Lavudine-AB (Tablets) Instructions for Use

Marketing Authorization Holder

Hetero Labs, Limited (India)

Manufactured By

Hetero Labs, Limited (India)

Or

Makiz-Pharma, LLC (Russia)

ATC Code

J05AR02 (Lamivudine and abacavir)

Active Substances

Lamivudine (Rec.INN registered by WHO)

Abacavir (Rec.INN registered by WHO)

Dosage Form

Lavudine-AB

Film-coated tablets, 600 mg+300 mg: 30 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets orange in color, capsule-shaped, biconvex; engraved with “H” on one side and “A1” on the other side.

Excipients: microcrystalline cellulose – 218.238 mg, sodium carboxymethyl starch – 96.25 mg, colloidal silicon dioxide – 27.5 mg, magnesium stearate – 30.25 mg.

Film coating composition Opadry orange YS-1-13065-A – 34.375 mg, (calculated on a dry substance basis): hypromellose (3 cP) – 32.17%, hypromellose (6 cP) – 32.17%, titanium dioxide – 22.42%, macrogol-400 – 8%, “Sunset Yellow” dye (15-18% solution) – 3.32%, polysorbate 80 – 1%, “Sunset Yellow” dye (38-42% solution) – 0.92%.

30 pcs. – bottles (1) – cardboard packs.
30 pcs. – jars (1) – cardboard packs.

Clinical-Pharmacological Group

Antiviral drug active against HIV

Pharmacotherapeutic Group

Antiviral [HIV] agent

Pharmacological Action

A combined antiviral drug. Abacavir and Lamivudine belong to the group of nucleoside reverse transcriptase inhibitors and are potent selective inhibitors of HIV-1 and HIV-2.

Abacavir and Lamivudine are sequentially metabolized by intracellular kinases to their respective triphosphates, which act as active metabolites. Lamivudine triphosphate and carbovir triphosphate (the active triphosphate of abacavir) act as substrates and are competitive inhibitors of HIV reverse transcriptase. However, the main antiviral effect of the drugs is due to the incorporation of the monophosphate into the DNA chain, which leads to the termination of replication. The triphosphates of abacavir and lamivudine have significantly less affinity for host cell DNA polymerases.

A study in which 20 HIV-infected patients received abacavir (300 mg twice daily and once 24 hours before sample collection for analysis) showed that the geometric mean terminal intracellular T_1/2 of carbovir triphosphate at steady state is 20.6 h. The geometric mean T_1/2 of abacavir from plasma in this study was 2.6 h. Steady-state pharmacokinetic parameters when taking abacavir at a dose of 600 mg once daily were the same as when taking abacavir at a dose of 300 mg twice daily in a crossover clinical study involving 27 HIV-infected patients. Intracellular carbovir triphosphate content in peripheral blood mononuclear cells was higher when taking abacavir at a dose of 600 mg once daily compared to taking abacavir at a dose of 300 mg twice daily (increase in steady-state AUC over 24 h (AUC_24,ss) by 32%, maximum daily steady-state concentration (C_{max 24,ss}) – by 99%). In patients taking Lamivudine at a dose of 300 mg once daily, the terminal intracellular T_1/2 of Lamivudine triphosphate increased from 16 to 19 h, and the T_1/2 of lamivudine from plasma increased from 5 to 7 h. A study of lamivudine pharmacokinetic parameters taken at a dose of 300 mg once daily for 7 days compared to taking lamivudine at a dose of 150 mg twice daily for 7 days, conducted with 60 healthy volunteers, showed that the AUC_24,ss and C_{max 24,ss} values for the intracellular concentration of Lamivudine triphosphate in peripheral blood mononuclear cells were the same, but the minimum values when taking lamivudine at a dose of 300 mg once daily were lower than when taking lamivudine at a dose of 150 mg twice daily.

The variability of lamivudine metabolite concentration inside the cell is higher than in plasma. These results are supported by data obtained when taking lamivudine at a dose of 300 mg and abacavir at a dose of 600 mg once daily (the efficacy and safety of this combination when taking the drugs once daily was also confirmed in the pivotal clinical study CNA30021).

Lamivudine acts synergistically with zidovudine, effectively suppressing HIV replication in cell culture. In vitro, abacavir acts synergistically in combination with amprenavir, nevirapine and zidovudine and additively with didanosine, zalcitabine, stavudine and lamivudine.

HIV-1 resistance to lamivudine is due to a mutation at codon M184V, located near the active site of the viral reverse transcriptase. This mutation is observed both in vitro and in HIV-1-infected patients who received combination therapy including Lamivudine. The M184V codon mutation significantly reduces sensitivity to lamivudine and substantially reduces the virus’s ability to replicate according to in vitro studies. In vitro studies have also established that zidovudine-resistant virus isolates can become susceptible to the drug’s action if resistance to lamivudine subsequently develops in these isolates. However, the clinical significance of such changes has not yet been definitively determined.

Abacavir-resistant HIV-1 isolates have been obtained in vitro. These isolates are characterized by specific genotypic changes in the reverse transcriptase codons (codons M184V, K65R, L74V and Y115F).

HIV resistance to abacavir in vitro and in vivo develops slowly. Multiple mutations of the viral genome are required for a clinically significant increase in the inhibitory concentration for 50% of strains IC₅₀ (an 8-fold increase in IC₅₀ (inhibitory concentration in 50% of cases) relative to the “wild-type” virus strain). Abacavir-resistant isolates may also have reduced sensitivity to lamivudine, zalcitabine, tenofovir, emtricitabine and/or didanosine, but retain sensitivity to zidovudine and stavudine.

The development of cross-resistance between abacavir and lamivudine and antiretroviral drugs of other classes (e.g., protease inhibitors and non-nucleoside reverse transcriptase inhibitors) is unlikely. HIV isolates with reduced sensitivity to abacavir have been isolated from patients with uncontrolled viral replication in whom previous treatment with other nucleoside reverse transcriptase inhibitors was ineffective.

Clinical virus isolates with three or more mutations associated with resistance to nucleoside reverse transcriptase inhibitors are also likely to be resistant to abacavir. Cross-resistance due to the M184V mutation of reverse transcriptase is limited to the class of nucleoside reverse transcriptase inhibitors. Zidovudine, stavudine, abacavir and tenofovir retain their antiretroviral activity against Lamivudine-resistant HIV-1 isolates carrying only the M184V mutation.

Pharmacokinetics

The drug is bioequivalent to abacavir and lamivudine used as monodrugs.

When taken on an empty stomach, no significant differences in the extent of absorption (in AUC and C_max values) of each component were detected. Also, no clinically significant changes in pharmacokinetic parameters were identified due to taking the abacavir+Lamivudine combination on an empty stomach or with food. These data indicate that the drug can be taken regardless of meals.

Abacavir and Lamivudine are rapidly and well absorbed after oral administration. The absolute bioavailability of abacavir and lamivudine in adults after oral administration is 83% and 80-85%, respectively. The average time to reach C_max in serum is about 1.5 h and 1.0 h for abacavir and lamivudine, respectively. After a single oral dose of abacavir 600 mg, the mean C_max is 4.26 µg/ml, and the mean AUC is 11.95 µg×h/ml. After multiple oral administration of lamivudine 300 mg once daily for 7 days, the mean C_ss^max is 2.04 µg/ml, and the mean AUC₂₄ is 8.87 µg×h/ml.

After IV administration, the mean apparent V_d of abacavir and lamivudine is 0.8 and 1.3 L/kg, respectively. At therapeutic doses, abacavir is poorly or moderately (approximately 49%) bound to human plasma proteins. Lamivudine exhibits linear changes in pharmacokinetic parameters when used at therapeutic doses and is poorly bound to plasma proteins (less than 36%). This indicates a low likelihood of interaction with other drugs involving displacement from plasma protein binding.

Abacavir and Lamivudine penetrate the CNS and enter the cerebrospinal fluid. The AUC for cerebrospinal fluid is from 30% to 44% of the plasma AUC value. The C_max of abacavir in cerebrospinal fluid when taking the drug at a dose of 600 mg twice daily is 9 times higher than the IC₅₀ of abacavir, which is 0.08 µg/ml or 0.26 µmol/L. The mean ratio of lamivudine concentration in cerebrospinal fluid to its concentration in serum 2 and 4 hours after oral administration of the drug is approximately 0.12.

After multiple oral administration at a dose of 300 mg twice daily, no significant accumulation of abacavir is observed.

Abacavir is metabolized mainly in the liver by alcohol dehydrogenase to form 5′-carboxylic acid and by conjugation with glucuronic acid to form 5′-glucuronide, which accounts for about 66% of the total administered dose of the drug. These metabolites are excreted in the urine.

Lamivudine is almost not metabolized and is predominantly excreted unchanged by the kidneys. The likelihood of metabolic interaction with lamivudine is low, since only a small part (less than 10%) of the administered dose is metabolized in the liver.

The mean T_1/2 of abacavir is approximately 1.5 h. The elimination of abacavir occurs through metabolism in the liver followed by excretion of metabolites mainly in the urine. Approximately 83% of the administered dose of abacavir is found in the urine as metabolites and unchanged. The remainder is excreted in the feces.

The T_1/2 of lamivudine is from 5 to 7 h. The mean total clearance of lamivudine is approximately 0.32 L/h/kg, most of which is renal clearance (more than 70%), carried out by the organic cation transport system.

Pharmacokinetics in special clinical cases

Patients with mild hepatic impairment require a reduced daily dose of abacavir. For the treatment of such patients, a drug containing only abacavir should be used. It is assumed that in patients with moderate and severe hepatic impairment, the plasma concentration of abacavir will be characterized by significant variability and will be significantly increased. Therefore, the use of the drug is contraindicated in this group of patients. Data obtained from the use of lamivudine in patients with moderate and severe hepatic impairment indicate that no significant changes in the pharmacokinetic parameters of the drug occur with impaired liver function.

There are data on the pharmacokinetics of abacavir and lamivudine in patients with impaired renal function, obtained with separate use of the drugs. Abacavir is metabolized mainly in the liver. Approximately 2% of abacavir is excreted unchanged by the kidneys. The pharmacokinetic parameters of abacavir in patients with end-stage renal failure and normal renal function are practically the same. Studies have shown that in patients with impaired renal function, the plasma concentration of lamivudine increases due to reduced clearance. Due to the need to reduce the dose of lamivudine in patients with CC less than 50 ml/min, lamivudine monodrug should be prescribed.

Indications

Treatment of HIV infection in adults and adolescents over 12 years of age (as part of combination antiretroviral therapy).

ICD codes

Dosage Regimen

Therapy should be carried out by a physician experienced in the treatment of HIV infection.

Due to the inability to adjust the dose when using fixed-dose combination drugs, the drug should not be prescribed to adults and adolescents weighing less than 40 kg.

The drug can be taken regardless of meals.

For adults and children aged 12 years and older, the drug is prescribed 1 tablet once daily.

It is not recommended to use the drug for the treatment of children under 12 years of age due to the lack of possibility of dose adjustment.

When treating elderly patients, the increased frequency of liver, kidney, heart dysfunction, other concomitant diseases, as well as the use of other medications should be taken into account.

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

Patients with mild hepatic impairment may require a reduction in the dose of abacavir. Due to the inability to reduce the dose when using the combination drug, a drug containing only abacavir should be used. The drug is contraindicated in patients with moderate and severe hepatic impairment.

Adverse Reactions

When using the combination drug, side effects characteristic of abacavir and lamivudine may occur. For many of the side effects listed below, it remains unclear whether their occurrence is related to the action of the active substances of this drug, the simultaneous use of other drugs (used to treat HIV), or whether they are a manifestation of the underlying disease.

In clinical studies, approximately 5% of patients taking abacavir developed a hypersensitivity reaction, which in rare cases was fatal. This reaction is characterized by the occurrence of symptoms indicating multi-organ damage. Symptoms of a hypersensitivity reaction can occur at any time during treatment with abacavir, but they usually appear within the first 6 weeks of starting the drug (the average is 11 days).

The signs and symptoms of a hypersensitivity reaction are listed below.

From the hematopoietic system: lymphopenia.

From the nervous system: headache, paresthesia.

From the respiratory system: shortness of breath, cough, sore throat, respiratory distress syndrome, respiratory failure.

From the digestive system: nausea, vomiting, diarrhea, abdominal pain, mouth ulcers, increased liver function tests, liver failure.

From the urinary system: increased creatinine concentration, renal failure.

From the skin and subcutaneous tissue: rash (maculopapular or urticarial).

From the musculoskeletal system: myalgia, rarely – myolysis, arthralgia, increased CPK activity.

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

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

Abacavir

From the immune system: common – hypersensitivity reactions.

From the nervous system: common – headache.

From the digestive system: common – anorexia, nausea, vomiting, diarrhea; rare – pancreatitis.

From the metabolism: common – hyperlactatemia; rare – lactic acidosis.

From the skin and subcutaneous tissue: common – rash (without systemic symptoms); very rare – exudative erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Other: common – fever, apathy, feeling tired.

Lamivudine

From the hematopoietic system: uncommon – neutropenia, anemia, thrombocytopenia; very rare – true erythrocyte aplasia.

From the metabolism: common – hyperlactatemia; rare – lactic acidosis.

From the nervous system: common – headache; very rare – paresthesia, peripheral neuropathy.

From the digestive system: common – nausea, vomiting, pain in the upper abdomen, diarrhea; uncommon – temporary increase in AST, ALT; rare – increased serum amylase activity, pancreatitis.

From the skin and subcutaneous tissue: common – rash, alopecia.

From the musculoskeletal system: common – arthralgia, muscle damage; rare – rhabdomyolysis.

Other: common – feeling tired, malaise, fever.

Some patients receiving combination antiretroviral therapy have experienced redistribution/accumulation of body fat. The frequency of this phenomenon depends on many factors, including the combination of antiretroviral drugs.

Contraindications

Moderate and severe hepatic impairment; age under 12 years (lack of possibility for dose adjustment); hypersensitivity to abacavir or lamivudine, or other components of the drug.

Use in Pregnancy and Lactation

The safety of using the drug in pregnant women has not been established. Data have been obtained from reproductive studies of lamivudine and abacavir in animals. Therefore, the issue of prescribing the drug during pregnancy should be considered only if the expected benefit to the mother outweighs the potential risk to the fetus. The drug should be used in accordance with current recommendations for the use of antiretroviral therapy in pregnant women to prevent vertical transmission of HIV.

Since HIV is present in breast milk, women are not recommended to breastfeed their infants to avoid transmitting the virus to the child through breast milk.

Lamivudine is excreted in milk at concentrations close to those in serum. Abacavir is also expected to be excreted in milk, although this has not been confirmed.

Use in Hepatic Impairment

The use of the drug is contraindicated in patients with moderate and severe hepatic impairment.

Use in Renal Impairment

In patients with renal impairment, the dose of lamivudine should be reduced proportionally to the decrease in creatinine clearance. Therefore, the use of the drug is not recommended when creatinine clearance is less than 50 ml/min.

Pediatric Use

The use of the drug for the treatment of children under 12 years of age is not recommended due to the inability to adjust the dose.

Geriatric Use

When treating elderly patients, the increased frequency of hepatic, renal, cardiac impairments, other concomitant diseases, as well as the use of other medications should be taken into account.

Special Precautions

Carriage of the HLA-B*5701 allele significantly increases the risk of developing a hypersensitivity reaction to abacavir. In clinical study CNA106030 (PREDICT-1), it was shown that hypersensitivity reactions to abacavir developed in 48-61% of patients carrying the HLA-B*5701 allele, compared to patients without this allele (incidence of hypersensitivity reactions 0-4%).

Clinicians are recommended to screen for carriage of the HLA-B*5701 allele in HIV-infected patients who have not previously been prescribed abacavir-containing drugs. Screening for the HLA-B*5701 allele is recommended before re-prescribing an abacavir-containing drug in patients with an unknown HLA-B*5701 status who previously tolerated abacavir-containing therapy well. The use of abacavir drugs is not recommended in such patients and should be considered only in exceptional cases under careful medical supervision, when the anticipated benefit outweighs the potential risk.

The clinical diagnosis of a suspected hypersensitivity reaction should remain the basis for the decision to use abacavir-containing drugs in all patients. Even in the absence of the HLA-B*5701 allele, abacavir must be discontinued and not restarted in all cases where a hypersensitivity reaction cannot be ruled out based on clinical data, due to the potential risk of serious adverse effects or even a fatal outcome.

Some patients with hypersensitivity initially believed they were suffering from respiratory (pneumonia, bronchitis, pharyngitis) or flu-like illnesses, gastroenteritis, or a reaction to other drugs. As a result, the hypersensitivity reaction was not diagnosed immediately, and patients continued (or resumed) taking the drug. This led to the development of a more severe hypersensitivity reaction (including fatal outcomes). Bearing this in mind, the possibility of such a reaction must be considered and ruled out in patients presenting with symptoms of these illnesses.

Symptoms caused by the hypersensitivity reaction worsened with continued treatment and usually resolved after discontinuation of abacavir.

Reintroduction of abacavir following a hypersensitivity reaction within a few hours leads to a rapid return of symptoms. Recurrence of the hypersensitivity reaction may be more severe than the initial reaction and may be accompanied by life-threatening hypotension (including fatal outcomes).

There are isolated reports of hypersensitivity reactions occurring after reintroduction of abacavir that was discontinued due to the appearance of individual key symptoms of hypersensitivity (rash, fever, malaise, gastrointestinal disorders, or respiratory symptoms). In very rare cases, hypersensitivity reactions have been reported after resuming the drug in patients who had not previously exhibited symptoms of hypersensitivity.

Patients, regardless of HLA-B*5701 status**, who develop signs and symptoms of hypersensitivity should immediately consult their treating physician for advice. If hypersensitivity is diagnosed, the drug should be discontinued immediately. Treatment with the abacavir+lamivudine combination or other medicinal products containing abacavir should never be resumed after a hypersensitivity reaction has occurred. This is due to the threat of severe symptoms appearing within hours of re-administration, which can be fatal.

To prevent delayed detection and reduce the risk of life-threatening hypersensitivity, the drug should be completely discontinued if hypersensitivity cannot be ruled out, even if other potential illnesses are present (respiratory diseases, flu-like illnesses, gastroenteritis, reactions to other medications). Treatment with the abacavir+lamivudine combination or other medicinal products containing abacavir should not be resumed, even if symptoms of hypersensitivity appear upon re-administration of other drugs.

If treatment with the drug is discontinued, regardless of HLA-B*5701 allele carriage, the reason for discontinuation should be carefully reviewed and the absence of symptoms of a hypersensitivity reaction in the patient should be confirmed before resuming the drug. The abacavir+lamivudine combination or other medicinal products containing abacavir should not be resumed if a hypersensitivity reaction cannot be ruled out.

A small number of cases of hypersensitivity reactions have been described upon resumption of abacavir treatment after its discontinuation due to the appearance of any one of the typical symptoms of hypersensitivity (rash, fever, malaise, fatigue, gastrointestinal disturbances, and respiratory system disorders). Since a hypersensitivity reaction cannot be ruled out in all such cases, and considering data on its more severe course upon re-exposure to abacavir, resumption of therapy with the abacavir+lamivudine combination or another abacavir-containing drug in these patients is not recommended.

Hypersensitivity reactions have been observed, albeit extremely rarely, even upon resumption of treatment with this drug in patients who had not previously experienced symptoms of this reaction, and the interruption in taking the abacavir-containing drug was due to other reasons. In such a case, resumption of the drug is possible but requires that the patient or people around them have rapid access to medical care.

Screening for the HLA-B*5701 allele is recommended before re-prescribing an abacavir-containing drug in patients with an unknown HLA-B*5701 status who previously tolerated therapy with an abacavir-containing drug well.

Re-prescription of an abacavir-containing drug to patients carrying the HLA-B*5701 allele is not recommended and may be considered only in exceptional cases under careful medical supervision, when the anticipated benefit of treatment with the drug outweighs the potential risk.

The use of antiretroviral nucleoside analogues (including abacavir and lamivudine), taken either individually or in combination, has been associated with the development of lactic acidosis, hepatomegaly, and severe hepatic steatosis, including fatal cases. These phenomena were observed mainly in women.

Clinical signs of developing lactic acidosis include general weakness, anorexia, sudden unexplained weight loss, symptoms of respiratory system involvement (dyspnea, tachypnea) and gastrointestinal tract involvement.

Caution should be exercised when prescribing the drug to all patients, especially those with risk factors for liver damage. The drug should be discontinued if clinical or laboratory signs of lactic acidosis or hepatotoxicity (which include hepatomegaly and steatosis, even in the absence of significant transaminase elevations) appear.

Some patients receiving combination antiretroviral therapy have experienced body fat redistribution/accumulation, an increase in fat tissue on the back of the neck and upper back (“buffalo hump”), a decrease in peripheral fat deposits, a decrease in facial subcutaneous fat, breast enlargement, and increases in serum glucose and lipid concentrations.

Lipodystrophy can develop with the use of any drugs from the protease inhibitor class or nucleoside reverse transcriptase inhibitors. However, available data indicate that the risk of developing these adverse effects differs among drugs within these classes. Furthermore, the development of lipodystrophy is influenced by many factors. HIV infection itself, older age, and the duration of antiretroviral therapy play an important and possibly mutually potentiating role.

During clinical examination, attention should be paid to signs of body fat redistribution. Serum lipid levels and blood glucose concentration should be monitored carefully. If necessary, appropriate treatment for lipid metabolism disorders should be instituted.

Clinical studies and post-marketing data on the use of lamivudine indicate that in some patients with concomitant hepatitis B virus (HBV) infection, clinical or laboratory signs of hepatitis relapse may appear after discontinuation of lamivudine. Discontinuation of lamivudine may have more severe consequences in patients with decompensated liver disease. Therefore, in patients with concomitant hepatitis B virus infection, liver function tests should be monitored and hepatitis B virus replication levels should be regularly assessed upon discontinuation of the abacavir+lamivudine combination.

In HIV-infected patients with severe immunodeficiency who have asymptomatic or minimally symptomatic opportunistic infections at the time of initiating antiretroviral therapy, such therapy may lead to an exacerbation of symptoms of opportunistic infections or other severe consequences. These reactions typically occur within the first few weeks or months after starting antiretroviral therapy. Typical examples are cytomegalovirus retinitis, generalized or focal mycobacterial infection, and pneumonia caused by Pneumocystis jirovecii. The appearance of any inflammatory symptoms requires immediate examination and, if necessary, treatment.

The use of the abacavir+lamivudine combination or other antiretroviral drugs does not preclude the development of opportunistic infections or other complications of HIV infection; therefore, patients should remain under the supervision of a physician experienced in treating these conditions.

Current antiretroviral therapy does not prevent the sexual transmission of HIV or contact with infected blood. It is important to remember the need to observe appropriate safety measures.

A prospective observational epidemiological study investigating the incidence of myocardial infarction in patients receiving combination antiretroviral therapy found an association between prior abacavir use (within the previous 6 months) and an increased risk of myocardial infarction. A pooled analysis of clinical trials did not show an increased risk of myocardial infarction associated with abacavir use. The biological mechanisms explaining the potentially increased risk are unknown. Available data from cohort studies and controlled clinical trials do not allow a definitive determination of the association between abacavir therapy and the risk of myocardial infarction. Nevertheless, antiretroviral therapy, including drugs containing abacavir, should be prescribed with caution to patients with a possible risk of coronary artery disease. Measures should be taken to minimize risk factors (such as hypertension, dyslipidemia, diabetes mellitus, and smoking).

Effect on Ability to Drive and Operate Machinery

No specific studies have been conducted on the effect of lamivudine on the ability to concentrate when driving/operating machinery. It is unlikely that the drug will negatively affect the ability to perform tasks requiring concentration, motor, or cognitive skills. Nevertheless, when assessing a patient’s ability to concentrate, their general condition, as well as the nature of potential side effects that may occur while taking the drug, should be taken into account.

Drug Interactions

The spectrum of drug interactions for the drug is determined by the interactions of abacavir and lamivudine, among which no clinically significant interactions have been identified to date. Abacavir and lamivudine are minimally metabolized by cytochrome P450 system enzymes (e.g., CYP3A4, CYP2C9, or CYP2D6) and do not have inhibitory or inducing effects on this enzyme system. Therefore, the likelihood of interaction of the drug with antiretroviral non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and other drugs metabolized by the major cytochrome P450 enzymes is low.

The likelihood of metabolic interaction with lamivudine is low because it is minimally metabolized, has low plasma protein binding, and is excreted almost exclusively by the kidneys. Lamivudine is eliminated mainly by active organic cation secretion. The possibility of interaction with other drugs should be considered, especially in cases where renal excretion is the primary route of elimination for the drug.

Drug Interactions Due to Abacavir

The metabolism of abacavir is impaired when taken concomitantly with ethanol, leading to an approximately 41% increase in the AUC of abacavir. Given the safety profile of abacavir, these data are not considered clinically significant. Abacavir does not affect the metabolism of ethanol.

In a pharmacokinetic study of drugs with concomitant administration of abacavir (at a dose of 600 mg twice daily) and methadone, a 35% decrease in the C_max of abacavir and a 1-hour decrease in the time to C_max were observed, but the AUC remained unchanged. The changes in abacavir pharmacokinetics 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 for the majority of patients; however, a dose adjustment of methadone may sometimes be necessary.

Drug Interactions Due to Lamivudine

Administration of trimethoprim/sulfamethoxazole 160 mg/800 mg (co-trimoxazole) causes a 40% increase in lamivudine exposure, which is due to the presence of trimethoprim. However, except in patients with renal failure, no dose adjustment of lamivudine is required. Lamivudine does not affect the pharmacokinetics of trimethoprim and sulfamethoxazole. Concomitant use of lamivudine with higher doses of co-trimoxazole used for the treatment of pneumonia (caused by Pneumocystis carinii) and toxoplasmosis has not been studied.

Lamivudine may suppress the intracellular phosphorylation of zalcitabine when these drugs are taken concomitantly. Therefore, the drug is not recommended to be taken in combination with zalcitabine.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.