Abacavir, dolutegravir, and lamivudine

Name: Abacavir, dolutegravir, and lamivudine

What is the most important information I should know about abacavir, dolutegravir, and lamivudine (Triumeq)?

You should not use this medicine if you have moderate or severe liver disease, or if you are also taking dofetilide (Tikosyn).

Stop using this medicine and call your doctor at once if you have any of these signs of an allergic reaction: fever; rash; nausea, vomiting, diarrhea, stomach pain; general ill feeling, extreme tiredness, body aches; shortness of breath, cough, sore throat.

Get emergency medical help if you have symptoms of lactic acidosis such as: muscle pain or weakness, numb or cold feeling in your arms and legs, trouble breathing, stomach pain, nausea with vomiting, fast or uneven heart rate, dizziness, or feeling very weak or tired.

If you have ever had hepatitis B, this condition may come back or get worse after you stop taking this medicine.

What other drugs will affect Triumeq?

Tell your doctor about all your current medicines and any you start or stop using, especially:

  • methadone, rifampin, St. John's wort;

  • any other medicine to treat HIV or AIDS;

  • medicine that contains metformin--Actos, Actoplus Met, Avandamet, Fortamet, Glucophage, Glucovance, Janumet, Jentadueto, Kazano, Kombiglyze, Metaglip, PrandiMet, Riomet, and others;

  • medicine to treat hepatitis--interferon, ribavirin; or

  • seizure medicine--carbamazepine, oxcarbazepine, phenobarbital, phenytoin.

This list is not complete. Other drugs may interact with Triumeq, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Precautions While Using abacavir, dolutegravir, and lamivudine

It is very important that your doctor check your progress at regular visits to make sure abacavir, dolutegravir, and lamivudine is working properly. Blood tests may be needed to check for unwanted effects.

You should not use abacavir, dolutegravir, and lamivudine together with dofetilide (Tikosyn®). Using these medicines together may cause serious or life-threatening side effects.

Serious allergic reactions may occur while taking abacavir, dolutegravir, and lamivudine. This reaction usually occurs within 6 weeks after the medicine is started, but may occur at any time. Check with your doctor right away if you have the following symptoms: a severe rash or rash with fever, blistering or peeling skin, diarrhea, nausea, vomiting, joint or muscle pain, sores in the mouth, swelling of the face, trouble breathing, unusual tiredness or weakness, or yellow eyes or skin.

When you begin taking abacavir, dolutegravir, and lamivudine, you will be given a warning card which describes symptoms of severe allergic reactions that may be caused by Triumeq®. The warning card also provides information about how to treat these allergic reactions. For your safety, you should carry the warning card with you at all times.

If you must stop using abacavir, dolutegravir, and lamivudine because of an allergic reaction, you should never use the medicine again. Return the unused medicine to your doctor or pharmacist. A worse reaction, possibly even death, can occur if you use the medicine again. Tell your doctor right away if you have ever taken abacavir, especially if you have experienced an allergic reaction to it in the past.

Two rare but serious reactions to abacavir, dolutegravir, and lamivudine are lactic acidosis (too much acid in the blood) and liver toxicity, which includes an enlarged liver. These are more common if you are female, very overweight (obese), or have been taking anti-HIV medicines for a long time. Call your doctor right away if you have more than one of these symptoms: abdominal or stomach discomfort or cramping, dark urine, decreased appetite, diarrhea, general feeling of discomfort, light-colored stools, muscle cramping or pain, nausea, unusual tiredness or weakness, trouble breathing, vomiting, or yellow eyes or skin.

Your immune system may get stronger when you start taking HIV medicines. Sometimes the immune system will start to fight infections that were hidden in your body, such as pneumonia or tuberculosis. Tell your doctor right away if you notice any changes in your health.

abacavir, dolutegravir, and lamivudine may cause you to have excess body fat. Tell your doctor right away if you notice changes in your body shape, including an increased amount of body fat in the neck or upper back, face, around the chest, or stomach area. You might also lose fat from your legs, arms, or face.

abacavir, dolutegravir, and lamivudine may increase your risk of having a heart attack. Symptoms include: chest pain or discomfort, pain or discomfort in the arms, jaw, back or neck, shortness of breath, nausea, sweating, or vomiting.

abacavir, dolutegravir, and lamivudine will not keep you from giving HIV to your partner during sex. Make sure you understand this and practice safe sex, even if your partner also has HIV, by using a latex condom or other barrier method. abacavir, dolutegravir, and lamivudine will also not keep you from giving HIV to other people if they are exposed to your blood. Do not re-use or share needles with anyone.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (eg, St. John's wort) or vitamin supplements.

Dosage Forms

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

Tablet, Oral:

Triumeq: Abacavir 600 mg, dolutegravir 50 mg, and lamivudine 300 mg

Pharmacology

Dolutegravir inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral DNA integration. Abacavir is converted by cellular enzymes to the active metabolite, carbovir triphosphate (CBV-TP), an analogue of deoxyguanosine-5′-triphosphate (dGTP). CBV-TP inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA. Intracellularly, lamivudine is phosphorylated to its active 5′-triphosphate metabolite, lamivudine triphosphate (3TC-TP). The principal mode of action of 3TC-TP is inhibition of reverse transcriptase via DNA chain termination after incorporation of the nucleotide analogue.

Dosing Hepatic Impairment

Mild impairment (Child-Pugh class A): Use is not recommended (use dose-adjusted individual component drugs).

Moderate to severe impairment (Child-Pugh class B or C): Use is contraindicated.

Storage

Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Dispense in original container; protect from moisture.

Warnings/Precautions

Also see individual agents.

Concerns related to adverse effects:

• Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance).

• Hypersensitivity reactions: [US Boxed Warning]: Serious hypersensitivity reactions (sometimes fatal) have occurred in patients taking abacavir (in Triumeq). Patients who carry the HLA-B*5701 allele are at a higher risk for a hypersensitivity reaction to abacavir, although hypersensitivity reactions have occurred in patients who do not carry the HLA-B*5701 allele. All patients should be screened for the HLA-B*5701 allele prior to initiating therapy with Triumeq or reinitiation of therapy with Triumeq unless patients have had a previously documented HLA-B*5701 allele assessment. Discontinue Triumeq if a hypersensitivity reaction is suspected. Triumeq is contraindicated in patients who have the HLA-B*5701 allele or in patients with a prior hypersensitivity reaction to abacavir. Reintroduction of Triumeq or any other abacavir-containing product can result in life-threatening or fatal hypersensitivity reactions, even in patients who have no history of hypersensitivity to abacavir therapy. Such reactions can occur within hours. Additionally, allele-positive patients (including abacavir treatment naive) should have an allergy to abacavir documented in their medical record. Reactions usually occur within 9 days of starting abacavir; ~90% occur within 6 weeks, although these reactions may occur at any time during therapy (HHS [adult] 2015). These reactions usualy include signs or symptoms in 2 or more of the following groups: fever, skin rash, GI symptoms (eg, abdominal pain, nausea, vomiting, diarrhea), constitutional (eg, generalized malaise, fatigue or achiness), or respiratory symptoms (eg, pharyngitis, dyspnea, cough). Other signs and symptoms include lethargy, headache, myalgia, edema, abnormal chest x-ray findings, arthralgia and paresthesia. Anaphylaxis, liver failure, renal failure, hypotension, adult respiratory distress syndrome, respiratory failure, myolysis, and death have occurred in association with hypersensitivity reactions. Physical findings (lymphadenopathy, mucous membrane lesions, and rash [maculopapular, urticarial or variable]) may occur. Erythema multiforme has also been reported. Laboratory abnormalities (eg, elevated liver function tests, elevated creatine phosphokinase, elevated creatinine, and lymphopenia) may occur. Triumeq should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible. Following a hypersensitivity reaction, Triumeq SHOULD NOT be restarted because more severe symptoms may occur within hours, including LIFE-THREATENING HYPOTENSION AND DEATH. If Triumeq is to be restarted following an interruption in therapy not associated with symptoms of a hypersensitivity reaction, carefully evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or cannot be ruled out regardless of HLA-B*5701 status. If Triumeq is restarted, continually monitor for symptoms of a hypersensitivity reaction. Make the patient aware that reintroduction should only take place if medical care is readily accessible.

- Hypersensitivity reactions reported with dolutegravir include rash, constitutional findings, and organ dysfunction (eg, liver injury). 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, liver function tests and initiate supportive therapy as appropriate. If hypersensitivity occurs, do not reinitiate therapy. Clinically, it is not possible to determine whether a hypersensitivity reaction is due to abacavir or dolutegravir. Do not restart Triumeq or any other abacavir or dolutegravir-containing product in patients who have stopped Triumeq therapy due to a hypersensitivity reaction.

• 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: [US Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with nucleoside analogues alone or in combination, including abacavir, lamivudine and other antiretrovirals. Discontinue if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur. Suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis).

• Pancreatitis: Pancreatitis has been observed with lamivudine and abacavir. Discontinue use if pancreatitis is suspected and resume only after pancreatitis has been ruled out.

Disease-related concerns:

• Chronic hepatitis B: [US Boxed Warning]: Exacerbation of hepatitis B has been reported with discontinuation of lamivudine in coinfected HIV/HBV patients; monitor hepatic function with clinical and laboratory evaluations closely for at least several months after discontinuing Triumeq in coinfected patients. Antihepatitis B therapy initiation may be warranted, if appropriate.

• Coronary heart disease: Use of abacavir within the previous 6 months was associated with an increased risk of myocardial infarction (MI) in observational studies; however, in a sponsor conducted pooled analysis of clinical trials, no excess risk of MI was observed. Available data are inconclusive. Consider using with caution in patients with risks for coronary heart disease and minimizing modifiable risk factors (eg, hypertension, hyperlipidemia, diabetes mellitus, smoking) prior to use.

• Emergence of lamivudine-resistant hepatitis B: HIV/HBV coinfected patients receiving lamivudine-containing antiretroviral regimens have developed lamivudine resistant HBV variants.

• Hepatic impairment: Triumeq, as a fixed-dose combination tablet, should not be used in patients with mild hepatic impairment; use is contraindicated in moderate to severe hepatic impairment.

• Renal impairment: Triumeq, as a fixed-dose combination tablet, should not be used in patients with CrCl <50 mL/minute.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

• Duplicate therapy: Concomitant use of other abacavir-, lamivudine-, or dolutegravir-containing products with the fixed-dose combination product should be avoided.

• Interferon alfa: Use with caution in combination with interferon alfa with or without ribavirin in HIV/HBV coinfected patients; monitor closely for hepatic decompensation (eg, Child-Pugh score >6), anemia, or neutropenia; dose reduction or discontinuation of interferon and/or ribavirin may be required if toxicity is evident.

Other warnings/precautions:

• Appropriate use: Triumeq, as a fixed-dose combination tablet, should not be used in patients requiring dosage adjustment.

• Laboratory abnormalities: HIV/HBV and HIV/HCV coinfected patients may be at increased risk for worsening or development of transaminase elevations. Some cases were consistent with immune reconstitution syndrome or HBV reactivation (especially when antihepatitis therapy was withdrawn). Laboratory tests should be performed at baseline and monitored during therapy in coinfected patients and those with underlying hepatic disease.

What special precautions should I follow?

Before taking abacavir, dolutegravir, and lamivudine,

  • tell your doctor and pharmacist if you are allergic to abacavir, dolutegravir, and lamivudine, any other medications, or any of the ingredients in abacavir, dolutegravir, and lamivudine tablets. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
  • tell your doctor if you are taking dofetilide (Tikosyn). Your doctor will probably tell you not to take abacavir, dolutegravir, and lamivudine if you are taking this medication.
  • tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, you are taking or plan to take. Be sure to mention any of the following: carbamazepine (Carbatrol, Equetro, Tegretol, others); other medications for HIV including abacavir (in Epzicom, in Trizivir, Ziagen), dolutegravir (Tivicay), efavirenz (Sustiva, in Atripla), emtricitabine (Emtriva, in Atripla, in Complera, in Truvada, others), etravirine (Intelence), fosamprenavir (Lexiva) taken with ritonavir (Norvir), lamivudine (Epivir, in Combivir, in Epzicom, in Trizivir, others), nevirapine (Viramune), and tipranavir (Aptivus) taken with ritonavir (Norvir); metformin (Fortomet, Glumetza, Glucophage, Riomet); methadone (Dolophine, Methadose); oxcarbazepine (Oxtellar XR, Trileptal); phenobarbital (Luminal); phenytoin (Dilantin, Phenytek); and rifampin (Rifadin, Rimactane, in Rifamate, in Rifater). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
  • if you are taking antacids or laxatives that contain aluminum, magnesium, or calcium; calcium supplements; iron supplements; sucralfate (Carafate); or buffered medications such as buffered aspirin, take abacavir, dolutegravir, and lamivudine at least 2 hours before or 6 hours after you take these medications.
  • tell your doctor what herbal products you are taking, especially St. John's wort. You should not take St. John's wort while you are taking abacavir, dolutegravir, and lamivudine.
  • tell your doctor if you smoke or drink alcohol, or if you have or have ever had high blood pressure, high cholesterol, diabetes, or heart or kidney disease.
  • tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while taking abacavir, dolutegravir, and lamivudine, call your doctor. You should not breastfeed if you are infected with HIV or if you are taking abacavir, dolutegravir, and lamivudine.
  • ask your doctor about the safe use of alcoholic beverages and medications that contain alcohol while you are taking abacavir, dolutegravir, and lamivudine.
  • you should be aware that your body fat may increase or move to different areas of your body, such as your upper back, neck (''buffalo hump''), breasts, and around your stomach. You may notice a loss of body fat from your face, legs, and arms.
  • you should know that while you are taking medications to treat HIV infection, your immune system may get stronger and begin to fight other infections that were already in your body. This may cause you to develop symptoms of those infections. If you have new or worsening symptoms at any time during your treatment with abacavir, dolutegravir, and lamivudine, be sure to tell your doctor.

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is within 4 hours of your next scheduled dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

In case of emergency/overdose

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Renal Dose Adjustments

CrCl less than 50 mL/min: Not recommended; individual components should be used.

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