Version October 2024
Emergence of lamivudine-resistant HBV:
All patients with HIV-1 should be tested for the presence of HBV prior to or when initiating dolutegravir and lamivudine. Emergence of lamivudine-resistant HBV variants associated with lamivudine-containing antiretroviral regimens has been reported. If dolutegravir and lamivudine is used in patients co-infected with HIV-1 and HBV, additional treatment should be considered for appropriate treatment of chronic HBV; otherwise, consider an alternative regimen.
Exacerbations of HBV:
Severe acute exacerbations of HBV have been reported in patients who are co-infected with HIV-1 and HBV and have discontinued lamivudine. Closely monitor hepatic function in these patients and, if appropriate, initiate anti-HBV treatment.
HIV-1 infection, treatment:
Oral: 1 tablet (dolutegravir 50 mg/lamivudine 300 mg) once daily. Note: Dolutegravir/lamivudine is not a recommended initial regimen in patients with HIV RNA >500,000 copies/mL, hepatitis B virus (HBV) coinfection, or if antiretroviral treatment is going to be started before the results of genotypic resistance testing for reverse transcriptase or HBV testing are available (Ref). In addition, there is a concern for lower treatment response in patients with CD4 count ≤200 cells/mm3 (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥30 mL/minute: No dosage adjustment necessary. Patients with CrCl consistently between 30 and <50 mL/minute should be monitored for lamivudine-associated hematologic toxicities. If new or worsening neutropenia or anemia develop, requiring dose adjustment of lamivudine, then use renal dose-adjusted individual components of dolutegravir and lamivudine.
CrCl <30 mL/minute: Use is not recommended (use renal dose-adjusted individual components).
Mild or 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).
Refer to adult dosing.
(For additional information see "Dolutegravir and lamivudine: Pediatric drug information")
HIV-1 infection, treatment: Note: Evaluate gene mutation and antiretroviral (ARV) resistance patterns (refer to https://www.iasusa.org and https://hivdb.stanford.edu/ for more information).
Children ≥12 years and Adolescents, weighing ≥25 kg: Dolutegravir 50 mg/lamivudine 300 mg per tablet: Oral: One tablet once daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children ≥12 years and Adolescents: Oral:
CrCl ≥30 mL/minute: No dosage adjustment necessary. Patients with CrCl consistently between 30 and <50 mL/minute should be monitored for lamivudine-associated hematologic toxicities. If new or worsening neutropenia or anemia develops that requires lamivudine dose adjustment, discontinue fixed-combination product (ie, Dovato) and use renal dose-adjusted individual components.
CrCl <30 mL/minute: Use is not recommended (use renal dose-adjusted individual components).
Children ≥12 years and Adolescents: Oral:
Mild or moderate impairment: No dosage adjustment necessary.
Severe impairment: Use is not recommended (has not been studied).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults. Also see individual agents.
1% to 10%:
Endocrine & metabolic: Weight gain (3%)
Nervous system: Insomnia (2%)
Frequency not defined: Hepatic: Exacerbation of hepatitis B
Postmarketing: Immunologic: Immune reconstitution syndrome
Hypersensitivity to dolutegravir, lamivudine, or any component of the formulation; concurrent use with dofetilide.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Concurrent use with organic cation transporter 2 substrates with narrow therapeutic windows (eg, fampridine).
Concerns related to adverse effects:
• Hepatotoxicity: Hepatic adverse events, including elevated serum liver biochemistries, hepatitis, and acute liver failure, have been reported with dolutegravir; 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 requiring liver transplantation 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 with dolutegravir. 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.
• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves disease, polymyositis, Guillain-Barré syndrome) later in therapy; further evaluation and treatment may be required.
• Lactic acidosis/hepatomegaly: Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues, including fatal cases. Use with caution and closely monitor patients with risk factors for liver disease (risk may be increased with female gender or obesity); suspend use in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis).
Disease-related concerns:
• Hepatic impairment: Not recommended for use in patients with severe hepatic impairment (Child-Pugh class C) (has not been studied).
• Renal impairment: Use is not recommended in patients with CrCl <30 mL/minute.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Dovato: Dolutegravir sodium 50 mg and lamivudine 300 mg
No
Tablets (Dovato Oral)
50-300 mg (per each): $119.07
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Dovato: Dolutegravir sodium 50 mg and lamivudine 300 mg
Oral: Administer with or without food. 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/lamivudine and supplements containing calcium or iron can be taken together with food.
Oral: May be administered with or without food. 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/lamivudine and supplements containing calcium or iron can be taken together with food.
HIV-1 infection, treatment: Treatment of HIV-1 infection in adults and adolescents ≥12 years of age and weighing ≥25 kg with no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen without history of treatment failure and with no known substitutions associated with resistance to dolutegravir or lamivudine.
Dovato may be confused with doravirine
DOR is an error-prone abbreviation (mistaken as doravirine)
Refer to individual components.
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 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
Atidarsagene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Atidarsagene Autotemcel. Risk X: Avoid combination
Belumosudil: May increase the serum concentration of UGT1A1 Substrates. Management: Avoid coadministration of belumosudil with substrates of UGT1A1 for which minimal concentration increases can cause serious adverse effects. If coadministration is required, dose reductions of the UGT1A1 substrate may be required. Risk D: Consider therapy modification
Betibeglogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Betibeglogene Autotemcel. Risk X: Avoid combination
Cabozantinib: MRP2 Inhibitors may increase the serum concentration of Cabozantinib. Risk C: Monitor therapy
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
Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Risk X: Avoid combination
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. Recommendations vary for combo products; see interaction monograph for details. Not recommended with Dovato or Juluca brand combos. 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
Fexinidazole: May increase the serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of fexinidazole with MATE1/2-K substrates when possible. If combined, monitor for increased MATE1/2-K substrate toxicities. Risk D: Consider therapy modification
Fexinidazole: May increase the serum concentration of OCT2 Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of fexinidazole with OCT2 substrates when possible. If combined, monitor for increased OCT2 substrate toxicities. 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
Foslevodopa: May increase the serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Fosphenytoin-Phenytoin: May decrease the serum concentration of Dolutegravir. Risk X: Avoid combination
Gilteritinib: May increase the serum concentration of OCT1 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Givinostat: May increase the serum concentration of OCT2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
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
Isoniazid: Dolutegravir may enhance the adverse/toxic effect of Isoniazid. Dolutegravir may increase the serum concentration of Isoniazid. Risk C: Monitor therapy
Lovotibeglogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Lovotibeglogene Autotemcel. Risk X: Avoid combination
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. Management: Prescribing information suggests avoiding the concomitant use of dolutegravir and nevirapine. HIV treatment guidelines suggest these drugs can be combined without dose adjustment. Monitor for reduced dolutegravir concentrations/effects if combined. Risk D: Consider therapy modification
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
Pacritinib: May increase the serum concentration of OCT1 Substrates (Clinically Relevant with Inhibitors). 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
Rifapentine: Dolutegravir may enhance the adverse/toxic effect of Rifapentine. Rifapentine may decrease the serum concentration of Dolutegravir. Risk C: Monitor therapy
Risdiplam: May increase the serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of risdiplam with MATE substrates if possible. If the combination cannot be avoided, monitor closely for adverse effects. Consider a reduced dose of the MATE substrate according to that substrate's labeling if appropriate. 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
Sorbitol: May decrease the serum concentration of LamiVUDine. Management: When possible, avoid chronic coadministration of sorbitol-containing solutions with lamivudine, but if this combination cannot be avoided, monitor patients more closely for possible therapeutic failure associated with decreased lamivudine exposure. 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
Tafenoquine: May increase the serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of MATE substrates with tafenoquine, and if the combination cannot be avoided, monitor closely for evidence of toxicity of the MATE substrate and consider a reduced dose of the MATE substrate according to that substrate's labeling. Risk D: Consider therapy modification
Tafenoquine: May increase the serum concentration of OCT2 Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of OCT2 substrates with tafenoquine, and if the combination cannot be avoided, monitor closely for evidence of toxicity of the OCT2 substrate and consider a reduced dose of the OCT2 substrate according to that substrate's labeling. 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
Trimethoprim: May increase the serum concentration of LamiVUDine. Risk C: Monitor therapy
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
Evaluate pregnancy status prior to use in patients who may become pregnant.
Contraception is not required to initiate or continue antiretroviral therapy (HHS [perinatal] 2023); however, the manufacturer recommends consistent use of effective contraception during therapy.
The US Department of Health and Human Services perinatal HIV guidelines do not recommend use of this fixed-dose 2-drug combination as a complete regimen in patients with HIV who are not yet pregnant but are trying to conceive (HHS [perinatal] 2023).
Refer to individual monographs for additional information.
The US Department of Health and Human Services perinatal HIV guidelines do not recommend use of this fixed-dose 2-drug combination as a complete regimen in pregnant patients with HIV who are antiretroviral naive, who have had antiretroviral therapy (ART) in the past but are restarting, or who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen). Although data are not available for use of 2-drug oral regimens in pregnancy, use may continue in patients who are virologically suppressed and present with this combination as a 2-drug regimen while pregnant; frequent viral load monitoring (every 1 to 2 months) is recommended (HHS [perinatal] 2023).
Refer to individual monographs for additional information.
Dolutegravir and lamivudine are present in breast milk.
Refer to individual monographs for additional information.
Take with or without food and 2 hours before or 6 hours after cation-containing antacids or laxatives, sucralfate, oral supplements containing iron or calcium, or buffered medications. Alternatively, dolutegravir/lamivudine and supplements containing calcium or iron can be taken together with food.
Hepatitis B virus testing prior to initiation; viral load, CD4 count; renal and hepatic function (baseline and during therapy); signs/symptoms of hypersensitivity reactions, lactic acidosis; monitor for new-onset or worsening hematologic toxicity (eg, neutropenia, anemia) in patients with CrCl <50 mL/minute (periodically and as clinically indicated). Evaluate pregnancy status prior to use in females of reproductive potential.
Dolutegravir, an integrase inhibitor, inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral DNA integration. Lamivudine is a cytosine analog. In vitro, lamivudine is triphosphorylated, the principle mode of action is inhibition of HIV reverse transcription via viral DNA chain termination; inhibits RNA- and DNA-dependent DNA polymerase activities of reverse transcriptase.
See individual agents.
Altered kidney function: Patients taking dolutegravir/lamivudine with CrCl between 30 and 49 mL/minute may experience a 1.6- to 3.3-fold higher lamivudine AUC compared to patients with CrCl ≥50 mL/minute.
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