Pancreatitis zidovudine

Didanosine (2 3 -dideoxyinosine or ddl) is a dideoxynucleoside purine analogue. Its mechanism of action is identical to that of zidovudine and resistance to didanosine is known to occur rapidly in patients who were already treated with zidovudine. Didanosine shows in vitro synergy with zidovudine while their toxicity profiles are different. Oral absorption is decreased by food and didanoside penetrates into the brain to a limited extend. Pancreatitis is the most serious complication. Other adverse reactions include peripheral neuropathy, diarrhoea and other gastrointestinal disturbances. 

Stavudine possesses several clinically significant interactions with other drugs. Although hydroxyurea enhances the antiviral activity of stavudine and didanosine, combination therapy that includes stavudine and didanosine, with or without hydroxyurea, increases the risk of pancreatitis. Combinations of stavudine and didanosine should not be given to pregnant women because of the increased risk of metabolic acidosis. Zidovudine inhibits the phosphorylation of stavudine thus, this combination should be avoided. 

The most common adverse effect produced by didanosine is diarrhea. Abdominal pain, nausea, vomiting, anorexia, and dose-related peripheral neuropathy may occur. Pancreatitis occurs rarely, as do hyperuricemia, bone marrow suppression, retinal depigmentation, and optical neuritis. Resistance to didanosine appears to result from mutations different from those responsible for zidovudine resistance. 

Lamivudine is the best-tolerated NRTI. Its most common adverse effects include headache, malaise, fatigue, and insomnia. Pancreatitis is rare. Gastrointestinal complaints are common with lamivudine-zidovudine therapy but are probably mainly due to the zidovudine component. Lamivudine resistance sometimes occurs early in treatment. Cross-resistance to zal-citabine, didanosine, and abacavir can occur simultaneously. Withdrawal of lamivudine in patients infected with both hepatitis B virus and HIV can cause a flare-up of hepatitis symptoms. 

Stavudine NRTI1 Immediate release 30-40 mg bid, depending on weight3 Peripheral neuropathy, lipodystrophy, hyperlipidemia, rapidly progressive ascending neuromuscular weakness (rare), pancreatitis Avoid concurrent zidovudine and neuropathic drugs (eg, ddl, zalcitabine, isoniazid)... 

Zalcitabine does not interact with zidovudine, and lamivudine inhibits its phosphorylation. It should not be administered with other drugs that cause neuropathy or pancreatitis including didanosine and stavudine. 

The use of stavudine in combination with isoniazid, vincristine, phenytoin and ethambutol may increase the risk of peripheral neuropathy and pancreatitis. It competes with zidovudine for phosphorylation and should not be used in combination. 

Recently, lamivudine [LAM ih vue deen] or (-)-2 -deoxy-3 -thiacyti-dine (3TC) has been approved for treatment of HIV in combination with zidovudine. This dideoxynucleoside terminates the synthesis of the proviral DNA chain and also inhibits reverse-transcriptase of both HIV and hepatitis B virus (HBV). However, it does not affect mitochondrial DNA synthesis or bone marrow precursor cells. Resistance to zidovudine develops more slowly with the combination. Lamivudine has good bioavailability on oral administration and depends on the kidney for excretion. Though generally well tolerated, pancreatitis develops in a significant number of pediatric... 

Lamivudine (3TC) is a reverse transcriptase inhibitor with a relatively long intracellular half-life (14 h plasma t 6 h). In combination with zidovudine, lamivudine appears to reduce viral load effectively and to be well tolerated, although bone marrow suppression may be produced. Rarely, pancreatitis may occur. Lamivudine has also been used for treatment of chronic hepatitis B infection, but resistant strains of virus have been reported. 

Lipemia retinalis and pancreatitis have been reported in a 39-year-old man with HIV infection associated with protease inhibitor therapy (13). He developed lipemia retinahs after switching to an antiretroviral regimen including ritonavir and saquinavir (together with zalci-tabine and delavirdine). He had previously been taking zidovudine, lamivudine, and indinavir. 

The most common adverse effect with stavudine is peripheral neuropathy which occurs in -12% of patients. Combining stavudine with zidovudine leads to increased risk and severity of peripheral neuropathy and potentially fatal pancreatitis, and these drugs shorrld not be used together under most circumstances. Lactic acidosis and hepatic steatosis also have been seen and are more common with stavudine than with zidovudine or abacavir. Of aU the nucleoside analogs, stavudine is most strongly linked to the HIV lipodystrophy syndrome, perhaps due to toxic effects on adipocytes. 

In the initial management of this patient, two nucleoside reverse transcriptase inhibitors (NRTIs) were administered. Hematologic suppression is a major adverse effect of zidovudine, while peripheral neuropathy and pancreatitis are important toxicities of didanosine. The gastrointestinal symptoms, together with the elevated amylase levels, were the reasons for discontinuance of didanosine and the substitution of another nucleoside reverse transcriptase inhibitor (lamivudine) in the drug regimen. See answer to question 3, above. 

Antiviral nucleoside inhibitor of HIV reverse transcriptase (NRTI). Used in combination regimens. Tox peripheral neuropathy, pancreatitis. Other NRTIs latnivudine (3TC), stavudine (d4T), zalcitabine (ddC), and the prototype, zidovudine (see below). 

Didanosine may cause pancreatitis or hepatic disease, and zidovudine may also rarely cause hepatic disease. It has been suggested that the hepatotoxicity of didanosine and paracetamol are augmented when they are given together. ... 

Tenofovir increases the levels of didanosine an increased risk of pancreatitis and peripheral neuropathy has been reported, and a high level of treatment failure. There is no pharmacokinetic interaction between tenofovir and abacavir, emtricitabine, lamivudine or stavudine. However, the combination of tenofovir, lamivudine and abacavir was unexpectedly associated with a high level of treatment failure. Triple-NRTI regimens invoiving tenofovir are not recommended, with the possibie exception of tenofovir, lamivudine and zidovudine. 

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