Registration number:
P N013843/01-070508Tradename : Videx®
International nonproprietary name:
didanosineChemical name: 2",3"-dideoxyinosine
Dosage form:
chewable tablets or for the preparation of suspension for oral administration; capsules, powder for the preparation of oral solution for children.Compound:
Each tablet contains active substance – didanosine 100 mg.
Excipients: calcium carbonate, magnesium hydroxide, aspartame, sorbitol, microcrystalline cellulose, crospovidone, tangerine orange flavor, magnesium stearate.
Capsules
Each capsule contains active substance– didanosine 125 mg, 200 mg, 250 mg or 400 mg.
Excipients:
Compound:
granules: sodium carboxymethyl starch, sodium carmellose.Compound:
suspensions for the shell of granules: methacrylic acid and ethacrylate copolymer, diethyl phthalate, water, talc.Compound:
capsule shell: sodium lauryl sulfate, titanium dioxide, colloidal silicon dioxide, gelatin.Compound:
ink: 125 mg capsules – shellac, propylene glycol, potassium hydroxide, titanium dioxide, red iron oxide dye and yellow iron oxide dye;200 mg capsules – shellac, propylene glycol, indigo carmine, titanium dioxide, yellow iron oxide dye; capsules 250 mg – shellac, propylene glycol, indigo carmine; capsules 400 mg – shellac, propylene glycol, simethicone, red iron oxide dye, aqueous ammonia.
Each bottle contains the active substance – didanosine 2 g. There are no excipients.
Description
Chewable tablets or for oral suspension
White or off-white to light yellow, round, flat, beveled-edge tablets marked “100” on one side of the tablet and “VIDEX” on the other. Slight marbling of the surface of the tablets is allowed.
Capsules
Hard gelatin capsules, consisting of two parts, opaque white. Capsule contents: white or almost white granules, enteric-coated.
125 mg capsules: Size No. 3. The inscriptions “BMS”, “125 mg” and “6671” are printed in yellow-brown color.
200 mg capsules: Size No. 2. The inscriptions “BMS”, “200 mg” and “6672” are applied green.
250 mg capsules: Size No. 1. The inscriptions “BMS”, “250 mg” and “6673” are printed in blue.
Capsules 400 mg: Size No. 0. The inscriptions “BMS”, “400 mg” and “6674” are printed in red.
Powder for the preparation of oral solution for children
White or almost white powder.
Pharmacotherapeutic group:
Antiviral (HIV) agent.Pharmacological properties:
PharmacodynamicsDidanosine (2",3"-dideoxyinosine or ddl), a synthetic analogue of the nucleoside dioxyadenosine, inhibits HIV replication in cultured human cells and in cell lines in vitro.
After entering the cell, didanosine is converted by cellular enzymes to the active metabolite dideoxyadenosine triphosphate (ddATO). During viral nucleic acid replication, the inclusion of a 2",3"-dideoxynucleoside prevents chain growth and thereby inhibits viral replication.
In addition, ddATO inhibits HIV reverse transcriptase activity by competing with dihydroxyadenosine 5-triphosphate (dATO) to bind to the active sites of the enzyme, preventing the synthesis of proviral DNA.
Pharmacokinetics
Absorption
The area under the concentration-time curve (AUC) of didanosine in the blood plasma and the maximum concentration in the blood plasma (Cmax) when taking capsules and tablets are equal. Compared to tablets, the rate of absorption of the drug from capsules is lower; the Cmax value of capsules is 60% of the Cmax value of tablets. The time to reach Cmax is approximately 2 hours for Videx capsules and 0.67 hours for Videx tablets.
Tablets and powder should be taken at least 30 minutes before or 2 hours after meals. If the drug is taken earlier than 2 hours after a meal, Cmax and AUC values decrease by approximately 55%. When taking the drug with food, the bioavailability of didanosine is reduced by approximately 50%.
Capsules should be taken on an empty stomach, at least 1.5 hours before or 2 hours after meals. When using capsules with fatty foods Cmax and AUC values decrease by 46% and 19%), respectively.
Metabolism
The metabolism of didanosine in humans has not been studied. Based on animal studies, it is assumed that in humans it occurs through the metabolism of endogenous purines.
Removal
After oral administration, the half-life of the drug averages 1.6 hours, and approximately 20% of the dose taken is found in the urine.
Renal clearance accounts for 50% of the total clearance (800 ml/min), indicating active tubular secretion during the excretion of didanosine through the kidneys along with glomerular filtration.
Pharmacokinetics in renal impairment
After oral administration, the half-life increases from an average of 1.4 hours in patients with normal function kidneys up to 4.1 hours in patients with severe renal impairment. Didanosine is not detected in peritoneal dialysis fluid, while during hemodialysis, after 3-4 hours, didanosine concentrations are 0.6-7.4% of the administered dose. Absolute bioavailability does not change in patients with severe renal impairment compared to patients with normal renal function, however, didanosine clearance decreases in proportion to creatinine clearance.
Pharmacokinetics in liver dysfunction
The metabolism of didanosine depends on the degree of liver dysfunction.
Pharmacokinetics in children and adolescents.
During pharmacokinetic studies in children aged 1 to 17 years, the absorption of didanosine varied over a wide range. Despite this, Cmax and AUC values increased proportionally to the dose. The absolute oral bioavailability of didanosine was approximately 36% after the first dose and 47% at steady state.
The half-life averages about 0.8 hours. After the first oral dose, urinary didanosine concentrations were 18% and 21% at steady state. Renal clearance was approximately 243 ml/m /min, which accounted for 46% of the total clearance from the body. As in adults, active tubular secretion was observed in children. When the drug is taken orally for 26 days, didanosine accumulation is not observed in children.
Indications for use:
Treatment HIV infection(in combination with other antiretroviral drugs).Contraindications:
Hypersensitivity to didanosine and/or any of the excipients of the drug, phenylketonuria, lactation period.Capsules are contraindicated for children under 3 years of age (contraindication due to method of administration).
Carefully
The drug should be used with caution in patients with increased risk development of pancreatitis, with a history of pancreatitis, with progressive HIV infection, in elderly patients, when treating patients with impaired renal function with uncorrected doses of the drug. It should be used with particular caution in patients with impaired liver function.
Pregnancy and lactation
Adequate and controlled studies have not been conducted in pregnant women. Videx should be used during pregnancy only if strictly indicated and only in cases where the potential benefit to the mother outweighs possible risk for the fetus. During treatment with the drug breast-feeding should be stopped.
Directions for use and dosage:
Inside.Capsules should be swallowed whole, without chewing, on an empty stomach.
Chewable tablets or for the preparation of a suspension for oral administration and powder for the preparation of an oral solution. Recommended daily dose depends on body weight. Tablets or powder are taken 1 or 2 times a day (see table). When taking the drug twice a day, the interval between doses should be 12 hours.
Pick up required dose can be a combination of tablets different dosages, avoiding possible overdose of antacids or phenylalanine contained in tablets. Each dose of the drug should consist of at least 2 tablets, but no more than 4 tablets, not exceeding the recommended dose. Children under 1 year of age should receive one tablet per dose that provides sufficient antacid for this period. age group.
Taking tablets for children under 3 years of age is recommended only in the form of a suspension. The tablets are taken at least 30 minutes before or 2 hours after meals. The tablet should be thoroughly chewed or dissolved in at least 30 ml of water, stirring thoroughly until a homogeneous suspension is obtained. For children, the recommended dose of 1 tablet is dissolved in 15 ml of water. To adjust the taste, you can add about 30 ml (for adults) or 15 ml (for children) apple juice no pulp.
After preparation, the resulting suspension should be mixed and drunk entirely. The resulting suspension is stable for 1 hour when stored at room temperature (17-23°C).
For newborns and children up to 8 months, the daily dose is calculated depending on the body surface area and is 100 mg/m2 day twice a day with an interval of 12 hours.
For children over 8 months, the daily dose is 120 mg/m2 twice a day with an interval of 12 hours.
Powder for oral solution for children should be taken at least 30 minutes before or 2 hours after meals only in a mixture with antacids containing aluminum and magnesium hydroxides (oxides). We propose to divide antacid drugs into three groups (A, B and C), depending on the content of these active ingredients. The first column indicates the content of magnesium hydroxide (oxide) in mg per 5 ml of the drug, the second - the amount of aluminum hydroxide that should be contained in the drug, the third - the group to which the drug belongs.
| Hydroxide content magnesium*, mg/5 ml. | Hydroxide content aluminum, mg/5 ml (**). | Group to which it belongs antacid drug. |
| 400 | 400 to 900 | A |
| 350 | 425 to 900 | A |
| 300 | 450 to 900 | A |
| 250 | 200 to 450 | IN |
| 200 | 213 to 450 | IN |
| 150 | 225 to 450 | IN |
| 125 | 100 to 225 | C |
| 100 | 107 to 225 | C |
| 75 | 113 to 225 | C |
Before preparing the solution, determine which group of antacid drugs yours belongs to.
* If the magnesium hydroxide content falls between the specified values, the drug can be used in cases where the minimum aluminum hydroxide content compensates for the reduced magnesium hydroxide content.
– For example, the drug contains 325 mg of magnesium hydroxide and a sufficient amount of aluminum hydroxide, then the drug belongs to group A. The minimum content of aluminum hydroxide is calculated as follows: a decrease in the content of magnesium hydroxide by 1 mg requires an increase in the content of aluminum hydroxide by at least 0.5 mg. In our example: a decrease in magnesium hydroxide content by 75 mg (from 400 mg to 325 mg) requires a minimum increase in aluminum hydroxide content of 37.5 mg (rounded up to 38 mg). Therefore, the content of aluminum hydroxide in the preparation must be at least 438 mg.
– For example, the drug contains 175 mg of magnesium hydroxide and a sufficient amount of aluminum hydroxide, the drug belongs to group B. The minimum content of aluminum hydroxide is calculated as follows: a decrease in the content of magnesium hydroxide by 1 mg requires an increase in the content of aluminum hydroxide by at least 0.25 mg. In our example: a decrease in magnesium hydroxide content by 75 mg (from 250 mg to 175 mg) requires a minimum increase in aluminum hydroxide content of 18.75 mg (rounded up to 19 mg). Therefore, the content of aluminum hydroxide in the preparation must be at least 219 mg.
– For example, if a drug contains 85 mg of magnesium hydroxide and a sufficient amount of aluminum hydroxide, the drug belongs to group C. The minimum aluminum hydroxide content is calculated as follows: a decrease in magnesium hydroxide content by 1 mg requires an increase in aluminum hydroxide content by at least 0.25 mg. In our example: a 40 mg decrease in magnesium hydroxide (from 125 mg to 85 mg) requires a minimum increase of 10 mg in aluminum hydroxide. Therefore, the content of aluminum hydroxide in the preparation should be at least 110 mg.
** If the drug contains aluminum oxide, its content is converted to aluminum hydroxide: 1 mg of oxide corresponds to 1.53 mg of aluminum hydroxide.
Preparation of a solution with drugs of group A.
Add 100 ml of water to the 100 ml mark on the bottle label to obtain a solution with a didanosine concentration of 20 mg/ml. Mix well. Add antacid suspension to the 200 ml mark on the bottle label. The concentration of didanosine in the suspension is 10 mg/ml. Mix well.
Preparation of a solution with drugs of group B.
Add 100 ml of antacid suspension to the 100 ml mark on the bottle label to obtain a suspension with a didanosine concentration of 20 mg/ml. Mix well. Add antacid suspension to the 200 ml mark on the bottle label. The concentration of didanosine in the suspension is 10 mg/ml. Mix well.
Preparation of a solution with drugs of group C.
Add 100 ml of antacid suspension to the 100 ml mark on the bottle label. Mix well. Add antacid suspension to the 200 ml mark on the bottle label. Mix well. Transfer the resulting suspension into a glass or plastic bottle of a suitable size and add another 200 ml of antacid suspension to it. The concentration of didanosine in the resulting suspension is 5 mg/ml; the resulting suspension will last half the days less than when using antacids of groups A and B.
Store the prepared mixture in a tightly closed bottle in the refrigerator (2 to 8°C) for no more than 30 days. Shake before use. Unused drug after 30 days of storage is thrown away.
| Creatinine clearance (ml/min/1.73 m²) | Capsules | Tablets and powder for preparing a solution for oral administration for children |
|---|---|---|
| Body weight > 60 kg | ||
| ≥60 (usual dose) | 400 mg 1 time per day | 400 mg once daily or 200 mg twice daily |
| 30-59 | 200 mg 1 time per day | 200 mg once daily or 100 mg twice daily |
| 10-29 | 125 mg 1 time per day | 150 mg 1 time per day |
| <10 | 125 mg 1 time per day | 100 mg 1 time per day |
| Body mass< 60 кг | ||
| ≥60 (usual dose) | 250 mg 1 time per day | 250 mg 1 time per day or 125 mg twice daily |
| 30-59 | 125 mg 1 time per day | 150 mg 1 time per day or 75 mg twice daily |
| 10-29 | 125 mg 1 time per day | 100 mg 1 time per day |
| <10 | - b | 75 mg 1 time per day |
b Patients with weight Patients on dialysis should take a daily dose of the drug after dialysis. There is no need for an additional dose of the drug.
Children with impaired renal function. There are no exact recommendations for adjusting the dose of the drug in children. It is possible to reduce the dose and/or increase the interval between doses of the drug.
For elderly patients Careful dose selection is necessary due to the possible decrease in renal function. It is necessary to monitor renal function and adjust the dose of the drug accordingly.
For patients with impaired liver function a dose reduction may be required. There are no exact recommendations for changing the dose of the drug in case of impaired liver function. During treatment with the drug, it is necessary to examine the level of liver enzymes. If the level of liver enzymes is clinically significant, it is necessary to suspend treatment with the drug. If aminotransferase levels rise rapidly, it may be necessary to discontinue or suspend treatment with any nucleoside analogues.
Side effect:
Pancreatitis is a severe toxic effect of the drug. Pancreatitis of varying severity, often fatal, can develop in a patient at different stages of treatment and does not depend on whether the drug is used as monotherapy or in combination with other drugs, or on the degree of immunosuppression. Pancreatitis is a dose-dependent complication. When using a suspension, it is necessary to take into account data on an increase in the level of pancreatitis markers to a clinically significant level, even in the absence of symptoms.Lactic acidosis/Severe steatosis with hepatomegaly, including fatal outcomes, are observed when using nucleoside analogs in monotherapy or in combination with other antiviral drugs, including didanosine. This side effect was mainly observed in women. Obesity and long-term use of nucleosides may be risk factors for this side effect. Treatment with the drug should be discontinued if patients develop clinical or laboratory signs of lactic acidosis or hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of obvious signs of increased transaminase activity).
Peripheral neuropathy usually accompanied by a bilateral symmetrical feeling of numbness of the extremities: tingling and pain in the soles of the feet and, less so, in the hands. In the early stages of the disease, these phenomena are less frequent. There is information that the course of peripheral neuropathy can be aggravated when taking antiretroviral drugs, including didanosine, and hydroxycarbamide together.
From the digestive system: anorexia, nausea, vomiting, abdominal pain, diarrhea and increased gas formation, hepatitis, pancreatitis, hypertrophy of the parotid salivary gland, lipodystrophy, lipoatrophy.
From the nervous system: paresthesia, pain in the hands and feet, headache.
From the senses: dry mouth, dry eyes.
From the musculoskeletal system: myalgia, arthralgia and myopathy, sialadenitis.
From the hematopoietic organs: anemia, granulocytopenia, leukopenia, thrombocytopenia.
From the organs of vision: Optic neuritis, retinal depigmentation.
Laboratory indicators: hypo- and hyperkalemia, hyperurecemia, increased concentrations of amylase and lipase, increased activity of “liver” transaminases and alkaline phosphatase, hyperbilirubinemia, hypo- and hyperglycemia.
Others: alopecia, anaphylactoid/allergic reactions, asthenia, chills, itching, rhabdomyolysis, skin rash.
Children. Side effects of the drug in children and adult patients are similar. The development of pancreatitis in children is observed in 3% of cases when taken in doses not exceeding the recommended ones and in 13% when treated with increased doses of the drug. Visual impairment is observed in children in rare cases and is characterized by changes in the retina and optic neuritis.
Overdose:
There is no antidote for didanosine overdose.The main manifestations of an overdose of the drug: pancreatitis, peripheral neuropathy, hyperuricemia, liver dysfunction.
Didanosine is not removed from the body by peritoneal dialysis and very little by hemodialysis. During hemodilysis sessions lasting 3-4 hours, approximately 25-30% of didanosine is removed from the total concentration of didanosine circulating in the blood at the start of hemodialysis.
Interaction with other medicinal products and other forms of interaction
When using Videx in combination with other drugs with similar toxicity (for example, stavudine), the risk of developing the described side effects increases significantly.
Allopurinol is not recommended for use simultaneously with Videx. The risk of developing pancreatitis increases in proportion to the increase in the concentration of the drug Videx.
Methadone. When using Videx tablets or powder in patients with opioid dependence during long-term treatment with methadone, a decrease in the AUC value of didanosine by 57% was observed. When using drugs simultaneously, the dose of Videx should be increased.
Tenofovir. When used together, a decrease in Videx levels is observed, so the dose of the drug must be adjusted.
Delavirdine or indinavir should be taken 1 hour before taking Videx tablets or powder. In the presence of the drug Videx, the AUC value of delavirdine or indinavir increases significantly. No drug interactions have been identified between indinavir and Videx capsules.
In special studies of multiple doses of the drug simultaneously with the drugs nevirapine, rifabutin, foscarnet, ritonavir, stavudine and zidovudine and a single dose of the drug simultaneously with the drugs loperamide, metoclopramide, ranitidine, sulfamethoxazole, trimethoprim, no drug interactions were identified.
Ketoconazole or itraconazole, whose absorption when taken orally is affected by the acidity of gastric juice, should be taken 2 hours before taking Videx tablets or powder. Videx capsules do not contain antacids, so there is no risk of interaction between these drugs.
When taking Videx (tablets or powder) 2 hours before or simultaneously with ganciclovir, the steady-state AUC of didanosine increases to an average of 111%. A slight decrease in the steady-state AUC (by 21%) of ganciclovir was observed when patients took Videx 2 hours before ganciclovir. No changes in renal clearance were observed for either of these two drugs. It is unknown whether these changes are related to changes in the safety of Videx or the effectiveness of ganciclovir. There is no evidence that didanosine enhances the myelosuppressive effects of ganciclovir.
The concentrations of tetracycline antibiotics and some fluoroquinolone antibiotics (for example, ciprofloxacin) in the blood plasma are reduced in the presence of antacids, as they form chelate compounds.
Therefore, Videx tablets containing antacids, or powder dissolved in an antacid suspension, should be taken at least 6 hours before or 2 hours after taking ciprofloxacin.
Videx capsules do not contain antacids, so there is no risk of interaction with tetracycline and fluoroquinolone antibiotics.
Ribavirin may increase intracellular levels of didanosine triphosphates and potentially increase the risk of side effects. Cases of fatal liver failure, as well as cases of pancreatitis, peripheral neuropathy and systemic hyperlactatemia/lactic acidosis have been reported when didanosine was co-administered with ribavirin, with or without stavudine. Concomitant use of didanosine and ribavirin should be avoided unless the potential benefits outweigh the risk of side effects.
Less than 5% of didanosine is bound to plasma proteins, indicating a low likelihood of drug interactions involving displacement from binding sites.
special instructions
The relationship between HIV sensitivity to didanosine in vitro and clinical response to treatment has not been established. In vitro susceptibility results vary widely. A positive in vivo correlation has been established between viral activity measurements (eg, RNA polymerase chain reaction assays) and clinical disease progression.The administration of chewable tablets or for the preparation of a suspension for oral administration to children under 3 years of age is recommended only in the form of a suspension.
When Videx is used concomitantly with drugs with known toxic effects on the peripheral nervous system or pancreas, the risk of these toxic effects increases significantly.
When simultaneously prescribing pentamidine intravenously or drugs that increase the activity of didanosine (hydroxycarbamide, allopurinol), it is recommended to use Videx in the form of a suspension.
You should have your vision checked periodically and note any visual disturbances, such as altered color perception or blurry vision of objects.
Children should have their retina examined every 6 months or when any vision changes occur.
Didanosine is quickly destroyed in the acidic contents of gastric juice. Therefore, to reduce acidity, the tablets contain antacids. The powder solution should be taken only in a mixture with antacids. The capsules contain didanosine in the form of granules coated with an enteric coating, as a result of which the absorption of the drug in the intestine increases.
In HIV-infected patients with severe immunodeficiency, signs of an inflammatory response to asymptomatic or residual opportunistic infections may occur during combination antiretroviral therapy. This syndrome was observed during the first few weeks or months after starting antiretroviral therapy. Signs of cytomegalovirus retinitis, generalized or focal mycobacterial infections and pneumonia caused by Pneumocystis jiroveci may occur.
If symptoms of pancreatitis appear, treatment with the drug should be suspended, and if the diagnosis is confirmed, treatment should be stopped. If there is a clinically significant increase in the level of biochemical parameters, even in the absence of symptoms of pancreatitis, the drug should be prescribed in the form of a suspension.
If clinically confirmed symptoms of hepatotoxicity or lactic acidosis occur (even if liver transaminases are slightly above the upper limit), treatment with the drug should be suspended. If these indicators are significantly exceeded, treatment should be stopped.
The absorption of didanosine, regardless of dosage form, in the presence of food is reduced by an average of 50%. Tablets and powder should be taken 30 minutes before or 2 hours after meals, capsules should be taken on an empty stomach.
When prescribing the drug to patients with impaired renal function, it should be taken into account that each tablet contains 8.6 mEq of magnesium.
When prescribing the drug to patients with phenylketonuria, it should be taken into account that: each 100 mg tablet contains 36.5 mg of phenylalanine aspartame.
Capsules and powder for oral solution for children do not contain phenylalanine.
When prescribing the drug to patients on a diet with limited salt intake, it should be taken into account that 100 mg of capsule contents contains at least 0.424 mg of sodium.
The tablets do not contain sodium salts.
The powder for preparing an oral solution for children does not contain sodium salts. However, sodium content should be taken into account when selecting and calculating the amount of antacids.
The dosage forms do not contain sucrose, so there are no restrictions for the use of the drug in patients with diabetes.
Release forms
Chewable tablets or for the preparation of a suspension for oral administration 100 mg. 60 tablets in a bottle made of high-density polyethylene with a screw cap made of polypropylene, inaccessible to children. 1 bottle along with instructions for use is placed in a cardboard box.
Capsules 125 mg, 200 mg, 250 mg and 400 mg. 10 capsules per blister made of PVC/aluminum foil. 3 blisters along with instructions for use in a cardboard box.
Powder for the preparation of an oral solution for children 2 g. 2 g in round glass bottles of transparent, colorless glass with a tightly screwed polypropylene cap that is inaccessible for children to open. The lid is marked with two arrows and the inscriptions “Close tightly” and “While pushing down turn”; the lid is equipped with a gasket made of foil and cellulose, covered with polyvinylidene chloride film. 1 bottle along with instructions for use is placed in a cardboard box.
Storage conditions:
Chewable tablets or for preparing a suspension for oral administration should be stored at a temperature of 15-30 °C.Store capsules at a temperature not exceeding 25 °C.
Store the powder for preparing an oral solution for children at a temperature of 15 to 30 °C.
Keep out of the reach of children.
Best before date:
Chewable tablets or for the preparation of oral suspension and capsules. 2 years.Powder for the preparation of an oral solution for children. 3 years.
Do not take the drug after the expiration date indicated on the package.
Conditions for dispensing from pharmacies:
.On prescription.
Manufacturer:
Chewable tablets or for the preparation of a suspension for oral administration; capsules - Bristol-Myers Squibb, France.Bristol-Myers Squibb, La-Goualle – 19250 MEYMAC, France.
Bristol-Myers Squibb, La Gualle - 19250 MAYMAK, France.
Powder for the preparation of oral solution for children - Bristol-Myers Squibb Company, USA.
Bristol-Myers Squibb Company, 2400 Lloyd Expressway, Evansville, Indiana 47721-0001, USA
Bristol-Myers Squibb Company, 2400 West Lloyd Expressway, Evansville, Indiana 47721-0001, USA
Consumer complaints are accepted at the representative office address:
123001, Moscow, Trekhprudny lane, 9, building 1B.
Compound
1 capsule includes:
active ingredient:
didanosine – 200 mg.
Granule fillers: sodium carboxymethyl starch, sodium carmellose.
Enteric coating of granules: copolymer of methacrylic acid and ethacrylate, diethyl phthalate, water, talc.
Capsule shell: sodium lauryl sulfate, titanium dioxide, aerosil, gelatin.
Ink for writing: shellac, propylene glycol, indigo carmine, titanium dioxide, yellow iron oxide.
pharmachologic effect
Videx is an antiviral drug effective against HIV infection.
Pharmacodynamics
The active component of the drug Videx is didanosine (2,3"-dideoxyinosine or ddI), which is an analogue of the nucleoside dioxyadenosine of synthetic origin. This substance has an inhibitory ability against further reproduction (division) of HIV in the cells of the human body, as well as in vitro.
Once in the cell, didanosine is metabolized with the participation of cellular enzymes with the formation of dideoxyadenosine triphosphate (ddATP), endowed with pharmacological activity.
The 2",3"-dideoxynucleoside attaches to the viral nucleic acid and prevents its further replication. In turn, ddATP, competing with dihydroxyadenosine 5-triphosphate (dATP) for binding to the active sites of the enzyme, inhibits the activity of HIV reverse transcriptase, thereby inhibiting the formation of proviral DNA.
Pharmacokinetics
The drug is characterized by a moderate degree of absorption, the time of maximum plasma concentration (Cmax) is 2 hours.
Videx in the form of hard gelatin capsules must be taken on an empty stomach - 1.5 hours before a meal or 2 hours after it. Taking with food (especially rich in fat) reduces Cmax (by 46%) and AUC (by 19%) of this drug. Plasma protein binding< 5 %.
The metabolism of didanosine in the human body has not been studied sufficiently. Based on the results of preclinical studies of the drug, the similarity of this process with the metabolism of endogenous purines was established.
When Videx is administered orally, its average T1/2 value is within 1.6 hours. 1/5 of the administered amount of the drug is determined in the urine.
Predominant tubular secretion of the drug is observed, which is confirmed by significant renal clearance, which is 400 ml/min (1/2 of the total clearance - 800 ml/min).
Pharmacokinetics in special clinical situations
Patients with nephron disorders
In patients in this group, an extension of T1/2 to 4.1 hours is observed.
3–4 hours after hemodialysis, the concentration of didanosine is 0.6–7.4% of the dose taken.
There is no change in the bioavailability of the drug in patients with renal impairment, but its clearance may decrease in proportion to QC.
Patients with hepatic disorders
In patients with liver pathologies, changes in metabolic processes are observed.
Pediatrics
The absorption capacity of the drug in patients from 1 to 17 years of age varies over a wide range. Cmax and AUC may increase in a dose-dependent manner.
The bioavailability of the drug after a single oral dose is 36%, when taken in a hospital setting – 47%. T 1/2 is approximately 0.8 hours.
The detectable amount of the drug in urine after a single oral dose is 18%, when used in a hospital setting - 21%.
The renal clearance of Videx is approximately 243 ml/m2/min (46% of the total clearance). When excreting the drug, its tubular secretion predominates.
Oral use of the drug in children for 26 days did not show any accumulation.
Indications for use
Videx is prescribed for the treatment of HIV infection as part of complex antiretroviral therapy.
Mode of application
Videx are gelatin capsules for oral use, which are recommended to be taken whole on an empty stomach (without opening or chewing). The dosage of the drug depends on the patient’s weight, namely:
- <60 кг – 250 мг 1 раз/сут.,
- ≥60 kg – 400 mg 1 time/day.
For younger pediatric patients, the drug is prescribed in the form of chewable tablets or tablets for the preparation of a suspension, which is most likely due to ease of use and the inability of the child to swallow the capsule whole.
Dosing in patients with nephropathologies
In patients of this clinical group, doses should be adjusted downward (according to body weight) and/or the interval between doses should be increased depending on the degree of CC.
Note: for patients whose body weight< 60 кг, при КК< 10 мл/мин следует рекомендовать данный препарат в другой ЛФ.
Dosing of the drug in special cases
If the patient is on dialysis, then the drug is prescribed in the usual daily dose (there is no need to change the recommended dosage regimen of the drug), but should be taken after the procedure.
In pediatrics in the presence of nephrological dysfunction There are no clear recommendations for dose adjustment. The attending physician determines this need on an individual basis. In this case, it may be necessary to reduce the dose and/or lengthen the interval between doses.
In gerontology the need to change the recommended dosage regimen depends on the patient's kidney function. In the presence of renal dysfunction, dose adjustment of the drug is required.
For hepatic disorders It may be necessary to reduce doses. Due to the lack of precise recommendations, dose adjustment in this case is carried out by the attending physician on an individual basis.
Therapy for patients in this group requires monitoring the level of liver enzymes; if it increases significantly, therapy should be interrupted. If increases in aminotransferase levels are observed, treatment with any nucleoside analogues may need to be interrupted or discontinued.
Side effects
|
Organs and systems of the body |
Side effects from taking the drug |
|---|---|
|
Gastrointestinal tract and digestion |
Hyposecretion of the salivary glands Loss of appetite Abdominal pain Fecal liquefaction Flatulence Liver inflammation Liver dysfunction Portal hypertension that is not associated with liver cirrhosis Inflammatory disorders of the pancreas Hyperactivity of liver transaminases and alkaline phosphatase Hyperconcentration of amylase and lipase Hyperbilirubinemia Hypertrophy of the parotid salivary gland Sialadenitis |
|
Nervous system |
Numbness and tingling of the limbs and trunk Headache |
|
Visual function |
Hyposecretion of the lacrimal glands Optic neuritis Retinal depigmentation |
|
Musculoskeletal system |
Muscle pain Bone and joint pain (mainly in the limbs) Dystrophic changes in muscles Destruction of muscle tissue (rhabdomyolysis) |
|
Hematopoietic system |
Decreased red blood cell levels Decrease in the number of granulocytes in peripheral blood Marked decrease in leukocytes and platelets in the patient’s blood |
|
Laboratory diagnostics |
Abnormal potassium levels in the blood Significant increase in uric acid levels in the blood Changes in blood glucose levels |
|
Dermatology |
Hair loss Itchy sensations Epidermal rashes |
|
Manifestations of allergies of anaphylactoid nature Severe asthenic symptoms Feverish state Pathological conditions of adipose tissue (dystrophy, atrophy) |
The following problems that arise when taking Videx require special attention:
- pancreatitis, the occurrence of which indicates a pronounced toxic effect of the drug. This condition can have different forms of severity and occur both at the beginning of the therapeutic course and at other stages; does not depend on the type of therapy (monotherapy using Videx or complex treatment), the level of immunosuppression caused by the initial pathology, and can lead to the death of the patient. Pancreatitis, which appears as a side effect, is dose-dependent;
- lactic acidosis/severe steatosis with hepatomegaly, which may result in death. These pathologies also occur regardless of the use of Videx (as a single drug or an additional agent in complex treatment). The vast majority of cases of this pathology occur in female patients. Risk factors for its occurrence are the patient’s large body weight and prolonged drug therapy. If laboratory diagnostics reveal signs of lactic acidosis/hepatotoxicity in patients, the drug must be discontinued;
- peripheral neuropathy, which is manifested by symmetrical numbness of both extremities (mainly pain and tingling of the feet (less often the hands)). Symptoms of the pathology are more pronounced in the later stages of the disease. The detrimental effect of simultaneous use of several antiretroviral drugs on the likelihood of occurrence and severity of this pathology has been established.
Side effects that accompany the use of Videx in pediatrics
There is a marked similarity in the harmful effects of Videx on the body of children and adults. Pancreatitis in children taking this drug according to the prescribed standard dosage regimen is observed in 3% of cases, and with increasing recommended doses - in 13% of cases. Visual pathologies in children are rare and are expressed by changes in the retina and optic neuritis.
Contraindications
The drug Videx in capsule form is contraindicated for use:
- children under 3 years old,
- patients with established phenylketonuria,
- women who are breastfeeding
- patients with established intolerance to the components of the drug.
Caution should be exercised when prescribing Videx:
- patients at risk for pancreatitis (as well as with a history of this diagnosis),
- patients with a progressive form of HIV infection,
- gerontological patients,
- patients with nephrodysfunctions (if adequate dose adjustment is not carried out).
Particular caution should be observed when prescribing the drug to patients with dysfunctional hepatic disorders.
Pregnancy
Experimental studies on the effectiveness and safety of Videx in women during pregnancy have not been conducted. The determination of the possibility of prescribing the drug to patients in this group is carried out by the attending physician, taking into account the individual characteristics of the woman’s body and all possible risks to the fetus.
Lactation is a contraindication for the use of Videx.
Drug interactions
|
Other drugs |
The result of simultaneous use with Videx |
|---|---|
|
Stavudin |
Additive toxicity observed |
|
Allopurinol |
The risk of pancreatitis increases in direct proportion to the increase in Videx content in the blood |
|
Tenofovir |
Dose adjustment of Videx is necessary due to a decrease in its plasma concentration in this type of interaction |
|
Ribavirin |
An intensification of the side effects of Videx may be observed, due to an increase in the level of intracellular didanosine triphosphates. Liver failure (including death), pancreatitis, peripheral neuropathy and systemic hyperlactatemia/lactic acidosis may occur. If the need for this co-administration has not been established, it should be avoided due to the high likelihood of serious side effects. |
The likelihood of interaction of Videx with other drugs involving the mechanism of displacement from binding sites is negligible due to the low degree of binding of didanosine to plasma proteins (< 5 %).
The tablet dosage form of the drug has a wider range of drug interactions.
Overdose
If the drug is overdosed, the patient may develop the following symptoms:
- pancreatitis,
- peripheral neuropathy,
- hyperconcentration of uric acid in the blood,
- pronounced hepatic disorders.
If these symptoms occur, consider:
- lack of antidote,
- ineffectiveness of peritoneal dialysis,
- low efficiency of hemodialysis (a procedure lasting 3–4 hours allows only 25–30% of the drug to be excreted from the body).
Release form
Videx is available in the form of hard gelatin capsules for internal use, size No. 2. The body and cap of the capsule are white (opaque), with green inscriptions “BMS”, “200 mg” and “6672”.
The encapsulation mass is white (a tint is allowed) granules coated with an enteric coating.
Capsules are packaged in blister pack No. 10, - 3 blisters in a cardboard pack with an annotation. Additional information about the manufacturer
Country of origin: France.
Registration Information
Registration certificate No.: P N011537/02 dated 05/12/11
Additionally
The drug is available on prescription.
Patients with hepatopathologies
When prescribing the drug to patients in this group, special care should be taken.
Patients with nephropathologies
Videx should be used with caution in this group of patients in the absence of adequate dose adjustment.
Pediatric patients
Videx in capsule form is not prescribed to children due to difficulties in administration. This group of patients is prescribed tablets (chewable or for the preparation of an oral suspension).
Patients of the gerontological group
When prescribing the drug to patients in this group, caution should be exercised.
Features of application
During the trials of the drug, no connection was established between the sensitivity of HIV to the drug in vitro and the severity of the therapeutic effectiveness of the drug; In addition, the obtained determination results have a wide range. There is a positive correlation in in vivo conditions between the degree of viral activity and the clinical progression of the pathology.
The simultaneous use of Videx and drugs that exhibit toxicity to the peripheral nervous system or pancreas should be avoided, since when they are prescribed together, a mutual reinforcement of these adverse effects is observed.
If there is a need for simultaneous administration of intravenous pentamidine or drugs that enhance the pharmacological effect of didanosine (hydroxycarbamide, allopurinol), Videx is prescribed in suspension form.
During therapy, the patient should regularly visit an ophthalmologist to identify possible visual pathologies. Pediatric patients should undergo a retinal examination once every 6 months.
Videx capsules do not contain antacid components, since the gelatin shell of the capsule and the presence of an enteric coating protect the active component from the aggressive effects of gastric juice. The absence of antacids in the composition allows you to avoid many drug interactions that are typical for the tablet form of the drug.
Authors
Attention!Description of the drug " Videx"on this page is a simplified and expanded version of the official instructions for use. Before purchasing or using the drug, you should consult your doctor and read the instructions approved by the manufacturer.
Information about the drug is provided for informational purposes only and should not be used as a guide to self-medication. Only a doctor can decide to prescribe the drug, as well as determine the dose and methods of its use.
Active substance
Didanosine
Release form, composition and packaging
Chewable tablets or for oral suspension white or off-white to light yellow, round, flat, with beveled edges, marked "100" on one side and "VIDEX" on the other; Slight marbling of the surface of the tablets is allowed.
Composition of granules:
Composition of the capsule shell:
Ink composition: shellac, propylene glycol, potassium hydroxide, titanium dioxide, red iron oxide dye, yellow iron oxide dye.
Capsules hard gelatin, size No. 2, consisting of two parts of opaque white color with the inscriptions “BMS”, “200 mg” and “6672” printed in green; The contents of the capsules are white or almost white granules coated with an enteric coating.
| 1 caps. | |
| didanosine | 200 mg |
Composition of granules: sodium carboxymethyl starch, sodium carmellose.
Composition of the suspension for the shell of granules: methacrylic acid-ethacrylate copolymer, diethyl phthalate, water, talc.
Composition of the capsule shell: sodium lauryl sulfate, titanium dioxide, colloidal silicon dioxide, gelatin.
Ink composition: shellac, propylene glycol, titanium dioxide, yellow iron oxide dye.
10 pieces. - blisters (3) - cardboard packs.
Capsules hard gelatin, size No. 1, consisting of two parts of opaque white color with the inscriptions “BMS”, “250 mg” and “6673” printed in blue; The contents of the capsules are white or almost white granules coated with an enteric coating.
| 1 caps. | |
| didanosine | 250 mg |
Composition of granules: sodium carboxymethyl starch, sodium carmellose.
Composition of the suspension for the shell of granules: methacrylic acid-ethacrylate copolymer, diethyl phthalate, water, talc.
Composition of the capsule shell: sodium lauryl sulfate, titanium dioxide, colloidal silicon dioxide, gelatin.
Ink composition: shellac, propylene glycol, indigo carmine.
10 pieces. - blisters (3) - cardboard packs.
Capsules hard gelatin, size No. 0, consisting of two parts of opaque white color with the inscriptions “BMS”, “400 mg” and “6674” printed in red; The contents of the capsules are white or almost white granules coated with an enteric coating.
| 1 caps. | |
| didanosine | 400 mg |
Composition of granules: sodium carboxymethyl starch, sodium carmellose.
Composition of the suspension for the shell of granules: methacrylic acid-ethacrylate copolymer, diethyl phthalate, water, talc.
Composition of the capsule shell: sodium lauryl sulfate, titanium dioxide, colloidal silicon dioxide, gelatin.
Ink composition: shellac, propylene glycol, simethicone, red iron oxide dye, aqueous.
10 pieces. - blisters (3) - cardboard packs.
pharmachologic effect
An antiviral drug active against HIV. Didanosine (2",3"-dideoxyinosine or ddI) is a synthetic analogue of the nucleoside dioxyadenosine, suppresses HIV replication in cultured human cells and in cell lines in vitro.
After entering the cell, didanosine is converted by cellular enzymes into the active metabolite dideoxyadenosine triphosphate (ddATP). During viral nucleic acid replication, the inclusion of a 2",3"-dideoxynucleoside prevents chain growth and thereby inhibits viral replication. In addition, ddATP inhibits HIV reverse transcriptase activity by competing with dioxyadenosine 5-triphosphate (dATP) for binding to the active sites of the enzyme, preventing the synthesis of proviral DNA.
Pharmacokinetics
Suction
From the digestive system: dry mouth, anorexia, nausea, vomiting, abdominal pain, diarrhea and increased gas formation, hepatitis, liver failure, portal hypertension not associated with liver cirrhosis, pancreatitis, increased activity of hepatic transaminases and alkaline phosphatase, increased concentrations of amylase and lipase, hyperbilirubinemia, hypertrophy parotid salivary gland, sialadenitis.
From the nervous system: paresthesia, headache.
From the side of the organ of vision: dry eyes, optic neuritis, retinal depigmentation.
From the musculoskeletal system: myalgia, arthralgia, myopathy, pain in the hands and feet, rhabdomyolysis.
From the hematopoietic organs: anemia, granulocytopenia, leukopenia, thrombocytopenia.
Laboratory indicators: hypo- and hyperkalemia, hyperuricemia, hypo- and hyperglycemia.
Dermatological reactions: alopecia, itching, skin rash.
Others: anaphylactoid/allergic reactions, asthenia, chills, lipodystrophy, lipoatrophy.
Children
Side effects of the drug in children and adult patients are similar. The development of pancreatitis in children is observed in 3% of cases when taken in doses not exceeding the recommended ones, and in 13% when treated with the drug in higher doses. Visual impairment is observed in children in rare cases and is characterized by changes in the retina and optic neuritis.
Overdose
There is no antidote for didanosine overdose.
Symptoms: pancreatitis, peripheral neuropathy, hyperuricemia, liver dysfunction.
Treatment: Didanosine is not removed from the body by peritoneal dialysis and very little by hemodialysis. During hemodialysis sessions lasting 3-4 hours, approximately 25-30% of didanosine is removed from the total concentration of didanosine circulating in the blood at the start of hemodialysis.
Drug interactions
When using the drug in combination with other drugs with similar toxicity (for example, stavudine), the risk of developing the described side effects increases significantly.
When using the drug Videx in the form of tablets in patients with opioid dependence during long-term treatment with methadone, a decrease in the AUC value of didanosine is observed (by 57%). When using drugs simultaneously, the dose of Videx should be increased.
When used together with tenofovir, a decrease in the concentration of didanosine in the blood plasma is observed, so the dose of the drug must be adjusted.
Delavirdine or indinavir should be taken 1 hour before taking Videx tablets. In the presence of the drug Videx, the AUC value of delavirdine or indinavir increases significantly. No drug interactions have been identified between indinavir and Videx capsules.
In special studies of the use of the drug Videx in multiple doses simultaneously with nevirapine, rifabutin, foscarnet, ritonavir, stavudine and zidovudine and the use of the drug Videx in a single dose simultaneously with loperamide, metoclopramide, ranitidine, sulfamethoxazole, trimethoprim, no drug interactions were identified.
Ketoconazole or itraconazole, the absorption of which when taken orally is affected by the acidity of gastric juice, should be taken 2 hours before taking Videx in tablet form. Videx capsules do not contain antacids, so there is no risk of interaction between these drugs.
When taking Videx in tablet form 2 hours before taking ganciclovir or simultaneously with it, the AUC of didanosine at steady state increases to an average of 111%. A slight decrease in the AUC of ganciclovir at steady state (by 21%) was observed in cases where patients took Videx 2 hours before ganciclovir. No changes in renal clearance were observed for either of these two drugs. It is unknown whether these changes are related to changes in the safety of Videx or the effectiveness of ganciclovir. There is no evidence that didanosine enhances the myelosuppressive effects of ganciclovir.
Plasma concentrations of tetracycline antibiotics and some fluoroquinolone antibiotics (for example, ciprofloxacin) are reduced in the presence of antacids, because form chelate compounds. Therefore, Videx tablets containing antacids should be taken at least 6 hours before or 2 hours after taking ciprofloxacin. Videx capsules do not contain antacids, so there is no risk of interaction with tetracycline and fluoroquinolone antibiotics.
Ribavirin may increase intracellular levels of didanosine triphosphates and potentially increase the risk of side effects. Cases of fatal liver failure, as well as cases of pancreatitis, peripheral neuropathy and systemic hyperlactatemia/lactic acidosis have been reported when didanosine was co-administered with ribavirin, with or without stavudine. Concomitant use of didanosine and ribavirin should be avoided unless the potential benefit outweighs the risk of side effects.
Less than 5% of didanosine is bound to plasma proteins, indicating a low likelihood of drug interactions involving displacement from binding sites.
special instructions
The relationship between HIV sensitivity to didanosine in vitro and clinical response to treatment has not been established. In vitro susceptibility results vary widely. A positive in vivo correlation has been established between viral activity measurements (eg, RNA polymerase chain reaction assays) and clinical disease progression.
Chewable tablets or for the preparation of a suspension for oral administration in children under 3 years of age are recommended to be used only in the form of a suspension.
When Videx is used concomitantly with drugs with known toxic effects on the peripheral nervous system or pancreas, the risk of these toxic effects increases significantly.
When simultaneously prescribing intravenous pentamidine or drugs that increase the activity of didanosine (hydroxycarbamide, allopurinol), it is recommended to use Videx in the form of a suspension.
You should have your vision checked periodically and note any visual disturbances, such as altered color perception or blurry vision of objects.
Children should have their retina examined every 6 months or when any vision changes occur.
Didanosine is quickly destroyed in the acidic contents of gastric juice. Therefore, to reduce acidity, the tablets contain antacids. The capsules contain didanosine in the form of granules coated with an enteric coating, as a result of which the absorption of the drug in the intestine increases.
In HIV-infected patients with severe immunodeficiency, signs of an inflammatory response to asymptomatic or residual opportunistic infections may occur during combination antiretroviral therapy. This syndrome was observed during the first few weeks or months after starting antiretroviral therapy. Signs of cytomegalovirus retinitis, generalized or focal mycobacterial infections and pneumonia caused by Pneumocystis jiroveci may occur.
If symptoms of pancreatitis appear, treatment with the drug should be suspended, and if the diagnosis is confirmed, treatment should be stopped. If there is a clinically significant increase in the level of biochemical parameters, even in the absence of symptoms of pancreatitis, the drug should be prescribed in the form of a suspension.
If clinically confirmed symptoms of hepatotoxicity or lactic acidosis appear (even if liver transaminases slightly exceed ULN), treatment with the drug should be suspended. If these indicators are significantly exceeded, treatment should be stopped.
In post-marketing studies, cases of portal hypertension not associated with cirrhosis have been reported, including cases leading to liver transplantation and deaths. Didanosine-induced portal hypertension not associated with liver cirrhosis was confirmed by liver biopsy results in patients with
unconfirmed viral hepatitis. Common signs of the development of portal hypertension included: increased activity of liver enzymes, esophageal varices, hematemesis, ascites, splenomegaly.
Patients taking Videx should be regularly monitored for early signs of portal hypertension (eg, thrombocytopenia and splenomegaly) during routine healthcare visits. Relevant laboratory
Studies including liver enzyme activity, serum bilirubin levels, serum albumin, complete blood count, INR and ultrasonography should be prescribed for such patients. Videx should be discontinued if the patient develops signs of portal hypertension not associated with liver cirrhosis.
The absorption of didanosine, regardless of dosage form, in the presence of food is reduced by an average of 50%. Tablets should be taken 30 minutes before or 2 hours after meals, capsules should be taken on an empty stomach.
When prescribing the drug to patients with impaired renal function, it should be taken into account that each tablet contains 8.6 mEq of magnesium.
When prescribing the drug to patients with phenylketonuria, it should be taken into account that each 100 mg tablet contains 36.5 mg of phenylalanine aspartame. The capsules do not contain phenylalanine.
When prescribing the drug to patients on a diet with limited salt intake, it should be taken into account that 100 mg of capsule contents contains at least 0.424 mg of sodium. The tablets do not contain sodium salts.
Tablets and capsules do not contain sucrose, so there are no restrictions for the use of the drug in patients with diabetes.
Pregnancy and lactation
Adequate and controlled studies have not been conducted in pregnant women. Videx should be used during pregnancy only if there are strict indications and only in cases where the potential benefit to the mother outweighs the possible risk to the fetus.
During treatment with the drug, breastfeeding should be stopped.
Use in childhood
The use of capsules in children under 3 years of age is contraindicated due to the method of administration.
For impaired renal function
WITH caution the drug should be used in the treatment of patients with impaired renal function with unadjusted doses of the drug.
The drug should be stored out of the reach of children.
| Capsules | 1 caps. |
| didanosine | 125 mg |
| 200 mg | |
| 250 mg | |
| 400 mg | |
| Excipients | |
| composition of granules: sodium carboxymethyl starch; sodium carmellose | |
| composition of the suspension for the shell of granules: copolymer of methacrylic acid and ethacrylate; diethyl phthalate; water; talc | |
| capsule shell composition: sodium lauryl sulfate; titanium dioxide; colloidal silicon dioxide; gelatin | |
| ink composition: capsules 125 mg - shellac; propylene glycol; potassium hydroxide; titanium dioxide; dyes - iron oxide red and iron oxide yellow; capsules 200 mg - shellac; propylene glycol; indigo carmine; titanium dioxide; iron oxide yellow; capsules 250 mg - shellac; propylene glycol; indigo carmine; capsules 400 mg - shellac; propylene glycol; simethicone; dye - red iron oxide; ammonia water |
10 pcs in blister; There are 3 blisters in a box.
in bottles of 60 pcs.; 1 bottle in a box.
1 bottle in a box.
pharmachologic effect
pharmachologic effect- antiviral.Directions for use and doses
Inside.
Capsules should be swallowed whole, without chewing, on an empty stomach.
Table 1
Chewable tablets or for the preparation of a suspension for oral administration and powder for the preparation of an oral solution.
table 2
You can select the required dose by using a combination of tablets of different dosages. Possible overdose of antacids or phenylalanine contained in tablets should be avoided. Each dose of the drug should consist of at least 2, but not more than 4 tablets, in total not exceeding the recommended dose. Children younger than 1 year of age should receive one tablet at a time that provides enough antacid for that age group.
Tablets are taken 30 minutes before or 2 hours after meals. Before taking, the tablet should be chewed thoroughly or dissolved in at least 30 ml of water, stirring thoroughly until a homogeneous suspension is obtained. For children, the recommended dose (1 tablet) is dissolved in 15 ml of water. To adjust the taste, you can add 30 ml (for adults) or 15 ml (for children) of apple juice without pulp. After preparation, the resulting suspension should be mixed and drunk entirely. The resulting suspension is stable for 1 hour when stored at room temperature (17-23 °C).
Newborns and children up to 8 months: The daily dose is calculated depending on the body surface area and is 100 mg/m2 2 times a day with an interval of 12 hours.
Children over 8 months: daily dose - 120 mg/m2 2 times a day with an interval of 12 hours.
Powder for the preparation of oral solution for children should be taken at least 30 minutes before or 2 hours after meals only in a mixture with antacids containing aluminum and magnesium hydroxides. Antacid preparations are divided into three groups (A, B and C), depending on the content of these active substances in them. Recommended ratios of aluminum and magnesium are presented in table 3:
Table 3
| Magnesium hydroxide content*, mg/5 ml | Aluminum hydroxide content**, mg/5 ml | The group to which the antacid drug belongs |
| 400 | 400-900 | A |
| 350 | 425-900 | A |
| 300 | 450-900 | A |
| 250 | 200-450 | B |
| 200 | 213-450 | B |
| 150 | 225-450 | B |
| 125 | 100-225 | C |
| 100 | 107-225 | C |
| 75 | 113-225 | C |
Before preparing the solution, determine which group of antacid drugs yours belongs to.
* If the magnesium hydroxide content falls between the specified values, the drug can be used in cases where the minimum aluminum hydroxide content compensates for the reduced magnesium hydroxide content.
For example, the drug contains 325 mg of magnesium hydroxide and a sufficient amount of aluminum hydroxide, then the drug belongs to group A. The minimum content of aluminum hydroxide is calculated as follows: a decrease in the content of magnesium hydroxide by 1 mg requires an increase in the content of aluminum hydroxide by at least 0.5 mg. In our example: a decrease in magnesium hydroxide content by 75 mg (from 400 to 325 mg) requires a minimum increase in aluminum hydroxide content of 37.5 mg (rounded up to 38 mg). Therefore, the content of aluminum hydroxide in the preparation must be at least 438 mg.
For example, a drug contains 175 mg of magnesium hydroxide and a sufficient amount of aluminum hydroxide; the drug belongs to group B. The minimum content of aluminum hydroxide is calculated as follows: a decrease in the content of magnesium hydroxide by 1 mg requires an increase in the content of aluminum hydroxide by at least 0.25 mg. In our example: a decrease in magnesium hydroxide content by 75 mg (from 250 to 175 mg) requires a minimal increase in aluminum hydroxide content by 18.75 mg (rounded up by 19 mg). Therefore, the content of aluminum hydroxide in the preparation must be at least 219 mg.
For example, if a drug contains 85 mg of magnesium hydroxide and a sufficient amount of aluminum hydroxide, the drug belongs to group C. The minimum aluminum hydroxide content is calculated as follows: a decrease in magnesium hydroxide content by 1 mg requires an increase in aluminum hydroxide content by at least 0.25 mg. In our example: a 40 mg decrease in magnesium hydroxide (from 125 to 85 mg) requires a minimum increase of 10 mg in aluminum hydroxide. Therefore, the content of aluminum hydroxide in the preparation must be at least 110 mg.
** If the drug contains aluminum oxide, its content is converted to aluminum hydroxide: 1 mg of oxide corresponds to 1.53 mg of aluminum hydroxide.
Preparation of a solution with drugs of group A
Add 100 ml of water to the 100 ml mark on the bottle label, a solution with a didanosine concentration of 20 mg/ml is formed. Mix well. Add the antacid suspension to the 200 ml mark on the bottle label. The concentration of didanosine in the suspension is 10 mg/ml. Mix well.
Preparation of a solution with drugs of group B
Add 100 ml of antacid suspension to the 100 ml mark on the bottle label, a suspension with a didanosine concentration of 20 mg/ml is formed. Mix well. Add the antacid suspension to the 200 ml mark on the bottle label. The concentration of didanosine in the suspension is 10 mg/ml. Mix well.
Preparation of a solution with drugs of group C
Add 100 ml of antacid suspension to the 100 ml mark on the bottle label. Mix well. Add the antacid suspension to the 200 ml mark on the bottle label. Mix well. Transfer the resulting suspension into a glass or plastic bottle of a suitable size and add another 200 ml of antacid suspension to it. The concentration of didanosine in the resulting suspension is 5 mg/ml; the resulting suspension will last half the days less than when using antacids of groups A and B.
The prepared mixture is 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. Unused drug after 30 days of storage is thrown away.
Adults with impaired kidney function It is recommended to reduce the dose and/or increase the interval between doses depending on creatinine clearance (see Table 4).
Table 4
| Creatinine clearance, ml/min/1.73 m2 | Capsules | Tablets* and powder for oral solution for children |
| Body weight ≥60 kg | ||
| ≥60 (usual dose) | 400 mg 1 time per day | 400 mg once daily or 200 mg twice daily |
| 30-59 | 200 mg 1 time per day | 200 mg once daily or 100 mg twice daily |
| 10-29 | 125 mg 1 time per day | 150 mg 1 time per day |
| <10 | 125 mg 1 time per day | 100 mg 1 time per day |
| Body mass<60 кг | ||
| ≥60 (usual dose) | 250 mg 1 time per day | 250 mg once daily or 125 mg twice daily |
| 30-59 | 125 mg 1 time per day | 150 mg once daily or 75 mg twice daily |
| 10-29 | 125 mg 1 time per day | 100 mg 1 time per day |
| <10 | -** | 75 mg 1 time per day |
* Each dose of the drug must consist of at least 2 tablets, but not more than 4 tablets, in total not exceeding the recommended dose. You can choose a dose using a combination of tablets of different dosages.
**Patients with weight<60 кг и Cl
креатинина <10 мл/мин следует назначать другую лекарственную форму.
Patients on dialysis should take a daily dose of the drug after dialysis. There is no need for an additional dose of the drug.
Children with impaired renal function: There are no precise recommendations for dose adjustment. It is possible to reduce the dose and/or increase the interval between doses.
Elderly patients: Careful dose selection is necessary due to the possible decrease in renal function. Kidney function should be monitored and the dose of the drug adjusted.
For patients with impaired liver function: a dose reduction may be required. There are no exact recommendations for adjusting drug doses in case of impaired liver function. During treatment, it is necessary to examine the level of liver enzymes. If the level of liver enzymes is clinically significant, stop treatment with the drug. If aminotransferase levels rise rapidly, it may be necessary to discontinue treatment with any nucleoside analogues.
Manufacturer
Powder for preparing an oral solution for children - Bristol Myers Squibb (USA).
Tablets and capsules - Bristol Myers Squibb (France).
Storage conditions for the drug Videx ®
At a temperature not exceeding 25 °C.Keep out of the reach of children.
Shelf life of the drug Videx ®
chewable tablets or for the preparation of a suspension for oral administration 100 mg - 2 years.
powder for the preparation of an oral solution for children 2 g - 3 years.
capsules 125 mg - 2 years.
capsules 200 mg - 2 years.
capsules 250 mg - 2 years.
capsules 400 mg - 2 years.
Do not use after the expiration date stated on the package.
An antiviral drug active against HIV.
Drug: VIDEX®
Active substance of the drug:
didanosine
ATX coding: J05AF02
KFG: Antiviral drug active against HIV
Registration number: P No. 011537/02
Registration date: 01/19/06
Owner reg. credential: BRISTOL-MYERS SQUIBB (France)
Videx release form, drug packaging and composition.
Tablets, chewable or for oral suspension, are round, flat, with beveled edges, white or off-white to light yellow in color, marked “100” on one side of the tablet and “VIDEX” on the other. Some marbling of the surface of the tablets is allowed.
1 tab.
didanosine
100 mg
Excipients: calcium carbonate, magnesium hydroxide, aspartame, sorbitol powder, microcrystalline cellulose, crospovidone, tangerine orange flavor, magnesium stearate.
60 pcs. — polyethylene bottles (1) — cardboard packs.
1 caps.
didanosine
250 mg
Ink composition: shellac, propylene glycol, indigo carmine.
Hard gelatin capsules, consisting of 2 parts, opaque white. Capsule contents: white or almost white granules, enteric-coated.
1 caps.
didanosine
400 mg
Composition of granules: sodium carboxymethyl starch, sodium carboxymethylcellulose.
Composition of the suspension for the shell of granules: suspension of methacrylic acid and ethacrylate copolymer 30%, diethyl phthalate, purified water, talc.
Composition of the capsule shell: sodium lauryl sulfate, titanium dioxide, anhydrous colloidal silicon, gelatin.
Ink composition: shellac, propylene glycol, simethicone, red iron oxide, ammonium hydroxide.
10 pieces. - blisters (3) - cardboard packs.
DESCRIPTION OF THE ACTIVE SUBSTANCE.
All information provided is provided for information only about the drug; you should consult your doctor about the possibility of use.
Pharmacological action of Videx
Antiviral agent, nucleoside reverse transcriptase inhibitor, synthetic analogue of deoxyadenosine (purine nucleoside). Active against HIV. After penetration of didanosine into the cell, it is metabolized by cellular enzymes to the active metabolite - dideoxyadenosine triphosphate, which inhibits HIV reverse transcriptase. Under the influence of didanosine, the number of cells with CD4+ receptors increases, which is considered confirmation of the antiviral effect. At the same time, peripheral blood parameters and the content of viral protein (P24 antigen) in the blood are normalized.
Pharmacokinetics of the drug.
Didanosine is rapidly destroyed at acidic pH values. Therefore, all dosage forms for oral administration contain buffering substances that increase the pH of gastric juice and thereby reduce the breakdown of didanosine and enhance its absorption. Cmax in plasma is reached after 0.5-1 hour. Penetrates through the BBB. Vd is 0.7-1 l/kg. T1/2 is 1.5 hours. It is excreted in the urine.
Indications for use:
Treatment of AIDS with pronounced clinical manifestations of infections with ineffectiveness or intolerance of zidovudine.
Dosage and method of administration of the drug.
When taken orally, depending on the dosage form, a single dose for adults with a body weight of 60 kg or more is 200-250 mg, with a body weight of less than 60 kg - 125-167 mg. Frequency of administration: 2 times/day.
In children, it is used at a dose of 240 mg/m2. The interval between doses should be 12 hours. Didanosine should be taken on an empty stomach.
Side effects of Videx:
From the digestive system: pancreatitis, diarrhea, nausea, vomiting, hyperbilirubinemia, increased activity of liver transaminases, alkaline phosphatase and amylase in the blood plasma, hepatitis.
From the central nervous system: peripheral neuropathy, headache, convulsions, general weakness, dizziness, insomnia.
From the hematopoietic system: leukopenia, thrombocytopenia, anemia.
Other: increased concentration of uric acid. When using didanosine in children, retinal depigmentation, diabetes mellitus and diabetes insipidus were also observed.
Contraindications to the drug:
Hypersensitivity to didanosine.
Use during pregnancy and lactation.
Adequate and strictly controlled studies of the safety of didanosine during pregnancy in humans have not been conducted. Use during pregnancy is possible only if there are clear indications and in cases where the potential benefit of therapy for the mother outweighs the risk to the fetus.
It is not known whether didanosine is excreted in breast milk. If use is necessary during lactation, breastfeeding should be discontinued.
Special instructions for the use of Videx.
There are currently no controlled studies of the effects of didanosine in HIV infection. Clinical trials are being conducted to evaluate its effectiveness and optimize the dosage regimen.
Didanosine should be used with caution if there is a history of pancreatitis.
During treatment, you should regularly monitor the level of amylase, transaminases, bilirubin, peripheral blood picture, kidney function indicators, and the content of T-lymphocytes.
Children need periodic ophthalmological examinations.
When using didanosine, men and women of childbearing age should use reliable methods of contraception.
Interaction of Videx with other drugs.
When used simultaneously with chloramphenicol, cisplatin, ethambutol, ethionamide, hydralazine, isoniazid, metronidazole, stavudine, zalcitabine, vincristine, peripheral neuropathy may develop.
With simultaneous use of didanosine with ganciclovir, the risk of developing myelodepression increases.
