Didanosine dosing

There are currently six major antiretroviral drug families (Table 5). Nucleoside reverse transcriptase inhibitors (NRTI) are nucleoside analogs (discussed in more detail in chapter by De Clercq and Neyts, this volume) and were the first approved antiretroviral agents. They include drugs such as AZT, didanosine (ddl), stavudine (d4T), abacavir (ABC), and lamivudine (3TC), the latest used at doses of 300 mg daily as anti-HIV agent (lOOmg/day is the dosing approved for treatment of HBV... 

NRTls are structural analogues of the natural nucleotides that form the building blocks of RNA and DNA in human cells. Their use as part of HAART has dramatically modified the natural history of HIV infection. They, however, cause a range of drag- or tissue-specific toxicides zidovudine (AZT) causes myopathy zalcitabine (ddC), didanosine (ddl), and lamivudine (3TC) cause neuropathy stavudine (d4T) causes neuropathy or myopathy and lactic acidosis (Dalakas 2001). During phase 1 and 11 trials, the dose-limiting toxicity of didanosine, zalcitabine, and stavudine was identified as peripheral neuropathy (Dalakas 2001). 

Administer oral doses of moxifloxacin at least 4 hours before or 8 hours after antacids containing magnesium or aluminum, sucralfate, metal cations such as iron, multivitamin preparations with zinc, or didanosine (chewable/buffered tablets or pediatric powder for oral solution). 

Didanosine (Videx) - The preferred dosing frequency of didanosine buffered is twice daily because there is more evidence to support the effectiveness of this dosing regimen. Once-daily dosing should be considered only for adult patients whose management requires once-daily dosing of didanosine. 

Didanosine (Videx) - The recommended dose of didanosine in pediatric patients is 120 mg/m twice daily. There are no data on once-daily dosing of didanosine in pediatric patients. 

Based on data with buffered didanosine formulations, patients with symptoms of peripheral neuropathy may tolerate a reduced dose after resolution of these symptoms following drug discontinuation. If neuropathy recurs after resumption of didanosine, consider permanent discontinuation. 

Renal function impairment- In adult patients with impaired renal function, adjust the dose of didanosine to compensate for the slower rate of elimination. 

Recommended Dose (mg) of Didanosine by Body Weight in Renal Function... 

Didanosine chewable/dispersible buffered tablets. Two didanosine tablets must be take with each dose different strengths of tablets may be combined to yield the recommende dose. 

Didanosine (Videx) - It is recommended that % of the total daily dose of didanosine be administered once daily. For patients with Ccr less than 10 mL/min, it is not necessary to administer a supplemental dose of didanosine following hemodialysis. 

Phenylketonuria Didanosine chewable/dispersible buffered tablets contain the following quantities of phenylalanine 73 mg phenylalanine per 2-tablet dose (36.5 mg phenylalanine per tablet). 

Sodium-restricted diets Each buffered tablet contains 264.5 mg sodium. Each single-dose packet of buffered powder for oral solution contains 1380 mg sodium. Hyperuricemia Didanosine has been associated with asymptomatic hyperuricemia consider suspending treatment if clinical measures aimed at reducing uric acid levels fail. 

Neurologic symptoms Motor weakness has been reported rarely. Most of these cases occurred in the setting of lactic acidosis. The evolution of motor weakness may mimic the clinical presentation of Guillain-Barre syndrome (including respiratory failure). Symptoms may continue or worsen following discontinuation of therapy. Stavudine therapy has been associated with peripheral neuropathy, which can be severe and is dose-related. Peripheral neuropathy has occurred more frequently in patients with advanced HIV disease, a history of neuropathy, or concurrent neurotoxic drug therapy, including didanosine (see Adverse Reactions). 

Ciprofloxacin (Cipro, Cipro XR, Proquin XR) [Antibiotic/ Fluoroquinolone] Uses Rx lower resp tract, sinuses, skin skin structure, bone/joints, urinary tract Infxns including prostatitis Action Quinolone antibiotic DNA gyrase Dose Adults. 250-750 mg PO ql2h XR 500-1000 mg PO q24h or 200-400 mg IV ql2h in renal impair Caution [C, /-] Children <18 y Contra Component sensitivity Disp Tabs, susp, inj SE Restlessness, N/V/D, rash, ruptured tendons, T LFTs Interactions T Effects Wf probenecid T effects OF diazepam, theophylline, caffeine, metoprolol, propranolol, phenytoin, warfarin effects W/ antacids, didanosine, Fe salts. Mg, sucralfate, Na bicarbonate,... 

Deravirdine (Rescnptor) [Antiretroviral/NNRTI] Uses HIV Infxn Action Nonnucleoside RT inhibitor Dose 400 mg PO tid Caution [C, ] CDC recommends HIV-infected mothers not to breast-feed (transmission risk) w/ renal/hepatic impair Contra Use w/ drugs dependent on CYP3A for clearance (Table VI-8) Disp Tabs SE Fat redistribution, immune reconstitution synd, HA, fatigue, rash, T transaminases, N/V/D Interactions T Effects W/ fluoxetine T effects OF benzodiazepines, cisapride, clarithromycin, dapsone, ergotamine, indinavir, lovastatin, midazolam, nifedipine, quinidine, ritonavir, simvastatin, terfena-dine, triazolam, warfarin effects W/ antacids, barbiturates, carbamazepine, cimetidine, famotidine, lansoprazole, nizatidine, phenobarbital, phenytoin, ranitidine, rifabutin, rifampin effects OF didanosine EMS Use of benzodiazepines and CCBs should be avoided may cause a widespread rash located on upper body and arms OD May cause an extension of nl SEs symptomatic and supportive Deferasirox (Exjade) [Iron Chelator] Uses Chronic iron overload d/t transfusion in pts >2 y Action Oral iron chelator Dose Initial 20 mg/kg... 

Foscarnet (Foscavir) [Antiviral] Uses CMV retinitis acyclovir-resistant hCTpes Infxns Action -1- Viral DNA polym ase RT Dose CMV retinitis Induction 60 mg/kg IV qSh or 100 mg/kg ql2h X 14—21 d Meant 90-120 mg/kg/dIV (Moo.-Fiti ) Acyclovir-resistant HSV Induction 40 mg/kg IV q8-12h x 14—21 d use central line -1- w/ renal impair Caution [C, —] T Sz potential w/ fluoroquinolones avoid n hrotoxic Rx (cyclosporine, aminoglycosides, ampho B, protease inhibitors) Contra CrCl <0.4 mL/min/kg Disp Inj SE Nephrotox, electrolyte abnormalities Interactions T Risks of Sz W/ quinolones t risks of n hrotox W/ aminoglycosides, amphotCTicin B, didanosine, pentamidine, vancomycin EMS Known to cause electrolyte disturbances (extremity numbness paresthesia indicates electrol5rte unbalance) monitor ECG OD May cause extremity numbing, and Szs hydrate w/ IV fluids... 

The higher dose should be used if the patient is taking concurrent enzyme inducers e.g. rifampacin and/or drugs which increase gastric pH e.g. antacids, didanosine (ddl). 

The adverse effects with which stavudine is most frequently associated are headache, diarrhea, skin rash, nausea, vomiting, insomnia, anorexia, myalgia, and weakness. Peripheral neuropathy consisting of numbness, tingling, or pain in the hands or feet is also common with higher doses of the drug. Significant elevation of hepatic enzymes may be seen in approximately 10 to 15% of patients. Lactic acidosis occurs more frequently with stavudine than with other NRTIs. Viral resistance to stavudine may develop, and cross-resistance to zidovudine and didanosine may occur. 

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