Usage
- Didanosine (ddI) is an antiretroviral medication, specifically a nucleoside reverse transcriptase inhibitor (NRTI), used in combination with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 (HIV-1) infection.
- Pharmacological Classification: Nucleoside Reverse Transcriptase Inhibitor (NRTI), Antiretroviral.
- Mechanism of Action: Didanosine inhibits HIV reverse transcriptase by competing with the natural substrate, deoxyadenosine triphosphate. This prevents the conversion of viral RNA into DNA, thereby blocking viral replication.
Alternate Names
- ddI
- Dideoxyinosine
- Brand Names: Videx, Videx EC
How It Works
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Pharmacodynamics: Didanosine, after intracellular phosphorylation to its active metabolite dideoxyadenosine triphosphate (ddATP), inhibits HIV reverse transcriptase, leading to a decrease in viral replication.
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Pharmacokinetics:
- Absorption: Oral absorption is variable. The delayed-release formulation (Videx EC) enhances absorption and reduces gastrointestinal side effects. Food reduces the absorption of didanosine; thus, it should be taken on an empty stomach.
- Metabolism: Didanosine is primarily metabolized intracellularly via phosphorylation to ddATP. It is not significantly metabolized by cytochrome P450 enzymes.
- Elimination: Primarily renally excreted, requiring dose adjustments in patients with renal impairment.
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Mode of Action: ddATP acts as a chain terminator during viral DNA synthesis, effectively halting HIV replication.
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Receptor Binding/Enzyme Inhibition: Inhibits HIV reverse transcriptase by competing with the natural substrate, deoxyadenosine triphosphate. Does not bind to specific receptors.
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Elimination Pathways: Primarily renal excretion.
Dosage
Standard Dosage
Adults:
- Weight ≥ 60 kg: 400 mg once daily (delayed-release capsules) or 200 mg twice daily (oral solution).
- Weight < 60 kg: 250 mg once daily (delayed-release capsules) or 125 mg twice daily (oral solution).
Children:
- Children ≥ 6 years and weight ≥ 20 kg who can swallow capsules: Same as adult dose based on weight.
- Children < 20 kg: Not recommended with delayed-release capsules; other formulations must be used. Specific dosing must be calculated for children based on body surface area and weight, with careful monitoring for toxicity. Didanosine is generally not recommended for children due to the availability of safer alternatives.
- Pediatric Safety Considerations: Monitor closely for pancreatitis, lactic acidosis, and peripheral neuropathy.
Special Cases:
- Elderly Patients: Caution is advised due to increased risk of renal impairment and other comorbidities. Monitor renal function. Data specific to elderly patients are limited.
- Patients with Renal Impairment: Dose reduction is necessary (refer to detailed dosing tables in prescribing information).
- Patients with Hepatic Dysfunction: No specific dose adjustment is recommended, but monitor closely for liver-related adverse effects.
- Patients with Comorbid Conditions: Monitor patients with a history of pancreatitis, peripheral neuropathy, diabetes, or other relevant conditions closely.
Clinical Use Cases
Didanosine is not specifically indicated for use in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. It is used for chronic management of HIV-1 infection.
Dosage Adjustments
- Renal Dysfunction: Dose reductions are necessary based on creatinine clearance (consult prescribing information for details).
- Hepatic Dysfunction: No specific adjustments, but close monitoring is warranted.
- Concomitant Medications: Dose adjustments may be required with tenofovir disoproxil fumarate, allopurinol, ribavirin, or other interacting medications.
Side Effects
Common Side Effects:
- Diarrhea
- Peripheral neuropathy (tingling, numbness, pain in hands or feet)
- Nausea
- Headache
- Vomiting
- Rash
- Abdominal pain
Rare but Serious Side Effects:
- Pancreatitis (potentially fatal)
- Lactic acidosis (potentially fatal)
- Hepatomegaly with steatosis (potentially fatal)
- Retinal changes/optic neuritis
- Severe peripheral neuropathy
- Liver dysfunction
Long-Term Effects:
- Lipodystrophy (changes in body fat distribution)
- Peripheral neuropathy
Adverse Drug Reactions (ADR):
- Pancreatitis
- Lactic acidosis
- Hepatotoxicity
- Anaphylaxis
Contraindications
- Hypersensitivity to didanosine
- Coadministration with allopurinol or ribavirin.
- Coadministration with stavudine (increased risk of pancreatitis and lactic acidosis).
Drug Interactions
- Allopurinol, Ribavirin: Contraindicated due to increased didanosine toxicity.
- Stavudine: Contraindicated due to increased risk of pancreatitis and lactic acidosis.
- Tenofovir Disoproxil Fumarate: Dose reduction of didanosine is necessary.
- Hydroxyurea: Should be avoided due to increased risk of pancreatitis and hepatotoxicity.
- Other NRTIs: Potential for additive mitochondrial toxicity with other NRTIs.
- Antacids: May reduce absorption of didanosine.
- Many other drugs: Consult a comprehensive drug interaction resource before co-prescribing.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Category B (animal studies show no risk, but adequate human studies are lacking). Didanosine is generally not recommended during pregnancy due to potential for serious side effects (e.g. lactic acidosis), especially when combined with stavudine.
- Breastfeeding: HIV-infected mothers should not breastfeed due to risk of transmission. Didanosine is excreted in breast milk.
Drug Profile Summary
- Mechanism of Action: NRTI, inhibits HIV reverse transcriptase.
- Side Effects: Diarrhea, peripheral neuropathy, nausea, pancreatitis, lactic acidosis, hepatotoxicity.
- Contraindications: Hypersensitivity, coadministration with allopurinol or ribavirin, coadministration with stavudine.
- Drug Interactions: Allopurinol, ribavirin, stavudine, tenofovir, many others.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: Weight-based dosing (consult prescribing information).
- Monitoring Parameters: Liver function tests, renal function tests, amylase/lipase (for pancreatitis), complete blood count, signs and symptoms of neuropathy.
Popular Combinations
Didanosine is no longer part of commonly recommended HIV treatment regimens due to its toxicity profile and the availability of safer and more effective options. Historically, it was used in combination with other NRTIs and protease inhibitors.
Precautions
- General Precautions: Monitor for pancreatitis, lactic acidosis, peripheral neuropathy, hepatotoxicity. Obtain baseline and periodic liver function tests, renal function tests, amylase/lipase, and complete blood counts.
- Specific Populations:
- Pregnant Women: Not recommended.
- Breastfeeding Mothers: Do not breastfeed.
- Children & Elderly: Use with caution. Monitor closely for toxicity.
- Lifestyle Considerations: Alcohol should be avoided or limited due to the potential for additive pancreatic toxicity.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Didanosine?
A: Dosage is based on weight and renal function. Refer to the detailed dosing guidelines provided above and in the prescribing information.
Q2: What are the most serious side effects of Didanosine?
A: Pancreatitis, lactic acidosis, hepatotoxicity, and severe peripheral neuropathy are the most serious potential side effects.
Q3: What are the contraindications to using Didanosine?
A: Hypersensitivity to didanosine, coadministration with allopurinol or ribavirin, and coadministration with stavudine are absolute contraindications.
Q4: Can Didanosine be used during pregnancy?
A: Didanosine is generally not recommended during pregnancy due to potential for serious side effects like lactic acidosis, especially when combined with stavudine.
Q5: How should Didanosine be administered?
A: Didanosine delayed-release capsules should be taken orally on an empty stomach (at least 30 minutes before or 2 hours after a meal). Capsules should be swallowed whole and not crushed or chewed.
Q6: What should patients be monitored for while taking Didanosine?
A: Monitor for signs and symptoms of pancreatitis, lactic acidosis, peripheral neuropathy, and hepatotoxicity. Obtain baseline and periodic liver and renal function tests, amylase/lipase levels, and complete blood counts.
Q7: What are the drug interactions to be aware of with Didanosine?
A: Didanosine has many clinically significant drug interactions. Some key interactions include allopurinol, ribavirin, stavudine, tenofovir disoproxil fumarate, and antacids. Consult a drug interaction checker or prescribing information for detailed information.
Q8: Can patients with renal impairment take Didanosine?
A: Yes, but dose adjustments are required based on the degree of renal impairment. Refer to prescribing information for specific recommendations.
Q9: What is the role of Didanosine in current HIV treatment guidelines?
A: Didanosine is no longer recommended in current HIV treatment guidelines due to its toxicity profile and the availability of safer and more effective alternatives.
