Abacavir-Dolutegravir-Lamivudine

Abacavir-Dolutegravir-Lamivudine is a combination medication used for the treatment of human immunodeficiency virus type 1 (HIV-1) infection.

• Abacavir-Dolutegravir-Lamivudine is available under the following different brand names: Triumeq, Triumeq PD

Common side effects of Abacavir-Dolutegravir-Lamivudine include:

• insomnia
• headache
• fatigue
• diarrhea
• nausea
• vomiting
• fever
• loss of appetite
• low energy
• nightmares or abnormal dreams
• abnormal body fat distribution
• numbness and tingling
• hypersensitivity reactions (fever, rash, shortness of breath, cough, or sore throat)
• joint pain or swelling
• muscle pain
• extremity swelling
• depression
• dizziness
• spinning sensation (vertigo)

Serious side effects of Abacavir-Dolutegravir-Lamivudine include:

• hives
• difficulty breathing
• swelling of the face, lips, tongue, or throat
• fever
• rash
• nausea
• vomiting
• diarrhea
• stomach pain
• general ill feelings
• extreme tiredness
• body aches
• shortness of breath
• cough
• sore throat
• unusual muscle pain
• trouble breathing
• stomach pain
• irregular heart rate
• dizziness
• feeling cold
• weakness
• tiredness
• swelling around the midsection
• right-sided upper stomach pain
• loss of appetite
• dark urine
• clay-colored stools
• yellowing of the skin or eyes (jaundice)
• chest pain or pressure
• pain spreading to the jaw or shoulder
• sweating

Rare side effects of Abacavir-Dolutegravir-Lamivudine include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Tablet for oral use

• 600 mg/50 mg/300 mg

Tablet for oral suspension

• 60 mg/5 mg/30 mg

HIV-1 Infection

Adult dosage

• 1 tablet (600 mg/50 mg/300 mg) orally once a day

Pediatric dosage

• Children weighing below 6 kg: Safety and efficacy not established.
• Triumeq PD: Weight 6 to less than 25 kg
• Triumeq: Weight at least 25 kg
• Triumeq PD (tablet for oral suspension)
  • Contains 60 mg/5 mg/30 mg per tablet; dissolve in 20 mL of drinking water before administration.
  • 6 to less than 10 kg: 3 tablets (180 mg abacavir, 15 mg dolutegravir, and 90 mg lamivudine) orally once a day.
  • 10 to less than 14 kg: 4 tablets (240 mg/20 mg/120 mg) orally once a day.
  • 14 to less than 20 kg: 5 tablets (300 mg/25 mg/150 mg) orally once a day.
  • 20 to less than 25 kg: 6 tablets (360 mg/30 mg/180 g) orally once a day.
• Triumeq (tablet for oral use)
  • Weighing 25 kg and more: 1 tablet (600 mg/50 mg/300 mg orally once a day.

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Abacavir-Dolutegravir-Lamivudine has severe interactions with the following drugs:
  • dofetilide
• elvitegravir/cobicistat/emtricitabine/tenofovir DF
• Abacavir-Dolutegravir-Lamivudine has serious interactions with at least 27 other drugs.
• Abacavir-Dolutegravir-Lamivudine has moderate interactions with at least 50 other drugs.
• Abacavir-Dolutegravir-Lamivudine has minor interactions with the following drugs:
  • ethanol
  • isavuconazonium sulfate

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Presence of HLA-B*5701 allele
• Previous hypersensitivity reaction to Abacavir, Dolutegravir, or Lamivudine
• Coadministration with dofetilide
• Moderate or severe hepatic impairment

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Abacavir-Dolutegravir-Lamivudine?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Abacavir-Dolutegravir-Lamivudine?”

Cautions

• Cases of hepatic toxicity, including elevated serum liver biochemistries, hepatitis, and acute liver failure, reported in patients, including pediatric patients receiving a raltegravir-containing regimen who had no preexisting hepatic disease or other identifiable risk factors; drug-induced liver injury leading to liver transplant reported with therapy; monitoring for hepatotoxicity recommended
• Hepatic adverse events reported in patients receiving raltegravir-containing regimens; patients with underlying hepatitis B or C may be at increased risk for worsening or development of transaminase elevations
• Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, reported with nucleoside analogs, including abacavir and lamivudine; suspend treatment if a patient develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity, including hepatomegaly and steatosis even if marked transaminase elevations are absent
• An ongoing observational study showed an association between dolutegravir and an increased risk for neural tube defects when dolutegravir was administered at the time of conception and in early pregnancy
• Different formulations of Abacavir-Dolutegravir-Lamivudine are not interchangeable; adjust the dose if pediatric patients switch from tablets for oral suspension to tablets
• Hypersensitivity
  • Hypersensitivity reactions were reported and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury
  • Discontinue immediately if signs or symptoms of hypersensitivity reactions develop (including but not limited to severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters or peeling of the skin, oral blisters or lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, difficulty breathing)
  • Delay in stopping treatment after hypersensitivity onset may result in a life-threatening reaction
  • Clinically, it is not possible to determine whether a hypersensitivity reaction was caused by abacavir or dolutegravir; therefore, never restart other abacavir- or dolutegravir-containing products
• HIV-1 and HBV coinfection
  • Test all patients for the presence of HBV before initiating treatment for HIV
  • Safety and efficacy of lamivudine have not been established for the treatment of chronic HBV in patients coinfected with HIV-1 and HBV; the emergence of HBV variants associated with resistance to lamivudine reported in HIV-1−infected patients who have received lamivudine-containing antiretroviral regimens in the presence of concurrent infection with HBV
  • If the lamivudine-containing product is used, consider additional treatment for appropriate treatment of chronic HBV; otherwise, consider an alternative regimen
  • Severe acute exacerbations of HBV were reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing lamivudine
  • Patients coinfected with HIV-1 and HBV who discontinue therapy should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment; if necessary, initiation of anti-HBV therapy may be warranted, especially in patients with advanced liver disease or cirrhosis, since posttreatment exacerbation of hepatitis may lead to hepatic decompensation and liver failure
• Immune reconstitution syndrome
  • Immune reconstitution syndrome reported with combination ART therapy
  • During the initial phase of antiretroviral treatment (ART), patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (eg, Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment
  • Autoimmune disorders (eg., Graves’ disease, polymyositis, Guillain-Barré syndrome, autoimmune hepatitis) are also reported to occur in the setting of immune reconstitution; however, time to onset is more variable and can occur many months after treatment initiation
• MI risk
  • Several prospective, observational, epidemiological studies report an association between abacavir and the risk of myocardial infarction (MI); meta-analyses of randomized, controlled clinical trials have observed no excess risk of MI in abacavir-treated patients compared with control subjects
  • To date, there is no established biological mechanism to explain a potential increased risk.
  • In totality, available data from observational studies and controlled clinical trials show inconsistency; therefore, evidence for a causal relationship between abacavir and MI is inconclusive
• Drug interactions overview
  • Dolutegravir is primarily metabolized by UGT1A1, with some contribution from CYP3A. It is also a substrate of UGT1A3, UGT1A9, BCRP, and P-gp
  • Coadministration with certain drugs may result in known or potentially significant drug interactions, some of which may lead to loss of therapeutic effect and possible resistance or significant adverse reactions of others from increased systemic exposure
  • UGT1A1 and CYP3A inducers
    • Avoid or modify dosage regimen with additional dolutegravir dose or additional ARTs (see prescribing information)
    • Inducers of UGT1A1 and CYP3A (eg, etravirine, efavirenz, oxcarbazepine, phenytoin, phenobarbital, carbamazepine, St John’s wort, rifampin) decrease dolutegravir.
  • Drugs containing polyvalent cations
    • Administer dolutegravir 2 hours before or 6 hours after polyvalent cations
    • Coadministration with medications containing polyvalent cations (eg, magnesium, aluminum, calcium, iron) decreases dolutegravir systemic exposure; examples include antacids, laxatives, sucralfate, iron supplements, calcium supplements, and buffered medications
  • Drugs eliminated via OCT2 or MATE1
    • Contraindicated with dofetilide owing to the potential for increased dofetilide levels
    • Monitor other OCT2 or MATE1 substrates for increased systemic exposure/toxicity
    • Dolutegravir may increase plasma concentrations of drugs eliminated via OCT2 or MATE1 (dofetilide, dalfampridine, and metformin)

Pregnancy and Lactation

• Pregnancy exposure registry to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263
• Dolutegravir has been shown to cross the placenta; there are insufficient data on the use of Abacavir-Dolutegravir-Lamivudine during pregnancy to evaluate the drug-associated risk for birth defects and miscarriage
• Pregnancy testing is recommended in women of childbearing potential before initiation
• Advice adolescents and adults of childbearing potential, including those actively trying to become pregnant, of the potential risk for neural tube defects; assess risks and benefits of therapy and discuss with the patient to determine if an alternative treatment should be considered at the time of conception through the first trimester of pregnancy or if pregnancy is confirmed in the first trimester
• Initiation of therapy is not recommended in individuals actively trying to become pregnant unless there is no suitable alternative; a benefit-risk assessment should consider factors such as the feasibility of switching, tolerability, ability to maintain viral suppression, and risk of transmission to infant against the risk for neural tube defects
• Contraception
  • Counsel adolescents and adults of childbearing potential regarding the consistent use of effective contraception
  • Potential risk for neural tube birth defects
  • Serious cases of neural tube birth defects involving the brain, spine, and spinal cord are reported in babies born to women treated with dolutegravir
  • Preliminary results from an ongoing observational study in Botswana found women who had received dolutegravir at the time of becoming pregnant or early in the first trimester appear to be at higher risk for these defects; to date, in this observational study there are no reported cases of babies born with neural tube defects to women starting dolutegravir later in pregnancy
• Recommendations
  • Patients should not discontinue dolutegravir without consulting a healthcare professional because stopping the medicine can worsen the HIV infection
  • Pregnant women discontinuing dolutegravir-containing regimens without switching to alternative HIV medicines could cause the amount of virus to increase and spread HIV to their baby
  • In patients who take a dolutegravir-containing regimen at the time of becoming pregnant and during the first trimester of pregnancy, there is a potential risk for neural tube defects; neural tube defects happen early in pregnancy before many women even know they are pregnant
  • Inform women of childbearing age about the potential risk for neural tube defects when a dolutegravir-containing regimen is used at the time of conception and early in pregnancy; women of childbearing age should consult their healthcare providers about other non-dolutegravir-containing antiretroviral medicine
  • Healthcare providers should weigh the benefits and the risks of dolutegravir when prescribing antiretroviral medicines to women of childbearing age; consider alternative antiretroviral medicines; discuss the relative risks and benefits of appropriate alternative antiretroviral therapies
  • Women of childbearing age who decide to take a dolutegravir-containing regimen should consistently use effective birth control (contraception) while on HIV treatment; women should discuss with their healthcare professionals an effective birth control method to use while taking a dolutegravir-containing regimen
  • Perform pregnancy testing before initiating a dolutegravir-containing regimen in women of childbearing age to exclude pregnancy
• Lactation
  • The Centers for Disease Control and Prevention (CDC) does not recommend HIV-1-infected mothers in the US to breastfeed their infants to avoid the risk for postnatal transmission of HIV-1 infection
  • Abacavir, dolutegravir, and lamivudine are present in human milk
  • When administered to lactating rats, dolutegravir was found to be present in milk
  • There is no information on the effects of Abacavir-Dolutegravir-Lamivudine or its components on the breastfed infant or milk production; instruct mothers not to breastfeed as there is a potential for HIV-1 transmission in HIV-negative infants, developing viral resistance (in HIV-positive infants), and serious adverse reactions in a breastfed infant