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Dolutegravir: Drug information

Dolutegravir: Drug information
(For additional information see "Dolutegravir: Patient drug information" and see "Dolutegravir: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Tivicay;
  • Tivicay PD
Brand Names: Canada
  • Tivicay
Pharmacologic Category
  • Antiretroviral, Integrase Inhibitor (Anti-HIV)
Dosing: Adult
HIV-1 infection, treatment

HIV-1 infection, treatment: Note: Must be given in combination with other antiretroviral agents.

Treatment naive or treatment-experienced integrase strand transfer inhibitor (INSTI)-naive: Oral: 50 mg once daily.

Treatment naive or treatment-experienced INSTI-naive when coadministered with carbamazepine, efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, or rifampin: Oral: 50 mg twice daily.

INSTI-experienced with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance (Note: Consult prescribing information for details): Oral: 50 mg twice daily.

Virologically suppressed (HIV-1 RNA <50 copies/mL) patients switching to dolutegravir plus rilpivirine: Oral: 50 mg once daily.

HIV-1 nonoccupational postexposure prophylaxis

HIV-1 nonoccupational postexposure prophylaxis (nPEP) (off-label use): Oral: 50 mg once daily for 28 days (in combination with other antiretroviral agents). Initiate therapy within 72 hours of exposure (HHS [nPEP] 2016).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Note: Patients with CrCl <30 mL/minute exhibited reduced dolutegravir exposures (~40%) in a single-dose pharmacokinetic study (Weller 2014); the mechanism for this is unknown and no dosage adjustments have been proposed (HHS [adult] 2022); however, use with caution in integrase strand transfer inhibitor (INSTI)–experienced patients (with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance) (Weller 2014).

Altered kidney function: Oral: No dosage adjustment necessary for any degree of kidney dysfunction (Weller 2014).

Hemodialysis, intermittent (thrice weekly): Minimally dialyzable (~7%) (Moltó 2016):

Oral: No supplemental dose or dosage adjustment necessary (Kreft 2019; Moltó 2016).

Peritoneal dialysis: Not expected to be significantly dialyzable (expert opinion):

Oral: No dosage adjustment necessary (expert opinion).

CRRT: Oral: No dosage adjustment necessary (expert opinion).

PIRRT (eg, sustained, low-efficiency diafiltration): Oral: No dosage adjustment necessary (expert opinion).

Dosing: Hepatic Impairment: Adult

Mild-to-moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.

Severe impairment (Child-Pugh class C): Use is not recommended (has not been studied).

Dosing: Pediatric

(For additional information see "Dolutegravir: Pediatric drug information")

Note: Dolutegravir tablets (Tivicay) and soluble tablets for oral suspension (Tivicay PD) are not bioequivalent and are not substitutable on a mg per mg basis.

HIV-1 infection, treatment

HIV-1 infection, treatment: Note: Use in combination with other antiretroviral (ARV) agents. Gene mutation and ARV resistance patterns should be evaluated (refer to https://www.iasusa.org for more information) when necessary.

Treatment-naive or treatment-experienced and integrase strand transfer inhibitor (INSTI)-naive:

Infants and Children weighing 3 to <14 kg: Oral:

Soluble tablets for oral suspension (Tivicay PD):

3 to <6 kg: 5 mg once daily.

6 to <10 kg: 15 mg once daily.

10 to <14 kg: 20 mg once daily.

Infants, Children, and Adolescents weighing ≥14 kg: Oral:

Soluble tablets for oral suspension (Tivicay PD): Preferred in patients <20 kg:

14 to <20 kg: 25 mg once daily.

≥20 kg: 30 mg once daily.

Tablets (Tivicay):

14 to <20 kg: 40 mg once daily.

≥20 kg: 50 mg once daily.

INSTI-experienced with any INSTI-associated resistance mutation or clinically suspected INSTI resistance: Limited data available (HHS [pediatric 2020]):

Children and Adolescents weighing ≥40 kg: Oral: Tablets (Tivicay): 50 mg twice daily.

HIV-1 nonoccupational postexposure prophylaxis

HIV-1 nonoccupational postexposure prophylaxis (nPEP): Limited data available (HHS [nPEP] 2016): Adolescents weighing ≥40 kg: Oral: Tablets (Tivicay): 50 mg once daily for 28 days in combination with other antiretroviral agents. Initiate therapy within 72 hours of exposure.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Treatment-naive or treatment-experienced integrase strand transfer inhibitor (INSTI)-naive: Infants, Children, and Adolescents: Mild, moderate, or severe impairment: No dosage adjustment required.

INSTI-experienced with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance: There are no dosage adjustments in the manufacturer's labeling; based on experience in adult patients, use with caution in severe renal impairment since the reduction in dolutegravir concentrations may result in loss of therapeutic effect and development of resistance to dolutegravir or other coadministered antiretroviral agents.

End-stage renal disease including hemodialysis: There are no dosage adjustments in the manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment: Pediatric

Infants, Children, and Adolescents:

Baseline:

Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.

Severe impairment (Child-Pugh class C): Not recommended (has not been studied).

Hepatoxicity during therapy: If asymptomatic hepatitis, consider discontinuation of therapy for ALT or AST >5 times ULN; if symptomatic hepatitis, discontinue therapy (HHS [pediatric 2020]).

Dosing: Older Adult

Refer to adult dosing; use with caution.

Dosage Forms: US

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

Tablet, Oral:

Tivicay: 10 mg, 25 mg, 50 mg

Tablet Soluble, Oral:

Tivicay PD: 5 mg

Generic Equivalent Available: US

No

Dosage Forms: Canada

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

Tablet, Oral:

Tivicay: 10 mg, 25 mg, 50 mg

Tablet Soluble, Oral:

Tivicay: 5 mg

Administration: Adult

Oral: Administer without regard to meals. Administer 2 hours before or 6 hours after cation-containing antacids or laxatives, sucralfate, oral supplements containing iron or calcium, or buffered medications. Alternatively, dolutegravir and supplements containing calcium or iron can be taken together with food.

Administration: Pediatric

Oral: May be administered without regard to meals. Take 2 hours before or 6 hours after cation-containing antacids or laxatives, sucralfate, oral supplements containing iron or calcium, or buffered medications. Alternatively, dolutegravir and supplements containing calcium or iron can be taken together with food.

Soluble tablets (Tivicay PD): May be administered dispersed in water as an oral suspension or swallowed whole. If swallowing whole, do not swallow more than 1 tablet at a time to reduce risk for choking. Do not chew, cut, or crush tablets.

Oral suspension preparation: Fill provided cup with 5 mL (if using ≤3 tablets) or 10 mL (if using 4 to 6 tablets) of drinking water; add tablets to water and swirl the suspension gently for 1 to 2 minutes so that no lumps remain (will have cloudy appearance); administer using provided oral syringe in infants or directly from cup in children; to ensure the full dose is received, add another 5 mL of water to the cup, swirl, and administer from cup directly (children) or pull up remaining liquid into oral syringe for infants. Administer within 30 minutes of mixing. If any medication is spilled during preparation, discard dose and prepare a new dose.

Tablets (Tivicay): For patients that have difficulty swallowing tablets whole, tablets may be split into halves (with both halves then administered) or crushed, added to a small amount of semisolid food or liquid, and consumed immediately (HHS [pediatric 2020]).

Use: Labeled Indications

HIV-1 infection, treatment: Treatment of HIV-1 infection in combination with other antiretroviral agents in treatment-naïve or -experienced adult patients and treatment-naïve or -experienced pediatric patients (but integrase strand transfer inhibitor naïve) at least 4 weeks of age and weighing at least 3 kg, or in combination with rilpivirine in adults to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 copies per mL) on a stable antiretroviral regimen for at least 6 months with no history of treatment failure or known substitutions associated with resistance to either antiretroviral agent.

Use: Off-Label: Adult

HIV-1 nonoccupational postexposure prophylaxis

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported with combination therapy.

>10%: Gastrointestinal: Increased serum lipase (2% to 11%)

1% to 10%:

Dermatologic: Pruritus (<2%)

Endocrine & metabolic: Hyperglycemia (≤9%)

Gastrointestinal: Abdominal distress (<2%), abdominal pain (<2%), diarrhea (≤2%), flatulence (<2%), nausea (≤1%), upper abdominal pain (<2%), vomiting (<2%)

Hematologic & oncologic: Neutropenia (4%; grades 3/4: 2% to 3%)

Hepatic: Hepatitis (<2%), hyperbilirubinemia (≤3%), increased serum alanine aminotransferase (1% to 4%), increased serum aspartate aminotransferase (1% to 5%)

Nervous system: Depression (≤1%), fatigue (≤2%), headache (≤2%), insomnia (≤7%), suicidal ideation (<2%), suicidal tendencies (<2%)

Neuromuscular & skeletal: Increased creatinine phosphokinase in blood specimen (2% to 7%), myositis (<2%)

Renal: Renal insufficiency (<2%)

<1%:

Dermatologic: Skin rash

Hypersensitivity: Hypersensitivity reaction

Nervous system: Abnormal dreams, dizziness

Frequency not defined:

Endocrine & metabolic: Increased HDL cholesterol, increased LDL cholesterol, increased serum cholesterol, increased serum triglycerides

Renal: Increased serum creatinine

Postmarketing:

Endocrine & metabolic: Diabetes mellitus (Hirigo 2022, O’Halloran 2022), weight gain

Hepatic: Acute hepatic failure, hepatotoxicity

Immunologic: Immune reconstitution syndrome

Nervous system: Anxiety

Neuromuscular & skeletal: Arthralgia, myalgia

Contraindications

Hypersensitivity to dolutegravir or any component of the formulation; concurrent use with dofetilide.

Canadian labeling: Additional contraindications (not in US labeling): Concurrent use with organic cation transporter 2 substrates with narrow therapeutic windows (eg, fampridine).

Warnings/Precautions

Concerns related to adverse effects:

• Hepatotoxicity: Hepatic adverse events, including elevated serum liver biochemistries, hepatitis, and acute liver failure, have been reported; these events have occurred in patients without underlying hepatic disease or other risk factors. Patients with hepatitis B or C may be at increased risk for worsening or development of increased transaminases; sometimes these increases were consistent with immune reconstitution syndrome or hepatitis B reactivation (particularly when anti-hepatitis therapy was withdrawn). Drug-induced liver injury has been reported with dolutegravir in combination with abacavir and lamivudine. Monitor patients for signs/symptoms of hepatotoxicity.

• Hypersensitivity reactions: Rash, constitutional findings, and organ dysfunction (eg, liver injury) have been reported. Discontinue immediately if signs of hypersensitivity (eg, severe rash, rash with fever, malaise, fatigue, muscle/joint aches, blistering or peeling of skin, oral blisters/lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, difficulty breathing) occur. Monitor clinical status and liver function tests, and initiate supportive therapy as appropriate. If hypersensitivity occurs, do not reinitiate therapy with dolutegravir.

• 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.

Disease-related concerns:

• Hepatic impairment: Not recommended for use in patients with severe hepatic impairment (has not been studied).

• Renal impairment: Use with caution in integrase strand transfer inhibitor (INSTI)-experienced patients with severe renal impairment; decreases in dolutegravir concentrations were observed and may result in loss of therapeutic effect and development of resistance to dolutegravir or other coadministered antiretroviral agents.

Dosage form specific issues:

• Product interchangeability: Dolutegravir tablets and soluble tablets for oral suspension (Tivicay PD) are not bioequivalent and not interchangeable on a milligram-per-milligram basis. If a patient switches from one formulation to another, adjust dose for the new dosage formulation. Incorrect dosing may result in underdosing, loss of therapeutic effect, and possible development of resistance, or adverse reactions from increased exposure to dolutegravir.

Other warnings/precautions:

• Appropriate use: Use in INSTI-experienced patients should be guided by the number and type of baseline INSTI substitutions. Efficacy with 50 mg twice daily is reduced in patients with an INSTI-resistance Q148 substitution plus 2 or more additional INSTI-resistance substitutions, including T66A, L74I/M, E138A/K/T, G140S/A/C, Y143R/C/H, E157Q, G163S/E/K/Q, or G193E/R.

• False elevations in serum creatinine: May inhibit tubular secretion of creatinine without affecting actual renal glomerular function; observed onset was within the first 4 weeks of therapy followed by stability through at least 96 weeks. Use caution when interpreting serum creatinine values in patients with medical conditions or receiving drugs needing to be monitored with estimated CrCl.

Metabolism/Transport Effects

Substrate of BCRP/ABCG2, CYP3A4 (minor), P-glycoprotein/ABCB1 (minor), UGT1A1, UGT1A3, UGT1A9; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits OCT2

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Aluminum Hydroxide: May decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after oral aluminum hydroxide. Administer the dolutegravir/rilpivirine combination product at least 4 hours before or 6 hours after oral aluminum hydroxide. Risk D: Consider therapy modification

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Betibeglogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Betibeglogene Autotemcel. Risk X: Avoid combination

Calcium Salts: May decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after oral calcium. Administer dolutegravir/rilpivirine at least 4 hours before or 6 hours after oral calcium salts. Alternatively, dolutegravir and oral calcium can be taken together with food. Risk D: Consider therapy modification

CarBAMazepine: May decrease the serum concentration of Dolutegravir. Management: Increase dolutegravir to 50 mg twice/day in adults. Increase weight-based dose to twice daily in pediatric patients. Specific recommendations vary for combination products; see interaction monograph for details. Risk D: Consider therapy modification

Clofarabine: OCT2 Inhibitors may increase the serum concentration of Clofarabine. Risk C: Monitor therapy

Dalfampridine: OCT2 Inhibitors may increase the serum concentration of Dalfampridine. Management: Consider alternatives to this combination. Carefully weigh the risk of seizures against the benefit of combining OCT2 inhibitors with dalfampridine. Risk D: Consider therapy modification

Dofetilide: Dolutegravir may increase the serum concentration of Dofetilide. Risk X: Avoid combination

Efavirenz: May decrease the serum concentration of Dolutegravir. Management: Increase dolutegravir to 50 mg twice/day in adults. Increase weight based dose to twice daily in pediatric patients. See interaction monograph for details. Not recommended with Dovato or Juluca combo products. Seek alternatives if INSTI resistance. Risk D: Consider therapy modification

Elivaldogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Elivaldogene Autotemcel. Management: Avoid use of antiretroviral medications for at least one month, or for the amount of time required for elimination of the retroviral medication, prior to stem cell mobilization and until the all apheresis cycles are finished Risk X: Avoid combination

Etravirine: May decrease the serum concentration of Dolutegravir. Management: Avoid etravirine with dolutegravir unless with atazanavir/ritonavir, darunavir/ritonavir or lopinavir/ritonavir; avoid use with Dovato brand combination. Canada recommends using dolutegravir 50 mg twice daily when with etravirine. Risk D: Consider therapy modification

Fosamprenavir: May decrease the serum concentration of Dolutegravir. Specifically, Fosamprenavir/Ritonavir may decrease the serum concentration of Dolutegravir. The individual contributions of Fosamprenavir and Ritonavir to this effect are unknown. Management: Increase dolutegravir to 50 mg twice/day in adults. Increase weight-based dose to twice daily in pediatric patients. Recommendations vary for combo products; see interaction monograph for details. Not recommended with Dovato or Juluca brand combos. Risk D: Consider therapy modification

Fosphenytoin-Phenytoin: May decrease the serum concentration of Dolutegravir. Risk X: Avoid combination

Iron Preparations: May decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after oral iron. Administer dolutegravir/rilpivirine at least 4 hours before or 6 hours after oral iron. Alternatively, dolutegravir and oral iron can be taken together with food. Risk D: Consider therapy modification

Magnesium Salts: May decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after oral magnesium salts. Administer the dolutegravir/rilpivirine combination product at least 4 hours before or 6 hours after oral magnesium salts. Risk D: Consider therapy modification

MetFORMIN: Dolutegravir may increase the serum concentration of MetFORMIN. Management: Consider alternatives to this combination or use of lower metformin doses. Carefully weigh the risk of metformin toxicities (including lactic acidosis) against the benefit of combining dolutegravir with metformin. Risk D: Consider therapy modification

Mitapivat: May decrease the serum concentration of UGT1A1 Substrates. Risk C: Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after multivitamins. Administer the dolutegravir/rilpivirine product at least 4 hours before or 6 hours multivitamins. Alternatively, dolutegravir and multivitamins can be taken together with food Risk D: Consider therapy modification

Multivitamins/Minerals (with AE, No Iron): May decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after multivitamins. Administer the dolutegravir/rilpivirine product at least 4 hours before or 6 hours multivitamins. Alternatively, dolutegravir and multivitamins can be taken together with food Risk D: Consider therapy modification

Nevirapine: May decrease the serum concentration of Dolutegravir. Risk X: Avoid combination

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

OXcarbazepine: May decrease the serum concentration of Dolutegravir. Risk X: Avoid combination

PHENobarbital: May decrease the serum concentration of Dolutegravir. Risk X: Avoid combination

Primidone: May decrease the serum concentration of Dolutegravir. Specifically, the Primidone metabolite phenobarbital may decrease Dolutegravir serum concentrations. Risk X: Avoid combination

Rifabutin: May decrease the serum concentration of Dolutegravir. Risk C: Monitor therapy

RifAMPin: May decrease the serum concentration of Dolutegravir. Management: Increase dolutegravir to 50 mg twice/day in adults. Increase weight-based dose to twice daily in pediatric patients. Specific recommendations vary for combination products; see interaction monograph for details. Risk D: Consider therapy modification

Selenium: May decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after oral selenium. Administer the dolutegravir/rilpivirine combination product at least 4 hours before or 6 hours after oral selenium. Risk D: Consider therapy modification

St John's Wort: May decrease the serum concentration of Dolutegravir. Risk X: Avoid combination

Sucralfate: May decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after sucralfate. Administer the dolutegravir/rilpivirine combination product at least 4 hours before or 6 hours after sucralfate. Risk D: Consider therapy modification

Tipranavir: May decrease the serum concentration of Dolutegravir. Specifically, Tipranavir/Ritonavir may decrease the serum concentration of Dolutegravir. The individual contributions of Tipranavir and Ritonavir to this effect are unknown. Management: Increase dolutegravir to 50 mg twice/day in adults. Increase weight-based dose to twice daily in pediatric patients. Recommendations vary for combo products; see interaction monograph for details. Not recommended with Dovato or Juluca brand combos. Risk D: Consider therapy modification

Valproate Products: May decrease the serum concentration of Dolutegravir. Risk C: Monitor therapy

Zinc Salts: May decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after oral zinc salts. Administer the dolutegravir/rilpivirine combination product at least 4 hours before or 6 hours after oral zinc salts. Risk D: Consider therapy modification

Reproductive Considerations

The Health and Human Services (HHS) Perinatal HIV guidelines recommend dolutegravir as a preferred integrase strand transfer inhibitor for patients with HIV infection who are not yet pregnant but are trying to conceive. Information related to neural tube defects following in utero exposure should be discussed with the patient.

The manufacturer recommends pregnancy testing prior to use in patients who may become pregnant. The manufacturer also recommends use of effective contraception during dolutegravir therapy.

Viral suppression sustained below the limits of detection with antiretroviral therapy (ART) and modification of therapy (if needed) is recommended in all patients with HIV infection who are planning a pregnancy. Optimization of the health of the person who will become pregnant and a discussion of the potential risks and benefits of ART during pregnancy is also recommended prior to conception. In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender diverse people assigned female sex at birth.

Health care providers caring for couples planning a pregnancy when one or both partners are diagnosed with HIV infection may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2021).

Pregnancy Considerations

Dolutegravir has a high level of transfer across the human placenta.

No increased risk of overall teratogenic effects has been observed following first trimester exposure according to data collected by the antiretroviral pregnancy registry. Preliminary data from a study in Botswana found a small but significant increase in neural tube defects (NTDs) in women who became pregnant while taking dolutegravir, but not in women who started dolutegravir during pregnancy. Continued surveillance suggests the risk of NTDs is no longer statistically different following maternal use of dolutegravir compared to other antiretrovirals. The study was completed in an area without routine folate fortification via food and may not predict the risk in the United States. It is not known if folic acid supplementation would decrease the risk of NTDs in patients taking dolutegravir; however, daily folic acid is recommended for all patients who are pregnant or who might conceive.

Maternal antiretroviral therapy (ART) may be associated with adverse pregnancy outcomes including preterm delivery, stillbirth, low birth weight, and small for gestational age infants. Actual risks may be influenced by maternal factors such as disease severity, gestational age at initiation of therapy, and specific ART regimen; therefore, close fetal monitoring is recommended. Because there is clear benefit to appropriate treatment, maternal ART should not be withheld due to concerns for adverse neonatal outcomes. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children not diagnosed with HIV infection but who were exposed to ART in utero or as a neonate and develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential metabolic dysfunction.

The Health and Human Services (HHS) Perinatal HIV Guidelines consider dolutegravir a preferred integrase strand transfer inhibitor (INSTI) for pregnant patients with HIV infection who are antiretroviral-naive, who have had ART therapy in the past but are restarting, and who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen). In addition, patients who become pregnant while taking dolutegravir may continue if viral suppression is effective and the regimen is well tolerated. Dolutegravir is also a preferred component of an initial regimen when acute HIV infection is detected during pregnancy (regardless of trimester).

The HHS Perinatal HIV Guidelines consider dolutegravir in combination with abacavir and lamivudine to be a preferred INSTI regimen for initial therapy in antiretroviral-naive pregnant patients. INSTIs can rapidly suppress viral load. A regimen with dolutegravir may be useful when drug interactions or the potential for preterm delivery with protease inhibitors are a concern. In addition, use of dolutegravir may be beneficial in patients with HIV infection who are not on ART and present for care late in pregnancy. Based on limited data, dolutegravir may also be used as a fourth drug in pregnant patients with high viral loads, or as part of a new regimen for a patient experiencing virologic failure on a non-INSTI regimen. Information related to NTDs following in utero exposure should be discussed with the patient.

Pharmacokinetics of dolutegravir may be altered, but dosing adjustments are not needed during pregnancy.

ART is recommended for all pregnant people with HIV infection to maximize their health, maintain the viral load below the limit of detection, and reduce the risk of perinatal transmission. Therapy should be individualized following a discussion of the potential risks and benefits of treatment during pregnancy. Information related to neural tube defects following in utero exposure to dolutegravir should be discussed with the patient. Monitoring of patients who are pregnant is more frequent than in patients who are not pregnant. ART initiated during pregnancy can be modified after delivery. In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender diverse people assigned female sex at birth.

Data collection to monitor pregnancy and infant outcomes following exposure to ART is ongoing. Health care providers are encouraged to enroll patients who are pregnant 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 pregnant patients with HIV infection and their infants may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2021).

Breastfeeding Considerations

Dolutegravir is present in breast milk.

Dolutegravir is a preferred component of a regimen when acute HIV infection is detected in patients who are breastfeeding. Breastfeeding should be interrupted when acute HIV infection is suspected and not continued if infection is confirmed. Milk may be expressed and stored while waiting for confirmation.

Maternal or infant antiretroviral therapy does not completely eliminate the risk of postnatal HIV transmission. In addition, multiclass-resistant virus has been detected in breastfeeding infants despite maternal therapy. In the United States, where formula is usually accessible, affordable, safe, and sustainable, and the risk of infant mortality due to diarrhea and respiratory infections is low, the Health and Human Services (HHS) perinatal HIV guidelines do not recommend breastfeeding for patients with HIV infection when safer infant feeding options are available.

Information is available for counseling and managing patients with HIV infection who are considering breastfeeding (1-888-448-8765). In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender diverse people assigned female sex at birth (HHS [perinatal] 2021).

Dietary Considerations

Take 2 hours before or 6 hours after cation-containing antacids or laxatives, sucralfate, oral supplements containing iron or calcium, or buffered medications. Alternatively, dolutegravir and supplements containing calcium or iron can be taken together with food.

Monitoring Parameters

Viral load, CD4 count, lipid profile; liver aminotransferases (baseline and during therapy); monitor for hypersensitivity. Pregnancy testing prior to use in patients who may become pregnant.

Mechanism of Action

Binds to the integrase active site and inhibits the strand transfer step of HIV-1 DNA integration necessary for the HIV replication cycle.

Pharmacokinetics

Note: The pharmacokinetics of dolutegravir in HIV-1-infected pediatric patients ≥4 weeks of age weighing ≥3 kg were similar to those observed in HIV-1-infected adults.

Absorption: Food increased the extent of absorption and slowed the rate of absorption of dolutegravir. Low-, moderate-, and high-fat meals increased dolutegravir AUC by 33%, 41%, and 66%, respectively; increased Cmax by 46%, 52%, and 67%, respectively; and prolonged Tmax to 3, 4, and 5 hours from 2 hours under fasted conditions, respectively.

Distribution: Vd/F = ~17.4 L.

Protein binding: ≥98.9%.

Metabolism: Primarily metabolized via UGT1A1 with some contribution from CYP3A.

Bioavailability: The relative bioavailability of the oral suspension is ~1.6-fold higher than the tablets.

Half-life elimination: ~14 hours.

Time to peak: 1 to 3 hours.

Excretion: Feces (53% as unchanged drug); urine (31% as metabolites, <1% as unchanged drug).

Pricing: US

Tablet,Dispersible (Tivicay PD Oral)

5 mg (per each): $8.05

Tablets (Tivicay Oral)

10 mg (per each): $16.09

25 mg (per each): $40.23

50 mg (per each): $80.46

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Tivicay (AT, AU, BB, BE, BH, BR, CH, CL, CN, CR, CZ, DE, DK, DO, EC, EE, EG, ES, FI, FR, GB, GR, GT, HK, HN, HR, HU, IE, IL, IS, JP, LB, LT, LU, LV, MT, MX, MY, NI, NL, NO, NZ, PA, PL, PT, RO, SA, SE, SG, SI, SK, SV, TH, TR, TW, ZW)


For country code abbreviations (show table)
  1. Cahn P, Pozniak A, Mingrone H, et al. Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study. Lancet. 2013;382(9893):700-708. [PubMed 23830355]
  2. Centers for Disease Control and Prevention (CDC), US Department of Health and Human Services (HHS). Updated guidelines for antiretroviral postexposure prophylaxis after sexual, injection drug use, or other nonoccupational exposure to HIV—United States, 2016. https://stacks.cdc.gov/view/cdc/38856. Published April 18, 2016. Accessed July 11, 2016.
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  12. US Department of Health and Human Services (HHS) Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/adult-adolescent-arv/guidelines-adult-adolescent-arv.pdf. Updated January 20, 2022. Accessed April 14, 2022.
  13. US Department of Health and Human Services (HHS) Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV. Guidelines for the use of antiretroviral agents in pediatric HIV infection. https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/pediatric-arv/guidelines-pediatric-arv.pdf. Updated April 2020. Accessed June 2, 2020.
  14. US Department of Health and Human Services (HHS) Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for the use of antiretroviral agents in pediatric HIV infection. https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/pediatric-arv/guidelines-pediatric-arv.pdf. Updated March 1, 2016. Accessed July 11, 2016.
  15. US Department of Health and Human Services (HHS) Panel on Treatment of HIV During Pregnancy and Prevention of Perinatal Transmission. Recommendations for the use of antiretroviral drugs during pregnancy and interventions to reduce perinatal HIV transmission in the United States. https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/Perinatal_GL.pdf. Updated December 30, 2021. Accessed January 3, 2022.
  16. Weller S, Borland J, Chen S, et al. Pharmacokinetics of dolutegravir in HIV-seronegative subjects with severe renal impairment. Eur J Clin Pharmacol. 2014;70(1):29-35. doi:10.1007/s00228-013-1590-9 [PubMed 24096683]
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