Study 073: Study 073 was a 48-week open-label, randomized clinical trial in subjects with stable, virologic suppression on combination antiretroviral therapy consisting of at least two nucleoside reverse transcriptase inhibitors (NRTIs) administered in combination with a protease inhibitor (with or without ritonavir) or a non-nucleoside reverse transcriptase inhibitor (NNRTI).
To be enrolled, subjects were to have HIV-1 RNA <200 copies/mL for at least 12 weeks on their current regimen prior to study entry with no known HIV-1 substitutions conferring resistance to the components of ATRIPLA and no history of virologic failure.
The study compared the efficacy of switching to ATRIPLA or staying on the baseline antiretroviral regimen (SBR). Subjects were randomized in a 2:1 ratio to switch to ATRIPLA (N=203) or stay on SBR (N=97). Subjects had a mean age of 43 years (range 22 to 73 years), 88% were male, 68% were white, 29% were black or African-American, and 3% were of other races. At baseline, median CD4+ cell count was 516 cells/mm3 and 96% had HIV-1 RNA <50 copies/mL. The median time since onset of antiretroviral therapy was 3 years and 88% of subjects were receiving their first antiretroviral regimen at study enrollment.
At Week 48, 89% and 87% of subjects who switched to ATRIPLA maintained HIV RNA <200 copies/mL and <50 copies/mL, respectively, compared to 88% and 85% who remained on SBR; this difference was not statistically significant. No changes in CD4+ cell counts from baseline to Week 48 were observed in either treatment arm.
ATRIPLA tablets are pink, capsule-shaped, film-coated, debossed with “123” on one side and plain-faced on the other side.
They are supplied by State of Florida DOH Central Pharmacy as follows:
|53808-0208-1||600 mg / 200 mg / 300 mg||30 TABLET||PINK||15584-0101-1|
Store at 25 °C (77 °F); excursions permitted to 15–30 °C (59–86 °F) [see USP Controlled Room Temperature].
- Keep container tightly closed.
- Dispense only in original container.
- Do not use if seal over bottle opening is broken or missing.
A statement to patients and healthcare providers is included on the product’s bottle labels: ALERT: Find out about medicines that should NOT be taken with ATRIPLA. ATRIPLA may interact with some drugs; therefore, patients should be advised to report to their doctor the use of any other prescription, nonprescription medication, or herbal products, particularly St. John’s wort.
Patients should be advised that:
- ATRIPLA is not a cure for HIV-1 infection and that they may continue to experience illnesses associated with HIV-1 infection, including opportunistic infections. Patients should remain under the care of a physician when using ATRIPLA.
- The use of ATRIPLA has not been shown to reduce the risk of transmission of HIV-1 to others through sexual contact or blood contamination. Patients should be advised to continue to practice safer sex and to use latex or polyurethane condoms to lower the chance of sexual contact with any body fluids such as semen, vaginal secretions or blood. Patients should be advised never to re-use or share needles.
- The long term effects of ATRIPLA are unknown.
- Redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy and that the cause and long-term health effects of these conditions are not known.
- ATRIPLA should not be coadministered with SUSTIVA, EMTRIVA, VIREAD, or TRUVADA, or drugs containing lamivudine, including Combivir, Epivir, Epivir-HBV, Epzicom, or Trizivir.
- ATRIPLA should not be administered with HEPSERA [See Warnings and Precautions (5.2)].
Patients should be informed that lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported. Treatment will be suspended in any patients who develop clinical symptoms suggestive of lactic acidosis or pronounced hepatotoxicity (including nausea, vomiting, unusual or unexpected stomach discomfort, and weakness) [See Warnings and Precautions (5.1)].
Patients with HIV-1 should be tested for hepatitis B virus (HBV) before initiating antiretroviral therapy.
Patients should be advised that severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV-1 and have discontinued EMTRIVA (emtricitabine) or VIREAD (tenofovir DF), which are components of ATRIPLA.
Renal impairment, including cases of acute renal failure and Fanconi syndrome, has been reported. ATRIPLA should be avoided with concurrent or recent use of a nephrotoxic agent [See Warnings and Precautions (5.7)].
Patients should be informed that decreases in bone mineral density have been observed with the use of tenofovir DF. Bone mineral density monitoring may be performed in patients who have a history of pathologic bone fracture or are at risk for osteopenia [See Warnings and Precautions (5.11)].
Patients should be advised to take ATRIPLA orally on an empty stomach and that it is important to take ATRIPLA on a regular dosing schedule to avoid missing doses.
Patients should be informed that central nervous system symptoms (NSS) including dizziness, insomnia, impaired concentration, drowsiness, and abnormal dreams are commonly reported during the first weeks of therapy with efavirenz. Dosing at bedtime may improve the tolerability of these symptoms, which are likely to improve with continued therapy. Patients should be alerted to the potential for additive effects when ATRIPLA is used concomitantly with alcohol or psychoactive drugs. Patients should be instructed that if they experience NSS they should avoid potentially hazardous tasks such as driving or operating machinery [See Warnings and Precautions (5.6), and Dosage and Administration (2)].
Patients should be informed that serious psychiatric symptoms including severe depression, suicide attempts, aggressive behavior, delusions, paranoia, and psychosis-like symptoms have been reported in patients receiving efavirenz. If they experience severe psychiatric adverse experiences they should seek immediate medical evaluation. Patients should be advised to inform their physician of any history of mental illness or substance abuse [See Warnings and Precautions (5.5)].
Patients should be informed that a common side effect is rash. Rashes usually go away without any change in treatment. However, since rash may be serious, patients should be advised to contact their physician promptly if rash occurs.
Women receiving ATRIPLA should be instructed to avoid pregnancy [See Warnings and Precautions (5.8)]. A reliable form of barrier contraception must always be used in combination with other methods of contraception, including oral or other hormonal contraception. Because of the long half-life of efavirenz, use of adequate contraceptive measures for 12 weeks after discontinuation of ATRIPLA is recommended. Women should be advised to notify their physician if they become pregnant or plan to become pregnant while taking ATRIPLA. If this drug is used during the first trimester of pregnancy, or if the patient becomes pregnant while taking this drug, she should be apprised of the potential harm to the fetus.
FDA-Approved Patient Labeling
ATRIPLA® (uh TRIP luh) Tablets
ALERT: Find out about medicines that should NOT be taken with ATRIPLA.
Please also read the section “MEDICINES YOU SHOULD NOT TAKE WITH ATRIPLA.”
Generic name: efavirenz, emtricitabine and tenofovir disoproxil fumarate
(eh FAH vih renz, em tri SIT uh bean and te NOE’ fo veer dye soe PROX il FYOU mar ate)
Read the Patient Information that comes with ATRIPLA before you start taking it and each time you get a refill since there may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment. You should stay under a healthcare provider’s care when taking ATRIPLA. Do not change or stop your medicine without first talking with your healthcare provider. Talk to your healthcare provider or pharmacist if you have any questions about ATRIPLA.
- Some people who have taken medicine like ATRIPLA (which contains nucleoside analogs) have developed a serious condition called lactic acidosis (build up of an acid in the blood). Lactic acidosis can be a medical emergency and may need to be treated in the hospital. Call your healthcare provider right away if you get the following signs or symptoms of lactic acidosis:
- You feel very weak or tired.
- You have unusual (not normal) muscle pain.
- You have trouble breathing.
- You have stomach pain with nausea and vomiting.
- You feel cold, especially in your arms and legs.
- You feel dizzy or lightheaded.
- You have a fast or irregular heartbeat.
- Some people who have taken medicines like ATRIPLA have developed serious liver problems called hepatotoxicity , with liver enlargement (hepatomegaly) and fat in the liver (steatosis). Call your healthcare provider right away if you get the following signs or symptoms of liver problems:
- Your skin or the white part of your eyes turns yellow (jaundice).
- Your urine turns dark.
- Your bowel movements (stools) turn light in color.
- You don’t feel like eating food for several days or longer.
- You feel sick to your stomach (nausea).
- You have lower stomach area (abdominal) pain.
- You may be more likely to get lactic acidosis or liver problems if you are female, very overweight (obese), or have been taking nucleoside analog-containing medicines, like ATRIPLA, for a long time.
- If you also have hepatitis B virus (HBV) infection and you stop taking ATRIPLA, you may get a “flare-up” of your hepatitis. A “flare-up” is when the disease suddenly returns in a worse way than before. Patients with HBV who stop taking ATRIPLA need close medical follow-up for several months, including medical exams and blood tests to check for hepatitis that could be getting worse. ATRIPLA is not approved for the treatment of HBV, so you must discuss your HBV therapy with your healthcare provider.
What is ATRIPLA?
ATRIPLA contains 3 medicines, SUSTIVA® (efavirenz), EMTRIVA® (emtricitabine) and VIREAD® (tenofovir disoproxil fumarate also called tenofovir DF) combined in one pill. EMTRIVA and VIREAD are HIV-1 (human immunodeficiency virus) nucleoside analog reverse transcriptase inhibitors (NRTIs) and SUSTIVA is an HIV-1 non-nucleoside analog reverse transcriptase inhibitor (NNRTI). VIREAD and EMTRIVA are the components of TRUVADA®. ATRIPLA can be used alone as a complete regimen, or in combination with other anti-HIV-1 medicines to treat people with HIV-1 infection. ATRIPLA is for adults age 18 and over. ATRIPLA has not been studied in children under age 18 or adults over age 65.
HIV infection destroys CD4+ T cells, which are important to the immune system. The immune system helps fight infection. After a large number of T cells are destroyed, acquired immune deficiency syndrome (AIDS) develops.
ATRIPLA helps block HIV-1 reverse transcriptase, a viral chemical in your body (enzyme) that is needed for HIV-1 to multiply. ATRIPLA lowers the amount of HIV-1 in the blood (viral load). ATRIPLA may also help to increase the number of T cells (CD4+ cells), allowing your immune system to improve. Lowering the amount of HIV-1 in the blood lowers the chance of death or infections that happen when your immune system is weak (opportunistic infections).
Does ATRIPLA cure HIV-1 or AIDS?
ATRIPLA does not cure HIV-1 infection or AIDS. The long-term effects of ATRIPLA are not known at this time. People taking ATRIPLA may still get opportunistic infections or other conditions that happen with HIV-1 infection. Opportunistic infections are infections that develop because the immune system is weak. Some of these conditions are pneumonia, herpes virus infections, and Mycobacterium avium complex (MAC) infection. It is very important that you see your healthcare provider regularly while taking ATRIPLA.
Does ATRIPLA reduce the risk of passing HIV-1 to others?
ATRIPLA has not been shown to lower your chance of passing HIV-1 to other people through sexual contact, sharing needles, or being exposed to your blood.
- Do not share needles or other injection equipment.
- Do not share personal items that can have blood or body fluids on them, like toothbrushes or razor blades.
- Do not have any kind of sex without protection. Always practice safer sex by using a latex or polyurethane condom or other barrier to reduce the chance of sexual contact with semen, vaginal secretions, or blood.
Who should not take ATRIPLA?
Together with your healthcare provider, you need to decide whether ATRIPLA is right for you.
Do not take ATRIPLA if you are allergic to ATRIPLA or any of its ingredients. The active ingredients of ATRIPLA are efavirenz, emtricitabine, and tenofovir DF. See the end of this leaflet for a complete list of ingredients.
What should I tell my healthcare provider before taking ATRIPLA?
Tell your healthcare provider if you:
- Are pregnant or planning to become pregnant (see “What should I avoid while taking ATRIPLA?”).
- Are breastfeeding (see “What should I avoid while taking ATRIPLA?”).
- Have kidney problems or are undergoing kidney dialysis treatment.
- Have bone problems.
- Have liver problems, including hepatitis B virus infection. Your healthcare provider may want to do tests to check your liver while you take ATRIPLA.
- Have ever had mental illness or are using drugs or alcohol.
- Have ever had seizures or are taking medicine for seizures.
What important information should I know about taking other medicines with ATRIPLA?
ATRIPLA may change the effect of other medicines, including the ones for HIV-1, and may cause serious side effects. Your healthcare provider may change your other medicines or change their doses. Other medicines, including herbal products, may affect ATRIPLA. For this reason, it is very important to let all your healthcare providers and pharmacists know what medications, herbal supplements, or vitamins you are taking.
MEDICINES YOU SHOULD NOT TAKE WITH ATRIPLA
- The following medicines may cause serious and life-threatening side effects when taken with ATRIPLA. You should not take any of these medicines while taking ATRIPLA: Vascor (bepridil), Propulsid (cisapride), Versed (midazolam), Orap (pimozide), Halcion (triazolam), ergot medications (for example, Wigraine and Cafergot).
- ATRIPLA also should not be used with Combivir (lamivudine/zidovudine), EMTRIVA, Epivir, Epivir-HBV (lamivudine), Epzicom (abacavir sulfate/lamivudine), Trizivir (abacavir sulfate/lamivudine/zidovudine), SUSTIVA, TRUVADA, or VIREAD.
- Vfend (voriconazole) should not be taken with ATRIPLA since it may lose its effect or may increase the chance of having side effects from ATRIPLA.
- Do not take St. John’s wort (Hypericum perforatum), or products containing St. John’s wort with ATRIPLA. St. John’s wort is an herbal product sold as a dietary supplement. Talk with your healthcare provider if you are taking or are planning to take St. John’s wort. Taking St. John’s wort may decrease ATRIPLA levels and lead to increased viral load and possible resistance to ATRIPLA or cross-resistance to other anti-HIV-1 drugs.
- ATRIPLA should not be used with HEPSERA® (adefovir dipivoxil).
It is also important to tell your healthcare provider if you are taking any of the following:
- Fortovase, Invirase (saquinavir), Biaxin (clarithromycin); or Sporanox (itraconazole); these medicines may need to be replaced with another medicine when taken with ATRIPLA.
- Calcium channel blockers such as Cardizem or Tiazac (diltiazem), Covera HS or Isoptin (verapamil) and others; Crixivan (indinavir); the immunosuppressant medicines cyclosporine (Gengraf, Neoral, Sandimmune, and others), Prograf (tacrolimus), or Rapamune (sirolimus); Methadone; Mycobutin (rifabutin); Rifampin; cholesterol-lowering medicines such as Lipitor (atorvastatin), Pravachol (pravastatin sodium), and Zocor (simvastatin); or Zoloft (sertraline); these medicines may need to have their dose changed when taken with ATRIPLA.
- Videx, Videx EC (didanosine); tenofovir DF (a component of ATRIPLA) may increase the amount of didanosine in your blood, which could result in more side effects. You may need to be monitored more carefully if you are taking ATRIPLA and didanosine together. Also, the dose of didanosine may need to be changed.
- Reyataz (atazanavir sulfate) or Kaletra (lopinavir/ritonavir); these medicines may increase the amount of tenofovir DF (a component of ATRIPLA) in your blood, which could result in more side effects. Reyataz is not recommended with ATRIPLA. You may need to be monitored more carefully if you are taking ATRIPLA and Kaletra together. Also, the dose of Kaletra may need to be changed.
- Medicine for seizures [for example, Dilantin (phenytoin), Tegretol (carbamazepine), or phenobarbital]; your healthcare provider may want to switch you to another medicine or check drug levels in your blood from time to time.
These are not all the medicines that may cause problems if you take ATRIPLA. Be sure to tell your healthcare provider about all medicines that you take.
Keep a complete list of all the prescription and nonprescription medicines as well as any herbal remedies that you are taking, how much you take, and how often you take them. Make a new list when medicines or herbal remedies are added or stopped, or if the dose changes. Give copies of this list to all of your healthcare providers and pharmacists every time you visit your healthcare provider or fill a prescription. This will give your healthcare provider a complete picture of the medicines you use. Then he or she can decide the best approach for your situation.
How should I take ATRIPLA?
- Take the exact amount of ATRIPLA your healthcare provider prescribes. Never change the dose on your own. Do not stop this medicine unless your healthcare provider tells you to stop.
- You should take ATRIPLA on an empty stomach.
- Swallow ATRIPLA with water.
- Taking ATRIPLA at bedtime may make some side effects less bothersome.
- Do not miss a dose of ATRIPLA. If you forget to take ATRIPLA, take the missed dose right away, unless it is almost time for your next dose. Do not double the next dose. Carry on with your regular dosing schedule. If you need help in planning the best times to take your medicine, ask your healthcare provider or pharmacist.
- If you believe you took more than the prescribed amount of ATRIPLA, contact your local poison control center or emergency room right away.
- Tell your healthcare provider if you start any new medicine or change how you take old ones. Your doses may need adjustment.
- When your ATRIPLA supply starts to run low, get more from your healthcare provider or pharmacy. This is very important because the amount of virus in your blood may increase if the medicine is stopped for even a short time. The virus may develop resistance to ATRIPLA and become harder to treat.
- Your healthcare provider may want to do blood tests to check for certain side effects while you take ATRIPLA.
- Women should not become pregnant while taking ATRIPLA and for 12 weeks after stopping it. Serious birth defects have been seen in the babies of animals and women treated with efavirenz (a component of ATRIPLA) during pregnancy. It is not known whether efavirenz caused these defects. Tell your healthcare provider right away if you are pregnant. Also talk with your healthcare provider if you want to become pregnant.
- Women should not rely only on hormone-based birth control, such as pills, injections, or implants, because ATRIPLA may make these contraceptives ineffective. Women must use a reliable form of barrier contraception, such as a condom or diaphragm, even if they also use other methods of birth control. Efavirenz, a component of ATRIPLA, may remain in your blood for a time after therapy is stopped. Therefore, you should continue to use contraceptive measures for 12 weeks after you stop taking ATRIPLA.
- Do not breast-feed if you are taking ATRIPLA. The Centers for Disease Control and Prevention recommend that mothers with HIV not breast-feed because they can pass the HIV through their milk to the baby. Also, ATRIPLA may pass through breast milk and cause serious harm to the baby. Talk with your healthcare provider if you are breast-feeding. You should stop breast-feeding or may need to use a different medicine.
- Taking ATRIPLA with alcohol or other medicines causing similar side effects as ATRIPLA, such as drowsiness, may increase those side effects.
- Do not take any other medicines, including prescription and nonprescription medicines and herbal products, without checking with your healthcare provider.
- Avoid doing things that can spread HIV-1 infection since ATRIPLA does not stop you from passing the HIV-1 infection to others.
What are the possible side effects of ATRIPLA?
ATRIPLA may cause the following serious side effects:
- Lactic acidosis (buildup of an acid in the blood). Lactic acidosis can be a medical emergency and may need to be treated in the hospital. Call your healthcare provider right away if you get signs of lactic acidosis. (See “What is the most important information I should know about ATRIPLA?”)
- Serious liver problems (hepatotoxicity) , with liver enlargement (hepatomegaly) and fat in the liver (steatosis). Call your healthcare provider right away if you get any signs of liver problems. (See “What is the most important information I should know about ATRIPLA?”)
- “Flare-ups” of hepatitis B virus (HBV) infection , in which the disease suddenly returns in a worse way than before, can occur if you have HBV and you stop taking ATRIPLA. Your healthcare provider will monitor your condition for several months after stopping ATRIPLA if you have both HIV-1 and HBV infection and may recommend treatment for your HBV. ATRIPLA is not approved for the treatment of hepatitis B virus infection. If you have advanced liver disease and stop treatment with ATRIPLA, the “flare-up” of hepatitis B may cause your liver function to decline.
- Serious psychiatric problems. A small number of patients may experience severe depression, strange thoughts, or angry behavior while taking ATRIPLA. Some patients have thoughts of suicide and a few have actually committed suicide. These problems may occur more often in patients who have had mental illness. Contact your healthcare provider right away if you think you are having these psychiatric symptoms, so your healthcare provider can decide if you should continue to take ATRIPLA.
- Kidney problems (including decline or failure of kidney function). If you have had kidney problems in the past or take other medicines that can cause kidney problems, your healthcare provider should do regular blood tests to check your kidneys. Symptoms that may be related to kidney problems include a high volume of urine, thirst, muscle pain, and muscle weakness.
- Changes in bone mineral density (thinning bones). Laboratory tests show changes in the bones of patients treated with tenofovir DF, a component of ATRIPLA. Some HIV patients treated with tenofovir DF developed thinning of the bones (osteopenia) which could lead to fractures. If you have had bone problems in the past, your healthcare provider may need to do tests to check your bone mineral density or may prescribe medicines to help your bone mineral density. Additionally, bone pain and softening of the bone (which may contribute to fractures) may occur as a consequence of kidney problems.
Common side effects:
Patients may have dizziness, headache, trouble sleeping, drowsiness, trouble concentrating, and/or unusual dreams during treatment with ATRIPLA. These side effects may be reduced if you take ATRIPLA at bedtime on an empty stomach. They also tend to go away after you have taken the medicine for a few weeks. If you have these common side effects, such as dizziness, it does not mean that you will also have serious psychiatric problems, such as severe depression, strange thoughts, or angry behavior. Tell your healthcare provider right away if any of these side effects continue or if they bother you. It is possible that these symptoms may be more severe if ATRIPLA is used with alcohol or mood altering (street) drugs.
If you are dizzy, have trouble concentrating, or are drowsy, avoid activities that may be dangerous, such as driving or operating machinery.
Rash may be common. Rashes usually go away without any change in treatment. In a small number of patients, rash may be serious. If you develop a rash, call your healthcare provider right away.
Other common side effects include tiredness, upset stomach, vomiting, gas, and diarrhea.
Other possible side effects with ATRIPLA:
- Changes in body fat. Changes in body fat develop in some patients taking anti HIV-1 medicine. These changes may include 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 fat changes are not known.
- Skin discoloration (small spots or freckles) may also happen with ATRIPLA.
- In some patients with advanced HIV infection (AIDS), signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is started. It is believed that these symptoms are due to an improvement in the body’s immune response, enabling the body to fight infections that may have been present with no obvious symptoms. If you notice any symptoms of infection, please inform your doctor immediately.
- Additional side effects are inflammation of the pancreas, allergic reaction (including swelling of the face, lips, tongue, or throat), shortness of breath, pain, stomach pain, weakness and indigestion.
Tell your healthcare provider or pharmacist if you notice any side effects while taking ATRIPLA.
Contact your healthcare provider before stopping ATRIPLA because of side effects or for any other reason.
This is not a complete list of side effects possible with ATRIPLA. Ask your healthcare provider or pharmacist for a more complete list of side effects of ATRIPLA and all the medicines you will take.
How do I store ATRIPLA?
- Keep ATRIPLA and all other medicines out of reach of children.
- Store ATRIPLA at room temperature 77 °F (25 °C).
- Keep ATRIPLA in its original container and keep the container tightly closed.
- Do not keep medicine that is out of date or that you no longer need. If you throw any medicines away make sure that children will not find them.
General information about ATRIPLA:
Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use ATRIPLA for a condition for which it was not prescribed. Do not give ATRIPLA to other people, even if they have the same symptoms you have. It may harm them.
This leaflet summarizes the most important information about ATRIPLA. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about ATRIPLA that is written for health professionals.
Do not use ATRIPLA if the seal over bottle opening is broken or missing.
What are the ingredients of ATRIPLA?
Active Ingredients: efavirenz, emtricitabine, and tenofovir disoproxil fumarate
Inactive Ingredients: croscarmellose sodium, hydroxypropyl cellulose, microcrystalline cellulose, magnesium stearate, sodium lauryl sulfate. The film coating contains black iron oxide, polyethylene glycol, polyvinyl alcohol, red iron oxide, talc, and titanium dioxide.
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