Dolutegravir (Monograph)

Drug class: HIV Integrase Inhibitors

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

Introduction

Antiretroviral; HIV integrase strand transfer inhibitor (INSTI).

Uses for Dolutegravir

Treatment of HIV Infection

Treatment of HIV type 1 (HIV-1) infection in adults who are antiretroviral-naive (have not previously received antiretroviral therapy) or antiretroviral-experienced (previously treated) and in pediatric patients ≥4 weeks of age weighing ≥3 kg who are antiretroviral-naive or antiretroviral-experienced but INSTI-naive. Used in conjunction with other antiretrovirals.

Commercially available as a single entity and in various fixed-combination preparations that contain additional antiretrovirals; refer to separate combination product monographs for information related to the specific uses of these products.

Single-entity dolutegravir is used in conjunction with rilpivirine as a complete regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen for ≥6 months with no history of treatment failure and no known substitutions associated with resistance to either agent; for more information on dolutegravir/rilpivirine as a complete regimen, refer to the monograph for the fixed-combination dolutegravir/rilpivirine preparation.

Dolutegravir is commonly used as part of a fully suppressive antiretroviral regimen in conjunction with 1 or 2 nucleotide/nucleoside reverse transcriptase inhibitors (NRTIs); consult guidelines for the most current information on recommended regimens. 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.

Postexposure Prophylaxis following Nonoccupational Exposure to HIV (nPEP)

Postexposure prophylaxis of HIV infection following nonoccupational exposure^{† [off-label]}(nPEP) in individuals exposed to blood, genital secretions, or other potentially infectious body fluids that might contain HIV when the exposure represents a substantial risk for HIV transmission. Used in conjunction with other antiretrovirals.

When nPEP is indicated following a nonoccupational exposure to HIV, the US Centers for Disease Control and Prevention (CDC) states that the preferred regimen in adults and adolescents 13 years of age or older with normal renal function is either raltegravir or dolutegravir used in conjunction with emtricitabine and tenofovir DF (administered as the fixed combination emtricitabine/tenofovir DF; e.g., Truvada). The alternative nPEP regimen recommended in these patients is ritonavir-boosted darunavir used in conjunction with emtricitabine/tenofovir DF (e.g., Truvada).

Consult infectious disease specialist, clinician with expertise in administration of antiretroviral agents, and/or the National Clinicians’ Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) if nPEP indicated in certain exposed individuals (e.g., pregnant women, children, those with medical conditions such as renal impairment) or if considering a regimen not included in CDC guidelines, source virus is known or likely to be resistant to antiretrovirals, or healthcare provider is inexperienced in prescribing antiretrovirals. Do not delay initiation of nPEP while waiting for expert consultation.

Dolutegravir Dosage and Administration

General

Pretreatment Screening

• Pregnancy testing is recommended in adolescents and adults of reproductive potential prior to treatment with dolutegravir.

• Perform testing for hepatitis B virus (HBV) infection and hepatitis C virus (HCV) infection in all patients with human immunodeficiency virus (HIV) infection prior to initiation of antiretroviral therapy.

Patient Monitoring

• Monitor for signs and symptoms of hepatotoxicity during treatment with dolutegravir.

Dispensing and Administration Precautions

• Dolutegravir is commercially available as a single entity and in various fixed-combination preparations that contain additional antiretrovirals. Refer to the full prescribing information for information on specific uses, cautions, precautions, contraindications, and drug interactions of the combination products.

• Dolutegravir tablets and dolutegravir tablets for oral suspension are notbioequivalent and are not interchangeable on a mg-per-mg basis.

Administration

Oral Administration

Commercially available as conventional tablets (Tivicay) and as tablets for oral suspension (Tivicay PD). Administer orally once or twice daily without regard to food. Must be used in conjunction with other antiretrovirals.

May swallow tablets for oral suspension whole (1 tablet at time if more than a single tablet is required for the dose, to reduce risk of choking) or disperse in drinking water to provide an oral suspension. Do not chew, cut, or crush.

To prepare an oral suspension, add indicated number of 5-mg tablets for oral suspension to the appropriate volume of clean drinking water in the plastic cup provided by manufacturer. To prepare a 5- or 15-mg dose of dolutegravir, place 5 mL of drinking water into the cup and add 1 or 3 tablets for oral suspension, respectively, to the water. To prepare a 20-, 25-, or 30-mg dose, place 10 mL of drinking water into the cup and add 4, 5, or 6 tablets for oral suspension, respectively, to the water. Gently swirl cup for 1–2 minutes until no lumps remain. After full dispersion, administer the oral suspension within 30 minutes of mixing. For infants who cannot drink from the plastic cup, administer oral suspension using the oral syringe provided by manufacturer. To ensure the child receives the full dose, place additional 5 mL of drinking water into the cup, swirl the cup, and administer to the child directly from the cup or using the oral syringe. For more specific instructions on preparation and administration of dolutegravir oral suspension, consult the manufacturer's instructions for use and labeling.

Fixed Combinations Containing Dolutegravir

Dolutegravir is also commercially available in the following fixed-combination tablets: abacavir, dolutegravir, and lamivudine (Triumeq); dolutegravir and lamivudine (Dovato); and dolutegravir and rilpivirine (Juluca). See the full prescribing information for administration of each of these combination products.

Dosage

Available as dolutegravir sodium; dosage expressed in terms of dolutegravir.

Dolutegravir tablets and dolutegravir tablets for oral suspension are not bioequivalent and are not interchangeable on a mg-per-mg basis. If patient is switched from one tablet formulation to the other, must adjust dosage to that recommended for specific formulation now being used.

Pediatric Patients

Dosage is based on weight. The tablets for oral suspension are labeled for pediatric patients ≥4 weeks of age weighing ≥3 kg; conventional tablets are labeled for use in pediatric patients ≥4 weeks of age weighing ≥14 kg.

Treatment of HIV-1 Infection

Antiretroviral-naive, or Antiretroviral-experienced but Integrase Strand Transfer Inhibitor (INSTI)-naive Pediatric Patients

Oral

Do not use conventional tablets in pediatric patients weighing 3–14 kg. See Table 1 for dosage of dolutegravir tablets for oral suspension in pediatric patients ≥4 weeks of age weighing ≥3 kg. Dolutegravir tablets for oral suspension are preferred for pediatric patients weighing <20 kg.

If dolutegravir is used concomitantly with certain UGT1A or CYP3A inducers (i.e., efavirenz, ritonavir-boosted fosamprenavir, ritonavir-boosted tipranavir, carbamazepine, rifampin), give the recommended weight-based dose twice daily.

See Table 2 for the recommended dosage of dolutegravir conventional tablets for the treatment of HIV-1 infection in pediatric patients 4 weeks of age or older weighing ≥14 kg.

If dolutegravir is used concomitantly with certain UGT1A or CYP3A inducers (i.e., efavirenz, ritonavir-boosted fosamprenavir, ritonavir-boosted tipranavir, carbamazepine, rifampin), give the recommended weight-based dose twice daily.

The fixed-dose combination containing abacavir, dolutegravir, and lamivudine (Triumeq) is used in the treatment of HIV-1 infection in pediatric patients; consult the full prescribing information for specific dosage of this combination product.

Adults

Treatment of HIV-1 Infection

Antiretroviral-naive, or Antiretroviral-experienced but INSTI-naive Adults

Oral

50 mg once daily.

In adults receiving certain UGT1A or CYP3A inducers (i.e., efavirenz, ritonavir-boosted fosamprenavir, ritonavir-boosted tipranavir, carbamazepine, rifampin): 50 mg twice daily. Whenever possible, consider alternative regimens that do not contain these inducers.

Virologically Suppressed Adults Switching to Dolutegravir Plus Rilpivirine

Oral

Virologically suppressed (HIV-1 RNA <50 copies/mL) adults switching to dolutegravir plus rilpivirine: 50 mg once daily. Rilpivirine dosage: 25 mg once daily for those switching to dolutegravir plus rilpivirine.

INSTI-experienced Adults

Oral

INSTI-experienced adults with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance: 50 mg twice daily.

Fixed-dose Combinations

Fixed-dose combinations containing abacavir, dolutegravir, and lamivudine (Triumeq); dolutegravir and lamivudine (Dovato); and dolutegravir and rilpivirine (Juluca) are used in the treatment of HIV-1 infection in adults. The usual dosage of dolutegravir is 50 mg in conjunction with other antiretrovirals for treatment of HIV-1 infection; consult the full prescribing information for specific dosage of each of the combination products.

Postexposure Prophylaxis following Nonoccupational Exposure to HIV † [off-label] (nPEP)

Oral

Dolutegravir 50 mg once daily. Use in conjunction with 2 NRTIs. Initiate nPEP as soon as possible (within 72 hours) following nonoccupational exposure that represents a substantial risk for HIV transmission and continue the regimen for 28 days.

nPEP not recommended if exposed individual seeks care >72 hours after exposure.

Special Populations

Hepatic Impairment

Dosage adjustments not needed in patients with mild or moderate hepatic impairment (Child-Pugh class A or B); do not use in those with severe hepatic impairment (Child-Pugh class C).

Renal Impairment

Dosage adjustments not needed in antiretroviral-naive, or antiretroviral-experienced but INSTI-naive patients, with mild, moderate, or severe renal impairment.

Dosage adjustments not needed in INSTI-experienced patients (with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance) with mild or moderate renal impairment. Use with caution in patients with severe renal impairment who are INSTI-experienced and have certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance.

Data insufficient to make specific dosage recommendations for patients requiring dialysis; unlikely that the drug would be removed by dialysis to any clinically important extent.

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

Contraindications

• Previous hypersensitivity reaction to dolutegravir.

• Concomitant use with dofetilide.

Warnings/Precautions

Hypersensitivity Reactions

Hypersensitivity reactions reported. Reactions include rash and constitutional findings and, occasionally, organ dysfunction including liver toxicity.

Immediately discontinue dolutegravir or any other suspect agents if signs or symptoms of hypersensitivity occur, including (but not limited to) severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters or peeling skin, oral blisters or lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, or difficulty breathing. Monitor clinical status, including liver aminotransferases, and initiate appropriate therapy.

Life-threatening reactions could occur if discontinuance of dolutegravir or any other suspect agents is delayed after onset of hypersensitivity reaction.

Hepatotoxicity

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

HIV-infected patients with HBV or HCV coinfection may be at increased risk for development or worsening of 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 a dolutegravir-containing regimen who had no preexisting hepatic disease or other identifiable risk factors. Drug-induced liver injury leading to liver transplant reported with abacavir/dolutegravir/lamivudine. Monitor for hepatotoxicity in patients receiving dolutegravir.

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.

However, Health and Human Services (HHS) Panel on Treatment of Pregnant Women with HIV Infection and Prevention of Perinatal Transmission reports that more recent data from Botswana indicate that the prevalence of neural tube defects in infants born to pregnant women with HIV receiving dolutegravir at conception is no longer statistically different than in those receiving other antiretrovirals (see Pregnancy under Specific Populations).

Assess risks and benefits of dolutegravir use, and discuss with patient to determine if an alternative to dolutegravir should be considered at the time of conception through the first trimester of pregnancy or if pregnancy is confirmed in the first trimester.

Pregnancy testing is recommended in adolescents and adults of reproductive potential before initiation of dolutegravir; counsel on the consistent use of effective contraception.

Immune Reconstitution Syndrome

During initial treatment, HIV-infected patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium, M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jirovecii); this may necessitate further evaluation and treatment.

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

Different Formulations Are Not Interchangeable

Dolutegravir conventional tablets and tablets for oral suspension are not bioequivalent and not interchangeable on a mg-per-mg basis. If pediatric patient is switched from one tablet formulation to the other, must adjust dosage to that recommended for the specific formulation now being used. Incorrect dosage of a given formulation may result in under-dosing and loss of therapeutic effect and possible development of resistance or may result in clinically important adverse effects from greater dolutegravir exposure.

Specific Populations

Pregnancy

Antiretroviral Pregnancy Registry (APR) monitors pregnancy outcomes in women exposed to dolutegravir during pregnancy. Clinicians encouraged to register patients in the APR by calling 800-258-4263 or visiting [Web].

Dolutegravir crosses placenta. Data regarding use of dolutegravir in pregnant women are insufficient to date to definitively assess a drug-associated risk for birth defects and miscarriage. Background risk for major birth defects for the indicated population unknown. No evidence of adverse effects on embryofetal or pre- and post-natal development reported in animal reproduction studies.

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. Health and Human Services (HHS) Panel on Treatment of Pregnant Women with HIV Infection and Prevention of Perinatal Transmission reports that more recent data from Botswana indicate that the prevalence of neural tube defects in infants born to pregnant women with HIV receiving dolutegravir at conception is no longer statistically different than in those receiving other antiretrovirals. Per the HHS, dolutegravir is a preferred antiretroviral for use in 3-drug antiretroviral regimens for treatment of HIV-1 infection in antiretroviral-naive and previously treated pregnant women (regardless of trimester) and is an alternative antiretroviral for such regimens in women of childbearing potential trying to conceive. The HHS also recommends the continuation of dolutegravir therapy in individuals who become pregnant on a fully suppressive, well-tolerated regimen.

Clinicians can consult the National Perinatal HIV Hotline at 888-448-8765 for additional guidance on use of dolutegravir and other antiretrovirals in women who are pregnant or planning to become pregnant.

Lactation

Dolutegravir distributed into human milk. Not known whether dolutegravir affects milk production or affects 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 a breast-fed infant.

Females and Males of Reproductive Potential

Pregnancy testing is recommended in all women and adolescents of reproductive potential before initiating dolutegravir.

In adolescents and adults of reproductive potential currently on dolutegravir who are actively trying to become pregnant or if pregnancy is confirmed in the first trimester, assess risks and benefits of continuing dolutegravir and discuss with the patient if an alternative treatment should be considered. Advise all women and adolescents of reproductive potential to consistently use effective contraception during dolutegravir therapy.

Pediatric Use

Safety and efficacy not established in pediatric patients <4 weeks of age or weighing <3 kg; safety and efficacy not established in INSTI-experienced pediatric patients who have documented or suspected resistance to other HIV INSTIs (e.g., elvitegravir, raltegravir).

Data from a clinical trial in pediatric patients 4 weeks to <18 years of age (IMPAACT P1093) indicate effectiveness and overall safety of dolutegravir in pediatric patients are comparable to those reported in adults receiving the drug. Pharmacokinetic parameters for dolutegravir reported in pediatric patients receiving weight-based dosages of the drug in clinical trials (IMPAACT P1093, ODYSSEY) indicate that peak plasma concentrations and AUC are comparable to those in adults receiving 50 mg of dolutegravir once or twice daily. Although mean peak plasma concentrations of the drug are higher in pediatric patients, this is not considered clinically important since the safety profile is similar in adult and pediatric patients.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether they respond differently to dolutegravir than younger adults.

Caution advised because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Hepatic Impairment

Should not be used in patients with severe hepatic impairment (Child-Pugh class C); pharmacokinetics not evaluated in such patients. Pharmacokinetics in patients with moderate hepatic impairment similar to those in healthy individuals; dosage adjustments not needed in those with mild or moderate hepatic insufficiency (Child-Pugh class A or B). Risk for further elevations in hepatic enzyme concentrations in patients with HBV or HCV coinfection.

Renal Impairment

Use with caution in patients with severe renal impairment who are INSTI-experienced and have documented or suspected INSTI resistance; dolutegravir plasma concentrations decreased in such patients and may result in loss of therapeutic effects and development of resistance to the drug or other antiretrovirals.

May be used in patients with mild or moderate renal impairment; no clinically important effect on dolutegravir pharmacokinetics. Dosage adjustments not needed in antiretroviral-naive or antiretroviral-experienced, INSTI-naive patients with mild, moderate, or severe renal impairment. Dosage adjustments not needed in INSTI-experienced patients with mild or moderate renal impairment.

Data regarding use of dolutegravir in dialysis patients insufficient to make dosage recommendations; unlikely that dialysis would have clinically important effect on pharmacokinetics since the drug is highly bound to plasma protein.

Dolutegravir increases S_cr by inhibiting tubular secretion of creatinine; does not cause clinically important change in GFR or renal plasma flow.

Common Adverse Effects

In patients receiving dolutegravir in an adult clinical trial, the most common adverse effects of moderate to severe intensity and incidence ≥2% were insomnia, headache, and fatigue.

Drug Interactions

The following drug interactions are based on studies using dolutegravir; refer to the full prescribing information for further details. Additional drug interactions exist for fixed-combinations containing abacavir, dolutegravir, and lamivudine (Triumeq); dolutegravir and lamivudine (Dovato); and dolutegravir and rilpivirine (Juluca). When a fixed combination is used, consider the interactions associated with each drug in the fixed combination; see the full prescribing information for drug interactions of each combination product.

CYP3A plays minor role in dolutegravir metabolism. Dolutegravir does not inhibit CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A; does not induce CYP1A2, 2B6, or 3A4.

Metabolized by UGT1A1; also a substrate for UGT1A3 and UGT1A9. Does not inhibit UGT1A1 or UGT2B7.

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

Inhibits multidrug and toxin extrusion transporter (MATE) 1.

Inhibits renal organic anion transporter (OAT) 1 and OAT3. Does not inhibit organic anion transporter polypeptide (OATP) 1B1 or OATP1B3; not a substrate of OATP1B1 or 1B3.

Does not inhibit bile salt export pump (BSEP) or multidrug resistance protein (MRP) 2 or MRP4.

Drugs Affecting Hepatic Microsomal Enzymes

CYP3A inducers: Possible decreased dolutegravir plasma concentrations and decreased therapeutic effects.

CYP3A inhibitors: Possible increased dolutegravir plasma concentrations.

Drugs Affecting UGT

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

UGT1A1 inhibitors: Possible increased dolutegravir plasma concentrations.

Drugs Affecting P-glycoprotein Transport

P-gp inducers: Possible decreased dolutegravir plasma concentrations.

P-gp inhibitors: Possible increased dolutegravir plasma concentrations.

Drugs Affecting Breast Cancer Resistance Protein

BCRP inducers: Possible decreased dolutegravir plasma concentrations.

BCRP inhibitors: Possible increased dolutegravir plasma concentrations.

Drugs Affected by Multidrug and Toxin Extrusion Transporter

Drugs eliminated by MATE1: Possible increased plasma concentrations of these drugs.

Drugs Affected by Renal Organic Cation Transporters

Drugs eliminated by OCT2: Possible increased plasma concentrations of these drugs.

Specific Drugs

Dolutegravir Pharmacokinetics

Absorption

Bioavailability

Dolutegravir conventional tablets: Following 50 mg orally once or twice daily, peak plasma concentrations occur 1–3 hours after a dose. Steady state achieved within approximately 5 days with once-daily dosing.

Dolutegravir conventional tablets and dolutegravir tablets for oral suspension are not bioequivalent; relative bioavailability of the tablets for oral suspension is approximately 1.6-fold higher than that of the conventional tablets.

Food

Dolutegravir: May be taken with or without food. Food increased the extent and slowed the rate of absorption of dolutegravir following a 50 mg dose.

Distribution

Extent

Dolutegravir distributed into CSF; clinical importance unknown.

Crosses placenta.

Distributed into human milk.

Plasma Protein Binding

Approximately 99%.

Elimination

Metabolism

Dolutegravir primarily metabolized by UGT1A1; CYP3A plays only minor role. Data from healthy individuals indicate that UGT1A1 genotypes conferring poor dolutegravir metabolism result in 32% lower clearance and 46% higher AUC of the drug compared with genotypes associated with normal UGT1A1 metabolism.

Elimination Route

Dolutegravir excreted in feces (53% as unchanged drug) and urine (31% of a dose; <1% as unchanged drug).

Half-life

Approximately 14 hours.

Special Populations

Moderate hepatic impairment (Child-Pugh class B): No clinically important effect on dolutegravir pharmacokinetics.

Severe hepatic impairment (Child-Pugh class C): Dolutegravir pharmacokinetics not evaluated.

HCV coinfection: No clinically important effect on dolutegravir pharmacokinetics.

Mild to moderate renal impairment: No clinically important effect on dolutegravir pharmacokinetics.

Severe renal impairment (Cl_cr <30 mL/minute): Dolutegravir AUC, peak plasma concentrations, and plasma concentrations measured 24 hours after dosing are 40, 23, and 43% lower, respectively, compared with healthy individuals.

HIV-1-infected pediatric patients 4 weeks to <18 years of age: Peak plasma concentrations and AUC reported with weight-based dosages of the tablets for oral suspension or conventional tablets are comparable to those in adults receiving dolutegravir 50 mg once or twice daily.

Polymorphism in UGT1A1: Genotypes of UGT1A1 conferring poor dolutegravir metabolism result in 32% lower clearance and 46% higher AUC compared with genotypes associated with normal UGT1A1 metabolism.

Stability

Storage

Oral

Tablets

Dolutegravir conventional tablets: 25°C (excursions permitted to 15–30°C).

Dolutegravir tablets for oral suspension: <30°C. Store and dispense in original bottle; do not remove desiccant; protect from moisture.

Actions

• Dolutegravir is an HIV integrase strand transfer inhibitor (INSTI). Binds to 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). Not active against HCV.

• Has been active against HIV-1 resistant to HIV nucleoside reverse transcriptase inhibitors (NRTIs), HIV nonnucleoside reverse transcriptase inhibitors (NNRTIs), or HIV protease inhibitors (PIs).

• HIV-1 resistant to dolutegravir have been produced in vitro and have emerged during dolutegravir therapy.

• Appears to have a different resistance profile than other HIV INSTIs and has been active in vitro against some HIV-1 resistant to other INSTIs (e.g., elvitegravir, raltegravir). However, cross-resistance between dolutegravir and other INSTIs (e.g., elvitegravir, raltegravir) reported.

Advice to Patients

• Inform patients of the critical nature of compliance with human immunodeficiency virus (HIV) therapy and importance of remaining under the care of a clinician. Advise patients that it is important to take the antiretroviral regimen as prescribed, and not to alter or discontinue the antiretroviral regimen without consulting clinician.

• Inform patients of the importance of using single-entity dolutegravir (Tivicay, Tivicay PD) in conjunction with other antiretrovirals—not for monotherapy.

• Inform patients and/or caregivers that dolutegravir tablets and dolutegravir tablets for oral suspension are not bioequivalent and are not interchangeable on a mg-per-mg basis and that dosage must be adjusted if a switch is made from one formulation to the other. To avoid dosage errors from using the wrong formulation of dolutegravir, strongly advise patients and/or caregivers to visually inspect the tablets to verify that they were given the correct formulation each time the prescription is filled.

• If the tablets for oral suspension are used, inform patients and/or caregivers that the tablets may be swallowed whole or dispersed in drinking water and should not be chewed, cut, or crushed. Inform patients that the amount of water needed to disperse the tablets depends on the dose (i.e., required number of tablets). Instruct patients to refer to the instructions for use regarding preparation and administration of the tablets for oral suspension.

• Advise patients and/or caregivers that if a dose of dolutegravir is missed, it should be taken as soon as it is remembered and the next dose taken at the regularly scheduled time. Advise patients that a double dose should not be taken to make up for a missed dose.

• Advise patients to immediately discontinue dolutegravir and other suspect agents 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 hepatotoxicity has been reported in patients receiving dolutegravir and that monitoring for hepatotoxicity is recommended.

• Advise patients that signs and symptoms of inflammation from previous infections may occur soon after initiation of antiretroviral therapy in some 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. Advise patients that there is a pregnancy registry to monitor fetal outcomes in those exposed to dolutegravir during pregnancy. Advise adolescents and women 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 adolescents and women of reproductive potential taking dolutegravir to consistently use effective contraception during treatment with the drug.

• 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.

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Frequently asked questions

• What drugs are contained in HIV treatment Juluca?

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