Didanosine

Indications

Didanosine is used for: HIV infection

Adult Dose

HIV Infection <60 kg: Extended-release 250 mg PO qDay; 125 mg PO q12hr >60 kg: Extended-release 400 mg PO qDay; suspension 200 mg PO q12hr Dosage Modifications Coadministration with tenofovir >60 kg: Decrease didanosine dose to 250 mg/day <60 kg: Decrease didanosine dose to 200 mg/day

Child Dose

HIV Infection Indicated for treatment of HIV infection in combination with other antiretroviral agents Oral solution NIH HIV guidelines (March 2016) 2 weeks to <3 months: 50 mg/m² PO q12hr 3-8 months: 100 mg/m² PO q12hr >8 months: 120 mg/m² (range 90-150 mg/m²) PO q12hr Manufacturer prescribing information 2 week to 8 months: 100 mg/m² PO q12hr >8 months: 120 mg/m² PO q12hr Capsule Weight-based dosing (6-18 years) Children who can safely swallow enteric-coated beadlets or delayed-release capsules 20 to <25 kg: 200 mg PO qDay 25 to <60 kg: 250 mg PO qDay >60 kg: As adults; 400 mg PO qDay (oral suspension: 200 mg PO q12hr)

Renal Dose

>60 kg CrCl >60 mL/min: Normal dose CrCl 30-59 mL/min: 200 mg PO qDay (extended release/solution) or divided q12hr (solution only) CrCl 10-29 mL/min: 125 mg (extended release) or 150 mg (solution) PO qDay CrCl <10 mL/min; PD/HD: 125 mg (extended release) or 100 mg (solution) PO qDay <60 kg CrCl >60 mL/min: Normal dose CrCl 30-59 mL/min: Extended release 125 mg PO qDay; solution 150 mg PO qDay or divided q12hr CrCl 10-29 mL/min: 125 mg (extended release) or 100 mg (solution) PO qDay CrCl <10 mL/min; PD/HD: Solution only: 75 mg PO qDay

Administration

Should be taken on an empty stomach. Take on an empty stomach ½ hr before or 2 hr after meals.

Contra Indications

Hypersensitivity; lactation.

Precautions

History of pancreatitis and liver disease; pregnancy; impaired hepatic and renal function; peripheral neuropathy; hyperuricaemia. Half-yrly dilated retinal examinations are recommended. May be associated with the development of non-cirrhotic portal hypertension; monitor patients for the development of portal hypertension and oesophageal varices. Suspend use in patients with suspected pancreatitis and discontinue use in patients with confirmed pancreatitis. Suspend use in patients who develop clinical symptoms or signs with or without laboratory findings of lactic acidosis and severe hepatomegaly with steatosis. Consider usage discontinuation or interruption in patients with worsening liver disease. Patients may develop peripheral neuropathy, retinal changes and optic neuritis, immune reconstitution syndrome and redistribution/accumulation of body fat. Lactation: Not known whether distributed into milk. Because of both the potential for HIV transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breastfeed.

Pregnancy-Lactation

Pregnancy To monitor maternal-fetal outcomes of pregnant women exposed to didanosine and other antiretroviral agents, an Antiretroviral Pregnancy Registry has been established; physicians are encouraged to register patients by calling 1-800-258-4263 There are no adequate and well-controlled studies of didanosine in pregnant women; drug should be used during pregnancy only if potential benefit justifies potential risk Lactation The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed infants to avoid risking postnatal transmission of HIV; a study in rats showed that following oral administration, didanosine and/or its metabolites were excreted into the milk of lactating rats; it is not known if didanosine is excreted in human milk; because of both potential for HIV transmission and potential for serious adverse reactions in nursing infants, mothers should be instructed not to breastfeed if they are receiving didanosine

Interactions

Increased effect with allopurinol and ganciclovir; hydroxyurea; increased toxicity with ribavirin or tenofovir. Decreased effects of quinolones, tetracyclines, indinavir. Increased risk of pancreatitis when used with pentamidine, stavudine or co-trimoxazole. Increased risk of liver toxicity when used with other antiretroviral agens, hydroxyurea or ribavirin.

Adverse Effects

Side effects of Didanosine : >10% Diarrhea (19-28%), Peripheral neuropathy (17-20%), Increased amylase (15-17%), Abdominal pain (7-13%) 1-10% Increased LFT, Increased uric acid, Pancreatitis (patients >65 years had higher frequency of pancreatitis than younger patients), Pruritus, Rash

Mechanism of Action

Didanosine is a nucleoside reverse transcriptase inhibitor that inhibits DNA synthesis of retroviruses by competitive inhibition of reverse transcriptase and incorporation into viral DNA.