution. The buffering agents contained in didanosine tablets and powder reduce tetracycline absorption. Administer oral doses of tetracycline antibiotics 1 hour before or 4 hours after didanosine tablet or powder administration. The delayed-release didanosine capsules do not contain a buffering agent and would not be expected to interact with tetracycline antibiotics.
Thyroid hormones: (Moderate) Oral thyroid hormones should be taken at least 2 hours before the administration of certain didanosine formulations to avoid an interaction. Certain didanosine, ddI formulations contain buffers (e.g., chewable/dispersible tablets and oral powder for solution) or are mixed with antacids (e.g., pediatric powder for oral solution). Thyroid hormones are susceptible to drug interactions with buffers/antacids containing aluminum, magnesium, or calcium, which may chelate thyroid hormones within the GI tract and decrease oral thyroid hormone absorption. Gastric acidity is also an essential requirement for adequate absorption of levothyroxine. Hypothyroidism may occur if doses are not separated. The delayed-release didanosine capsules (e.g., Videx EC) do not contain a buffering agent and are not expected to interact with thyroid hormones.
Tipranavir: (Moderate) Concurrent administration of tipranavir and ritonavir with didanosine, ddI results in decreased didanosine concentrations. For optimal absorption, tipranavir and ritonavir should not be administered within 2 hours of buffered didanosine.
Valganciclovir: (Moderate) Valganciclovir may increase the concentration of didanosine, ddI, when given concurrently. Patients should be monitored closely for didanosine toxicity (e.g., pancreatitis) when receiving valganciclovir concurrently.

Didanosine/Videx EC Oral Cap DR Pellets: 125mg, 200mg, 250mg, 400mg
Videx Oral Pwd F/Recon: 1mL, 10mg

weight 60 kg or more: 400 mg/day PO.
weight less than 60 kg: 250 mg/day PO.

weight 60 kg or more: 400 mg/day PO.
weight less than 60 kg: 250 mg/day PO.

weight 60 kg or more: 400 mg/day PO for extended-release capsules; 240 mg/m2/day PO for pediatric powder for oral solution is the FDA-approved maximum dosage; however, doses as high as 300 mg/m2/day (Max: 400 mg/day) have been used off-label.
weight 25 to 59 kg: 250 mg/day PO for extended-release capsules; 240 mg/m2/day PO for pediatric powder for oral solution is the FDA-approved maximum dosage; however, doses as high as 300 mg/m2/day (Max: 250 mg/day) have been used off-label.
weight 20 to 24 kg: 200 mg/day PO for extended-release capsules; 240 mg/m2/day PO for pediatric powder for oral solution is the FDA-approved maximum dosage; however, doses as high as 300 mg/m2/day (Max: 250 mg/day) have been used off-label.

6 to 12 years and weight 60 kg or more: 400 mg/day PO for extended-release capsules; 240 mg/m2/day PO for pediatric powder for oral solution is FDA-approved maximum dosage; however, doses as high as 300 mg/m2/day (Max: 400 mg/day) have been used off-label.
6 to 12 years and weight 25 to 59 kg: 250 mg/day PO for extended-release capsules; 240 mg/m2/day PO for pediatric powder for oral solution is FDA-approved maximum dosage; however, doses as high as 300 mg/m2/day (Max: 250 mg/day) have been used off-label.
6 to 12 years and weight 20 to 24 kg: 200 mg/day PO for extended-release capsules; 240 mg/m2/day PO for pediatric powder for oral solution is FDA-approved maximum dosage; however, doses as high as 300 mg/m2/day (Max: 250 mg/day) have been used off-label.
1 to 5 years or weight less than 20 kg: 240 mg/m2/day PO for pediatric powder for oral solution is FDA-approved maximum dosage; however, doses as high as 300 mg/m2/day have been used off-label; safety and efficacy of extended-release capsules have not been established. 

9 to 12 months: 240 mg/m2/day PO for oral solution is FDA-approved maximum dosage; however, doses as high as 300 mg/m2/day have been used off-label; safety and efficacy of other formulations have not been established.
3 to 8 months: 200 mg/m2/day PO for oral solution; safety and efficacy of other formulations have not been established.
1 to 2 months: 200 mg/m2/day PO for oral solution is FDA-approved maximum dosage; however, many limit dosage to 100 mg/m2/day in this age group to decrease toxicity; safety and efficacy of other formulations have not been established.

14 to 29 days: 200 mg/m2/day PO for pediatric powder for oral solution is FDA-approved maximum dosage; however, many limit dosage to 100 mg/m2/day in this age group to decrease toxicity; safety and efficacy of other formulations have not been established.
0 to 13 days: Safety and efficacy have not been established.

Didanosine inhibits the activity of viral RNA-directed DNA polymerase (i.e., reverse transcriptase). Antiviral activity is dependent on intracellular conversion to the active triphosphorylated form. The rate of didanosine phosphorylation varies, depending on cell type. It is believed that inhibition of reverse transcriptase interferes with the generation of DNA copies of viral RNA, which, in turn, are necessary for the synthesis of new virions. Intracellular enzymes subsequently eliminate the HIV particle that previously had been uncoated, and left unprotected, during entry into the host cell. Thus, reverse transcriptase inhibitors are virustatic and do not eliminate HIV from the body. Even though human DNA polymerase is less susceptible to the pharmacologic effects of triphosphorylated didanosine, this action may nevertheless account for some of the drug's toxicity.[29580] [52942] [52952]
 
Although resistance to reverse transcriptase inhibitors has been induced in vitro by propagating the virus in the presence of subinhibitory concentrations of the drug, it appears that resistance to didanosine and zidovudine occurs as a result of mutations at different genetic loci. Thus, while didanosine and zidovudine possess a similar mechanism of action, didanosine may be an effective alternative in patients with HIV infection who deteriorate while receiving zidovudine.[23646]

Didanosine is administered orally. Protein binding of didanosine is less than 5%, which contributes to its extensive distribution. CSF concentrations of didanosine reach 21—85% of plasma concentrations.
 
Metabolism of didanosine has not been well studied in humans, but it is assumed to follow normal purine metabolism and elimination. In HIV-infected adults, the plasma half-life is 1.3—1.6 hours. Elimination from the intracellular compartment, however, is much slower. In vitro, it ranges from 8—24 hours, thus allowing for bid dosing. Renal clearance of the drug is 50% of total body clearance.

Didanosine, ddI is acid-labile and susceptible to degradation by stomach acid. Absorption of didanosine from the GI tract therefore varies among individuals and is also affected by the dosage form, presence of food, and gastric pH. Because of this, didanosine tablets and powder contain buffering agents. The extended release capsules contain enteric-coated didanosine beadlets that protect against degradation by stomach acid. The enteric coating dissolves when the beadlets empty into the small intestine. Didanosine should be given 1 hour before meals, on an empty stomach. Oral absorption is approximately 33—43% in the fasting state. Administration within 5 minutes of a meal reduces didanosine peak blood levels by about 50%. The didanosine Cmax administered as the delayed-release capsules is reduced 40% relative to didanosine buffered tablets. However, the AUC of the delayed-release capsules is equivalent to the buffered tablets. Didanosine chewable tablets are 20—25% more bioavailable than the powder for oral solution. The dosing recommendations for each product reflect these pharmacokinetic differences. The Tmax for didanosine increases from approximately 0.67 hours for the buffered tablets to 2 hours for the delayed-release capsules.

Antiretroviral therapy should be provided to all patients during pregnancy, regardless of HIV RNA concentrations or CD4 cell count. Using highly active antiretroviral combination therapy (HAART) to maximally suppress viral replication is the most effective strategy to prevent the development of resistance and to minimize the risk of perinatal transmission. Begin HAART as soon as pregnancy is recognized, or HIV is diagnosed. Didanosine is not recommended as part of an antiretroviral regimen in pregnant patients due to an increased risk of serious toxicity. If a patient becomes pregnant while taking didanosine, consider switching to an alternative treatment regimen. Available data from the Antiretroviral Pregnancy Registry (APR), which includes more than 420 first trimester exposures to didanosine, show an increased risk of overall major birth defects when compared to the 2.7% background rate among pregnant women in the US. When didanosine exposure occurred in the first trimester, the prevalence of defects was 4.68% (95% CI: 2.88 to 7.14). No pattern of defects was identified upon review of all reported cases. Nucleoside reverse transcriptase inhibitors (NRTIs) are known to induce mitochondrial dysfunction. An association of mitochondrial dysfunction in infants and in utero antiretroviral exposure has been suggested, but not established. While the development of severe or fatal mitochondrial disease in exposed infants appears to be extremely rare, more intensive monitoring of hematologic and electrolyte parameters during the first few weeks of life is advised. Nucleoside analogs have been associated with the development of lactic acidosis, especially during pregnancy. It is unclear if pregnancy augments the incidence of lactic acidosis/hepatic steatosis in patients receiving nucleoside analogs. However, because pregnancy itself can mimic some early symptoms of the lactic acid/hepatic steatosis syndrome or be associated with other significant disorders of liver metabolism, clinicians need to be alert for early diagnosis of this syndrome. Pregnant patients receiving nucleoside analogs should have LFTs and serum electrolytes assessed more frequently during the last trimester of pregnancy, and any new symptoms should be evaluated thoroughly. Cases of lactic acidosis, some fatal, have been reported in pregnant patients receiving didanosine and stavudine together; concurrent use of these antiretroviral agents is contraindicated. Regular laboratory monitoring is recommended to determine antiretroviral efficacy. Monitor CD4 counts at the initial visit. Patients who have been on HAART for at least 2 years and have consistent viral suppression and CD4 counts consistently greater than 300 cells/mm3 do not need CD4 counts monitored after the initial visit during the pregnancy. However, CD4 counts should be monitored every 3 months during pregnancy for patients on HAART less than 2 years, patients with CD4 count less than 300 cells/mm3, or patients with inconsistent adherence or detectable viral loads. Monitor plasma HIV RNA at the initial visit (with review of prior levels), 2 to 4 weeks after initiating or changing therapy, monthly until undetectable, and then at least every 3 months during pregnancy. Viral load should also be assessed at approximately 36 weeks gestation, or within 4 weeks of delivery, to inform decisions regarding mode of delivery and optimal treatment for newborns. Patients whose HIV RNA levels are above the threshold for resistance testing (usually greater than 500 copies/mL but may be possible for levels greater than 200 copies/mL in some laboratories) should undergo antiretroviral resistance testing (genotypic testing, and if indicated, phenotypic testing). Resistance testing should be conducted before starting therapy in treatment-naive patients who have not been previously tested, starting therapy in treatment-experienced patients (including those who have received pre-exposure prophylaxis), modifying therapy in patients who become pregnant while receiving treatment, or modifying therapy in patients who have suboptimal virologic response to treatment that was started during pregnancy. DO NOT delay initiation of antiretroviral therapy while waiting on the results of resistance testing; treatment regimens can be modified, if necessary, once the testing results are known. First trimester ultrasound is recommended to confirm gestational age and provide an accurate estimation of gestational age at deliver. A second trimester ultrasound can be used for both anatomical survey and determination of gestational age in those patients not seen until later in gestation. Perform standard glucose screening in patients receiving antiretroviral therapy, although it should be noted that some experts would perform earlier screening with ongoing chronic protease inhibitor-based therapy initiated prior to pregnancy at 24 to 28 weeks gestation, similar to recommendations for patients with high-risk factors for glucose intolerance. Liver function testing is recommended within 2 to 4 weeks after initiating or changing antiretroviral therapy, and approximately every 3 months thereafter during pregnancy (or as needed). All pregnant patients should be counseled about the importance of adherence to their antiretroviral regimen to reduce the potential for development of resistance and perinatal transmission. It is strongly recommended that antiretroviral therapy, once initiated, not be discontinued. If a patient decides to discontinue therapy, a consultation with an HIV specialist is recommended. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to didanosine; information about the registry can be obtained at www.apregistry.com or by calling 1-800-258-4263.

HIV treatment guidelines recommend clinicians provide mothers with evidence-based, patient-centered counseling to support shared decision-making regarding infant feeding. Inform patients that use of replacement feeding (i.e., formula or banked pasteurized donor human milk) eliminates the risk of HIV transmission; thus, replacement feeding is recommended for use when mothers with HIV are not on antiretroviral therapy (ART) or do not have suppressed viral load during pregnancy, as well as at delivery. For patients on ART who have achieved and maintained viral suppression during pregnancy (at minimum throughout the third trimester) and postpartum, the transmission risk from breast-feeding is less than 1%, but not zero. Virologically suppressed mothers who choose to breast-feed should be supported in this decision. If breast-feeding is chosen, counsel the patient about the importance of adherence to therapy and recommend that the infant be exclusively breast-fed for up to 6 months of age, as exclusive breast-feeding has been associated with a lower rate of HIV transmission as compared to mixed feeding (i.e., breast milk and formula). Promptly identify and treat mastitis, thrush, and cracked or bleeding nipples, as these conditions may increase the risk of HIV transmission through breast-feeding. Breast-fed infants should undergo immediate diagnostic and virologic HIV testing. Testing should continue throughout breast-feeding and up to 6 months after cessation of breast-feeding. For expert consultation, healthcare workers may contact the Perinatal HIV Hotline (888-448-8765). There are limited data regarding the use of didanosine during breast-feeding and excretion of didanosine into human breast milk is unknown. Antiretroviral medications whose passage into human breast milk have been evaluated include nevirapine, zidovudine, lamivudine, and nelfinavir.