Didanosine
(ddI, dideoxyinosine)
Didanosine (Videx)
ddI (Videx)
Dideoxyinosine (Videx)
Didanosine
(die- DAN-oh-seen)
Pregnancy Category: B Videx (Rx)

Classification: Antiviral

See Also: See also Antiviral Agents .

Action/Kinetics: A nucleoside analog of deoxyadenosine. After entering the cell, it is converted to the active dideoxyadenosine triphosphate (ddATP) by cellular enzymes. Due to the chemical structure of ddATP, its incorporation into viral DNA leads to chain termination and therefore inhibition of viral replication. ddATP also inhibits viral replication by interfering with the HIV-RNA-dependent DNA polymerase by competing with the natural nucleoside triphosphate for binding to the active site of the enzyme. Didanosine has shown in vitro antiviral activity in a variety of HIV-infected T cell and monocyte/macrophage cell cultures. Is broken down quickly at acidic pH; therefore, PO products contain buffering agents to increase the pH of the stomach. Food decreases the rate of absorption. t 1/2, elimination: 1.6 hr for adults and 0.8 hr for children. Metabolized in the liver and excreted mainly through the urine.

Uses: Advanced HIV infection in adult and pediatric (over 6 months of age) clients who are intolerant of AZT therapy or who have demonstrated decreased effectiveness of AZT therapy. Use in adults with HIV infection who have received prolonged AZT therapy. Treatment of HIV infection when antiretroviral therapy is indicated. AZT should be considered as initial therapy for the treatment of advanced HIV infection, unless contraindicated, since this drug prolongs survival and decreases the incidence of opportunistic infections. May be used as monotherapy for the treatment of AIDS. As first-line component for HIV-1 infections with stavudine plus a protease inhibitor or the nonnucleoside efavirenz.

Contraindications: Lactation.

Special Concerns: Use with caution in renal and hepatic impairment and in those on sodium-restricted diets. Opportunistic infections and other complications of HIV infection may continue to develop; thus, keep clients under close observation. Fatal and nonfatal pancreatitis in both treatment naive or treatment experienced clients, regardless of the degree of immunosuppression; especially seen in those receiving stavudine with or without hydroxyurea.

Side Effects: Commonly pancreatitis and peripheral neuropathy (manifested by distal numbness, tingling, or pain in the feet or hands). Neuropathy occurs more frequently in clients with a history of neuropathy or neurotoxic drug therapy.
In adults. G I: Diarrhea, abdominal pain, N&V;, anorexia, dry mouth, ileus, colitis, constipation, eructation, flatulence, gastroenteritis, GI hemorrhage severe hepatomegaly with steatosis, oral moniliasis, stomatitis, mouth sores, sialadenitis, stomach ulcer hemorrhage melena, oral thrush, liver abnormalities, pancreatitis. CNS: Headache, tonic-clonic seizures abnormal thinking, anxiety, nervousness, twitching, confusion, depression, acute brain syndrome, amnesia, aphasia, ataxia, dizziness, hyperesthesia, hypertonia, incoordination, intracranial hemorrhage paralysis, paranoid reaction, psychosis, insomnia, sleep disorders, speech disorders, tremor. Hematologic: Leukopenia, granulocytopenia, thrombocytopenia, microcytic anemia, hemorrhage ecchymosis, petechiae. Dermatologic: Rash, pruritus, herpes simplex, skin disorder, sweating, eczema, impetigo, excoriation, erythema. Musculoskeletal: Asthenia, myopathy, arthralgia, arthritis, myalgia, muscle atrophy, decreased strength, hemiparesis, neck rigidity, joint disorder, leg cramps. CV: Chest pain, hypertension, hypotension, migraine, palpitation, peripheral vascular disorder, syncope, vasodilation, arrhythmias. Body as a whole: Chills, fever, infection, allergic reaction, pain, abscess, cellulitis, cyst, dehydration, malaise, flu syndrome, numbness of hands and feet, weight loss, alopecia, lactic acidosis. Respiratory: Pneumonia, dyspnea, asthma, bronchitis, increased cough, rhinitis, rhinorrhea, epistaxis, laryngitis, decreased lung function, pharyngitis, hypoventilation, sinusitis, rhonchi, rales, congestion, interstitial pneumonia, respiratory disorders. Ophthalmic: Blurred vision, conjunctivitis, diplopia, dry eye, glaucoma, retinitis, photophobia, strabismus, optic neuritis. Otic: Ear disorder, otitis (externa and media), ear pain. GU: Impotency, kidney calculus, kidney failure, abnormal kidney function, nocturia, urinary frequency, vaginal hemorrhage. Miscellaneous: Peripheral edema, sarcoma, hernia, hypokalemia, lymphoma-like reaction.
In children. G I: Diarrhea, N&V;, liver abnormalities, abdominal pain, stomatitis, mouth sores, pancreatitis, anorexia, increase in appetite, constipation, oral thrush, melena, dry mouth. CNS: Headache, nervousness, insomnia, dizziness, poor coordination, lethargy, neurologic symptoms, seizures. Hematologic: Ecchymosis, hemorrhage petechaie, leukopenia, granulocytopenia, thrombocytopenia, anemia. Dermatologic: Rash, pruritus, skin disorder, eczema, sweating, impetigo, excoriation, erythema. Musculoskeletal: Arthritis, myalgia, muscle atrophy, decreased strength. Body as a whole: Chills, fever, asthenia, pain, malaise, failure to thrive, weight loss, flu syndrome, alopecia, dehydration, lactic acidosis. CV: Vasodilation, arrhythmia. Respiratory: Cough, rhinitis, dyspnea, asthma, rhinorrhea, epistaxis, pharyngitis, hypoventilation, sinusitis, rhonchi, rales, congestion, pneumonia. Ophthalmic: Photophobia, strabismus, visual impairment, optic neuritis. Otic: Ear pain, otitis. Miscellaneous: Urinary frequency, diabetes mellitus, diabetes insipidus, liver abnormalities.

Laboratory Test Alterations: AST, ALT, alkaline phosphatase, bilirubin, uric acid, amylase, lipase.

Overdose Management: Symptoms: Pancreatitis, peripheral neuropathy, diarrhea, hyperuricemia, hepatic dysfunction. Treatment: There are no antidotes; treatment should be symptomatic.

Drug Interactions: Allopurinol / Didanosine plasma levels Antacids, Mg- or Al-containing / Risk of side effects due to antacid components Antifungal drugs (azoles) / Absorption of azole antifungals Antiretroviral drugs (Delavirdine, Indinavir) / Significant plasma levels of antiretroviral drugs Ganciclovir / Didanosine plasma levels; ganciclovir plasma levels Ketoconazole / Ketoconazole absorption R/T gastric pH change caused by buffering agents in didanosine Pentamidine (IV) / Risk of pancreatitis Quinolone antibiotics / Plasma quinolone levels R/T absorption Ranitidine / Ranitidine absorption R/T gastric pH change caused by buffering agents in didanosine Tetracyclines / Tetracycline absorption from the stomach R/T the buffering agents in didanosine

How Supplied: Chew Tablet: 25 mg, 50 mg, 100 mg, 150 mg, 200 mg; Powder for Oral Solution: 100 mg, 167 mg, 250 mg; Powder for Oral Solution, Pediatric: 2 g, 4 g

Dosage
?Chewable/Dispersible Buffered Tablets, Buffered Powder for Oral Solution, Powder for Pediatric Oral Solution
Adults, initial, over 60 kg: 200 mg q 12 hr (with 250 mg buffered powder q 12 hr). Alternatively, 2-200 mg tablets once daily with clients taking 2 or more of the appropriate strength tablets to assure adequate gastric buffering. Adults, less than 60 kg: 125 mg q 12 hr (with 167 mg buffered powder q 12 hr). Alternatively, 250 mg once daily. Pediatric: 120 mg/m ² b.i.d.
For adults with impaired renal function, the following dosage regimens are used: (1) C _CR 60 mL or more/min: 400 mg daily or 200 mg b.i.d. (with 250 mg buffered powder b.i.d.) if 60 kg or more; 250 mg daily or 125 mg b.i.d. (with 167 mg buffered powder) if less than 60 kg. (2) C _CR, 30-50 mL/min: 200 mg daily or 100 mg b.i.d. (with 100 mg buffered powder b.i.d.) if 60 kg or more; 150 mg daily or 75 mg b.i.d. with 100 mg buffered powder b.i.d. if less than 60 kg. (3) C _CR, 10-20 mL/min: 150 mg daily with 167 mg buffered powder daily if 60 kg or more; 100 mg daily with 100 mg buffered powder daily if less than 60 kg; (4) C _CR, less than 10 mL/min: 100 mg daily with 100 mg buffered powder daily if more than 60 kg; 75 mg daily with 100 mg buffered powder daily if less than 60 kg.