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Information ⬇

abacavir/dolutegravir/lamivudine

a-bak-a-veer/doe-loo-teg-ra-vir/lamiv-yoo-deen

Trade Name(s): (Triumeq, Triumeq PD)

BLACK BOX ALERT Serious, sometimes fatal hypersensitivity reactions, lactic acidosis, severe hepatomegaly with steatosis (fatty liver) have occurred with abacavir-containing products, esp. in pts who carry the HLA-B*5701 allele. Restarting abacavir following a hypersensitivity reaction may be life-threatening. May cause hepatitis B virus reactivation.

Do not confuse abacavir with entecavir, or dolutegravir with elvitegravir or raltegravir, or lamivudine with telbivudine or lamotrigine.

FIXED-COMBINATION(S)

abacavir/dolutegravir/lamivudine (antiretrovirals): Tablet: 600 mg/50 mg/300 mg. Tablet for Oral Suspension: 60 mg/5 mg/30 mg.

Classification ⬆ ⬇

Uses ⬆ ⬇

Treatment of HIV-1 infection in adults and children weighing at least 10 kg.

Precautions ⬆ ⬇

Contraindications: Hypersensitivity to abacavir, dolutegravir, lamivudine. Pts who test positive for the HLA-B*5701 allele. Concomitant use of dofetilide. Pts with moderate to severe hepatic impairment. Cautions: Diabetes, hepatic/renal impairment, coronary artery disease, history of hepatitis or tuberculosis, prior hypersensitivity reaction to INSTIs. Use in children with history of pancreatitis or risk factors for developing pancreatitis. Not recommended in pts with resistance-associated integrase substitutions or clinically suspected integrase strand transfer inhibitor resistance; creatinine clearance less than 50 mL/min; mild hepatic impairment; children weighing less than 40 kg.

Action ⬆ ⬇

Abacavir inhibits activity of HIV-1 reverse transcriptase. Dolutegravir inhibits HIV integrase by blocking strand transfer step of retroviral DNA integration (essential for HIV replication cycle). Lamivudine inhibits reverse transcriptase by viral DNA chain termination. Therapeutic Effect: Interferes with HIV replication, slowing progression of HIV infection.

Pharmacokinetics ⬆ ⬇

Abacavir, lamivudine rapidly absorbed and widely distributed. Abacavir distributes into cerebrospinal fluid (CSF) and erythrocytes. Abacavir metabolized by alcohol dehydrogenase and glucuronyl transferase. Dolutegravir metabolized in liver. Protein binding: abacavir: 50%; dolutegravir: 98.9%; lamivudine: less than 36%. Peak plasma concentration: dolutegravir: 2–3 hrs. Excretion: abacavir: urine (primary); dolutegravir: feces (53%), urine (31%); lamivudine: urine (70%). Half-life: abacavir: 1.5 hrs; dolutegravir: 14 hrs; lamivudine: 5–7 hrs.

Lifespan Considerations ⬆ ⬇

Pregnancy/Lactation: Breastfeeding not recommended due to risk of postnatal HIV transmission. Unknown if distributed in breast milk. Children: Safety and efficacy not established in pts weighing less than 10 kg. Elderly: May have increased risk of adverse effects; worsening of hepatic, renal, cardiac function.

Interactions ⬆ ⬇

DRUG: Dolutegravir may increase concentration/effect of dofetilide (contraindicated). Fosphenytoin, phenytoin, nevirapine, oxcarbazepine, phenobarbital, primidone may decrease concentration of dolutegravir. Lamivudine may increase adverse/toxic effects of emtricitabine. HERBAL: St. John's wort may decrease effect of dolutegravir. FOOD: None known. LAB VALUES: May increase serum amylase, ALT, AST, bilirubin, cholesterol, creatine kinase (CK), creatinine, glucose, lipase, triglycerides. May decrease Hgb, Hct, neutrophils.

Availability ⬆ ⬇

Fixed-Dose Combination Tablet: abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg. Fixed-Dose Combination Tablet for Oral Suspension: abacavir 60 mg/dolutegravir 5 mg/lamivudine 30 mg.

Administration/Handling ⬆ ⬇

PO
  • Give without regard to food. Administer tablet whole; do not break, cut, or crush. Tablets cannot be chewed.
  • Administer at least 2 hrs before or at least 6 hrs after giving medications containing aluminum, calcium, iron, magnesium (supplements, antacids, laxatives).
  • Fully disperse tablets for oral suspension in 20 mL of water. Swirl suspension until no lumps remain. Give within 30 min of mixing.

Indications/Routes/Dosage ⬆ ⬇

HIV Infection

PO: ADULTS, ELDERLY, CHILDREN WEIGHING 25 KG OR MORE: 1 tablet once daily. 20–24 KG: 6 tablets for oral suspension once daily. 14–19 KG: 5 tablets for oral suspension once daily. 10–13 KG: 4 tablets for oral suspension once daily.

Dosage in Renal Impairment

Creatinine clearance less than 50 mL/min: Not recommended.

Dosage in Hepatic Impairment

Mild impairment: Consider use of individual components. Moderate to severe impairment: Contraindicated.

Side Effects ⬆ ⬇

Rare (3%–1%): Insomnia, fatigue, headache, abdominal pain/distension, dyspepsia, flatulence, gastroesophageal reflux disease, fever, lethargy, anorexia, arthralgia, myositis, somnolence, pruritus, depression, abnormal dreams, dizziness, nausea, diarrhea, rash.

Adverse Effects/Toxic Reactions ⬆ ⬇

Serious and sometimes fatal hypersensitivity reactions including anaphylaxis, severe diarrhea, dyspnea, hypotension, intractable nausea/vomiting, multiorgan failure, pharyngitis may occur within the first 6 wks of treatment with abacavir (8% of pts). If therapy is discontinued, pts co-infected with hepatitis B or C virus have an increased risk for viral replication, worsening of hepatic function, and may experience hepatic decompensation and/or failure. May induce immune recovery syndrome (inflammatory response to dormant opportunistic infections such as Mycobacterium avium, cytomegalovirus, PCP, tuberculosis, or acceleration of autoimmune disorders such as Graves' disease, polymyositis, Guillain-Barré). Fatal cases of lactic acidosis, severe hepatomegaly with steatosis have been reported. Hepatic failure occurred in 1% of pts taking dolutegravir-containing products. Abacavir-containing products may increase risk of myocardial infarction, erythema multiform, Stevens-Johnson Syndrome, toxic epidermal necrolysis. May increase risk of pancreatitis.

Nursing Considerations ⬆

  • BASELINE ASSESSMENT Obtain CBC, BMP, LFT, CD4+ count, viral load, HIV-1 RNA level. Obtain weight in kilograms. Screen for HLA-B* 5701 allele, hepatitis B or C virus infection before initiating therapy. Question for prior hypersensitivity reactions (especially to abacavir-containing products); history of diabetes, coronary artery disease, hepatic/renal impairment. Receive full medication history, including herbal products. Offer emotional support. INTERVENTION/EVALUATION Monitor CBC, BMP, LFT periodically. Immediately discontinue if hypersensitivity reaction is suspected, even when other diagnoses are possible (e.g., pneumonia, bronchitis, pharyngitis, influenza, gastroenteritis, reactions to other medications). Stop treatment if 3 or more of the following symptoms occur: rash, fever, GI disturbances (diarrhea, nausea, vomiting), flu-like symptoms, respiratory distress. If hypersensitivity reaction is related to abacavir, do not restart treatment (may cause more severe reactions and/or death within hours). Assess for hepatic impairment (bruising, hematuria, jaundice, right upper abdominal pain, nausea, vomiting, weight loss). Screen for immune recovery syndrome, rhabdomyolysis (muscle weakness, myalgia, decreased urinary output). Pediatric pts should be closely monitored for symptoms of pancreatitis (severe, steady abdominal pain often radiating to the back; clammy skin, reduced B/P; nausea and vomiting accompanied by abdominal pain). Monitor daily stool pattern, consistency; I&Os. Assess dietary pattern; monitor for weight loss. Screen for toxic skin reactions. Monitor for symptoms of MI (jaw/chest/left arm pain or pressure, dyspnea, diaphoresis, vomiting). PATIENT/FAMILY TEACHING
  • Treatment does not cure HIV infection nor reduce risk of transmission. Practice safe sex with barrier methods or abstinence.
  • As immune system strengthens, it may respond to dormant infections hidden within the body. Report any new fever, chills, body aches, cough, night sweats, shortness of breath.
  • Antiretrovirals may cause excess body fat in upper back, neck, breast, trunk; may cause decreased body fat in legs, arms, face.
  • Drug resistance can form if therapy is interrupted for even a short time; do not run out of supply.
  • Report signs of abdominal pain, darkened urine, decreased urine output, yellowing of skin or eyes, clay colored stools, weight loss.
  • Do not breastfeed.
  • Small, frequent meals may offset anorexia, nausea.
  • Do not take newly prescribed medications, including OTC drugs, unless approved by doctor who originally started treatment.