Dolutegravir and Lamivudine (Monograph)

Drug class: HIV Integrase Inhibitors

Medically reviewed by Drugs.com on Mar 10, 2024. Written by ASHP.

Warning

Test all HIV-infected patients for presence of HBV prior to initiating fixed combination of dolutegravir and lamivudine (dolutegravir/lamivudine). Emergence of lamivudine-resistant HBV associated with use of lamivudine-containing antiretroviral regimens. If dolutegravir/lamivudine used in patients coinfected with HIV and HBV, consider appropriate treatment for chronic HBV or consider alternative antiretroviral regimen.
Severe, acute exacerbations of HBV infection reported following discontinuance of lamivudine in patients coinfected with HIV and HBV. Monitor hepatic function closely. If appropriate, initiation of HBV treatment may be warranted.

Introduction

Antiretroviral; fixed combination of dolutegravir and lamivudine (dolutegravir/lamivudine). Dolutegravir is an HIV integrase strand transfer inhibitor (INSTI) and lamivudine is an HIV nucleoside reverse transcriptase inhibitor (NRTI).

Uses for Dolutegravir and Lamivudine

Treatment of HIV Infection

Used as a complete regimen for the treatment of HIV-1 infection in antiretroviral-naive (have not previously received antiretroviral therapy) adults or to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen with no history of treatment failure and no known substitutions associated with resistance to dolutegravir or lamivudine.

Consult guidelines for the most current information on the place in therapy for dolutegravir/lamivudine. Selection of an initial antiretroviral regimen should be individualized based on factors such as virologic efficacy, toxicity, pill burden, dosing frequency, drug-drug interaction potential, resistance test results, comorbid conditions, access, and cost.

Dolutegravir and lamivudine are available as a fixed-combination preparation (dolutegravir/lamivudine) and as separate single-entity products. Refer to the full prescribing information for the single-entity products for information on specific uses.

Dolutegravir and Lamivudine Dosage and Administration

General

Pretreatment Screening

Perform testing for hepatitis B virus (HBV) infection prior to initiation of dolutegravir/lamivudine.
Perform pregnancy testing in individuals of reproductive potential prior to initiation of dolutegravir/lamivudine.

Patient Monitoring

Monitor for hepatotoxicity during treatment with dolutegravir/lamivudine.
Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months after discontinuing treatment with dolutegravir/lamivudine in patients who are coinfected with HBV and HIV-1.
Monitor closely for lactic acidosis and severe hepatomegaly with steatosis in patients with known risk factors for liver disease.
Monitor for hematologic toxicities in patients with a sustained creatinine clearance between 30–49 mL/minute who receive dolutegravir/lamivudine.

Administration

Oral Administration

Administer orally once daily with or without food.

Dosage

Available as fixed-combination tablets containing dolutegravir sodium and lamivudine; dosages expressed in terms of dolutegravir and lamivudine, respectively.

Each fixed-combination tablet contains 50 mg of dolutegravir and 300 mg of lamivudine.

Adults

Treatment of HIV-1 Infection

Oral

1 tablet of dolutegravir/lamivudine (dolutegravir 50 mg and lamivudine 300 mg) once daily.

If coadministered with carbamazepine or rifampin, recommended dosage is 1 tablet (dolutegravir 50 mg and lamivudine 300 mg) once daily and a 50-mg tablet of single-entity dolutegravir once daily given 12 hours after the fixed-combination tablet.

Special Populations

Hepatic Impairment

Mild or moderate hepatic impairment (Child-Pugh class A or B): Dosage adjustments not needed.

Severe hepatic impairment (Child-Pugh class C): Use not recommended.

Renal Impairment

Cl_cr <30 mL/minute: Use not recommended.

Geriatric Patients

No specific dosage recommendations; use with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.

Cautions for Dolutegravir and Lamivudine

Contraindications

Prior hypersensitivity to dolutegravir or lamivudine.
Concomitant use with dofetilide because of potential for serious and/or life-threatening adverse effects resulting from increased dofetilide plasma concentrations.

Warnings/Precautions

Warnings

HIV and HBV Coinfection.

Test all patients with HIV for presence of HBV prior to or when initiating dolutegravir/lamivudine (see Boxed Warning).

Lamivudine-resistant strains of HBV have emerged in patients coinfected with HBV and HIV receiving lamivudine-containing antiretroviral regimens.

In patients with HIV and HBV coinfection, severe acute exacerbations of HBV infection, including liver decompensation and liver failure, reported following discontinuance of lamivudine. Such reactions could occur following discontinuance of dolutegravir/lamivudine.

Some experts state do not use a 2-drug antiretroviral regimen of dolutegravir and lamivudine in patients coinfected with HBV.

Manufacturer states that if a decision is made to use dolutegravir/lamivudine in patients coinfected with HIV-1 and HBV, consider appropriate treatment for chronic HBV infection; alternatively, consider a different antiretroviral regimen.

Closely monitor hepatic function using both clinical and laboratory follow-up for at least several months after dolutegravir/lamivudine is discontinued in patients coinfected with HIV-1 and HBV. If appropriate, initiation of HBV treatment may be warranted, especially in patients with advanced liver disease or cirrhosis.

Other Warnings and Precautions

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., rash, constitutional findings, and, sometimes, organ dysfunction including liver injury) reported in patients receiving dolutegravir.

Immediately discontinue dolutegravir/lamivudine if signs or symptoms of hypersensitivity reactions occur (including, but not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters or peeling of the skin, oral blisters or lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, difficulty breathing). Monitor clinical status, including aminotransferase concentrations, and initiate appropriate therapy. Delay in stopping dolutegravir/lamivudine treatment or other suspect agents after onset of a hypersensitivity reaction may result in a life-threatening reaction.

Hepatotoxicity

Adverse hepatic effects reported in patients receiving dolutegravir-containing regimens.

Patients with underlying HBV or HCV may be at increased risk for development or worsening of serum aminotransferase elevations. In some patients receiving a dolutegravir-containing regimen, serum aminotransferase elevations were consistent with immune reconstitution syndrome or HBV reactivation, particularly in the setting where HBV therapy had been discontinued.

Cases of hepatic toxicity, including elevated serum liver biochemistries, hepatitis, and acute liver failure, also reported in patients receiving dolutegravir-containing regimens who had no preexisting hepatic disease or other identifiable risk factors. Drug-induced liver injury leading to liver transplantation has been reported with the fixed combination of abacavir, dolutegravir, and lamivudine (abacavir/dolutegravir/lamivudine).

Monitor for hepatotoxicity during dolutegravir/lamivudine therapy.

Fetal/Neonatal Morbidity and Mortality

Data from an observational study in Botswana showed an association between dolutegravir and an increased risk of neural tube defects when the drug is administered at the time of conception and during early pregnancy.

Inform individuals of reproductive potential, including those actively trying to become pregnant, about potential increased risk of neural tube defects. Assess risks and benefits of dolutegravir/lamivudine and discuss with the patient to determine if an alternative should be considered at the time of conception through the first trimester of pregnancy or if pregnancy is confirmed in the first trimester.

Perform pregnancy testing in individuals of reproductive potential before initiation of dolutegravir/lamivudine; counsel on consistent use of effective contraception.

May consider dolutegravir during second and third trimesters of pregnancy if expected benefits justify potential risks to pregnant woman and fetus.

Lactic Acidosis and Severe Hepatomegaly with Steatosis

Lactic acidosis and severe hepatomegaly with steatosis (sometimes fatal) reported in patients receiving nucleoside analogs, including lamivudine. These cases reported most frequently in women; obesity also may be a risk factor.

Monitor closely if dolutegravir/lamivudine is used in patients with known risk factors for liver disease.

Discontinue dolutegravir/lamivudine in patients who develop 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).

Drug Interactions

Concomitant use of dolutegravir/lamivudine with certain other drugs may result in known or potentially clinically important drug interactions, some of which may lead to loss of therapeutic effect of dolutegravir/lamivudine and possible development of resistance or may increase plasma concentrations of the concomitant drugs.

Consider potential for drug interactions prior to and during treatment with dolutegravir/lamivudine; review concomitant drugs during dolutegravir/lamivudine therapy and monitor for adverse effects.

Immune Reconstitution Syndrome

Immune reconstitution syndrome reported in HIV-infected patients receiving multiple-drug antiretroviral therapy, including dolutegravir/lamivudine. During the initial phase of treatment, HIV-infected patients whose immune systems respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium infection, cytomegalovirus [CMV], Pneumocystis jirovecii, tuberculosis); such responses may necessitate further evaluation and treatment.

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

Use of Fixed Combinations

Consider cautions, precautions, contraindications, and interactions associated with both components of dolutegravir/lamivudine.

Consider cautionary information applicable to specific populations (e.g., pregnant or nursing women, individuals with hepatic or renal impairment, geriatric patients) for each drug in the fixed combination.

Specific Populations

Pregnancy

Antiretroviral Pregnancy Registry (APR) at 800-258-4263 or [Web].

Dolutegravir and lamivudine cross the placenta.

Data in pregnant women insufficient to definitively assess a drug-associated risk for birth defects and miscarriage with the fixed combination.

Reports from the pregnancy registry suggest higher prevalence of defects in live births following first-trimester and second-/third-trimester exposure to dolutegravir compared to background birth defect rate in US; no difference between overall risk of birth defects for lamivudine compared with background birth defect rate.

Results of an observational study in Botswana showed an increased risk of neural tube defects with dolutegravir-containing regimens at time of conception and during early pregnancy compared with use of antiretroviral regimens not containing dolutegravir.

Advise individuals of reproductive potential, including those actively trying to become pregnant, of the potential risk of neural tube defects.

Assess risks and benefits and discuss with the patient to determine if alternative treatment should be considered at the time of conception through the first trimester of pregnancy or if pregnancy is confirmed in the first trimester. Benefit-risk assessment should address factors such as feasibility of switching to a different regimen, tolerability, ability to maintain viral suppression, and risk of HIV-1 transmission to the infant versus risk of neural tube defects.

May consider use of dolutegravir/lamivudine during second and third trimesters of pregnancy if expected benefits justify potential risks to the pregnant woman and fetus.

HHS Panel reports that more recent data from Botswana indicate the prevalence of neural tube defects in infants born to pregnant women with HIV receiving dolutegravir at conception is no longer statistically different from that reported with other antiretrovirals. HHS states that a 2-drug regimen of dolutegravir/lamivudine is not recommended in antiretroviral-naive or antiretroviral-experienced pregnant women or women of childbearing potential trying to conceive because data not available regarding use of 2-drug regimens for treatment of HIV-1 infection during pregnancy.

Lactation

Dolutegravir and lamivudine: Distributed into human milk.

Dolutegravir/lamivudine: Not known whether the fixed combination or individual drug components affect human milk production or affect the breast-fed infant.

Instruct HIV-infected women not to breast-feed because of potential for HIV‑1 transmission in HIV-negative infants, development of viral resistance in HIV-positive infants, and adverse reactions in the breast-fed infant.

Females and Males of Reproductive Potential

Perform pregnancy testing in all individuals of reproductive potential before initiating dolutegravir/lamivudine.

In individuals of reproductive potential currently on dolutegravir/lamivudine who are actively trying to become pregnant or if pregnancy is confirmed in the first trimester, assess risks and benefits of continuing dolutegravir/lamivudine and discuss possible alternative treatments with the patient.

Advise individuals of reproductive potential to consistently use effective contraception during dolutegravir/lamivudine therapy.

Pediatric Use

Safety and efficacy not established in pediatric patients.

Geriatric Use

Experience in patients ≥65 years of age insufficient to determine whether they respond differently than younger adults.

Use with caution in geriatric patients because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.

Hepatic Impairment

Mild or moderate hepatic impairment (Child-Pugh class A or B): Dosage adjustments not needed.

Severe hepatic impairment (Child-Pugh class C): Dolutegravir/lamivudine not studied; not recommended in such patients.

Renal Impairment

Cl_cr <30 mL/minute: Dolutegravir/lamivudine not recommended because dosage of the components cannot be adjusted individually. Use single-entity dolutegravir and single-entity lamivudine in patients with Cl_cr <30 mL/minute if a reduction of lamivudine dosage required in such patients.

Patients with Cl_cr between 30–49 mL/minute receiving dolutegravir/lamivudine may experience a 1.6–3.3-fold higher lamivudine exposure than patients with a Cl_cr ≥50 mL/minute. Monitor for hematologic toxicities in patients with a sustained Cl_cr between 30–49 mL/minute who receive dolutegravir/lamivudine. If new or worsening neutropenia or anemia develop, adjust lamivudine dosage per the prescribing information for lamivudine. If lamivudine dose adjustment indicated, discontinue dolutegravir/lamivudine, and use single-entity dolutegravir and single-entity lamivudine to construct treatment regimen.

Common Adverse Effects

Common adverse effects (≥2%): headache, nausea, diarrhea, insomnia, fatigue, anxiety.

Drug Interactions

Dolutegravir: CYP isoenzyme 3A plays minor role in dolutegravir metabolism. Does not inhibit CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A; does not induce CYP1A2, 2B6, or 3A4.

Dolutegravir: Metabolized by UGT1A1; substrate for UGT1A3 and UGT1A9. Does not inhibit UGT1A1 or UGT2B7.

Dolutegravir: Substrate of P-glycoprotein (P-gp) transport system and breast cancer resistance protein (BCRP); does not inhibit P-gp or BCRP.

Dolutegravir: Inhibits multidrug and toxin extrusion transporter (MATE) 1, renal organic anion transporter (OAT) 1 and OAT3, and renal organic cation transporter (OCT) 2. Does not inhibit bile salt export pump (BSEP), hepatic organic anion transporter polypeptide (OATP) 1B1, OATP1B3, OCT1, or multidrug resistance protein (MRP) 2 or MRP4; not a substrate of OATP1B1 or 1B3.

Lamivudine: Not metabolized by CYP isoenzymes to any clinically important extent.

Lamivudine: Substrate of P-gp transport system and BCRP; does not inhibit P-gp or BCRP.

Lamivudine: Substrate of MATE1, MATE2-K, and OCT2. Does not inhibit MATE1, MATE2-K, OATP1B1/3, OCT1, OCT2, or OCT3.

The following drug interactions are based on studies using the individual components of dolutegravir/lamivudine or are predicted to occur with the fixed combination. When dolutegravir/lamivudine used, consider interactions associated with both drugs in the fixed combination.

Drugs Affecting Hepatic Microsomal Enzymes

CYP3A inducers: Possible decreased dolutegravir plasma concentrations; may lead to decreased therapeutic effects of dolutegravir.

CYP3A inhibitors: Possible increased dolutegravir plasma concentrations.

Drugs Affecting UGT

UGT1A1, 1A3, or 1A9 inducers: Possible decreased dolutegravir plasma concentrations and decreased therapeutic effects of dolutegravir.

UGT1A1 inhibitors: Possible increased dolutegravir concentrations.

Drugs Affecting or Affected by P-glycoprotein Transport

P-gp inducers: Possible decreased dolutegravir plasma concentrations and decreased therapeutic effects of dolutegravir. Unlikely to affect lamivudine concentrations.

P-gp inhibitors: Possible increased dolutegravir plasma concentrations. Unlikely to affect lamivudine concentrations.

Drugs Affecting or Affected by Breast Cancer Resistance Protein

BCRP inducers: Possible decreased dolutegravir plasma concentrations and decreased therapeutic effects of dolutegravir. Unlikely to affect lamivudine concentrations.

BCRP inhibitors: Possible increased dolutegravir plasma concentrations. Unlikely to affect lamivudine concentrations.

Drugs Affecting or Affected by Multidrug and Toxin Extrusion Transporter

MATE1 and MATE2-K inhibitors: Possible increased lamivudine concentrations.

Drugs eliminated by MATE1 and MATE2-K: Dolutegravir may increase plasma concentrations of MATE1 substrates.

Drugs Affected by Organic Cation Transporters

Drugs eliminated by OCT2: Dolutegravir may increase plasma concentrations of OCT2 substrates.

Specific Drugs

Drug	Interaction	Comments
Antacids, aluminum-, calcium-, or magnesium-containing	Decreased dolutegravir concentrations and AUC	Give dolutegravir/lamivudine ≥2 hours before or ≥6 hours after aluminum-, calcium-, or magnesium-containing antacids
Antiarrhythmic agents	Dofetilide: Possible increased dofetilide concentrations and increased risk of serious and/or life-threatening adverse effects	Dofetilide: Concomitant use with dolutegravir/lamivudine contraindicated
Anticonvulsants	Carbamazepine: Decreased dolutegravir concentrations and AUC Oxcarbazepine, phenobarbital, phenytoin: Possible decreased dolutegravir concentrations	Carbamazepine: If used with dolutegravir/lamivudine, give 50 mg of single-entity dolutegravir once daily 12 hours after the usual daily dose of dolutegravir/lamivudine Oxcarbazepine, phenobarbital, phenytoin: Avoid concomitant use with dolutegravir/lamivudine; data insufficient to make dosage recommendations
Antidiabetic agents	Metformin: Increased metformin concentrations and AUC if used with dolutegravir	Metformin: Consider risks and benefits if considering use with dolutegravir/lamivudine; some experts state use lowest initial metformin dose and titrate dosage based on glycemic control while monitoring metformin adverse effects; may need to adjust metformin dosage when starting or stopping dolutegravir-containing regimens
Antimycobacterial agents (rifabutin, rifampin, rifapentine)	Rifabutin: No clinically important effect on dolutegravir pharmacokinetics Rifampin: Decreased dolutegravir concentrations and AUC Rifapentine: Decreased dolutegravir concentrations expected	Rifabutin: Dosage adjustments not needed Rifampin: If used with dolutegravir/lamivudine, give 50 mg of single-entity dolutegravir once daily 12 hours after the usual daily dose of dolutegravir/lamivudine Rifapentine: Concomitant use not recommended
Bosentan	Possible decreased dolutegravir concentrations	Dosage adjustments not needed
Buffered preparations	Buffered preparations containing polyvalent cations: Possible decreased dolutegravir absorption and decreased dolutegravir concentrations	Buffered preparations containing polyvalent cations: Give dolutegravir/lamivudine ≥2 hours before or ≥6 hours after such preparations
Calcium supplements	Decreased dolutegravir concentrations when given concomitantly in fasted state	Give dolutegravir/lamivudine ≥2 hours before or ≥6 hours after oral calcium supplements; alternatively, may be given concomitantly if taken with food
Dalfampridine	Increased dalfampridine concentrations and increased risk of seizures	Weigh potential benefits of concomitant therapy against risk of seizures
Interferon alfa	No clinically important effects on lamivudine pharmacokinetics
Iron preparations	Possible decreased dolutegravir concentrations when given concomitantly in fasted state	Give dolutegravir/lamivudine ≥2 hours before or ≥6 hours after oral iron; alternatively, may be given concomitantly if taken with food
Laxatives containing polyvalent cations	Possible decreased dolutegravir absorption and decreased dolutegravir concentrations	Give dolutegravir/lamivudine ≥2 hours before or ≥6 hours after laxatives containing polyvalent cations
Magnesium preparations	Possible decreased dolutegravir absorption and decreased dolutegravir concentrations	Give dolutegravir/lamivudine ≥2 hours before or ≥6 hours after magnesium
Methadone	Dolutegravir: No clinically important effect on methadone pharmacokinetics	Dosage adjustments not needed
Multivitamins	Decreased dolutegravir concentrations when given concomitantly in fasted state	Give dolutegravir/lamivudine ≥2 hours before or ≥6 hours after multivitamins; alternatively, may be given concomitantly if taken with food
Sorbitol	Lamivudine: Decreased lamivudine AUC and plasma concentrations	Sorbitol-containing drugs: Avoid concomitant use with dolutegravir/lamivudine
St. John's wort (Hypericum perforatum)	Possible decreased dolutegravir concentrations	Avoid concomitant use with dolutegravir/lamivudine; data insufficient to make dosage recommendations
Sucralfate	Possible decreased dolutegravir concentrations	Give dolutegravir/lamivudine ≥2 hours before or ≥6 hours after sucralfate

Dolutegravir and Lamivudine Pharmacokinetics

Absorption

Bioavailability

Dolutegravir: Absolute bioavailability not established.

Lamivudine: Absolute bioavailability 86%.

Food

High-fat meal does not have clinically important effect on pharmacokinetics of dolutegravir or lamivudine after administration of fixed combination containing both drugs.

Plasma Concentrations

Dolutegravir: Peak concentrations attained 2.5 hours after an oral dose in fasted state.

Lamivudine: Peak concentrations attained 1 hour after an oral dose in fasted state.

Distribution

Extent

Dolutegravir: Crosses placenta. Distributed into human milk.

Lamivudine: Crosses placenta. Distributed into human milk.

Plasma Protein Binding

Dolutegravir: Approximately 99%.

Lamivudine: 36%.

Elimination

Metabolism

Dolutegravir: Primarily metabolized by UGT1A1; CYP3A plays only minor role.

Lamivudine: Not significantly metabolized and is not metabolized by CYP isoenzymes to any clinically important extent.

Elimination Route

Dolutegravir: 64% of a dose eliminated in feces (53% as unchanged drug); 31% eliminated in urine (<1% as unchanged drug).

Lamivudine: Principally eliminated in urine by active cationic secretion; approximately 71% of a dose eliminated in urine.

Half-life

Dolutegravir: Approximately 14 hours.

Lamivudine: 13-19 hours.

Special Populations

Dolutegravir, lamivudine: No clinically significant differences in pharmacokinetics of either drug observed based on age, sex, or race.

Lamivudine: Pharmacokinetics in pregnant women similar to those observed in non-pregnant and postpartum women.

Stability

Storage

Oral

Tablets

<30°C.

Actions and Spectrum

Dolutegravir/lamivudine is a fixed-combination antiretroviral containing dolutegravir and lamivudine.
Dolutegravir is an HIV INSTI. The drug binds to the active site of HIV integrase and blocks the strand transfer step of retroviral DNA integration, which is essential for HIV replication. Active against HIV-1; also has in vitro activity against HIV type 2 (HIV-2).
Lamivudine is an HIV NRTI. Prodrug that is inactive until converted intracellularly to an active 5′-triphosphate metabolite (lamivudine triphosphate). After conversion, acts as a reverse transcriptase inhibitor via DNA chain termination after incorporation of the nucleotide analogue. Active against HIV-1; also active against HBV.
HIV-1 resistant to dolutegravir produced in vitro and have emerged in HIV-infected patients receiving the drug; amino acid substitution G118R confers tenfold decrease in in vitro susceptibility to dolutegravir. HIV-1 resistant to lamivudine produced in vitro and have emerged in HIV-infected patients receiving lamivudine-containing regimens; HIV-1 resistance to lamivudine often involves amino acid substitutions M184V or M184I.
In a phase 3 clinical study evaluating 2-drug regimen of dolutegravir and lamivudine in antiretroviral-naive adults, treatment-emergent INSTI- or NRTI-resistance substitutions not reported in any patients at 48, 96, or 144 weeks. In preliminary studies evaluating 2-drug regimen of dolutegravir and lamivudine for switch therapy in previously treated HIV-1-infected adults, emergence of dolutegravir resistance-associated mutations not reported; presence of M184V lamivudine resistance-associated mutation was not a predictor of virologic failure. In a phase 3 clinical study evaluating 2-drug regimen of dolutegravir and lamivudine in virologically suppressed patients, no patients met protocol-defined confirmed virologic withdrawal criteria through week 144; no emergent INSTI- or NRTI-resistance detected in a patient who received dolutegravir/lamivudine with HIV-1 RNA ≥400 copies/mL at withdrawal.
Cross-resistance occurs among HIV INSTIs (e.g., dolutegravir, elvitegravir, raltegravir). Cross-resistance also occurs among HIV NRTIs (e.g., abacavir, emtricitabine, lamivudine, zidovudine).
No in vitro evidence of antagonistic anti-HIV effects between dolutegravir and lamivudine.

Advice to Patients

Inform patients about the critical nature of compliance with human immunodeficiency virus (HIV) therapy and importance of remaining under the care of a clinician. Inform patients to take the antiretroviral regimen as prescribed and to not alter or discontinue the antiretroviral regimen without consulting a clinician.
Advise patients to take dolutegravir/lamivudine once every day at a regularly scheduled time with or without food. Inform patients that dolutegravir/lamivudine is used alone as a complete regimen for the treatment of HIV-1 infection.
If a dose of dolutegravir/lamivudine is missed, instruct patients to take the dose as soon as it is remembered. Advise patients not to double their next dose and not to take more than the prescribed dose.
Inform patients that testing for hepatitis B virus (HBV) infection is recommended before antiretroviral therapy is initiated. Advise patients that emergence of HBV resistant to lamivudine has been reported in HIV-infected patients coinfected with HBV who have received lamivudine-containing antiretroviral regimens. Also advise patients that severe acute exacerbations of HBV infection have been reported following discontinuance of lamivudine in HIV-infected patients coinfected with HBV and may occur with dolutegravir/lamivudine. Inform patients with HIV and HBV coinfection that it is important to discuss with their clinician whether additional treatment for chronic HBV is warranted.
Advise patients to immediately discontinue dolutegravir/lamivudine and seek medical attention if rash occurs and is associated with fever, generally ill feeling, extreme tiredness, muscle or joint aches, breathing difficulty, blisters or peeling skin, oral blisters or lesions, eye inflammation, swelling of the face, eyes, lips, or mouth, and/or signs and symptoms of liver problems (e.g., yellowing of skin or whites of the eyes, dark or tea-colored urine, pale stools/bowel movements, nausea, vomiting, loss of appetite, or pain, aching, or sensitivity on right side below ribs). Advise patients that close monitoring and appropriate laboratory testing and treatment may be required if a hypersensitivity reaction occurs.
Inform patients that hepatotoxicity has been reported in patients receiving the components of dolutegravir/lamivudine and that monitoring for hepatotoxicity is recommended.
Inform patients that some HIV drugs, including dolutegravir/lamivudine, can cause a rare, but serious condition called lactic acidosis with liver enlargement (hepatomegaly).
Advise patients that signs and symptoms of inflammation from other previous infections may occur soon after initiation of antiretroviral therapy in some HIV-infected individuals. Advise patients to immediately inform their clinician if any signs or symptoms of infection occur.
Advise women to inform their clinician if they plan to become pregnant, or if pregnancy is confirmed in the first trimester, during treatment with dolutegravir/lamivudine. Advise individuals of reproductive potential, including those actively trying to become pregnant, to discuss the risks and benefits of dolutegravir with their clinician to determine if an alternative treatment should be considered at the time of conception through the first trimester. Advise individuals of reproductive potential taking dolutegravir/lamivudine to consistently use effective contraception during treatment.
Advise women to inform their clinician if they plan to breast-feed. Advise HIV-infected women not to breast-feed.
Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements (e.g., St. John’s wort), as well as any concomitant illnesses.
Advise patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.