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Tivicay

Last reviewed on RxList: 4/3/2020
Tivicay Side Effects Center

What Is Tivicay?

Tivicay (dolutegravir) is an integrase strand transfer inhibitor (INSTI) used in combination with other antiretroviral agents to treat human immunodeficiency virus type 1 (HIV-1) infection in adults and children aged 12 years and older.

What Are Side Effects for Tivicay?

Common side effects of Tivicay include:

  • trouble sleeping (insomnia),
  • tiredness,
  • headache,
  • allergic reactions such as rash,
  • changes in liver tests,
  • changes in body fat (especially in your back, neck, and trunk),
  • changes in your immune system,
  • depression,
  • abnormal dreams,
  • dizziness,
  • headache,
  • nausea,
  • diarrhea,
  • skin rash,
  • fatigue, and
  • spinning sensation (vertigo).

Dosage for Tivicay

The recommended dose of Tivicay is 50 mg administered orally once or twice daily.

What Drugs, Substances, or Supplements Interact with Tivicay?

Tivicay may interact with:

  • other HIV/AIDS medicines;
  • antacids or laxatives that contain aluminum, magnesium or calcium;
  • sucralfate;
  • iron or calcium supplements, or
  • buffered medicines;
  • anti-seizure medicines,
  • St. John's wort,
  • metformin, or
  • rifampin

Tell your doctor all medications and supplements you use.

Tivicay During Pregnancy and Breastfeeding

It is unknown if Tivicay will harm a fetus. Tell your doctor if you become pregnant while taking this drug. There is a registry for women who take antiviral medicines during pregnancy. It is unknown if this drug passes into breast milk. Because breast milk can transmit HIV, do not breastfeed.

Additional Information

Our Tivicay (dolutegravir) 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.

SLIDESHOW

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Tivicay Professional Information

SIDE EFFECTS

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

  • Hypersensitivity reactions [see WARNINGS AND PRECAUTIONS].
  • Hepatotoxicity [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 practice.

Clinical Trials Experience In Adult Subjects

Treatment-Naive Subjects

The safety assessment of TIVICAY in HIV-1–infected treatmentnaive subjects is based on the analyses of data from 2 international, multicenter, double-blind trials, SPRING-2 (ING113086) and SINGLE (ING114467) and data from the international, multicenter, open-label FLAMINGO (ING114915) trial.

In SPRING-2, 822 subjects were randomized and received at least 1 dose of either TIVICAY 50 mg once daily or raltegravir 400 mg twice daily, both in combination with fixed-dose dual nucleoside reverse transcriptase inhibitor (NRTI) treatment (either abacavir sulfate and lamivudine [EPZICOM] or emtricitabine/tenofovir [TRUVADA]). There were 808 subjects included in the efficacy and safety analyses. Through 96 weeks, the rate of adverse events leading to discontinuation was 2% in both treatment arms.

In SINGLE, 833 subjects were randomized and received at least 1 dose of either TIVICAY 50 mg with fixed-dose abacavir sulfate and lamivudine (EPZICOM) once daily or fixed-dose efavirenz/emtricitabine/tenofovir (ATRIPLA) once daily (study treatment was blinded through Week 96 and open-label from Week 96 through Week 144). Through 144 weeks, the rates of adverse events leading to discontinuation were 4% in subjects receiving TIVICAY 50 mg once daily + EPZICOM and 14% in subjects receiving ATRIPLA once daily.

Treatment-emergent adverse reactions (ARs) of moderate to severe intensity observed in at least 2% of subjects in either treatment arm in SPRING-2 and SINGLE trials are provided in Table 3. Side-by-side tabulation is to simplify presentation; direct comparisons across trials should not be made due to differing trial designs.

Table 3. Treatment-Emergent Adverse Reactions of at Least Moderate Intensity (Grades 2 to 4) and at Least 2% Frequency in Treatment-Naive Subjects in SPRING-2 (Week 96 Analysis) and SINGLE Trials (Week 144 Analysis)

System Organ Class/ Preferred TermSPRING-2SINGLE
TIVICAY
50 mg Once
Daily + 2 NRTIs
(n = 403)
Raltegravir
400 mg Twice
Daily + 2 NRTIs
(n = 405)
TIVICAY
50 mg + EPZICOM Once Daily
(n = 414)
ATRIPLA
Once Daily
(n = 419)
Psychiatric
  Insomnia<1%<1%3%3%
  Depression<1%<1%1%2%
  Abnormal dreams<1%<1%<1%2%
Nervous System
  Dizziness<1%<1%<1%5%
  Headache<1%<1%2%2%
Gastrointestinal
  Nausea1%1%<1%3%
  Diarrhea<1%<1%<1%2%
Skin and Subcutaneous
Tissue
  Rasha0<1%<1%6%
General Disorders
  Fatigue<1%<1%2%2%
Ear and Labyrinth
  Vertigo0<1%02%
a Includes pooled terms: rash, rash generalized, rash macular, rash maculo-papular, rash pruritic, and drug eruption.

In addition, Grade 1 insomnia was reported by 1% and less than 1% of subjects receiving TIVICAY and raltegravir, respectively, in SPRING-2; whereas in SINGLE the rates were 7% and 4% for TIVICAY and ATRIPLA, respectively. These events were not treatment limiting. In a multicenter, open-label trial (FLAMINGO), 243 subjects received TIVICAY 50 mg once daily versus 242 subjects who received darunavir 800 mg/ritonavir 100 mg once daily, both in combination with investigator-selected NRTI background regimen (either EPZICOM or TRUVADA). There were 484 subjects included in the efficacy and safety analyses. Through 96 weeks, the rates of adverse events leading to discontinuation were 3% in subjects receiving TIVICAY and 6% in subjects receiving darunavir/ritonavir. The ARs observed in FLAMINGO were generally consistent with those seen in SPRING-2 and SINGLE.

Treatment-Experienced, Integrase Strand Transfer Inhibitor-Naive Subjects

In an international, multicenter, double-blind trial (ING111762, SAILING), 719 HIV-1–infected, antiretroviral treatment-experienced adults were randomized and received either TIVICAY 50 mg once daily or raltegravir 400 mg twice daily with investigator-selected background regimen consisting of up to 2 agents, including at least one fully active agent. At 48 weeks, the rates of adverse events leading to discontinuation were 3% in subjects receiving TIVICAY 50 mg once daily + background regimen and 4% in subjects receiving raltegravir 400 mg twice daily + background regimen.

The only treatment-emergent AR of moderate to severe intensity with at least 2% frequency in either treatment group was diarrhea, 2% (6 of 354) in subjects receiving TIVICAY 50 mg once daily + background regimen and 1% (5 of 361) in subjects receiving raltegravir 400 mg twice daily + background regimen.

Treatment-Experienced, Integrase Strand Transfer Inhibitor-Experienced Subjects

In a multicenter, open-label, single-arm trial (ING112574, VIKING-3), 183 HIV-1–infected, antiretroviral treatment-experienced adults with virological failure and current or historical evidence of raltegravir and/or elvitegravir resistance received TIVICAY 50 mg twice daily with the current failing background regimen for 7 days and with optimized background therapy from Day 8. The rate of adverse events leading to discontinuation was 4% of subjects at Week 48.

Treatment-emergent ARs in VIKING-3 were generally similar compared with observations with the 50-mg once-daily dose in adult Phase 3 trials.

Virologically Suppressed Subjects: The ARs observed for TIVICAY plus rilpivirine in the Week 48 analysis of pooled data from 2 identical, international, multicenter, open-label trials (SWORD-1 and SWORD-2) of 513 HIV-1–infected, virologically suppressed subjects switching from their current antiretroviral regimen to dolutegravir plus rilpivirine, were consistent with the AR profiles and severities for the individual components when administered with other antiretroviral agents. There were no ARs (Grades 2 to 4) with an incidence of at least 2% in either treatment arm. The rates of adverse events leading to discontinuation were 4% in subjects receiving TIVICAY plus rilpivirine once daily and less than 1% in subjects who remained on their current antiretroviral regimen.

Less Common Adverse Reactions Observed in Treatment-Naive and Treatment-Experienced Trials

The following ARs occurred in less than 2% of treatment-naive or treatment-experienced subjects receiving TIVICAY in a combination regimen in any one trial. These events have been included because of their seriousness and assessment of potential causal relationship.

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

Hepatobiliary Disorders: Hepatitis.

Musculoskeletal Disorders: Myositis.

Psychiatric Disorders: 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.

Laboratory Abnormalities

Treatment-Naive Subjects: Selected laboratory abnormalities (Grades 2 to 4) with a worsening grade from baseline and representing the worst-grade toxicity in at least 2% of subjects are presented in Table 4. The mean change from baseline observed for selected lipid values is presented in Table 5. Side-by-side tabulation is to simplify presentation; direct comparisons across trials should not be made due to differing trial designs.

Table 4. Selected Laboratory Abnormalities (Grades 2 to 4) in Treatment-Naive Subjects in SPRING-2 (Week 96 Analysis) and SINGLE Trials (Week 144 Analysis)

Laboratory Parameter Preferred TermSPRING-2SINGLE
TIVICAY
50 mg Once
Daily + 2 NRTIs
(n = 403)
Raltegravir
400 mg Twice
Daily + 2 NRTIs
(n = 405)
TIVICAY
50 mg + EPZICOM
Once Daily
(n = 414)
ATRIPLA
Once Daily (n = 419)
ALT
  Grade 2 (>2.5-5.0 x ULN)4%4%3%5%
  Grade 3 to 4 (>5.0 x ULN)2%2%1%<1%
AST
  Grade 2 (>2.5-5.0 x ULN)5%3%3%4%
  Grade 3 to 4 (>5.0 x ULN)3%2%1%3%
Total Bilirubin
  Grade 2 (1.6-2.5 x ULN)3%2%<1%<1%
  Grade 3 to 4 (>2.5 x ULN)<1%<1%<1%<1%
Creatine kinase
  Grade 2 (6.0-9.9 x ULN)2%5%5%3%
  Grade 3 to 4 (≥10.0 x ULN)7%4%7%8%
Hyperglycemia
  Grade 2 (126-250 mg/dL)6%6%9%6%
  Grade 3 (>250 mg/dL)<1%2%2%<1%
Lipase
  Grade 2 (>1.5-3.0 x ULN)7%7%11%11%
  Grade 3 to 4 (>3.0 x ULN)2%5%5%4%
Total neutrophils
  Grade 2 (0.75-0.99 x 109)4%3%4%5%
  Grade 3 to 4 (<0.75 x 109)2%2%3%3%
ULN = Upper limit of normal.

Table 5. Mean Change from Baseline in Fasted Lipid Values in Treatment-Naive Subjects in SPRING-2 (Week 96 Analysisa) and SINGLE Trials (Week 144 Analysisa)

Laboratory Parameter
Preferred Term
SPRING-2SINGLE
TIVICAY
50 mg Once
Daily + 2 NRTIs
(n = 403)
Raltegravir
400 mg Twice
Daily + 2 NRTIs
(n = 405)
TIVICAY
50 mg + EPZICOM
Once Daily
(n = 414)
ATRIPLA
Once Daily
(n = 419)
Cholesterol (mg/dL)8.110.124.026.7
HDL cholesterol (mg/dL)2.02.35.47.2
LDL cholesterol (mg/dL)5.16.116.014.6
Triglycerides (mg/dL)6.76.613.631.9
a Subjects on lipid-lowering agents at baseline were excluded from these analyses (19 subjects in each arm in SPRING-2, and in SINGLE: TIVICAY + EPZICOM n = 30 and ATRIPLA n = 27). Ninety-four subjects initiated a lipid-lowering agent post-baseline; their last fasted ontreatment values (prior to starting the agent) were used regardless if they discontinued the agent (SPRING-2: TIVICAY n = 9, raltegravir n = 13; SINGLE: TIVICAY + EPZICOM n = 36, ATRIPLA n = 36).

Laboratory abnormalities observed in the FLAMINGO trial were generally consistent with observations in SPRING-2 and SINGLE.

Treatment-Experienced, Integrase Strand Transfer Inhibitor-Naive Subjects: Laboratory abnormalities observed in SAILING were generally similar compared with observations seen in the treatment-naive (SPRING-2 and SINGLE) trials.

Treatment-Experienced, Integrase Strand Transfer Inhibitor-Experienced Subjects: The most common treatment-emergent laboratory abnormalities (greater than 5% for Grades 2 to 4 combined) observed in VIKING-3 at Week 48 were elevated ALT (9%), AST (8%), cholesterol (10%), creatine kinase (6%), hyperglycemia (14%), and lipase (10%). Two percent (4 of 183) of subjects had a Grade 3 to 4 treatment-emergent hematology laboratory abnormality, with neutropenia (2% [3 of 183]) being the most frequently reported.

Virologically Suppressed Adults: Laboratory abnormalities observed in SWORD-1 and SWORD-2 were generally similar compared with observations seen in the other Phase 3 trials.

Hepatitis B and/or Hepatitis C Virus Co-infection: In Phase 3 trials, subjects with hepatitis B and/or C virus co-infection were permitted to enroll provided that baseline liver chemistry tests did not exceed 5 times the upper limit of normal. Overall, the safety profile in subjects with hepatitis B and/or C virus co-infection was similar to that observed in subjects without hepatitis B or C co-infection, although the rates of AST and ALT abnormalities were higher in the subgroup with hepatitis B and/or C virus co-infection for all treatment groups. Grades 2 to 4 ALT abnormalities in hepatitis B and/or C co-infected compared with HIV monoinfected subjects receiving TIVICAY were observed in 18% vs. 3% with the 50-mg once-daily dose and 13% vs. 8% with the 50-mg twice-daily dose. Liver chemistry elevations consistent with immune reconstitution syndrome were observed in some subjects with hepatitis B and/or C at the start of therapy with TIVICAY, particularly in the setting where anti-hepatitis therapy was withdrawn [see WARNINGS AND PRECAUTIONS].

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 and remained stable through 96 weeks. In treatment-naive subjects, a mean change from baseline of 0.15 mg per dL (range: -0.32 mg per dL to 0.65 mg per dL) was observed after 96 weeks of treatment. Creatinine increases were comparable by background NRTIs and were similar in treatment-experienced subjects.

Clinical Trials Experience In Pediatric Subjects

IMPAACT P1093 is an ongoing multicenter, open-label, non-comparative trial of approximately 160 HIV-1–infected pediatric subjects aged 4 weeks to less than 18 years, of which 46 treatmentexperienced, INSTI-naive subjects aged 6 to less than 18 years have been enrolled [see Use In Specific Populations, Clinical Studies].

The adverse reaction profile was similar to that for adults. Grade 2 ARs reported by more than one subject were decreased neutrophil count (n = 3) and diarrhea (n = 2). There were no Grade 3 or 4 drug-related ARs reported. No ARs led to discontinuation.

The Grade 3 or 4 laboratory abnormalities reported in more than one subject were elevated total bilirubin (n = 3) and decreased neutrophil count (n = 2). The changes in mean serum creatinine were similar to those observed in adults.

Postmarketing Experience

In addition to adverse reactions reported from clinical trials, the following adverse reactions have been identified during postmarketing use. Because these 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.

Hepatobiliary Disorders

Acute liver failure, hepatotoxicity.

Investigations

Weight increased.

Musculoskeletal

Arthralgia, myalgia.

Psychiatric

Anxiety

Read the entire FDA prescribing information for Tivicay (Doutegravir 50mg Tablets)

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

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