Abacavir, Dolutegravir, and Lamivudinepronounced as (a bak' a vir) (doe" loo teg' ra vir) (la miv' ue deen)
AUDIENCE: Infectious Disease, Health Professional, Patient
ISSUE: Serious cases of neural tube birth defects involving the brain, spine, and spinal cord have been reported in babies born to women treated with dolutegravir used to treat human immunodeficiency virus (HIV). Preliminary results from an ongoing observational study in Botswana found that women who received dolutegravir at the time of becoming pregnant or early in the first trimester appear to be at higher risk for these defects.
Neural tube defects are birth defects that can occur early in pregnancy when the spinal cord, brain, and related structures do not form properly. 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. We are investigating this new safety issue and will update the public when we have more information.
BACKGROUND: Dolutegravir is an FDA-approved antiretroviral medicine used in combination with other antiretroviral medicines to treat HIV, the virus that can cause acquired immunodeficiency syndrome (AIDS). Dolutegravir works by blocking integrase, an HIV enzyme, to prevent the virus from multiplying and can reduce the amount of HIV in the body. Stopping dolutegravir without first talking to a prescriber can cause the HIV infection to become worse. Approved in 2013, dolutegravir has been on the market for 5 years and is available as a single ingredient product under the brand name Tivicay and as a fixed-dose combination tablet with other HIV medicines under the brand names Juluca and Triumeq.
RECOMMENDATION: Patients should not stop taking dolutegravir without first talking to your healthcare professional because stopping your medicine can cause the HIV infection to worsen. In addition:
- If you are already pregnant, stopping your dolutegravir-containing regimen without switching to alternative HIV medicines could cause the amount of virus to increase and spread HIV to your baby.
- If you take a dolutegravir-containing regimen at the time of becoming pregnant and during the first trimester of pregnancy, there is a risk that your baby may develop neural tube defects. Neural tube defects happen early in pregnancy, before many women even know they are pregnant. For this reason, women of childbearing age should talk to their healthcare professional about other nondolutegravir-containing antiretroviral medicines.
- You should tell your healthcare professional if you are pregnant or are planning to become pregnant before you start a dolutegravir-containing regimen. Your healthcare professional may discuss other treatment options with you.
- 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 talk to their healthcare professionals about an effective birth control method to use while taking a dolutegravir-containing regimen.
- Before you start a dolutegravir-containing regimen you will need a pregnancy test to determine if you are already pregnant.
Healthcare professionals should inform women of childbearing age about the potential risk of neural tube defects when a dolutegravir-containing regimen is used at the time of conception and early in pregnancy. In addition:
- Healthcare professionals should weigh the benefits and the risks of dolutegravir when prescribing antiretroviral medicines to women of childbearing age. Alternative antiretroviral medicines should be considered. Discuss the relative risks and benefits of appropriate alternative antiretroviral therapies.
- If the decision is made to use dolutegravir in women of childbearing age, healthcare professionals should reinforce the consistent use of effective birth control.
- Perform pregnancy testing before initiating a dolutegravir-containing regimen in women of childbearing age to exclude pregnancy.
For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety.
Abacavir, dolutegravir, and lamivudine may cause a serious or life-threatening allergic reaction. Call your doctor immediately if you develop one symptom from two or more of the following groups to see if you should stop taking abacavir, dolutegravir, and lamivudine:
- Group 1: fever
- Group 2: rash
- Group 3: nausea, vomiting, diarrhea, or stomach area pain
- Group 4: generally ill feeling, extreme tiredness, or achiness
- Group 5: shortness of breath, cough, or sore throat
Also, call your doctor immediately if you experience any of the following symptoms: headache; muscle or joint pain; swelling of the face, hands, feet, ankles, or lower legs; pain, burning, or tingling in the hands or feet; itching; blistering or peeling of the skin; difficulty swallowing or breathing; red, swollen, itchy or teary eyes; or sores in the mouth.
Your pharmacist will give you a Warning Card when you receive your medication to carry with you. The Warning Card contains the groups of symptoms listed above to make it easy for you and the people around you to recognize if you are having an allergic reaction. Be sure to carry this Warning Card with you at all times.
Some people may be more likely to have an allergic reaction to abacavir, dolutegravir, and lamivudine based on their heredity or genetic make-up. Your doctor may order a genetic lab test prior to starting abacavir, dolutegravir, and lamivudine or if you have not been previously tested to determine if you are more likely to have an allergic reaction to this medication. Tell your doctor and pharmacist if you are allergic to abacavir, dolutegravir, and lamivudine or any other medications that contain abacavir or dolutegravir or if you know that you have that particular genetic makeup. If you have ever had a previous allergic reaction to abacavir (in Epzicom, in Trizivir, Ziagen) or dolutegravir (Tivicay) or any other medication containing abacavir or dolutegravir, your doctor will probably tell you not to take abacavir, dolutegravir, and lamivudine. If your doctor tells you to stop taking abacavir, dolutegravir, and lamivudine because you had an allergic reaction, never take abacavir, dolutegravir, and lamivudine or a medication containing abacavir or dolutegravir again. If you stop taking abacavir, dolutegravir, and lamivudine for any other reason, including missing several doses in a row or running out of medication, do not start taking it again without first talking to your doctor. You will need to be around people who can provide or call for emergency medical care, if needed, when you restart this medication.
Tell your doctor if you have or think you may have hepatitis B virus infection (HBV; an ongoing liver infection) or hepatitis C virus infection (HCV; an ongoing liver infection). If you have HBV and you take abacavir, dolutegravir, and lamivudine, your condition may suddenly worsen when you stop taking abacavir, dolutegravir, and lamivudine. Your doctor will examine you and order lab tests regularly for several months after you stop taking abacavir, dolutegravir, and lamivudine to see if your HBV has worsened. If you have HCV and are taking interferon alfa with or without ribavirin (Copegus, Rebetol, Ribasphere) and you take abacavir, dolutegravir, and lamivudine, your condition may worsen and become life-threatening. If you are taking abacavir, dolutegravir, and lamivudine and interferon alfa with or without ribavirin, tell your doctor if you have any new symptoms of worsening liver disease.
Keep all appointments with your doctor and the laboratory. Your doctor will order certain tests to check your body's response to abacavir, dolutegravir, and lamivudine.
Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with abacavir, dolutegravir, and lamivudine and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) or the manufacturer's website to obtain the Medication Guide.
Talk to your doctor about the risks of taking abacavir, dolutegravir, and lamivudine.
Why is this medication prescribed?
The combination of abacavir, dolutegravir, and lamivudine is used alone or along with other medications to treat HIV infection. Abacavir and lamivudine are in a class of medications called nucleoside analogue reverse transcriptase inhibitors (NRTIs) and dolutegravir is in a class of medications called integrase strand transfer inhibitors (INSTIs). They work by decreasing the amount of HIV in your blood and increasing the number of immune cells that help fight infections in your body. Although abacavir, dolutegravir, and lamivudine will not cure HIV, these medications may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses such as serious infections or cancer. Taking these medications along with practicing safer sex and making other lifestyle changes may decrease the risk of getting or transmitting the HIV virus to other people.
How should this medicine be used?
The combination of abacavir, dolutegravir, and lamivudine comes as a tablet to take by mouth. It is usually taken once daily with or without food. Take abacavir, dolutegravir, and lamivudine at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take abacavir, dolutegravir, and lamivudine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Abacavir, dolutegravir, and lamivudine help to control HIV infection but do not cure it. Continue to take abacavir, dolutegravir, and lamivudine even if you feel well. Do not stop taking abacavir, dolutegravir, and lamivudine without talking to your doctor.
Other uses for this medicine
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
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; 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 liver, 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 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 special dietary instructions should I follow?
Unless your doctor tells you otherwise, continue your normal diet.
What should I do if I forget a dose?
Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.
What side effects can this medication cause?
Some side effects can be serious. If you experience any of the following symptoms, or those mentioned in the IMPORTANT WARNING section, call your doctor immediately or get emergency medical treatment:
- excessive tiredness; weakness, dizziness or lightheadedness; fast or irregular heartbeat; muscle pain; stomach pain with nausea and vomiting; shortness of breath or difficulty breathing; flu-like symptoms such as fever, chills, or cough; or feeling cold, especially in the arms or legs
- light-colored bowel movements; yellowing of the skin or eyes; loss of appetite; unusual bleeding or bruising; dark yellow or brown urine; or pain in the upper right part of stomach
Abacavir, dolutegravir, and lamivudine may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).
What should I know about storage and disposal of this medication?
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Do not remove the desiccant (small packet included with medication to absorb moisture) from your bottle.
It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org
Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.
In case of emergency/overdose
In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.
What other information should I know?
Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.
Keep a supply of abacavir, dolutegravir, and lamivudine on hand. Do not wait until you run out of medication to refill your prescription.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.