Didanosine (Videx) is a purine nucleoside analog and potent anti-retroviral medicine that inhibits the replication of HIV.

Indications of Didanosine (Videx):

• HIV infection:
  • It is indicated for the treatment of HIV-1 infection in combination with other antiretroviral agents.

Didanosine dose in adults:

Didanosine (Videx) Treatment dose of HIV-1 infection: 

• Dosing based on patient weight:
  • Pediatric powder for oral solution:
    • <60 kg: 125 mg per oral twice daily (preferred) or 250 mg once daily.
    • ≥60 kg: 200 mg per oral twice daily (preferred) or 400 mg once daily.
  • Delayed-release capsule:
    • 20 kg to <25 kg: 200 mg per oral once daily.
    • 25 kg to <60 kg: 250 mg once daily.
    • ≥60 kg: 400 mg once daily.
• Dosage adjustment for concomitant therapy:
  • When taken with tenofovir:
    • <60 kg and CrCl ≥60 mL/minute:
      • 200 mg per oral once daily.
    • ≥60 kg and CrCl ≥60 mL/minute:
      • 250 mg once daily.

Didanosine (Videx) dose in children:

Didanosine (Videx) Treatment dose of HIV-1 infection: 

• Use in combination with other antiretroviral agents:
  • Infants 1 to 8 months (HHS): Oral solution:
    • Infants 1 to <3 months:
      • 50 mg/m²/dose every 12 hours.
      • Note:
        • Manufacturer's labeling not recommended (100 mg/m²/dose).
        • Toxicity can occur with higher doses as per pharmacokinetic data.
    • Infants ≥3 to 8 months:
      • 100 mg/m²/dose every 12 hours.
  • Infants >8 months, Children, and Adolescents:
    • Manufacturer's labeling:
      • Oral solution: 120 mg/m²/dose every 12 hours; do not exceed weight-based adult dose.
    • AIDS info recommendation (HHS):
      • Oral solution: 120 mg/m²/dose (range: 90 to 150 mg/m /dose) every 12 hours, do not exceed weight-based adult dose.
    • Alternate once-daily dosing for treatment-naive children ≥3 years and Adolescents:
      • 240 mg/m²/dose once daily.
      • maximum dose: 400 mg/dose.
• Delayed-release capsule:
  • Children ≥6 years weighing ≥20 kg who are able to swallow a capsule whole:
    • 20 kg to <25 kg:
      • 200 mg per oral once daily.
    • 25 kg to <60 kg:
      • 250 mg once daily.
    • ≥60 kg:
      • 400 mg once daily.
  • Dosing adjustment for concomitant tenofovir therapy:
    • There are no pediatric-specific recommendations; in adult patients, dosing adjustment suggested.

Didanosine (Videx) Pregnancy Risk Category: B

• Didanosine is able to transfer from the human placenta at a low-to-moderate level.
• Data from the Antiretroviral Pregnancy Registry show that didanosine usage during pregnancy in the early and late trimesters of pregnancy increases the rate of birth defects.
• However, there is no evidence of a pattern and clinical relevance.
• Preterm births are possible due to maternal antiviral treatment.
• However, information is not available due to variability in maternal factors such as gestational age at the start of therapy and severity of disease.
• Some cases had a higher risk of stillbirth, low birthweight, and small gestational infants.
• Maternal ART should not be stopped despite concerns about adverse neonatal outcomes. There is a substantial response to the proper treatment.
• Long-term monitoring is necessary for infants who have been exposed to antiretroviral medication.
• Children who have significant organ dysfunctions of unknown etiology (especially the heart or CNS) should be evaluated for mitochondrial dysfunction.
• [US Boxed Warning]: Combining didanosine with stavudine during pregnancy can lead to life-threatening lactosis.
• Non-reverse transcriptase inhibits can cause lactic acidosis or hepatic Steatosis due to mitochondrial toxicities.
• These adverse events are very similar to other life-threatening, rare syndromes that can occur during pregnancy (eg HELLP syndrome).
• Combination therapy with didanosine/stavudine increases the risk of neurodevelopmental disabilities and birth defects.
• The Health and Human Services' Perinatal HIV Guidelines do not recommend didanosine as a first therapy for pregnant women who are antiretroviral-naive.
• Due to the high risk for toxicities, didanosine should not be administered to females who are pregnant. An alternative treatment should be used.
• All HIV-positive women should receive ART during pregnancy to lower their viral load and decrease the chance of perinatal transmission.
• During pregnancy, it is necessary to monitor more frequently. All females with HIV should continue ART postpartum. It can also be modified after birth.

Didanosine use during breastfeeding:

• It is not known if breast milk contains didanosine.
• Postnatal HIV transmission can still be a problem even with infant or maternal antiretroviral treatment.
• Breastfeeding infants are multiclass-resistant despite maternal therapy.
• Breastfeeding should be avoided in areas where it is affordable, safe, sustainable, and easy to obtain.
• There is also a low risk of infant death from diarrhea or respiratory infections.  

Didanosine (Videx) Dose adjustment in renal disease:

Dosing based on patient weight, creatinine clearance, and dosage form: See table.

Recommended Dose (mg) of Didanosine by Body Weight

• Patients requiring hemodialysis or CAPD:
  • Dose per CrCl <10 mL/minute. Didanosine is not removed via CAPD and a minimal amount of dose (≤7%) is removed by hemodialysis.
  • No supplemental dosing necessary.

Dose adjustment in liver disease:

No dosage adjustment is necessary.  

Common Side Effects of Didanosine (Videx):

• Central nervous system:
  • Peripheral neuropathy
• Endocrine & metabolic:
  • Increased amylase
• Gastrointestinal:
  • Diarrhea
  • Abdominal pain

Rare Side Effects of Didanosine (Videx):

• Dermatologic:
  • Pruritus
  • Skin rash
• Endocrine & metabolic:
  • Increased uric acid
• Gastrointestinal:
  • Pancreatitis
• Hepatic:
  • Increased serum AST
  • Increased serum ALT
  • Increased serum alkaline phosphatase

Contraindications to Didanosine (Videx):

• Allopurinol or ribavirin can be co-administrated with stavudine, ribavirin, and /or allopurinol
• Hypersensitivity to didanosine and any component of the formulation

Warnings and precautions

• Immune reconstitution syndrome:
  • An immune reconstitution syndrome, which can result in an inflammatory reaction to an indolent, residual opportunistic HIV infection, or activation of autoimmune diseases (eg, Graves’ disease, polymysitis, Guillain Barre syndrome) later on in HIV treatment, is possible.
  • Additional management is required.
• Lactic acidosis/hepatomegaly: [US Boxed Warning]:
  • Monotherapy with nucleoside analogs or in combination can cause lactic acidosis, severe hepatomegaly and steatosis, which can prove fatal.
  • Obesity, prolonged exposure, and female gender are all associated with increased risk.
  • Combining didanosine with stavudine in pregnancy can cause life-threatening lactosis.
  • It should not be used in patients who have known risk factors for liver disease.
  • Therapy should be stopped if there are any laboratory or clinical findings that suggest lactic acidosis, hepatotoxicity, or transaminitis (transaminitis can/may not accompany Hepatomegaly or Steatosis).
• Lipoatrophy
  • Didanosine can lead to loss of subcutaneous fat in the buttocks, face, and limbs.
  • Lipoatrophy severity depends on cumulative exposure. It is possible to reverse it partially.
  • Patients with signs of lipoatrophy should be monitored regularly.
  • If didanosine causes lipoatrophy, alternate therapy should be used.
• Noncirrhotic portal hypertension
  • Didanosine therapy can cause noncirrhotic portal Hypertension when it is administered for long periods of time, such as months or years. This may manifest as transaminitis and esophageal varices as well as as ascites and splenomegaly.
  • Death and/or liver failure can be the final result
  • This condition should not be treated.
• Ocular effects
  • It is important to have a periodic retinal exam as didanosine can cause retinal damage, such as optic neuritis and retinal depigmentation in children and adults.
• Pancreatitis: [US Boxed Warning]
  • Patients using monotherapy or combination in both treatment-naive and treatment-experienced can experience fatal pancreatitis regardless of the degree of immunosuppression.
  • Treatment should be stopped if there is suspicion that pancreatitis has occurred. In the event of confirmed inflammation, it should be continued. Dose-related factors determine the frequency of the disease.
  • Patients at high risk for pancreatitis should exercise extreme caution.
  • Pancreatitis risk is higher in older age, advanced HIV-1 infection and renal impairment.
  • High-risk patients require close monitoring and dosage adjustment.
• Peripheral neuropathy:
  • Antiviral therapy may cause peripheral neuropathy, which can manifest as numbness, pain, or tingling in the hands and feet.
  • Patients who have had a history or are being treated with neurotoxic drugs, advanced HIV disease, and patients with neuropathy are at greater risk.
  • If neuropathy develops, therapy should be stopped.
• Hepatic impairment
  • Patients with severe hepatic impairment should exercise caution as safety and efficacy are not known.
  • Patients who receive antiretroviral therapy in combination with hepatic impairment are at greater risk of liver toxicities.
  • Temporary or permanent withdrawal may be required in the event of a worsening of hepatic functions.
• Renal impairment
  • Patients with impaired renal function should exercise caution. Dosage reduction is necessary when CrCl is below 60 mL/minute

Didanosine: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• CBC with differential count
• LFTs
• RFTs
• Serum amylase, serum potassium, uric acid
• INR
• Weight gain
• CD4 cells; viral load
• perform dilated retinal exam every 6 months
• Ultrasonography (if portal hypertension suspected)  

How to administer Didanosine (Videx)?

Oral Pediatric powder for oral solution:

• Shake well before use.
• It should be taken on an empty stomach at least 30 minutes before or 2 hours after eating.

Videx EC:

• The capsule should be swallowed as a whole on an empty stomach at least 30 minutes before or 2 hours after eating.

Mechanism of action of Didanosine (Videx):

• Didanosine, a purine aminoside (adenosine), and the deamination product deoxyadenosine(ddA), inhibit HIV replication in vitro in T cells and monocytes.
• The cell converts didanosine into the mono-, tri-, and triple phosphates of DdA.
• These ddA Triphosphates are known to block viral DNA synthesis, suppress HIV replication and act as substrates and inhibitors of HIV reverse transcriptase.

Absorption

• Acidic pH of the stomach can cause it to be destroyed.
• Some formulations have a buffer to resist acidic pH.
• Food can cause a 55% to 65% drop in plasma concentration.
• The delayed-release capsules are made with enteric-coated beads that dissolve in small intestine.

Distribution

• Extensive intracellular distribution
• CSF/plasma ratio for infants 8 months through teenagers 19 years: 46% (range 12% to 15%); adults: 21%

Protein binding:

• Less than 5%

Metabolism:

• It has not been evaluated in humans.
• Studies conducted in dogs show extensive metabolism with allantoin, hypoxanthine, xanthine, and uric acid being the major metabolites found in urine.

Bioavailability:

• The bioavailability is variable and affected by the presence of food in the GI tract, gastric pH, and the dosage form administered.
• Infants 8 months to Adolescents 19 years: 25% ± 20%
• Adults: 42% ± 12%

Half-life elimination:

• Plasma:
  • Newborns (1 day old): 2 ± 0.7 hours
  • Infants 2 weeks to 4 months: 1.2 ± 0.3 hours
  • Infants 8 months to Adolescents 19 years: 0.8 ± 0.3 hours
  • Adults with normal renal function: 1.5 ± 0.4 hours
• Intracellular:
  • Adults: 25 to 40 hours

Elimination: Elimination is increased as CrCl is decreased

• Children 20 kg to <25 kg:
  • 0.75 ± 0.13 hours
• Children 25 kg to <60 kg:
  • 0.92 ± 0.09 hours
• Children ≥60 kg:
  • 1.26 ± 0.19 hours
• Adults ≥60 kg:
  • 1.19 ± 0.21 hours; 2 ± 0.3 hours (renal impairment [CrCl <30 mL/minute]); 4.1 ± 1.2 hours (dialysis)

Time to peak:

• Delayed-release capsules: 2 hours;
• Powder for suspension: 0.25 to 1.5 hours

Excretion:

• Unchanged drug excreted in urine
• Infants 8 months to Adolescents 19 years: 18% ± 10%
• Adults: 18% ± 8%  

International Brands of Didanosine:

• Videx
• Videx EC
• Bandotan
• Bristol-Videx EC
• Cipladinex
• Didasten
• Didnosine
• Dinex
• Dinex EC
• Divir
• Dycon-SR
• Vidanovir
• Videx
• Videx DDI
• Videx EC
• Videx EC SR
• Videx Pediatric  

Didanosine Brands in Pakistan: