Combivir is an antiviral agent that is active against the human immunodeficiency virus (HIV).
Release form and composition
Combivir dosage form - coated tablets (oval, white or almost white, on both sides of the risk and the engraved inscription "GXFC3"), 10 pcs. in aluminum or polyvinyl chloride blisters, in a cardboard bundle 6 blisters.
Active ingredients of the drug (in 1 tablet):
- Zidovudine - 300 mg;
- Lamivudin - 150 mg.
Auxiliary components: colloidal anhydrous silicon, sodium carboxymethyl starch (type A), microcrystalline cellulose, magnesium stearate.
The composition of the film shell: opadry white, including titanium dioxide, hypromellose, polysorbate 80 and macrogol 400.
Indications for use
Treatment of HIV infection in adults and children weighing at least 14 kg.
- Severe anemia, in which the hemoglobin level is less than 7.5 g / dL or 4.65 mmol / l).
- Severe neutropenia (if the number of neutrophils is less than 0.75 × 10 9 / l);
- Hypersensitivity to the drug.
It has been established that the treatment of pregnant women with zidovudine and the subsequent introduction of this drug to the newborn reduces the frequency of mother-to-child transmission of HIV. Concerning lamivudine, there is no such data, therefore, during pregnancy, Combivir is prescribed only if the expected benefit to the woman outweighs the possible risks to the fetus.
Dosing and Administration
Combivir is taken orally, at any convenient time without reference to meals. Tablets preferably swallow whole. People who have difficulty swallowing can be crushed and added to a small amount of liquid or semi-solid food, but the entire amount of the mixture obtained should be taken immediately.
- Adults and adolescents weighing more than 30 kg - 1 tablet 2 times a day;
- Children weighing 21-30 kg - 1/2 tablet in the morning and 1 tablet in the evening;
- Children weighing 14-21 kg - 1/2 tablet 2 times a day.
For children weighing up to 14 kg, as well as in cases when it is necessary to reduce the dose or cancel one of the components, separate preparations containing only lamivudine (Epivir) or only zidovudine (Retrovir) are prescribed.
Patients with impaired renal function, severely impaired liver function, reduced hemoglobin content of less than 9 g / dL (5.59 mmol / l) and neutropenia need to individually select the dose of zidovudine and lamivudine, so they are recommended to prescribe certain drugs.
Since Combivir contains two active ingredients, the drug may have side effects that are characteristic of each of them. There is currently no evidence that the combination of lamivudine and zidovudine has additive (total) toxicity.
Possible side effects from lamivudine:
- Hematopoietic and lymphatic systems: infrequently - thrombocytopenia, anemia, neutropenia; very rarely - true red cell aplasia;
- Nervous system: often - headache; in some cases, paresthesia, there are reports of the development of peripheral neuropathy, but the causal relationship with the use of lamivudine has not been reliably established;
- Metabolism and nutrition: often - hyperlactatemia; rarely lactic acidosis;
- Gastrointestinal tract: often - diarrhea, nausea, epigastric pain, vomiting; rarely, elevated serum amylase, pancreatitis, which has not been established to connect with lamivudine;
- Musculoskeletal system and connective tissue: often - muscular disorders, arthralgia; rarely - rhabdomyolysis;
- Liver and biliary tract: infrequent - transient increase in liver enzymes;
- Skin and subcutaneous fat: often - a rash, alopecia;
- General and local reactions: often - general malaise, fatigue, fever.
Possible side effects due to zidovudine:
- Hematopoietic and lymphatic system: often - neutropenia, leukopenia, anemia (these disorders often occur when taking high doses and in patients with advanced stages of HIV infection and, in particular, in patients with a CD4 cell count less than 100 / mm 3 ); infrequently, pancytopenia and thrombocytopenia with bone marrow hypoplasia; rarely - true red cell aplasia; in individual cases - aplastic anemia;
- Nervous system: rarely - anxiety and depression;
- Metabolism and nutrition: often - hyperlactatemia; rarely - anorexia, lactic acidosis;
- Cardiovascular system: rarely - cardiomyopathy;
- Liver and biliary tract: often - increased levels of bilirubin and liver enzymes; rarely severe hepatomegaly with steatosis;
- Respiratory system, organs of the chest and mediastinum: infrequently - shortness of breath; rarely cough;
- Nervous system: very often - headache; often - dizziness; rarely - drowsiness, paresthesia, decreased mental activity, insomnia, convulsions;
- Kidneys and urinary tract: rarely - urinating;
- Gastrointestinal tract: very often - nausea; often - abdominal pain and diarrhea, vomiting; infrequently - flatulence; rarely - dyspepsia, taste perversion, pigmentation of the oral mucosa, pancreatitis;
- Skin and subcutaneous fat: infrequently - rash and itching; rarely - urticaria, pigmentation of the nails and skin, sweating;
- Musculoskeletal system and connective tissue: often - myalgia; infrequently - myopathy;
- Reproductive system and mammary glands: rarely –ginecomastia;
- General and local reactions: often - general malaise; infrequently - asthenia, generalized pain syndrome, fever; rarely - flu-like syndrome, chest pain, chills.
Despite taking Combivir or any other antiretroviral drug, there is a likelihood of opportunistic infections and other complications of HIV infection, so treatment should be carried out under the close supervision of doctors who have experience in treating HIV infection.
All patients should be informed that Combivir does not prevent the risk of transmitting HIV to other people through blood transfusion and sexual contact, therefore, appropriate precautions should be observed.
Specific data on the use of the drug in the elderly is not, however, it is recommended to take into account age-related changes, for example, impaired renal function and changes in hematological parameters.
At the beginning of treatment (usually during the first weeks or months) of patients with severe immunodeficiency, the inflammatory process may worsen with the development of a residual or asymptomatic opportunistic infection, which can lead to a serious deterioration of the condition or worsening of symptoms. The most significant examples are pneumocystic pneumonia, focal and / or generalized mycobacterial infection, cytomegalovirus retinitis. For this reason, it is very important to carefully monitor the condition of the patients in order to detect any symptoms of inflammation in time and, if necessary, initiate appropriate treatment.
With extreme caution, Combivir treatment is carried out in patients with decompensated liver cirrhosis caused by chronic hepatitis B, since with the abolition of lamivudine may exacerbate hepatitis. During therapy, liver function and hepatitis B virus replication markers should be monitored.
- Possible interactions involving lamivudine.
With the simultaneous use of a combination of trimethoprim and sulfamethoxazole, it is possible to increase the concentration of lamivudine in the plasma by 40%. For this reason, the condition of patients with renal insufficiency should be monitored.
Lamivudine may inhibit the intracellular phosphorylation of zalcitabine, so this combination is undesirable.
Since lamivudine is derived mainly through the cationic transport system, it is necessary to remember about the possibility of interaction of Combivir with drugs that have the same route of elimination.
- Possible interactions involving zidovudine.
Atovakvon reduces the degree of zidovudine metabolism to its glucuronide. If necessary, the use of such a combination for more than 3 weeks in a row should carefully monitor the clinical condition of the patient.
Clarithromycin reduces zidovudine absorption, therefore between their reception it is necessary to observe intervals not less than 2 hours.
With the simultaneous use of phenytoin, there are known cases of both a decrease in its concentration in the blood and an increase. These data suggest the need to control the content of this substance in patients taking such a combination.
Probenecid reduces the renal excretion of glucuronide and, possibly, zidovudine itself.
According to limited data, rifampicin reduces the total plasma concentration of zidovudine by 48 ± 34%; however, the clinical values of this observation are unknown.
The simultaneous use of Combivir with stavudine is not recommended, since zidovudine can inhibit the process of its intracellular phosphorylation.
Isoprinosine, clofibrate, morphine, codeine, methadone, acetylsalicylic acid, indomethacin, oxazepam, naproxen, lorazepam, dapsop, cimetidine, ketoprofen can alter zidovudine metabolism. Before prescribing these drugs in combination with Combivir, especially when long-term use is necessary, it is necessary to evaluate possible drug interactions.
The simultaneous use, especially for the treatment of acute conditions, potentially nephrotoxic or myelosuppressive drugs (for example, pyrimethamine, dapsone, co-trimoxazole, ganciclovir, flucytosine, interferon, amphotericin B, vincristine, doxorubicin, vinblastine pentamidine) may increase the risk of the effects of these effects. If necessary, the use of Combivir in combination with any of the listed drugs should monitor kidney function and hematological parameters, if necessary, reduce the dose.
Since some patients, despite the use of Combivir, are likely to develop opportunistic infections, additional antimicrobial therapy may be required to prevent them. Most often for these purposes pentamidine is used in the form of an aerosol, acyclovir, pyrimethamine, co-trimoxazole. According to limited data from clinical studies, an increase in the incidence of side effects when using zidovudine simultaneously with these drugs is not observed.
Terms and conditions of storage
Store at temperatures up to 30 ºC in a place with limited access to children.
Shelf life - 2 years.