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Dolutegravir and Lamivudine

Medically reviewed by Drugs.com. Last updated on Oct 8, 2020.

Pronunciation

(DOE loo TEG ra vir & la MIV ue deen)

Index Terms

  • Dolutegravir Sodium and Lamivudine
  • Lamivudine and Dolutegravir

Dosage Forms

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

Tablet, Oral:

Dovato: Dolutegravir sodium 50 mg and lamivudine 300 mg

Brand Names: U.S.

  • Dovato

Pharmacologic Category

  • Antiretroviral, Integrase Inhibitor (Anti-HIV)
  • Antiretroviral, Reverse Transcriptase Inhibitor, Nucleoside (Anti-HIV)

Pharmacology

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.

Use: Labeled Indications

HIV-1 infection, treatment: Treatment of HIV-1 infection in adults 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.

Contraindications

Hypersensitivity to dolutegravir, lamivudine, 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).

Dosing: Adult

HIV-1 infection, treatment:

Oral: One 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 (HHS [adult 2019]).

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

Dosing: Geriatric

Refer to adult dosing.

Administration

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.

Dietary Considerations

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.

Storage

Store below 30°C (86°F).

Drug Interactions

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. Consider therapy modification

Cabozantinib: MRP2 Inhibitors may increase the serum concentration of Cabozantinib. 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. 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. See interaction monograph for details. Seek alternative to carbamazepine if suspected INSTI resistance. Consider therapy modification

Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Avoid combination

Dalfampridine: Dolutegravir may increase the serum concentration of Dalfampridine. Management: Consider alternatives to this combination. Carefully weigh the risk of seizures against the benefit of combining dolutegravir with dalfampridine. Non-US labels list this combination as contraindicated. Consider therapy modification

Dofetilide: Dolutegravir may increase the serum concentration of Dofetilide. 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. Consider therapy modification

Emtricitabine: LamiVUDine may enhance the adverse/toxic effect of Emtricitabine. 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 without a boosted PI. 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. See interaction monograph for details. Not recommended with Dovato or Juluca combo products. Seek alternatives if INSTI resistance. Consider therapy modification

Fosphenytoin-Phenytoin: May decrease the serum concentration of Dolutegravir. 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. Exceptions: Ferric Carboxymaltose; Ferric Derisomaltose; Ferric Gluconate; Ferric Hydroxide Polymaltose Complex; Ferric Pyrophosphate Citrate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. 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. 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. Consider therapy modification

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 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 Consider therapy modification

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

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

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

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

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

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. See interaction monograph for details. Seek alternative to rifampin if suspected INSTI resistance. 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. 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. Consider therapy modification

St John's Wort: May decrease the serum concentration of Dolutegravir. 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. 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. See interaction monograph for details. Not recommended with Dovato or Juluca combo products. Seek alternatives if INSTI resistance. Consider therapy modification

Trimethoprim: May increase the serum concentration of LamiVUDine. 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. Consider therapy modification

Adverse Reactions

See individual agents.

ALERT: U.S. Boxed Warning

Patients co-infected with hepatitis B virus (HBV) and human immunodeficiency virus (HIV-1):

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.

Warnings/Precautions

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:

• Chronic hepatitis B: [US Boxed Warning]: Severe acute exacerbations of hepatitis B virus (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.

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

• HBV resistance [US Boxed Warning]: All patients with HIV-1 should be tested for the presence of HBV prior to or when initiating dolutegravir/lamivudine. Emergence of lamivudine-resistant HBV variants in patients receiving lamivudine-containing antiretroviral regimens has been reported. If dolutegravir/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.

• Renal impairment: Use is not recommended in patients with CrCl <50 mL/minute.

Monitoring Parameters

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. Evaluate pregnancy status prior to use in females of reproductive potential.

Reproductive Considerations

Evaluate pregnancy status prior to use in females of reproductive potential. 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 females living with HIV who are not yet pregnant but are trying to conceive (2-drug regimens are not recommended during pregnancy) (HHS [perinatal] 2019).

Refer to individual monographs for additional information.

Pregnancy Considerations

The manufacturer does not recommend use of this combination during the first trimester of pregnancy. The US Department of Health and Human Services perinatal HIV guidelines do not recommend use of this fixed-dose 2-drug combination in pregnant females living 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). For females who become pregnant while taking this combination as a complete regimen, the regimen should be changed, or additional agents added (2-drug regimens are not recommended during pregnancy) (HHS [perinatal 2019]).

Refer to individual monographs for additional information.

Patient Education

What is this drug used for?

• It is used to treat HIV infection.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache

• Diarrhea

• Nausea

• Trouble sleeping

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.

• Lactic acidosis like fast breathing, fast heartbeat, abnormal heartbeat, vomiting, fatigue, shortness of breath, severe loss of strength and energy, severe dizziness, feeling cold, or muscle pain or cramps.

• Pancreatitis like severe abdominal pain, severe back pain, severe nausea, or vomiting.

• Muscle pain

• Joint pain

• Mouth sores

• Eye irritation

• Shortness of breath

• Severe loss of strength and energy

• Infection

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.