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 health care 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 health care professional about other non-dolutegravir-containing antiretroviral medicines.
- You should tell your health care professional if you are pregnant or are planning to become pregnant before you start a dolutegravir-containing regimen. Your health care 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 health care 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, health care 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.
Why is this medication prescribed?
Dolutegravir is used with other medications to treat human immunodeficiency virus (HIV) infection in adults and children who are at least 12 years of age and weigh at least 88 lb (40 kg). Dolutegravir is in a class of medications called HIV integrase inhibitors. It works by decreasing the amount of HIV in your blood and increasing the number of immune cells that help fight infections in your body. Although dulotegravir does not cure HIV, using it along with other 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 transmitting (spreading) the HIV virus to other people.
How should this medicine be used?
Dolutegravir comes as a tablet to take by mouth once or twice a day with or without food. Take dolutegravir at around the same time(s) 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 dolutegravir exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Continue to take dolutegravir even if you feel well. Do not stop taking dolutegravir without talking to your doctor. When your supply of dolutegravir runs low, get more from your doctor or pharmacist. If you stop taking dolutegravir or miss doses, your condition may become worse and more difficult to treat with medication.
Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.
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 dolutegravir,
- tell your doctor and pharmacist if you are allergic to dolutegravir, any other medications, or any of the ingredients in dolutegravir tablets. Ask your pharmacist or check the manufacturer's patient information for a list of the ingredients.
- tell your doctor if you are taking dofetilide (Tikosyn). Your doctor will probably tell you not to take dolutegravir if you are taking this medication.
- tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins ,and nutritional supplements, you are taking or plan to take. Be sure to mention any of the following: other medications for HIV including efavirenz (Sustiva, in Atripla), etravirine (Intelence), fosamprenavir (Lexiva) taken with ritonavir (Norvir), nevirapine (Viramune), and tipranavir (Aptivus) taken with ritonavir (Norvir); certain medications for seizures including carbamazepine (Carbatrol, Equetro, Tegretol), oxcarbazepine (Oxtellar XR, Trileptal), phenobarbital (Luminal), and phenytoin (Dilantin, Phenytek); metformin (Fortomet, Glumetza, Glucophage, Riomet); 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 them 2 hours after or 6 hours before you take dolutegravir.
- tell your doctor what herbal products you are taking, especially St. John's wort.
- tell your doctor if you have or have ever had kidney disease or liver disease including hepatitis B or hepatitis C.
- tell your doctor if you are pregnant or plan to become pregnant. If you become pregnant while taking dolutegravir, call your doctor. Also tell your doctor if you are breastfeeding. You should not breastfeed if you are infected with HIV or if you are taking dolutegravir.
- 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 after starting treatment with dolutegravir, 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 less than 4 hours before you are scheduled to take your 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?
Dolutegravir may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- difficulty falling asleep or staying asleep
- stomach pain
Some side effects can be serious. If you experience any of these symptoms or those listed in the SPECIAL PRECAUTION section, stop taking dolutegravir and call your doctor immediately or get emergency medical attention:
- feeling sick
- excessive tiredness
- muscle or joint pain
- blistering or peeling skin
- blisters or sores in the mouth
- red or swollen eyes
- swelling of the eyes, face, lips, mouth, tongue, or throat
- difficulty breathing or swallowing
- dark urine
- pale colored bowel movements
- loss of appetite
- pain in the upper right part of the stomach
Dolutegravir 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). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.
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
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?
Keep all appointments with your doctor and the laboratory. Your doctor may order certain lab tests to check your body's response to dolutegravir.
Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling 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.
- Juluca® (as a combination product containing dolutegravir, rilpivirine)