Lamivudine 300 MG Oral Tablet
DRUG INTERACTIONS
7 Lamivudine is predominantly eliminated in the urine by active organic cationic secretion.
The possibility of interactions with other drugs administered concurrently should be considered, particularly when their main route of elimination is active renal secretion via the organic cationic transport system (e.g., trimethoprim).
No data are available regarding interactions with other drugs that have renal clearance mechanisms similar to that of lamivudine.
Zalcitabine is not recommended for use in combination with lamivudine.
( 7.2 ) 7.1 Interferon- and Ribavirin-Based Regimens Although no evidence of a pharmacokinetic or pharmacodynamic interaction (e.g., loss of HIV-1/HCV virologic suppression) was seen when ribavirin was coadministered with lamivudine in HIV-l/HCV co-infected patients, hepatic decompensation (some fatal) has occurred in HIV–l/HCV co-infected patients receiving combination antiretroviral therapy for HIV-1 and interferon alfa with or without ribavirin [see Warnings and Precautions (5.4) , Clinical Pharmacology (12.3) ] .
7.2 Zalcitabine Lamivudine and zalcitabine may inhibit the intracellular phosphorylation of one another.
Therefore, use of lamivudine in combination with zalcitabine is not recommended.
7.3 Trimethoprim/Sulfamethoxazole (TMP/SMX) No change in dose of either drug is recommended.
There is no information regarding the effect on lamivudine pharmacokinetics of higher doses of TMP/SMX such as those used to treat PCP.
7.4 Drugs with No Observed Interactions With lamivudine A drug interaction study showedno clinically significant interaction between lamivudine and zidovudine.
OVERDOSAGE
10 There is no known antidote for lamivudine.
One case of an adult ingesting 6 g of lamivudine was reported; there were no clinical signs or symptoms noted and hematologic tests remained normal.
Two cases of pediatric overdose were reported in Study ACTG300.
One case involved a single dose of 7 mg/kg of lamivudine; the second case involved use of 5 mg/kg of lamivudine twice daily for 30 days.
There were no clinical signs or symptoms noted in either case.
Because a negligible amount of lamivudine was removed via (4-hour) hemodialysis, continuous ambulatory-peritoneal dialysis, and automated peritoneal dialysis, it is not known if continuous hemodialysis would provide clinical benefit in a lamivudine overdose event.
If overdose occurs, the patient should be monitored, and standard supportive treatment applied as required.
DESCRIPTION
11 Lamivudine USP (also known as 3TC), a synthetic nucleoside analogue with activity against HIV-1 and HBV.
The chemical name of lamivudine USP is 2(1H) – Pyrimidinone, 4-amino-1- [2- (hydroxymethyl)-1,3-oxathio-lan-5-yl], (2R-cis)-.
It has a molecular formula of C 8 H 11 N 3 O 3 S and a molecular weight of 229.26.
It has the following structural formula: Lamivudine USP is a white to an off white solid and soluble in water.
Lamivudine tablets are for oral administration.
Each film-coated tablet contains 150 mg or 300 mg of lamivudine USP and the following inactive ingredients: crospovidone, isomalt, isopropyl alcohol, magnesium stearate and methylene chloride.
The tablets are coated with opadry white containing hypromellose, polyethylene glycol, polysorbate 80 and titanium dioxide.
structure.jpg
CLINICAL STUDIES
14 The use of lamivudine is based on the results of clinical studies in HIV-1-infected patients in combination regimens with other antiretroviral agents.
Information from trials with clinical endpoints or a combination of CD4+ cell counts and HIV-l RNA measurements is included below as documentation of the contribution of lamivudine to a combination regimen in controlled trials.
14.1 Adults Clinical Endpoint Study : NUCB3007 (CAESAR) was a multi-center, double-blind, placebo-controlled study comparing continued current therapy (zidovudine alone [62% of patients] or zidovudine with didanosine or zalcitabine [38% of patients]) to the addition of lamivudine or lamivudine plus an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI), randomized 1:2:1.
A total of 1,816 HIV-l-infected adults with 25 to 250 CD4+ cells/mm 3 (median = 122 cells/mm 3 ) at baseline were enrolled: median age was 36 years, 87% were male, 84% were nucleoside-experienced, and 16% were therapy-naive.
The median duration on study was 12 months.
Results are summarized in Table 8.
Table 8.
Number of Patients (%) With at Least One HIV-1 Disease Progression Event or Death Endpoint Current Therapy (n= 460) Lamivudine plus Current Therapy (n=896) Lamivudine plus an NNRTI a plus Current Therapy (n=460) HIV-1 progression or death 90 (19.6%) 86 (9.6%) 41 (8.9%) Death 27 (5.9%) 23 (2.6%) 14 (3.0%) a An investigational non-nucleoside reverse transcriptase inhibitor not approved in the United States Surrogate Endpoint Studies : Dual Nucleoside Analogue Studies : Principal clinical trials in the initial development of lamivudine compared lamivudine/zidovudine combinations with zidovudine monotherapy or with zidovudine plus zalcitabine.
These studies demonstrated the antiviral effect of lamivudine in a 2-drug combination.
More recent uses of lamivudine in treatment of HIV-1 infection incorporate it into multiple- drug regimens containing at least 3 antiretroviral drugs for enhanced viral suppression.
Dose Regimen Comparison Surrogate Endpoint Studies in Therapy-Naive Adults : EPV20001 was a multi-center, double-blind, controlled study in which patients were randomized 1:1 to receive lamivudine 300 mg once daily or lamivudine 150 mg twice daily, in combination with zidovudine 300 mg twice daily and efavirenz 600 mg once daily.
A total of 554 antiretroviral treatment-naive HIV-1-infected adults enrolled: male (79%), Caucasian (50%), median age of 35 years, baseline CD4+ cell counts of 69 to 1,089 cells/mm 3 (median = 362 cells/mm 3 ), and median baseline plasma HIV-1 RNA of 4.66 log 10 copies/mL.
Outcomes of treatment through 48 weeks are summarized in Figure 2 and Table 9.
Figure 2.
Virologic Response Through Week 48, EPV20001 ab (Intent-to-Treat) a Roche AMPLICOR HIV-1 MONITOR.
b Responders at each visit are patients who had achieved and maintained HIV-1 RNA<400 copies/mL without discontinuation by that visit.
Table 9.
Outcomes of Randomized Treatment Through 48 Weeks (Intent-to- Treat) Outcome Lamivudine300mg Once Daily plus Zidovudine plus Efavirenz (n = 278) Lamivudine150mg Twice Daily plus Zidovudine plus Efavirenz (n = 276) Responder a 67% 65% Virologic failure b 8% 8% Discontinued due to clinical progression <1% 0% Discontinued due to adverse events 6% 12% Discontinued due to other reasons c 18% 14% a Achieved confirmed plasma HIV-1 RNA <400 copies/mL and maintained through 48 weeks.
b Achieved suppression but rebounded by Week 48, discontinued due to virologic failure, insufficient viral response according to the investigator, or never suppressed through Week 48.
c Includes consent withdrawn, lost to followup, protocol violation, data outside the study-defined schedule, and randomized but never initiated treatment.
The proportions of patients with HIV-l RNA <50 copies/mL (via Roche Ultrasensitive assay) through Week 48 were 61% for patients receiving lamivudine 300 mg once daily and 63% for patients receiving lamivudine 150 mg twice daily.
Median increases in CD4+ cell counts were 144 cells/mm 3 at Week 48 in patients receiving lamivudine 300 mg once daily and 146 cells/mm 3 for patients receiving lamivudine 150 mg twice daily.
A small, randomized, open-label pilot study, EPV40001, was conducted in Thailand.
A total of 159 treatment-naive adult patients (male 32%, Asian 100%, median age 30 years, baseline median CD4+ cell count 380 cells/mm 3 , median plasma HIV-1 RNA 4.8 log 10 copies/mL) were enrolled.
Two of the treatment arms in this study provided a comparison between lamivudine 300 mg once daily (n = 54) and lamivudine 150 mg twice daily (n = 52), each in combination with zidovudine 300 mg twice daily and abacavir 300 mg twice daily.
In intent-to-treat analyses of 48-week data, the proportions of patients with HIV-1 RNA below 400 copies/mL were 61% (33/54) in the group randomized to once-daily lamivudine and 75% (39/52) in the group randomized to receive all 3 drugs twice daily; the proportions with HIV-l RNA below 50 copies/mL were 54% (29/54) in the once-daily lamivudine group and 67% (35/52) in the all-twice- daily group; and the median increases in CD4+ cell counts were 166 cells/mm 3 in the once-daily lamivudine group and 216 cells/mm 3 in the all-twice-daily group.
Figure2.jpg 14.2 Pediatric Patients Clinical Endpoint Study: ACTG300 was a multi-center, randomized, double-blind study that provided for comparison of lamivudine plus RETROVIR (zidovudine) with didanosine monotherapy.
A total of 471 symptomatic, HIV-1-infected therapy-naive (≤56 days of antiretroviral therapy) pediatric patients were enrolled in these 2 treatment arms.
The median age was 2.7 years (range: 6 weeks to 14 years), 58% were female, and 86% were non-Caucasian.
The mean baseline CD4+ cell count was 868 cells/mm 3 (mean: 1,060 cells/mm3 and range: 0 to 4,650 cells/mm3 for patients ≤5 years of age; mean: 419 cells/mm 3 and range: 0 to 1,555 cells/mm 3 for patients >5 years of age) and the mean baseline plasma HIV-1 RNA was 5.0 log 10 copies/mL.
The median duration on study was 10.1 months for the patients receiving lamivudine plus zidovudine and 9.2 months for patients receiving didanosine monotherapy.
Results are summarized in Table 10.
Table 10.
Number of Patients (%) Reaching a Primary Clinical Endpoint (Disease Progression or-Death) Endpoint Lamivudine plus Zidovudine (n = 236) Didanosine (n = 235) HIV-1 disease progression or death (total) 15 (6.4%) 37 (15.7%) Physical growth failure 7 (3.0%) 6 (2.6%) Central nervous system deterioration 4 (1.7%) 12 (5.1%) CDC Clinical Category C 2 (0.8%) 8 (3.4%) Death 2 (0.8%) 11 (4.7%)
HOW SUPPLIED
16 /STORAGE AND HANDLING Lamivudine Scored Tablets, 150 mg White capsule shaped, biconvex, scored film coated tablets debossed with ‘J’ on one side and ‘16’ on the other side, 1 and 6 seperated by a score line.
NDC 50268-459-15 10 tablets per card, 5 cards per carton Lamivudine Tablets, 300 mg White capsule shaped, biconvex, film coated tablets debossed with ‘17’ on one side and ‘J’ on the other side.
NDC 50268-460-13 10 tablets per card, 3 cards per carton Dispensed in blister punch material.
For Institutional Use Only.
Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
Preserve in well-closed, light-resistant containers.
RECENT MAJOR CHANGES
Warnings and Precautions, Immune —————(11/2011) Reconstitution Syndrome ( 5.6 )
GERIATRIC USE
8.5 Geriatric Use Clinical studies of lamivudine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
In particular, because lamivudine is substantially excreted by the kidney and elderly patients are more likely to have decreased renal function, renal function should be monitored and dosage adjustments should be made accordingly [see Dosage and Administration (2.3) , Clinical Pharmacology (12.3) ] .
DOSAGE FORMS AND STRENGTHS
3 DOSAGE FORMS & STRENGTHS • Lamivudine Scored Tablets 150 mg, are white capsule shaped, biconvex, scored film coated tablets debossed with ‘J’ on one side and ‘16’ on the other side, 1 and 6 seperated by a score line.
• Lamivudine Tablets 300 mg, are white capsule shaped, biconvex, film coated tablets debossed with ‘17’ on one side and ‘J’ on the other side.
• Tablets: 300 mg ( 3 ) • Tablets: Scored 150 mg ( 3 )
MECHANISM OF ACTION
12.1 Mechanism of Action Lamivudine is an antiviral agent [see Clinical Pharmacology (12.4) ] .
INDICATIONS AND USAGE
1 INDICATIONS & USAGE Lamivudine Tablet is a nucleoside analogue indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-l) infection.
Limitation of use: The dosage of this product is for HIV-1and not for HBV.
Lamivudine tablet is a nucleoside analogue reverse transcriptase inhibitor indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection.
Limitation of Use: The dosage of this product is for HIV-1 and not for HBV.
( 1 )
PEDIATRIC USE
8.4 Pediatric Use The safety and effectiveness of twice-daily lamivudine in combination with other antiretroviral agents have been established in pediatric patients 3 months and older [see Adverse Reactions (6.1) , Clinical Pharmacology (12.3) , Clinical Studies (14.2) ].
PREGNANCY
8.1 Pregnancy Teratogenic Effects : Pregnancy Category C.
There are no adequate and well- controlled studies of lamivudine in pregnant women.
Animal reproduction studies in rats and rabbits revealed no evidence of teratogenicity.
Increased early embryolethality occurred in rabbits at exposure levels similar to those in humans.
Lamivudine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Lamivudine pharmacokinetics were studied in pregnant women during 2 clinical studies conducted in South Africa.
The study assessed pharmacokinetics in: 16 women at 36 weeks gestation using 150 mg lamivudine twice daily with zidovudine, 10 women at 38 weeks gestation using 150 mg lamivudine twice daily with zidovudine, and 10 women at 38 weeks gestation using lamivudine 300 mg twice daily without other antiretrovirals.
These studies were not designed or powered to provide efficacy information.
Lamivudine pharmacokinetics in the pregnant women were similar to those seen in non-pregnant adults and in postpartum women.
Lamivudine concentrations were generally similar in maternal, neonatal, and umbilical cord serum samples.
In a subset of subjects, lamivudine amniotic fluid specimens were collected following natural rupture of membranes.
Amniotic fluid concentrations of lamivudine were typically 2 times greater than maternal serum levels and ranged from 1.2 to 2.5 mcg/mL (150 mg twice daily) and 2.1 to 5.2 mcg/mL (300 mg twice daily).
It is not known whether risks of adverse events associated with lamivudine are altered in pregnant women compared with other HIV-1- infected patients.
Animal reproduction studies performed at oral doses up to 130 and 60 times the adult dose in rats and rabbits, respectively, revealed no evidence of teratogenicity due to lamivudine.
Increased early embryolethality occurred in rabbits at exposure levels similar to those in humans.
However, there was no indication of this effect in rats at exposure levels up to 35 times those in humans.
Based on animal studies, lamivudine crosses the placenta and is transferred to the fetus.
[see Non clinical Toxicology (13.2) ].
Antiretroviral Pregnancy Registry: To monitor maternal-fetal outcomes of pregnant women exposed to lamivudine, a Pregnancy Registry has been established.
Physicians are encouraged to register patients by calling 1-800-258-4263.
NUSRING MOTHERS
8.3 Nursing Mothers The Centers for Disease Control and Prevention recommend that HIV-1-infected mothers in the United States not breastfeed their infants to avoid risking postnatal transmission of HIV-l infection.
Because of the potential for serious adverse reactions in nursing infants and HIV-l transmission, mothers should be instructed not to breastfeed if they are receiving lamivudine.
Lamivudine is excreted into human milk.
Samples of breast milk obtained from 20 mothers receiving lamivudine monotherapy (300 mg twice daily) or combination therapy (150 mg lamivudine twice daily and 300 mg zidovudine twice daily) had measurable concentrations of lamivudine.
BOXED WARNING
WARNING: RISK OF LACTIC ACIDOSIS, EXACERBATIONS OF HEPATITIS B IN CO- INFECTED PATIENTS UPON DISCONTINUATION OF LAMIVUDINE, DIFFERENT FORMULATIONS OF LAMIVUDINE.
Lactic Acidosis and Severe Hepatomegaly: Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including lamivudine and other antiretrovirals.
Suspend treatment if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur [see Warnings and Precautions (5.1) ].
Exacerbations of Hepatitis B: Severe acute exacerbations of hepatitis B have been reported in patients who are co-infected with hepatitis B virus (HBV) and human immunodeficiency virus (HIV-l) and have discontinued lamivudine.
Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue lamivudine and are co-infected with HIV-l and HBV.
If appropriate, initiation of anti-hepatitis B therapy may be warranted [see Warnings and Precautions (5.2) ] .
Important Differences Among Lamivudine-Containing Products: Lamivudine Tablets (used to treat HIV-l infection) contain a higher dose of the active ingredient (lamivudine) than EPIVIR-HBV ® Tablets (used to treat chronic HBV infection).
Patients with HIV-l infection should receive only dosage forms appropriate for treatment of HIV-1 [see Warnings and Precautions (5.2) ] .
WARNING: LACTIC ACIDOSIS, POSTTREATMENT EXACERBATIONS OF HEPATITS B IN CO-INFECTED PATIENTS, DIFFERENT FORMULATIONS OF LAMIVUDINE See full prescribing information for complete boxed warning • Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues.
Suspend treatment if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur.( 5.1 ) • Severe acute exacerbations of hepatitis B have been reported in patients who are co-infected with hepatitis B virus (HBV) and human immunodeficiency virus(HIV-l)and have discontinued lamivudine.
Monitor hepatic function closely in these patients and, if appropriate, initiate anti- hepatitis B treatment.( 5.2 ) • Patients with HIV-1 infection should receive only dosage forms of lamivudine appropriate for treatment of HIV-l.( 5.2 )
WARNING AND CAUTIONS
5 WARNINGS AND PRECAUTIONS • Lactic acidosis and severe hepatomegaly with steatosis: Reported with the use of nucleoside analogues.
Suspend treatment if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatoxicity occur.
( 5.1 ) • Severe acute exacerbations of hepatitis: Reported in patients who are co-infected with hepatitis B virus and HIV-1 and discontinued lamivudine.
Monitor hepatic function closely in these patients and, if appropriate, initiate anti-hepatitis B treatment.
( 5.2 ) • Patients with HIV-1 infection should receive only dosage forms of lamivudine appropriate for treatment of HIV-1.
( 5.2 ) • Co-infected HIV-1/HBV Patients: Emergence of lamivudine-resistant HBV variants associated with lamivudine-containing antiretroviral regimens has been reported.
( 5.2 ) • Emtricitabine should not be administered concomitantly with lamivudine-containing products.
( 5.3 ) • Hepatic decompensation (some fatal) has occurred in HIV-1/HCV co-infected patients receiving interferon and ribavirin-based regimens.
Monitor for treatment- associated toxicities.
Discontinue lamivudine as medically appropriate and consider dose reduction or discontinuation of interferon alfa, ribavirin, or both.
( 5.4 ) • Pancreatitis: Use with caution in pediatric patients with a history of pancreatitis or other significant risk factors for pancreatitis.
Discontinue treatment as clinically appropriate.
( 5.5 ) • Immune reconstitution syndrome ( 5.6 ) and redistribution/accumulation of body fat ( 5.7 ) have been reported in patients treated with combination antiretroviral therapy.
5.1 Lactic Acidosis/Severe Hepatomegaly With Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including lamivudine and other antiretrovirals.
A majority of these cases have been in women.
Obesity and prolonged nucleoside exposure may be risk factors.
Particular caution should be exercised when administering lamivudine to any patient with known risk factors for liver disease; however, cases also have been reported in patients with no known risk factors.
Treatment with lamivudine should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).
5.2 Patients With HIV-1 and Hepatitis B Virus Co-infection Posttreatment Exacerbations of Hepatitis: In clinical trials in non-HIV-1- infected patients treated with lamivudine for chronic hepatitis B, clinical and laboratory evidence of exacerbations of hepatitis have occurred after discontinuation of lamivudine.
These exacerbations have been detected primarily by serum ALT elevations in addition to re-emergence of HBV DNA.
Although most events appear to have been self-limited, fatalities have been reported in some cases.
Similar events have been reported from postmarketing experience after changes from lamivudine-containing HIV-1 treatment regimens to non-lamivudine-containing regimens in patients infected with both HIV-1 and HBV.
The causal relationship to discontinuation of lamivudine treatment is unknown.
Patients should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment.
There is insufficient evidence to determine whether re-initiation of lamivudine alters the course of posttreatment exacerbations of hepatitis.
Important Differences Among Lamivudine-Containing Products: Lamivudine Tablets contain a higher dose of the same active ingredient (lamivudine) than EPIVIR- HBV Tablets.
EPIVIR-HBV was developed for patients with chronic hepatitis B.
The formulation and dosage of lamivudine in EPIVIR-HBV are not appropriate for patients co-infected with HIV-1 and HBV.
Safety and efficacy of lamivudine have not been established for treatment of chronic hepatitis B in patients co-infected with HIV-1 and HBV.
If treatment with EPIVIR-HBV is prescribed for chronic hepatitis B for a patient with unrecognized or untreated HIV-1 infection, rapid emergence of HIV-1 resistance is likely to result because of the subtherapeutic dose and the inappropriateness of monotherapy HIV-1 treatment.
If a decision is made to administer lamivudine to patients co-infected with HIV-1 and HBV, lamivudine tablets, COMBIVIR ® (lamivudine/zidovudine) Tablets, EPZICOM ® (abacavir sulfate and lamivudine) Tablets, or TRIZIVIR ® (abacavir sulfate, lamivudine, and zidovudine) Tablets should be used as part of an appropriate combination regimen.
Emergence of Lamivudine-Resistant HBV: In non-HIV-l-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 prescribing information for EPIVIR-HBV 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.
5.3 Use With Other Lamivudine- and Emtricitabine-Containing Products Lamivudine should not be administered concomitantly with other lamivudine- containing products including EPIVIR-HBV Tablets,COMBIVIR (lamivudine/zidovudine) Tablets, EPZICOM (abacavir sulfate and lamivudine) Tablets, or TRIZIVIR (abacavir sulfate, lamivudine, and zidovudine) or emtricitabine-containing products, including ATRIPLA ® (efavirenz, emtricitabine, and tenofovir), EMTRIVA ® (emtricitabine), or TRUVADA ® (emtricitabine and tenofovir), or COMPLERA TM (rilpivirine/emtricitabine/tenofovir).
5.4 Use With Interferon- and Ribavirin-Based Regimens In vitro studies have shown ribavirin can reduce the phosphorylation of pyrimidine nucleoside analogues such as lamivudine.
Although no evidence of a pharmacokinetic or pharmacodynamic interaction (e.g., loss of HIV-l/HCV virologic suppression) was seen when ribavirin was coadministered with lamivudine in HIV-l/HCV co-infected patients [see Clinical Pharmacology (12.3) ], hepatic decompensation (some fatal) has occurred in HIV-l/HCV co-infected patients receiving combination antiretroviral therapy for HIV -1 and interferon alfa with or without ribavirin.
Patients receiving interferon alfa with or without ribavirin and lamivudine should be closely monitored for treatment-associated toxicities, especially hepatic decompensation.
Discontinuation of lamivudine should be considered as medically appropriate.
Dose reduction or discontinuation of interferon alfa, ribavirin, or both should also be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh >6).
See the complete prescribing information for interferon and ribavirin.
5.5 Pancreatitis In pediatric patients with a history of prior antiretroviral nucleoside exposure, a history of pancreatitis, or other significant risk factors for the development of pancreatitis, lamivudine should be used with caution.
Treatment with lamivudine should be stopped immediately if clinical signs, symptoms, or laboratory abnormalities suggestive of pancreatitis occur [see Adverse Reactions (6.1) ] .
5.6 Immune Reconstitution Syndrome Immune reconstitution syndrome has been reported in patients treated with combination antiretrovira1 therapy, including lamivudine.
During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.
Autoimmune disorders (such as Graves’ disease, polymyositis, and Guillain-Barré 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.
5.7 Fat Redistribution Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance” have been observed in patients receiving antiretroviral therapy.
The mechanism and long-term consequences of these events are currently unknown.
A causal relationship has not been established.
INFORMATION FOR PATIENTS
17 PATIENT COUNSELING INFORMATION 17.1 Advice for the Patient Lactic Acidosis/Hepatomegaly: Patients should be informed that some HIV medicines, including lamivudine, can cause a rare, but serious condition called lactic acidosis with liver enlargement (hepatomegaly) [see Warnings and Precautions (5.1) ].
HIV-1/HBV Co-infection: Patients co-infected with HIV-1 and HBV should be informed that deterioration of liver disease has occurred in some cases when treatment with lamivudine was discontinued.
Patients should be advised to discuss any changes in regimen with their physician [see Warnings and Precautions (5.2) ].
Differences in Formulations of Lamivudine: Patients should be advised that lamivudine tablets contain a higher dose of the same active ingredient (lamivudine) as EPIVIR-HBV Tablets.
If a decision is made to include lamivudine in the HIV-1 treatment regimen of a patient co-infected with HIV-1 and HBV, the formulation and dosage of lamivudine in EPIVIR (not EPIVIR-HBV) should be used [see Warnings and Precautions (5.2) ].
Use With Other Lamivudine- and Emtricitabine-Containing Products: Lamivudine should not be coadministered with drugs containing lamivudine or emtricitabine, including COMBIVIR (lamivudine/zidovudine) Tablets, EPZICOM (abacavir sulfate and lamivudine) Tablets, TRIZIVIR (abacavir sulfate, lamivudine, and zidovudine), ATRIPLA (efavirenz, emtricitabine, and tenofovir), EMTRIVA (emtricitabine), TRUVADA (emtricitabine and tenofovir), or COMPLERA (rilpivirine/emtricitabine/tenofovir) [see Warnings and Precautions (5.3) ].
HIV-1/HCV Co-Infection: Patients with HIV-1/HCV co-infection should be informed that hepatic decompensation (some fatal) has occurred in HIV-1/HCV co-infected patients receiving combination antiretroviral therapy for HIV-1 and interferon alfa with or without ribavirin [see Warnings and Precautions (5.4) ].
Risk of Pancreatitis: Parents or guardians should be advised to monitor pediatric patients for signs and symptoms of pancreatitis [see Warnings and Precautions (5.5) ].
Redistribution/Accumulation of Body Fat: Patients should be informed that redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy, including lamivudine, and that the cause and long-term health effects of these conditions are not known at this time [see Warnings and Precautions (5.7) ].
Information About HIV-1 Infection: Lamivudine is not a cure for HIV-1 infection and patients may continue to experience illnesses associated with HIV-1 infection, including opportunistic infections.
Patients should remain under the care of a physician when using lamivudine.
Patients should be advised to avoid doing things that can spread HIV-1 infection to others.
• Do not share needles or other injection equipment .
• Do not share personal items that can have blood or body fluids on them, like toothbrushes and razor blades.
• Do not have any kind of sex without protection.
Always practice safe sex by using a latex or polyurethane condom or other barrier method to lower the chance of sexual contact with semen, vaginal secretions, or blood.
• Do not breastfeed.
Lamivudine is excreted in human breast milk.
Mothers with HIV-1 should not breastfeed because HIV-1 can be passed to the baby in the breast milk.
Patients should be informed to take all HIV medications exactly as prescribed.
COMBIVIR, EPZICOM and TRIZIVIR are registered trademarks of ViiV Healthcare.
The other brands listed are trademarks of their respective owners and are not trademarks of Hetero Labs Limited.
The makers of these brands are not affiliated with and do not endorse Hetero Labs Limited or its products.
Manufactured for: AvKARE, Inc.
Pulaski, TN 38478 Mfg.
Rev.
12/11 AV 07/15 (P) AvPAK
DOSAGE AND ADMINISTRATION
2 DOSAGE & ADMINISTRATION • Adults and adolescents >16 years of age: 300 mg daily, administered as either 150 mg twice daily or 300 mg once daily.
( 2.1 ) • Pediatric patients 3 months up to 16 years of age: Dosage should be based on body weight.
( 2.2 ).
• Patients With Renal Impairment: Doses of lamivudine must be adjusted in accordance with renal function.
( 2.3 ) 2.1 Adults and Adolescents >16 years of age The recommended oral dose of lamivudine in HIV-1-infected adults and adolescents >16 years of age is 300 mg daily, administered as either 150 mg twice daily or 300 mg once daily, in combination with other antiretroviral agents.
If lamivudine is administered to a patient infected with HIV-1 and HBV, the dosage indicated for HIV-l therapy should be used as part of an appropriate combination regimen [see Warnings and Precautions (5.2) ] .
2.2 Pediatric Patients Lamivudine is also available as a scored tablet for HIV-l-infected pediatric patients who weigh ≥14 kg for whom a solid dosage form is appropriate.
Before prescribing lamivudine tablets, children should be assessed for the ability to swallow tablets.
If a child is unable to reliably swallow lamivudine tablets, the oral solution formulation should be prescribed.
The recommended oral dosage of lamivudine tablets for HIV-1-infected pediatric patients is presented in Table 1.
Table 1.
Dosing Recommendations for Lamivudine Tablets in Pediatric Patients Weight (kg) Dosage Regimen Using Scored 150 mg Tablet Total Daily Dose AM Dose 14 to 21 ½ tablet (75 mg) ½ tablet (75 mg) 150 mg >21 to <30 ½ tablet (75 mg) 1 tablet (150 mg) 225 mg ≥30 1 tablet (150 mg) 1 tablet (150 mg) 300 mg 2.3 Patients With Renal Impairment Dosing of lamivudine is adjusted in accordance with renal function.
Dosage adjustments are listed in Table 2 [see Clinical Pharmacology (12.3) ].
Table 2.
Adjustment of Dosage of Lamivudine in Adults and Adolescents (≥30 kg) in Accordance With Creatinine Clearance Creatinine Clearance (mL/min) Recommended Dosage of Lamivudine ≥50 150 mg twice daily or 300 mg once daily 30-49 150 mg once daily 15-29 150 mg first dose, then 100 mg once daily 5-14 150 mg first dose, then 50 mg once daily <5 50 mg first dose, then 25 mg once daily No additional dosing of lamivudine is required after routine (4-hour) hemodialysis or peritoneal dialysis.
Although there are insufficient data to recommend a specific dose adjustment of lamivudine in pediatric patients with renal impairment, a reduction in the dose and/or an increase in the dosing interval should be considered.