Didanosine

Oral
HIV-1 infection

As chewable or dispersible tab/soln:
<60 kg:

CrCl (mL/min)	Dosage
<10	75 mg once daily.
10-29	100 mg once daily.
30-59	150 mg in 1-2 divided doses.

≥60 kg:

CrCl (mL/min)	Dosage
<10	100 mg once daily.
10-29	150 mg once daily.
30-59	200 mg in 1-2 divided doses.

As delayed-release cap:
<60 kg:

CrCl (mL/min)	Dosage
<10	Contraindicated.
10-59	125 mg once daily.

≥60 kg:

CrCl (mL/min)	Dosage
<30	125 mg once daily.
30-59	200 mg once daily.

Should be taken on an empty stomach. Take 30 min before or 2 hr after meals.

Hypersensitivity to didanosine. Renal (CrCl <10 mL/min) impairment (delayed-release cap). Lactation. Concomitant use w/ allopurinol, ribavirin, tenofovir, stavudine, and hydroxyurea.

Patient w/ history and risk of pancreatitis, history of neuropathy, hepatomegaly. Hepatic (e.g. chronic active hepatitis) and renal impairment. Childn. Pregnancy.

Significant: Peripheral neuropathy, immune reconstitution syndrome, fat redistribution (e.g. central obesity, peripheral and facial wasting, breast enlargement, buffalo hump, cushingoid appearance), osteonecrosis. Rarely, retinal changes (e.g. depigmentation), optic neuritis.
Nervous: Headache, anxiety, insomnia, irritability, restlessness, seizures, fatigue, asthenia.
CV: Increased risk of MI, cardiomyopathy.
GI: Diarrhoea, nausea, vomiting, abdominal pain, anorexia, constipation, dyspepsia, dry mouth, flatulence, parotid gland enlargement, sialedenitis.
Hepatic: Hepatitis, abnormal LFT.
Endocrine: DM, hypo- and hyperglycaemia, hypertriglyceridaemia, hypercholesterolaemia, insulin resistance, hyperlactataemia, hyperuricaemia.
Haematologic: Anaemia, leucopenia, thrombocytopenia.
Musculoskeletal: Increased creatine phosphokinase, myalgia, arthralgia, myopathy, myositis, rhabdomyolysis.
Ophthalmologic: Diplopia, dry eyes, optic atrophy, blindness.
Dermatologic: Rash, alopecia, pruritus, mild erythematous macular eruption.
Immunologic: Anaphylaxis.
Others: Chills, fever, hypokalaemia, pain.
Potentially Fatal: Pancreatitis, lactic acidosis associated w/ hepatomegaly and steatosis. Rarely, noncirrhotic portal HTN, hepatic failure.

PO: B

Monitor serum K, uric acid, creatinine, Hb, CBC w/ neutrophil and platelet count, CD4 cells, viral load, LFT, serum bilirubin, albumin, INR, amylase, wt gain. Monitor for signs and symptoms of peripheral neuropathy, hepatotoxicity, GI pain, and visual changes regularly during therapy. Perform dilated retinal exam every 6 mth.

Symptoms: Pancreatitis, peripheral neuropathy, diarrhoea, hyperuricaemia and hepatic dysfunction. Management: Supportive and symptomatic treatment. Induce emesis or perform gastric lavage.

Decreased plasma concentration w/ methadone. Increased plasma concentration w/ ganciclovir and valganciclovir. Decreased effects of quinolones, tetracyclines, ketoconazole w/ buffered didanosine preparations. Increased risk of pancreatitis when used w/ pentamidine. Increased bioavailability of didanosine when concomitantly used w/ antacid.
Potentially Fatal: Increased toxicity w/ allopurinol. Increased plasma concentration and risk of adverse effects (hepatic failure, peripheral neuropathy, pancreatitis, lactic acidosis) w/ ribavirin, tenofovir, stavudine, and hydroxyurea.

Food decreases rate of absorption. Enhanced adverse effects w/ alcohol.

Description:
Mechanism of Action: Didanosine is converted intracellularly to dideoxyadenosine triphosphate which inhibits HIV nucleoside reverse transcriptase, hence blocking viral DNA synthesis and suppressing HIV replication.
Pharmacokinetics:
Absorption: Rapidly hydrolysed in the gastric acid. Reduced bioavailability w/ food. Bioavailability: 20-40%. Time to peak plasma concentration: Approx 1 hr.
Distribution: Extensive intracellular distribution. Crosses placenta and distributed into cord blood and amniotic fluid. Plasma protein binding: <5%.
Metabolism: Undergoes intracellular phosphorylation to the active metabolite, dideoxyadenosine triphosphate.
Excretion: Via urine (20% as unchanged drug). Elimination half-life: Approx 1.5 hr.

Source: National Center for Biotechnology Information. PubChem Database. Didanosine, CID=135398739, https://pubchem.ncbi.nlm.nih.gov/compound/Didanosine (accessed on Jan. 21, 2020)

Tab/Oral Soln: Store between 15-30°C. Cap: Store at 25°C.

Antivirals

J05AF02 - didanosine ; Belongs to the class of nucleoside and nucleotide reverse transcriptase inhibitors. Used in the systemic treatment of viral infections.

Anon. Didanosine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 21/02/2017.

Buckingham R (ed). Didanosine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 21/02/2017.

Joint Formulary Committee. Didanosine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 21/02/2017.

McEvoy GK, Snow EK, Miller J et al (eds). Didanosine. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 21/02/2017.

Videx EC Capsule, Delayed Release (Bristol-Myers Squibb Company). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 21/02/2017.

Videx Powder, For Solution (Bristol-Myers Squibb Company). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 21/02/2017.