Dovato

Last updated on RxList: 4/23/2021
Dovato Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Dovato?

Dovato (dolutegravir and lamivudine) is a combination of an integrase strand transfer inhibitor (INSTI) and a nucleoside analogue reverse transcriptase inhibitor (NRTI) indicated as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults with no antiretroviral treatment history and with no known substitutions associated with resistance to the individual components of Dovato.

What Are Side Effects of Dovato?

Common side effects of Dovato include:

  • headache,
  • diarrhea,
  • nausea,
  • insomnia,
  • fatigue, and
  • dizziness

Dosage for Dovato

The dose of Dovato is one tablet taken orally once daily with or without food.

What Drugs, Substances, or Supplements Interact with Dovato?

Dovato may interact with:

  • other antiretroviral drugs for the treatment of HIV-1 infection,
  • dofetilide,
  • metformin,
  • anticonvulsants,
  • rifampin,
  • St. John's wort,
  • cation-containing antacids or laxatives,
  • sucralfate,
  • buffered medications,
  • oral calcium and iron supplements (including multivitamins containing calcium or iron), and
  • sorbitol

Dovato During Pregnancy and Breastfeeding

Tell your doctor all medications and supplements you use. Dovato is not recommended for use from conception through the first trimester of pregnancy due to the risk of neural tube defects. Pregnancy testing and contraception are recommended. There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to Dovato during pregnancy. Breastfeeding while using Dovato is not recommended due to the potential for HIV-1 transmission.

Additional Information

Our Dovato (dolutegravir and lamivudine) Tablets, for Oral Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

QUESTION

What is HIV? See Answer
Dovato Consumer Information

Stop taking this medicine and get emergency medical help if you have signs of an allergic reaction: fever, general ill feeling, trouble breathing, tiredness; joint or muscle pain, blisters or mouth sores, redness or swelling in your eyes; blistering or peeling skin; swelling of your face, lips, tongue, or throat.

Mild symptoms of lactic acidosis may worsen over time, and this condition can be fatal. Get emergency medical help if you have: unusual muscle pain, trouble breathing, stomach pain, vomiting, fast or irregular heart rate, dizziness, feeling cold, or feeling very weak or tired.

Call your doctor at once if you have:

  • the first sign of any skin rash, no matter how mild; or
  • liver problems--nausea, vomiting, loss of appetite, upper stomach pain, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Dolutegravir and lamivudine affects your immune system, which may cause certain side effects (even weeks or months after you've taken this medicine). Tell your doctor if you have:

  • signs of a new infection--fever, night sweats, swollen glands, cold sores, cough, wheezing, diarrhea, weight loss;
  • trouble speaking or swallowing, problems with balance or eye movement, weakness or prickly feeling; or
  • swelling in your neck or throat (enlarged thyroid), menstrual changes, impotence.

Common side effects may include:

  • headache;
  • tiredness;
  • nausea, diarrhea; or
  • sleep problems (insomnia).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Dovato (Dolutegravir and Lamivudine Tablets)

SLIDESHOW

A Timeline of the HIV/AIDS Pandemic See Slideshow
Dovato Professional Information

SIDE EFFECTS

The following adverse reactions are discussed in other sections of the labeling:

  • Patients co-infected with HIV-1 and HBV [see WARNINGS AND PRECAUTIONS]
  • Hypersensitivity reactions [see WARNINGS AND PRECAUTIONS]
  • Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
  • Lactic acidosis and severe hepatomegaly with steatosis [see WARNINGS AND PRECAUTIONS]
  • Immune reconstitution syndrome [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Clinical Trials In Adults With No Antiretroviral Treatment History

The safety assessment of DOVATO in HIV-1-infected adults with no antiretroviral treatment history and with a plasma viral load ≤500,000 HIV-1 RNA copies/mL at the screening visit, is based on the pooled primary Week 96 analyses of data from 2 identical, multicenter, double-blind, controlled trials, GEMINI-1 and GEMINI-2. A total of 1,433 HIV-1-infected adults with no antiretroviral treatment history received either dolutegravir (TIVICAY) 50 mg plus lamivudine (EPIVIR) 300 mg, as a complete regimen once daily, or TIVICAY 50 mg plus fixed-dose combination tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) (TRUVADA), administered once daily.

The rates of adverse events leading to discontinuation in the pooled analysis were 3% of subjects in both treatment arms. The most common adverse events leading to discontinuation were psychiatric disorders: 1% of subjects in both treatment arms.

Adverse reactions (all grades) observed in at least 2% of subjects in either treatment arm of the Week 96 pooled analysis from GEMINI-1 and GEMINI-2 trials are provided in Table 2.

The adverse reactions observed for TIVICAY plus EPIVIR in the Week 96 analysis of the pooled data from GEMINI-1 and GEMINI-2 were generally consistent with the adverse reaction profiles and severities for the individual components when administered with other antiretroviral agents.

Table 2: Adverse Reactions (All Grades) Reported in ≥2% of Subjects in Any Treatment Group in Adults with No Antiretroviral Treatment History in GEMINI-1 and GEMINI-2 (Week 96 Pooled Analysis)

Adverse Reaction TIVICAY plus EPIVIR
(n = 716)
TIVICAY plus TRUVADA
(n = 717)
Headache 3% 4%
Nausea 2% 5%
Diarrhea 2% 3%
Insomnia 2% 3%
Fatiguea 2% 2%
Anxiety 2% 1%
Dizziness 1% 2%
a Fatigue: includes fatigue, asthenia, and malaise.

Adverse reactions of at least Grade 2 occurring in ≥1% of subjects treated with TIVICAY plus EPIVIR were headache, anxiety, and suicidal ideation (all at 1%).

Less Common Adverse Reactions

The following adverse reactions occurred in <2% of subjects receiving dolutegravir plus lamivudine or are from studies described in the prescribing information of the individual components, TIVICAY (dolutegravir) and EPIVIR (lamivudine). Some events have been included because of their seriousness and assessment of potential causal relationship.

Blood and Lymphatic Systems Disorders: Anemia, neutropenia, thrombocytopenia.

Gastrointestinal Disorders: Abdominal discomfort, abdominal pain, flatulence, upper abdominal pain, vomiting.

General: Fever.

Hepatobiliary Disorders: Hepatitis.

Immune System Disorders: Hypersensitivity, immune reconstitution syndrome.

Musculoskeletal Disorders: Myositis.

Nervous System Disorders: Somnolence.

Psychiatric Disorders: Abnormal dreams, depression. Suicidal ideation, attempt, behavior, or completion; these events were observed primarily in subjects with a pre-existing history of depression or other psychiatric illness.

Renal and Urinary Disorders: Renal impairment.

Skin and Subcutaneous Tissue Disorders: Pruritus, rash.

Clinical Trials In Virologically Suppressed Adults

The safety of DOVATO in virologically suppressed adults was based on Week 48 data from 740 subjects in a randomized, parallel-group, open-label, multicenter, non-inferiority controlled trial (TANGO). Subjects who were on a stable suppressive tenofovir alafenamide-based regimen (TBR) were randomized to receive DOVATO once daily or continue with their TBR for up to 200 weeks. Overall, the safety profile of DOVATO in virologically suppressed adult subjects in the TANGO trial was similar to that of TIVICAY plus EPIVIR in subjects with no antiretroviral treatment history in the GEMINI trials [see Clinical Studies].

Laboratory Abnormalities

Selected laboratory abnormalities with a worsening grade from baseline and representing the worst-grade toxicity are presented in Table 3. The mean change from baseline observed for selected lipid values is presented in Table 4.

Table 3: Selected Laboratory Abnormalities (Grades 2 to 4; Week 96 Pooled Analyses) in GEMINI-1 and GEMINI-2 Trials

Laboratory Parameter Abnormality TIVICAY plus EPIVIR
(n = 716)
TIVICAY plus TRUVADA
(n = 717)
Alanine aminotransferase (ALT)
Grade 2 (2.5 to <5.0 x ULN) 3% 4%
Grade 3 to 4 (≥5.0 x ULN) 3% 3%
Aspartate aminotransferase (AST)
Grade 2 (2.5 to <5.0 x ULN) 4% 4%
Grade 3 to 4 (≥5.0 x ULN) 3% 3%
Total bilirubin
Grade 2 (1.6 to <2.6 x ULN) 2% 3%
Grade 3 to 4 (≥2.6 x ULN) 1% 1%
Creatine kinase
Grade 2 (6.0 to <10 x ULN) 4% 4%
Grade 3 to 4 (≥10.0 x ULN) 6% 7%
Hyperglycemia (glucose)
Grade 2 (126 to 250 mg/dL) 9% 6%
Grade 3 to 4 (>250 mg/dL) 1% 1%
Hypophosphatemia (phosphate)
Grade 2 (1.4 to <2.0 mg/dL) 9% 10%
Grade 3 to 4 (<1.4 mg/dL) 1% 1%
Lipase
Grade 2 (1.5 to <3.0 x ULN) 6% 6%
Grade 3 to 4 (≥3.0 x ULN) 2% 4%
ULN = Upper limit of normal.

Table 4: Mean Change from Baseline in Fasted Lipid Values (Week 96 Pooled Analysesa) in GEMINI-1 and GEMINI-2 Trials

Laboratory Parameter Preferred Term TIVICAY plus EPIVIR
(n = 716)
TIVICAY plus TRUVADA
(n = 717)
Cholesterol (mg/dL) 15 -6
HDL cholesterol (mg/dL) 7 3
LDL cholesterol (mg/dL) 6 -7
Triglycerides (mg/dL) 11 -11
Total cholesterol/HDL cholesterol ratio -0.1 -0.4
a Subjects on lipid-lowering agents at baseline are excluded (TIVICAY plus EPIVIR, n = 30; TIVICAY plus TRUVADA, n = 23). The last available fasted, on-treatment lipid value prior to initiation of a lipid-lowering agent was carried forward in place of observed values after initiation of a lipid-lowering agent. A total of 40 and 16 subjects receiving TIVICAY plus EPIVIR and TIVICAY plus TRUVADA, respectively, initiated lipid-lowering agents post-baseline.

Changes In Serum Creatinine

Dolutegravir has been shown to increase serum creatinine due to inhibition of tubular secretion of creatinine without affecting renal glomerular function [see CLINICAL PHARMACOLOGY]. Increases in serum creatinine occurred within the first 4 weeks of treatment in both arms and remained stable through 96 weeks. A mean change from baseline of 0.138 mg/dL and 0.176 mg/dL was observed after 96 weeks of treatment with TIVICAY plus EPIVIR and TIVICAY plus TRUVADA, respectively. These changes are not considered to be clinically relevant.

Postmarketing Experience

The following adverse reactions have been identified during postmarketing experience in patients receiving a dolutegravir-or lamivudine-containing regimen. Because postmarketing reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Body as a Whole

Redistribution/accumulation of body fat.

Endocrine and Metabolic

Hyperglycemia.

General

Weakness.

Hemic and Lymphatic

Anemia (including pure red cell aplasia and severe anemias progressing on therapy).

Hepatic and Pancreatic

Lactic acidosis and hepatic steatosis [see WARNINGS AND PRECAUTIONS], pancreatitis, posttreatment exacerbations of HBV [see WARNINGS AND PRECAUTIONS].

Hepatobiliary Disorders

Acute liver failure, hepatotoxicity.

Hypersensitivity

Anaphylaxis, urticaria.

Investigations

Weight increased.

Musculoskeletal

Arthralgia, CPK elevation, muscle weakness, myalgia, rhabdomyolysis.

Nervous System

Paresthesia, peripheral neuropathy.

Skin

Alopecia.

DRUG INTERACTIONS

Coadministration With Other Antiretroviral Drugs

DOVATO is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended [see INDICATIONS AND USAGE]. Information regarding potential drug-drug interactions with other antiretroviral drugs is not provided [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, CLINICAL PHARMACOLOGY].

Potential For DOVATO To Affect Other Drugs

Dolutegravir, a component of DOVATO, inhibits the renal organic cation transporters (OCT)2 and multidrug and toxin extrusion transporter (MATE)1; thus, it may increase plasma concentrations of drugs eliminated via OCT2 or MATE1 such as dofetilide, dalfampridine, and metformin [see CONTRAINDICATIONS, DRUG INTERACTIONS, CLINICAL PHARMACOLOGY].

Potential For Other Drugs To Affect The Components Of DOVATO

Dolutegravir is metabolized by uridine diphosphate (UDP)-glucuronosyl transferase (UGT)1A1 with some contribution from cytochrome P450 (CYP)3A. Dolutegravir is also a substrate of UGT1A3, UGT1A9, breast cancer resistance protein (BCRP), and P-glycoprotein (P-gp) in vitro. Drugs that induce those enzymes and transporters may decrease dolutegravir plasma concentrations and reduce the therapeutic effect of DOVATO [see DRUG INTERACTIONS, CLINICAL PHARMACOLOGY]. Coadministration of DOVATO and other drugs that inhibit these enzymes may increase dolutegravir plasma concentrations.

Coadministration of dolutegravir with polyvalent cation-containing products may lead to decreased absorption of dolutegravir [see DRUG INTERACTIONS, CLINICAL PHARMACOLOGY].

Established And Other Potentially Significant Drug Interactions

No drug interaction studies were conducted with DOVATO. The drug interactions described are based on studies conducted with dolutegravir or lamivudine when administered alone [see CLINICAL PHARMACOLOGY]. Information regarding potential drug interactions with DOVATO are provided in Table 5. These recommendations are based on either drug interaction trials or predicted interactions due to the expected magnitude of interaction and potential for serious adverse events or loss of efficacy [see CONTRAINDICATIONS, CLINICAL PHARMACOLOGY].

Table 5: Established and Other Potentially Significant Drug Interactions for DOVATO: Alterations in Dose May Be Recommended Based on Drug Interaction Trials or Predicted Interactions

Coadministered Drug Class: Drug Name Effect on Concentration Clinical Comment
Antiarrhythmic:
Dofetilide
↑Dofetilide Coadministration is contraindicated with DOVATO [see CONTRAINDICATIONS].
Anticonvulsant: Carbamazepinea ↓Dolutegravir An additional dolutegravir 50-mg dose should be taken, separated by 12 hours from DOVATO [see DOSAGE AND ADMINISTRATION].
Anticonvulsants: Oxcarbazepine
Phenytoin
Phenobarbital
↓Dolutegravir Avoid coadministration with DOVATO because there are insufficient data to make dosing recommendations.
Antidiabetic:
Metformina
↑Metformin Refer to the prescribing information for metformin for assessing the benefit and risk of concomitant use of DOVATO and metformin.
Antimycobacterial:
Rifampina
↓Dolutegravir An additional 50-mg dose of dolutegravir should be taken, separated by 12 hours from DOVATO [see DOSAGE AND ADMINISTRATION].
Herbal product: St. John’s wort (Hypericum perforatum) ↓Dolutegravir Avoid coadministration with DOVATO because there are insufficient data to make dosing recommendations.
Medications containing polyvalent cations (e.g., Mg or Al): Cation-containing antacidsa or laxatives
Sucralfate Buffered medications
↓Dolutegravir Administer DOVATO 2 hours before or 6 hours after taking medications containing polyvalent cations.
Oral calcium and iron supplements, including multivitamins containing calcium or irona ↓Dolutegravir When taken with food, DOVATO and supplements or multivitamins containing calcium or iron can be taken at the same time. Under fasting conditions, DOVATO should be taken 2 hours before or 6 hours after taking supplements containing calcium or iron.
Potassium channel blocker: Dalfampridine ↑Dalfampridine Elevated levels of dalfampridine increase the risk of seizures. The potential benefits of taking dalfampridine concurrently with DOVATO should be considered against the risk of seizures in these patients.
Sorbitola ↓Lamivudine When possible, avoid use of sorbitol-containing medicines with DOVATO.
↑ = Increase, ↓ = Decrease.
a See CLINICAL PHARMACOLOGY  Table 8 or Table 9 for magnitude of interaction.

Read the entire FDA prescribing information for Dovato (Dolutegravir and Lamivudine Tablets)

© Dovato Patient Information is supplied by Cerner Multum, Inc. and Dovato Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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