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LamiVUDine

Pronunciation

Pronunciation

(la MI vyoo deen)

Index Terms

  • 3TC

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Oral:

Epivir: 10 mg/mL (240 mL) [contains methylparaben, propylene glycol, propylparaben; strawberry-banana flavor]

Epivir HBV: 5 mg/mL (240 mL) [contains methylparaben, propylene glycol, propylparaben; strawberry-banana flavor]

Generic: 10 mg/mL (240 mL)

Tablet, Oral:

Epivir: 150 mg [scored]

Epivir: 300 mg

Epivir HBV: 100 mg

Generic: 100 mg, 150 mg, 300 mg

Brand Names: U.S.

  • Epivir
  • Epivir HBV

Pharmacologic Category

  • Antihepadnaviral, Reverse Transcriptase Inhibitor, Nucleoside (Anti-HBV)
  • Antiretroviral, Reverse Transcriptase Inhibitor, Nucleoside (Anti-HIV)

Pharmacology

Lamivudine is a cytosine analog. In vitro, lamivudine is triphosphorylated, the principle mode of action is inhibition of HIV reverse transcription via viral DNA chain termination; inhibits RNA- and DNA-dependent DNA polymerase activities of reverse transcriptase. In hepatitis B, the monophosphate form of lamivudine is incorporated into the viral DNA by hepatitis B virus polymerase, resulting in DNA chain termination.

Absorption

Rapid

Distribution

Into extravascular spaces

Children (n=38): CSF concentrations were 14.2 ± 7.9% of the serum concentration

Vd: 1.3 ± 0.4 L/kg

Metabolism

Minor; only known metabolite is trans-sulfoxide metabolite

Excretion

Primarily urine (majority as unchanged drug); weight-corrected oral clearance is highest at age 2 years, then declines from age 2 to 12 years, where values then remain comparable to adult values

Time to Peak

Pediatric patients 0.5 to 17 years: Median: 1.5 hours (range: 0.5 to 4 hours) (Lewis 1996)

Adolescents 13 to 17 years: 0.5 to 1 hour

Adults: Fed: 3.2 hours; Fasted: 0.9 hours

Half-Life Elimination

Intracellular: 10 to 15 hours

Elimination:

Children 4 months to 14 years: 2 ± 0.6 hours

Adults: 5 to 7 hours; increased with renal impairment

Protein Binding

Plasma: <36%

Special Populations: Renal Function Impairment

AUC, and Cmaxare increased.

Use: Labeled Indications

Chronic hepatitis B (Epivir HBV): Treatment of chronic hepatitis B associated with evidence of hepatitis B viral replication and active liver inflammation.

Limitations of use: Use only when an alternative antiviral agent with a higher genetic barrier to resistance is not available or appropriate; has not been evaluated in patients with HBV-HIV-1 coinfection, hepatitis C virus or hepatitis delta virus; has also not been evaluated in patients with chronic HBV infection with decompensated liver disease or in liver transplant recipients.

HIV-1 infection (Epivir): Treatment of HIV-1 in combination with other antiretroviral agents

Contraindications

Hypersensitivity (eg, anaphylaxis) to lamivudine or any component of the formulation

Dosing: Adult

Note: The formulation and dosage of Epivir HBV are not appropriate for patients infected with both HBV and HIV; tenofovir and lamivudine are a preferred NRTI backbone in a fully suppressive antiretroviral regimen and for the treatment of HBV coinfection (HHS [adult] 2015).

HIV-1 infection (Epivir): Oral (use in combination with other antiretroviral agents): 150 mg twice daily or 300 mg once daily.

Note: Lamivudine is a component of recommended initial regimens for any ART-naive patient (when coadministered with tenofovir plus dolutegravir, with tenofovir plus raltegravir, or with tenofovir plus darunavir/ritonavir) or for ART-naive patients who are HLA-B*5701 negative (when coadministered with abacavir plus dolutegravir) (HHS [adult] 2015).

HIV-1 nonoccupational postexposure prophylaxis (nPEP) (off-label use) (HHS [nPEP] 2016): Oral: Note: Initiate therapy within 72 hours of exposure and continue for 28 days; use in combination with other antiretroviral agents.

CrCl ≥60 mL/minute: Lamivudine is not a component of the recommended antiretroviral regimens for these patients.

CrCl <60 mL/minute: Dose should be adjusted based on renal function.

Treatment of hepatitis B (Epivir HBV, Heptovir [Canadian product]): Oral: 100 mg once daily

Treatment duration (AASLD practice guidelines): Treatment duration for nucleos(t)ide analog-based therapy (eg, lamivudine) is variable and influenced by HBeAg status, duration of HBV suppression, and presence of cirrhosis/decompensation (AASLD [Terrault 2016):

Patients without cirrhosis:

Hepatitis B e antigen (HBeAg) positive immune-active chronic hepatitis: Treat until HBeAg seroconversion; after seroconversion, prolonged duration of therapy is often required in patients treated with nucleos(t)ide anaglogues. Optimal duration is unknown; however, consolidation therapy is generally a minimum of 12 months of persistently normal ALT and undetectable serum HBV DNA levels after HBeAg seroconversion

HBeAg-negative immune-active chronic hepatitis: Indefinite antiviral therapy is suggested unless there is competing rationale for discontinuation (risk/benefit decision); treatment discontinuation may be considered in patients with loss of HBsAg; however, there is insufficient evidence to guide decisions in these patients.

Patients with cirrhosis:

HBeAg-positive immune-active chronic hepatitis: In patients who seroconvert on therapy, continue antiviral therapy indefinitely due to concerns with decompensation and death, unless there is a strong competing rationale for discontinuation.

HBeAg-negative immune-active chronic hepatitis: Treatment discontinuation is not recommended due to potential for decompensation and death (limited data).

Viral breakthrough (AASLD practice guidelines): Patients with confirmed viral breakthrough (HBV DNA ≥100 units/mL with previously undetectable levels [<10 units/mL] or >1 log increase in HBV DNA) should either be switched to an alternative antiviral monotherapy agent with a high genetic barrier to resistance or receive a second antiviral agent with a complementary resistance profile; consult current clinical practice guidelines for recommended agents (AASLD [Terrault 2016]).

Treatment of hepatitis B/HIV coinfection (in patients with both infections requiring treatment): Note: The formulation and dosage of Epivir HBV are not appropriate for patients infected with both HBV and HIV. Tenofovir and/or lamivudine are a preferred NRTI backbone in a fully suppressive antiretroviral regimen for the treatment of HIV/HBV coinfection (HHS [adult] 2015).

Oral: 150 mg twice daily or 300 mg/dose once daily, in combination with other antiretrovirals in an antiretroviral (ARV) regimen (HHS [adult] 2015)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

HIV-1 infection, treatment: Note: Use in combination with other antiretroviral agents.

Infants 1 to 3 months (off-label dose): Epivir: Oral solution (10 mg/mL): 4 mg/kg/dose twice daily (HHS [pediatric] 2016; Tremoulet 2007)

Infants ≥3 months, Children, and Adolescents: Note: Once-daily dosing is not recommended as initial therapy, especially with use of the oral solution in infants and young children. Efficacy of once-daily dosing has only been demonstrated in patients who transitioned from twice-daily dosing after 36 weeks of treatment. Some experts recommend reserving once-daily therapy for use as a component of a once-daily regimen in clinically stable patients ≥3 years who have undetectable viral loads and stable CD4 counts (HHS [pediatric] 2016).

Oral solution:

Epivir (10 mg/mL): 8 mg/kg/day in 1 to 2 divided doses (maximum: 300 mg/day)

Alternative recommendations (3TC Canadian product labeling 2016):

<25 kg: 8 mg/kg/day in 1 to 2 divided doses (maximum: 300 mg/day)

≥25 kg: 150 mg twice daily or 300 mg once daily (maximum: 300 mg/day)

Alternate recommendations: 8 to 10 mg/kg/dose once daily; maximum dose: 300 mg/dose (HHS [pediatric] 2016)

Oral tablets: Weight-band dosing for patients weighing ≥14 kg who are able to swallow tablets (using scored 150 mg tablets):

14 to <20 kg: 75 mg twice daily or 150 mg once daily

≥20 to <25 kg: 75 mg in the morning, 150 mg in the evening or 225 mg once daily

≥25 kg: 150 mg twice daily or 300 mg once daily

HIV-1 nonoccupational postexposure prophylaxis (nPEP) (off-label use) (HHS [nPEP] 2016): Note: Initiate therapy within 72 hours of exposure and continue for 28 days in combination with other antiretroviral agents; Oral: Epivir:

Infants, Children, and Adolescents <16 years:

Weight-directed dosing: Oral solution (10 mg/mL): 4 mg/kg/dose twice daily (maximum: 150 mg/dose)

Weight-band dosing: Oral tablet: For patients ≥14 kg who are able to swallow tablets (scored 150 mg tablets):

14 to <20 kg: 75 mg twice daily

20 to <25 kg: 75 mg in the morning and 150 mg in the evening

≥25 kg: 150 mg twice daily

Adolescents ≥16 years: Oral solution (10 mg/mL) or oral tablet:

<50 kg: 4 mg/kg/day twice daily (maximum: 150 mg/dose)

≥50 kg: 150 mg twice daily or 300 mg once daily

Prevention of perinatal HIV transmission (off-label use; HHS [perinatal] 2016): Note: To be used as part of a 3-drug regimen with zidovudine and nevirapine in infants at higher risk of HIV acquisition. Initiate therapy as soon as possible after birth, preferably within 6 to 12 hours of delivery. Continue regimen from birth through 2 to 6 weeks.

≥32 weeks’ gestation at birth:

Birth to 4 weeks: Oral: 2 mg/kg twice daily

4 weeks to 6 weeks: Oral: 4 mg/kg twice daily

Treatment of hepatitis B/HIV coinfection (in patients with both infections requiring treatment): Note: The formulation and dosage of Epivir HBV are not appropriate for patients infected with both HBV and HIV.

Infants and Children: Oral: 4 mg/kg/dose (maximum: 150 mg) twice daily, in combination with other antiretrovirals in an ARV regimen (DHHS [pediatric] 2013)

Adolescents: Refer to adult dosing.

Treatment of hepatitis B (Epivir HBV):Note: Tablets and oral solution may be used interchangeably; for doses <100 mg, oral solution is recommended.

Children and Adolescents 2 to 17 years: Oral: 3 mg/kg/dose once daily (maximum: 100 mg/day)

Dosing: Renal Impairment

HIV-1 infection:

Adults:

End stage renal disease (ESRD) requiring hemodialysis: Administer 50 mg first dose, then 25 mg once daily (IDSA [Lucas 2014]). Negligible amounts are removed by 4-hour hemodialysis or peritoneal dialysis. Supplemental dosing not needed; however, dosing after dialysis is recommended (HHS [adult] 2015).

Adolescents ≥25 kg and Adults:

CrCl ≥50 mL/minute: No dosage adjustment necessary

CrCl 30 to 49 mL/minute: Administer 150 mg once daily

CrCl 15 to 29 mL/minute: Administer 150 mg first dose, then 100 mg once daily

CrCl 5 to 14 mL/minute: Administer 150 mg first dose, then 50 mg once daily

CrCl <5 mL/minute: Administer 50 mg first dose, then 25 mg once daily

Infants ≥3 months, Children, and Adolescents <25 kg: There are no dosage adjustments provided in the manufacturer’s labeling (insufficient data); however, dose reduction should be considered.

Alternative recommendations (3TC Canadian product labeling 2016):

CrCl 30 to 50 mL/minute: Administer 4 mg/kg once daily

CrCl 15 to 29 mL/minute: Administer 4 mg/kg first dose, then 2.6 mg/kg once daily

CrCl 5 to 14 mL/minute: Administer 4 mg/kg first dose, then 1.3 mg/kg once daily

CrCl <5 mL/minute: Administer 1.3 mg/kg first dose, then 0.7 mg/kg once daily

Treatment of hepatitis B patients: Adults:

CrCl ≥50 mL/minute: No dosage adjustment necessary.

CrCl 30 to 49 mL/minute: Administer 100 mg first dose, then 50 mg once daily.

CrCl 15 to 29 mL/minute: Administer 100 mg first dose, then 25 mg once daily.

CrCl 5 to 14 mL/minute: Administer 35 mg first dose, then 15 mg once daily.

CrCl <5 mL/minute: Administer 35 mg first dose, then 10 mg once daily.

ESRD requiring hemodialysis: Negligible amounts are removed by 4-hour hemodialysis or peritoneal dialysis. Supplemental dosing not needed; however, dosing after dialysis is recommended (HHS [adult] 2015).

Dosing: Hepatic Impairment

No dosage adjustment necessary. However, has not been studied in the setting of decompensated liver disease.

Administration

Oral: May be administered without regard to meals.

Dietary Considerations

Some products may contain sucrose.

Storage

Oral solution:

Epivir: Store at 25°C (77°F) tightly closed.

Epivir HBV: Store at 20°C to 25°C (68°F to 77°F) tightly closed.

Tablet: Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

Drug Interactions

Cabozantinib: MRP2 Inhibitors may increase the serum concentration of Cabozantinib. Monitor therapy

Emtricitabine: LamiVUDine may enhance the adverse/toxic effect of Emtricitabine. Avoid combination

Orlistat: May decrease the serum concentration of Antiretroviral Agents. Monitor therapy

Trimethoprim: May increase the serum concentration of LamiVUDine. Monitor therapy

Adverse Reactions

Incidence data include patients on combination therapy with other antiretroviral agents.

>10%:

Central nervous system: Headache (21% to 35%), fatigue (24% to 27%), neuropathy (12%), insomnia (11%)

Gastrointestinal: Nausea (15% to 33%), diarrhea (14% to 18%), pancreatitis (≤18%; higher percentage in pediatric patients), abdominal pain (9% to 16%), vomiting (13% to 15%), sore throat (13%)

Hematologic & oncologic: Neutropenia (7% to 15%)

Hepatic: Increased serum transaminases (2% to 11%)

Infection: Infection (25%; includes ear, nose, and throat)

Neuromuscular & skeletal: Myalgia (8% to 14%), musculoskeletal pain (12%)

Respiratory: Nasal signs and symptoms (20%), cough (18%)

1% to 10%:

Central nervous system: Dizziness (10%), depression (9%), chills (7% to 10%)

Dermatologic: Skin rash (5% to 9%)

Gastrointestinal: Anorexia (10%), increased serum lipase (10%), abdominal cramps (6%), dyspepsia (5%), increased amylase (≤4%), heartburn

Hematologic & oncologic: Thrombocytopenia (1% to 4%), hemoglobinemia (2% to 3%)

Neuromuscular & skeletal: Increased creatine phosphokinase (9%), arthralgia (5% to 7%)

Miscellaneous: Fever (7% to 10%)

<1% (Limited to important or life-threatening): Alopecia, anaphylaxis, anemia, exacerbation of hepatitis B, hepatomegaly, hyperbilirubinemia, hyperglycemia, immune reconstitution syndrome, lactic acidosis, liver steatosis, lymphadenopathy, myasthenia, paresthesia, peripheral neuropathy, pruritus, pure red cell aplasia, redistribution of body fat, rhabdomyolysis, splenomegaly, stomatitis, urticaria, weakness, wheezing

ALERT: U.S. Boxed Warning

Lactic acidosis and severe hepatomegaly with steatosis:

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination, including lamivudine and other antiretrovirals. Discontinue lamivudine if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur.

Exacerbations of hepatitis B:

Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti–hepatitis B therapy (including lamivudine-HBV) or are coinfected with hepatitis B virus (HBV) and HIV 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 anti–hepatitis B therapy or who discontinue lamivudine and are coinfected with HIV-1 and HBV. If appropriate, initiation of anti–hepatitis B therapy may be warranted.

Important differences among lamivudine-containing products:

Lamivudine tablets and oral solution (used to treat HIV-1 infection) contain a higher dose of lamivudine than lamivudine-HBV tablets and oral solution (used to treat chronic hepatitis B infection). Patients with HIV-1 infection should receive only dosage forms appropriate for treatment of HIV-1.

HIV counseling/testing:

Offer HIV counseling and testing to all patients before beginning lamivudine-HBV and periodically during treatment because lamivudine-HBV contains a lower dose of the same active ingredient as lamivudine tablets and oral solution used to treat HIV-1. If treatment with lamivudine-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 because of the subtherapeutic dose and inappropriate monotherapy.

Warnings/Precautions

Concerns related to adverse effects:

• Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance).

• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves’ disease, polymyositis, Guillain-Barré syndrome) later in therapy; further evaluation and treatment may be required.

• Lactic acidosis/hepatomegaly: [US Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues, including fatal cases; suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity; use with caution in patients with risk factors for liver disease (risk may be increased with female gender, obesity, pregnancy or prolonged exposure); transaminase elevation may/may not accompany hepatomegaly and steatosis.

• Pancreatitis: Has been reported, particularly in HIV-infected children with a history of nucleoside use.

Disease-related concerns:

• Chronic hepatitis B: [US Boxed Warning]: Monitor patients closely for several months following discontinuation of therapy for chronic hepatitis B; clinical exacerbations may occur, including fatal cases. Monitor hepatic function with clinical and laboratory follow up for at least several months after hepatitis B treatment discontinuation. Initiate antihepatitis B (HBV) medications if clinically appropriate.

• Renal impairment: Use with caution in patients with renal impairment; dosage reduction recommended.

• Risk of resistance: [US Boxed Warning]: HIV-1 resistance may emerge in chronic hepatitis B-infection patients with unrecognized or untreated HIV-1 infection. Counseling and (HIV) testing should be offered to all patients before beginning treatment with lamivudine for hepatitis B and then periodically during treatment. Lamivudine dosing for hepatitis B is subtherapeutic if used for HIV-1 infection treatment. Lamivudine monotherapy is not appropriate for HIV-1 infection treatment. Lamivudine resistant HIV-1 can develop rapidly and limit treatment options if used in unrecognized or untreated HIV-1 infection or if a patient becomes coinfected during HBV treatment. Lamivudine dosing for hepatitis B is also subtherapeutic if used for HIV-1/HBV coinfection treatment. If lamivudine is chosen as part of a HIV-1 treatment regimen in coinfected patients, the higher lamivudine dosage indicated for HIV-1 therapy should be used, with other drugs, in an appropriate combination regimen. Emergence of lamivudine resistant HBV variants has also been reported in HIV-1 /HBV coinfected patients who have received lamivudine-containing antiretroviral regimens.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information

• Duplicate therapy: Concomitant use of other lamivudine-containing products should be avoided.

• Interferon alfa: Use with caution in combination with interferon alfa with or without ribavirin in HIV/HBV coinfected patients; monitor closely for hepatic decompensation, anemia, or neutropenia; dose reduction or discontinuation of interferon and/or ribavirin may be required if toxicity evident.

Special populations:

• Pediatric: Use with extreme caution in children with history of pancreatitis or risk factors for development of pancreatitis.

Dosage form specific issues:

• Appropriate product selection: Epivir HBV: [US Boxed Warning]: Do not use Epivir HBV tablets or Epivir HBV oral solution for the treatment of HIV.

• Oral solution: Use of lamivudine oral solution has been associated with lower rates of virologic suppression, lower plasma lamivudine exposure, and increased rates of resistance when compared to lamivudine tablets in pediatric clinical trials. Lamivudine scored tablet is the preferred formulation for HIV-1 infected pediatric patients weighing ≥14 kg and for whom a solid dosage form is appropriate; consider more frequent monitoring of HIV-1 viral load if oral solution is used.

• Sucrose: Lamivudine oral solutions contains 3 g of sucrose/15 mL; advise diabetic patients of sucrose content.

• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures and respiratory depression; use caution (AAP 1997; Zar 2007).

Other warnings/precautions:

• Appropriate use:

HIV: Do not use as monotherapy in treatment of HIV. Treatment of HIV in patients with unrecognized/untreated HBV may lead to rapid HBV resistance; HIV-infected patients should be screened for hepatitis B prior to starting lamivudine HIV therapy. Lamivudine combined with emtricitabine is not recommended as a dual-NRTI combination due to similar resistance patterns and negligible additive antiviral activity; lamivudine in combination with abacavir or tenofovir is recommended as the NRTIs in a fully suppressive antiretroviral regimen. Do not use lamivudine/abacavir (plus efavirenz or plus atazanavir/ritonavir) in adolescent and adult HIV-1 patients with a pre-ART HIV RNA >100,000 copies/mL (HHS [adult] 2015).

HBV: Current clinical hepatitis B practice guidelines do not recommend lamivudine for initial use in the management of chronic HBV due to low barrier to resistance; other antiviral agents with a high genetic barrier to drug resistance are preferred (eg, tenofovir or entecavir) (AASLD [Terrault 2016]).

HIV/HBV coinfection: Lamivudine and/or tenofovir are a recommended NRTI backbone in a fully suppressive antiretroviral regimen to provide activity against both HIV and HBV (HHS [adult] 2015).

Monitoring Parameters

Manufacturer’s labeling:

All patients: Hepatic function, signs/symptoms of lactic acidosis; signs/symptoms of pancreatitis

HIV patients: Coinfection with HBV (prior to therapy); HIV viral load and CD4 count; immune reconstitution syndrome

Hepatitis B patients: Coinfection with HIV (prior to therapy); following discontinuation, monitor hepatic function closely with both clinical and laboratory follow/up for signs/symptoms of HBV relapse/exacerbation (continue for at least several months after stopping treatment)

Alternate recommendations:

Chronic Hepatitis B: HBV DNA and ALT (HBV DNA usually done every 3 months until undetectable and then every 3 to 6 months thereafter); HBeAg; anti-HBe (in patients who are HBeAg-positive to monitor for seroconversion); HBsAg; during therapy, consider monitoring amylase (if symptoms of pancreatitis) and lactic acid levels (if clinical concern); following discontinuation, monitor for recurrent viremia, ALT flares, seroreversion, and clinical decompensation every 3 months for at least 1 year (AASLD [Terrault 2016]). As antivirals do not eliminate the risk of hepatocellular carcinoma, continued monitoring for this complication is recommended in at-risk patients.

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events were observed in some animal reproduction studies. Lamivudine has a high level of transfer across the human placenta. No increased risk of overall birth defects has been observed following first trimester exposure according to data collected by the antiretroviral pregnancy registry. Maternal antiretroviral therapy may increase the risk of preterm delivery, although, available information is conflicting possibly due to variability of maternal factors (disease severity; initiation of therapy); however, maternal antiretroviral medication should not be withheld due to concerns of preterm birth. Based on data collected by the antiretroviral pregnancy registry, the risk of spontaneous abortions, induced abortions, and preterm birth is less in lamivudine-containing regimens compared with regimens without lamivudine. Information related to stillbirth, low birth weight, and small for gestational age infants is limited. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children who develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential mitochondrial dysfunction. Cases of lactic acidosis and hepatic steatosis related to mitochondrial toxicity have been reported with use of nucleoside reverse transcriptase inhibitors (NRTIs). These adverse events are similar to other rare but life-threatening syndromes that occur during pregnancy (eg, HELLP syndrome). In general, NRTIs are well tolerated and the benefits of use generally outweigh potential risk.

Combination antiretroviral therapy (cART) therapy is recommended for all HIV-infected pregnant women to keep the viral load below the limit of detection and reduce the risk of perinatal transmission. When HIV is diagnosed during pregnancy in a woman who has never received antiretroviral therapy, cART should begin as soon as possible after diagnosis. The Health and Human Services (HHS) Perinatal HIV Guidelines consider lamivudine in combination with either abacavir or tenofovir disoproxil fumarate to be a preferred NRTI backbone for initial therapy in antiretroviral-naive pregnant women. The lamivudine/abacavir backbone is not recommended with atazanavir/ritonavir or efavirenz if pretreatment HIV RNA is >100,000 copies/mL. The guidelines consider lamivudine with zidovudine to be an alternative NRTI backbone for initial therapy in antiretroviral-naive pregnant women. The guidelines also consider lamivudine plus tenofovir disoproxil fumarate a recommended dual NRTI backbone in regimens for HIV/HBV-coinfected pregnant women. Use caution with hepatitis B coinfection; hepatitis B flare may occur if lamivudine is discontinued. The pharmacokinetics of lamivudine during pregnancy are not significantly altered and dosage adjustment is not required. In general, women who become pregnant on a stable cART regimen may continue that regimen if viral suppression is effective, appropriate drug exposure can be achieved, contraindications for use in pregnancy are not present, and the regimen is well tolerated. Monitoring during pregnancy is more frequent than in non-pregnant adults; cART should be continued postpartum.

For HIV-infected couples planning a pregnancy, maximum viral suppression with cART is recommended prior to conception for the HIV-infected partner(s) and expert consultation is recommended; modification of therapy (if needed) and optimization of the woman's health should be done prior to conception. HIV-infected women not planning a pregnancy may use any available type of contraception, considering possible drug interactions and contraindications of the specific method. In addition, consistent use of condoms is also recommended (even during pregnancy) to prevent transmission of HIV or other sexually transmitted diseases.

In hepatitis B-infected women (not coinfected with HIV), the AASLD chronic hepatitis B treatment guidelines suggest antiviral therapy to reduce the risk of perinatal transmission of hepatitis B in HBsAg-positive pregnant women with an HBV DNA >200,000 units/mL. There are limited data on the level of HBV DNA for when antiviral therapy is routinely recommended (>200,000 units/mL is a conservative recommendation); however, the AASLD recommends against antiviral therapy to reduce the risk of perinatal transmission in HBsAg-positive pregnant women with an HBV DNA ≤200,000 units/mL. Lamivudine is one of the antivirals that has been studied in pregnant women, with most studies initiating antiviral therapy at 28 to 32 weeks gestation and discontinuing antiviral therapy between birth to 3 months postpartum (monitor for ALT flares every 3 months for 6 months following discontinuation). There is insufficient long-term safety data in infants born to mothers who took antiviral agents during pregnancy (AASLD [Terrault 2016]).

Health care providers are encouraged to enroll pregnant women exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or www.APRegistry.com). Health care providers caring for HIV-infected women and their infants may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation (HHS [perinatal] 2016).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache, nausea, vomiting, diarrhea, loss of strength and energy, rhinitis, rhinorrhea, cough, dizziness, muscle pain, insomnia, pharyngitis, or ear irritation. Have patient report immediately to prescriber signs of too much lactic acid in the blood (lactic acidosis; fast breathing, fast heartbeat, abnormal heartbeat, vomiting, drowsiness, shortness of breath, feeling very tired or weak, severe dizziness, feeling cold, or muscle pain or cramps), signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of a pancreas problem (pancreatitis; severe abdominal pain, severe back pain, severe nausea, vomiting), change in body fat, burning or numbness feeling, mood changes, or signs of infection (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.