Didanosine - instructions for use, dose, side effects, contraindications

Didanosine in the cell is metabolized to the active form - dideoxyadenosine triphosphate (ddATP), structurally close to deoxyadenosine triphosphate - the nucleotide used by HIV reverse transcriptase for the synthesis of viral DNA de novo. Due to structural similarity, ddATF is built into the synthesized chain of viral DNA, it disrupts its further elongation, which leads to inhibition of the synthesis of new virions. Didanosine does not affect existing virions.

Pharmacokinetics:

In the acidic environment of the stomach didanosine is unstable, therefore its preparations must either contain buffer components that increase the pH value of gastric juice, which helps to prevent the destruction of didanosine and increase its absorption, or to have an acid-resistant protective coating.The drug is taken on an empty stomach, because taking during or after 5 minutes after a meal causes a decrease in C_max and AUС by 50%. Bioavailability is variable and depends on the age of the patient, the dosage form of the drug and the duration of its use. In adults, it is 20-40%, in infants (from 7 months), adolescents and boys (up to 19 years) varies in the range from 2 to 89%; the bioavailability of didanosine from chewing tablets is 20-25% higher than that of other dosage forms. In the blood, only 5% of didanosine is associated with proteins. C_max is achieved through 0.5-1.0 hours, varies from 0.6 to 2.9 μg / ml (an average of 1.6 μg / ml) in adults and depends on the dose in patients between the ages of 8 months to 18 years - from 0.8 to 1.7 μg / ml. T_1/2 didanosine is 0.8-2.7 hours (an average of 1.5 hours) in adults; 0,5-1,2 h (average 0,8 h) - in children and boys (from 8 months to 18 years). The volume of distribution varies between 0.7-1.0 l / kg in adults and 18.4-60.7 l / m² (an average of 35.6 l / m²) - in patients between the ages of 8 months to 18 years. The ratio of concentrations of CSF / plasma is 21%. In metabolism, in addition to ddATP, allantoin, hypoxanthine, xanthine, uric acid are secreted with urine. Excretion of Didanosine and products of its metabolism is carried out due to glomerular filtration and tubular secretion. The drug does not cumulate.

Indications:

Treatment of HIV-1 infection in adults and children (as part of combination antiretroviral therapy, as well as in ineffectiveness or intolerance to zidovudine).

ICD-10

I.B20-B24.B23.8 The disease caused by HIV, with manifestations of other specified states

Contraindications:

Hypersensitivity to didanosine and / or to any auxiliary substance of the drug, resistance, the period of breastfeeding, children under 3 years old with a body weight of up to 25 kg (for capsules: reception in the form of powder for the preparation of oral solution is recommended), hypertriglyceridemia, pancreatitis, in t.ch. (history of acute pancreatitis, sometimes fatal), hepatomegaly with steatosis, lactate acidosis, heart failure, cirrhosis or severe impairment of liver function, peripheral edema and / or stasis in the small circulation, toxicosis of pregnant women, phenylketonuria (chewing and disperse tablets contain phenylalanine).

Carefully:

Pancreatitis in history, violations of the liver and kidneys (creatinine clearance less than 60 ml / min: possible cumulation and development of toxic effects), peripheral polyneuropathy, retinal diseases.

Pregnancy and lactation:

When appointing didanosine, pregnant women need to control the level of lactic acid for the timely diagnosis of lactic acidosis.

Pre-clinical studies have shown that didanosine penetrates into the mother's milk of rats. The penetration of didanosine into the milk of women has not been investigated. However, there are recommendations for HIV-infected women to avoid breastfeeding because of the risk of infection of the child. Given these recommendations, patients receiving didanosine, breastfeeding should be prohibited.

Dosing and Administration:

Inside, on an empty stomach. The recommended daily dose is calculated based on the patient's body weight.

Adults every 12 hours: with a body weight of up to 60 kg - 125 mg, above 60 kg - 200 mg.

For children, the doctor calculates the dose according to the body surface area: newborns and children up to 8 months - 100 mg / m², older than 8 months:, - 120 mg / m² every 12 hours.

When taking Didanosine in the form of capsules, a single daily dose is: for patients weighing 20-25 kg - 200 mg, 25-60 kg - 250 mg, more than 60 kg - 400 mg. In renal failure, dose adjustment of didanosine depends on the level of creatinine clearance.

Side effects:

From the nervous system: Peripheral neuropathy, headache;

From the gastrointestinal tract: pancreatitis, hepatotoxicity, nausea, vomiting,

Metabolic disorders: lactate acidosis, hyperuricemia,

Other: depigmentation of the retina, rarely - myalgia, rhabdomyolysis, alopecia.

Overdose:

Symptoms: pancreatitis, peripheral neuropathy, diarrhea, hyperuricemia, liver dysfunction. There is no specific antidote for didanosine. Hemodialysis has some effectiveness, peritoneal dialysis is not effective.

Interaction:

Contraindicated the simultaneous use of didanosine with allopurinol (due to the risk of toxic reactions), ribavirin (the latter increases the concentration in the blood plasma of the active metabolite didanosine ddATP, which leads to the development of pancreatitis, peripheral neuropathy and lactate acidosis). Tenofovir increases the concentration of didanosine in the blood plasma.

Drugs that have a potential toxic effect on the pancreas (asparaginase, azathioprine, valproic acid and its derivatives, methyldopa, derivatives of sulfonamides, thiazide diuretics and furosemide, tetracyclines, estrogens) increase the risk of developing pancreatitis. The decrease in the pH of the stomach environment, which is necessary to prevent the destruction of didanosine, can lead to a decrease in the absorption of drugs that require an acidic medium for absorptiondapsone, ketoconazole, itraconazole and etc.). Magnesium and aluminum salts of the buffer system of didanosine form chelate compounds with fluoroquinolones, tetracyclines, which sharply reduces their absorption.

Fluoroquinolones, tetracyclines, dapsone, ketoconazole, itraconazole are prescribed 2 hours before or 2 hours after didanosine.

Special instructions:

During the treatment period, the development of infections caused by opportunistic microorganisms is possible.

Before the onset of active antiretroviral therapy, a complete clinical and laboratory examination of the patient is performed, incl. the level of viral load on the plasma and the number of CD4-T-lymphocytes are determined. During the treatment, a regular (every 3-6 months) assessment of the level of the replication process, the viral load on plasma and the level of CD4 cells is shown. In the presence of clinical symptoms of HIV infection, it is necessary to start therapy without taking into account the number of CD4 cells and the level of viral load on the plasma.

Instructions

Didanosine (Didanosinum)