Abacavir, dolutegravir, and lamivudine

Name: Abacavir, dolutegravir, and lamivudine

What happens if I overdose?

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

What do I need to tell my doctor BEFORE I take Abacavir, Dolutegravir, and Lamivudine?

  • If you have an allergy to abacavir, dolutegravir, and lamivudine or any part of this medicine.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have been tested and know that you have a gene type called HLA-B*5701.
  • If you have any of these health problems: Kidney disease or liver disease.
  • If you are taking any of these drugs: Dofetilide, nevirapine, oxcarbazepine, phenobarbital, phenytoin, or St. John's wort.
  • If you are taking another drug that has abacavir, emtricitabine, or lamivudine in it.
  • If you are breast-feeding. Do not breast-feed while you take abacavir, dolutegravir, and lamivudine.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take abacavir, dolutegravir, and lamivudine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some things I need to know or do while I take Abacavir, Dolutegravir, and Lamivudine?

  • Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • This medicine may raise the chance of heart attack. Talk with the doctor.
  • Use care if you have risks for heart disease (high blood pressure, high cholesterol, overweight, high blood sugar or diabetes, cigarette smoking, man older than 40 years of age, other family members with early heart disease, woman after change of life). Talk with your doctor.
  • If abacavir, dolutegravir, and lamivudine is stopped because you have an allergy to it, do not restart it. It may not be safe to restart this medicine. Throw away any of abacavir, dolutegravir, and lamivudine that you have not taken. If you are not sure how to throw away unused drugs, check with your pharmacist.
  • If this medicine is stopped for any other reason, do not restart it without talking to the doctor. It could be very risky to restart on your own.
  • Do not run out of abacavir, dolutegravir, and lamivudine.
  • Talk with your doctor before you drink alcohol.
  • If you have had hepatitis B or C, talk with your doctor.
  • Do not take this medicine within 2 hours before or 6 hours after taking antacids.
  • Some other drugs may need to be taken at some other time than abacavir, dolutegravir, and lamivudine. If you take other drugs, check with your doctor or pharmacist to see if you need to take them at some other time than this medicine.
  • This medicine is not a cure for HIV. Stay under the care of your doctor.
  • This medicine does not stop the spread of diseases like HIV or hepatitis that are passed through blood or having sex. Do not have any kind of sex without using a latex or polyurethane condom. Do not share needles or other things like toothbrushes or razors. Talk with your doctor.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using abacavir, dolutegravir, and lamivudine while you are pregnant.

How is this medicine (Abacavir, Dolutegravir, and Lamivudine) best taken?

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • Take with or without food.
  • Keep taking abacavir, dolutegravir, and lamivudine as you have been told by your doctor or other health care provider, even if you feel well.
  • It is important that you do not miss or skip a dose of this medicine during treatment.

What do I do if I miss a dose?

  • Take a missed dose as soon as you think about it.
  • If the next dose is less than 4 hours away, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
  • If you are not sure what to do if you miss a dose, call your doctor.

Pronunciation

(a BAK a veer, doe loo TEG ra vir, & la MI vyoo deen)

Pharmacologic Category

  • Antiretroviral, Integrase Inhibitor (Anti-HIV)
  • Antiretroviral, Reverse Transcriptase Inhibitor, Nucleoside (Anti-HIV)

Dosing Geriatric

Refer to adult dosing.

Drug Interactions

Aluminum Hydroxide: May decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after oral aluminum hydroxide. Consider therapy modification

Cabozantinib: MRP2 Inhibitors may increase the serum concentration of Cabozantinib. Monitor therapy

Calcium Salts: May decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after oral calcium. Alternatively, dolutegravir and oral calcium can be taken together with food. Consider therapy modification

CarBAMazepine: May decrease the serum concentration of Dolutegravir. Management: Increase dolutegravir dose to 50 mg twice daily when used together with carbamazepine. Patients with known or suspected integrase strand inhibitor resistance should use an alternative to carbamazepine when possible. Consider therapy modification

Dofetilide: Dolutegravir may increase the serum concentration of Dofetilide. Avoid combination

Efavirenz: May decrease the serum concentration of Dolutegravir. Management: Increase dolutegravir dose to 50 mg twice daily in adults or children. Consider alternatives to efavirenz for INSTI experienced patients with clinically suspected INSTI resistance or certain INSTI associated resistance substitutions. Consider therapy modification

Emtricitabine: LamiVUDine may enhance the adverse/toxic effect of Emtricitabine. Avoid combination

Etravirine: May decrease the serum concentration of Dolutegravir. Management: US recommends avoiding the use of etravirine with dolutegravir unless used with atazanavir/ritonavir, darunavir/ritonavir or lopinavir/ritonavir. Canada recommends increasing dolutegravir to 50 mg twice daily when used with etravirine without a boosted PI Consider therapy modification

Fosamprenavir: May decrease the serum concentration of Dolutegravir. Specifically, Fosamprenavir/Ritonavir may decrease the serum concentration of Dolutegravir. The individual contributions of Fosamprenavir and Ritonavir to this effect are unknown. Management: Increase dolutegravir to 50 mg twice daily in adults and pediatric patients (12 yrs or older and at least 40 kg). Seek alternatives to fosamprenavir/ritonavir in INSTI-experienced patients with suspected or certain INSTI resistance. Consider therapy modification

Fosphenytoin-Phenytoin: May decrease the serum concentration of Dolutegravir. Avoid combination

Iron Salts: May decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after oral iron. Alternatively, dolutegravir and oral iron can be taken together with food. Exceptions: Ferric Carboxymaltose; Ferric Gluconate; Ferric Hydroxide Polymaltose Complex; Ferric Pyrophosphate Citrate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Consider therapy modification

Magnesium Salts: May decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after oral magnesium salts. Consider therapy modification

MetFORMIN: Dolutegravir may increase the serum concentration of MetFORMIN. Management: Limit the daily metformin dose to 1,000 mg when used together with dolutegravir. Metformin dose adjustments may also be needed upon discontinuation of dolutegravir. Monitor patient response to metformin closely. Consider therapy modification

Methadone: May diminish the therapeutic effect of Abacavir. Abacavir may decrease the serum concentration of Methadone. Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after the dose of a multivitamin that contains polyvalent cations (e.g., calcium, iron, magnesium, selenium, zinc). Alternatively, dolutegravir and multivitamins can be taken together with food. Consider therapy modification

Multivitamins/Minerals (with AE, No Iron): May decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after the dose of a multivitamin that contains polyvalent cations (e.g., calcium, iron, magnesium, selenium, zinc). Alternatively, dolutegravir and multivitamins can be taken together with food. Consider therapy modification

Nevirapine: May decrease the serum concentration of Dolutegravir. Avoid combination

Orlistat: May decrease the serum concentration of Antiretroviral Agents. Monitor therapy

OXcarbazepine: May decrease the serum concentration of Dolutegravir. Avoid combination

PHENobarbital: May decrease the serum concentration of Dolutegravir. Avoid combination

Primidone: May decrease the serum concentration of Dolutegravir. Specifically, the Primidone metabolite phenobarbital may decrease Dolutegravir serum concentrations. Avoid combination

Protease Inhibitors: May decrease the serum concentration of Abacavir. Monitor therapy

RifAMPin: May decrease the serum concentration of Dolutegravir. Management: Increase dolutegravir dose to 50 mg twice daily in adults or children. Consider alternatives to rifampin for INSTI experienced patients with clinically suspected INSTI resistance or certain INSTI associated resistance substitutions. Consider therapy modification

Selenium: May decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after oral selenium. Consider therapy modification

St John's Wort: May decrease the serum concentration of Dolutegravir. Avoid combination

Sucralfate: May decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after sucralfate. Consider therapy modification

Tipranavir: May decrease the serum concentration of Dolutegravir. Specifically, Tipranavir/Ritonavir may decrease the serum concentration of Dolutegravir. The individual contributions of Tipranavir and Ritonavir to this effect are unknown. Management: Increase dolutegravir dose to 50 mg twice daily in patients receiving tipranavir/ritonavir. Seek alternatives to tipranavir/ritonavir in INSTI experienced patients with suspected INSTI resistance or certain INSTI associated resistance substitutions. Consider therapy modification

Trimethoprim: May increase the serum concentration of LamiVUDine. Monitor therapy

Zinc Salts: May decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after oral zinc salts. Consider therapy modification

ALERT U.S. Boxed Warning

Hypersensitivity reactions:

Serious and sometimes fatal hypersensitivity reactions, with multiple organ involvement, have occurred with abacavir. Patients who carry the HLA-B*5701 allele are at a higher risk of a hypersensitivity reaction to abacavir; although, hypersensitivity reactions have occurred in patients who do not carry the HLA-B*5701 allele.

Abacavir/dolutegravir/lamivudine is contraindicated in patients with a prior hypersensitivity reaction to abacavir and in HLA-B*5701-positive patients. All patients should be screened for the HLA-B*5701 allele prior to initiating therapy with abacavir/dolutegravir/lamivudine or reinitiation of therapy with abacavir/dolutegravir/lamivudine unless patients have a previously documentedan HLA-B*5701 allele assessment. Discontinue abacavir/dolutegravir/lamivudine immediately if a hypersensitivity reaction is suspected, regardless of status and even when other diagnoses are possible.

Following a hypersensitivity reaction to abacavir/dolutegravir/lamivudine, never restart abacavir/dolutegravir/lamivudine or any other abacavir-containing product because more severe symptoms, including death, can occur within hours. Similar severe reactions have also occurred rarely following reintroduction of abacavir-containing products in patients who have no history of abacavir hypersensitivity.

Lactic acidosis and severe hepatomegaly with steatosis:

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including abacavir, lamivudine, and other antiretrovirals. Discontinue abacavir/dolutegravir/lamivudine if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur.

Exacerbations of hepatitis B:

Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with hepatitis B virus (HBV) and human immunodeficiency virus (HIV-1) and have discontinued lamivudine. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue abacavir/dolutegravir/lamivudine and are coinfected with HIV-1 and HBV. If appropriate, initiation of antihepatitis B therapy may be warranted.

Pregnancy Risk Factor C Pregnancy Considerations

Animal reproduction studies have not been conducted with this combination. In general, women who become pregnant on a stable combination antiretroviral therapy (cART) regimen may continue that regimen if viral suppression is effective, appropriate drug exposure can be achieved, contraindications for use in pregnancy are not present, and the regimen is well tolerated (HHS [perinatal] 2016). Evaluate individual components when choosing initial therapy for antiretroviral-naive pregnant women.

What special dietary instructions should I follow?

Unless your doctor tells you otherwise, continue your normal diet.

Abacavir / dolutegravir / lamivudine Pregnancy Warnings

Animal studies with abacavir (high-dose) have revealed evidence of embryonic and fetal toxicity, including developmental toxicity, fetal anasarca, skeletal malformations, and increased incidence of stillbirth. Animal studies with dolutegravir have failed to reveal evidence of impaired fertility or fetal harm. Animal studies with lamivudine have failed to reveal evidence of teratogenicity; while early embryolethality was observed in rabbit studies (exposure levels similar to human levels), this effect was not seen in high-dose studies in rats. Abacavir, dolutegravir, and lamivudine were transferred to the fetus through the placenta in animal studies; placental transfer of abacavir and lamivudine has been observed in humans. Data on pregnant women using abacavir with lamivudine (as the individual components), abacavir, and lamivudine (more than 400, 600, and 3000 outcomes from first trimester exposures, respectively) showed no malformative toxicity. There are no controlled data in human pregnancy with this combination drug. To monitor maternal-fetal outcomes of pregnant women exposed to antiretroviral therapy, an Antiretroviral Pregnancy Registry (APR) has been established. Healthcare providers are encouraged to prospectively register patients. For additional information: apregistry.com The APR has received prospective reports of over 2000 exposures to abacavir (over 900 exposed in the first trimester) and over 11,000 exposures to lamivudine (over 4300 exposed in the first trimester) resulting in live births; there was no difference between abacavir or lamivudine and overall birth defects compared with the background birth defect rate of 2.7% in the reference population. The prevalence of defects in the first trimester was 3% for abacavir and 3.1% for lamivudine. No increased risk of major birth defects observed for either drug compared to background rate. In 2 clinical trials, maternal, neonatal, and umbilical cord serum lamivudine levels were generally comparable. Amniotic fluid samples collected after natural rupture of membranes from a subset of patients confirmed placental transfer in humans. Amniotic fluid levels of lamivudine were usually 2 times greater than maternal serum levels, ranging from 1.2 to 2.5 mcg/mL (150 mg twice a day) and 2.1 to 5.2 mcg/mL (300 mg twice a day). AU TGA pregnancy category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

This drug should be used during pregnancy only if the benefit outweighs the risk to the fetus. AU TGA pregnancy category: B3 US FDA pregnancy category: C Comments: A pregnancy exposure registry is available.

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