Source: Health Products and Food Branch (CA) Revision Year: 2022
3TC is contraindicated in patients with previously demonstrated clinically significant hypersensitivity to any of the components of the products (see section 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING).
Please see 3 Serious Warnings and Precautions Box at the beginning of Part I: Health Professional Information.
3TC should not be administered concomitantly with other products containing lamivudine including HEPTOVIR Tablets and Oral solution, COMBIVIR Tablets, KIVEXA Tablets, TRIUMEQ Tablets, or DOVATO Tablets.
3TCshould also not be administered concomitantly with emtricitabine containing products, including ATRIPLA Tablets, EMTRIVA Capsules, TRUVADA Tablets, COMPLERA Tablets, STRIBILD Tablets, GENVOYA Tablets, DESCOVY Tablets, BIKTARVY Tablets, SYMTUZA Tablets, or ODEFSEY Tablets.
Evidence for once-daily dosing using the 300 mg tablets is mainly in antiretroviral naive patients.
Patients receiving 3TC or any other antiretroviral therapy may continue to develop opportunistic infections and other complications of HIV infection. Therefore, patients should remain under close observation by physicians experienced in the treatment of patients with HIV-associated diseases.
While effective viral suppression with antiretroviral therapy has been proven to substantially reduce the risk of sexual transmission, a residual risk cannot be excluded. Precautions to prevent transmission should be taken in accordance with national guidelines.
Diabetic patients should be advised that an adult dose of 3TC oral solution contains 3 g of sucrose.
Serum lipid and blood glucose levels may increase during antiretroviral therapy. Disease control and life style changes may also be contributing factors. Consideration should be given to the measurement of serum lipids and blood glucose. Lipid disorders and blood glucose elevations should be managed as clinically appropriate.
Very rare occurrences of pure red cell aplasia have been reported with lamivudine use. Discontinuation of lamivudine has resulted in normalization of hematologic parameters in patients with suspected lamivudine-induced pure red cell aplasia.
Pancreatitis has been observed in some patients receiving nucleoside analogues, including lamivudine. However, it is unclear whether this was due to treatment with the medicinal product or to the underlying HIV disease. Pancreatitis must be considered whenever a patient develops abdominal pain, nausea, vomiting or elevated biochemical markers. Discontinue use of lamivudine until diagnosis of pancreatitis is excluded.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of antiretroviral nucleoside analogues either alone or in combination, including lamivudine. A majority of these cases have been in women. Female sex and obesity may be risk factors.
Clinical features which may be indicative of the development of lactic acidosis include generalized weakness, anorexia and sudden unexplained weight loss, gastrointestinal symptoms and respiratory symptoms (dyspnea and tachypnea).
Caution should be exercised when administering 3TC or other nucleoside analogues, particularly to those with known risk factors for liver disease. Treatment with 3TC should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis with or without hepatitis (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).
Clinical trials and marketed use of 3TC have shown that some patients with chronic hepatitis B virus (HBV) disease may experience clinical or laboratory evidence of recurrent hepatitis upon discontinuation of 3TC, which may have more severe consequences in patients with decompensated liver disease. If 3TC is discontinued in a patient with HIV and HBV coinfection, periodic monitoring of both liver function tests and markers of HBV replication should be considered.
In non–HIV 1 infected patients treated with lamivudine for chronic hepatitis B, emergence of lamivudine resistant HBV has been detected and has been associated with diminished treatment response (see full Product Monograph for HEPTOVIR for additional information). Emergence of hepatitis B virus variants associated with resistance to lamivudine has also been reported in HIV 1 infected patients who have received lamivudine containing antiretroviral regimens in the presence of concurrent infection with hepatitis B virus.
Immune reconstitution inflammatory syndrome (IRIS) has been reported in HIV-infected patients treated with combination antiretroviral therapy, including 3TC. During the initial phase of treatment, patients responding to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections [such as Mycobacterium avium-complex (MAC), cytomegalovirus (CMV), Pneumocystis jirovecii pneumonia (PCP), and tuberculosis(TB)], which may necessitate further evaluation and treatment.
Autoimmune disorders (such as Graves' disease, polymyositis, autoimmune hepatitis and Guillain-Barre syndrome) have also been reported to occur in the setting of immune reconstitution, however the time to onset is more variable, and can occur many months after initiation of treatment and sometimes can be an atypical presentation.
Patients with impaired renal function may be at a greater risk of toxicity from 3TC due to decreased renal clearance of the drug. Consideration should be given to appropriate reduction in the dose of lamivudine (see 4.2 Recommended Dose and Dosage Adjustment).
3TC has not been studied in pregnant women. Therefore, 3TC should not be used in pregnant women unless the potential benefits to the mother outweigh the potential risk to the fetus (see 10 CLINICAL PHARMACOLOGY).
There have been reports of developmental delay, seizures and other neurological disease. However, a causal relationship between these events and NRTI exposure in utero or peri partum has not been established. Findings of developmental toxicity were also observed in animal toxicology studies (see 16 NON-CLINICAL TOXICOLOGY).
There have also been reports of mild, transient elevations in serum lactate levels, which may be due to mitochondrial dysfunction, in neonates and infants exposed in utero or peri partum to nucleoside reverse transcriptase inhibitors (NRTIs). The clinical relevance of transient elevations in serum lactate is unknown.
Antiretroviral Pregnancy Registry:
To monitor maternal-fetal outcomes of pregnant women exposed to ART (antiretroviral therapy), including 3TC, an Antiretroviral Pregnancy Registry has been established. Healthcare providers are encouraged to register patients: http://www.apregistry.com, Telephone: (800) 258-4263, Fax: (800) 800-1052
The Antiretroviral Pregnancy Registry has received reports of over 11,000 exposures to lamivudine during pregnancy resulting in live birth. These consist of over 4,200 exposures during the first trimester, over 6, 900 exposures during the second/third trimester and included 135 and 198 birth defects respectively. The prevalence (95% CI) of defects in the first trimester was 3.2% (2.6, 3.7%) and in the second/third trimester, 2.8% (2.4, 3.2%). Among pregnant women in the reference population, the background rate of birth defects is 2.7%. The Antiretroviral Pregnancy Registry does not show an increased risk of major birth defects for lamivudine compared to the background rate.
HIV-1 infected mothers should not breast-feed their infants to avoid risking postnatal transmission of HIV. Lamivudine is excreted in breast milk at similar concentrations to those found in serum. Because of both the potential for HIV transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breast-feed if they are receiving 3TC.
The safety and effectiveness of 3TC have been established in pediatric patients aged 3 months and older. Use of 3TC is supported by pharmacokinetic trials and evidence from adequate and wellcontrolled trials of 3TC in adults and pediatric subjects (see 4.2 Recommended Dose and Dosage Adjustment, 10.3 Pharmacokinetics, Special Populations and Conditions, Pediatrics, 14.1 Clinical Trials by Indication, Table 14 and 14.1 Clinical Trials by Indication, Study Results, Clinical Endpoint Study in Pediatric Patients).
Lower Virologic Suppression with Oral Solutions in Pediatrics:
An all-tablet antiretroviral regimen should be used when possible. When an all-tablet regimen cannot be used, 3TC oral solution may be used concomitantly with sorbitol-containing medicines only if the benefits of treatment outweigh possible risks, including lower virologic suppression. Consider more frequent monitoring of HIV-1 viral load when 3TC oral solution is used with chronically-administered, sorbitol-containing medicines (see 9.4 Drug-Drug Interactions).
Pediatric patients who received 3TC oral solution concomitantly with other antiretroviral oral solutions at any time up to 96 weeks in the ARROW study had lower rates of virologic suppression, lower plasma lamivudine exposure, and developed viral resistance more frequently than those receiving 3TC tablets (see 10.3 Pharmacokinetics, Special Populations and Conditions, Pediatrics; 15 MICROBIOLOGY, Resistance and15 MICROBIOLOGY, Pediatrics). The proportion of subjects with HIV-1 RNA of less than 80 copies per mL through 96 weeks was higher in patients who had received tablet formulations (71% [213/301] and 74% [221/300]) than in those who had received any solution formulations (57% [17/30] and 50% [13/26] for once-daily and twice-daily dosing, respectively.
Clinical studies of 3TC did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger patients. In general, caution should be exercised in the administration and monitoring of 3TC in elderly patients, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.
The following adverse reactions are discussed in the 3 SERIOUS WARNINGS AND PRECAUTIONS BOX and 7 WARNINGS AND PRECAUTIONS sections:
Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use.
Selected clinical adverse events in therapy-naive patients receiving either 3TC 300 mg once daily or 3TC 150 mg twice daily in combination with RETROVIR 300mg twice daily and efavirenz 600 mg once daily are listed in Table 5 and Table 6. The most frequent clinical adverse events (≥5% frequency) reported during therapy with 3TC 150 mg b.i.d. plus RETROVIR (AZT) 600 mg per day compared with RETROVIR (AZT) are listed in Table 7.
Table 5. Most Common Adverse Events (>10%)a Occurring in Subjects in EPV20001 Safety Population during 48 Weeks:
| Adverse Event | 3TC 300 mg q.d. plus RETROVIR plus Efavirenz (n = 272) | 3TC 150 mg b.i.d. plus RETROVIR plus Efavirenz (n = 273) |
|---|---|---|
| At Least One Adverse Event | 94% | 97% |
| Nausea | 39% | 44% |
| Dizziness | 30% | 36% |
| Fatigue | 31% | 31% |
| Dreams | 26% | 24% |
| Headaches | 25% | 22% |
| Rashes | 24% | 20% |
| Viral respiratory infections | 22% | 21% |
| Diarrhea | 20% | 21% |
| Ear, nose, & throat infections | 15% | 21% |
| Sleep disorders | 17% | 19% |
| Vomiting | 14% | 16% |
| Abdominal pain | 10% | 19% |
| Anorexia | 13% | 9% |
| Mood disorders | 12% | 10% |
| Musculoskeletal pain | 7% | 14% |
| Sinus disorders | 9% | 10% |
| Fever | 7% | 12% |
a >10% of subjects in either treatment group
Table 6. Severe Adverse Events (Grade ¾) Occurring in More Than One Subject a
in EPV20001 Safety Population during 48 Weeks:
| Adverse Event | 3TC 300 mg q.d. plus RETROVIR plus Efavirenz (n = 272) | 3TC 150 mg b.i.d. plus RETROVIR plus Efavirenz (n = 273) |
|---|---|---|
| At Least One Severe Adverse Event | 24% | 26% |
| Increased creatine phosphokinase levels | 3% | 4% |
| Nausea | 3% | 3% |
| Increased liver function tests | 2% | 3% |
| Decreased white cells | 2% | 2% |
| Fatigue | 1% | 2% |
| Hypertriglyceridemia | 2% | 1% |
| Dizziness | 1% | 1% |
| Vomiting | 1% | <1% |
| Sleep disorders | 1% | 1% |
| Abdominal pain | 1% | <1% |
| Dreams | <1% | 1% |
| Increased amylase levels | 1% | <1% |
| Anxiety | 1% | <1% |
| Rashes | 0% | 2% |
| Anemia | <1% | 1% |
| Depressive disorders | <1% | 1% |
| Mood disorders | 1% | <1% |
| Skin infections | <1% | <1% |
| Ear, nose, & throat infections | <1% | <1% |
| Diarrhea | <1% | <1% |
| Headaches | <1% | <1% |
| Suicide & attempted suicide | <1% | <1% |
| Viral respiratory infections | <1% | <1% |
| Confusion | <1% | <1% |
| Migraines | <1% | <1% |
| General signs & symptoms | <1% | <1% |
| Malaise | 0% | <1% |
| Viral Infection | <1% | 0% |
| Lower respiratory infections | <1% | <1% |
| Hypotension | 0% | <1% |
a more than one subject in any treatment group.
Table 7. Most Frequent Clinical Adverse Events (≥5% Frequency) Reported in Four Controlled Clinical Trials (NUCA3001, NUCA3002, NUCB3001 and NUCB3002):
| Adverse Event | 3TC 150 mg b.i.d. plus RETROVIR (AZT) (n = 251) | RETROVIR (AZT) (n = 230) |
|---|---|---|
| Body as a whole | ||
| Headache | 35% | 27% |
| Malaise and fatigue | 27% | 23% |
| Fever or chills | 10% | 12% |
| Digestive | ||
| Nausea | 33% | 29% |
| Diarrhea | 18% | 22% |
| Nausea and vomiting | 13% | 12% |
| Anorexia and/or decreased appetite | 10% | 7% |
| Abdominal pain | 9% | 11% |
| Abdominal cramps | 6% | 3% |
| Dyspepsia | 5% | 5% |
| Nervous | ||
| Neuropathy | 12% | 10% |
| Dizziness | 10% | 7% |
| Insomnia & other sleep disorders | 11% | 4% |
| Depressive disorders | 9% | 4% |
| Respiratory | ||
| Nasal signs & symptoms | 20% | 11% |
| Cough | 18% | 13% |
| Skin & appendages | ||
| Skin rashes | 9% | 6% |
| Musculoskeletal | ||
| Musculoskeletal pain | 12% | 10% |
| Myalgia | 8% | 6% |
| Arthralgia | 5% | 5% |
Selected clinical adverse events and physical findings with a ≥5% frequency during therapy with 3TC 4 mg/kg twice daily plus RETROVIR (AZT) 160mg/m2 three times daily compared with didanosine in patients without, or with, minimal (≤56 days) prior antiretroviral therapy are listed in Table 8.
Table 8. Selected Clinical Adverse Events and Physical Findings (≥5% Frequency) in Pediatric Patients in Study ACTG300:
| Adverse Event | 3TC plus RETROVIR (AZT) (n = 236) | Didanosine (n = 235) |
|---|---|---|
| Body as a whole | ||
| Fever | 25% | 32% |
| Digestive | ||
| Hepatomegaly | 11% | 11% |
| Nausea & vomiting | 8% | 7% |
| Diarrhea | 8% | 6% |
| Stomatitis | 6% | 12% |
| Splenomegaly | 5% | 8% |
| Respiratory | ||
| Cough | 15% | 18% |
| Abnormal breath sounds/wheezing | 7% | 9% |
| Ear, Nose and Throat | ||
| Signs or symptoms of ears* | 7% | 6% |
| Nasal discharge or congestion | 8% | 11% |
| Other | ||
| Skin rashes | 12% | 14% |
| Lymphadenopathy | 9% | 11% |
* Includes pain, discharge, erythema, or swelling of an ear.
Pancreatitis, which has been fatal in some cases, has been observed in antiretroviral nucleosideexperienced pediatric patients receiving 3TC alone or in combination with other antiretroviral agents. In an open-label dose-escalation study (NUCA2002), 14 patients (14%) developed pancreatitis while receiving monotherapy with 3TC. Three of these patients died of complications of pancreatitis. In a second open-label study (NUCA2005), 12 patients (18%) developed pancreatitis. In Study ACTG300, pancreatitis was not observed in 236 patients randomized to 3TC plus RETROVIR (AZT). Pancreatitis was observed in one patient in this study who received open-label 3TC in combination with RETROVIR (AZT) and ritonavir following discontinuation of didanosine monotherapy.
Paresthesias and peripheral neuropathies were reported in 15 patients (15%) in Study NUCA2002, six patients (9%) in Study NUCA2005, and two patients (<1%) in Study ACTG300.
The safety of once-daily compared with twice-daily dosing of 3TC was assessed in the ARROW trial. Primary safety assessment in the ARROW trial was based on Grade 3 and Grade 4 adverse events. The frequency of Grade 3 and 4 adverse events was similar among subjects randomized to once-daily dosing compared with subjects randomized to twice-daily dosing. One event of Grade 4 hepatitis in the once-daily cohort was considered as uncertain causality by the investigator and all other Grade 3 or 4 adverse events were considered not related by the investigator.
Other clinical adverse events reported in controlled clinical trials in association with 3TC 150 mg b.i.d. plus RETROVIR (AZT) 600 mg per day in at least 1% of patients were:
Gastrointestinal: abdominal discomfort and pain (3%), abdominal distension (3%), dyspepsia (2%), gastrointestinal discomfort and pain (3%), gastrointestinal gas (4%), hyposalivation (2%), oral ulceration (1%)
Musculoskeletal: muscle atrophy/weakness/tiredness (1%), muscle pain (2%)
Neurological: mood disorders (1%), sleep disorders (4%), taste disturbances (1%)
Other: breathing disorders (2%), general signs and symptoms (1%), pain (2%), sexual function disturbances (1%), temperature regulation disturbance (1%)
Skin: pruritis (1%), skin rashes (1%), sweating (1%)
Pancreatitis was observed in 9 of 2613 adult patients (0.3%) in controlled clinical trials EPV20001, NUCA3001, NUCB3001, NUCA3002, NUCB3002, and NUCB3007.
Six percent (6%) of patients treated with 3TC 150 mg b.i.d. plus RETROVIR (AZT) 200 mg t.i.d. in controlled clinical trials permanently discontinued treatment due to an investigator-attributed drugrelated adverse event, compared with 7% of patients receiving monotherapy with RETROVIR (AZT) and 13% of patients receiving RETROVIR (AZT) plus zalcitabine. The most frequent adverse events necessitating such permanent discontinuation of therapy with 3TC 150 mg b.i.d. plus RETROVIR (AZT) 200 mg t.i.d. were nausea (2%), malaise and fatigue (1%), and anemia (1%).
The frequencies of selected laboratory abnormalities (Grades 3 and 4) in adults during therapy are listed in Table 9.
Table 9. Selected Laboratory Abnormalities in Studies of 3TC in Adults:
| Test (Abnormal Level) | 24-Week Surrogate Endpoint Studies (NUCA3001, NUCA3002, NUCB3001, NUCB3002) | Clinical Endpoint Study* (NUCB3007) | Study EPV20001* | |||
|---|---|---|---|---|---|---|
| 3TC plus RETROVIR | RETROVIR | 3TC plus current therapy† | Placebo plus current therapy† | 3TC 300 mg q.d.♠ | 3TC 150 mg b.i.d.♠ | |
| Neutropenia | ||||||
| (ANC <750/mm³) | 7% | 5% | 15% | 13% | 6% | 6% |
| Anemia (Hgb <8.0 g/dL) | 3% | 2% | 2% | 3% | <1% | <1% |
| Thrombocytopenia | ||||||
| (platelets <50000/mm³) | <1% | 1% | 3% | 4% | 0% | <1% |
| ALT (>5.0 × ULN) | 4% | 4% | 4% | 2% | 3% | 5% |
| AST (>5.0 × ULN) | 2% | 2% | 4% | 2% | 2% | 4% |
| Bilirubin (>2.5 × ULN) | <1% | <1% | ND | ND | 0% | <1% |
| Amylase (>2.0 × ULN) | 4% | 2% | 2% | 1% | 3% | 2% |
* The median duration on study was 12 months.
† Current therapy was either zidovudine, zidovudine plus didanosine, or zidovudine plus zalcitabine.
♠ Therapy was 3TC plus RETROVIR plus efavirenz.
ULN = Upper limit of normal
ANC = Absolute neutrophil count
ND = Not done
Selected laboratory abnormalities experienced by pediatric patients without or minimal (≤56 days) prior antiretroviral therapy are listed in Table 10.
Table 10. Frequencies of Selected Laboratory Abnormalities in Pediatric Patients in Study ACTG300:
| Test (Abnormal Level) | 3TC plus RETROVIR (AZT) | Didanosine |
|---|---|---|
| Neutropenia (ANC <400/mm³) | 8% | 3% |
| Anemia (Hgb <7.0 g/dL) | 4% | 2% |
| Thrombocytopenia (platelets <50,000/mm³) | 1% | 3% |
| ALT (>10 x ULN) | 1% | 3% |
| AST (>10 x ULN) | 2% | 4% |
| Lipase (>2.5 x ULN) | 3% | 3% |
| Total Amylase (>2.5 x ULN) | 3% | 3% |
ULN = Upper limit of normal.
ANC = Absolute neutrophil count.
The following additional adverse experiences have been reported in post-marketing experience without regard to causality. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to either their seriousness, frequency of reporting, potential causal connection to lamivudine, or a combination of these factors.
Body as a whole: anaphylaxis, fatigue, fever, malaise, weakness
Digestive: stomatitis
Endocrine/Metabolic: hyperglycemia, hyperlactatemia, lactic acidosis and hepatic steatosis (see 7 WARNINGS AND PRECAUTIONS, Hepatic/Biliary/Pancreatic)
Gastrointestinal: diarrhea, nausea, pancreatitis, rises in serum amylase, upper abdominal pain, vomiting
Hematological: pure red cell aplasia
Hepatic: transient rises in liver enzymes
Hemic and Lymphatic: anemia, lymphadenophathy, neutropenia, splenomegaly, thrombocytopenia
Immune System: Immune Reconstitution Inflammatory Syndrome (see 7 WARNINGS AND PRECAUTIONS, Immune)
Musculoskeletal: arthralgia, muscle disorders including very rarely rhabdomyolysis
Nervous: headache, paresthesia, peripheral neuropathy
Other: alopecia
Skin: pruritus, rash, urticaria
Lamivudine is predominantly eliminated by active organic cationic secretion.
The possibility of interactions with other drugs administered concurrently should be considered, particularly when the main route of elimination is renal.
In vitro, lamivudine demonstrates no or weak inhibition of the drug transporters organic anion transporter 1B1 (OATP1B1), OATP1B3, breast cancer resistance protein (BCRP) or P-glycoprotein (Pgp), multidrug and toxin extrusion protein 1 (MATE1), MATE2-K or organic cation transporter 3 (OCT3). Lamivudine is therefore not expected to affect the plasma concentrations of drugs that are substrates of these drug transporters.
Lamivudine is an inhibitor of OCT1 and OCT2 in vitro with IC50 values of 17 and 33 µM, respectively, however lamivudine has low potential to affect the plasma concentrations of OCT1 and OCT2 substrates at therapeutic drug exposures (up to 300 mg).
Lamivudine is a substrate of MATE1, MATE2-K and OCT2 in vitro. Trimethoprim (an inhibitor of these drug transporters) has been shown to increase lamivudine plasma concentrations, however this interaction is not considered clinically significant as no dose adjustment of lamivudine is needed.
Lamivudine is a substrate of the hepatic uptake transporter OCT1. As hepatic elimination plays a minor role in the clearance of lamivudine, drug interactions due to inhibition of OCT1 are unlikely to be of clinical significance.
Lamivudine is a substrate of Pgp and BCRP, however due to its high bioavailability it is unlikely that these transporters play a significant role in the absorption of lamivudine. Therefore co-administration of drugs that are inhibitors of these efflux transporters is unlikely to affect the disposition and elimination of lamivudine.
The drugs listed in this table are based on either drug interaction case reports or studies, or potential interactions due to the expected magnitude and seriousness of the interaction (i.e., those identified as contraindicated).
Table 11. Established or Potential Drug-Drug Interactions:
| Proper name | Effect | Clinical comment |
|---|---|---|
| Emtricitabine | Lamivudine may inhibit the intracellular phosphorylation of emtricitabine when the two medicinal products are used concurrently. Additionally, the mechanism of viral resistance for both lamivudine and emtricitabine is mediated via mutation of the same viral reverse transcriptase gene (M184V) and therefore the therapeutic efficacy of these drugs in combination therapy may be limited. | Lamivudine is not recommended for use in combination with emtricitabine or emtricitabinecontaining fixed dose combinations. |
| Sorbitol | Coadministration of sorbitol solution (3.2 g, 10.2 g, 13.4 g) with a single 300 mg dose of lamivudine oral solution resulted in dose-dependent decreases of 14%, 32%, and 36% in lamivudine exposure (AUC∞) and 28%, 52%, and 55% in the Cmax of lamivudine in adults. | When possible, avoid use of lamivudine with sorbitol-containing medicines or consider more frequent monitoring of HIV-1 viral load when chronic coadministration cannot be avoided (see 7 WARNINGS AND PRECAUTIONS, General). |
| Trimethoprim | Administration of trimethoprim, a constituent of co-trimoxazole, causes a 40% increase in lamivudine plasma levels. | However, unless the patient has renal impairment, no dosage adjustment of lamivudine is necessary. Lamivudine has no effect on the pharmacokinetics of co-trimoxazole. Administration of co-trimoxazole with the 3TC/RETROVIR (AZT) combination in patients with renal impairment should be carefully assessed. The effect of co-administration of 3TC with higher doses of co-trimoxazole for the treatment of Pneumocystis jiroveci pneumonia (also referred to as PCP) and toxoplasmosis has not been studied. |
| Zidovudine | Zidovudine has no effect on the pharmacokinetics of lamivudine (see 10 CLINICAL PHARMACOLOGY section) | A modest increase in Cmax (28%) was observed for zidovudine when administered with lamivudine, however overall exposure (AUC) was not significantly altered. Zidovudine plasma levels are not significantly altered when coadministered with 3TC. |
Interactions with food have not been established.
Interactions with herbal products have not been established.
Interactions with laboratory tests have not been established.
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