DIDANOSINE
Clinical safety rating: safe
Animal studies have demonstrated safety
Didanosine is a nucleoside reverse transcriptase inhibitor (NRTI) that is converted to its active metabolite, dideoxyadenosine triphosphate (ddATP), which inhibits HIV reverse transcriptase and competes with the natural substrate dATP, leading to chain termination of viral DNA synthesis.
| Metabolism | Didanosine is metabolized via purine nucleoside phosphorylase to hypoxanthine and then to uric acid; it is also partially metabolized by xanthine oxidase. Renal excretion accounts for approximately 50% of the administered dose. |
| Excretion | Renal excretion of unchanged drug accounts for approximately 50-60% of the administered dose. Biliary/fecal elimination is minimal (<20%). |
| Half-life | Terminal elimination half-life is 1.5-2 hours in adults with normal renal function; prolonged to 4-8 hours in renal impairment. |
| Protein binding | Less than 5% bound to plasma proteins. |
| Volume of Distribution | Approximately 1.0 L/kg, indicating extensive distribution into total body water. |
| Bioavailability | Oral bioavailability is 30-40% (fasting) and 20-25% with food; tablets have higher bioavailability than buffered powder. |
| Onset of Action | Oral: Peak plasma concentrations achieved in 0.5-2 hours; clinical antiviral effect begins within days. |
| Duration of Action | Oral: Antiviral effect persists for 8-12 hours; dosing interval is 12-24 hours due to intracellular active metabolite half-life of 25-40 hours. |
Weight-adjusted oral dose: 400 mg once daily (tablets) or 250 mg once daily (buffered powder) for adults ≥60 kg; 250 mg once daily (tablets) or 167 mg once daily (buffered powder) for adults <60 kg. Administer on an empty stomach (at least 30 minutes before or 2 hours after a meal).
| Dosage form | CAPSULE, DELAYED REL PELLETS |
| Renal impairment | For CrCl ≥60 mL/min: standard dose. CrCl 30-59 mL/min: reduce dose by 50% (e.g., 200 mg tablets or 125 mg powder once daily for ≥60 kg). CrCl <30 mL/min: reduce dose by 75% (e.g., 100 mg tablets or 125 mg powder every 48 hours for ≥60 kg). Hemodialysis: administer after dialysis or 100 mg tablets every 48 hours. Peritoneal dialysis: 100 mg tablets every 48 hours. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 25% (300 mg tablets or 200 mg powder once daily for ≥60 kg). Child-Pugh Class C: reduce dose by 50% (200 mg tablets or 125 mg powder once daily for ≥60 kg). |
| Pediatric use | Oral dose (tablets or powder) based on body surface area: 240 mg/m² once daily (tablets) or 180 mg/m² once daily (powder). Alternatively weight-based for tablets: ≥6 years: 200 mg/m² once daily; <6 years: 150 mg/m² once daily. Maximum adult dose not to exceed 400 mg daily. |
| Geriatric use |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Drugs that cause pancreatitis or peripheral neuropathy increase risk Can cause severe pancreatitis and peripheral neuropathy.
| Breastfeeding | Didanosine is excreted into human breast milk; the milk-to-plasma ratio is approximately 0.8. The estimated infant dose via breast milk is about 1% of the maternal dose. Due to the risk of HIV transmission via breastfeeding in HIV-positive mothers, breastfeeding is generally not recommended in the US. For other indications, caution is advised because of potential adverse effects in the nursing infant, including gastrointestinal disturbances and pancreatitis. |
| Teratogenic Risk | Didanosine is classified as FDA Pregnancy Category B. Animal studies have not shown teratogenic effects, but there are no adequate and well-controlled studies in pregnant women. In humans, didanosine has been associated with lactic acidosis and hepatic steatosis in pregnant women, especially when used in combination with other antiretrovirals. First trimester exposure is not associated with a significant increase in birth defects. There is a potential for mitochondrial toxicity in the fetus. Risk during second and third trimesters is low, but monitoring for lactic acidosis is recommended. |
■ FDA Black Box Warning
Pancreatitis, which can be fatal, has been reported. 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.
| Common Effects | Peripheral neuropathy |
| Serious Effects |
Hypersensitivity to didanosine or any component of the formulation; concurrent use with allopurinol, ribavirin, or stavudine (due to increased risk of pancreatitis, lactic acidosis, and hepatotoxicity).
| Precautions | Pancreatitis (discontinue if suspected), lactic acidosis/hepatomegaly with steatosis, retinal changes and optic neuritis, peripheral neuropathy, immune reconstitution syndrome, increased risk of hepatotoxicity in patients with hepatitis B or C co-infection, and risk of pancreatitis in patients with renal impairment. |
Loading safety data…
| No specific dose adjustment except based on renal function. Monitor renal function closely; use renal adjustment guidelines. Elderly may have reduced CrCl and increased risk of peripheral neuropathy or pancreatitis. |
| Fetal Monitoring | Monitor for signs and symptoms of lactic acidosis and hepatic steatosis, especially in pregnant women with risk factors. Perform liver function tests, serum lactate, and amylase regularly. Monitor for pancreatitis in mothers. Fetal monitoring may include ultrasound for growth and development if maternal condition warrants. In neonates, monitor for hyperlactatemia and mitochondrial dysfunction if maternal exposure near delivery. |
| Fertility Effects | Didanosine has been associated with reversible decreases in sperm motility and count in animal studies and in some human reports. There is no evidence of permanent infertility. In women, no significant effects on ovulation or fertility have been reported. Men attempting conception should be counseled about potential temporary effects on sperm parameters. |