Didanosine pancreatitis with

The most serious toxicities with didanosine are peripheral neuropathy and pancreatitis, both due to mitochondrial toxicity. It should be avoided in patients with a history of pancreatitis or neuropathy and should not be coadministered with other drugs that can cause neuropathy. Diarrhea is reported more frequently with didanosine than with other nucleoside analogs, perhaps related to the antacid in the oral preparations. The buffering agents also can impair the bioavailability of other coadministered drugs. 

Additive pancreatic toxicity has been described with zalcitabine and intravenous pentamidine, and is expected when didanosine or stavudine are given with other drugs that can cause pancreatitis. An isolated case describes pancreatitis with lamivudine and aza-thioprine. 

The manufacturers of didanosine have a similar recommendation and state that, if concurrent use is unavoidable, there should be close observation. Similarly, other authors recommend temporarily discontinuing didanosine in patients needing systemic pentamidine or sulfonamide-containing regimens. The UK manufacturer of stavudine recommends that patients receiving concurrent treatment with drugs known to cause pancreatitis should be carefully observed, and the US manufacturer specifically recommends caution with combined use of didanosine and stavudine, see NRTIs + NRTIs , p.800. Note that hydroxycarbamide (hydroxyurea) may increase the risk of pancreatitis with didanosine and stavudine, and the combination should probably be avoided, see NRTIs + Hydroxycarbamide , p.799. 

Blanchard JN, Wohlfeder M, Canas A King K, Lonergan JT. Pancreatitis with didanosine and tenofovir disoproxil fumarate. CUn IrfectDis (2003) 37, e57-e62. Correction ibid 995. 

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. 

Fatal and nonfatal pancreatitis has occurred during therapy with didanosine alone or in combination regimens in treatment-naive and treatment-experienced patients, regardless of degree of immunosuppression. Suspend didanosine in patients with suspected pancreatitis, and discontinue therapy in patients with confirmed pancreatitis (see Warnings). 

Coadministration of didanosine buffered tablets, buffered powder for oral solution, and pediatric powder for oral solution with drugs that are known to cause peripheral neuropathy or pancreatitis or patients who have a history of neuropathy or neurotoxic drug therapy may have increased risk of toxicities. Closely observe patients who receive these drugs or have a history of neuropathy or neurotoxic drug therapy. 

A serious toxicity of didanosine is pancreatitis, which may be fatal (see Warnings). Other important toxicities include lactic acidosis/severe hepatomegaly with steatosis retinal changes and optic neuritis and peripheral neuropathy (see Warnings and Precautions). 

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... 

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. 

Didanosine should be used with great caution in individuals who have a history of pancreatitis. Didanosine tablets contain phenylalanine and should not be taken by phenylketonurics. Didanosine should be used cautiously in patients with gout, peripheral neuropathy, and advanced AIDS. 

Buffering agents that are compounded with didanosine to counteract its degradation by gastric acid may interfere with the absorption of other drugs that require acidity (e.g., indinavir, delavirdine, ketoconazole, fluoroquinolones, tetracyclines, dapsone). An enteric-coated formulation Videx EC) that dissolves in the basic pH of the small intestine is not susceptible to these interactions. Ganciclovir and valganciclovir can increase blood levels of didanosine. The use of zalcitabine with didanosine is not recommended because that combination carries an additive risk of peripheral neuropathy. The combination of didanosine with stavudine increases the risk of pancreatitis, hepatotoxicity, and peripheral neuropa-... 

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. 

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. 

Didanosine (ddl) NRTT1 Tablets, 400 mg daily,3 adjusted for weight. 30 min before or 2 h after meals. Separate dosing from fluoroquinolones and tetracyclines by 2 h Peripheral neuropathy, pancreatitis, diarrhea, nausea, hyperuricemia. Possible increase in myocardial infarction Avoid concurrent neuropathic drugs (eg, stavudine, zalcitabine, isoniazid), ribavirin, and alcohol. Do not administer with tenofovir... 

Allopurinol increases didanosine plasma concentrations and their coadministration is not recommended. Ganciclovir, tenofovir and disoproxil also increase didanosine plasma concentrations, and dose reduction is recommended. Conversely, methadone decreases didanosine plasma concentrations, and appropriate doses for the combination have not been established. Didanosine should not be administered with drugs that cause pancreatic or neurotoxicity. Ribavirin increases its risk of toxicity and should not be coadministered. 

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. 

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. 

NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS RIBAVIRIN 1. t side-effects, risk of lactic acidosis, peripheral neuropathy, pancreatitis, hepatic decompensation, mitochondrial toxicity and anaemia with didanosine and stavudine 2.1 efficacy of lamivudine 1. Additive side-effects t intracellular activation of didanosine and stavudine 2. J intracellular activation of lamivudine 1. Not recommended. Use with extreme caution monitor lactate, LFTs and amylase closely. Stop co-administration if peripheral neuropathy occurs. Stavudine and didanosine carry a higher risk 2. Monitor HIV RNA levels if they T, review treatment combination... 

DIDANOSINE STAVUDINE t adverse effects, including pancreatitis and neuropathy Additive effect Monitor more closely, especially for pancreatitis and peripheral neuropathy. Relative risk of neuropathy stavudine alone 1.39 compared with didanosine combined use 3.5. Sometimes fatal lactic acidosis is reported in pregnancy... 

DIDANOSINE TENOFOVIR Possibly t adverse effects, including pancreatitis, lactic acidosis and neuropathy t plasma levels of didanosine additive effects Co-administration not recommended. Monitor closely for antiviral efficacy and side-effects (pancreatitis, neuropathy, lactic acidosis, renal failure). Not recommended in patients with a high viral load and low CD4 count (enteric-coated and buffered tablets), i dose of didanosine to 250 mg has been tried. Do not use in combination as triple therapy with lamivudine as there is a high level of treatment failure... 

Adverse effects are most commonly manifest as acute pancreatitis. The strongest association is with alcohol abuse. High plasma calcium, including that caused by hypervitaminosis D, and parenteral nutrition also increase the risk. Corticosteroids, didanosine, azathoipurine, diuretics (including thiazides and frusemide), sodium valproate, mesalazine and paracetamol (in overdose) have also been causally related. 

Didanosine/Videx EC (ddl) 125, 200, 250, or 400 mg enteric-coated capsules Body weight >60 kg 400 mg once daily <60kg 250mg once daily Peripheral neuropathy, pancreatitis, lactic acidosis with hepatic steatosis 0.11... 

Pancreatitis has been observed in patients treated with didanosine, lamivudine, stavudine, and zalcitabine (29), but its incidence is also increased in drug-naive patients with advanced HIV infection (30). 

Two HIV-1-positive women, both of whom had taken regimens containing stavudine and didanosine for at least 2 years, presented in the third trimester of pregnancy, one with acute lactic acidosis and one with acute pancreatitis and lactic acidosis (32). In the first case both mother and baby died. It is not known whether pregnancy is a risk factor for NRTI-induced lactic acidosis, perhaps in combination with riboflavin deficiency or a metabolic defect in the fetus, or whether NRTIs independently cause lactic acidosis through mitochondrial toxicity. 

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