Liver didanosine

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. 

When didanosine is used in combination with other agents with similar toxicities, the incidence of these toxicities may be higher than when didanosine is used alone. Thus, patients treated with didanosine in combination with stavudine, with or without hydroxyurea, may be at increased risk for pancreatitis and liver function P.1093... 

Walker, U.A. et al. (2004) Depletion of mitochondrial DNA in liver rmder antiretroviral therapy with didanosine, stavudine, or zalcitabine. Hepatology,... 

Peripheral neuropathy occurs in up to 50% of patients taking zalcitabine. Stomatitis, esophageal ulceration, hepatotoxicity, rash, and pancreatitis may occur. Zalcitabine should be used with caution in individuals with a history of pancreatitis, liver disease, or alcohol abuse. Dosage adjustment is necessary for individuals with renal impairment. Zalcitabine should not be used in combination with didanosine, lamivudine, or stavudine. 

In combination with other antiretroviral agents, stavudine has caused fatal lactic acidosis in some patients. It is also associated with motor weakness in which case it should be discontinued. Peripheral neuropathy is the most common toxicity associated with stavudine, which is more prevalent at high doses (4mg/kg per day). Neuropathy in these patients generally is associated with numbness, tingling or pain in feet or hands. Patients treated with the combination of stavudine and didanosine may also exhibit liver function abnormalities (hepatic steatosis) and pancreatitis. It may also be associated with the etiology of HIV lipodystrophy syndrome. 

Antiretroviral nucleoside analogues have been associated with hepatic steatosis and lactic acidosis. These compounds require phosphorylation to active triphosphate derivatives by cellular phosphokinases. The triphosphate nucleotide inhibits the growing proviral DNA chain, but it also inhibits host DNA polymerases, and this can result in compensatory glycolysis and lactic acidosis. Abnormal mitochondrial oxidation of free fatty acids causes the accumulation of neutral fat in liver cells, and this manifests as hepatomegaly with macrovesicular steatosis. Hepatic steatosis and lactic acidosis have been reported previously with zidovudine, didanosine, zalcita-bine, Combivir (zidovudine plus lamivudine), and lamivudine. Of 349 Australian patients studied for 18 months (516 patient-years) taking NRTIs only two had severe lactic acidosis (847). 

Brivet FG, Nion I, Megarbane B, Slama A, Brivet M, Rustin P, Munnich A. Fatal lactic acidosis and liver steatosis associated with didanosine and stavudine treatment a respiratory chain dysfunction J Hepatol 2000 32(2) 364-5. 

Delavirdine NNRTI 400 mg tid Separate dosing from didanosine or antacids by 1 hour. Rash, liver function abnormalities Teratogenic see footnote 2 for concurrent drug contraindication s... 

Indinavir PI 800 mg tid With water or other liquids, 1 hour before or 2 hours after a meal. Drink at least 48 oz of liquid daily. Separate dosing with didanosine by 1 hour. Nephrolithiasi s, nausea, liver function abnormalities Store in original container, which contains dessicant see footnote 2 for concurrent drug contraindication s... 

PARACETAMOL ANTIVIRALS Cases of hepatotoxicity have been reported when paracetamol was added to either didanosine or zidovudine Uncertain possible additive hepatotoxic effect Monitor liver function regularly during co-administration... 

Didanosine, DDI pancreatitis (major and dose-limiting)—peripheral neuropathy, hyperuricemia, liver dysfunction... 

Pancreatic dysfunction, heralded by large increases in serum amylase and lipase, is associated with the use of several reverse-transcriptase inhibitors (RTIs). Didanosine appears to be the worst offender, and pancreatitis is the most characteristic adverse effect of this particular NRTI. Conditions enhancing susceptibility to drug-induced pancreatic dysfunction include hypertriglyceridemia, hypercalcemia, and history of excessive ethanol use. Liver dysfunction including hepatitis may occur with the antitu-bercular drugs, isoniazid, and pyrazinamide. Cholestasis is associated with the estolate form of erythromycin. 

SLC28A2 CNT2 Purine nucleosides, uridine Didanosine, ribavirin Kidney, liver, heart, brain. Gray et al., 2004 Kong... 

Uncertain. It appears that methadone reduces the bioavailability of dida-nosine, and to a lesser extent, stavudine, possibly because it delays gastric emptying. Thus, the enteric-coated didanosine preparation appears not to be affected. Conversely, methadone apparently reduces the glucuroni-dation of the zidovudine by the liver, resulting in an increase in its serum levels. Methadone may also reduce renal clearance of zidovudine."... 

Established interactions. With the NRTTs that are actively excreted via the kidneys (e.g. lamivudine, stavudine, and zaicitabine), it is unlikely that dosage alterations are necessary unless the patient has renal impairment. However, when both drugs are needed, patients should be closely monitored for signs of toxicity. Moreover, the UK manufacturer of lamivudine recommends that the use of lamivudine with high-dose co-trimoxazole for the treatment of Pneumocystis pneumonia and toxoplasmosis should be avoided. Since renal clearance represents only 20 to 30% of the total clearance of zidovudine, the authors of two of these reports " suggest that this interaction is unlikely to be clinically important for zidovudine unless the glucuronidation by the liver is impaired by liver disease or other drugs. Didanosine also does not appear to interact to a clinically relevant extent. 

Limited and unconfirmed evidence su ests that paracetamol po ibly increases the bone marrow suppressant effects of zidovudine. Single case reports describe severe liver toxicity when patients were given paracetamol with either zidovudine or didanosine. 

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