Abacavir/dolutegravir/lamiVUDine

Abacavir, dolutegravir, and lamivudine are antiviral medications that prevent human immunodeficiency virus (HIV) cells from multiplying in your body.

Abacavir dolutegravir, and lamivudine (Triumeq) is a combination medicine used to treat HIV, which causes the acquired immunodeficiency syndrome (AIDS). This medicine is not a cure for HIV or AIDS.

Abacavir, dolutegravir, and lamivudine may also be used for purposes not listed in this medication guide.

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.

Triumeq may also cause a serious condition called lactic acidosis. Get emergency medical help if you have even mild symptoms 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 Triumeq.

You should not use Triumeq if you are allergic to abacavir, dolutegravir, or lamivudine, or if you have:

• moderate or severe liver disease;
• a gene variation called HLA-B*5701 allele (your doctor will test you for this); or
• a history of allergic reaction to Combivir, Epivir, Epzicom, Tivicay, Trizivir, or Ziagen.

Once you have had an allergic reaction to abacavir or dolutegravir, you must never use these medicines again.

Some medicines can cause unwanted or dangerous effects when used with Triumeq. You should not take Triumeq if you also use:

• dofetilide (Tikosyn);
• abacavir (Epizicom, Trizivir, Ziagen);
• lamivudine (Combivir, Epivir, Epzicom, Trizivir); or
• emtricitabine (Emtriva, Atripla, Complera, Stribild, Truvada).

Triumeq can cause severe or life-threatening effects on your liver, especially if you have hepatitis C.

To make sure Triumeq is safe for you, tell your doctor if you have:

• liver disease (especially hepatitis B or C);
• kidney disease;
• risk factors for heart disease (such as diabetes, smoking, high blood pressure, high cholesterol); or
• if you drink alcohol.

Some people taking Triumeq develop a serious condition called lactic acidosis. This may be more likely in women, in people who are overweight or have liver disease, and in people who have taken HIV/AIDS medication for a long time. Talk with your doctor about your risk.

It is not known whether Triumeq will harm an unborn baby. However, HIV can be passed to your baby if you are not properly treated during pregnancy. Take all of your HIV medicines as directed to control your infection.

Women with HIV or AIDS should not breast feed a baby. Even if your baby is born without HIV, the virus may be passed to the baby in your breast milk.

Triumeq is not approved for use by anyone younger than 18 years old.

HIV/AIDS is usually treated with a combination of drugs. Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice. Every person with HIV or AIDS should remain under the care of a doctor.

Follow all directions on your Triumeq prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

The usual dose of Triumeq is 1 tablet per day. However, you may need to take a separate dolutegravir tablet (Tivicay) 12 hours after taking Triumeq if you also take certain other HIV medicines as part of your complete treatment plan. Follow your doctor's dosing instructions very carefully.

You may take Triumeq with or without food.

Triumeq comes with a Medication Guide and a Warning Card that lists the symptoms of an allergic reaction. Carry this Warning Card with you at all times so you will know what symptoms to watch for.

While using Triumeq, you may need frequent blood tests. You may need a blood test before you start taking this medicine for the first time, or if you are restarting the medication after stopping for reasons not related to an allergic reaction.

If you have ever had hepatitis B, this condition may come back or get worse after you stop taking Triumeq. You may need frequent blood tests to check your liver function for several months after you stop using this medicine.

Store at room temperature away from moisture and heat.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Take the missed dose as soon as you remember. Skip the missed dose if your next dose is less than 4 hours away. Do not take extra medicine to make up the missed dose. Get your prescription refilled before you run out of medicine completely.

Dosage Forms & Strengths

abacavir/dolutegravir/lamivudine

tablet

• 600mg/50mg/300mg

HIV Infection

1 tablet PO qDay

Dosage Modifications

If coadministered with efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, or rifampin: Take an additional dolutegravir (as single-entity) 50-mg tablet, separated by 12 hr from abacavir/dolutegravir/lamivudine dose

Moderate-to-severe hepatic impairment: Contraindicated

Dosing Considerations

Not recommended alone for use in patients with current or past history of resistance to any components of Triumeq

Not recommended alone in patients with resistance-associated integrase substitutions or clinically suspected INSTI resistance because the dose of dolutegravir in Triumeq is insufficient in these populations

Before initiating treatment with abacavir-containing products, screening for the presence of a genetic marker, the HLA-B*5701 allele, should be performed in any HIV-infected patient, irrespective of racial origin

Products containing abacavir should not be used in patients known to carry the HLA-B*5701 allele; these patients are at high risk for hypersensitivity reactions

Administration

May take with or without food

Bottle contains desiccant packet should not be removed

<18 years: Safety and efficacy not established

Mechanism of Action

Abacavir: Nucleoside reverse transcriptase inhibitor (NRTI); guanosine analog that inhibits HIV-1 reverse transcriptase by competing with dGTP as substrate, which, in turn, inhibits viral replication

Dolutegravir: Integrase strand transfer inhibitor (INSTI); inhibits catalytic activity of HIV-1 integrase, an HIV encoded enzyme required for viral replication

Lamivudine: NRTI; following phosphorylation, inhibits HIV reverse transcriptase by viral DNA chain termination; cytosine analog

Absorption

Peak plasma concentration

• Abacavir: 4.26 mcg/mL
• Dolutegravir: 3.67 mcg/mL
• Lamivudine: 2.04 mcg/mL

Peak plasma time

• Dolutegravir: 2-3 hr

AUC

• Abacavir: 11.95 mcg•hr/mL
• Dolutegravir: 53.6 mcg•hr/mL
• Lamivudine: 8.87 mcg•hr/mL

Distribution

Protein bound

• Abacavir: 50%
• Dolutegravir: ≥98.9%
• Lamivudine: Low

Vd

• Dolutegravir: 17.4 L

Metabolism

Abacavir: Primarily metabolized by alcohol dehydrogenase to form the 5′-carboxylic acid and glucuronyl transferase to form the 5′-glucuronide

Dolutegravir: Primarily metabolized via UGT1A1 with some contribution from CYP3A

Lamivudine: Negligible

Elimination

Half-life

• Abacavir: 1.54 hr
• Dolutegravir: 14 hr
• Lamivudine: 5-7 hr

Total body clearance

• Abacavir: 0.8 L/hr/kg
• Dolutegravir: 1 L/hr
• Lamivudine: 398.5 mL/min

Excretion

• Dolutegravir: 53% feces (unchanged); 31% urine
• Lamivudine: 70% urine (unchanged)

Pharmacogenomics

Patients who carry the HLA-B*5701 allele are at high risk for experiencing a hypersensitivity reaction to abacavir

Prior to initiating therapy with abacavir, screen for the HLA-B*5701 allele

For HLA-B*5701-positive patients, treatment with an abacavir-containing regimen is contraindicated