Abamune-L (Abacavir and Lamivudine) – buy generic Kivexa from Cipla. Medicinal reference book geotar Release form and packaging

Russian name

Abacavir + Lamivudine

Latin name of the substances Abacavir + Lamivudine

Abacavirum + Lamivudinum ( genus. Abacaviri + Lamivudini)

Pharmacological group of substances Abacavir + Lamivudine

Use during pregnancy and breastfeeding

Typical clinical and pharmacological article 1

Pharmaceutical action. Combined antiviral (HIV) agent, nucleoside reverse transcriptase inhibitor, powerful selective inhibitor of HIV-1 and HIV-2. Abacavir and lamivudine are metabolized by intracellular kinases to the corresponding triphosphates, which act as active metabolites. Lamivudine triphosphate and carbovir triphosphate (the active triphosphate of abacavir) are competitive inhibitors of HIV reverse transcriptase. However, the main antiviral effect is due to the incorporation of monophosphate into the DNA chain, which as a result is broken. Triphosphates of abacavir and lamivudine have significantly lower affinity for DNA polymerases of host cells.

Pharmacokinetics. With mild liver failure (5-6 on the Child-Pug scale), AUC of abacavir increases by 1.89 times, T 1/2 - by 1.58 times. The AUC of individual metabolites does not change, but the rate of their formation and elimination is reduced. In renal failure, the AUC of lamivudine increases due to decreased clearance.

Indications. HIV (as part of combination therapy with other antiretroviral drugs).

Contraindications. Hypersensitivity, liver failure, chronic renal failure (creatinine clearance less than 50 ml/min), concomitant use with zalcitabine, body weight less than 40 kg, childhood(up to 12 years), lactation period.

With caution. Age over 65 years, pregnancy (taking into account the expected benefits for the mother and possible risk for the fetus).

Dosing. Orally, regardless of food intake, 600 mg of abacavir + 300 mg of lamivudine once a day.

Side effect. In 5% of patients taking abacavir, a hypersensitivity reaction (including death) may develop, which most often develops in the first 6 weeks from the start of taking the drug (on average after 11 days) in the form of symptoms of multiple organ damage.

Almost all patients (with the exception of isolated cases) experienced an increase in body temperature and/or the appearance of a maculopapular rash or urticaria.

From the skin: 10% or more - maculopapular rash or urticaria.

From the digestive system: 10% or more - nausea, vomiting, diarrhea, abdominal pain, increased activity of liver enzymes; liver failure, ulceration of the oral mucosa.

From the respiratory system: 10% or more - shortness of breath, cough; sore throat, respiratory distress syndrome, respiratory failure.

From the nervous system: 10% or more - headache; paresthesia.

From the hematopoietic organs: lymphopenia.

From the musculoskeletal system: 10% or more - myalgia; rarely myolysis, arthralgia, increased CPK.

From the urinary system: hypercreatinemia, renal failure.

Other: 10% or more - increased body temperature, feeling tired, malaise; edema, lymphadenopathy, decreased blood pressure, conjunctivitis, anaphylaxis.

Side effects of abacavir or lamivudine are grouped by frequency: very often (more than 1/10), often (more than 1/100 less than 1/10), less often (more than 1/1000 and less than 1/100), rarely (more than 1/10000 and less than 1/1000) and very rarely (less than 1/10000).

According to clinical studies.

Abacavir.

From the digestive system: often - nausea, vomiting, diarrhea.

Metabolic disorders: often - anorexia.

Other: often hypersensitivity, increased body temperature, apathy, feeling tired.

Lamivudine.

From the nervous system: often - headache.

From the hematopoietic organs: less often - neutropenia, anemia, thrombocytopenia.

From the digestive system: often - nausea, vomiting, pain in the upper abdominal cavity, diarrhea; less often - temporary increase in the activity of ALT, AST.

From the skin: often - rash.

Other: often - feeling tired, malaise, increased body temperature.

Post-registration data.

Abacavir.

From the digestive system: rarely - pancreatitis ( causation with taking the drug has not been established).

From the skin: often - rash (without systemic symptoms); very rarely - exudative erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis.

Lamivudine.

From the nervous system: very rarely - paresthesia, peripheral neuropathy (a causal relationship has not been established).

From the digestive system: rarely - increased activity of serum amylase, pancreatitis (a causal relationship has not been established).

From the hematopoietic organs: very rarely - true erythrocyte aplasia.

From the musculoskeletal system: often - arthralgia, muscle damage; rarely - rhabdomyolysis.

From the skin: often - alopecia.

Metabolism: often - hyperlactatemia, rarely - lactic acidosis.

With combination antiretroviral therapy, redistribution/accumulation of fat in the body is observed, the frequency of which depends on many factors (including the combination of antiretroviral drugs) and lactic acidosis.

Overdose. Symptoms: increased side effects.

Treatment: symptomatic, hemodialysis (to remove lamivudine).

Interaction. Abacavir and lamivudine are slightly metabolized by enzymes of the cytochrome P450 system (CYP3A4, CYP2C9, CYP2D6) and do not have an inhibitory or inducing effect on them, therefore the likelihood of interaction with anti-retroviral non-nucleoside protease inhibitors and other drugs, the metabolism of which occurs with the participation of enzymes of the cytochrome P450 system, is low.

When administered concomitantly with ethanol, the AUC of abacavir increases by 41%.

When taking abacavir (600 mg 2 times a day) with methadone, the Cmax of abacavir decreases by 35%, TCmax increases by 1 hour, AUC does not change; methadone clearance increases by 22%.

Administration of trimethoprim/sulfamethaxozole at a dose of 160 mg/800 mg causes an increase in the AUC of lamivudine by 40%.

Lamivudine suppresses the intracellular phosphorylation of zalcitabine when taken simultaneously and significantly enhances the effect of zidovudine.

Abacavir enhances the effect of amprenavir, nevirapine and zidovudine. The effect of the drug is enhanced in combination with didanosine, zalcitabine, stavudine and lamivudine.

Special instructions. Treatment should be carried out by a doctor experienced in using the drug.

The drug should not be used in cases where dose adjustment is necessary (creatinine clearance less than 50 ml/min, liver failure) due to the presence of fixed doses of individual components in one tablet. In such cases, monotherapy is carried out with abacavir or lamivudine.

In 5% of patients taking abacavir, a hypersensitivity reaction is observed (usually in the first 6 weeks), which in rare cases leads to death. If symptoms of multiple organ damage appear (fever and/or rash, weakness, malaise, nausea, vomiting, diarrhea, abdominal pain, shortness of breath, sore throat, cough, radiological signs of organ damage chest(infiltrates)), you should stop and never resume taking the drug, as well as other drugs containing abacavir. Recurrence of a hypersensitivity reaction is more severe (compared to the first reaction) and may be accompanied by a decrease in blood pressure (even death).

The risk of developing a hypersensitivity reaction to abacavir is determined by a genetic factor (the presence of the HLA-B5701 allele), which is present in 50% of Caucasian patients, 8% of Black patients and 22% of Hispanic patients. However, the basis of diagnosis is the presence clinical symptoms hypersensitivity reactions regardless of whether the HLA-B5701 allele is present or not.

When taking the drug, it is possible to develop lactic acidosis, severe hepatomegaly with steatosis, incl. with fatal outcome. The drug should be suspended even in the absence of a significant increase in transaminase activity.

Some patients experience a redistribution of fat in the body: an increase in the back of the neck and back (“buffalo hump”), enlargement of the mammary glands, and a decrease in fat in the periphery and in the face. The development of lipodystrophy, hyperglycemia and hyperlipidemia is possible.

When prescribing the drug in patients with concomitant viral hepatitis Liver function tests and markers of hepatitis B viral replication should be monitored.

When taking the drug, opportunistic infections and other complications of HIV may develop.

Abacavir-resistant patients have reduced sensitivity to lamivudine, zalcitabine, tenofovir, emtricitabine and/or didanosine, but remain sensitive to zidovudine and stavudine.

Development of cross-resistance between abacavir, lamivudine and antiretroviral drugs

Abamune-L (Abacavir and Lamivudine) – buy generic Kivexa from Cipla:

The drug Abamune-L from Cipla (India) is an analogue of the drug Kivexa and combines two active antiviral substances Abacavir 600 mg. and Lamivudine 300 mg. in each tablet. Generic Abamune-L is an excellent, effective and high-quality antiviral drug for treating patients suffering from severe HIV types 1 and 2. It blocks the spread and development (replication) of the virus in the blood, reducing the number of microbes in the body. Buy and use generic Kivexa, namely Lamivudine and Abacavir, recommended by infectious disease doctors around the world, it is approved and licensed.

Method of using the pharmaceutical substance Abamune-L (Abacavir and Lamivudine):

Tablets with the active ingredients Lamivudine and Abacavir are taken only orally (orally by swallowing) both before and after meals, washed down with regular fresh water. The standard dosage is 1 pill per day. In cases of impaired liver or kidney function in a patient, its use is not advisable, since there is no possibility of adjusting the required quantitative ratio of one of active ingredients Abacavir or Lamivudine. In such a situation, medications should be used separately - as monotherapy. Before you buy and start using a rehabilitation course, you need a consultation and a full examination of the whole body with all the necessary tests. Therapy should be carried out under the full supervision of the attending physician and in cases of deterioration of health, treatment may be discontinued. The medication is prescribed only to adults over 18 years of age and weighing more than 40 kg. If the patient is over 65 years old, the doctor may reduce the dosage.

Side and negative effects of the Kivex analogue:

As a rule, the substance is accepted by the body without any undesirable effects, but there may be: general fatigue or drowsiness; mild to severe headaches or migraines; allergic reaction and rash on the body; nausea or vomiting; gastrointestinal disorders; dizziness, anxiety, depression, anxiety; sleep disturbance or insomnia. If two or more side effects occur, you should immediately inform your doctor. It is not recommended to buy and use medicine for self-medication without confidence in the diagnosis.

Shelf life of Lamivudine and Abacavir:

The drug must be stored in a dry and cool place with a temperature of 15-25 degrees Celsius. Valid for 24 months from the date of manufacture. Consuming expired pills can lead to worsening and even fatal consequences. We recommend buying original and proven medicine directly from India from the factory, from fresh batches released for sale.

How to profitably purchase a biological product:

Our company is ready to offer the purchase of Lamivudine and Abacavir in the drug Abamune-L (Kivexa) from the manufacturer Cipla at the best and most favorable price for patients suffering from HIV. The guarantee of reliability and originality of biological products directly from India gives great confidence to the buyer. We guarantee that you will receive only real, fresh and high-quality generics. Delivery occurs within 10 to 14 days after payment. Packages of tablets are delivered directly to your home via courier services EMS, DHL, India Post both in Russia and the CIS.

Dosage form:  film-coated tablets Compound:

Composition for 1 tablet

Active ingredients: abacavir sulfate 702.6 mg (equivalent to 600 mg of abacavir), lamivudine 300 mg.

Excipients: lactose monohydrate 40 mg, microcrystalline cellulose 44.4 mg, sodium carboxymethyl starch 7 mg, povidone-K 30 10 mg, talc 3 mg, magnesium stearate 3 mg.

Shell composition: povidone-K 30 1.5 mg, hypromellose 5 mg, talc 2 mg, titanium dioxide 1.44 mg, sunset yellow dye (E110) 0.06 mg.

Description:

Capsule-shaped tablets, biconvex, film-coated, yellow. On a cross section, the core is white to almost white.

Pharmacotherapeutic group:Antiviral (HIV) agent ATX:  

J.05.A.R.02 Abacavir + Lamivudine

Pharmacodynamics:

In all patients receiving therapy with HSR, the clinical diagnosis of suspected HSR should remain the basis for clinical decision making.

If HSR is suspected, drug therapy should be stopped immediately even if the allele is absent HLA - B *5701. Delay in stopping drug therapy after HSR occurs may result in a life-threatening reaction.

Patients who develop HSR should be advised to hand over remaining tablets of the drug to their prescriber to avoid restarting abacavir.

Resumption of use of drugs containing HSR after a suspected HSR may result in a rapid return of symptoms within hours, which may include life-threatening hypotension and death.

When considering restarting abacavir therapy afterWhen stopping treatment with any drug containing a drug for any reason, the reason for stopping therapy must be established, regardless of whether the patient is a carrier of the allele HLA -B*5701. If HSR cannot be ruled out, the drug or any other medicines containing .

- If HSR is excluded, drug therapy may be resumed. In rare cases, patients who discontinued abacavir for reasons other than HSR symptoms have also experienced life-threatening reactions within a few hours of resuming abacavir therapy (see Selected Adverse Reactions section). Patients should be informed of the possibility of developing HSR when restarting therapy with the drug or other medicinal products containing , and that restarting therapy with the drug or other medicinal products containing , should only be done if they have prompt access to medical care.

Clinical picture HSR for abacavir

HSRs have not been well studied in clinical trials and during post-marketing surveillance. Symptoms usually appear within the first weeks (median time of onset of this reaction is 11 days) after starting abacavir therapy, but these reactions can develop at any time during therapy.

Almost all HSR reactions include fever and/or rash as part of the syndrome. Other signs and symptoms that are noted as manifestations of HSR include respiratory symptoms and gastrointestinal tract, which may lead to incorrect diagnosis of HSR as a respiratory disease (pneumonia, bronchitis, pharyngitis) or gastroenteritis (see sections “Side effects”, “Description of individual adverse reactions”). As treatment continues, symptoms associated with HSR increase in severity and may become life-threatening. In most cases similar symptoms disappear when you stop taking abacavir.

Lactic acidosis and severe hepatomegaly with steatosis

There are reports of the development of lactic acidosis, severe hepatomegaly with steatosis, including death, due to APT nucleoside analogues in the form of individual drugs, including, or combinations thereof. Similar phenomena were observed mainly in women.

Clinical signs of developing lactic acidosis include gastrointestinal symptoms (nausea, vomiting and abdominal pain), general weakness, anorexia, loss of appetite, rapid unexplained weight loss, gastrointestinal and respiratory symptoms (shortness of breath and tachypnea), or neurological symptoms (including motor weakness).

Caution should be exercised when prescribing the drug, especially to patients with hepatomegaly, hepatitis or other risk factors for liver damage and hepatic steatosis (including certain drugs and alcohol).

Patients coinfected with hepatitis C and patients receiving alpha-interferon and ribavirin treatment may be at particular risk. The use of the drug should be discontinued if 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 activity) appear, in the setting of symptomatic hyperlactatemia and metabolic acidosis/lactic acidosis, progressive hepatomegaly, or with a rapid increase in aminotransferase activities .

Lipodystrophy

In some patients receiving combination A.P.T. Redistribution and/or accumulation of subcutaneous fat may be observed, including central obesity, dorsocervical fat deposition (“buffalo hump”), decreased subcutaneous fat on the face and extremities, enlarged mammary glands, increased serum lipid concentrations and glucose concentrations in the blood, both individually and together.

Although all drugs in the PI and NRTI classes can cause one or more of the adverse reactions listed above, associated with a common syndrome often called lipodystrophy, accumulating evidence suggests that there are differences between individual members of these drug classes in the ability to cause these adverse reactions.

It should also be noted that lipodystrophy syndrome has a multifactorial etiology: for example, the stage of HIV infection, advanced age and duration APT play an important, possibly synergistic role in the development of this complication.

The long-term consequences of these adverse events are still unknown.

During the clinical examination, attention should be paid to signs of redistribution of subcutaneous fat. You need to carefully monitorserum lipid concentration and blood glucose concentration. If lipid metabolism is disrupted, appropriate treatment is prescribed.

Immune reconstitution syndrome

If HIV-infected patients with severe immunodeficiency have asymptomatic opportunistic infections or their residual effects at the time of initiation of ART, such therapy may lead to increased symptoms of opportunistic infections or other serious consequences. These reactions usually occur within the first weeks or months after the onset of APT. Typical examples are cytomegalovirus retinitis, generalized or focal infection caused by mycobacteria, and pneumonia caused byPneumocystis jiroveci (R.carinii). The appearance of any symptoms of inflammation requires immediate examination and, if necessary, treatment.

Autoimmune diseases (such as Graves' disease, polymyositis and Guillain-Barre syndrome) have also been observed in the setting of immune reconstitution, but the timing of initial manifestations varies and the disease may occur many months after the start of therapy and have an atypical course.

Opportunistic infections

The use of the drug or other antiretroviral drugs does not exclude the possibility of developing opportunistic infections or other complications of HIV infection, so patients should remain under the supervision of a physician experienced in treating these HIV-associated diseases.

HIV transmission

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

Myocardial infarction

As a result of a prospective observational epidemiological study to study the incidence of myocardial infarction in patients receiving combination A.P.T. a connection was found between prior use of abacavir within 6 months and an increased risk of myocardial infarction. According to a pooled analysis of clinical studies, there was no increase in the risk of myocardial infarction associated with taking abacavir. The biological mechanisms explaining the potentially increased risk are unknown. Overall, available data from observational cohorts and controlled clinical trials do notallow us to unambiguously determine the relationship of abacavir therapy with the risk of myocardial infarction.

However, caution should be exercised when prescribing A.P.T. including drugs containing , in patients with a possible risk of coronary disease hearts. All measures must be taken to minimize risk factors (such as arterial hypertension, hyperlipidemia, diabetes mellitus and smoking).

Pancreatitis

Cases of pancreatitis have been reported, although a causal relationship with the use of lamivudine and abacavir has not been clearly established.

Kidney diseases

The drug should not be prescribed to patients with creatinine clearance less than 50 ml/min.

Liver diseases

The effectiveness and safety of the drug have not been established in patients with severe concomitant liver diseases. The drug is not recommended for use in patients with impaired liver function.

In patients with pre-existing liver dysfunction, including active chronic hepatitis, there is an increased incidence of liver dysfunction with combined APT. Such patients should be monitored in accordance with standard clinical practice.

Patients with chronic hepatitis B or C

Clinical studies and post-marketing surveillance data on the use of lamivudine indicate that in some patients with concomitant hepatitis B viral infection(HBV) Clinical or laboratory signs of relapse of hepatitis may occur after discontinuation of lamivudine, which may have more severe consequences in patients with decompensated liver disease. As a result, in patients with concomitant viral hepatitis B, when discontinuing the drug, liver function tests should be monitored and markers of hepatitis B virus replication should be regularly determined.

Due to the fact that both have the same phosphorylation pathways, an interaction between these substances is expected, which may lead to a decrease in intracellular phosphorylation of ribavirin metabolites and potentially leads to a decrease in the likelihood of achieving a sustained virological response in hepatitis C-coinfected HIV-infected patients receiving pegylated interferon therapy and ribavirin.

Conflicting data have been published regarding the concomitant use of abacavir and ribavirin. Some data suggest that HIV-infected patients receiving abacavir-containing drugs may be at risk of low response rates to antiviral therapy with pegylated interferon and ribavirin. Caution should be exercised when taking these drugs concomitantly.

Mitochondrial dysfunction

Research in vitro And in vivoshowed that nucleoside and nucleotide analogues are capable of causing varying degrees of mitochondrial damage. Cases of mitochondrial dysfunction have been reported in HIV-negative children receiving nucleoside analogues in utero and/or after birth. The main adverse reactions were hematological disorders (anemia, neutropenia), metabolic disorders (hyperlactatemia, hyperlipasemia). These adverse reactions are often transient. Some late-onset neurological disorders (increased muscle tone, seizures, behavioral disturbances) have been reported. Whether these neurological disorders are transient or permanent is currently unknown. Any child, even HIV-negative, exposed in utero to nucleoside and nucleotide analogues should undergo clinical and laboratory evaluation to rule out mitochondrial dysfunction if signs or symptoms are detected. These data do not influence current national recommendations for use APT in pregnant women to prevent vertical transmission of HIV infection.

Osteonecrosis

Although the etiology of this disease is multifactorial (including taking glucocorticosteroids, alcohol consumption, severe immunosuppression, high body mass index), cases of osteonecrosis most often occurred in patients late stage HIV infection and/or long-term use of combination APT. Patients should consult a doctor if they experience joint pain and stiffness or difficulty moving.

Risk of virological failure

Triple nucleoside therapy: High rates of virologic failure and early resistance have been reported when abacavir and lamivudine were coadministered with tenofovir disoproxil fumarate in a once-daily dosing regimen. Contains sunset yellow dye, which may cause allergic reactions.

Impact on the ability to drive vehicles. Wed and fur.:

No specific studies have been conducted on the effect of lamivudine on the ability to drive vehicles or operate machinery. Besides, negative impact Such activities cannot be predicted based on the pharmacology of these drugs. When assessing a patient's ability to drive vehicles or operate machinery, his or her general condition, as well as the profile of adverse reactions of the drug.

Release form/dosage:Film-coated tablets, 600 mg + 300 mg. Package:

10 tablets in a blister made of aluminum foil and amber PVC film. 1, 3 or 10 blisters along with instructions for use in a cardboard box.

100, 500 or 1000 tablets in a plastic bag. 1 packet per HDPE jar with silica gel, sealed with polyethylene-coated aluminum foil, with a screw cap. A self-adhesive label made of label or writing paper or polymer materials is glued onto the jar. 1.6, 12 or 24 cans along with an equal number of instructions for use are placed in a group package - a corrugated cardboard box (for hospitals).

Storage conditions:

At a temperature not higher than 25 °C.

Best before date: 2 years. Do not use after the expiration date stated on the packaging. Conditions for dispensing from pharmacies: By prescription Registration number: LP-004209 Registration date: 21.03.2017 Expiration date: 21.03.2022 Owner of the Registration Certificate: India Manufacturer:   Representative office:  Lock-Beta Pharmaceuticals (I) Pvt.Ltd Information update date:   25.04.2017 Illustrated instructions

INN: Abacavir, Lamivudine

Manufacturer: Aurobindo Pharma Limited

Anatomical-therapeutic-chemical classification: Lamivudine and abacavir

Registration number in the Republic of Kazakhstan: No. RK-LS-5 No. 020716

Registration period: 23.07.2014 - 23.07.2019

KNF (medicine included in the Kazakhstan National Formulary of Medicines)

ALO (Included in the List of free outpatient drug provision)

ED (Included in the List of drugs within the framework of the guaranteed volume of free medical care, subject to purchase from the Single Distributor)

Limit purchase price in the Republic of Kazakhstan: 988.75 KZT

Instructions

Trade name

Abacavir and lamivudine

International nonproprietary name

Dosage form

Film-coated tablets, 600 mg/300 mg

Compound

One tablet contains

active substances- abacavir sulfate 702.78 mg (equivalent to abacavir 600.00 mg), lamivudine 300 mg,

excipients: microcrystalline cellulose (Ceolus KG-802), sodium starch glycolate (type A), purified water, magnesium stearate,

shell composition: shell Opadry YS-1-13065-A Orange: hydroxypropyl methylcellulose 2910/hypromellose 6 cP, hydroxypropyl methylcellulose 2910/hypromellose 3 cP, titanium dioxide (E 171), macrogol/PEG 400, FD&C Yellow #6/Sunset yellow FCF Aluminum varnish ( 5% - 18%) (E 110), Polysorbate 80, FD&C Yellow #6/Sunset Yellow FCF Aluminum Varnish (38% - 42%) (E 110).

Description

Modified capsule-shaped tablets, orange film-coated, engraved “H” on one side and “27” on the other side.

Pharmacotherapeutic group

Antiviral drugs for systemic use. Antiviral drugs for the treatment of HIV infection, combinations. Lamivudine and abacavir.

ATX code J05AR02

Pharmacological properties

Pharmacokinetics

Absorption

After oral administration, abacavir and lamivudine are rapidly and well absorbed. In adults, the absolute bioavailability of abacavir and lamivudine is 83% and 80-85%, respectively. The maximum concentration in blood serum is observed after 1.5 hours and 1.0 hours, respectively. After a single oral dose of 600 mg of abacavir, the Cmax value is 4.26 μg/ml (28%) and the AUC∞ value is 11.95 μg·h/ml (21%). After repeated oral administration of 300 mg lamivudine for 7 days, the Cmax value was 2.04 μg/ml (26%) and the AUC∞ value was 8.87 μg·h/ml (21%). Food intake does not have a significant effect on the effect of the drug, so Abacavir and lamivudine can be taken regardless of food intake.

Distribution

The average apparent volume of distribution is 0.8 and 1.3 l/kg, respectively. Abacavir in therapeutic concentrations binds to human plasma proteins to a small or moderate extent (about 49%). Lamivudine exhibits linear pharmacokinetics above the therapeutic concentration range and low plasma protein binding (less than 36%), indicating a low likelihood of interactions with other drugs. Abacavir and lamivudine penetrate into the central nervous system and cerebrospinal fluid. The AUC ratio in cerebrospinal fluid and blood plasma is 30-44%. The observed peak concentrations are 9 times greater than the IC50 of abacavir (0.08 µg/ml or 0.26 µmol) when abacavir is administered at 600 mg twice daily. The average lamivudine concentration ratio in cerebrospinal fluid/serum within 2-4 hours after dosing is about 12%.

Metabolism

Metabolism of abacavir occurs primarily in the liver. About 2% of the dose taken is excreted unchanged in the urine. The metabolism of abacavir in the human body is associated with the action of alcohol dehydrogenase and the formation of glucuronide conjugates - 5'-carboxylic acid and 5'-glucuronide. Their amount is about 66% of the dose taken and is excreted in the urine. Lamivudine undergoes little hepatic metabolism (5 - 10%) and is excreted in the urine mainly unchanged.

Elimination

The half-life of abacavir is 1.5 hours. After repeated oral administration of the drug at a dose of 300 mg 2 times a day, no significant accumulation of the drug is observed. Elimination of abacavir occurs through hepatic metabolism followed by excretion of metabolites in the urine. About 83% of the dose taken is excreted in the urine in the form of metabolites and unchanged drug, the rest is excreted in feces. The half-life of lamivudine is 5-7 hours. The average total clearance of lamivudine is approximately 0.32 L/h/kg, which is predominantly renal clearance (more than 70%) via the organic cationic transport system.

Patients with liver dysfunction

Abacavir is metabolized primarily by the liver. In patients with mild hepatic impairment (Child-Pugh score 5-6), the AUC of abacavir was increased by an average of 1.89 times and the half-life by 1.58 times. Minor liver dysfunction did not affect the AUC of abacavir metabolites, but the rate of formation and elimination of metabolites was reduced.

In patients with mild hepatic impairment, data are not available. The pharmacokinetics of abacavir have not been studied in patients with moderate to severe hepatic impairment. It is expected that in such patients the plasma concentration of abacavir will be variable and, in most cases, elevated, and therefore the drug is contraindicated in this category of patients.

Moderate and severe liver pathologies do not have a significant effect on the pharmacokinetics of lamivudine.

Patients with impaired renal function

The pharmacokinetic parameters of abacavir in patients with end-stage renal failure and in patients with normal renal function are similar.

Due to reduced clearance in patients with renal dysfunction, the concentration-time ratio (AUC) of lamivudine is increased. Due to the need to reduce the dose, patients with creatinine clearance less than 50 ml/min should be prescribed lamivudine alone.

Pharmacodynamics

Abacavir and lamivudine is a combination drug that contains abacavir and lamivudine and has an antiviral effect.

Abacavir and lamivudine belong to the group of nucleoside reverse transcriptase inhibitors of HIV-1 and HIV-2. Abacavir and lamivudine are sequentially metabolized by intracellular kinases into the corresponding active forms of the drug - triphosphates (TP). Lamivudine triphosphate and carbovir triphosphate (the active form of abacavir triphosphate) are substrates and competitive inhibitors of HIV reverse transcriptase. Their main antiviral action is the conversion of monophosphate forms into the viral DNA strand, leading to subsequent chain termination. Abacavir and lamivudine triphosphates show little similarity to host cell DNA polymerases.

Lamivudine in combination with zidovudine exhibits synergism and suppresses the replication of the human immunodeficiency virus (HIV) in cell culture.

Abacavir exhibits synergism in combination with amprenavir, nevirapine and zidovudine and has an additive effect in combination with didanosine, zalcitabine, stavudine, lamivudine.

HIV-1 resistance to lamivudine involves the development of changes in the amino acid M184V close to the active site of viral reverse transcriptase. The M184V mutation reduces susceptibility to lamivudine. Viral strains resistant to zidovudine may become sensitive to zidovudine while simultaneously acquiring resistance to lamivudine. The development of resistance to abacavir is associated with specific genotypic changes in a specific codon region of reverse transcriptase (codons M184V, K65R, L74V and Y115F). Viral resistance to abacavir develops relatively slowly; multiple mutations are required to increase the IC50 concentration by 8 times compared to the wild strain of the virus, which can be clinically significant. Strains resistant to abacavir may have reduced sensitivity to lamivudine, zalcitabine, tenofovir, emtricitabine and/or didanosine, but sensitivity to zidovudine and stavudine remains. Cross-resistance is unlikely to develop between abacavir or lamivudine and other classes of antiretroviral drugs, such as protease inhibitors or non-nucleoside reverse transcriptase inhibitors.

Reduced sensitivity to abacavir has been demonstrated in clinically isolated strains from patients with uncontrolled viral replication who have previously received treatment and are resistant to other nucleoside inhibitors. Clinically isolated strains with three or more mutations associated with nucleoside reverse transcriptase inhibitors are unlikely to be susceptible to abacavir.

The cross-resistance inherent in M184V RT is limited to the nucleoside inhibitor class of antiretroviral drugs. Zidovudine, stavudine, abacavir and tenofovir retain their antiretroviral activity against lamivudine-resistant HIV-1 containing only the M184V mutation.

Indications for use

HIV infection as part of combination antiretroviral therapy in adults

Directions for use and doses

Abacavir and lamivudine should be prescribed by specialists with experience in treating HIV infection.

Adults weighing more than 40 kg Abacavir and lamivudine can be taken without regard to meals. The maximum daily dose is 1 tablet (600 mg/300 mg) 1 time per day, daily.

Elderly patients

The pharmacokinetics of abacavir and lamivudine have not been studied in patients over 65 years of age. When treating elderly patients, the increased incidence of liver, kidney, heart and other concomitant diseases, as well as the use of other medications, should be taken into account.

Patients suffering from kidney failure

Patients suffering from liver failure

In patients with mild hepatic impairment (Child-Pugh grade A), a dose reduction of abacavir may be required. Since it is not possible to reduce the individual components of the drug, it is necessary to prescribe abacavir and lamivudine separately. The use of this drug in patients with moderate or severe hepatic impairment (Child-Pugh grades B and C) is contraindicated.

Side effects

This drug contains two active components- abacavir and lamivudine, and below are the adverse reactions that may occur with their use. It is unclear whether the reactions listed are related to taking medicine, concomitant therapy or are a consequence of a general disease.

Frequency of occurrence: very common (>1/10), common (>1/100,<1/10), нечасто (>1/1,000, <1/100), редко (>1/10,000, <1/1000), очень редко (<1/10,000).

Many of the reactions listed below are common (nausea, vomiting, diarrhea, fever, drowsiness, rash) and may indicate a hypersensitivity reaction. Therefore, if any of these symptoms occur, the patient should be carefully evaluated for their relationship to a hypersensitivity reaction. If the drug was discontinued due to the development of any of the listed symptoms, but a decision was later made to resume therapy, Abacavir and lamivudine should be taken under strict medical supervision.

Reactions to abacavir

Often

Hypersensitivity reactions

Anorexia

Headache

Nausea, vomiting, diarrhea

Fever, drowsiness, fatigue

Reactions to lamivudine

Often

Headache

Nausea, vomiting, upper abdominal pain, diarrhea

Weakness, fatigue, fever

Uncommon

Transient increase in the activity of liver enzymes (AST, ALT)

Anemia, neutropenia, thrombocytopenia

Post-marketing data

Reactions to abacavir

Often

Hyperlactatemia

Rash (without systemic manifestations)

Rarely

Pancreatitis, but no connection with abacavir has been established

Very rarely

Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis

Reactions to lamivudine

Often

Hyperlactatemia

Alopecia

Arthralgia, muscle disorders

Rarely

Lactic acidosis (redistribution/accumulation of fat has been identified in patients taking antiretroviral therapy. This pathology has a multifactorial etiology, including the combined use of antiretroviral drugs)

Increased serum amylase levels, pancreatitis, although no connection with lamivudine has been established

Rhabdomyolysis

Very rarely

Peripheral neuropathy, paresthesia, although no relationship with lamivudine has been established

Hypersensitivity reactions to abacavir

In clinical studies, during screening, approximately 5% of subjects were found to have the HLA B*5701 allele, which was associated with a significant risk of developing hypersensitivity reactions to abacavir, in rare cases with a fatal outcome. These reactions are manifested by symptoms that indicate multiple organ damage. In most cases, one of the manifestations of a hypersensitivity reaction is fever or rash (maculopapular or urticaria), however, hypersensitivity reactions can occur in the absence of these symptoms.

Symptoms of hypersensitivity can appear at any time while taking abacavir, but more often this happens during the first 6 weeks of therapy (on average, on the 11th day of therapy). The signs and symptoms of this hypersensitivity reaction are listed below. Those signs that were found at least in 10% of patients, in bold:

- rash(usually maculopapular or urticarial)

Lesions of the oral mucosa, abdominal pain, nausea, vomiting, diarrhea

- shortness of breath, cough, sore throat, respiratory failure, respiratory distress syndrome

- fever, fatigue, malaise, edema, lymphadenopathy, hypotension, conjunctivitis, anaphylaxis

- headache, paresthesia

Lymphopenia

- increase in liver function tests, liver failure

Increased creatinine levels, renal failure

- myalgia, myolysis, arthralgia, increased levels of creatine phosphokinase

In some cases, hypersensitivity reactions may be interpreted as diseases of the respiratory system (pneumonia, bronchitis, pharyngitis), influenza-like illnesses, gastroenteritis, or reactions to other drugs. A delay in the diagnosis of hypersensitivity reactions may lead to continued use of abacavir and, accordingly, to the development of more severe hypersensitivity reactions while taking it. Thus, if a hypersensitivity reaction is suspected, even in cases where the possibility of another diagnosis cannot be excluded, all listed symptoms should be carefully considered for a possible relationship with a hypersensitivity reaction. If a hypersensitivity reaction cannot be excluded, the drug and other abacavir-containing products should be discontinued and should never be prescribed in the future.

Symptoms associated with a hypersensitivity reaction worsen with continued therapy, and usually disappear after discontinuation of abacavir and other abacavir-containing drugs.

Resumption of abacavir in the setting of hypersensitivity reactions results in a return of symptoms within a few hours.

Symptoms that develop while you continue to take Abacavir and lamivudine may be much more severe than those that develop when you first take the drug and can lead to life-threatening hypotension and death.

Regardless ofHLAB*5701 patient status If any symptoms of hypersensitivity develop, the drug should be discontinued immediately. If a hypersensitivity reaction occurs, Abacavir and lamivudine and any other abacavir-containing products should never be prescribed subsequently.

Several cases of a hypersensitivity reaction have been identified when abacavir was reintroduced after discontinuation due to the development of any one hypersensitivity symptom (rash, fever, malaise/fatigue, gastrointestinal or respiratory symptoms).

In rare cases, hypersensitivity reactions may develop when abacavir therapy is resumed in the absence of previous signs and symptoms of hypersensitivity.

Contraindications

Hypersensitivity to abacavir, lamivudine or any of the components of the drug

Moderate and severe liver failure

Renal failure with creatinine clearance less than 50 ml/min

Pregnancy and lactation

Children and teenagers up to 18 years of age

Drug interactions

Because this drug contains abacavir and lamivudine, any interactions that have been identified with these agents individually may occur. Abacavir and lamivudine are slightly metabolized by cytochrome P450 enzymes (such as CYP 3A4, CYP 2C9 or CYP 2D6) and do not have an inhibitory or inducing effect on this enzyme system. Therefore, the drug is unlikely to interact with anti-retroviral protease inhibitors, non-nucleosides and other drugs that are metabolized by major P450 enzymes.

The likelihood of interactions involving lamivudine is extremely low due to its limited metabolism and low binding to plasma proteins and almost complete elimination through renal clearance. Caution must be exercised when concomitantly prescribing those drugs that are also eliminated through the renal mechanism.

Abacavir interactions

With ethanol

The metabolism of abacavir is disrupted when combined with ethanol, which is accompanied by an increase in AUC by 41% and has no clinical significance. Abacavir does not affect ethanol metabolism.

With methadone

With simultaneous use of abacavir at a dose of 600 mg 2 times a day day and methadone, Cmax of abacavir decreased by 35%, and Tmax increased by 1 hour, AUC did not change. These data have no clinical significance. Abacavir increases the systemic clearance of methadone by 22%, so methadone dosage may sometimes need to be re-adjusted.

With retinoids

Retinoid compounds excreted from the body using the enzyme alcohol dehydrogenase. Interactions with abacavir are possible but not studied.

Lamivudine interactions

With trimethoprim

Trimethoprim/sulfamethoxazole 160 mg/800 mg (co-trimoxazole) increased lamivudine exposure by 40%. If renal function is not impaired, then no dose adjustment of lamivudine is required. Lamivudine does not affect the pharmacokinetics of trimethoprim or sulfamethoxazole. The effect of using lamivudine with high doses of co-trimoxazole for the treatment of Pneumocystis pneumonia and toxoplasmosis has not been studied.

With zalcitabine

Lamivudine may inhibit intracellular phosphorylation of zalcitabine. The drug is not recommended for use together with zalcitabine.

With emtricitabine

Lamivudine may inhibit intracellular phosphorylation of emtricitabine when these drugs are used together. Also, the mechanism of development of viral resistance for both drugs occurs through mutation of the same parts of the viral transcriptase gene (M184V), accordingly, the therapeutic effectiveness of these products when used in combination may be limited. Lamivudine is not recommended for use with emtricitabine or fixed-dose products containing emtricitabine.

Special instructions

Hypersensitivity to abacavir

In clinical studies, it was found that the presence of HLA B* 5701 in patients was associated with a significant risk of developing hypersensitivity reactions to abacavir (in 5% of those studied), in rare cases leading to death.

Clinical studies have shown that carriage of the HLA B*5701 allele was associated with a significantly increased risk of developing hypersensitivity reactions to abacavir. In studies that screened patients for the HLA B*5701 allele before treatment, the rate of expected clinical hypersensitivity reactions to abacavir decreased from 7.8% (66 of 847 patients) to 3.4% (27 of 803 patients); and cases of hypersensitivity reactions confirmed by a skin test - from 2.7% (23 patients out of 842) to 0% (0 cases out of 802). Based on the study data, it was confirmed that 48-61% of patients who carried the HLA B*5701 allele developed a hypersensitivity reaction while taking abacavir compared to those patients who did not have the HLA B*5701 allele (0-4%).

The treating physician should consider the importance of screening patients for the presence of the HLA B*5701 allele before initiating treatment with Abacavir and lamivudine. Screening is also recommended before restarting the drug in patients with unknown HLA B*5701 status who have previously received this drug and have demonstrated tolerance to abacavir. If you carry the HLA B*5701 allele, the use of abacavir is not recommended; Prescribing abacavir-containing drugs is possible only under strict medical supervision and only when the potential benefits outweigh the possible risks.

It must be remembered that in patients using Abacavir and lamivudine, any decision about the possibility of developing hypersensitivity reactions should remain paramount when deciding to prescribe the drug. Even in the absence of carriage of the HLA B*5701 allele, it is important to remember the need to discontinue the drug if it is impossible to exclude the development of hypersensitivity reactions based on available clinical data and not to prescribe abacavir-containing products in the future due to the potential for death.

Hypersensitivity reactions are manifested by symptoms that indicate multiple organ damage. In most cases, one of the manifestations of hypersensitivity syndrome is a fever or rash, but hypersensitivity reactions can also be accompanied by other symptoms (fatigue, malaise, gastrointestinal symptoms such as nausea, vomiting, diarrhea, abdominal pain; respiratory symptoms such as dyspnea , sore throat, cough, infiltrates in the chest area).

Hypersensitivity reactions can develop at any stage of treatment with Abacavir and lamivudine, but usually appear within the first 6 weeks of starting the drug. When the drug was discontinued, hypersensitivity symptoms usually disappeared. With continued treatment, the symptoms intensify, which can threaten the patient's life.

Regardless ofHLAB*5701 status, the patient should immediately notify the attending physician if any symptoms of hypersensitivity develop. If the diagnosis of a hypersensitivity reaction is confirmed, Abacavir and lamivudine should be discontinued immediately. If a hypersensitivity reaction occurs, Abacavir and lamivudine and any other abacavir-containing products should never be subsequently prescribed as the most severe symptoms, including life-threatening hypotension, return within hours and can be fatal.

To avoid delay in diagnosis and reduce the risk of life-threatening reactions, this drug should be discontinued if hypersensitivity reactions are suspected, even when another diagnosis cannot be ruled out (eg, respiratory disease, influenza-like illness, gastroenteritis, or reactions for other drugs).

The drug and other abacavir-containing products should not be resumed if hypersensitivity symptoms recur when alternative therapy is prescribed.

Regardless of the carriage of the HLA B*5701 allele, if therapy with Abacavir and lamivudine has been suspended and a decision is made to continue it, the reasons for discontinuing the drug must be carefully analyzed to exclude the possibility of symptoms of a hypersensitivity reaction. If hypersensitivity reactions cannot be excluded, the drug or other abacavir-containing products should not be resumed.

In cases where a decision has been made to resume therapy in patients who have temporarily stopped taking Abacavir and lamivudine, it should be carried out in an appropriate medical facility and the patient should be able to receive urgent medical care.

In some cases, hypersensitivity reactions may develop when abacavir therapy is resumed in the absence of previous signs and symptoms of hypersensitivity. If a decision is made to restart therapy, the drug should be taken only if it is possible to immediately provide assistance to the patient.

It is recommended to screen for HLA B*5701 carriage in patients of unknown status who are tolerant to previous abacavir treatment. If you carry the HLA B*5701 allele, the use of abacavir is not recommended; Prescribing abacavir-containing drugs is possible only under strict medical supervision and only when the potential benefits outweigh all possible risks.

When prescribing the drug, the doctor must be sure that the patient is informed of the following data on hypersensitivity reactions:

The patient should be aware of the possible hypersensitivity reactions to Abacavir and lamivudine, which can manifest as life-threatening or fatal symptoms, as well as the increased risk of developing hypersensitivity reactions if carriers of the HLA B*5701 allele

The patient should be aware that even in the absence of the HLA B*5701 allele, the development of hypersensitivity reactions to taking this drug is possible. If the patient experiences symptoms that may be due to a hypersensitivity reaction, he must immediately consult his doctor

Patients with hypersensitivity to Abacavir and lamivudine should know that they should never again take it or another drug containing Abacavir, despite HLA B*5701 status

To avoid self-resumption of therapy with Abacavir and lamivudine after the development of hypersensitivity reactions, the patient should return the remaining tablets to the doctor.

Patients who stop taking the drug for any reason should consult their doctor before resuming the drug.

Lactic acidosis/severe hepatomegaly with steatosis

In HIV-infected patients (mainly women) who took antiretroviral drugs from the group of nucleoside analogues as monotherapy or as part of complex therapy, cases of lactic acidosis and hepatomegaly with fatty liver degeneration (including fatal outcomes) have been described.

Clinical features suggestive of lactic acidosis include general weakness, anorexia and sudden unexplained weight loss, gastrointestinal and respiratory symptoms (shortness of breath and rapid breathing).

Caution should be exercised when treating with Abacavir and lamivudine, especially if patients have risk factors for developing liver disease. If clinical or laboratory signs of lactic acidosis with or without signs of hepatitis appear (which may include hepatomegaly and steatosis, even in the absence of increased transaminase levels), the drug should be discontinued.

Lipodystrophy

Some patients receiving combination antiretroviral therapy have experienced redistribution/accumulation of body fat, including general obesity, dorsocervical obesity (Buffalo hump), decreased peripheral fat, facial thinning, breast enlargement, and increased serum glucose and lipid levels. .

Side effects related to lipodystrophy can occur with any drug from the protease inhibitor or nucleoside reverse transcriptase inhibitor class. However, available evidence suggests that the risk of developing these side effects varies among different drugs in these classes.

In addition, many factors contribute to the development of lipodystrophy. An important and possibly mutually potentiating role is played by the presence of HIV infection, advanced age and duration of antiretroviral therapy.

The long-term consequences of these violations are currently unknown.

During the clinical examination, attention should be paid to signs of redistribution of fat in the body. Serum lipid levels and blood glucose levels should be closely monitored. If necessary, appropriate treatment for lipid metabolism disorders is carried out.

Immune reconstitution syndrome

In HIV-infected patients who are severely immunocompromised at the start of antiretroviral therapy (ART), the inflammatory response to asymptomatic or residual opportunistic infections may cause worsening of clinical symptoms of comorbidities. Cytomegalovirus rhinitis, generalized and/or focal mycobacterial infections, and Pneumocystis pneumonia were commonly observed during the first few weeks or months after ART initiation. Any inflammatory symptoms should be promptly identified and appropriate anti-inflammatory therapy administered if necessary. Autoimmune disorders (polymyositis, Jullian-Barr syndrome, diffuse toxic goiter) have also been reported when taking Abacavir and lamivudine, however, the timing of disease attacks is quite variable and can occur many months after the start of therapy.

Patients with concomitant viral hepatitis B

In some patients with concomitant hepatitis B virus (HBV) may cause clinical or laboratory signs of relapse of hepatitis after discontinuation of lamivudine, which, in turn, can lead to more severe consequences in patients with decompensated liver disease. If Abacavir and lamivudine have been discontinued in patients with concomitant viral hepatitis B, liver function tests should be monitored and the level of HBV replication markers should be regularly determined.

Opportunistic infections

Patients using Abacavir and lamivudine or other antiretroviral drugs may develop infections caused by opportunistic microorganisms and other complications of HIV infection, so patients should be under constant supervision of doctors experienced in treating HIV infection.

Transmission of infection

Patients should be informed that current antiretroviral therapy, including this drug, does not prevent the transmission of HIV to others through sexual contact or transfusion of infected blood. Please remember to follow appropriate safety precautions.

Cardiovascular diseases

In studies designed to determine the incidence of myocardial infarction in patients on combination antiretroviral therapy, use of abacavir for 6 months was associated with an increased risk of myocardial infarction. Analysis of clinical studies did not confirm an increase in the risk of myocardial infarction while taking abacavir. The biological mechanism for the potential increase in myocardial infarction is unknown. Therefore, the relationship between abacavir use and increased incidence of myocardial infarction remains unclear.

When prescribing antiretroviral therapy, including the drug Abacavir and lamivudine, to prevent the development of coronary heart disease, precautions should be taken to reduce all risk factors, such as hypertension, hyperlipidemia, diabetes mellitus, and smoking.

Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms

No special studies have been conducted on the effect of lamivudine and abacavir on the ability to concentrate when driving vehicles/machines. The drug is unlikely to adversely affect the ability to perform tasks requiring alertness, motor or cognitive skills. However, when assessing a patient's ability to concentrate, one should take into account his general condition, as well as the nature of the side effects that may occur while taking Abacavir and lamivudine.

Overdose

Symptoms: increased side effects.

Treatment: in case of overdose, the patient should be under medical supervision (in order to identify signs of toxic effects of the drug). If necessary, standard maintenance therapy is carried out. Due to the fact that lamivudine can be eliminated from the body by dialysis, treatment of overdose should include continuous hemodialysis. It is currently unknown whether peritoneal dialysis and hemodialysis eliminate abacavir from the body.

Release form and packaging

The active ingredient in the drug is a whole complex of compounds, which includes lamivudine, abacavir and zidovudine. Trizivir belongs to the pharmacological group of combinatorial antiviral agents. It is used in the treatment of HIV infection in both adults and children.

Trizivir

Mechanism of action

All three active ingredients included in Trizivir have the ability to block a specific viral enzyme called reverse transcriptase. This drug plays a critical role in the reproduction of viral particles. Suppressing its activity stops the process of HIV DNA replication

Application protocol

Trizivir is available in tablet form for oral use. The standard dosage of the drug is 1 tablet administered into the patient’s body 2 times a day, regardless of meal time.

Efficiency of use

In clinical trials of Trizivir, it was shown that lamivudine, abacavir and zidovudine have the ability to significantly enhance the pharmacological effects of each other. In the presence of all three compounds, the suppression of the replication of viral particles occurs much more intensely. In addition, the researchers specifically noted the low chemical affinity of the drug components to the DNA enzymes of ordinary human cells.

Contraindications:

• allergic reactions to lamivudine, zidovudine or abacavir, as well as any other components included in Trizivir;
• liver function failure;
• neutropenia;
• hemoglobin deficiency;
• the patient's age is less than 12 years.

Side effects of Trizivir:

• cardiomyopathy;
• anemic conditions, neutro-, leuko- and thrombocytopenia;
• nausea, sometimes vomiting;
• intestinal disorder;
• stomach pain;
• loss of appetite and body weight;
• changes in the color of the oral mucosa;
• increased production of gases in the intestines;
• pancreatitis;
• increase in liver size;
• joint and muscle pain;
• headaches and dizziness;
• sleep disturbances in the form of insomnia or, conversely, drowsiness;
• sensitivity disorders;
• convulsive syndrome;
• anxiety and depression;
• cough and shortness of breath;
• rash, itching and pigmentation of the skin;
• hives;
• hair loss;
• increased sweating;
• increased body temperature with chills;
• increasing weakness and fatigue;
• increased frequency of urination,
• gynecomastia.

Interaction with other drugs

Trizivir should be used under close medical supervision in conjunction with pharmacological agents such as:

• methadone;
• retinoid compounds;
• trimethoprim;
• zalcitabine;
• phenytoin;
• substances that block tubular secretion;
• ribavirin;
• rifampicin;
• stavudine

Transportation and storage conditions

When transporting and storing Trizivir, it is necessary to maintain a temperature regime not exceeding 30°C.