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. |
| Molecular Weight | 236.23 |
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 | Use only if clear benefit; associated with lactic acidosis and hepatic steatosis. Avoid if alternative available. |
| 2nd trimester | Use only if clear benefit; monitor mitochondrial toxicity. |
| 3rd trimester | Use only if clear benefit; risk of lactic acidosis increases in third trimester. |
Clinical note
Drugs that cause pancreatitis or peripheral neuropathy increase risk Can cause severe pancreatitis and peripheral neuropathy.
| Placental transfer | Extensive placental transfer with cord blood concentrations approximately 50-100% of maternal levels. Active transport via nucleoside transporters. |
| Breastfeeding | Didanosine is excreted into human breast milk at low levels. Limited data suggest no adverse effects in infants, but theoretical risk of mitochondrial toxicity. Consider alternatives such as zidovudine. |
■ 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 componentConcurrent use with stavudine due to increased risk of mitochondrial toxicity and lactic acidosisPhenylketonuria (tablets contain aspartame)
| 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. |
| Food/Dietary |
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| 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. |
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
| Take on an empty stomach; food reduces absorption by up to 50%. Avoid food within 2 hours of dosing. Do not take with acidic fruits or juices. Didanosine is buffered to prevent acid degradation; therefore, avoid taking with acidic beverages (e.g., orange juice, lemonade) as they may reduce buffer effectiveness. |
| Clinical Pearls | Monitor for pancreatitis, especially in patients with advanced HIV, history of pancreatitis, or concurrent use of other pancreas-toxic drugs. Didanosine should be taken on an empty stomach; avoid food within 2 hours of dosing. Dose adjustment required for renal impairment (CrCl <60 mL/min). Watch for peripheral neuropathy, lactic acidosis, and hepatic steatosis. Didanosine tablets must be chewed or dissolved in water; do not swallow whole. Avoid concurrent use with allopurinol, ganciclovir, and ribavirin. Co-administration with stavudine increases risk of pancreatitis and lactic acidosis. Didanosine is inactivated by stomach acid; formulation includes buffer. |
| Patient Advice | Take didanosine on an empty stomach, at least 30 minutes before or 2 hours after a meal. · If you are taking the tablet, chew it thoroughly or dissolve it in at least 1 ounce of water; stir until dispersed and drink immediately. · Do not swallow the tablet whole. · Store tablets at room temperature away from moisture and heat. · Do not take didanosine with alcohol because it increases the risk of pancreatitis. · Report symptoms of pancreatitis (severe stomach pain, nausea, vomiting) or peripheral neuropathy (tingling or numbness in hands/feet) to your doctor immediately. · Didanosine can cause lactic acidosis; seek medical help if you have unexplained fatigue, muscle pain, trouble breathing, or irregular heartbeat. · Inform your doctor about all medications you take, especially allopurinol, ganciclovir, ribavirin, and other HIV drugs. |