Disaverox
Disaverox: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Dizaverox
ATX code: J05AR01
Active ingredient: Zidovudine (Zidovudine), Lamivudine (Lamivudine)
Manufacturer: FARMASINTEZ JSC (Russia)
Description and photo update: 18.10.2018
Prices in pharmacies: from 752 rubles.
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Disaverox is a combined antiviral drug that is active against HIV infection.
Release form and composition
The dosage form of the release is film-coated tablets: oval spherical, white, the core in the cross section is white with a yellowish tinge or white (10 pcs. In blisters, 2, 3, 6 or 10 packages are placed in a cardboard box; in cans of 60 or 100 pcs., 1 can is placed in a cardboard box).
Active ingredients in 1 tablet:
- zidovudine - 300 mg;
- lamivudine - 150 mg.
Additional components:
- core: microcrystalline cellulose - 78 mg; primogel (sodium carboxymethyl starch) - 22.5 mg; magnesium stearate - 4.5 mg; colloidal silicon dioxide (aerosil brand A-300) - 2.5 mg; pregelatinized starch - 22.5 mg;
- shell: ready-made film water-soluble shell (titanium dioxide - 25%; polyethylene glycol 6000 - 9.5%; hypromellose - 25%; copovidone - 22.5%; polydextrose - 15%; glyceryl caprylocaprate - 3%) - 15 mg.
Pharmacological properties
Pharmacodynamics
Disaverox is one of the combined antiviral agents. Its active components - lamivudine and zidovudine - are highly effective selective inhibitors of HIV-1 and HIV-2.
The antiviral activity of the active substances is mainly due to the inclusion of their monophosphate form in the viral DNA chain, as a result of which the chain breaks. The triphosphates of zidovudine and lamivudine have a significantly lower affinity for DNA polymerases of human cells.
The combined use of lamivudine and zidovudine slows the development of zidovudine resistance in patients who have not received antiretroviral therapy before.
Disaverox increases the CD4 + cell count and decreases viral load, as well as the risk of disease progression, including death.
Pharmacokinetics
The active ingredients of Disaverox are well absorbed from the digestive tract (bioavailability of lamivudine in adult patients is 80–85%, zidovudine is from 60 to 70%). The components weakly bind to plasma proteins, penetrate into the cerebrospinal fluid and the central nervous system. Lamivudine is excreted unchanged from the body mainly by the kidneys. The half-life (T 1/2) is in the range from 5 to 7 hours. Zidovudine is metabolized in the liver, where it is conjugated with glucuronic acid. It is excreted mainly in the form of glucuronide by the kidneys. T 1/2 zidovudine - about 1 hour.
Indications for use
Disaverox is indicated for the treatment of HIV infection in patients over 12 years of age with progressive immunodeficiency (CD4 + cell count <500 / μl).
Contraindications
Absolute:
- anemia (hemoglobin <7.5 g / dl, or 4.65 mmol / l);
- neutrophil count (<750 / μl);
- chronic renal failure (with creatinine clearance <50 ml / min);
- liver failure;
- age up to 12 years and weight up to 30 kg;
- lactation period;
- individual intolerance to the components of the drug.
Relative (diseases / conditions in which the appointment of Disaverox requires caution):
- hepatomegaly;
- hepatitis;
- cirrhosis of the liver;
- obesity;
- the presence of risk factors predisposing to liver damage;
- pregnancy.
Instructions for the use of Disaverox: method and dosage
Disaverox is taken orally, regardless of food intake.
Recommended dosage regimen: 2 times a day, 1 tablet.
Side effects
The disorders described below were observed in the treatment of HIV infection with the active ingredients of Disaverox in the form of monotherapy or in the form of their combination. For many side effects, it is unclear whether they are therapy-related or complications of HIV infection.
Disaverox can cause disturbances specific to each of the two components. There is currently no evidence that the combination of zidovudine and lamivudine has additive toxicity.
Estimation of the incidence of adverse reactions:> 10% - very often; > 1% and 0.1% and 0.01% and <0.1% - rarely; <0.01%, including isolated messages - very rare.
Lamivudine
- lymphatic and hematopoietic systems: infrequently - thrombocytopenia, anemia, neutropenia; rarely - true erythrocytic aplasia;
- digestive system: often - diarrhea, vomiting, nausea, epigastric pain; rarely - increased serum amylase activity in the blood, pancreatitis;
- musculoskeletal system and connective tissue: often - muscle disorders, arthralgia; rarely - rhabdomyolysis;
- nervous system: often - headache; rarely - peripheral neuropathy, paresthesia;
- nutrition and metabolism: often - hyperlactatemia; rarely - lactic acidosis;
- subcutaneous fat and skin: alopecia, rash;
- liver and biliary tract: infrequently - a transient increase in the activity of liver enzymes; rarely - hepatitis;
- others: general accumulation / redistribution of subcutaneous fat, malaise, fatigue, fever.
Zidovudine
- digestive system: often - stomach pain, vomiting, nausea, diarrhea; infrequently - flatulence; rarely - taste perversion, pigmentation of the oral mucosa, pancreatitis, dyspepsia;
- respiratory system: infrequently - shortness of breath; rarely - sinusitis, rhinitis, cough;
- cardiovascular system: rarely - cardiomyopathy;
- nervous system: very often - headache; often - dizziness; rarely - confusion, paresthesia, insomnia, decreased mental activity, drowsiness, convulsions;
- lymphatic and hematopoietic systems: often - anemia (blood transfusion may be required), leukopenia, neutropenia; infrequently - pancytopenia and thrombocytopenia (with bone marrow hypoplasia); rarely - true erythrocytic aplasia; very rarely - aplastic anemia;
- reproductive system and mammary glands: rarely - gynecomastia;
- musculoskeletal system and connective tissue: often - myalgia; infrequently - myopathy;
- psyche: rarely - depression, anxiety;
- nutrition and metabolism: often - hyperlactatemia; rarely - anorexia, lactic acidosis;
- biliary tract and liver: often - an increase in the concentration of bilirubin and the activity of liver enzymes; rarely - liver damage (severe hepatomegaly with stenosis);
- kidneys and urinary tract: rarely - frequent urination;
- subcutaneous fat and skin: infrequently - itching, rash; rarely - pigmentation of the skin and nails, increased sweating, urticaria;
- others: chest pain, general malaise, fever, flu-like syndrome, asthenia, accumulation / redistribution of subcutaneous fat, chills, generalized pain syndrome.
Overdose
In acute overdose, no specific dose-dependent symptoms have been identified (except for those listed in the side effects).
For treatment, it is recommended to monitor the patient's condition and standard maintenance therapy, continuous hemodialysis.
special instructions
Patients who need to adjust the dose of lamivudine and zidovudine individually are not recommended to use Disaverox.
The patient's condition should be monitored continuously (due to the likelihood of developing opportunistic infections and other complications of HIV infection).
The use of Disaverox does not prevent the risk of transmitting HIV to other people through infected blood transfusion or sexual intercourse, therefore, patients should take appropriate precautions.
During the period of therapy, careful monitoring of hematological parameters should be carried out (due to the likelihood of anemia, neutropenia and leukopenia). As a rule, hematological changes appear not earlier than 4-6 weeks after the start of treatment.
It is recommended to monitor blood tests in patients with a late stage of clinically expressed HIV infection at least once every 14 days during the first 3 months of therapy, and then at least once a month.
Adverse reactions from the blood system in patients with an early stage of HIV infection are rare. Blood tests may be done less frequently (for example, once every 1–3 months). You should focus on the general condition of patients. If severe myelosuppression or anemia develops, a special selection of zidovudine may be required. Since it is impossible to individually select the dose of Disaverox, it is recommended to transfer the patient to taking these drugs separately.
In cases of the appearance of clinical symptoms of pancreatitis or laboratory data indicating the development of the disease (vomiting, nausea, abdominal pain or an increase in the values of biochemical markers), Disaverox is immediately canceled.
In case of lethargy, stiffness, joint pain, difficulty in movement, it is necessary to consult a specialist (due to the likelihood of developing osteonecrosis).
There is information about the development in rare cases of lactic acidosis and severe hepatomegaly with fatty degeneration of the liver (possibly fatal). Most often, these violations were observed in women. The main clinical symptoms: general weakness, loss of appetite and sudden unexplained weight loss, respiratory and gastrointestinal disturbances (rapid breathing, shortness of breath).
In the presence of risk factors for liver damage, Disaverox should be administered with caution. If clinical and laboratory symptoms of lactic acidosis or hepatotoxicity (including hepatomegaly and steatosis, even in the absence of an increase in transaminase activity) appear, therapy should be suspended.
In some patients, during therapy, there may be an accumulation / redistribution of adipose tissue, including central obesity, dorsovisceral fat deposition, weight loss of the face and limbs, enlargement of the mammary glands, increased serum glucose and blood lipids.
When conducting a clinical examination of patients, an assessment of the physical signs of redistribution of adipose tissue should be included. Lipid disorders should be treated based on their clinical manifestations.
There are reports of mitochondrial damage of varying degrees associated with therapy. There is evidence of mitochondrial dysfunction in HIV-negative children who have been exposed to nucleoside analogs in utero or immediately after birth. The main manifestations of mitochondrial dysfunction: neutropenia, anemia, increased plasma lipase activity in the blood, hyperlactatemia. Also, later manifestations of this disorder were noted, including convulsions, muscle hypertonicity, and behavioral abnormalities.
At the beginning of therapy, there may be an exacerbation of the inflammatory process against the background of residual / asymptomatic opportunistic infection. This can seriously worsen symptoms or worsen the condition. As a rule, such reactions are observed during the first weeks / months after the start of the use of Disaverox. The most significant examples are cytomegalovirus retinitis, pneumocystis pneumonia, focal / generalized mycobacterial infection. Any symptoms of inflammation should be identified and, if necessary, treated. Against the background of restoration of immunity, autoimmune diseases were observed (such as Guillain-Barré syndrome, Graves' disease, polymyositis), however, the time of primary manifestations varied,and the disease could develop many months after starting therapy and have an atypical course.
In case of previously identified liver diseases (including chronic hepatitis), during the use of Disaverox, the incidence of functional liver disorders increases. In this group of patients, therapy should be carried out with caution with careful monitoring of the condition. In cases of deterioration of hepatic function, the drug can be canceled.
With a combination of HIV infection with the hepatitis B or C virus, the likelihood of developing the hepatotoxic effect of Disaverox is higher than with only HIV infection. Such patients belong to the group of increased risk of influence on the liver with a possible fatal outcome (clinical / laboratory monitoring of the patient's condition is required).
When HIV infection is combined with the hepatitis B virus, Disaverox should be prescribed with caution. After cessation of lamivudine therapy, clinical / laboratory signs of exacerbation of hepatitis may appear (severe consequences are possible with decompensation of liver function). After the end of therapy, it is necessary to monitor the biochemical indicators of hepatic function and markers of hepatitis B virus replication.
With the combined use of ribavirin and zidovudine with concomitant viral hepatitis C, an aggravation of anemia may be observed. Despite the fact that the mechanism of this disorder is unclear, the combined use of these drugs is not recommended, especially with a burdened history of zidovudine-induced anemia (it is recommended to consider the possibility of changing therapy in order to cancel zidovudine).
Influence on the ability to drive vehicles and complex mechanisms
The likelihood of the influence of Disaverox on the ability to drive vehicles is low, however, it is necessary to take into account the clinical condition of the patient, as well as the nature of the adverse reactions of the active components of the drug.
Application during pregnancy and lactation
For pregnant women, Disaverox can be prescribed only in cases where the expected benefit outweighs the possible harm.
You should not breastfeed your baby during therapy.
Pediatric use
For children under 12 years of age and weighing up to 30 kg, Disaverox is contraindicated.
With impaired renal function
In patients with chronic renal failure (with creatinine clearance <50 ml / min), Disaverox is not prescribed, since in this case individual selection of doses of lamivudine and zidovudine is required (they are used as separate drugs).
For violations of liver function
According to the instructions, Disaverox is contraindicated for use in patients with hepatic insufficiency, since in this case individual selection of doses of lamivudine and zidovudine is required (they are used as separate drugs).
Use in the elderly
There is no specific information on the use of Disaverox in elderly patients. However, for this group of patients, special care is recommended, taking into account age-related changes (functional disorders of the kidneys and changes in hematological parameters).
Drug interactions
Since Disaverox is a combined drug, it can enter into any interactions that are characteristic of each of the components.
The likelihood of metabolic interactions with lamivudine is low, since the drug is almost completely excreted unchanged by the kidneys.
Zidovudine also binds to plasma proteins to a small extent, but is eliminated mainly through hepatic metabolism to inactive glucuronide.
Potentially, drugs with a predominantly hepatic metabolism, especially through glucuronidation, can inhibit the metabolism of zidovudine.
Lamivudine interactions
- drugs excreted using the cationic transport system: the combination requires caution;
- trimethoprim, sulfamethoxazole (160 mg + 800 mg, co-trimoxazole): a significant increase in the plasma concentration of lamivudine; in the absence of functional renal impairment, dose adjustment of lamivudine is not required; the pharmacokinetics of trimethoprim / sulfamethoxazole does not change; in patients with renal insufficiency, the combination with co-trimoxazole requires caution; the effectiveness of the combination of lamivudine with high doses of co-trimoxazole for the treatment of toxoplasmosis and Pneumocystis pneumonia has not been studied;
- zalcitabine: inhibition of its intracellular phosphorylation (the combination is not recommended).
Zidovudine interactions
- atovahone: its pharmacokinetics does not change; the degree of metabolism of zidovudine to its glucuronide decreases; with the appointment of zidovudine at a dose of 500-600 mg per day and the concomitant use of atovachon for a course of 3 weeks in the treatment of acute pneumocystis pneumonia, an increase in the incidence of side effects is unlikely; in cases of longer use of this combination of drugs, the patient's condition must be carefully monitored;
- clarithromycin: decreased absorption of zidovudine (the interval between the use of these drugs should be at least 2 hours);
- lamivudine: an increase in the time of exposure to zidovudine and its maximum plasma concentrations while its total exposure remains unchanged; the pharmacokinetics of lamivudine does not change;
- phenytoin: a decrease in its concentration in the blood, in one case - an increase (monitoring of this indicator is required);
- probenecid: the average half-life of zidovudine increases; possibly decreased renal excretion of zidovudine;
- stavudine: inhibition of the process of its intracellular phosphorylation (the combination is not recommended);
- lorazepam, ketoprofen, acetylsalicylic acid, morphine, codeine, clofibrate, indomethacin, naproxen, oxazepam, cimetidine, dapsone, isoprinosine: changes in the metabolism of zidovudine (before prescribing a combination, especially a long course, an assessment of drug interactions is required);
- myelosuppressive / nephrotoxic drugs, including ganciclovir, co-trimoxazole, vinblastine, pentamidine, pyrimethamine, dapsone, amphotericin, flucytosine, interferon, vincristine, doxorubicin: an increase in the likelihood of adverse reactions with zidovudine, if necessary, careful monitoring of the functional status of gematological the dose of the drug / drugs is being adjusted);
- ribavirin: blocking the antiviral activity of zidovudine.
Analogs
Analogs of Disaverox are: Virokomb, Zilacomb, Zidovudine + Lamivudine, Zidovudine + Lamivudine-Vial, Combivir, Lazevun, LAMI-ZIDOX.
Terms and conditions of storage
Store at temperatures up to 25 ° C in the original manufacturer's packaging. Keep out of the reach of children.
Shelf life is 2 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Disaverox
There are few reviews about Disaverox, indicating the effectiveness of the drug and its relatively low cost.
Price for Disaverox in pharmacies
The price of Disaverox (60 tablets) can vary between 1500–1900 rubles.
Disaverox: prices in online pharmacies
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Drug name Price Pharmacy |
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Disaverox 300 mg + 150 mg film-coated tablets 60 pcs. 752 RUB Buy |
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
