IMPORTANT SAFETY INFORMATION
What is the most important information I should know about efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets?
Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets can cause serious side effects, including:
- Worsening of hepatitis B virus (HBV) infection. Your healthcare provider will test you for HBV before starting treatment with efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets. If you have HBV infection and take efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets, your HBV may get worse (flare-up) if you stop taking efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets. A “flare-up” is when your HBV infection suddenly returns in a worse way than before.
- Do not stop taking efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets without first talking with your healthcare provider.
- Do not run out of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets. Refill your prescription or talk to your healthcare provider before your efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets is all gone.
- If you stop taking efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets, your healthcare provider will need to check your health often and do blood tests regularly for several months to check your HBV infection, or give you a medication to treat hepatitis B. Tell your healthcare provider about any new or unusual symptoms you may have after you stop taking efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets.
For more information about side effects see the section, “What are the possible side effects of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets?”
Who should not take efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets?
Do not take efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets if you:
- are allergic to efavirenz
- take the medicine called voriconazole, elbasvir or grazoprevir
Ask your healthcare provider if you are not sure if you take any of these medicines.
Before taking efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets, tell your healthcare provider about all of your medical conditions, including if you:
- have liver problems, including hepatitis B or C virus infection
- have heart problems
- have or have had mental problems
- have a history of drug or alcohol abuse
- have nervous system problems
- have kidney problems or receive kidney dialysis treatment
- have bone problems
- have had seizures or take medicines used to treat seizures
- are pregnant or plan to become pregnant. Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets can harm your unborn baby. If you are able to become pregnant, your healthcare provider should do a pregnancy test before you start treatment with efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets. You should not become pregnant during treatment with efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets and for 12 weeks after stopping treatment. Tell your healthcare provider if you become pregnant or think you may be pregnant during treatment with efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets.
- Females who are able to become pregnant should use 2 effective forms of birth control (contraception) during treatment with efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets and for 12 weeks after stopping treatment.
- A barrier form of birth control should always be used along with another type of birth control. Barrier forms of birth control may include condoms, contraceptive sponges, diaphragm with spermicide, and cervical cap.
- Birth control methods that contain the hormone progesterone such as birth control pills, injections, vaginal rings, or implants, may not work as well while taking efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets.
- Talk to your healthcare provider about birth control methods that may be right for you during treatment with efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets.
- Pregnancy Registry: There is a pregnancy registry for women who take efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. Talk to your healthcare provider about how you can take part in this registry.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements.
Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine.
Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets and some medicines may interact with each other causing serious side effects.
You can ask your healthcare provider or pharmacist for a list of medicines that interact with efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets. Do not start a new medicine without telling your healthcare provider. Your healthcare provider can tell you if it is safe to take efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets with other medicines.
What should I avoid while taking efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets?
- Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets can cause dizziness, impaired concentration and drowsiness. If you have these symptoms, do not drive a car, use heavy machinery, or do anything that requires you to be alert.
What are the possible side effects of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets?
Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets may cause serious side effects, including:
- See “What is the most important information I should know about efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets?”
- Rash. Rash is a serious side effect but may also be common. Rashes will usually go away without any change in your treatment. Tell your healthcare provider right away if you develop a rash during treatment with efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets.
- Severe liver problems. In rare cases, severe liver problems can happen that can lead to death. Tell your healthcare provider right away if you get these symptoms: skin or the white part of your eyes turns yellow, dark “tea-colored” urine, light-colored stools, loss of appetite for several days or longer, nausea, or stomach-area pain.
- Mental problems. Serious mental problems including severe depression, suicidal thoughts and actions, aggressive behavior, delusions, catatonia, and paranoid and manic reactions have happened in people who take efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets. These mental health problems may happen more often in people who have a history of mental problems or drug use, or who take medicines to treat mental problems. Tell your healthcare provider right away if you develop serious mental problems during treatment with efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets.
- Nervous system problems. Nervous system problems usually begin during the first or second day of treatment with efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets and usually go away after 2 to 4 weeks of treatment. Some symptoms may occur months to years after beginning efavirenz, emtricitabine and tenofovir disoproxil fumarate therapy. These symptoms may become more severe if you drink alcohol or take mood altering (street) drugs while taking efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets. Tell your healthcare provider right away if you develop nervous system problems during treatment with efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets. Symptoms of nervous system problems may include:
- dizziness
- problems sleeping
- problems concentrating
- excessive sleepiness or difficulty awakening
- abnormal dreams
- seeing or hearing things that are not real (hallucinations)
- unusually happy mood
- confusion
- agitation
- memory problems
- thought problems
- lack of coordination or difficulty with balance
- slow thoughts and physical movement
If you have dizziness, trouble concentrating or sleepiness, do not drive a car, use machinery, or do anything that needs you to be alert.
- New or worse kidney problems, including kidney failure. Your healthcare provider should do blood and urine tests to check your kidneys before you start and during treatment with efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets. Your healthcare provider may tell you to stop taking efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets if you develop new or worse kidney problems during treatment with efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets.
- Bone problems can happen in some people who take efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets. Bone problems include bone pain or softening or thinning of bones, which may lead to fractures. Your healthcare provider may need to do tests to check your bones.
- Seizures. Your healthcare provider may do blood tests during treatment with efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets if you take certain medicines used to prevent seizures.
- Too much lactic acid in your blood (lactic acidosis). Too much lactic acid is a serious but rare medical emergency that can lead to death. Tell your healthcare provider right away if you develop any of these symptoms:
- weakness or being more tired than usual
- unusual muscle pain
- being short of breath or fast breathing
- stomach pain with nausea and vomiting
- cold or blue hands and feet
- feel dizzy or lightheaded
- fast or abnormal heartbeat
- Changes in your immune system (Immune Reconstitution Syndrome) can happen when an HIV-1 infected person starts taking HIV-1 medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your healthcare provider right away if you develop any new symptoms after starting treatment with efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets.
- Changes in body fat. Changes in body fat distribution or accumulation have happened in some people taking HIV-1 medicines, including an increased amount of fat in the upper back and neck ("buffalo hump"), in the breasts, and around the trunk. Loss of fat from the legs, arms, and face may also happen. The cause and long-term health effects of these body fat changes are not known.
The most common side effects of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets include diarrhea, nausea, tiredness, headache, dizziness, depression, problems sleeping, abnormal dreams, and rash.
These are not all the possible side effects of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets.
Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call .
Please read the Patient Information Leaflet in the full including Boxed Warning.
APPROVED USES
What are efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets?
This prescription medicine combines efavirenz, emtricitabine, and tenofovir disoproxil fumarate in one tablet. Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets is used alone as a complete regimen or in combination with other anti-HIV-1 medicines to treat people with HIV-1 infection who weigh at least 88 lbs. (40 kg).
It is not known if efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets are safe and effective for use in children with HIV-1 infection who weigh less than 88 lbs. (40 kg).
IMPORTANT SAFETY INFORMATION
WARNING: POSTTREATMENT ACUTE EXACERBATION OF HEPATITIS B
Severe acute exacerbations of hepatitis B virus (HBV) have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets.
Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets. If appropriate, initiation of anti-hepatitis B therapy may be warranted.
Contraindications: Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets are contraindicated in patients with previously demonstrated clinically significant hypersensitivity (e.g., Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to efavirenz, a component of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets. Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets are contraindicated to be coadministered with voriconazole or elbasvir/grazoprevir.
Severe Acute Exacerbation of Hepatitis B in Patients Coinfected with HIV-1 and HBV
All patients should be tested for the presence of chronic HBV before or when initiating antiretroviral therapy. Severe acute exacerbations of hepatitis B (e.g., liver decompensation and liver failure) have been reported in patients who are coinfected with HBV and HIV-1 and have discontinued FTC or TDF, two of the components of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets. Patients who are coinfected with HIV-1 and HBV should be closely monitored, with both clinical and laboratory follow-up for at least several months after stopping treatment with efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets. If appropriate, initiation of antihepatitis B therapy may be warranted, especially in patients with advanced liver disease or cirrhosis, since posttreatment exacerbation of hepatitis may lead to hepatic decompensation and liver failure.
Rash
In controlled clinical trials, 26% of adult subjects treated with 600 mg EFV experienced new-onset skin rash compared with 17% of those treated in control groups. Rashes are usually mild-to-moderate maculopapular skin eruptions that occur within the first 2 weeks of initiating therapy with EFV and, in most subjects continuing therapy with EFV, rash resolves within 1 month. Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets should be discontinued in patients developing severe rash associated with blistering, desquamation, mucosal involvement, or fever. For patients who have had a life-threatening cutaneous reaction (e.g., Stevens-Johnson syndrome), alternative therapy should be considered.
Rash was reported in 32% of pediatric subjects treated with EFV. The median time to onset of rash in pediatric subjects was 28 days. Prophylaxis with appropriate antihistamines before initiating therapy with efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets in pediatric patients should be considered.
Hepatotoxicity
Postmarketing cases of hepatitis, including fulminant hepatitis progressing to liver failure requiring transplantation or resulting in death, have been reported in patients treated with EFV, a component of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets.
Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets are not recommended for patients with moderate or severe hepatic impairment. Careful monitoring is recommended for patients with mild hepatic impairment receiving efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets.
Monitoring of liver enzymes before and during treatment is recommended for all patients. Consider discontinuing efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets in patients with persistent elevations of serum transaminases to greater than five times the upper limit of the normal range.
Discontinue efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets if elevation of serum transaminases is accompanied by clinical signs or symptoms of hepatitis or hepatic decompensation.
Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions
The concomitant use of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets and other drugs may result in potentially significant drug interactions, some of which may lead to:
- Loss of therapeutic effect of concomitant drug or efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets and possible development of resistance.
- Possible clinically significant adverse reaction from greater exposures of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets or concomitant drug.
QTc prolongation has been observed with the use of EFV. Consider alternatives to efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets when coadministered with a drug with a known risk of Torsade de Pointes or when administered to patients at higher risk of Torsade de Pointes.
Psychiatric Symptoms
Serious psychiatric adverse experiences have been reported in patients treated with EFV, a component of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets including severe depression, suicidal ideation, nonfatal suicide attempts, aggressive behavior, paranoid reactions, and manic reactions.
Patients with serious psychiatric adverse experiences should seek immediate medical evaluation to assess the possibility that the symptoms may be related to the use of EFV, and if so, to determine whether the risks of continued therapy outweigh the benefits.
Nervous System Symptoms
Fifty-three percent of subjects receiving EFV in controlled trials reported central nervous system symptoms (any grade, regardless of causality) compared to 25% of subjects receiving control regimens. These symptoms included dizziness, insomnia, impaired concentration, somnolence, abnormal dreams, and hallucinations. Other reported symptoms were euphoria, confusion, agitation, amnesia, stupor, abnormal thinking, and depersonalization. Patients should be informed that these common symptoms were likely to improve with continued therapy and were not predictive of subsequent onset of the less frequent psychiatric symptoms.
Late-onset neurotoxicity, including ataxia and encephalopathy (impaired consciousness, confusion, psychomotor slowing, psychosis, delirium), may occur months to years after beginning EFV therapy. Patients presenting with signs and symptoms of serious neurologic adverse experiences should be evaluated promptly to assess the possibility that these events may be related to EFV use, and whether discontinuation of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets is warranted.
Patients receiving efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets should be alerted to the potential for additive central nervous system effects when efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets are used concomitantly with alcohol or psychoactive drugs.
Patients who experience central nervous system symptoms such as dizziness, impaired concentration, and/or drowsiness should avoid potentially hazardous tasks such as driving or operating machinery.
New Onset or Worsening Renal Impairment
Emtricitabine and tenofovir are principally eliminated by the kidney; however, EFV is not. Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported with the use of TDF, a component of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets.
Prior to initiation and during use of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets, on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus. Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets are not recommended in patients with moderate or severe renal impairment (estimated creatinine clearance below 50 mL/min).
Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets should be avoided with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]). Cases of acute renal failure after initiation of high-dose or multiple NSAIDs have been reported in HIV-infected patients with risk factors for renal dysfunction who appeared stable on TDF. Alternatives to NSAIDs should be considered, if needed, in patients at risk for renal dysfunction.
Persistent or worsening bone pain, pain in extremities, fractures, and/or muscular pain or weakness may be manifestations of proximal renal tubulopathy and should prompt an evaluation of renal function in patients at risk of renal dysfunction.
Discontinue efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome.
Embryo-Fetal Toxicity
Efavirenz may cause fetal harm when administered during the first trimester of pregnancy. Advise adults and adolescents of childbearing potential who are receiving efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets to avoid pregnancy while receiving efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets and for 12 weeks after discontinuation.
Bone Loss and Mineralization Defects
Bone Mineral Density
In clinical trials in HIV-1 infected adults, TDF (a component of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets) was associated with slightly greater decreases in bone mineral density (BMD) and increases in biochemical markers of bone metabolism, suggesting increased bone turnover relative to comparators. Serum parathyroid hormone levels and 1,25 Vitamin D levels were also higher in subjects receiving TDF.
Under normal circumstances, BMD increases rapidly in pediatric patients. In HIV-1 infected subjects aged 2 years to less than 18 years, bone effects were similar to those observed in adult subjects and suggest increased bone turnover. Total body BMD gain was less in the TDF-treated HIV-1 infected pediatric subjects as compared to the control groups. Similar trends were observed in chronic hepatitis-B infected adolescent subjects aged 12 years to less than 18 years.
Mineralization Defects
Cases of osteomalacia associated with proximal renal tubulopathy, manifested as bone pain or pain in extremities and which may contribute to fractures, have been reported in association with TDF use. Arthralgias and muscle pain or weakness have also been reported in cases of proximal renal tubulopathy. Hypophosphatemia and osteomalacia secondary to proximal renal tubulopathy should be considered in patients at risk of renal dysfunction who present with persistent or worsening bone or muscle symptoms while receiving TDF-containing products.
Convulsions
Convulsions have been observed in adult and pediatric patients receiving EFV, generally in the presence of known medical history of seizures. Caution must be taken in any patient with a history of seizures.
Lactic Acidosis/Severe Hepatomegaly with Steatosis
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including TDF and FTC, components of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets, alone or in combination with other antiretrovirals. Treatment with efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).
Immune Reconstitution Syndrome
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including the components of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.
Autoimmune disorders (such as Graves’ disease, polymyositis, Guillain-Barré syndrome, and autoimmune hepatitis) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment.
Fat Redistribution
Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance," has been observed in patients receiving antiretroviral therapy, including EFV.
Common Adverse Reactions: In clinical trials, the most common adverse reactions (incidence greater than or equal to 10%, any severity) in HIV-1 infected subjects included diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash.
Please see full including Boxed Warning.
APPROVED USES
Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets are indicated as a complete regimen or in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 40 kg.
