Abacavir + Zidovudine + Lamivudine: instructions for using the medicine, structure, Contraindications

Registration certificate holder: ATOLL, LTD (Russia)

Made: OZONE, LTD (Russia)

ATX code: J05AR04 (Zidovudine, lamivudine and abacavir)

Active substances Abacavir + Zidovudine + Lamivudine

• zidovudine (zidovudine)WHO registered
• Abacavir (abacavir) WHO registered
• lamivudine (lamivudine) WHO registered

Dosage form Abacavir + Zidovudine + Lamivudine

[The drug is released under the prescription] Abacavir + Zidovudine + Lamivudine

Tab., cover. film-coated, 300 mg + 150 mg + 300 mg: 3, 6, 9, 10, 12, 15, 18, 20, 24, 30, 36, 40, 50, 60 or 100 PC.

reg. №: LP-005757 from 28.08.19 – Current

Product form, packaging and composition of the drug Abacavir + Zidovudine + Lamivudine

Pills, film-coated white or nearly white, Oval, lenticular, with Valium; on the cross section of the tablets are visible 2 layer: the core is white or white with a yellowish or brownish tint and the shell.

Excipients: microcrystalline cellulose (MKC-101) – 303.4 mg, krospovydon – 48.8 mg, povidone K-25 – 36 mg, magnesium stearate – 24.4 mg, colloidal silicon dioxide – 6.1 mg.

The composition of the shell: Opadry II 85F48105 white – 30 mg, incl. polyvinyl alcohol – 14.07 mg, macrogol – 7.08 mg, talc – 5.22 mg, Titanium dioxide – 3.63 mg.

3 PC. – packings Valium planimetric (PVC/aluminum foil) (1) – packs cardboard.
3 PC. – packings Valium planimetric (PVC/aluminum foil) (2) – packs cardboard.
3 PC. – packings Valium planimetric (PVC/aluminum foil) (3) – packs cardboard.
3 PC. – packings Valium planimetric (PVC/aluminum foil) (4) – packs cardboard.
3 PC. – packings Valium planimetric (PVC/aluminum foil) (5) – packs cardboard.
3 PC. – packings Valium planimetric (PVC/aluminum foil) (6) – packs cardboard.
3 PC. – packings Valium planimetric (PVC/aluminum foil) (10) – packs cardboard.
6 PC. – packings Valium planimetric (PVC/aluminum foil) (1) – packs cardboard.
6 PC. – packings Valium planimetric (PVC/aluminum foil) (2) – packs cardboard.
6 PC. – packings Valium planimetric (PVC/aluminum foil) (3) – packs cardboard.
6 PC. – packings Valium planimetric (PVC/aluminum foil) (4) – packs cardboard.
6 PC. – packings Valium planimetric (PVC/aluminum foil) (5) – packs cardboard.
6 PC. – packings Valium planimetric (PVC/aluminum foil) (6) – packs cardboard.
6 PC. – packings Valium planimetric (PVC/aluminum foil) (10) – packs cardboard.
10 PC. – packings Valium planimetric (PVC/aluminum foil) (1) – packs cardboard.
10 PC. – packings Valium planimetric (PVC/aluminum foil) (2) – packs cardboard.
10 PC. – packings Valium planimetric (PVC/aluminum foil) (3) – packs cardboard.
10 PC. – packings Valium planimetric (PVC/aluminum foil) (4) – packs cardboard.
10 PC. – packings Valium planimetric (PVC/aluminum foil) (5) – packs cardboard.
10 PC. – packings Valium planimetric (PVC/aluminum foil) (6) – packs cardboard.
10 PC. – packings Valium planimetric (PVC/aluminum foil) (10) – packs cardboard.
10 PC. – banks (1) – packs cardboard.
20 PC. – banks (1) – packs cardboard.
30 PC. – banks (1) – packs cardboard.
40 PC. – banks (1) – packs cardboard.
50 PC. – banks (1) – packs cardboard.
60 PC. – banks (1) – packs cardboard.
100 PC. – banks (1) – packs cardboard.

Clinical and pharmacological group: Viricide, active against HIV
Pharmaco-therapeutic group: Antiviral [HIV] means

Pharmacological action Abacavir + Zidovudine + Lamivudine

Combined antiviral agents. Abacavir, lamivudine and zidovudine – HIV nucleoside reverse transcriptase inhibitors, selectively inhibit HIV-1 and HIV-2 replication. Abacavir, lamivudine and zidovudine undergo successive stages of metabolism involving intracellular kinases and are converted into the corresponding 5'-triphosphates (TF). Abacavir-TF, lamivudine-TF and zidovudine-TF are substrates and competitive inhibitors of HIV reverse transcriptase.

The main antiviral effect of the active substances lies in their ability to be incorporated as a monophosphate into the synthesized HIV DNA., leading to a break in replication. Kinship of lamivudine, abacavir and zidovudine to DNA- host cell polymerases are much lower.

In in vitro obtained HIV strains, resistant to abacavir, mutations have been found in several codons of the reverse transcriptase gene (FROM) – M184V, K65R, L74Vи Y115F. HIV resistance to abacavir develops slowly in vitro and in vivo. For a clinically significant increase in inhibitory concentration in relation to 50% strains IC50 (in 8 times regarding the virus “wild” type) multiple mutations of the viral genome are required. Isolates, resistant to abacavir, may be less sensitive to the action of lamivudine, zalcitabine and / or didanosine, but completely retain sensitivity to zidovudine and stavudine. Failure of abacavir combination, lamivudine and zidovudine at the very beginning of treatment is usually due to only one mutation – M184V, therefore, the use of this combination preserves the possibility of a wide choice of second-line therapy regimens..

Pharmacokinetics Abacavir + Zidovudine + Lamivudine

Oral lamivudine, abacavir and zidovudine are rapidly and well absorbed from the gastrointestinal tract. Absolute bioavailability of lamivudine, abacavir and zidovudine after oral administration in adults is respectively 80-85%, 83% and 60-70%.

Vd lamivudine, abacavir and zidovudine with intravenous administration is an average 1.3, 0.8 and 1.6 l/kg respectively. Binding of lamivudine to the main plasma protein, albumin, insignificantly (in vitro less 36% serum albumin), the pharmacokinetics of lamivudine is linear. Zidovudine binds to plasma proteins at 34-38%. According to in vitro studies, Abacavir at therapeutic doses binds to serum proteins for approximately 49%.

Lamivudine, abacavir and zidovudine cross the BBB and are found in the cerebrospinal fluid (CSF). The ratio of serum concentrations of lamivudine and zidovudine to the corresponding drug concentrations in the CSF through 2-4 h after oral administration averages about 0.12 for lamivudine and 0.5 for zidovudine. According to studies in HIV-infected patients, abacavir penetrates well into the CSF, while the AUC of abacavir in the CSF is 30-44% from AUC of abacavir in plasma. In a clinical study 1 phase to study the pharmacokinetics of abacavir is shown, that through 1.5 hours after administration of abacavir at a dose 300 g 2 times/day its concentration in the CSF is 0.14 ug / ml. When using abacavir at a dose 600 mg 2 times/day, its concentration in the CSF increases with 0.13 ug / mL in 0.5-1 h after injection, to 0.74 ug / mL in 3-4 no. Thus, even if the concentration of abacavir in the CSF through 4 h after its administration at a dose 600 mg 2 times/day and does not reach a maximum, it exceeds IC50 (0.8 ug / ml or 0.6 mmol / l) about 9 time.

Abacavir is predominantly metabolized in the liver, only 2 % from the accepted dose is excreted unchanged by the kidneys. In humans, abacavir is metabolized, primarily, under the action of alcohol dehydrogenase with the formation of 5′- carboxylic acid and by conjugation with glucuronic acid to form 5'- glucuronide, that accounted for about 66% of total, drug excreted through the kidneys.

Lamivudine is eliminated unchanged by renal excretion..

Zidovudine, primarily, metabolised in the liver. The main metabolite of zidovudine in plasma and urine is zidovudine 5'-glucuronide., which is excreted by the kidneys and is approximately 50-80% of the dose. Other metabolites of zidovudine when administered parenterally are 3′-amino-3′-deoxygimidine (AMT).

T1 / 2 lamivudine is 5-7 no. The mean systemic clearance of lamivudine is about 0.32 l / h kg, most of it is renal clearance (more 70%), via the organic cation transport system. Studies in patients with renal insufficiency have shown, that impaired renal function affects the excretion of lamivudine.

Plasma levels of zidovudine are increased in patients with severe renal impairment.

The average T1 / 2 of abacavir is about 1.5 no. After multiple doses of abacavir at a dose 300 mg orally 2 times/day significant cumulation is not observed. Elimination of abacavir is via hepatic metabolism, followed by excretion of metabolites predominantly by the kidneys.. About 83% the administered dose of abacavir is excreted by the kidneys in the form of metabolites and unchanged, the remaining amount is excreted through the intestines.

In studies involving patients with renal insufficiency,, that impaired renal function affects the excretion of lamivudine due to a decrease in renal clearance. It was also shown, that in patients with severely impaired renal function, plasma concentrations of zidovudine are increased. Abacavir is metabolized primarily in the liver., less 2% it is excreted by the kidneys unchanged. The pharmacokinetics of abacavir in patients with end-stage renal disease is similar to that in patients with normal renal function..

Abacavir is metabolized, mainly, liver. The pharmacokinetics of abacavir has been studied in patients with mild hepatic impairment. (5-6 points on the Child-Pugh). The results of the study indicate an increase in the AUC of abacavir on average 1.89 times and an increase in T1 / 2 of abacavir in 1.58 times. Impaired liver function does not affect the AUC of abacavir metabolites, however, the rate of their formation and excretion is reduced.

Indications of the active substances of the drug Abacavir + Zidovudine + Lamivudine

Treatment of HIV infection in adults and older children 12 years in antiretroviral therapy.

Dosing regimen Abacavir + Zidovudine + Lamivudine

The method of application and dosing regimen of a particular drug depends on its form of release and other factors.. The optimal dosing regimen is determined by the doctor. Compliance of the dosage form of a particular drug with indications for use and dosing regimen should be strictly observed..

Orally. A single dose of the combination drug is taken 2 times / day.

If the body weight of a teenager or adult is below 40 kg this combination is not applicable, since the dose of each active substance is fixed and it is not possible to reduce the dose for each active substance separately.

In case of impaired liver and / or kidney function, correction of the dosing regimen is required..

Side effects Abacavir + Zidovudine + Lamivudine

Symptoms of a hypersensitivity reaction (RGCH)

From the hematopoietic system: lymphopenia.

From the nervous system: headache, paresthesia.

The respiratory system: breathlessness, cough, sore throat, respiratory distress syndrome, respiratory insufficiency.

From the digestive system: nausea, vomiting, diarrhea, abdominal pain, ulceration in the mouth, increase in liver function tests, hepatic failure.

From the urinary system: increase in serum creatinine, renal failure.

Skin and subcutaneous fat: rash (maculopapular or urticarial).

On the part of the musculoskeletal system: myalgia, rarely – myolysis, arthralgia, Increase CPK activity.

Other: fever, feeling tired, malaise, edema, lymphadenopathy, low blood pressure, conjunctivitis, anaphylaxis.

If any of these symptoms appear, a thorough examination of the patient is necessary to exclude a hypersensitivity reaction.. If a hypersensitivity reaction cannot be ruled out, re-prescribing the combination of abacavir + lamivudine + zidovudine or other drugs, containing abacavir, strictly contraindicated.

Determination of the frequency of adverse reactions: Often (≥1/10); often (≥1/100, <1/10); infrequently (≥1/1000, <1/100); rarely (≥1/10 000, <1/1000); rarely (<1/10 000).

Abacavir – side effects

On the part of the immune system: often – hypersensitivity reactions.

From the nervous system: often – headache.

From the digestive system: often – anorexia, nausea, vomiting, diarrhea; rarely – pancreatitis.

Metabolism: often – hyperlactataemia; rarely – Lactic acidosis.

Skin and subcutaneous fat: often – rash (no systemic symptoms); rarely – mnogoformnaya Erythema ekssoudatus, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Other: often – fever, apathy, feeling tired.

Lamivudine – side effects

From the hematopoietic system: infrequently – neutropenia, anemia, thrombocytopenia; rarely – istinnaya эritrotsitarnaya aplasia.

Metabolism: often – hyperlactataemia; rarely – Lactic acidosis.

From the nervous system: often – headache; rarely – paresthesia, perifericheskaya neuropathy.

From the digestive system: often – nausea, vomiting, pain in the upper abdomen, diarrhea; infrequently – temporary increase in AST, GOLD; rarely – increase in serum amylase activity, pancreatitis.

Skin and subcutaneous fat: often – rash, alopecia.

On the part of the musculoskeletal system: often – arthralgia, muscle damage; rarely – raʙdomioliz.

Other: often – feeling tired, malaise, temperature rise.

Some patients, who received combination antiretroviral therapy, there was a redistribution/accumulation of adipose tissue in the body. The frequency of this phenomenon depends on many factors., incl. from a combination of antiretroviral drugs.

Zidovudine – side effects

From the hematopoietic system: often- anemia (blood transfusion may be required), neutropenia and leukopenia. These side effects are more likely to occur with high doses of zidovudine. (1200–1500 mg / day), in patients with advanced HIV infection (especially with reduced bone marrow reserve before treatment) and, in particular, in patients with CD4+ cell count less than 100/mcL. In some patients, it is necessary to reduce the dose of zidovudine up to withdrawal. Neutropenia occurs more frequently in those patients, who have a neutrophil count, serum hemoglobin and vitamin B12 levels are reduced at the time of initiation of zidovudine treatment. Infrequently – thrombocytopenia and pancytopenia (with bone marrow hypoplasia); rarely – istinnaya эritrotsitarnaya aplasia; rarely – aplasticheskaya anemia.

Metabolism: often – hyperlactataemia; rarely- Lactic acidosis, anorexia; redistribution/accumulation of adipose tissue (The frequency of this side effect depends on many factors., incl. from a specific combination of antiretroviral drugs).

On the part of the psyche: rarely – anxiety and depression.

From the nervous system: Often – headache; often – dizziness; rarely – insomnia, paresthesia, drowsiness, decreased mental activity, convulsions.

On the part of the organ of vision: Frequency unknown – macular edema, amblyopia, photophobia.

On the part of the organ of hearing: vertigo, hearing loss.

Cardio-vascular system: rarely – cardiomyopathy.

The respiratory system: infrequently – breathlessness; rarely – cough.

From the digestive system: Often – nausea; often – vomiting, abdominal pain and diarrhea, increased activity of liver enzymes and bilirubin concentration; infrequently – flatulence; rarely – pigmentation of the oral mucosa, disgevziya, dyspepsia, pancreatitis, liver disease, such as severe hepatomegaly with steatosis.

Skin and subcutaneous fat: infrequently – rash and itching; rarely – pigmentation of nails and skin, Sweating.

On the part of the musculoskeletal system: often – myalgia; infrequently – myopathy.

From the urinary system: rarely – frequent urination.

From the reproductive system and mammary gland: rarely – gynecomastia.

Allergic reactions: rarely – hives.

Other: often – general malaise; infrequently – fever, generalized pain syndrome and asthenia; rarely – chills, chest pain, flu-like symptoms.

Contraindications to the use of Abacavir + Zidovudine + Lamivudine

Moderate to severe liver failure (class B and C on the Child scale- Drink); mild liver failure (Class A on Child-Pugh); impairment of renal function (CC <50 ml / min); pronounced decrease in the content of neutrophils (less than 0.75×109l) or hemoglobin concentration (less 7.5 g / dl, or 4.65 mmol / l) due to the content of zidovudine; Age to 12 years (due to the inability to adjust the dose); weight less 40 kg.

Carefully

Suppression of bone marrow hematopoiesis (at a hemoglobin concentration less than 9 g / l (5.59 mmol / l) or the content of neutrophils in the blood is less than 1.0 × 109 / l) dose adjustment of zidovudine may be required (with the development of these adverse reactions, abacavir, zidovudine and lamivudine are used as separate preparations); pancreatitis (incl. history); gepatomegaliya, hepatitis, any risk factors for liver disease; the presence of risk factors for the development of coronary artery disease; Elderly patients.

Abacavir + Zidovudine + Lamivudine – use during pregnancy and lactation

The safety of this combination in women during pregnancy has not yet been studied.. There is evidence from studies on the effects of abacavir, lamivudine and zidovudine on fetal development in animals. Therefore, during pregnancy, drugs, containing this combination is used only if, if the expected benefit to the mother outweighs the risk to the fetus.

Influence of abacavir, lamivudine and zidovudine on fertility in women has not yet been studied. For zidovudine,, that its use in men does not affect the number, morphology and motility of spermatozoa.

Experts do not recommend breastfeeding to HIV-infected patients, to avoid passing HIV to a child. Because abacavir, its metabolites and HIV pass into breast milk, breastfeeding is contraindicated.

Application for violations of liver function – Abacavir + Zidovudine + Lamivudine

The use of the drug is contraindicated in cases of moderate and severe liver dysfunction..

Abacavir + Zidovudine + Lamivudine – Application for violations of renal function

In patients with impaired renal function, the dose of lamivudine should be reduced in proportion to the decrease in CC.. In this regard, it is not recommended to use the drug for CC less 50 ml / min.

Use in children Abacavir + Zidovudine + Lamivudine

Contraindicated in children under the age of 12 years due to the inability to adjust the dose.

Cautions – Abacavir + Zidovudine + Lamivudine

Use of drugs, containing this combination is associated with a risk of developing a hypersensitivity reaction (RGCH), characterized by fever and/or rash and other symptoms, indicative of multiple organ damage. HSR can be life threatening and in rare cases can be fatal if left untreated. The risk of developing HSR with this combination is significantly increased in patients with a positive test result for the presence of the HLA-B * 5701 allele.. However, HSR for abacavir were observed at a lower frequency in patients, not carrying this allele.

Testing for the presence of the HLA-B*5701 allele should be performed prior to starting therapy with the combination, and also before resuming therapy with this combination in patients with unknown status for the HLA-B*5701 allele., who have previously tolerated abacavir therapy well.

Not recommended for use in patients with the HLA-B * 5701 allele, if patients, in whom HSR was suspected during the use of any other drug, containing abacavir, regardless of status with respect to the HLA-B*5701 allele.

All patients, treated with this combination, the clinical diagnosis of suspected HSR should remain the basis for clinical decision making.

If HSR is suspected, therapy with this combination should be stopped immediately even in the absence of the HLA-B*5701 allele.. Delay in stopping therapy with this combination after the onset of HSR can lead to a life-threatening situation..

Resuming the use of drugs, containing abacavir after suspected abacavir HSR, can lead to a rapid return of symptoms within a few hours, which may include life-threatening hypotension and death.

When considering resuming abacavir therapy after stopping treatment with any drug, containing abacavir for any reason, the reason for discontinuing therapy should be established, regardless of whether the patient carries the HHA-B * 5701 allele. If MIRV cannot be ruled out, drugs cannot be restarted, containing this combination, as well as any other drugs, containing abacavir.

If MIRV is excluded, it is possible to resume therapy with this combination. In rare cases, patients, discontinued abacavir for reasons, other than the symptoms of HSR, also noted the development of life-threatening reactions within a few hours after the resumption of therapy with abacavir. Restarting therapy with this combination or other drugs, containing abacavir, should only be carried out if there is quick access to medical care.

There are reports of the development of lactic acidosis and severe hepatomegaly with steatosis., incl. fatal, due to antiretroviral therapy with nucleoside analogues in the form of separate drugs, including abacavir. lamivudine and zidovudine, or their combinations. Similar phenomena were noted mainly in women..

Caution should be exercised when using this combination, especially in patients with hepatomegaly, hepatitis or other risk factors for liver damage and hepatic steatosis (including certain drugs and alcohol). Patients co-infected with hepatitis C virus and patients, who are being treated with alpha interferon and ribavirin, may constitute a particular risk group. This combination should be discontinued if there are clinical or laboratory signs of lactic acidosis with or without hepatitis. (which include hepatomegaly and steatosis, even in the absence of a significant increase in aminotransferase activities), symptomatic hyperlacgatemia and metabolic acidosis/lactic acidosis, progressive hepatomegaly or with a rapid increase in aminotransferase activity.

In vitro and in vivo studies have shown, that nucleoside and nucleotide analogs are capable of causing varying degrees of mitochondrial damage. There have been cases of mitochondrial dysfunction in HIV-negative children, treated intrauterine and/or postnatally with nucleoside analogs. The main adverse reactions were hematological disorders (anemia, neutropenia), metabolic disorders (hyperlactataemia, hyperlipasemia). These adverse reactions are often transient. Some neurological disorders with late onset have been reported (increase in muscle tone, convulsions, behavioral disturbances). Are these neurological disorders transient or permanent?, currently unknown. Any child, even HIV negative, exposed in utero to nucleoside and nucleotide analogues, should undergo clinical and laboratory examination to rule out mitochondrial dysfunction if relevant signs or symptoms are identified. These data do not affect current national recommendations for the use of APT in pregnant women to prevent vertical transmission of HIV infection..

Treatment with zidovudine was accompanied by loss of subcutaneous fat. The incidence and severity of lipoatrophy are related to cumulative exposure. This fat loss, which is most pronounced on the face, limbs and buttocks, can only be partially reversible, and improvement may not occur until a few months after switching to a treatment regimen, not containing zidovudine. During therapy with zidovudine and other drugs, containing zidovudine, patients should be monitored regularly for signs of lipoatrophy, and if lipoatrophy is suspected, if possible, switch to an alternative regimen of therapy.

Serum lipid and blood glucose concentrations may increase during antiretroviral therapy.. Disease control and lifestyle changes may also contribute to this process.. The need to determine the concentration of serum lipids and blood glucose should be considered.. Lipid disorders need to be treated, according to their clinical manifestations.

During treatment, it is necessary to carefully monitor hematological parameters..

If symptoms or laboratory evidence of pancreatitis occur, treatment should be discontinued immediately..

In patients with pre-existing hepatic impairment, including active chronic hepatitis, there is an increase in the frequency of liver dysfunction with combined APT. These patients should be monitored in accordance with standard clinical practice.. If liver function worsens in such patients, suspension or discontinuation of this combination should be considered..

In patients with chronic hepatitis B or C, receiving combined APT, increased risk of serious and deadly liver side effects. In the case of concomitant use of antiviral therapy for hepatitis B or C, refer to the instructions for use of these medicinal products. When treatment is discontinued in patients with concomitant viral hepatitis B, liver function tests should be monitored and viral load should be measured regularly., tk. possible recurrence of hepatitis after discontinuation of lamivudine, which may be more severe in patients with decompensated liver disease.

The results of clinical studies and post-registration data indicate that, that in some patients with chronic hepatitis B, when lamivudine is discontinued, clinical and laboratory signs of hepatitis recurrence may occur, which may have more severe consequences in patients with decompensated liver disease. If this combination is discontinued in patients with concomitant viral hepatitis B, consideration should be given to periodic monitoring of liver function and markers of hepatitis B virus replication..

When using zidovudine as part of an HIV treatment regimen, there have been cases of exacerbation of anemia while taking ribavirin, the exact mechanism of this phenomenon remains unknown.. In this regard, the simultaneous use of zidovudine with ribavirin is not recommended.. If zidovudine is already included in a combination antiretroviral therapy regimen, should consider replacing it. This is especially important for patients with a history of zidovudine-induced anemia..

If HIV-infected patients with severe immunodeficiency have asymptomatic opportunistic infections or their residual effects at the time of initiation of antiretroviral therapy, its administration may activate the inflammatory process and lead to an increase in the symptoms of opportunistic infections or other serious consequences. These reactions usually occur within the first weeks or months of starting antiretroviral therapy..

Autoimmune diseases (such as Grace's disease, polymyositis and Guillain's syndrome- Barre) were observed against the background of restoration of immunity, however, the time to onset varied, and the disease could occur many months after the start of therapy and have an atypical course.

The use of this combination or other antiretroviral drugs does not exclude the possibility of developing opportunistic infections or other complications of HIV infection., therefore, patients should remain under medical supervision, experienced in the treatment of these diseases.

Despite, that the etiology of osteonecrosis is multifactorial (including taking corticosteroids, alcohol consumption, severe immunosuppression, High BMI), cases of osteonecrosis were most common in patients with advanced HIV infection and/or long-term use of combined APT. Patients should see a doctor, if they experience pain and stiffness in the joints or difficulty moving.

Patients should be warned about, that treatment with antiretroviral drugs does not prevent the risk of transmission of HIV to others through sexual contact and blood contamination. Therefore, patients should take appropriate precautions.

Antiretroviral therapy should be used with caution, including abacavir, patients at risk for coronary artery disease. All measures must be taken to minimize modifiable risk factors (such as hypertension, hyperlipidemia, diabetes and smoking).

Patients should be warned against self-medication with any drugs..

This combination should not be used with drugs, containing lamivudine or emtricitabine.

The concomitant use of stavudine and zidovudine should be avoided..

The use of lamivudine with cladribine is not recommended..

Drug interactions Abacavir + Zidovudine + Lamivudine

Drug Interactions, due to the presence of abacavir

The metabolism of abacavir is impaired when taken concomitantly with ethanol, resulting in an increase in the AUC of abacavir by approximately 41%. Given the safety profile of abacavir, these data are not regarded as clinically significant. Abacavir has no effect on ethanol metabolism.

In a study of the pharmacokinetics of drugs while taking abacavir (dose 600 mg 2 times / day) and methadone, there was a decrease in Cmax of abacavir by 35% and reducing the time to reach Cmax by 1 no, however, AUC remained unchanged. Changes in the pharmacokinetics of abacavir were not considered clinically significant.. In this study, abacavir increased the mean total clearance of methadone by 22%. This change was not considered clinically significant in most patients., however, sometimes it may be necessary to adjust the dose of methadone.

Drug Interactions, due to the presence of lamivudine

Taking trimethoprim/sulfamethoxazole 160 mg / 800 mg (co-trimoxazole) causes an increase in lamivudine exposure to 40%, due to the presence of trimethoprim. But, except in patients with renal insufficiency, dose adjustment of lamivudine is not required.

Lamivudine may inhibit intracellular phosphorylation of zalcitabine while taking these drugs. In this regard, the use in combination with zalcitabine is not recommended..

Cooperation, due to the presence of zidovudine

Zidovudine does not affect the pharmacokinetics of atovaquone. However, pharmacokinetic data suggest that, that atovaquone reduces the rate of metabolism of zidovudine to its glucuronide (at steady state, the AUC of zidovudine increases by 33%, Cmax in plasma glucuronide is reduced by 19%). When prescribing zidovudine at doses of 500-600 mg / day and a concomitant 3-week course of treatment of acute pneumocystis pneumonia with atovaquone, an increase in the frequency of adverse reactions, associated with elevated plasma zidovudine concentrations, unlikely. If more prolonged combined use of these drugs is necessary, careful monitoring of the patient's clinical condition is recommended..

Absorption of zidovudine is reduced when clarithromycin tablets are taken concomitantly.. It is necessary to observe the interval between taking clarithromycin and zidovudine for at least 2 no.

Some patients, treated with zidovudine plus phenytoin, a decrease in the concentration of phenytoin in the blood was detected, and in one case there was an increase in the concentration of phenytoin. These observations indicate the need to control blood concentrations of phenytoin in patients, who are taking the combination of zidovudine + lamivudine and phenytoin at the same time.

According to some reports, probenecid increases the mean T1 / 2 of zidovudine and AUC as a result of inhibition of the formation of glucuronide. In the presence of probenecid, renal excretion of glucuronide is reduced and, perhaps, the zidovudine itself.

Limited data show, that the combined use of zidovudine and rifampicin reduces the AUC of zidovudine by 48±34%. However, the clinical significance of this observation is unknown..

Zidovudine can inhibit the process of intracellular phosphorylation of stavudine with their simultaneous use.. Thus, the simultaneous use of stavudine and the combination of zidovudine + lamivudine is not recommended.

Nucleoside analogs, disrupting DNA replication, such as Ribavirin, may reduce the antiviral activity of zidovudine in vitro. The concomitant use of these medicinal products with zidovudine is not recommended.. There was an increase in anemia, caused by ribavirin when zidovudine is included in the complex therapy of HIV infection. The use of zidovudine in combination with ribavirin is not recommended due to an increased risk of anemia..

The simultaneous use of zidovudine and doxorubicin is not recommended due to the mutual weakening of the activity of each of the drugs in vitro..

With simultaneous use with fluconazole, an increase in the AUC of zidovudine by 74% by inhibition of UDP-glucuronosyltransferase. Given the limited data, the clinical significance is unknown. It is necessary to control the toxic effects of zidovudine.

With simultaneous use with valproic acid, an increase in the AUC of zidovudine by 80% by inhibition of UDP-glucuronosyltransferase. Given the limited data, the clinical significance is unknown. It is necessary to control the toxic effects of zidovudine.

Acetylsalicylic acid, codeine, morphine, Indomethacin, Ketoprofen, naproxen, oxazepam, Lorazepam, cimetidine, clofibrate, dapsone, inosine pranobex (drug Groprinosin) able to change the metabolism of zidovudine as a result of competitive inhibition of the process of glucuronidation or direct suppression of the metabolism of zidovudine by microsomal liver enzymes. Before prescribing these drugs in combination with the combination of zidovudine + lamivudine, especially for long-term treatment, potential drug interactions need to be assessed.

The simultaneous use of, especially for the treatment of acute conditions, zidovudine and potentially nephrotoxic or myelosuppressive drugs (eg, systemic administration of pentamidine, dapsone, pyrimethamine, co-trimoxazole, Amphotericin B, Flucytosine, ganciclovir, interferon, vinchristina, vinblastine and doxorubicin) may also increase the risk of side effects of zidovudine. If zidovudine+lamivudine is co-administered with any of these agents, renal function and haematological parameters should be closely monitored and the dose of one or more agents reduced if necessary..

Unnecessarily. some patients, despite the combination, opportunistic infections may develop, additional therapy may be required to prevent infections. For such prophylaxis, co-trimoxazole is used., pentamidine aerosol, pyrimethamine and acyclovir. Limited data from clinical studies suggest that there is no significant increase in the incidence of side effects of zidovudine when it is used concomitantly with these drugs..