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Lamivudine

Pronunciation

Class: Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
VA Class: AM800
Chemical Name: (2R-cis) 4-Amino-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-2(1H)-pyr imidinone
Molecular Formula: C8H11N3O3S
CAS Number: 134678-17-4
Brands: Combivir, Epivir, Epivir-HBV, Epzicom, Trizivir

Warning(s)

  • Lactic Acidosis and Severe Hepatomegaly
  • Lactic acidosis and severe hepatomegaly with steatosis (including some fatalities) reported in patients receiving nucleoside reverse transcriptase inhibitors (NRTIs) alone or in conjunction with other antiretrovirals.1 18 227 228 229 Discontinue if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur.1 227 (See Lactic Acidosis and Severe Hepatomegaly with Steatosis under Cautions.)

  • Exacerbations of HBV
  • Severe, acute exacerbations of HBV reported following discontinuance of lamivudine in patients coinfected with HBV and HIV.1 18 227 228 229 Monitor hepatic function closely with both clinical and laboratory follow-up for at least several months after a lamivudine-containing preparation is discontinued in patients coinfected with HBV and HIV.1 18 227 228 229 If appropriate, initiation of treatment for HBV infection may be warranted.1 18 227 228 229 (See Exacerbations of HBV Infection under Cautions.)

  • Differences Between Epivir and Epivir-HBV
  • Epivir tablets and oral solution (used to treat HIV infection) contain a higher dose of lamivudine than Epivir-HBV tablets and oral solution (used to treat HBV infection).1 HIV-infected patients should only receive the dosage forms appropriate for treatment of HIV.1

  • Offer HIV counseling and testing to all patients prior to and periodically during Epivir-HBV therapy.18 Epivir-HBV tablets and oral solution (used to treat HBV infection) contain a lower dose of lamivudine than Epivir tablets and oral solution (used to treat HIV infection).18 Use of Epivir-HBV in patients with unrecognized or untreated HIV infection may result in rapid emergence of HIV resistance because of subtherapeutic dose and inappropriate monotherapy.18 (See Considerations in Patients Coinfected with HIV and HBV under Cautions.)

  • Fixed Combinations
  • If using Combivir or Trizivir, consider that zidovudine has been associated with hematologic toxicity (including neutropenia and severe anemia), particularly in those with advanced HIV-1 disease,227 229 and that prolonged zidovudine use has been associated with symptomatic myopathy.227 229

  • If using Epzicom or Trizivir, consider that abacavir has been associated with serious and sometimes fatal hypersensitivity reactions.229 228 Because individuals with human leukocyte antigen (HLA)-B*5701 allele are at high risk for abacavir hypersensitivity reactions,228 229 screening for HLA-B*5701 allele recommended prior to initiation of Epzicom or Trizivir.228 229 Discontinue Epzicom or Trizivir as soon as a hypersensitivity reaction is suspected.228 229 Regardless of patient’s HLA-B*5701 status, permanently discontinue if hypersensitivity cannot be ruled out.228 229

Introduction

Antiretroviral; nucleoside reverse transcriptase inhibitor (NRTI); also has antiviral activity against HBV.1 4 9 200

Uses for Lamivudine

Treatment of HIV

Treatment of HIV-1 infection in conjunction with other antiretrovirals.1 200 201 227 228 229

Used with another NRTI (dual NRTIs) in conjunction with a nonnucleoside reverse transcriptase inhibitor (NNRTI) or HIV protease inhibitor (PI) in NNRTI- or PI-based regimens.200 201 Also used with another NRTI (dual NRTIs) in conjunction with an HIV integrase inhibitor or HIV entry inhibitor.200

For initial treatment in HIV-infected adults and adolescents, some experts state that tenofovir used with either emtricitabine or lamivudine is the preferred dual NRTI option.200 Abacavir and either emtricitabine or lamivudine is an alternative (not preferred) dual NRTI option for initial treatment in these patients.200

Zidovudine and either emtricitabine or lamivudine is considered an acceptable (not preferred or alternative) dual NRTI option for initial treatment regimens in HIV-infected adults and adolescents, but is the preferred dual NRTI option in antiretroviral-naive pregnant women.200 202 Acceptable dual NRTI options may be selected for some patients, but are less satisfactory than preferred or alternative options.200

Dual NRTI option of didanosine and either lamivudine or emtricitabine not recommended for initial antiretroviral regimens in adults or adolescents because of inferior virologic efficacy and limited clinical trial experience.200

For HIV-infected adults and adolescents coinfected with HBV, dual NRTI option of tenofovir and either emtricitabine or lamivudine is preferred since these drugs have some activity against HBV; regimens containing only 1 of these antiretrovirals not recommended in such patients (increased risk of HBV resistance).200

When PI- or NNRTI-based regimens are used for initial treatment in HIV-infected children, preferred dual NRTI options are zidovudine and either lamivudine or emtricitabine; abacavir and either lamivudine or emtricitabine (children ≥3 months of age negative for HLA-B*5701 allele), or tenofovir and either lamivudine or emtricitabine (adolescents ≥12 years of age and Tanner stage 4 or 5).201

Slideshow: Flashback: FDA Drug Approvals 2013

Fixed combination containing lamivudine and zidovudine (Combivir) used when dual NRTI option of zidovudine and lamivudine is indicated in conjunction with other antiretrovirals.200 227

Fixed combination containing abacavir and lamivudine (Epzicom) used when dual NRTI option of abacavir and lamivudine is indicated in conjunction with other antiretrovirals.200 228 Consider that Epzicom is recommended for use with antiretrovirals from other classes (not another NRTI).228

Fixed combination containing abacavir, lamivudine, and zidovudine (Trizivir) used for triple NRTI regimen;200 229 used alone or in conjunction with other antiretrovirals.229 Consider that Trizivir is intended only for regimens that require all 3 drugs and that data are limited regarding use of the fixed combination in patients with higher viral loads (>100,000 copies/mL) at baseline.229

Triple NRTI regimen of abacavir, lamivudine, and zidovudine not generally recommended because of inferior antiretroviral activity;200 201 consider use only in special circumstances when other regimens cannot be used (e.g., because of concerns regarding drug interactions, toxicities, or regimen complexity).200 201

Triple NRTI regimen of abacavir, lamivudine, and tenofovir not recommended at any time because of high rate of virologic failure.200 201

Prevention of Perinatal HIV Transmission

Has been used for prevention of perinatal HIV transmission.202

Multiple-drug antiretroviral regimens are considered the standard of care in the US for treatment of HIV infection in pregnant women and for prevention of perinatal HIV transmission.202 In addition, to decrease risk of perinatal HIV transmission, certain pregnant HIV-infected women in the US should receive an intrapartum IV zidovudine prophylaxis regimen and all neonates born to HIV-infected women should receive an oral or IV zidovudine prophylaxis regimen.202

In situations when an HIV-infected woman received no antiretrovirals prior to and/or during labor, a multiple-drug prophylaxis regimen should be initiated in the neonate as soon as possible after birth.202 Although 3-drug neonatal regimen that includes lamivudine and nelfinavir in addition to the usual neonatal zidovudine regimen has been used, there is some evidence that a 2-drug regimen (i.e., 3 nevirapine doses given during first week of life in addition to usual 6-week neonatal zidovudine regimen) is as effective and less toxic.202

Decisions regarding use of multiple-drug neonatal prophylaxis regimens in situations associated with increased risk of perinatal HIV transmission should be made in consultation with a pediatric HIV specialist.202

Clinicians can consult National Perinatal HIV Hotline at 888-448-8765 for information regarding antiretroviral treatment of pregnant HIV-infected women and their infants and prevention of perinatal HIV transmission.202 Maternal and neonatal regimens recommended for prevention of perinatal HIV transmission in the US may differ from those used in other countries.202

Postexposure Prophylaxis of HIV

Postexposure prophylaxis of HIV infection in health-care workers and others exposed occupationally via percutaneous injury or mucous membrane or nonintact skin contact with blood, tissues, or other body fluids associated with risk for transmission of the virus.199 Used in conjunction with other antiretrovirals.199

Postexposure prophylaxis of HIV infection in individuals who have had nonoccupational exposure to blood, genital secretions, or other potentially infectious body fluids of a person known to be infected with HIV when that exposure represents a substantial risk for HIV transmission.198 Used in conjunction with other antiretrovirals.198

Chronic HBV Infection

Treatment of chronic HBV infection associated with evidence of HBV replication and active liver inflammation.18 65 67 68 69 70 71 72 75 97

American Association for the Study of Liver Diseases (AASLD) states that lamivudine is not a preferred antiviral for long-term treatment of chronic HBV; high rate of lamivudine resistance reported with such treatment.97 Manufacturer states consider use of lamivudine only when other antivirals with higher genetic barrier to resistance are unavailable or inappropriate.18

Safety and efficacy not established in patients with decompensated liver disease.18

Safety and efficacy not established for treatment of chronic HBV infection in patients coinfected with HIV.18 (See Considerations in Patients Coinfected with HIV and HBV under Cautions.)

Safety and efficacy not established for treatment of chronic HBV infection in patients coinfected with HCV or hepatitis D virus (HDV).18

Safety and efficacy not established in organ transplant recipients.18 May reduce risk of HBV reinfection in orthotopic liver transplant recipients.72 73 74

Not studied in pregnant women with HBV infection; no data regarding effect on vertical transmission of HBV.18

Treatment of chronic HBV infection is complex and rapidly evolving and should be directed by clinicians familiar with the disease; consult a specialist to obtain the most up-to-date information.97

Lamivudine Dosage and Administration

Administration

Oral Administration

Administer single-entity preparations (Epivir, Epivir-HBV) or fixed-combination preparations (Combivir, Epzicom, Trizivir) orally without regard to meals.1 18 227 228 229

Treatment of HIV infection (Epivir): Use lamivudine oral solution containing 10 mg/mL or lamivudine film-coated tablets containing 150 mg or 300 mg.1 The 150-mg scored tablets may be used in children weighing ≥14 kg if they can reliably swallow tablets.1

Treatment of chronic HBV infection (Epivir-HBV): Use lamivudine oral solution containing 5 mg/mL or lamivudine film-coated tablets containing 100 mg.18

Combivir: Because dosages of drugs in this fixed combination (lamivudine, zidovudine) cannot be adjusted individually, do not use in children or adolescents weighing <30 kg, patients with impaired renal function (i.e., Clcr <50 mL/minute), patients with impaired hepatic function, patients who experience dose-limiting adverse effects, or others requiring dosage adjustment.227

Epzicom: Because dosages of drugs in this fixed combination (abacavir, lamivudine) cannot be adjusted individually, do not use in patients <18 years of age, patients with impaired renal function (i.e., Clcr <50 mL/minute), patients with hepatic impairment, or others requiring dosage adjustment.228

Trizivir: Because dosages of drugs in this fixed combination (abacavir, lamivudine, zidovudine) cannot be adjusted individually, do not use in pediatric patients, adolescents weighing <40 kg, patients with impaired renal function (i.e., Clcr <50 mL/minute), patients with impaired hepatic function, or others requiring dosage adjustment.229

Dosage

Dosage of Combivir, Epzicom, and Trizivir expressed as number of tablets.227 228 229

Epivir, Epzicom, and Combivir must be used in conjunction with other antiretrovirals;1 227 228 Trizivir may be used alone or in conjunction with other antiretrovirals.229

Pediatric Patients

Treatment of HIV Infection
Oral

Neonates <4 weeks of age (Epivir oral solution): 2 mg/kg twice daily suggested by some experts.201

Infants and children 3 months to 16 years of age (Epivir oral solution): 4 mg/kg (up to 150 mg) twice daily.1 Some experts suggest this dosage also can be used in infants >4 weeks of age.201

Table 1. Children 3 Months to 16 Years of Age Weighing ≥14 kg (Epivir 150-mg Tablets)1

Weight (kg)

AM dose

PM dose

14–21

75 mg (half tablet)

75 mg (half tablet)

>21 to <30

75 mg (half tablet)

150 mg

≥30

150 mg

150 mg

Epivir (adolescents ≥16 years of age): 150 mg twice daily or 300 mg once daily.1 Some experts recommend that those weighing <50 kg receive 4 mg/kg (up to 150 mg) twice daily and those weighing ≥50 receive 150 mg twice daily or 300 mg once daily.201

Combivir (children or adolescents weighing ≥30 kg): 1 tablet twice daily.201 227

Trizivir (adolescents weighing ≥40 kg): 1 tablet twice daily.201 229

Chronic HBV Infection
Oral

Children and adolescents 2–17 years of age (Epivir-HBV tablets or oral solution): 3 mg/kg (up to 100 mg) once daily.18 97

Optimal duration of treatment unknown; manufacturer states safety and efficacy >1 year not established.18

Adults

Treatment of HIV Infection
Oral

Epivir: 150 mg twice daily or 300 mg once daily.1 200

Combivir (adults weighing ≥30 kg): 1 tablet twice daily.200 227

Epzicom: 1 tablet once daily.200 228

Trizivir: 1 tablet twice daily.200 229

Postexposure Prophylaxis of HIV
Occupational Exposure
Oral

Epivir: 300 mg once daily or 150 mg twice daily. ).199

Initiate postexposure prophylaxis as soon as possible following exposure (within hours rather than days) and continue for 4 weeks, if tolerated.199

Nonoccupational Exposure
Oral

Epivir: 300 mg once daily or 150 mg twice daily.198

Initiate postexposure prophylaxis as soon as possible following exposure (preferably ≤72 hours after exposure) and continue for 28 days.198

Chronic HBV Infection
Oral

Epivir-HBV: 100 mg once daily.18 97

Optimal duration of treatment unknown; manufacturer states safety and efficacy >1 year not established.18 AASLD recommends at least 12 months; in HBsAg-positive patients, continue for at least 6 months after HBeAg seroconversion (loss of HBeAg and detection of anti-HBe).97

Prescribing Limits

Pediatric Patients

Treatment of HIV Infection
Oral

Children 3 months to 16 years of age (Epivir): Maximum 150 mg twice daily.1

Chronic HBV Infection
Oral

Children 2–17 years of age (Epivir-HBV): Maximum 100 mg daily.18

Special Populations

Hepatic Impairment

Treatment of HIV Infection
Oral

Epivir: Dosage adjustment not needed.1 Safety and efficacy not established in those with decompensated liver disease.1

Combivir, Epzicom, Trizivir: Do not use in patients with hepatic impairment.228 229

Chronic HBV Infection
Oral

Epivir-HBV: Dosage adjustment not needed.18 Safety and efficacy not established in those with decompensated liver disease.1

Renal Impairment

Treatment of HIV Infection
Oral

Pediatric patients with renal impairment (Epivir): Consider reducing dose and/or increasing dosing interval; data insufficient to make specific recommendations.1

Table 2. Dosage in Adults and Adolescents with Renal Impairment Weighing ≥30 kg (Epivir).1

Clcr (mL/minute)

Dosage

≥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

Hemodialysis Patients

Supplemental doses unnecessary with routine (4-hour) hemodialysis

Peritoneal Dialysis Patients

Supplemental doses unnecessary after peritoneal dialysis

Combivir, Epzicom, Trizivir: Do not use in patients with Clcr <50 mL/minute.228 229

Chronic HBV Infection
Oral

Pediatric patients with renal impairment (Epivir-HBV): Consider reducing dose; data insufficient to make specific recommendations.18

Table 3. Dosage in Adults with Renal Impairment (Epivir-HBV).18

Clcr (mL/minute)

Dosage

≥50

100 mg once daily

30–49

100 mg first dose, then 50 mg once daily

15–29

100 mg first dose, then 25 mg once daily

5–14

35 mg first dose, then 15 mg once daily

<5

35 mg first dose, then 10 mg once daily

Hemodialysis Patients

Supplemental doses unnecessary with routine (4-hour) hemodialysis

Peritoneal Dialysis Patients

Supplemental doses unnecessary after peritoneal dialysis

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.1

Cautions for Lamivudine

Contraindications

  • Epivir, Epivir-HBV, Combivir, Epzicom, Trizivir: Clinically important hypersensitivity reaction (e.g., anaphylaxis, Stevens-Johnson syndrome) to lamivudine or any ingredient in the formulation.1 18 227 228 229

  • Epzicom, Trizivir: Hepatic impairment.228 229

Warnings/Precautions

Warnings

Lactic Acidosis and Severe Hepatomegaly with Steatosis

Lactic acidosis and severe hepatomegaly with steatosis (sometimes fatal) reported in patients receiving NRTIs (including lamivudine) alone or in conjunction with other antiretrovirals.1 18 227 228 229 Reported most frequently in women; obesity and long-term NRTI therapy also may be risk factors.1 18 227 228 229 Has been reported in patients with no known risk factors.1 18 227 228 229

Use particular caution in patients with known risk factors for liver disease.1 18 227 228 229

Interrupt lamivudine therapy if there are clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (e.g., hepatomegaly and steatosis even in the absence of markedly increased serum aminotransferase concentrations).1 18 227 228 229

Exacerbations of HBV Infection

Posttreatment exacerbations of HBV infection and emergence of resistant strains of HBV reported following discontinuance of lamivudine therapy for HBV in non-HIV-infected patients.1 18 31 41

Exacerbations of HBV infection also reported when lamivudine discontinued from antiretroviral regimens in HIV-infected patients coinfected with HBV.1 18

Such exacerbations of HBV infection detected principally by increases in serum ALT in addition to re-emergence of serum HBV DNA.1 18 Most events appear to have been self-limited and causal relationship to lamivudine discontinuance unknown; some fatalities reported.1 18

After discontinuing lamivudine, closely monitor patients with both clinical and laboratory follow-up for at least several months.18 If appropriate, initiation or resumption of anti-HBV therapy may be warranted.1 Insufficient evidence to determine whether reinitiation of therapy alters the course of posttreatment exacerbations of hepatitis.18

Considerations in Patients Coinfected with HIV and HBV

Epivir-HBV not appropriate for patients coinfected with HBV and HIV since it contains a lower dose of lamivudine than Epivir.1 18

Use of Epivir-HBV for treatment of HBV infection in patients with unrecognized or untreated HIV infection may result in rapid emergence of lamivudine-resistant HIV and limit antiretroviral treatment options.18

Prior to and periodically during Epivir-HBV treatment of chronic HBV infection, offer HIV counseling and testing to all patients.18

If a decision is made to use lamivudine in patients coinfected with HBV and HIV, Epivir should be used in dosages appropriate for treatment of HIV infection in conjunction with other antiretrovirals.1 18

Other Warnings and Precautions

HBV Resistance

Lamivudine-resistant HBV detected in patients receiving the drug for treatment of HBV; diminished treatment response reported.1 18 Lamivudine-resistant HBV also detected in HIV-infected patients coinfected with HBV who received a lamivudine-containing antiretroviral regimen.1 18

Monitoring ALT and HBV DNA levels during lamivudine treatment may assist in treatment decisions if emergence of resistant HBV is suspected.18

Considerations in Patients Coinfected with HIV and HCV

Hepatic decompensation, sometimes fatal, reported in HIV-infected patients coinfected with HCV receiving antiretroviral therapy concomitantly with interferon alfa (or peginterferon alfa) with or without ribavirin.1 109 (See Specific Drugs under Interactions.)

Use of Fixed Combinations

Do not use multiple lamivudine-containing preparations concomitantly.1 18

Do not use lamivudine concomitantly with emtricitabine (Emtriva) or fixed combinations containing emtricitabine (Atripla, Complera, Truvada).1 200

When fixed combination containing lamivudine and zidovudine (Combivir) used, consider cautions, precautions, and contraindications associated with both drugs.227

When fixed combination containing abacavir and lamivudine (Epzicom) used, consider cautions, precautions, and contraindications associated with both drugs.228

When fixed combination containing abacavir, lamivudine, and zidovudine (Trizivir) used, consider cautions, precautions, and contraindications associated with all 3 drugs.229

Adipogenic Effects

Possible redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement (“buffalo hump”), peripheral wasting, breast enlargement, and general cushingoid appearance.1

Immune Reconstitution Syndrome

During initial treatment, patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jiroveci [formerly P. carinii]); this may necessitate further evaluation and treatment.1 227 228 229

Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome) reported in the setting of immune reconstitution; time to onset is more variable and can occur many months after initiation of antiretroviral therapy.1 227 228 229

Diabetes Mellitus

Epivir oral solution: Contains 3 g of sucrose per 15 mL of solution.1

Epivir-HBV oral solution: Contains 4 g of sucrose per 20 mL of solution.18

Possible Prescribing and Dispensing Errors

Ensure accuracy of the prescription; similarity of spelling lamotrigine (Lamictal) and lamivudine may result in errors.102

Specific Populations

Pregnancy

Epivir, Epivir-HBV, Combivir, Epzicom, Trizivir: Category C.1 18 227 228 229

Antiretroviral Pregnancy Registry at 800-258-4263 or .1 18 202

Lamivudine and zidovudine is a preferred dual NRTI option for use in multiple-drug antiretroviral regimens in HIV-infected pregnant women; the preferred dual NRTI option in those who are antiretroviral-naive.202

Lamivudine has not been shown to affect transmission of HBV from mother to infant; neonate must be immunized to prevent neonatal acquisition of HBV.18

Lactation

Lamivudine is distributed into human milk.1 18

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.1 202

Instruct HBV-infected women not to breast-feed because of the risks of adverse effects in the infant.18

Pediatric Use

Epivir: Safety and efficacy established for treatment of HIV infection in pediatric patients >3 months of age.1

Epivir-HBV: Safety and efficacy established for management of chronic HBV infection in pediatric patients 2–17 years of age.18 Safety and efficacy for this indication not established in children <2 years of age.18

Limited pharmacokinetic and safety data available regarding lamivudine in neonates ≤1 week of age who received the drug for prevention of perinatal HIV transmission.1

If regimen for prevention of perinatal HIV transmission contains lamivudine and zidovudine, reassess hemoglobin and neutrophil counts 4 weeks after such prophylaxis initiated.202

Pancreatitis, sometimes fatal, reported in antiretroviral nucleoside-experienced HIV-infected pediatric patients.1 Caution in pediatric patients with prior antiretroviral nucleoside exposure, history of pancreatitis, or other risk factors for pancreatitis.1 18 Discontinue lamivudine if sign, symptoms, or laboratory abnormalities suggestive of pancreatitis occur.1

Combivir: Do not use in children or adolescents weighing <30 kg.227

Epzicom: Do not use in pediatric patients <18 years of age.228

Trizivir: Do not use in pediatric patients or in adolescents weighing <40 kg.229

Geriatric Use

Epivir, Epivir-HBV, Combivir, Epzicom, Trizivir: Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults.1 18 227 228 229

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.1 18

Substantially eliminated by the kidneys; geriatric patients more likely to have decreased renal function; monitor renal function and adjust dosage accordingly.1 18

Hepatic Impairment

Epivir, Epivir-HBV: Safety and efficacy not established in the presence of decompensated liver disease.1 18

Combivir, Epzicom, Trizivir: Do not use in patients with impaired hepatic function.227 228 229

Renal Impairment

Epivir, Epivir-HBV: Dosage adjustments recommended based on degree of renal impairment.1 18 (See Renal Impairment under Dosage and Administration.)

Combivir, Epzicom, Trizivir: Do not use in patients with Clcr <50 mL/minute.227 228 229

Common Adverse Effects

Nausea, fatigue and/or malaise, headache, nasal symptoms, diarrhea, cough.1

Interactions for Lamivudine

Eliminated in urine by active organic cationic secretion; possibility of interactions with other drugs eliminated by active renal secretion via the organic cationic transport system.1 18

Specific Drugs

Drug

Interaction

Comments

Abacavir

No clinically important pharmacokinetic interactions216

In vitro evidence of additive or synergistic antiretroviral effects1 14 216

Atazanavir

No in vitro evidence of antagonistic antiretroviral effects203

Buprenorphine

No clinically important pharmacokinetic interactions200

Dosage adjustments not needed200

Co-trimoxazole

Increased lamivudine AUC; no change in pharmacokinetics of trimethoprim or sulfamethoxazole1

Dosage adjustments not needed1

Darunavir

Ritonavir-boosted darunavir: Pharmacokinetic interactions unlikely204

No in vitro evidence of antagonistic antiretroviral effects204

Delavirdine

In vitro evidence of additive or synergistic antiretroviral effects212

Efavirenz

No effect on lamivudine peak concentrations or AUC213

In vitro evidence of additive antiretroviral effects213

Dosage adjustments not needed213

Emtricitabine

In vitro evidence of additive antiretroviral effects218

Do not use concomitantly;1 200 201 no potential benefit since emtricitabine is an analog of lamivudine and the drugs have same resistance profile and minimal additive antiretroviral effects200 201

Enfuvirtide

In vitro evidence of additive to synergistic antiretroviral effects223

Etravirine

No in vitro evidence of antagonistic antiretroviral effects214

Fosamprenavir

No evidence of pharmacokinetic interactions in studies using amprenavir (active metabolite of fosamprenavir)205

In vitro evidence of synergistic antiretroviral effects with amprenavir205

Interferon (interferon alfa, peginterferon alfa)

No clinically important pharmacokinetic interactions18

Possible increased risk of potentially fatal hepatic decompensation in HIV-infected patients coinfected with HCV receiving antiretroviral agents and interferon alfa (or peginterferon alfa) with or without ribavirin1 109

If lamivudine used in patients receiving interferon alfa (or peginterferon alfa) with or without ribavirin, closely monitor for toxicities, especially hepatic decompensation; consider discontinuing lamivudine as medically appropriate; consider discontinuing or reducing dosage of interferon alfa (or peginterferon alfa) and/or ribavirin if worsening toxicities, including hepatic decompensation (Child-Pugh >6), occur1 109

Lopinavir

No clinically important pharmacokinetic interactions207

Maraviroc

No effect on lamivudine pharmacokinetics224

No in vitro evidence of antagonistic antiretroviral effects224

Recommended maraviroc dosage is 300 mg twice daily when used in conjunction with NRTIs, provided regimen does not include a potent CYP3A inhibitor or inducer224

Methadone

No clinically important pharmacokinetic interactions200

Dosage adjustments not needed200

Nelfinavir

Increased lamivudine peak concentrations and AUC208

In vitro evidence of additive or synergistic antiretroviral effects14 208

Nevirapine

In vitro evidence of additive or synergistic antiretroviral effects215

Raltegravir

No clinically important effect on lamivudine pharmacokinetics225

In vitro evidence of additive to synergistic antiretroviral effects225

Ribavirin

In vitro evidence that ribavirin can reduce phosphorylation of lamivudine; no evidence of pharmacokinetic or pharmacodynamic interactions (e.g., loss of virologic suppression of HIV or HBV) in HIV patients coinfected with HCV receiving lamivudine and ribavirin1 109

Possible increased risk of potentially fatal hepatic decompensation in HIV-infected patients coinfected with HCV receiving antiretroviral agents and interferon alfa (or peginterferon alfa) with or without ribavirin1 109

If lamivudine used in patients receiving interferon alfa (or peginterferon alfa) with or without ribavirin, closely monitor for toxicities, especially hepatic decompensation; consider discontinuing lamivudine as medically appropriate; consider discontinuing or reducing dosage of interferon (or peginterferon) and/or ribavirin if worsening toxicities, including hepatic decompensation (Child-Pugh >6), occur1 109

Rilpivirine

Pharmacokinetic interactions unlikely226

No in vitro evidence of antagonistic antiretroviral effects226

Saquinavir

In vitro evidence of additive or synergistic antiretroviral effects14 210

Stavudine

No clinically important pharmacokinetic interactions1

In vitro evidence of additive or synergistic antiretroviral effects1 14 216

Tenofovir

Decreased lamivudine concentrations; no effect on lamivudine AUC or tenofovir concentrations or AUC221

In vitro evidence of additive or synergistic antiretroviral effects221

No in vitro evidence of antagonistic antiviral effects against HBV221

Tipranavir

Ritonavir-boosted tipranavir: No clinically important effect on lamivudine pharmacokinetics211

In vitro evidence of additive antiretroviral effects211

Zidovudine

No clinically important pharmacokinetic interactions 1 222

In vitro evidence of additive or synergistic antiretroviral effects1 14 222

Dosage adjustments not needed222

Lamivudine Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed from GI tract; peak plasma concentrations achieved within 0.5–2 hours.1 18

Absolute bioavailability of tablets and oral solution is similar (86 and 87%, respectively, in HIV-infected adults).1

Comparison of steady-state pharmacokinetics of once-daily regimen (300-mg tablet once daily) or twice-daily regimen (150-mg tablet twice daily) indicates AUC is similar with both regimens; peak plasma concentrations are 66% higher and trough concentrations 53% lower with once-daily regimen.1

Fixed-combination tablet containing lamivudine 150 mg and zidovudine 300 (Combivir) is bioequivalent to one 150-mg tablet of lamivudine and one 300-mg tablet of zidovudine given simultaneously.227

Fixed-combination tablet containing abacavir 600 mg and lamivudine 300 (Epzicom) is bioequivalent to two 300-mg tablets of abacavir and two 150-mg tablets of lamivudine given simultaneously.228

Fixed-combination tablet containing abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg (Trizivir) is bioequivalent to a 300-mg abacavir tablet, a 150-mg lamivudine tablet, and a 300-mg zidovudine tablet given simultaneously.229

Food

Food does not appear to affect AUC.1 18

Special Populations

HIV-infected pediatric patients 5 months to 12 years of age: Absolute bioavailability of oral solution is 66%;1 reason for lower bioavailability in infants and children compared with adults unknown.1

Hepatic impairment: Peak plasma concentration and AUC similar to those in patients with normal hepatic function.1 18

Renal impairment: Peak plasma concentration and AUC increased depending on degree of renal impairment.1 18

Distribution

Extent

Not well characterized; distributes into extravascular spaces.1 18

Distributed into CSF; concentrations in CSF may be 5.6–30.9% of concurrent serum concentrations in HIV-infected children.1

Crosses the placenta and is distributed into milk.1 18

Plasma Protein Binding

<36%.1 18

Elimination

Metabolism

Metabolism is a minor route of elimination;1 18 only known metabolite is the trans-sulfoxide metabolite.1 18

Intracellularly, lamivudine is phosphorylated and converted by cellular enzymes to the active 5′-triphosphate metabolite.1 18

Elimination Route

Majority of dose eliminated unchanged in urine by active organic cationic secretion.1 18 Within 24 hours, approximately 5% of an oral dose excreted in urine as the trans-sulfoxide metabolite.1

Half-life

5–7 hours.1 18

HIV-infected children 4 months to 14 years of age: 2 hours.1

Special Populations

Hepatic impairment: Pharmacokinetics not altered.1 18

Renal impairment: Half-life increased with diminishing renal function.1 18

Hemodialysis increases clearance; length of time of hemodialysis (4 hours) insufficient to substantially alter mean lamivudine exposure after single-dose administration.1 18 Not known whether lamivudine is removed by peritoneal dialysis or continuous (24 hour) hemodialysis.1 18

Stability

Storage

Oral

Solution

Epivir: 25°C in tightly closed bottles.1

Epivir-HBV: 20–25°C in tightly closed bottles.18

Tablets

Epivir and Epivir-HBV: 25°C (may be exposed to 15–30°C).1 18

Combivir: 2–30°C.227

Epzicom: 25°C (may be exposed to 15–30°C).228

Trizivir: 25°C (may be exposed to 15–30°C).229

Actions and Spectrum

  • Lamivudine is a dideoxy analogue of cytidine.1

  • Pharmacologically related to, but structurally different from, other NRTIs and other currently available antiretrovirals.1

  • A prodrug that is inactive until converted intracellularly to lamivudine triphosphate.1

  • Active in vitro against HIV-1 and HIV-2.1 2 3 10 Also active against HBV.11 12 18 24 26 59

  • Inhibits replication of HIV by interfering with viral RNA-directed DNA polymerase (reverse transcriptase).1

  • Inhibits replication of HBV by interfering with HBV polymerase.18

  • HIV-1 with reduced susceptibility to lamivudine have been produced in vitro and have emerged during therapy with the drug.1 10 31

  • Lamivudine-resistant HIV may be cross-resistant to some other NRTIs (e.g., abacavir, didanosine, emtricitabine, tenofovir, stavudine).1 216 221

  • HBV with reduced susceptibility to lamivudine have emerged during therapy, including YMDD-mutant HBV associated with diminished treatment response.18 Prevalence of YMDD-mutants increases with long-term lamivudine therapy.18

  • Some lamivudine-resistant HBV remain susceptible to adefovir, but have reduced susceptibility to entecavir and telbivudine.18 Other lamivudine-resistant HBV have reduced susceptibility to telbivudine and/or tenofovir.18 221

Advice to Patients

  • For treatment of HIV, lamivudine used in conjunction with other antiretrovirals—not for monotherapy.1 Importance of using Epivir (not Epivir-HBV) for treatment of HIV infection.1

  • Critical nature of compliance with HIV therapy and importance of remaining under the care of a clinician.1 Importance of taking as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinician.1 1

  • Antiretroviral therapy is not a cure for HIV infection; opportunistic infections and other complications associated with HIV disease may still occur.1

  • Advise patients that sustained decreases in plasma HIV RNA have been associated with reduced risk of progression to AIDS and death.226

  • Advise patients that effective antiretroviral regimens can decrease HIV concentrations in blood and genital secretions and strict adherence to such regimens in conjunction with risk-reduction measures may decrease, but cannot absolutely eliminate, the risk of secondary transmission of HIV to others.200 Importance of continuing to practice safer sex (e.g., using latex or polyurethane condoms to minimize sexual contact with body fluids), never sharing personal items that can have blood or body fluids on them (e.g., toothbrushes, razor blades), and never reusing or sharing needles.1 200

  • For treatment of HBV infection, lamivudine is not a cure; long-term benefits unknown, worsening of disease possible.18 Importance of reporting any new symptoms to a clinician.18 Advise patients that deterioration of liver disease has occurred when treatment is discontinued, and that any change in treatment should be discussed with a clinician.1

    Importance of testing for HIV prior to and periodically during Epivir-HBV therapy used for treatment of chronic HBV infection.18

  • Importance of reading the patient package insert for Epivir-HBV provided by the manufacturer.18

  • Advise diabetic patients receiving Epivir oral solution that each 15 mL contains 3 g of sucrose.1 Advise diabetic patients receiving Epivir-HBV oral solution that each 20 mL contains 4 g of sucrose.18

  • If taking Epivir or Epivir-HBV, importance of not taking another lamivudine-containing preparation.1 If taking Epzicom, importance of not taking another abacavir- or lamivudine-containing preparation.228 If taking Trizivir, importance of not taking another abacavir-, lamivudine-, or zidovudine-containing preparation.229

  • Possibility of pancreatitis in pediatric patients; advise parents or guardians to monitor pediatric patients for signs and symptoms.1

  • Redistribution/accumulation of body fat may occur, with as yet unknown long-term health effects.1

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products, and any concomitant illnesses.1 18

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 18 Advise HIV-infected women not to breast-feed.1

  • Importance of advising patients of other important precautionary information.1 18 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Lamivudine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Solution

5 mg/mL

Epivir-HBV

GlaxoSmithKline

10 mg/mL

Epivir

ViiV

Tablets, film-coated

100 mg

Epivir-HBV

GlaxoSmithKline

300 mg

Epivir

ViiV

Tablets, film-coated, scored

150 mg

Epivir

ViiV

Lamivudine Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

150 mg with Abacavir Sulfate 300 mg (of abacavir) and Zidovudine 300 mg

Trizivir

ViiV

150 mg with Zidovudine 300 mg

Combivir

ViiV

300 mg with Abacavir Sulfate 600 mg (of abacavir)

Epzicom

ViiV

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Combivir 150-300MG Tablets (VIIV HEALTHCARE): 30/$488.01 or 60/$949.93

Epivir 10MG/ML Solution (VIIV HEALTHCARE): 240/$109.99 or 720/$309.96

Epivir 150MG Tablets (VIIV HEALTHCARE): 60/$450.01 or 180/$1,277.98

Epivir 300MG Tablets (VIIV HEALTHCARE): 30/$443.13 or 90/$1,268.10

Epivir HBV 100MG Tablets (GLAXO SMITH KLINE): 60/$771.96 or 180/$2,291.89

Epzicom 600-300MG Tablets (VIIV HEALTHCARE): 30/$1,031.96 or 90/$2,972.02

LamiVUDine 150MG Tablets (APOTEX): 30/$199.99 or 90/$560.00

LamiVUDine 300MG Tablets (APOTEX): 30/$379.99 or 90/$1,079.91

Lamivudine-Zidovudine 150-300MG Tablets (TEVA PHARMACEUTICALS USA): 30/$425.99 or 90/$1,249.97

Trizivir 300-150-300MG Tablets (VIIV HEALTHCARE): 60/$1,562.95 or 180/$4,374.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions October 10, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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2. Soudeyns H, Yao XJ, Gao Q et al. Anti-human immunodeficiency virus type 1 activity and in vitro toxicity of 2′-deoxy-3′-thiacytidine (BCH-189), a novel heterocyclic nucleoside analog. Antimicrob Agents Chemother. 1991; 35:1386-90. [PubMed 1929298]

3. Coates JAV, Cammack N, Jenkinson HJ et al. The separated enantiomers of 2′-deoxy-3′-thiacytidine (BCH 189) both inhibit human immunodeficiency virus replication in vitro. Antimicrob Agents Chemother. 1992; 36:202-5. [PubMed 1590690]

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36. Goodgame JC, Pottage JC, Jablonowski H et al. Amprenavir in combination with lamivudine and zidovudine versus lamivudine and zidovudine alone in HIV-1-infected antiretroviral-naive adults. Antiviral Ther. 2000; 5:215-25.

40. Gulick RM, Mellors JW, Havlir D et al. Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy. N Engl J Med. 1997; 337:734-9. [IDIS 390958] [PubMed 9287228]

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48. Puro V, Ippolito G, Guzzanti E et al. Zidovudine prophylaxis after accidental exposure to HIV: the Italian experience AIDS. 1992; 6:963-9.

50. Gerberding J. Is antiretroviral treatment after percutaneous HIV exposure justified? Ann Intern Med. 1993; 18:979-80. Editorial.

55. Anon. Case-control study of HIV seroconversion in health-care workers after percutaneous exposure to HIV-infected blood—France, United Kingdom, and United States, January 1988-August 1994 MMWR. 1995; 44:929-33.

58. Beekman SE, Henderson DK. HIV infection in healthcare workers: risks for infection and methods of prevention. Semin Dermatol. 1995; 14:212-8. [PubMed 7488537]

59. Benhamou Y, Katlama C, Lunel F et al. Effects of lamivudine on replication of hepatitis B virus in HIV-infected men. Ann Intern Med. 1996; 125:705-12. [IDIS 376781] [PubMed 8929003]

61. Centers for Disease Control and Prevention. Report of the NIH panel to define principles of therapy of HIV infection. MMWR Recomm Rep. 1998; 47(No. RR-5):1-42.

65. Dienstag JL, Perrillo RP, Schiff ER et al A preliminary trial of lamivudine for chronic hepatitis B infection. N Engl J Med. 1995; 333:1657-61.

66. Dore GJ, Cooper DA, Barrett C et al. Dual efficacy of lamivudine treatment in human immunodeficiency virus/hepatitis B virus–coinfected persons in a randomized, controlled study (CAESAR). J Infect Dis. 1999; 180:607-13. [IDIS 434666] [PubMed 10438346]

67. Benhamou Y, Katlama C, Lunel F et al. Effects of lamivudine on replication of hepatitis B virus in HIV-infected men. Ann Intern Med. 1996; 125:705-12. [IDIS 376781] [PubMed 8929003]

68. Nevens F, Main J, Honkoop P et al. Lamivudine therapy for chronic hepatitis B: A six-month randomized dose-ranging study. Gastroenterology. 1997; 113:1258-63. [IDIS 394667] [PubMed 9322520]

69. Lai C, Chien R, Leung N et al. A one-year trial of lamivudine for chronic hepatitis B. N Engl J Med. 1998; 339:61-8. [IDIS 407405] [PubMed 9654535]

70. Omata M. Treatment of chronic hepatitis B infection. N Engl J Med. 1998; 339:114-5. [IDIS 407408] [PubMed 9654543]

71. Lai CL, Ching CK, Tung AK et al. Lamivudine is effective in suppressing hepatitis B virus DNA in Chinese hepatitis B surface antigen carriers: a placebo-controlled trial. Hepatology. 1997; 25:241-4. [PubMed 8985298]

72. Nery JR, Weppler D, Rodriguez M et al. Efficacy of lamivudine in controlling hepatitis B virus recurrence after liver transplantation. Transplantation. 1998; 65:1615-21. [IDIS 410178] [PubMed 9665079]

73. Bartholomew MM, Jansen RW, Jeffers LJ et al. Hepatitis-B resistance to lamivudine given for recurrent infection after orthotopic liver transplant. Lancet. 1997; 349:20-2. [IDIS 377952] [PubMed 8988118]

74. Grellier L, Mutimer D, Ahmed M. Lamivudine prophylaxis against reinfection in liver transplantation for hepatitis B cirrhosis. Lancet. 1996; 348-1212-15.

75. Schalm SW. Clinical implications of lamivudine resistance by HBV. Lancet. 1997; 349:3-4. [IDIS 377947] [PubMed 8988109]

76. Anon. Glaxo Epivir-HBV therapy duration should be until loss of response—cmte. F-D-C Rep. October 12, 1998.

78. Cohen Stuart JWT, Schuurman R, burger DM et al. Randomized trial comparing squinavir soft gelatin capsules versus indinavir as part of triple therapy (CHEESE study). AIDS. 1999; 13:F53-8.

83. Conway B, Montessori V, Rouleau D et al. Primary lamivudine resistance in acute/early human immunodeficiency virus infection. Clin Infect Dis. 1999; 28:910-1. [IDIS 427014] [PubMed 10825060]

84. Saez-Llorens X, Nelson RP, Wiznia A et al. A randomized, double-blind study of triple nucleoside therapy of abacavir, lamivudine, and zidovudine versus lamivudine and zidovudine in previously treated human immunodeficiency virus type 1-infected children. Pediatrics. 2001; 107:E4. [IDIS 458530] [PubMed 11134468]

86. Funk MB, Linde R, Wintergerst U et al. Preliminary experiences with triple therapy including nelfinavir and two reverse transcriptase inhibitors in previously untreated HIV-infected children. AIDS. 1999; 13:1653-8. [PubMed 10509566]

87. Solder B, Wintergerst U, Notheis G et al. Effect of antiretroviral combination therapy (zidovudine/didanosine) or zidovudine/lamivudine) on quantitative plasma human immunodeficiency virus-ribonucleic acid in children and adolescents infected with human immunodeficiency virus. J Pediatr. 1997; 130:293-9. [IDIS 382125] [PubMed 9042135]

88. Horneff G, Adams O, Wahn V. Pilot study of zidovudine-lamivudine combination therapy in vertically HIV-infected antiretroviral-naive children. AIDS. 1998; 12:489-94. [PubMed 9543447]

89. McKinney RE, Johnson GM, Stanley K et al. A randomized study of combined zidovudine-lamivudine versus didanosine monotherapy in children with symptomatic therapy-naive HIV-1 infection. The Pediatric AIDS Clinical Trials Group Protocol 300 Study Team. J Pediatr. 1998; 133:500-8. [IDIS 416487] [PubMed 9787687]

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91. Moodley J, Moodley D, Phillay K et al. Pharmacokinetics and antiretroviral activity of lamivudine alone or when coadministered with zidovudine in human immunodeficiency virus type 1-infected pregnant women and their offspring. J Infect Dis. 1998; 178:1327-33. [IDIS 418532] [PubMed 9780252]

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102. Pattishall EN. Dear healthcare provider letter regarding dispensing errors involving Lamictal (lamotrigine). Research Triangle Park, NC; GlaxoSmithKline; 2001 Aug.

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106. DART Virology group and trial team. Virologic response to a triple nucleoside/nucleotide analogue regimen over 48 weeks in HIV-1 infected adults in Africa. AIDS. 2006; 20:1391-9. [PubMed 16791013]

109. Genentech USA. Pegasys (peginterferon alfa-2a) solution for subcutnaeous injection prescribing information. South San Francisco, CA; 2011 Feb.

121. Moyle G, Higgs C, Teague A et al. An open-label, randomized comparative pilot study of a single-class quadruple therapy regimen versus a 2-class triple therapy regimen for individuals initiating antiretroviral therapy. Antivir Ther. 2006; 11:73-8. [PubMed 16518962]

122. Puls RL, Srasuebkul P, Petoumenos K et al. Efavirenz versus boosted atazanavir or zidovudine and abacavir in antiretroviral treatment-naive, HIV-infected subjects: week 48 data from the Altair study. Clin Infect Dis. 2010; 51:855-64. [PubMed 20735258]

190. Kaplan JE, Benson C, Holmes KH et al. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2009; 58(RR-4):1-207; quiz CE1-4.

191. Mofenson LM, Brady MT, Danner SP et al. Guidelines for the Prevention and Treatment of Opportunistic Infections among HIV-exposed and HIV-infected children: recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics. MMWR Recomm Rep. 2009; 58(RR-11):1-166. [PubMed 19730409]

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199. Center for Disease Control and Prevention. Updated U.S. public health service guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis. MMWR Recomm Rep. 2005; 54(No. RR-9):1-17.

200. Panel on Antiretroviral Guidelines for Adults and Adolescents, US Department of Health and Human Services (HHS). Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (April 18, 2012). Updates may be available at HHS AIDS Information (AIDSinfo) website.

201. Panel on Antiretroviral Therapy and Medical Management of HIV-infected Children, US Department of Health and Human Services (HHS). Guidelines for the use of antiretroviral agents in pediatric HIV infection (August 11, 2011). Updates may be available at HHS AIDS Information (AIDSinfo) website.

202. Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission, US Department of Health and Human Services (HHS). Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States (July 31, 2012). Updates may be available at HHS AIDS Information (AIDSinfo) website.

203. Bristol-Myers Squibb. Reyataz (atazanavir sulfate) capsules prescribing information. Princeton, NJ; 2012 Mar.

204. Janssen. Prezista (darunavir) oral suspension and tablets prescribing information. Titusville, NJ; 2012 Jun.

205. ViiV Healthcare. Lexiva (fosamprenavir calcium) tablets and oral suspension prescribing information. Research Triangle Park, NC; 2012 Feb.

207. Abbott Laboratories. Kaletra (lopinavir/ritonavir) tablets and oral solution prescribing information. North Chicago, IL; 2012 Feb.

208. ViiV Healthcare. Viracept (nelfinavir mesylate) tablets and oral powder prescribing information. Research Triangle Park, NC; 2012 Apr.

209. Abbott Laboratories. Norvir (ritonavir) tablets and oral solution prescribing information. North Chicago, IL; 2012 Feb.

210. Genentech USA. Invirase (saquinavir mesylate) capsules and tablets prescribing information. South San Francisco, CA; 2012 Feb.

211. Boehringer Ingelheim. Aptivus (tipranavir) capsules and oral solution prescribing information. Ridgefield, CT; 2012 Apr.

212. ViiV Healthcare. Rescriptor (delavirdine mesylate) tablets prescribing information. Research Triangle Park, NC; 2010 Sep.

213. Bristol-Myers Squibb. Sustiva (efavirenz) capsules and tablets prescribing information. Princeton, NJ; 2012 Jun.

214. Janssen. Intelence (etravirine) tablets prescribing information. Raritan, NJ; 2012 Mar.

215. Boehringer Ingelheim. Viramune (nevirapine) tablets and oral suspension prescribing information. Ridgefield, CT; 2011 Nov.

216. ViiV Healthcare. Ziagen (abacavir sulfate) tablets and oral solution prescribing information. Research Triangle Park, NC; 2012 May.

217. Bristol-Myers Squibb. Videx EC (didanosine) delayed-release capsules enteric-coated beadlets prescribing information. Princeton, NJ; 2011 Nov.

218. Gilead Sciences. Emtriva (emtricitabine) capsules and oral solution prescribing information. Foster City, CA; 2011 Nov.

220. Bristol-Myers Squibb. Zerit (stavudine) capsules and oral solution prescribing information. Princeton, NJ; 2012 Jan.

221. Gilead Sciences. Viread (tenofovir disoproxil fumarate) tablets prescribing information. Foster City, CA; 2012 Jan.

222. ViiV Healthcare. Retrovir (zidovudine) tablets, capsules, and syrup prescribing information. Research Triangle Park, NC; 2012 May.

223. Genentech USA. Fuzeon (enfuvirtide) for injection prescribing information. South San Francisco, CA; 2011 Aug.

224. ViiV Healthcare. Selzentry (maraviroc) tablets prescribing information. Research Triangle Park, NC; 2011 Nov.

225. Merck Sharp & Dohme. Isentress (raltegravir) film-coated tablets and chewable tablets prescribing information. Whitehouse Station, NJ; 2012 Apr.

226. Tibotec Therapeutics. Edurant (rilpivirine) tablets prescribing information. Raritan, NJ; 2011 May.

227. ViiV Healthcare. Combivir (lamivudine and zidovudine) tablets prescribing information. Research Triangle Park, NC; 2011 Nov.

228. ViiV Healthcare. Epzicom (abacavir sulfate and lamivudine) tablets prescribing information. Research Triangle Park, NC; 2012 May.

229. ViiV Healthcare. Trizivir (abacavir sulfate, lamivudine, and zidovudine) tablets prescribing information. Research Triangle Park, NC; 2012 May.

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