Didanosine

Adverse reactions reported with didanosine include headache, peripheral neuropathy, rhinitis, cough, diarrhea, nausea, vomiting, anorexia, hepatotoxicily, and pancreatitis. 

This drug is used cautiously in patients with peripheral vascular disease, neuropathy, chronic pancreatitis, or impaired liver function. Didanosine is a Pregnancy Category B drug and is used cautiously during pregnancy and lactation. There may be a decrease in the effectiveness of dapsone in preventing Pneumocystis carinii pneumonia when didanosine is administered with dapsone Use of didanosine with zalcitabine may cause additive neuropathy. Absorption of didanosine is decreased when it is administered with food. 

DIDANOSINE Although rare, pancreatitis and peripheral neuropathy are possible adverse reactions seen with didanosine The nurse must be alert for symptoms of pancreatitis (nausea, vomiting, abdominal pain, jaundice, elevated enzymes) and for signs of peripheral neuropathy (numbness, tingling, or pain in the feet or hands). It is important to immediately report these signs to the primary health care provider. 

Didanosine Take this drug on an empty stomach because food decreases absorption. Follow the instructions for administration carefully. Crush the drug and mix it with water. Discontinue use of the drug and notify the primary health care provider if any numbness or tingling of the extremities is experienced. Report any signs of abdominal pain, nausea, or vomiting. Didanosine is not a cure for AIDS and does not prevent the spread of the disease, but it may decrease the symptoms of AIDS. 

At present there are seven NRTIs, which have been formally approved for the treatment of AIDS 3 -azido-2, 3 -dideoxythymidine (AZT, zidovudine), 2, 3 -dideoxyinosine (ddl, didanosine), 2, 3 -dideoxycytidine (ddC, zalcitabine), 2, 3 -didehydro-2, 3 -dideoxythymidine (d4T, stavudine), (—)-L-3 -thia-2, 3 -dideoxycytidine (3TC, lamivudine), cyclopentenyl V -cyclopropylaminopurine (abacavir, ABC), and (—)-L-5-fluoro-3 -thia-2, 3 -dideoxycytidine ((—)FTC, emtricitabine) (De Clercq 2004a) (Fig. 3). 

Podzamczer D, Ferrer E, GateU JM, Niubo J, Dalmau D, Leon A, Knobel H, Polo C, Iniguez D, Ruiz I (2005) Early virological failure with a combination of tenofovir, didanosine and efavirenz. Antivir Ther 10 171-177... 

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... 

Zidovudine Didanosine Stavudine Lamivudine Abacavir Tenofovir Emtricitabine Nevirapine Efavirenz TMC125 Saquinavir Indinavir Lopinavir Fosamprenavir Atazanavir Tipranavir Darunavir Raltegravir Elvitegravir Enluvirtide Maraviroc Vicriviroc Bevirimat... 

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). 

Moore RD, Wong WM et al (2000) Incidence of neuropathy in HIV-infected patients on monotherapy versus those on combination therapy with didanosine, stavudine and hydroxyurea. AIDS 14(3) 273-278... 

Zhu Y, Antony J et al (2006) CD8-t lymphocyte-mediated injury of dorsal root ganghon neurons during lentiviras infection CD 154-dependent ceU contact neurotoxicity. J Neurosci 26(13) 3396-3403 Zhu Y, Antony JM et al (2007) Didanosine causes sensory neuropathy in an HIV/AIDS animal model impaired mitochondrial and neurotrophic factor gene expression. Brain 130(Pt 8) 2011-2023... 

Alcohol, amiodarone, didanosine, 1-asparaginase, piroxicam, stavudine, tamoxifen, tetracycline derivatives, valproic acid, and zidovudine... 

Didanosine, 1-asparaginase, lamivudine, metformin, pentamidine, statins, stavudine, sulindac, valproic acid, and zalcitabine... 

Azithromycin, fluoroquinolones, ketoconazole, isoniazid, penicillin, rifampin, and tetracycline ° Didanosine, indinavir, stavudine, and zidovudine ° Aledronate, risedronate, and levodopa... 

Efavirenz and (didanosine or abacavir or stavudine) and (lamivudine or emtricitabine)... 

Atazanavir or fosamprenavir or nelfinavir or saquinavir/ ritonavir, and zidovudine or stavudine or tenofovir or abacavir or didanosine, and lamivudine or emtricitabine... 

Triple NRTI therapy is recommended only when a first-line or alternative first-line therapy with either an NNRTI-based or Pi-based regimen cannot be used. Abacavir plus zidovudine plus lamivudine is the only regimen approved by the DHHS. The following triple nucleoside therapy combinations have shown poor or limited efficacy, and should be avoided abacavir plus tenofovir plus lamivudine (or emtricitabine), and didanosine plus tenofovir plus lamivudine (or emtricitabine). 

Therapies not recommended for initial treatment due to poor potency or significant toxicity include delavirdine, nevirapine in patients with moderate to high CD4+ T-cell counts, indinavir or saquinavir used without ritonavir ( unboosted ), ritonavir used without another protease inhibitor, and tenofovir plus didanosine with an NNRTI. 

Drugs that should not be combined due to overlapping toxi-cities include amprenavir oral solution plus ritonavir oral solution, atazanavir plus indinavir (due to enhanced hyperbilirubinemia), and any combination of didanosine, stavudine, and zalcitabine. Emtricitabine and lamivudine should not be combined because of their similar chemical structures, and antagonism can result when lamivudine is combined with zalcitabine, or stavudine is combined with zidovudine. 

Didanosine (ddl) 125-, 200-, 250-, Greater than 60 kg CrCI Take 30 minutes Pancreatitis Renal excretion... 

Generic didanosine Less than 60 kg 30-59 200 mg 125 mg 2 hours after neuropathy ... 

APV, amprenavir ATV, atazanavir CNS, central nervous system CVD, cardiovascular disease D/C, discontinue ddC, zalcitabine ddl, didanosine DEXA, dual-energy x-ray absorptiometry d4T, stavudine EFV, efavirenz HDL, high-density lipoprotein HIV, human immunodeficiency virus HTN, hypertension IDV, indinavir LDL, low-density lipoprotein LPV/r, lopinavir+ ritonavir MRI, magnetic resonance imaging NNRTI, nonnucleoside reverse transcriptase inhibitor NRTI, nucleoside reverse transcriptase inhibitor NVP, nevirapine PI, protease inhibitor RTV, ritonavir SQV, saquinavir TDF, tenofovir disoproxil fumarate TG, triglyceride TPV/r, tipranivir + ritonavir ZDV, zidovudine. 

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