Class: Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
VA Class: AM800
Chemical Name: 2′,3′-Dideoxyinosine
CAS Number: 69655-05-6
Brands: Videx
Fatal and nonfatal pancreatitis reported.1 248 Temporarily interrupt didanosine therapy in patients with suspected pancreatitis; discontinue in patients with confirmed pancreatitis.1 248 (See Pancreatitis under Cautions.)
Lactic acidosis and severe hepatomegaly with steatosis (including some fatalities) reported rarely in patients receiving nucleoside reverse transcriptase inhibitors (NRTIs) alone or in conjunction with other antiretrovirals.1 248 (See Lactic Acidosis and Severe Hepatomegaly with Steatosis under Cautions.)
Fatal lactic acidosis reported in pregnant women receiving didanosine and stavudine with other antiretrovirals.1 248 Didanosine in conjunction with stavudine should be used with caution in pregnant women and only if potential benefits outweigh potential risks.1 248 (See Pregnancy under Cautions.)
REMS:
FDA approved a REMS for didanosine to ensure that the benefits of a drug outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page () or the ASHP REMS Resource Center ().
Introduction
Antiretroviral; nucleoside reverse transcriptase inhibitor (NRTI).1 2 3 8 21 30 34 36 40 44 72
Uses for Didanosine
Treatment of HIV Infection
Treatment of HIV-1 infection in conjunction with other antiretrovirals.1 248
Used in 3-drug antiretroviral regimens that include another NRTI (dual NRTIs) and either a nonnucleoside reverse transcriptase inhibitor (NNRTI) or an HIV protease inhibitor (PI) (NNRTI- or PI-based regimens).165 207 Monotherapy or 2-drug regimens that include only NRTIs are no longer recommended for treatment of HIV infection in adults, adolescents, or children.165 207
For initial therapy in adults and adolescents, some experts state that didanosine in conjunction with either emtricitabine or lamivudine is an acceptable (not a preferred or alternative) dual NRTI option for use in conjunction with efavirenz in an NNRTI-based regimen.207 Acceptable dual NRTI options may be selected for some patients, but are less satisfactory than preferred or alternative dual NRTI options.207
When PI- or NNRTI-based regimens are used in children, some experts state that didanosine and emtricitabine is a preferred dual NRTI option and didanosine and zidovudine is an alternative dual NRTI option.165
Because of insufficient data in treatment-naive patients, the dual NRTI option of didanosine and abacavir is not recommended for use in initial antiretroviral regimens in adults and adolescents.207
The dual NRTI option of didanosine and tenofovir is not recommended for use in initial regimens in treatment-naive adults and adolescents because limited data indicate such regimens are associated with early virologic failure, rapid selection of resistant mutations, and potential for immunologic nonresponse or decline in CD4+ T-cell counts.207
The dual NRTI option of didanosine and stavudine has been associated with a high incidence of toxicities (e.g., peripheral neuropathy, pancreatitis, lactic acidosis)1 207 212 248 and is not recommended except in special circumstances when there are no other options and potential benefits outweigh risks.1 165 207 212 248 (See Pregnancy under Cautions.)
Postexposure Prophylaxis of HIV
Postexposure prophylaxis of HIV infection† in health-care workers and others exposed occupationally via percutaneous injury or mucous membrane or nonintact skin contact with blood, tissues, or other body fluids associated with risk for transmission of the virus.95 Used in conjunction with other antiretrovirals.95
Postexposure prophylaxis of HIV infection† in individuals who have had nonoccupational exposure to blood, genital secretions, or other potentially infectious body fluids of a person known to be infected with HIV when that exposure represents a substantial risk for HIV transmission.258 Used in conjunction with other antiretrovirals.258
Didanosine Dosage and Administration
Administration
Oral Administration
Delayed-release capsules containing enteric-coated pellets of didanosine are administered once daily without food and should be swallowed intact.248
Didanosine pediatric oral solution admixed with antacid is administered orally at least 30 minutes before or 2 hours after a meal.1 165 207 The pediatric oral solution is administered twice daily in children.1 Twice-daily administration also preferred in adults and adolescents,1 165 207 but a once-daily regimen of the oral solution can be considered in adults and adolescents if needed.1 165
Reconstitution and Dilution
The pediatric powder for oral solution must be reconstituted and admixed with an antacid at time of dispensing.1 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.1 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.1 Shake the final admixture thoroughly prior to removing each dose.1
Dosage
Adult dosage is based on weight.1 248 Dosage in pediatric patients is based on body surface area or weight.1 248
Delayed-release capsules are used in adults and also can be used in children weighing ≥20 kg who can swallow capsules.248 Pediatric oral solution generally used in children, but may be used in adults.1
Must be given in conjunction with other antiretrovirals.1 248 If used with atazanavir, darunavir, delavirdine, indinavir, lopinavir, nelfinavir, tenofovir, or tipranavir, adjustment in the treatment regimen necessary.1 248 (See Specific Drugs under Interactions.)
Pediatric Patients
Treatment of HIV Infection
Oral
Pediatric oral solution admixed with antacid: Infants and children 2 weeks through 8 months of age: 100 mg/m2 twice daily.1 165
Pediatric oral solution admixed with antacid: Children >8 months of age: 120 mg/m2 twice daily.1 165
Pediatric oral solution admixed with antacid: Adolescents: 200 mg twice daily in those weighing ≥60 kg or 125 mg twice daily in those weighing <60 kg.165 Alternatively, in adolescents whose management requires once-daily dosing, 400 mg once daily in those weighing ≥60 kg or 250 mg once daily in those weighing <60 kg.165
Delayed-release capsules: Children and adolescents weighing 20 to <25 kg: 200 mg once daily.165 248
Delayed-release capsules: Children and adolescents weighing 25 to <60 kg: 250 mg once daily.165 248
Delayed-release capsules: Children and adolescents weighing ≥60 kg: 400 mg once daily.165 248
Adults
Treatment of HIV Infection
Treatment in Adults Weighing <60 kg
Oral
Delayed-release capsules: 250 mg once daily.207 248
Pediatric oral solution admixed with antacid: 125 mg twice daily.1 If once-daily administration required, 250 mg once daily.1
Treatment in Adults Weighing ≥60 kg
Oral
Delayed-release capsules: 400 mg once daily.207 248
Pediatric oral solution admixed with antacid: 200 mg twice daily.1 If once-daily administration required, 400 mg once daily.1
Postexposure Prophylaxis of HIV†
Occupational Exposure†
Oral
Delayed-release capsules: Adults weighing <60 kg: 250 mg once daily.95 207
Delayed-release capsules: Adults weighing ≥60 kg: 400 mg once daily.95 207
Initiate postexposure prophylaxis as soon as possible following exposure and continue for 4 weeks, if tolerated.95
Nonoccupational Exposure†
Oral
Delayed-release capsules: Adults weighing <60 kg: 250 mg once daily.207 258
Delayed-release capsules: Adults weighing ≥60 kg: 400 mg once daily.207 258
Initiate postexposure prophylaxis as soon as possible following exposure (preferably ≤72 hours after exposure) and continue for 28 days.258
Special Populations
Renal Impairment
Treatment of HIV Infection
Oral
Dosage in Adults with Renal Impairment (Delayed-release Capsules)248
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
|
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.1 248 Although data are insufficient to date to make specific dosage recommendations for pediatric patients with impaired renal function,1 248 manufacturer recommends that dosage reduction be considered.1 248
Hepatic Impairment
Dosage adjustment not needed.1 248
Cautions for Didanosine
Contraindications
Warnings/Precautions
Warnings
FDA required and approved a Risk Evaluation and Mitigation Strategy (REMS) for didanosine;269 goal of the didanosine REMS is to inform patients of the serious risks associated with the drug.269 The REMS requires that a didanosine medication guide be provided to the patient each time the drug is dispensed and requires the manufacturer to periodically submit REMS assessments to FDA.269
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.1 19 29 34 36 39 41 44 47 49 69 145 248
Interrupt didanosine therapy in patients with signs or symptoms of pancreatitis; discontinue the drug in patients with confirmed pancreatitis.1 248
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).1 248 Patients with renal impairment also are at increased risk for pancreatitis if didanosine dosage is not reduced.1 248
Discontinue didanosine if treatment with a life-sustaining drug known to cause pancreatic toxicity is required.1 248
Lactic Acidosis and Severe Hepatomegaly with Steatosis
Lactic acidosis and severe hepatomegaly with steatosis (sometimes fatal) reported in patients receiving NRTIs (including didanosine) alone or in conjunction with other antiretrovirals.1 65 82 129 248 Reported most frequently in women; obesity and long-term NRTI therapy also may be risk factors.1 248 Has been reported in patients with no known risk factors.1 248
Reported in pregnant women receiving didanosine in conjunction with stavudine.1 248 (See Pregnancy under Cautions.)
Use with caution in patients with known risk factors for liver disease.1 248
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).1 248
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.1 248 268 271
Didanosine-associated noncirrhotic portal hypertension was confirmed by liver biopsy in patients with no evidence of viral hepatitis or other alternative etiologies.1 248 268
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.1 248 268 271 Medical interventions consisted of banding or ligation of esophageal varices, transjugular intrahepatic portosystemic shunting (TIPSS), and liver transplantation.268 There were 4 deaths among 42 reported postmarketing cases.268
Although a causal relationship is difficult to determine, after excluding other causes of portal hypertension (e.g., alcohol-related cirrhosis, hepatitis C virus [HCV] infection), FDA concluded that there is an association between use of didanosine and development of noncirrhotic portal hypertension.268 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.268
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).1 248 271 Discontinue didanosine in patients with evidence of noncirrhotic portal hypertension.1 248 271
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.1 248
Consider discontinuance of didanosine if peripheral neuropathy occurs.1 248
Ocular Effects
Retinal changes and optic neuritis reported in adults and pediatric patients.1 66 82 248 Consider periodic retinal examinations.1 248
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 jiroveci [formerly P. carinii]); this may necessitate further evaluation and treatment.1 248
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.1 248
The mechanisms and long-term consequences of these adipogenic effects are unknown.1 248 A causal relationship has not been established.1 248
Cardiovascular Effects
There is some evidence that recent use of didanosine (within 6 months) is associated with an increased risk of MI.207 267
Specific Populations
Pregnancy
Category B.1 248
Antiretroviral Pregnancy Registry at 800-258-4263.1 248
An alternative (not a preferred) NRTI for dual NRTI option for use in multiple-drug antiretroviral regimens in pregnant women.212
Fatal lactic acidosis reported in pregnant women receiving didanosine and stavudine with other antiretrovirals.1 248 Unclear whether pregnancy potentates risk of lactic acidosis and severe hepatotoxicity with steatosis that occurs in NRTI-treated individuals.1 248 The dual NRTI option of didanosine and stavudine should be used with caution in pregnant women and only if there are no other treatment options and potential benefits outweigh risks.1 212 248
Clinicians caring for pregnant patients receiving didanosine should be alert for early diagnosis of lactic acidosis and hepatitis steatosis syndrome.1 248
Lactation
Didanosine and/or its metabolites distributed into milk in rats; not known whether distributed into human milk.1 248
Instruct HIV-infected women not to breast-feed1 212 248 because of risk of HIV transmission and risk of adverse effects in the infant.1 248
Pediatric Use
Delayed-release capsules: Use in children weighing ≥20 kg supported by pharmacokinetic data.248
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.1
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.1 35 45 131 237
Geriatric Use
Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults.1 248
Substantially eliminated by kidneys; risk of toxic reactions may be greater in patients with decreased renal function.1 248 Consider age-related decreases in renal function when selecting dose.1 248 Monitor renal function and adjust dosage as necessary.1 248
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).1 248
Use with caution and monitor patients with liver disease.1 248 Interrupt or discontinue if liver disease worsens.1 248
Because noncirrhotic portal hypertension has been reported rarely in patients receiving didanosine,1 248 268 271 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).1 248 271 Discontinue didanosine if there is evidence of noncirrhotic portal hypertension.1 248 271 (See Noncirrhotic Portal Hypertension under Cautions.)
Renal Impairment
Risk of toxic reactions may be greater in patients with decreased renal function.1 248
Dosage adjustment needed based on degree of renal impairment.1 248 (See Renal Impairment under Dosage and Administration.)
Common Adverse Effects
Diarrhea, peripheral neurologic symptoms/neuropathy, rash/pruritus, nausea, headache, vomiting, abdominal pain, pancreatitis.1 248
Interactions for Didanosine
Drug interaction studies have used buffered preparations of didanosine (chewable/dispersible, buffered tablets [no longer commercially available in the US], pediatric oral solution admixed with antacid) or didanosine delayed-release capsules.248 Although there are a few exceptions (e.g., ciprofloxacin, indinavir, ketoconazole),48 248 results of drug interaction studies that used buffered preparations of didanosine are expected to apply to delayed-release capsules.248
Specific Drugs
Drug
|
Interaction
|
Comments
|
|---|
Allopurinol
|
Increased didanosine concentrations and AUC;1 207 248 possible increased risk of didanosine toxicity1 207 248
|
Concomitant use contraindicated1 207 248
|
Antacids
|
Aluminum- and magnesium-containing antacids increase oral bioavailability of didanosine1 2 3 38 39 62
Possible increased antacid adverse effects if additional antacids are used in patients receiving didanosine pediatric oral solution admixed with antacid1
|
Used to therapeutic advantage; didanosine pediatric oral solution is admixed with antacid prior to administration1
Additional antacids should be used with caution in patients receiving didanosine pediatric oral solution admixed with antacid1
|
Antifungals, azoles
|
Itraconazole: Decreased itraconazole concentrations with buffered didanosine preparations1 132
Ketoconazole: Decreased ketoconazole peak plasma concentrations and AUC with buffered didanosine preparations;1 no changes in ketoconazole concentrations with didanosine delayed-release capsules48 248
|
Administer itraconazole or ketoconazole at least 2 hours before buffered didanosine (pediatric oral solution admixed with antacid)1
|
Antimycobacterials
|
Rifabutin: Pharmacokinetic interaction unlikely238
Isoniazid: Pharmacokinetic interaction unlikely78
|
|
Atazanavir
|
Decreased plasma concentrations and AUC of atazanavir if administered concomitantly with buffered didanosine preparations260
Decreased didanosine concentrations and AUC if administered concomitantly with didanosine delayed-release capsules207 260
No in vitro evidence of antagonistic antiretroviral effects260
|
Administer atazanavir (with food) 2 hours before or 1 hour after buffered didanosine (pediatric oral solution admixed with antacid) or delayed-release capsules207 260
|
Dapsone
|
No effect on dapsone concentrations or AUC1 181 248
Some reports of failure of dapsone to prevent Pneumocystis carinii pneumonia in HIV-infected patients receiving didanosine concomitantly71
|
Some clinicians suggest that didanosine be administered at least 2 hours after dapsone71 207
|
Darunavir
|
Didanosine delayed-release capsules: No change in didanosine or darunavir concentrations261
Conflicting administration instructions with regard to food261
|
Administer didanosine 1 hour before or 2 hours after ritonavir-boosted darunavir261
|
Delavirdine
|
Decreased delavirdine and didanosine concentrations if given at the same time as buffered didanosine preparations;1 210 clinically important pharmacokinetic interaction not observed when buffered didanosine administered 1 hour after delavirdine1
In vitro evidence of additive or synergistic antiretroviral effects210
|
Administer at least 1 hour before or at least 1 hour after buffered didanosine (pediatric oral solution admixed with antacid)1 210
|
Drugs associated with pancreatitis (pentamidine, co-trimoxazole)
|
Increased risk of pancreatitis1 19 36 39 248
|
Use with extreme caution and only if other alternative agents are not available; if clearly indicated, consider discontinuing didanosine1 19 36 39 248
|
Drugs associated with neurotoxicity
|
Increased risk of neuropathy1 248
|
Use with caution1 248
|
Efavirenz
|
In vitro evidence of additive antiretroviral effects217
|
|
Fluoroquinolones (ciprofloxacin, levofloxacin moxifloxacin, ofloxacin)
|
Decreased absorption and lower concentrations of fluoroquinolones with buffered didanosine preparations1 262 263 264
Studies using ciprofloxacin indicate didanosine delayed-release capsules do not affect pharmacokinetics of the fluoroquinolone48 248
|
Ciprofloxacin: Administer 2 hours before or 6 hours after buffered didanosine (pediatric oral solution admixed with antacid)1
Levofloxacin: Administer at least 2 hours before or 2 hours after buffered didanosine (pediatric oral solution admixed with antacid)262
Moxifloxacin: Administer at least 4 hours before or 8 hours after buffered didanosine (pediatric oral solution admixed with antacid)263
Ofloxacin: Administer at least 2 hours before or 2 hours after buffered didanosine (pediatric oral solution admixed with antacid)264
|
Ganciclovir and valganciclovir
|
Didanosine given 2 hours before ganciclovir results in increased didanosine AUC1 207 248 and decreased ganciclovir AUC1 207
Concomitant administration of didanosine with IV ganciclovir results in increased didanosine AUC and peak plasma concentrations; no change in ganciclovir pharmacokinetics250
Because valganciclovir is rapidly and completely converted to ganciclovir, didanosine interaction reported with ganciclovir is expected to occur with valganciclovir251
|
Appropriate dosages for concomitant use with respect to safety and efficacy not established207
Manufacturer of didanosine states that, if there is no suitable alternative to ganciclovir, the drugs should be used with caution and the patient monitored for didanosine toxicity1 248
|
Histamine H2-receptor antagonists
|
Pharmacokinetic interaction unlikely with ranitidine and buffered didanosine preparations1
|
|
Hydroxyurea
|
Concomitant use of didanosine and hydroxyurea: Potential for increased risk of pancreatitis1 228 248
Concomitant use of didanosine, hydroxyurea, and stavudine: Potential for increased risk of fatal hepatotoxicity1 248
In vitro evidence of synergistic antiretroviral effects221 227 229 235
|
Avoid concomitant use of didanosine and hydroxyurea (with or without stavudine)1 248
|
Indinavir
|
When buffered didanosine preparations administered at the same time as indinavir, decreased AUC of indinavir1
No evidence of pharmacokinetic interaction with didanosine delayed-release capsules248
In vitro evidence of synergistic antiretroviral effects187
|
Administer buffered didanosine (pediatric oral solution admixed with antacid) and indinavir at least 1 hour apart; indinavir and buffered didanosine oral solution should be administered on an empty stomach1 187
|
Loperamide
|
Concomitant administration with didanosine pediatric oral solution admixed with antacid decreases peak didanosine plasma concentrations but does not affect didanosine AUC1
|
|
Lopinavir
|
Fixed-combination oral solution containing lopinavir and ritonavir: Conflicting administration instructions with regard to food244
|
Fixed-combination oral solution containing lopinavir and ritonavir: Administer didanosine (without food) 1 hour before or 2 hours after lopinavir (with food)244
Fixed-combination tablets containing lopinavir and ritonavir: May be administered at the same time as didanosine244
|
Macrolides (clarithromycin)
|
Pharmacokinetic interaction with clarithromycin unlikely158
|
|
Methadone
|
Decreased didanosine concentrations and AUC;1 243 248 no change in methadone concentrations243
|
If concomitant use is considered necessary, manufacturer of didanosine states that didanosine delayed-release capsules (not pediatric oral solution admixed with antacid) should be used and patients monitored closely for adequate clinical response to the antiretroviral agent (e.g., monitor for changes in viral load)1 248
|
Metoclopramide
|
Concomitant administration with didanosine pediatric oral solution admixed with antacid results in slight increase in peak didanosine plasma concentrations but does not affect didanosine AUC1
|
|
Nelfinavir
|
No change in nelfinavir concentrations when didanosine administered 1 hour before nelfinavir1 211 248
In vitro evidence of additive or synergistic antiretroviral effects186 211
|
Administer didanosine (without food) 1 hour before or 2 hours after nelfinavir (with food) 1 211 248
|
Nevirapine
|
No effect on nevirapine or didanosine pharmacokinetics204
In vitro evidence of additive or synergistic antiretroviral effects204
|
|
Ribavirin
|
Pharmacokinetic interaction;1 248 increased intracellular concentrations of active didanosine metabolite1 248
Serious adverse effects (fatal hepatic failure, peripheral neuropathy, pancreatitis, hyperlactatemia/lactic acidosis) reported with concomitant use1 207 248
|
Concomitant use contraindicated1 207 248
|
Ritonavir
|
Slight decrease in didanosine peak plasma concentrations and AUC;172 no effect on ritonavir peak plasma concentrations or AUC172
In vitro evidence of additive or synergistic antiretroviral effects172 186
|
|
Saquinavir
|
In vitro evidence of additive or synergistic antiretroviral effects163 186
|
|
Stavudine
|
Pharmacokinetic interactions unlikely1
Concomitant use of didanosine and stavudine: Possible increased risk of toxicities (pancreatitis, peripheral neuropathy, hyperlactatemia)1 212 207 248
Concomitant use of didanosine, hydroxyurea, and stavudine: Potential for increased risk of fatal hepatic events1 248
In vitro evidence of additive or synergistic antiretroviral effects189
|
Concomitant use of didanosine and stavudine not recommended;1 165 207 212 248 use with caution and only in special circumstances when there are no other options and potential benefits outweigh risks1 165 207 212 248
Avoid concomitant use of didanosine, hydroxyurea, and stavudine1 248
|
Sulfamethoxazole
|
Pharmacokinetic interaction unlikely1
|
|
Tenofovir
|
Increased plasma concentrations and AUC of didanosine; no effect on tenofovir pharmacokinetics1 207 248 265
Limited data indicate early virologic failure, rapid selection of resistant mutants, and potential for immunologic nonresponse or decline in CD4+ T-cell counts207
Possible increased risk of didanosine-associated adverse effects (e.g., pancreatitis, neuropathy)1 248 265
In vitro evidence of additive or synergistic antiretroviral effects265
|
Avoid concomitant use of didanosine and tenofovir if possible207
Concomitant use not recommended for initial therapy in adults or adolescents;207 triple NRTI regimen of tenofovir, didanosine, and lamivudine (or emtricitabine) not recommended in pediatric patients165
If didanosine and tenofovir used concomitantly in adults and adolescents, reduce didanosine dosage1 207 248 265
If didanosine and tenofovir used concomitantly in any patient, use caution and closely monitor for didanosine-associated adverse effects and clinical response; discontinue didanosine if necessary1 207 248 265
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;1 207 248 administer didanosine delayed-release capsules and tenofovir without food or with a light meal;248 administer didanosine pediatric oral solution and tenofovir without food or administer pediatric oral solution on an empty stomach (i.e., ≥30 minutes before or 2 hours after food) if tenofovir is taken with food1
|
Tetracyclines
|
Decreased tetracycline concentrations with buffered didanosine preparations1
|
Caution if used with buffered didanosine (pediatric oral solution admixed with antacid)1
|
Tipranavir
|
Decreased didanosine concentrations;207 259 clinical importance unknown259
In vitro evidence of additive antiretroviral effects259
|
Administer ritonavir-boosted tipranavir at least 2 hours before or 2 hours after didanosine delayed-release capsules |
