Dolutegravir Sodium And Lamivudine (Monograph)

Drug class: HIV Integrase Inhibitors

Medically reviewed by Drugs.com on Feb 10, 2025. Written by ASHP.

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 Sodium And Lamivudine

Treatment of HIV Infection

Used as a complete regimen for the treatment of HIV-1 infection in antiretroviral-naïve (have not previously received antiretroviral therapy) adults and adolescents ≥12 years of age and weighing ≥25 kg 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 Sodium And Lamivudine Dosage and Administration

General

Pretreatment Screening

• Perform testing for hepatitis B virus (HBV) infection 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.

Dispensing and Administration Precautions

• The Institute for Safe Medication Practices (ISMP) list of error-prone abbreviations, symbols, and dose designations states that the use of abbreviations for antiretroviral medications (e.g., DOR, TAF, TDF) during the medication use process should be avoided as their use has been associated with serious medication errors.

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.

Pediatric Patients

Treatment of HIV-1 Infection

Oral

Adolescents ≥12 years of age weighing ≥25 kg: 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.

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 Sodium 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.

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; however, registry data involving the individual components of the fixed combination do not indicate an increased risk of birth defects.

Data from two, ongoing birth outcome surveillance studies in Botswana and Eswatini, which together include over 14,000 individuals evaluated during pregnancy, reveal a comparable prevalence of neural tube defects among infants born to individuals taking dolutegravir at the time of conception compared to those born to individuals taking non-dolutegravir-containing regimens at conception or infants born to HIV-negative individuals.

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.

The HHS perinatal HIV transmission guideline provides updated recommendations on infant feeding. The guideline states that patients with HIV should receive evidence-based, patient-centered counseling to support shared decision making about infant feeding. During counseling, patients should be informed that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates the risk of postnatal HIV transmission to the infant. Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces the risk of breastfeeding HIV transmission to <1%, but does not completely eliminate the risk. Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery.

Pediatric Use

The efficacy and safety of dolutegravir/lamivudine for the treatment of HIV-1 infection have been established in adolescents ≥12 years of age and weighing ≥25 kg. Use is supported by results from a clinical trial in treatment-naïve adolescents and evidence from adequate and well-controlled trials in adults.

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

Dolutegravir Sodium 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-naïve 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 patients to inform their clinician if they are or plan to become pregnant, or they plan 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.

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