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Didanosine

Class: HIV Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
- Reverse Transcriptase Inhibitors
VA Class: AM800
Chemical Name: 2′,3′-Dideoxyinosine
CAS Number: 69655-05-6
Brands: Videx

Medically reviewed by Drugs.com on Feb 1, 2021. Written by ASHP.

Warning

  • Fatal and nonfatal pancreatitis reported in both antiretroviral-naive and antiretroviral-experienced patients, regardless of degree of immunosuppression. Temporarily interrupt didanosine in patients with suspected pancreatitis; discontinue in patients with confirmed pancreatitis. (See Pancreatitis under Cautions.)

  • Lactic acidosis and severe hepatomegaly with steatosis (including some fatalities) reported in patients receiving HIV nucleoside reverse transcriptase inhibitors (NRTIs) alone or in conjunction with other antiretrovirals. (See Lactic Acidosis and Severe Hepatomegaly with Steatosis under Cautions.)

  • Fatal lactic acidosis reported in pregnant women who received didanosine and stavudine with other antiretrovirals. Didanosine in conjunction with stavudine should be used with caution in pregnant women and only if potential benefits outweigh potential risks. (See Pregnancy under Cautions.)

Introduction

Antiretroviral; HIV nucleoside reverse transcriptase inhibitor (NRTI).

Uses for Didanosine

Treatment of HIV Infection

Treatment of HIV-1 infection in adults, adolescents, and pediatric patients ≥2 weeks of age; used in conjunction with other antiretrovirals.

Experts state didanosine not recommended for initial treatment regimens in antiretroviral-naive adults and adolescents.

Dual NRTI option of didanosine and lamivudine (or emtricitabine) not recommended for initial treatment regimens in adults and adolescents because of inferior virologic efficacy, limited clinical trial experience in antiretroviral-naive patients, and didanosine toxicities (e.g., pancreatitis, peripheral neuropathy).

Dual NRTI option of didanosine and tenofovir disoproxil fumarate (tenofovir DF) not recommended at any time because of high rate of early virologic failure, rapid selection of resistance mutations, potential for immunologic nonresponse or decline in CD4+ T-cell counts, and increased didanosine concentrations and serious didanosine toxicities. Consider altering the NRTIs in those clinically stable on a regimen that contains both didanosine and tenofovir DF.

Dual NRTI option of didanosine and stavudine not recommended at any time because of high incidence of toxicity (e.g., peripheral neuropathy, pancreatitis, hyperlactatemia). (See Pregnancy under Cautions.)

For initial treatment regimens in antiretroviral-naive pediatric patients, experts state that didanosine and zidovudine or didanosine and either lamivudine or emtricitabine are alternative (not preferred) dual NRTI options for use in conjunction with an HIV protease inhibitor (PI) or HIV nonnucleoside reverse transcriptase inhibitor (NNRTI) in PI- or NNRTI-based regimens in children ≥2 weeks of age.

Didanosine Dosage and Administration

Administration

Oral Administration

Delayed-release capsules containing enteric-coated pellets of didanosine: Administer orally once daily without food. Swallow whole capsule; do not open, crush, chew, or dissolve.

Didanosine pediatric oral solution admixed with antacid: Administer orally at least 30 minutes before or 2 hours after a meal. Administer oral solution twice daily in children. Twice-daily regimen also preferred in adults and adolescents, but once-daily regimen can be considered in adults and adolescents if needed.

Reconstitution and Dilution

Pediatric powder for oral solution must be reconstituted and admixed with an antacid at time of dispensing. Reconstitute by adding 100 or 200 mL of water to the bottle containing 2 or 4 g of didanosine, respectively, to provide a solution containing 20 mg/mL. Immediately after reconstitution, mix the 20-mg/mL solution with an equal amount of Maximum Strength Mylanta oral liquid to provide a final admixture containing 10 mg/mL. Shake final admixture thoroughly prior to removing each dose.

Dosage

Adult dosage is based on weight. Pediatric dosage is based on body surface area or weight.

Delayed-release capsules are used in adults and also can be used in children weighing ≥20 kg who can swallow capsules. Pediatric oral solution generally used in children, but may be used in adults.

Pediatric Patients

Treatment of HIV Infection
Oral

Neonates and infants 2 weeks through 8 months of age (pediatric oral solution admixed with antacid): 100 mg/m2 twice daily. Some experts recommend 50 mg/m2 every 12 hours in those 2 weeks to <3 months of age.

Children >8 months of age (pediatric oral solution admixed with antacid): 120 mg/m2 twice daily.

Children and adolescents weighing 20 to <25 kg (delayed-release capsules): 200 mg once daily.

Children and adolescents weighing 25 to <60 kg (delayed-release capsules): 250 mg once daily.

Children and adolescents weighing ≥60 kg (delayed-release capsules): 400 mg once daily.

Adults

Treatment of HIV Infection
Treatment in Adults Weighing <60 kg
Oral

Delayed-release capsules: 250 mg once daily.

Pediatric oral solution admixed with antacid: 125 mg twice daily. If once-daily administration required, 250 mg once daily.

Treatment in Adults Weighing ≥60 kg
Oral

Delayed-release capsules: 400 mg once daily.

Pediatric oral solution admixed with antacid: 200 mg twice daily. If once-daily administration required, 400 mg once daily.

Special Populations

Renal Impairment

Treatment of HIV Infection
Oral
Didanosine Dosage in Adults with Renal Impairment (Delayed-release Capsules)217

Clcr (mL/minute)

Weighing <60 kg

Weighing ≥60 kg

≥60

250 mg once daily

400 mg once daily

30–59

125 mg once daily

200 mg once daily

10–29

125 mg once daily

125 mg once daily

<10

Not recommended; use alternative didanosine formulation

125 mg once daily

Hemodialysis or CAPD patients

Not recommended; use alternative didanosine formulation

125 mg once daily; supplemental doses unnecessary after hemodialysis

Didanosine Dosage in Adults with Renal Impairment (Pediatric Oral Solution Admixed with Antacid)1

Clcr (mL/minute)

Weighing <60 kg

Weighing ≥60 kg

≥60

125 mg twice daily or 250 mg once daily

200 mg twice daily or 400 mg once daily

30–59

150 mg once daily or 75 mg twice daily

200 mg once daily or 100 mg twice daily

10–29

100 mg once daily

150 mg once daily

<10

75 mg once daily

100 mg once daily

Hemodialysis or CAPD patients

75 mg once daily; supplemental doses unnecessary after hemodialysis

100 mg once daily; supplemental doses unnecessary after hemodialysis

Didanosine clearance may be decreased in pediatric patients with impaired renal function. Although data are insufficient to date to make specific dosage recommendations for pediatric patients with impaired renal function, manufacturer recommends that dosage reduction be considered.

Hepatic Impairment

Dosage adjustment not needed.

Cautions for Didanosine

Contraindications

  • Concomitant use with allopurinol. (See Specific Drugs under Interactions.)

  • Concomitant use with ribavirin. (See Specific Drugs under Interactions.)

Warnings/Precautions

Warnings

Pancreatitis

Fatal and nonfatal pancreatitis reported in patients receiving didanosine alone or in conjunction with other antiretrovirals in both treatment-naive and previously treated patients, regardless of degree of immunosuppression.

Interrupt didanosine therapy in patients with signs or symptoms of pancreatitis; discontinue the drug in patients with confirmed pancreatitis.

Use with extreme caution and only if clearly needed in patients at increased risk for pancreatitis, including those receiving didanosine in conjunction with stavudine and those with advanced HIV infection (especially geriatric individuals). Patients with renal impairment also are at increased risk for pancreatitis if didanosine dosage is not reduced.

Discontinue didanosine if treatment with a life-sustaining drug known to cause pancreatic toxicity is required.

Lactic Acidosis and Severe Hepatomegaly with Steatosis

Lactic acidosis and severe hepatomegaly with steatosis (sometimes fatal) reported in patients receiving HIV NRTIs (including didanosine) alone or in conjunction with other antiretrovirals. Reported most frequently in women; obesity and long-term NRTI therapy also may be risk factors. Has been reported in patients with no known risk factors.

Reported in pregnant women receiving didanosine in conjunction with stavudine. (See Pregnancy under Cautions.)

Use caution in patients with known risk factors for liver disease.

Interrupt didanosine therapy if there are clinical or laboratory findings suggestive of symptomatic hyperlactatemia, lactic acidosis, or pronounced hepatotoxicity (e.g., hepatomegaly and steatosis even in the absence of marked increases in serum aminotransferase concentrations).

Other Warnings and Precautions

Noncirrhotic Portal Hypertension

Rare, but serious, cases of noncirrhotic portal hypertension reported in patients 10–66 years of age receiving didanosine; some cases resulted in liver transplantation or death.

Didanosine-associated noncirrhotic portal hypertension was confirmed by liver biopsy in patients with no evidence of viral hepatitis or other alternative etiologies.

Onset of signs and symptoms ranged from months to years after initiation of didanosine therapy; common presenting features included elevated liver enzymes, esophageal varices, hematemesis, ascites, and splenomegaly. Medical interventions consisted of banding or ligation of esophageal varices, transjugular intrahepatic portosystemic shunting (TIPSS), and liver transplantation. There were 4 deaths among 42 reported postmarketing cases.

Although a causal relationship is difficult to determine, after excluding other causes of portal hypertension (e.g., alcohol-related cirrhosis, HCV infection), FDA concluded that there is an association between use of didanosine and development of noncirrhotic portal hypertension. However, FDA states that the clinical benefits of the drug for some patients continue to outweigh potential risks and that the decision to use didanosine must be made on an individual basis.

Monitor patients for early signs of portal hypertension (e.g., thrombocytopenia, splenomegaly) and esophageal varices; consider use of appropriate laboratory tests (e.g., liver enzymes, serum bilirubin, albumin, CBC, INR, ultrasonography). Discontinue didanosine in patients with evidence of noncirrhotic portal hypertension.

Peripheral Neuropathy

Peripheral neuropathy, manifested by numbness, tingling, or pain in the hands or feet, reported; these effects occur more frequently in patients with advanced HIV, a history of neuropathy, or those receiving other neurotoxic drugs, including stavudine.

Consider discontinuing didanosine if peripheral neuropathy occurs.

Ocular Effects

Retinal changes and optic neuritis reported in adults and pediatric patients. Consider periodic retinal examinations.

Immune Reconstitution Syndrome

During initial treatment, patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jirovecii [formerly P. carinii]); this may necessitate further evaluation and treatment.

Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome) reported in the setting of immune reconstitution; time to onset is more variable and can occur many months after initiation of antiretroviral therapy.

Adipogenic Effects

Possible redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement (“buffalo hump”), peripheral wasting, breast enlargement, and general cushingoid appearance. Mechanisms and long-term consequences of fat redistribution unknown; causal relationship not established.

Cardiovascular Effects

There is some evidence that recent use of didanosine (within 6 months) is associated with an increased risk of MI.

Specific Populations

Pregnancy

Category B.

Antiretroviral Pregnancy Registry at 800-258-4263 or [Web].

Experts state didanosine not recommended for initial treatment regimens in antiretroviral-naive pregnant women because of toxicity.

Although the manufacturers state use dual NRTI option of stavudine and didanosine with caution and only if potential benefits clearly outweigh potential risks, experts state do not use dual NRTI option of stavudine and didanosine at any time, including during pregnancy.

Fatal lactic acidosis reported in pregnant women receiving didanosine and stavudine with other antiretrovirals. Unclear whether pregnancy potentiates risk of lactic acidosis and severe hepatotoxicity with steatosis that occurs in NRTI-treated individuals.

Clinicians caring for pregnant patients receiving didanosine should be alert for early diagnosis of lactic acidosis and hepatitis steatosis syndrome.

Lactation

Didanosine and/or its metabolites distributed into milk in rats; not known whether distributed into human milk.

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.

Pediatric Use

Delayed-release capsules: Use in children weighing ≥20 kg supported by pharmacokinetic data.

Pediatric oral solution admixed with antacid: Safety and efficacy in pediatric patients 2 weeks of age through adolescence supported by evidence from adequate and well-controlled studies in adult and pediatric patients.

Adverse effects reported in pediatric patients 2 weeks through 18 years of age are similar to those in adults and include pancreatitis, peripheral neuropathy, ophthalmic effects, GI effects, and hepatic effects.

Geriatric Use

Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults.

Substantially eliminated by kidneys; risk of toxic reactions may be greater in patients with decreased renal function. Consider age-related decreases in renal function when selecting dose. Monitor renal function and adjust dosage as necessary.

Hepatic Impairment

Safety and efficacy not evaluated in patients with clinically important underlying liver disease; risk of liver function abnormalities, including severe and potentially fatal adverse hepatic events, in patients with underlying liver dysfunction (e.g., chronic active hepatitis).

Use caution and monitor patients with liver disease. Interrupt or discontinue if liver disease worsens.

Because noncirrhotic portal hypertension reported rarely in patients receiving didanosine, monitor patients for early signs of portal hypertension (e.g., thrombocytopenia, splenomegaly) and esophageal varices; consider obtaining appropriate laboratory tests (e.g., liver enzymes, serum bilirubin, albumin, CBC, INR, ultrasonography). Discontinue didanosine if there is evidence of noncirrhotic portal hypertension. (See Noncirrhotic Portal Hypertension under Cautions.)

Renal Impairment

Risk of toxic reactions may be greater in patients with decreased renal function.

Dosage adjustment needed based on degree of renal impairment. (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

GI effects (diarrhea, nausea, vomiting, abdominal pain), peripheral neurologic symptoms/neuropathy, rash/pruritus, headache, pancreatitis.

Interactions for Didanosine

Drug interaction studies have used buffered didanosine (chewable/dispersible, buffered tablets [no longer commercially available in the US], pediatric oral solution admixed with antacid) or didanosine delayed-release capsules. With a few exceptions (e.g., ciprofloxacin, indinavir, ketoconazole), results of interaction studies that used buffered preparations are expected to apply to delayed-release capsules.

Specific Drugs

Drug

Interaction

Comments

Allopurinol

Substantially increased didanosine concentrations and AUC; possible increased risk of didanosine toxicity

Concomitant use contraindicated

Antacids

Aluminum- and magnesium-containing antacids increase oral bioavailability of didanosine

Possible increased antacid adverse effects if additional antacids are used in patients receiving didanosine pediatric oral solution admixed with antacid

Used to therapeutic advantage; didanosine pediatric oral solution is admixed with antacid prior to administration

Additional antacids should be used with caution in patients receiving didanosine pediatric oral solution admixed with antacid

Antifungals, azoles

Itraconazole: Decreased itraconazole concentrations with buffered didanosine

Ketoconazole: Decreased ketoconazole peak plasma concentrations and AUC with buffered didanosine; no changes in ketoconazole concentrations with didanosine delayed-release capsules

Administer itraconazole or ketoconazole at least 2 hours before buffered didanosine (pediatric oral solution admixed with antacid)

Antimycobacterials

Rifabutin: Slightly increased didanosine concentrations; no clinically important pharmacokinetic interactions

Atazanavir

Buffered didanosine: Decreased atazanavir concentrations and AUC; decreased didanosine concentrations and AUC

Didanosine delayed-release capsules: Decreased didanosine concentrations and AUC if given with atazanavir and food; no change in atazanavir concentrations

No in vitro evidence of antagonistic antiretroviral effects

Administer atazanavir (with food) 2 hours before or 1 hour after buffered or delayed-release didanosine preparations (without food)

Buprenorphine

No clinically important pharmacokinetic interactions

Dosage adjustments not needed

Dapsone

No effect on dapsone concentrations or AUC

Some reports of failure of dapsone to prevent Pneumocystis carinii pneumonia in HIV-infected patients receiving didanosine concomitantly

Some clinicians suggest didanosine be administered at least 2 hours after dapsone

Darunavir

Didanosine delayed-release capsules: No change in didanosine or darunavir concentrations

No in vitro evidence of antagonistic antiretroviral effects

Administer didanosine (without food) 1 hour before or 2 hours after ritonavir-boosted darunavir (with food)

Delavirdine

Buffered didanosine: Decreased delavirdine and didanosine concentrations if given simultaneously; slightly increased delavirdine concentrations if delavirdine given 1 hour before didanosine

In vitro evidence of additive or synergistic antiretroviral effects

Administer delavirdine at least 1 hour before or at least 1 hour after buffered didanosine (pediatric oral solution admixed with antacid)

Drugs associated with pancreatitis (pentamidine, co-trimoxazole)

Increased risk of pancreatitis

Use with extreme caution and only if other alternative agents are not available; if clearly indicated, consider discontinuing didanosine

Drugs associated with neurotoxicity

Increased risk of neuropathy

Use caution

Efavirenz

In vitro evidence of additive antiretroviral effects

Etravirine

No clinically important effect on plasma concentrations or AUC of either drug

No in vitro evidence of antagonistic antiretroviral effects

Dosage adjustments not needed

Fluoroquinolones (ciprofloxacin, levofloxacin moxifloxacin, ofloxacin)

Decreased absorption and lower concentrations of fluoroquinolones with buffered didanosine

Studies using ciprofloxacin indicate didanosine delayed-release capsules do not affect pharmacokinetics of the fluoroquinolone

Ciprofloxacin: Administer 2 hours before or 6 hours after buffered didanosine (pediatric oral solution admixed with antacid)

Levofloxacin: Administer at least 2 hours before or 2 hours after buffered didanosine (pediatric oral solution admixed with antacid)

Moxifloxacin: Administer at least 4 hours before or 8 hours after buffered didanosine (pediatric oral solution admixed with antacid)

Ofloxacin: Administer at least 2 hours before or 2 hours after buffered didanosine (pediatric oral solution admixed with antacid)

Fosamprenavir

In vitro evidence of synergistic antiretroviral effects

Ganciclovir and valganciclovir

Didanosine given 2 hours before ganciclovir results in increased didanosine AUC and decreased ganciclovir AUC

Concomitant administration of didanosine with IV ganciclovir results in increased didanosine AUC and peak plasma concentrations; no change in ganciclovir pharmacokinetics

Because valganciclovir is rapidly and completely converted to ganciclovir, didanosine interaction reported with ganciclovir is expected to occur with valganciclovir

If no suitable alternatives to ganciclovir are available, use caution and monitor for didanosine toxicity

Histamine H2-receptor antagonists

Ranitidine: Slightly increased didanosine AUC and slightly decreased ranitidine AUC if given 2 hours prior to buffered didanosine

Hydroxyurea

Concomitant use of didanosine and hydroxyurea: Potential for increased risk of pancreatitis

Concomitant use of didanosine, hydroxyurea, and stavudine: Potential for increased risk of fatal hepatotoxicity

In vitro evidence of synergistic antiretroviral effects

Avoid concomitant use of didanosine and hydroxyurea (with or without stavudine)

Indinavir

Buffered didanosine (Videx): Substantially decreased indinavir concentrations and AUC if administered simultaneously

Delayed-release capsules (Videx EC): No effect on indinavir concentrations and AUC

In vitro evidence of synergistic antiretroviral effects

Buffered didanosine (Videx): Administer 1 hour after indinavir

Loperamide

Buffered didanosine: Decreased didanosine concentrations; no effect on didanosine AUC

Lopinavir/ritonavir

Lopinavir/ritonavir oral solution: Conflicting administration instructions regarding food

Lopinavir/ritonavir oral solution: Administer didanosine (without food) 1 hour before or 2 hours after lopinavir/ritonavir (with food)

Lopinavir/ritonavir tablets: May be administered at the same time as didanosine

Macrolides (clarithromycin)

Clarithromycin: Pharmacokinetic interaction unlikely

Maraviroc

No in vitro evidence of antagonistic antiretroviral effects

Methadone

Buffered didanosine: Substantially decreased didanosine concentrations and AUC; no change in methadone concentrations

Didanosine delayed-release capsules: Decreased didanosine concentrations and AUC

Didanosine pediatric oral solution: Concomitant use not recommended

Didanosine delayed-release capsules: Dosage adjustments not needed; monitor closely for adequate clinical response to didanosine (e.g., changes in viral load)

Metoclopramide

Buffered didanosine: Slightly increased didanosine concentrations; no effect on didanosine AUC

Nelfinavir

No change in nelfinavir concentrations when didanosine administered 1 hour before nelfinavir

In vitro evidence of additive or synergistic antiretroviral effects

Administer didanosine (without food) 1 hour before or 2 hours after nelfinavir (with food)

Nevirapine

No effect on nevirapine or didanosine pharmacokinetics

In vitro evidence of additive or synergistic antiretroviral effects

Raltegravir

In vitro evidence of additive to synergistic antiretroviral effects

Ribavirin

Increased intracellular concentrations of active didanosine metabolite

Serious adverse effects (fatal hepatic failure, peripheral neuropathy, pancreatitis, hyperlactatemia/lactic acidosis) reported with concomitant use

Concomitant use contraindicated

Rilpivirine

No effect on rilpivirine or didanosine concentrations when administered 2 hours apart

No in vitro evidence of antagonistic antiretroviral effects

Administer didanosine (without food) at least 2 hours before or 4 hours after rilpivirine (with food); dosage adjustments not needed

Ritonavir

Full-dose ritonavir: Decreased didanosine concentrations and AUC; no clinically important effect on ritonavir pharmacokinetics

In vitro evidence of additive or synergistic antiretroviral effects

Saquinavir

In vitro evidence of additive or synergistic antiretroviral effects

Simeprevir

Clinically important interactions not expected

Stavudine

No clinically important pharmacokinetic interactions

Concomitant use of didanosine and stavudine (with or without hydroxyurea): Increased risk of toxicities (pancreatitis, peripheral neuropathy, hyperlactatemia)

In vitro evidence of additive or synergistic antiretroviral effects; antagonism also reported

Experts state concomitant use of didanosine and stavudine not recommended at any time, including in pregnant women

Manufacturers state use concomitantly with caution; avoid concomitant use during pregnancy unless potential benefits outweigh risks

Avoid concomitant use of didanosine, hydroxyurea, and stavudine

Sulfamethoxazole

Pharmacokinetic interaction unlikely

Tenofovir

Buffered or delayed-release didanosine: Increased didanosine concentrations and AUC; no effect on tenofovir pharmacokinetics

Early virologic failure, rapid selection of resistant mutants, potential for immunologic nonresponse or decline in CD4+ T-cell counts reported

Increased risk of didanosine-associated adverse effects (e.g., pancreatitis, lactic acidosis, neuropathy)

No in vitro evidence of antagonistic antiretroviral effects

Experts state concomitant use of didanosine and tenofovir DF not recommended at any time

Manufacturers state use concomitantly with caution and reduced didanosine dosage; closely monitor for didanosine-associated adverse effects; discontinue didanosine if necessary

In adults or adolescents weighing ≥60 kg with Clcr ≥60 mL/minute, reduce didanosine dosage to 250 mg once daily; in those weighing <60 kg with Clcr ≥60 mL/minute, reduce didanosine dosage to 200 mg once daily

If using didanosine delayed-release capsules, administer didanosine and tenofovir DF at same time without food or with a light meal; if using didanosine pediatric oral solution, administer didanosine and tenofovir DF at same time without food or administer didanosine on an empty stomach (i.e., ≥30 minutes before or 2 hours after food) if tenofovir DF is taken with food

Tetracyclines

Buffered didanosine: Possible decreased tetracycline concentrations

Buffered didanosine (pediatric oral solution): Some clinicians recommend giving didanosine oral solution 1–2 hours before or after tetracycline dose

Tipranavir

Ritonavir-boosted tipranavir: Decreased didanosine concentrations; no effect on tipranavir concentrations; clinical importance unknown

In vitro evidence of additive antiretroviral effects

Administer ritonavir-boosted tipranavir at least 2 hours before or 2 hours after didanosine

Trimethoprim

Pharmacokinetic interaction unlikely

Zidovudine

Buffered didanosine: Decreased zidovudine concentrations and AUC; no effect on didanosine concentrations or AUC

In vitro evidence of synergistic antiretroviral effects

Didanosine Pharmacokinetics

Absorption

Bioavailability

Extent of absorption is variable and depends on several factors including dosage form administered, gastric pH, and presence of food in GI tract. Bioavailability is 42%.

Rapidly degraded at acidic pH; gastric secretions may inactivate the drug following oral administration.

Delayed-release capsules contain enteric-coated pellets of the drug to maximize GI absorption.

Powder for oral solution must be admixed with antacids prior to administration.

Following administration of delayed-release capsules, AUC is similar to, but peak plasma concentrations are 40% lower than, values reported following administration of chewable/dispersible tablets (no longer commercially available in the US).

No clinically important changes in pharmacokinetics of didanosine during pregnancy.

Food

Presence of food in GI tract decreases rate and extent of absorption.

Distribution

Extent

Distributed into CSF; concentrations in CSF may be 46% of concurrent plasma concentrations.

Crosses placenta and is distributed into cord blood and amniotic fluid. Distributed into milk in rats; not known whether distributed into human milk.

Plasma Protein Binding

<5%.

Elimination

Metabolism

Metabolism presumably occurs via same pathways responsible for elimination of endogenous purines.

Intracellularly, didanosine is phosphorylated and converted by cellular enzymes to the active metabolite, dideoxyadenosine 5′-triphosphate.

Elimination Route

Eliminated in urine by glomerular filtration and active tubular secretion.

Half-life

Adults: 0.97–1.6 hours.

Plasma half-life averages 1.2 hours in neonates and children 2 weeks to 4 months of age and 0.8 hours in children 8 months to 19 years of age.

Special Populations

The apparent oral clearance of didanosine decreases and half-life of the drug increases as Clcr decreases. Mean half-life is 1.42 hours in patients with Clcr ≥90 mL/minute or 1.59, 1.75, or 2 hours in those with Clcr 60–90, 30–59, or 10–29 mL/minute, respectively. In dialysis patients, mean half-life is 4.1 hours.

Removed by hemodialysis. Absolute bioavailability not affected in patients requiring dialysis. Does not appear to be removed by peritoneal dialysis.

Peak plasma concentrations and AUC in individuals with moderate or severe hepatic impairment (Child-Pugh class B or C) similar to values in individuals without hepatic impairment.

Stability

Storage

Oral

Delayed-release Capsules

25°C (may be exposed to 15–30°C); tight containers.

Pediatric Powder for Oral Solution

15–30°C.

Following reconstitution with water and admixture with a liquid antacid as directed, stable for 30 days when refrigerated at 2–8°C. Discard unused portions of reconstituted and admixed pediatric didanosine oral solutions after 30 days.

Actions and Spectrum

  • Analog of inosine, a naturally occurring purine nucleoside.

  • Pharmacologically related to other HIV NRTIs (e.g., abacavir, emtricitabine, lamivudine, stavudine, zidovudine); differs structurally from these drugs; also differs pharmacologically and structurally from other currently available antiretrovirals.

  • Active in vitro against HIV-1 and HIV-2.

  • Inhibits replication of HIV by interfering with viral RNA-directed DNA polymerase (reverse transcriptase).

  • Strains of HIV-1 with reduced susceptibility to didanosine have been produced in vitro and have emerged during therapy with the drug.

  • Strains of HIV resistant to didanosine may be cross-resistant to some other HIV NRTIs.

Advice to Patients

  • Didanosine medication guide must be provided to the patient each time the drug is dispensed; importance of patient reading the medication guide prior to initiating didanosine therapy and each time prescription is refilled.

  • Critical nature of compliance with HIV therapy and importance of remaining under the care of a clinician during therapy. Importance of taking as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinician.

  • Importance of using in conjunction with other antiretrovirals–not for monotherapy.

  • Antiretroviral therapy is not a cure for HIV infection; opportunistic infections and other complications associated with HIV disease may still occur.

  • Advise patients that sustained decreases in plasma HIV RNA have been associated with reduced risk of progression to AIDS and death.

  • Advise patients that effective antiretroviral regimens can decrease HIV concentrations in blood and genital secretions and strict adherence to such regimens in conjunction with risk-reduction measures may decrease, but cannot absolutely eliminate, the risk of secondary transmission of HIV to others. Importance of continuing to practice safer sex (e.g., using latex or polyurethane condoms to minimize sexual contact with body fluids), never sharing personal items that can have blood or body fluids on them (e.g., toothbrushes, razor blades), and never reusing or sharing needles.

  • If a dose is missed, it should be taken as soon as possible; if it is almost time for the next dose, the missed dose should be skipped and the next dose taken at the regularly scheduled time.

  • Possibility of pancreatitis, including fatal pancreatitis.

  • Possibility of peripheral neuropathy; manifestations include numbness, tingling, or pain in hands or feet. Advise patients that peripheral neuropathy occurs most frequently in patients with advanced HIV disease or a history of peripheral neuropathy, and that discontinuance of the drug may be required if peripheral neuropathy occurs.

  • Advise patients that lactic acidosis and severe hepatomegaly with steatosis, including fatalities, have been reported.

  • Advise patients that hepatotoxicity, including fatal events, have been reported in patients with preexisting liver dysfunction and that safety and efficacy not established in HIV-infected individuals with substantial underlying liver disease.

  • Advise patients that noncirrhotic portal hypertension (sometimes resulting in liver transplantation or death) have been reported.

  • Possibility of retinal changes and optic neuritis.

  • Redistribution/accumulation of body fat may occur, with as yet unknown long-term health effects.

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products, and any concomitant illnesses.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. Advise HIV-infected women not to breast-feed.

  • Importance of advising patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Didanosine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules, delayed-release (containing enteric-coated pellets)

125 mg*

Didanosine Delayed-release Capsules

Videx EC

Bristol-Myers Squibb

200 mg*

Didanosine Delayed-release Capsules

Videx EC

Bristol-Myers Squibb

250 mg*

Didanosine Delayed-release Capsules

Videx EC

Bristol-Myers Squibb

400 mg*

Didanosine Delayed-release Capsules

Videx EC

Bristol-Myers Squibb

For solution

2 g/bottle*

Didanosine for Oral Solution

Videx Pediatric

Bristol-Myers Squibb

4 g/bottle*

Didanosine for Oral Solution

Videx Pediatric

Bristol-Myers Squibb

AHFS DI Essentials™. © Copyright 2021, Selected Revisions February 9, 2015. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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