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

Didanosine (2 ', 3'-dideoxyinosine or ddl) - a synthetic analogue of deoxyadenosine nucleoside, which inhibits HIV reverse transcriptase. It is proved that didanosine suppresses HIV replication both in cultured human cells and in cell lines in vitro.

After entering the cage didanosine under the action of cellular enzymes is converted into an active metabolite dideoxyadenosine-5'-triphosphate (ddATO). During the replication of the nucleic acid of the virus, the incorporation of the 2 ', 3'-dideoxynucleoside results in the interruption of the growth of the DNA strand and, therefore, stops the replication of the virus.Besides, ddATO suppresses the activity of HIV-1 reverse transcriptase due to competition with deoxyadenosine-5'-triphosphate (dATO) for binding to active regions of the enzyme. Linking to the active site of the enzyme, ddATO thereby inhibiting the growth of the strand of proviral DNA.

Pharmacokinetics:

Suction

After oral administration didanosine quickly absorbed. The maximum concentration of the drug in the blood plasma (FROMmOh) dose-dependent and when taken in the form of capsules with a dosage of up to 400 mg is achieved after 30 - 90 minutes. The bioavailability of didanosine is about 42%.

Area under the curve "concentration - time" (AUC) in the equilibrium state averages 2.60 mg * h / l for both adult and pediatric patients.

The drug should be taken at least 30 minutes before or 2 hours after eating. Taking the drug earlier than 2 hours after eating leads to a decrease in the values of Cmah and AUC by about 55%. When the drug is taken with food, the bioavailability of didanosine is reduced by about 50%.

Distribution

The apparent volume of distribution of didanosine averages about 300 liters for adults and 100 liters for children. Binding to plasma proteins - no more than 5%.

Metabolism

The metabolism of didanosine in the human body has not been studied.However, according to animal studies, it is assumed that the metabolism of didanosine in the human body occurs along the pathway of endogenous purine metabolism.

Excretion

After oral administration, the half-life (T1 / 2) of didanosine averages 1.6 hours, in urine approximately 20% of the dose is detected. The clearance of didanosine is approximately 175 l / h in adults and 90 l / h in children.

Kidney clearance is 50% of the total clearance (800 ml / min), which indicates active tubular secretion when dedating dedanosine through the kidneys, along with glomerular filtration.

Pharmacokinetics the separate patient groups

Patients with impaired renal function

After oral administration, the half-life of didanosine increases on average from 1.4 hours in patients with normal renal function to 4.1 hours in patients with severe renal dysfunction. In peritoneal dialysis fluid didanosine is not found, while during hemodialysis for 3-4 hours of the procedure, 0.6-7.4% of the administered dose of didanosine is excreted.

The absolute bioavailability of didanosine is not different in patients with severe renal dysfunction and in patients with normal renal function, however, the clearance of didanosine decreases in proportion to the creatinine clearance.

Patients with hepatic impairment

In patients with impaired hepatic function, the mean Cmah and AUC were slightly higher than in patients with normal liver function (by 13% and 19%, respectively). However, dose adjustment didanosine for this category of patients is not required, since the spread of individual indices in patients with impaired liver function is the same.

Children and teens

In children aged 1 to 17 years, the absorption of didanosine varied over a wide range. The values of Cmah and AUC increased in proportion to the dose. The absolute bioavailability of didanosine during oral administration of the drug was approximately 36% after the first dose and 47% in the equilibrium state.

T1/2 didanosine averages about 0.8 hours. The concentration of didanosine in urine was 18% of the administered dose after oral administration of the first dose of didanosine and 21% in the equilibrium state. Kidney clearance is about 243 ml / m²/ min, which corresponds to 46% of the total clearance of the drug from the body. As in adult patients, the active tubular secretion of didanosine was observed in children. With oral administration of the drug for 26 days, cumulation didanosine in children was not observed.

Indications:Treatment of HIV-1 infection (in combination with other antiretroviral drugs).

Contraindications:

- Hypersensitivity to didanosine.

- Simultaneous application with allopurinol, ribavirin.

- Breastfeeding period.

Carefully:

A drug Didanosine-native should be used with caution in patients with an increased risk of developing pancreatitis, with a history of pancreatitis, in patients with risk factors for lactic acidosis (obesity, long-term treatment with nucleotide analogues), with progressive HIV infection, in patients with a history of peripheral neuropathy, (increased risk of peripheral neuropathy), in elderly and elderly patients, in the treatment of patients with impaired renal function (corrective Ia dose) in patients with eye diseases (due to the risk of developing neuritis and retinal changes). With particular caution, the drug should be used in patients with impaired liver function due to the risk of developing severe hepatomegaly with steatosis.

Pregnancy and lactation:

Adequate and controlled clinical studies didanosine in pregnant women were not conducted. Apply the drug Didanosine-native during pregnancy should only be in the presence of strict indications and only if the potential benefit to the mother exceeds the possible risk to the fetus.

During treatment with the drug Didanosine-native should stop breastfeeding.

Dosing and Administration:

Inside, on an empty stomach, at least 30 minutes before or 2 hours after a meal, it is necessary in a mixture with antacids containing aluminum and magnesium hydroxides.

Adults

The recommended daily dose of the drug depends on the patient's body weight (see Table 1). The drug is taken 1 or 2 times a day. With a two-time use of the drug, the interval between doses should be 12 hours.

Dosage of the drug depending on body weight

Table 1

Body mass	Dosing regimen
≥ 60 kg	400 mg once a day or 200 mg 2 times a day
<60 kg	250 mg once a day or 125 mg 2 times a day

Children

For children, the dose of the drug is calculated according to the surface area of the body.

- Newborns and children under 8 months of age: daily dose - 100 mg / m² twice a day with an interval of 12 hours.

- Children older than 8 months: daily dose - 120 mg / m² twice a day with an interval of 12 hours.

Preparation of the drug solution in mixture with antacids

Before the first use of the drug, the doctor prepares the drug solution, teaches the patient (or the parents of the patient) the preparation of the solution, and also determines the exact dose for the individual patient, depending on the type of antacid, the weight of the patient, etc. A suitable syringe can be used to dispense the prepared drug solution.

Instructions for preparation of the drug solution in mixture with antacids

In Table 2 antacid preparations are divided into three groups (A, B and C), depending on the content of active substances in them. The left column of the table indicates the magnesium hydroxide content in mg per 5 ml of the antacid preparation, in the middle - the amount of aluminum hydroxide that should be contained in the preparation, the right column indicates the group to which the antacid drug belongs.

table 2

Antacid preparations

Magnesium hydroxide content, mg / 5 ml *	Aluminum hydroxide content, mg / 5 ml **	The group to which the antacid drug belongs
400	400 to 900	A
350	425 to 900	A
300	450 to 900	A

250	200 to 450	AT
200	213 to 450	AT
150	225 to 450	AT

125	100 to 225	FROM
100	107 to 225	FROM
75	113 to 225	FROM

* If the magnesium content of the hydroxide falls between the values indicated in the table, the preparation is possible only if the minimum aluminum hydroxide content compensates for the reduced magnesium hydroxide content.

** If the preparation contains aluminum oxide, the aluminum oxide is recalculated on aluminum hydroxide: 1 mg of oxide corresponds to 1.53 mg of aluminum hydroxide.

Before preparing the solution, you should determine to which group of antacid preparations the drug at your disposal belongs.

Examples

1. If the antacid preparation contains 325 mg of magnesium hydroxide and a sufficient amount of aluminum hydroxide, the preparation belongs to group A. The minimum aluminum hydroxide content is calculated as follows: a decrease in the magnesium hydroxide content by 1 mg requires an increase in the aluminum hydroxide content by at least 0.5 mg. In our example, reducing the magnesium hydroxide content by 75 mg (from 400 mg to 325 mg) requires a minimum increase in the aluminum hydroxide content by 37.5 mg (if rounded off - by 38 mg). Therefore, the content of aluminum hydroxide in the preparation should be at least 438 mg.

2. If the antacid preparation contains 175 mg of magnesium hydroxide and a sufficient amount of aluminum hydroxide, the preparation belongs to group B. The minimum aluminum hydroxide content is calculated as follows: a decrease in the magnesium hydroxide content by 1 mg requires an increase in the aluminum hydroxide content by at least 0.25 mg. In our example: a decrease in the magnesium hydroxide content by 75 mg (from 250 mg to 175 mg) requires a minimum increase in the aluminum hydroxide content by 18.75 mg (if rounded by 19 mg). Therefore, the content of aluminum hydroxide in the preparation should be at least 219 mg.

3. If the antacid preparation contains 85 mg of magnesium hydroxide and a sufficient amount of aluminum hydroxide, the preparation belongs to group C. The minimum aluminum hydroxide content is calculated as follows: a decrease in the magnesium hydroxide content by 1 mg requires an increase in the aluminum hydroxide content by at least 0.25 mg. In our example: reducing the magnesium hydroxide content by 40 mg (from 125 mg to 85 mg) requires a minimum increase in the aluminum hydroxide content by 10 mg. Therefore, the content of aluminum hydroxide in the preparation should be at least 110 mg.

Preparation of solution with preparations of group A

Add 100 ml of water to the vial to the 100 ml mark on the vial label. A solution with a didanosine concentration of 20 mg / ml is formed. Mix well. Add the antacid suspension to the label of 200 ml on the vial label. The concentration of didanosine in the suspension is 10 mg / ml. Mix well.

Preparation of solution with preparations of group B

Add 100 ml of the antacid suspension to the 100 ml bottle on the vial label. A suspension with a didanosine concentration of 20 mg / ml is formed. Mix well. Add the antacid suspension to the label of 200 ml on the vial label. The concentration of didanosine in the suspension is 10 mg / ml. Mix well.

Preparation of solution with preparations of group C

Add 100 ml of the antacid suspension to the 100 ml mark on the vial label. Mix well. Add the antacid suspension to the label of 200 ml on the vial label. Mix well. Transfer the resulting suspension to a glass or plastic bottle of a suitable size and add to it another 200 ml of antacid suspension. The concentration of didanosine in the resulting suspension is 5 mg / ml. It should be noted that the resulting suspension is enough for half a day less than with the use of Group A and B antacids.

The prepared mixture should be stored in a tightly closed bottle in the refrigerator (at a temperature of 2 to 8 ° C) for no more than 30 days.

Shake before use.

The unused medication after 30 days of storage is discarded.

Use in special patient groups

Adult patients with impaired renal function

It is recommended that the dose be reduced and / or the intervals between doses are increased due to the slowing down of the didanosine excretion rate (Table 3).

Table 3

Dosing regimen in patients with impaired renal function

Creatinine clearance (ml / min / 1.73 m²)	Dosing regimen
Body weight ≥60 kg
≥ 60 (usual dose)	400 mg once a day or 200 mg 2 times a day
30-59	200 mg once a day or 100 mg 2 times a day
10-29	150 mg once a day
< 10	100 mg once a day
Body weight <60 kg
≥ 60 (usual dose)	250 mg once a day or 125 mg 2 times a day
30-59	150 mg once a day or 75 mg twice daily
10-29	100 mg once a day
<10	75 mg once a day

Patients on peritoneal dialysis or hemodialysis should take a daily dose of the drug after dialysis, following recommendations for patients whose creatinine clearance is less than 10 ml / min. The need for an additional dose of the drug after the hemodialysis session is absent.

Children with impaired renal function

Excretion of didanosine from the body is carried out mainly with urine, so its clearance may vary in children with impaired renal function. Precise recommendations for correcting the dose of the drug in children are absent. Correction of the dosing regimen (dose reduction and / or increase in the interval between doses of the drug) should be carried out depending on the creatinine clearance, using a principle similar to that recommended for adult patients with impaired renal function.

Older and older patients

For elderly and elderly patients, the usual dosage regimen is recommended, as for adult patients. However, in view of the possible disruption of the kidney function in elderly patients, it is necessary to monitor their function and, accordingly, adjust the dose of the drug according to the recommendations for adult patients with impaired renal function.

Patients with hepatic impairment

For patients with impaired liver function, a dose reduction is not required. During treatment with the drug, it is necessary to monitor the activity of liver enzymes.With a clinically significant increase in the activity of liver enzymes, it is necessary to suspend treatment with the drug. With rapidly increasing aminotransferase activity, it may be necessary to stop or stop therapy with nucleoside analogues.

Dosing regimen didanosine with simultaneous use with tenofovir

For patients who simultaneously use didanosine and Tenofovir, a reduction in the daily dose of didanosine is required:

- for adults with a body weight of at least 60 kg and creatinine clearance of at least 60 ml / min, the dose of didanosine is 250 mg once a day on an empty stomach along with tenofovir (alternatively, if Tenofovir taken with food, then the drug Didanosine-native - on an empty stomach, 30 minutes before or 2 hours after eating);

- for adults weighing less than 60 kg and creatinine clearance of at least 60 ml / min, the dose of didanosine is 200 mg once a day on an empty stomach along with tenofovir (alternatively, if Tenofovir taken with food, then the drug Didanosine-native - on an empty stomach, 30 minutes before or 2 hours after a meal).

Side effects:

The undesirable reactions presented below are listed in accordance with the damage to organs and organ systems.

Disorders from the gastrointestinal tract: dyspepsia, nausea, vomiting, abdominal pain, diarrhea and increased gassing, pancreatitis, dry mouth, hypertrophy of the parotid salivary gland, sialadenitis.

Disorders from the liver and bile ducts: hepatitis, hepatic insufficiency, portal hypertension (not associated with cirrhosis of the liver), symptomatic hyperlactatemia (lactic acidosis), severe form of steatosis with hepatomegaly.

Disorders from the metabolism and nutrition: anorexia, redistribution / accumulation of adipose tissue (lipodystrophy / lipoatrophy), including obesity by the central type, an increase in the amount of fat in the dorso-corvus zone ("buffalo hump"), a decrease in the amount of fatty tissue of the limbs and face, breast enlargement, "Cushingoid face, diabetes.

Violations from the blood and lymphatic system: Anemia, granulocytopenia, leukopenia, thrombocytopenia.

Immune system disorders: anaphylactoid / allergic reactions.

Impaired nervous system: peripheral neuropathy, paresthesia, pain in the hands and feet, headache.

Disorders from the side of the organ of vision: dry eye, optic neuritis, depigmentation of the retina.

Disturbances from the musculoskeletal and connective tissue: myalgia (with or without increased creatine kinase activity), arthralgia, myopathy, rhabdomyolysis.

Disturbances from the skin and subcutaneous tissues: skin rash, itching, alopecia.

Laboratory and instrumental data: hypo- and hyperkalemia, hyperuricemia, increased concentrations of amylase and lipase, increased activity of "liver" transaminases and alkaline phosphatase, hyperbilirubinemia, hypo- and hyperglycemia.

General disorders and disorders at the site of administration: asthenia, fatigue, chills / fever.

Side effect with combined therapy

With the simultaneous use of didanosine and drugs with a similar toxicity profile (stavudine and / or hydroxycarbamide), undesirable phenomena such as pancreatitis, hepatotoxicity (including fatal), and severe peripheral neuropathy are more frequent than in the absence of such combination therapy.

Side effect the children

The side effects of didanosine in children and adult patients are similar.The development of pancreatitis in children was observed in 3% of cases with didanosine in doses not exceeding recommended, and in 13% - when treated with higher doses of the drug. Also, the children observed changes in the retina and optic neuritis, but the frequency of these side effects is not established.

Overdose:

Antidote for an overdose of didanosine.

With long-term use of didanosine in doses significantly exceeding the recommended (in 10 times), the following undesirable phenomena were observed: pancreatitis, peripheral neuropathy, hyperuricemia, hepatic dysfunction. Treatment is symptomatic, control over vital vital functions is necessary.

Didanosine is not removed from the body by peritoneal dialysis and is very poorly removed by hemodialysis. During hemodialysis sessions lasting 3-4 hours approximately 25-30% of the total concentration of didanosine circulating in the blood at the time of onset of hemodialysis is removed.

Interaction:

When didanosine is used in combination with other drugs with similar toxicity (for example, with stavudine), the risk of side effects increases significantly.

With the simultaneous use of didanosine with drugs that have toxic effects on the peripheral nervous system or pancreas, as well as in patients with a history of peripheral neuropathy, the risk of peripheral neuropathy or pancreatitis will increase significantly.

Allopurinol. The risk of developing pancreatitis caused by the combined use of didanosine and allopurinol increases in proportion to the increased dose of didanosine. In this regard, the combined use of allopurinol and didanosine is contraindicated.

Methadone. When didanosine is used in patients with opioid dependence on the background of long-term methadone treatment, the area under the concentration-time curve decreases (AUC) didanosine by 57%. With simultaneous use with methadone dose doanosine should be increased.

Tenofovir. With the combined use of didanosine and tenofovir, there is an increase in the concentration of didanosine in the blood plasma, so the dose of the drug must be adjusted (see the section "Method of administration and dose., Didanosine dosage regimen with simultaneous use with tenofovir."

Delavirdine or indinavir. Delavirdine or indinavir should be taken 1 hour before taking didanosine. When used simultaneously with didanosine, the value AUC delavirdine or indinavir is significantly increased.

Nelfinavir. Nelfinavir should be taken 1 hour after taking didanosine. There were no clinically significant changes in the pharmacokinetic parameters of nelfinavir when taken together with light food 1 hour after didanosine in the form of a powder.

Multiple application of didanosine concomitantly with drugs dapsone, nevirapine, rifabutin, foscarnet, ritonavir, stavudine and zidovudine, as well as a single dose of didanosine concomitantly with drugs loperamide, metoclopramide, ranitidine, sulfamethoxazole, trimethoprim does not lead to any drug interactions.

Ketoconazole or itraconazole, the absorption of which, when administered orally, is affected by the acidity of the gastric juice, should be taken 2 hours before taking didanosine.

Ganciclovir. When applying didanosine 2 hours before ganciclovir or at the same time the indicator AUC didanosine in the steady state increases to an average of 111%. Slight decrease AUC In a steady state (by 21%) ganciclovir was noted in cases when patients took didanosine 2 hours before taking ganciclovir. No changes in renal clearance were observed for either of these two drugs. There is no information to support the increase in didanosine myelosuppressive effects of ganciclovir.

Concentrations in blood plasma antibiotics of tetracycline and some fluoroquinolone antibiotics (for example, ciprofloxacin) decrease in the presence of antacids due to the formation of chelate complexes. In connection with this, the drug didanosine, dissolved in the suspension of antacids, should be taken at least 6 hours before or 2 hours after taking these drugs. Ribavirin can increase the level of intracellular didanosine triphosphates and potentially increase the risk of side effects. With the combined use of didanosine with ribavirin in combination with stavudine or without it, cases of hepatic insufficiency with a lethal outcome, as well as cases of pancreatitis, peripheral neuropathy and symptomatic hyperlactatemia / lactic acidosis occurred.In this regard, the combined use of didanosine and ribavirin is contraindicated.

Drugs that have a neurotoxic effect.

When joint use with didanosine drugs that have a neurotoxic effect, should be careful because of the increased risk of neuropathy.

Less than 5% didanosine is in a bound state with blood plasma proteins, which indicates a fairly low probability of drug interactions involving the mechanism of displacement from the binding sites.

Special instructions:

The relationship between HIV sensitivity to didanosine in vitro and no clinical response to didanosine therapy has been established. The results of determining the sensitivity in vitro vary over a wide range. Positive correlation is established in vitro between the results of measurements of viral activity (for example, determination by the method of polymerase chain reaction of HIV RNA) and clinical progression of the disease.

The administration of didanosine to children up to 3 years is recommended only in the form of a suspension.

With the simultaneous use of didanosine with drugs,having a toxic effect on the peripheral nervous system or pancreas, the risk of these toxic effects is significantly increased.

With simultaneous application pentamidine intravenously or drugs that increase the activity of didanosine (hydroxycarbamide, allopurinol), drug therapy Didanosine-native it is recommended to suspend.

Visual disturbances

It is necessary to periodically check the vision and note any visual impairment, such as altered perception of color or a vague vision of objects. Children should conduct a retina scan every 6 months or more if any changes in vision are detected.

The decision to change therapy can be made on the basis of a patient's examination and an assessment of the benefit / risk relationship from the use of the drug.

Diseases of the liver

Hepatotoxicity and hepatic insufficiency with a fatal outcome were observed in HIV-infected patients during combined antiretroviral therapy with hydroxycarbamide. Cases of hepatic dysfunction were fatal in such patients when a combination of hydroxycarbamide,didanosine and stavudine, and therefore the joint use of these drugs should be avoided.

The efficacy and safety of didanosine in patients with severe impairment of liver function in history has not been established. During combined antiretroviral therapy in such patients, including patients with active chronic hepatitis, the frequency of liver function abnormalities, including severe and potentially life-threatening, increases. Monitoring the status of such

patients should be conducted in accordance with standard practice. In the case of worsening of such patients, as well as increasing the activity of "hepatic" enzymes above the clinically significant level, ddI should be suspended or canceled.

Immunodeficiency Syndrome

In HIV-infected patients with severe immunodeficiency during combined antiretroviral therapy, there may be signs of an inflammatory response to asymptomatic or residual opportunistic infections. This syndrome occurs during the first few weeks or months after initiation of antiretroviral therapy.There may be signs of cytomegalovirus retinitis, generalized or focal mycobacterial infections and pneumonia caused by Pneumocystis jiroveci. If necessary, appropriate therapy is prescribed. There were cases of autoimmune diseases (for example, Graves' disease) that occurred with the restoration of immunity, but the timing of the onset of such diseases varied in different patients and could occur many months after initiation of therapy.

Pancreatitis

Pancreatitis is a severe toxic effect developing with didanosine. Pancreatitis of varying severity, often fatal, can develop in patients at different stages of treatment and does not depend on whether the didanosine in the form of monotherapy or in combination with other drugs, as well as regardless of the degree of immunosuppression. Pancreatitis is a dose-related complication. Patients receiving didanosine in combination with stavudine or hydroxycarbamide, are at a higher risk of developing this side effect. The risk of developing pancreatitis increases in elderly patients,in patients with pancreatitis in anamnesis, in patients with impaired renal function in the absence of appropriate dose adjustment, as well as in patients with progressive HIV infection.

In patients with risk factors for pancreatitis didanosine should be used with caution.

When symptoms of pancreatitis appear, treatment with didanosine should be stopped, and if the diagnosis is confirmed, discontinue. With a clinically significant excess of the level of biochemical markers, even with no symptoms of pancreatitis, treatment with didanosine should also be suspended.

Lactic acidosis / severe steatosis with hepatomegaly

Lactoacidosis / severe form of steatosis with hepatomegaly, including fatal cases, is noted with the use of nucleoside reverse transcriptase inhibitors both during monotherapy with these drugs and in combination with other antiretroviral drugs, including didanosine. Most often, the development of this undesirable phenomenon is observed in women. Obesity and long-term administration of nucleoside reverse transcriptase inhibitors may be a risk factor for this side effect.In pregnant women with the intake of didanosine in combination with stavudine or other antiretroviral drugs, the risk of developing lactic acidosis with a lethal outcome increases, so the use of a combination of these drugs in pregnant women is possible only with extreme caution. If clinically confirmed symptoms of hepatotoxicity or lactic acidosis (which may include hepatomegaly and steatosis, even if there are no obvious signs of an increase in the activity of "liver" transaminases), ddI treatment should be stopped. At a significant excess of the activity of "liver enzymes" and bilirubin (an increase of 3-4 degrees: 5 times higher than normal for "liver" transaminases and alkaline phosphatase, 2 times higher than the norm for lipase, 2.6 times higher than the norm for bilirubin) didanosine should be discontinued.

Portal hypertension, not associated with liver cirrhosis

There are cases of development of portal hypertension, not associated with cirrhosis of the liver, including cases leading to the need for liver transplantation, as well as to death. Unrelated to cirrhosis of the portal portal hypertension caused by didanosine was observed in patients with unconfirmed viral hepatitis.The first signs and symptoms of portal hypertension are manifested in the period from several months to several years after initiation of didanosine therapy. Common signs of development of portal hypertension include increased activity of liver enzymes, varicose veins of the esophagus, bloody vomiting, ascites and splenomegaly.

Patients receiving didanosine, during scheduled visits to the doctor should be regularly monitored for the presence of early signs of portal hypertension (eg, thrombocytopenia and splenomegaly). Such patients should be assigned appropriate laboratory tests, including a study of the activity of liver enzymes, bilirubin concentrations, albumin in the serum, an expanded blood test, an international normalized ratio (MPO), and ultrasonography.

When a patient develops symptoms of portal hypertension, not associated with cirrhosis of the liver, the use of didanosine should be discontinued.

Peripheral Neuropathy

Peripheral neuropathy is usually accompanied by a bilateral symmetrical sense of numbness of the limbs: tingling and pain in the feet and, less often, in the hands.In the early stages of the disease, these phenomena are less common. There is evidence that the course of peripheral neuropathy can be burdened by the combined use of antiretroviral drugs, including didanosine, stavudine and hydroxycarbamide. If there are symptoms of peripheral neuropathy, didanosine therapy should be stopped until they are eliminated. After eliminating these symptoms, the patient can again take a reduced dose of didanosine.

Redistribution / accumulation of fatty tissue (lipodystrophy / lipoatrophy)

In patients receiving antiretroviral therapy, there were cases of redistribution / accumulation of fatty tissue (lipodystrophy / lipoatrophy), which manifested itself as obese in the central type, an increase in the amount of fat in the dorso-corvus zone ("buffalo hump"), a decrease in the amount of fatty tissue of the limbs and face, an increase breasts, "cushingoid face." The mechanism and long-term consequences, as well as the causes of these phenomena are unknown.

Didanosine is rapidly destroyed in the acidic content of gastric juice. The powder solution should be taken only in admixture with antacids.

The absorption of didanosine, regardless of the dosage form in the presence of food, is reduced by an average of 50%. Powder should be taken 30 minutes before or 2 hours after eating.

Powder for solution for oral administration does not contain sodium salts, however, the sodium content should be taken into account when selecting and calculating the amount of antacids.

Powder for solution for oral administration does not contain sucrose, therefore, there are no restrictions for the use of the drug for patients with diabetes mellitus.

Effect on the ability to drive transp. cf. and fur:

There is no information on the ability of didanosine to affect the ability to drive vehicles and mechanisms. In case of development of such undesirable reactions as headache, paresthesia, pain in hands and feet, etc., one should refrain from controlling vehicles and mechanisms, as well as from engaging in other potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Powder for solution for oral administration.

Packaging:

To 2 g in bottles of colorless glass with a screw cap with a capacity of 250 ml.A label is attached to the vial.

One bottle together with the instruction for use is placed in a cardboard box.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

2 years. Do not use after the time specified on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-004553

Date of registration:23.11.2017

Expiration Date:23.11.2022

The owner of the registration certificate:NATIVA, LLC NATIVA, LLC Russia

Manufacturer: & nbsp

NATIVA, LLC Russia

Information update date: & nbsp18.12.2017

Illustrated instructions

Instructions

Didanosine-native (Didanosine-nativ)