Truvada

Truvada is a combination antiviral tablet that may be used to reduce the risk of getting HIV-1 infection in at-risk adults and adolescents (this is called HIV PrEP [pre-exposure prophylaxis]) OR to treat HIV-1 infection in combination with other HIV-1 medications.

• Truvada is FDA-approved for HIV PrEP in at-risk adults and adolescents who weigh at least 77 pounds (35 kg). Before starting, you must have a negative HIV-1 test.
• Truvada can be used for HIV-1 treatment in adults and children who weigh at least 37 pounds (17 kg) and who are able to swallow a tablet.
• Truvada is not a cure for HIV or AIDS (acquired immunodeficiency syndrome).

Truvada (emtricitabine/tenofovir disoproxil fumarate) gained FDA approval on August 2, 2004. Generic Truvada is available.

Take Truvada exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets.

• If you take Truvada to treat HIV-1 infection, you need to take other HIV-1 medicines. Your healthcare provider will tell you what medicines to take and how to take them.
• If you take Truvada for HIV PrEP, it may be the only tablet you take, unless you have other medical conditions.

Take Truvada 1 time each day. You may take this medicine with or without food.

• Children who take Truvada are prescribed a lower-strength tablet than adults. Children should swallow the Truvada tablet whole. Tell your healthcare provider if your child cannot swallow the tablet, because they may need a different HIV-1 medicine.
• Your healthcare provider will change the dose of Truvada as needed based on your child's weight, so your child's weight should be checked regularly.

Do not change your dose or stop taking Truvada without first talking with your healthcare provider. Stay under a healthcare provider's care when taking Truvada.

Truvada has a boxed warning, which is the most serious warning the FDA requires. It covers two separate risks.

Worsening of hepatitis B after stopping Truvada

Severe flare-ups of hepatitis B, including liver decompensation and liver failure, have been reported in people with hepatitis B virus (HBV) infection who stopped taking Truvada. If you have HBV and you stop Truvada, your healthcare provider will monitor your liver function with clinical checks and blood tests for at least several months afterward. Anti-hepatitis B treatment may be needed, particularly if you have advanced liver disease or cirrhosis. If you do not have HBV, you should be offered vaccination.

Risk of drug resistance if you have undiagnosed early HIV-1 infection

Truvada used for HIV-1 PrEP must only be prescribed to people confirmed to be HIV negative immediately before starting and at least every 3 months while taking it. Drug-resistant HIV-1 has been found in people who started Truvada for PrEP while they had an undetected new HIV-1 infection. Truvada for PrEP should not be started if you have signs or symptoms of acute HIV-1 infection unless a negative HIV-1 status is confirmed.

Truvada is a prescription medicine that contains 2 antivirals, emtricitabine and tenofovir disoproxil fumarate. Both are nucleoside reverse transcriptase inhibitors (NRTIs). Inside your cells, each one is converted into an active form (emtricitabine 5'-triphosphate and tenofovir diphosphate) that competes with the natural building blocks HIV uses to copy itself. Once the drug is built into the growing viral DNA chain, the chain stops. This blocks reverse transcriptase, the enzyme HIV needs to infect cells and make more virus.

When used for HIV PrEP, Truvada acts as a preventive measure to stop the virus from multiplying and spreading from the site of infection if you are exposed to it. Consistent blood levels must be maintained to do this, which requires taking the tablet every day.

When used to treat HIV-1 infection, Truvada needs to be taken in combination with at least one other HIV-1 medicine. By blocking reverse transcriptase, Truvada reduces the amount of HIV in your blood, lowering your viral load and improving your CD4+ T cell count. Truvada will not cure HIV infection or AIDS, but it may prevent damage to your immune system and the development of infections and diseases associated with AIDS.

Truvada for HIV-1 PrEP is contraindicated, meaning it must not be used, in anyone with unknown or positive HIV-1 status.

You must be HIV-1 negative to start Truvada. You must get tested to make sure that you do not already have HIV-1 infection. Some HIV-1 tests can miss HIV-1 infection in a person who has recently become infected. If you have flu-like symptoms, you could have recently become infected with HIV. Tell your healthcare provider if you had a flu-like illness within the last month before starting Truvada or at any time while taking it, or if you have symptoms of a new HIV-1 infection such as:

• tiredness
• fever
• joint or muscle aches
• headache
• sore throat
• vomiting or diarrhea
• rash
• night sweats
• enlarged lymph nodes in the neck or groin.

If you may have been exposed to HIV-1 in the past month, or you have symptoms that could be a new HIV-1 infection, your healthcare provider should use a test that is FDA-approved or cleared to help diagnose acute or primary HIV-1 infection.

You must stay HIV negative to keep taking Truvada for HIV-1 PrEP. Know your HIV-1 status and the HIV-1 status of your partners. Ask your partners with HIV-1 if they are taking anti-HIV-1 medicines and have an undetectable viral load. An undetectable viral load is when the amount of virus in the blood is too low to be measured in a lab test. To maintain an undetectable viral load, your partners must keep taking HIV-1 medicines every day. Your risk of getting HIV-1 is lower if your partners with HIV-1 are taking effective treatment.

• Get tested for HIV-1 at least every 3 months, and whenever you are diagnosed with any other STI.
• Get tested for other STIs such as syphilis, chlamydia, and gonorrhea. These infections make it easier for HIV-1 to infect you.

Truvada for PrEP should be used as part of a complete prevention plan that also includes taking it every day and using condoms. If you think you were exposed to HIV-1, tell your healthcare provider right away. They may want to do more tests to be sure you are still HIV-1 negative.

Do not miss any doses of Truvada. Missing doses increases your risk of getting HIV-1 infection. Some people, including adolescents, may benefit from more frequent visits and counseling to help them keep taking it every day.

If you do become HIV-1 positive, you need more medicine than Truvada alone to treat HIV-1. Truvada by itself is not a complete treatment for HIV-1. If you have HIV-1 and take only Truvada, over time your HIV-1 may become harder to treat. Talk to your healthcare provider immediately if you do become HIV-1 positive.

Tell your healthcare provider about all of your medical conditions, including if you:

• have liver problems, including HBV infection
• have kidney problems or receive kidney dialysis treatment
• have bone problems
• are pregnant or plan to become pregnant
• are breastfeeding or plan to breastfeed.

Tests before and during treatment

• You will be tested for hepatitis B virus infection before or when you start Truvada.
• Before you start and while you are taking Truvada, your healthcare provider will check your kidneys on a schedule that suits you. This includes blood creatinine, estimated creatinine clearance, urine glucose, and urine protein. If you have chronic kidney disease, your serum phosphorus will also be checked.
• If you are taking Truvada for PrEP, you will be tested for HIV-1 before starting, at least every 3 months while taking it, and whenever you are diagnosed with another STI.

Pregnancy

Data from observational studies of Truvada use in pregnancy have not shown an increased risk of major birth defects. Antiretroviral Pregnancy Registry data show no significant difference in the overall risk of major birth defects after first trimester exposure to emtricitabine (2.3%) or tenofovir disoproxil fumarate (2.1%) compared with the background rate of 2.7% in a US reference population.

Being pregnant raises the risk of getting HIV-1, and a new HIV-1 infection during pregnancy raises the risk of passing HIV to the baby. If you are at risk of getting HIV-1, talk with your healthcare provider about continuing or starting Truvada for PrEP during pregnancy.

Tell your healthcare provider if you become pregnant during treatment with Truvada. There is a pregnancy registry for people who take Truvada during pregnancy. Healthcare providers can register patients by calling the Antiretroviral Pregnancy Registry at 1-800-258-4263.

Breastfeeding

Emtricitabine and tenofovir pass into human breast milk. Do not breastfeed if you have HIV-1, because of the risk of passing HIV to your baby. Do not breastfeed if you think you may have recently become infected with HIV.

If you take Truvada for HIV PrEP and you are HIV negative, talk with your healthcare provider about the best way to feed your baby. The benefits of breastfeeding and your need for Truvada should be weighed against any possible effects on your baby.

Most common side effects

The table below shows how often side effects were reported in clinical trials, alongside the rate in people who took a placebo or a comparison treatment.

Abnormal dreams were also among the most common side effects reported in people taking Truvada with other antivirals for HIV-1 treatment. Skin discoloration from hyperpigmentation occurred in 3% of adults taking emtricitabine plus tenofovir disoproxil fumarate, and was generally mild and caused no symptoms. In children aged 3 months to under 18 years treated with emtricitabine, hyperpigmentation was reported in 32% and anemia in 7%.

Serious side effects and warnings

Do not take Truvada if you also take other medicines that contain emtricitabine, tenofovir, lamivudine, or adefovir.

Truvada can cause the following serious side effects.

Worsening of hepatitis B virus infection (HBV). This is part of the boxed warning above. Your healthcare provider will test you for HBV before or when you start Truvada. If you have HBV and take Truvada, your HBV may flare up if you stop taking it. A flare-up is when your HBV infection suddenly returns in a worse way than before.

• Do not run out of Truvada. Refill your prescription or talk to your healthcare provider before it is all gone.
• Do not stop taking Truvada without first talking to your healthcare provider.
• If you stop taking Truvada, 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 medicine to treat hepatitis B. Tell your healthcare provider about any new or unusual symptoms you may have after you stop taking Truvada.

New or worse kidney problems, including kidney failure. Kidney problems, including acute kidney failure and Fanconi syndrome (kidney tubule injury with very low phosphate levels), have been reported with tenofovir disoproxil fumarate, one of the medicines in Truvada. Your healthcare provider should do blood and urine tests to check your kidneys before you start and during treatment. Truvada should be avoided if you are taking, or have recently taken, a medicine that can harm the kidneys, such as high-dose or multiple nonsteroidal anti-inflammatory drugs (NSAIDs). Tell your healthcare provider if you have any kidney problems such as swelling, urinating less, or feeling tired or short of breath. Ongoing or worsening bone pain, pain in your arms or legs, fractures, or muscle pain or weakness can also be signs of a kidney tubule problem and should be checked.

Changes in your immune system (immune reconstitution syndrome) can happen when you start taking medicines to treat HIV-1 infection. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time, such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia, or tuberculosis. Tell your doctor if you have signs of a new infection such as fever, night sweats, swollen glands, cold sores, cough, wheezing, diarrhea, or weight loss. Autoimmune disorders such as Graves' disease, polymyositis, Guillain-Barre syndrome, and autoimmune hepatitis have also been reported in this setting. These can start many months after treatment begins.

Bone problems can happen in some people who take Truvada. Bone problems include bone pain, or softening or thinning of bones, which may lead to fractures. In an iPrEx substudy of 503 people taking Truvada for PrEP, average bone mineral density fell by 0.4% to 1.0% across the hip, spine, femoral neck, and trochanter compared with placebo, and returned toward starting levels after treatment stopped. Bone fractures were reported in 1.7% of the Truvada group and 1.4% of the placebo group, with no link found between bone density and fractures. Your healthcare provider may need to do tests to check your bones. Tell your healthcare provider right away if you have sudden or unusual bone pain.

Too much lactic acid in your blood (lactic acidosis) and severe liver problems. Lactic acidosis and severe liver enlargement with fat build-up, including fatal cases, have been reported with medicines in the same class as Truvada. Tell your healthcare provider right away if you get 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, feeling dizzy or lightheaded, a fast or abnormal heartbeat, skin or the white part of your eyes turning yellow, dark tea-colored urine, light-colored stools, or loss of appetite for several days or longer.

Side effects caused by drug interactions. Taking Truvada with certain other medicines can raise the levels of those medicines in your body and lead to side effects. Tell your healthcare provider about all the medicines you take, and check with them before starting anything new.

Truvada does not prevent other sexually transmitted infections (STIs). Practice safer sex by using a latex or polyurethane condom to reduce the risk of getting STIs.

Side effects reported after Truvada was approved

The following have been reported since tenofovir disoproxil fumarate came into use. Because these reports are voluntary, it is not always possible to know how often they happen or whether the medicine caused them.

• Allergic reaction, including angioedema (swelling under the skin)
• Lactic acidosis, low potassium, low phosphate
• Shortness of breath
• Pancreatitis, raised amylase, stomach-area pain
• Fatty liver, hepatitis, raised liver enzymes
• Rash
• Rhabdomyolysis, osteomalacia (softening of the bones, which can contribute to fractures), muscle weakness, myopathy
• Acute kidney failure, kidney failure, acute tubular necrosis, Fanconi syndrome, kidney tubule damage, interstitial nephritis, nephrogenic diabetes insipidus, reduced kidney function, raised creatinine, protein in the urine, passing large amounts of urine
• Weakness (asthenia)

These are not all the possible side effects of Truvada. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Get emergency medical help if you have signs of an allergic reaction to Truvada: hives, difficulty breathing, swelling of your face, lips, tongue, or throat.

Truvada comes in the following strengths of emtricitabine and tenofovir disoproxil fumarate:

• 100 mg/150 mg
• 133 mg/200 mg
• 167 mg/250 mg
• 200 mg/300 mg.

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

For the prevention of HIV infection (HIV PrEP)

Adults and adolescents weighing 77 pounds (35 kg) or more: 1 tablet (200 mg/300 mg) once a day, with or without food.

Truvada for PrEP has not been studied in people weighing less than 77 pounds (35 kg), so it is not used in this group.

For the treatment of HIV-1 infection

Adults and children weighing 77 pounds (35 kg) or more: 1 tablet (200 mg/300 mg) once a day, with or without food.

Children weighing 37 pounds (17 kg) up to 77 pounds (35 kg) who can swallow a whole tablet are dosed by body weight:

Truvada is not approved for treating HIV-1 in children who weigh less than 37 pounds (17 kg). Because it is a fixed-dose combination tablet, the dose cannot be adjusted for smaller children.

Dose changes if you have kidney problems

If you are taking Truvada to treat HIV-1 infection, your dose may need to be spaced out further apart depending on your kidney function, measured as creatinine clearance.

No dose change is needed for mild kidney impairment (creatinine clearance 50 to 80 mL/min). The every 48 hours schedule has not been tested in clinical trials, so your response to treatment and your kidney function will be monitored closely. There is no information to guide dosing in children with kidney problems.

If you are taking Truvada for HIV-1 PrEP, it is not recommended if your estimated creatinine clearance is below 60 mL/min. If your kidney function falls while you are using Truvada for PrEP, your healthcare provider will look into why and reassess whether you should keep taking it.

For HIV PrEP

Truvada for PrEP was studied in two large randomized, double-blind, placebo-controlled trials. In both, how well it worked was strongly linked to how consistently people took it.

In both trials, the reduction in risk was greatest in people who had detectable drug levels in their blood or cells, which shows that taking Truvada every day matters.

For HIV-1 treatment

Study 934 compared emtricitabine plus tenofovir disoproxil fumarate with zidovudine/lamivudine, both given with efavirenz, in 511 adults who had not taken HIV medicines before. At 48 weeks, 84% of the emtricitabine plus tenofovir group had HIV-1 RNA below 400 copies/mL compared with 73% of the zidovudine/lamivudine group. At 144 weeks, the figures were 71% and 58%. Average CD4+ cell counts rose by 190 cells/mm3 and 158 cells/mm3 at 48 weeks, and by 312 cells/mm3 and 271 cells/mm3 at 144 weeks. More people in the zidovudine/lamivudine group stopped treatment because of side effects, which accounts for much of the difference.

Do not miss a dose of Truvada. If you are taking Truvada for PrEP, missing doses increases your risk of getting HIV-1 infection. If you are taking Truvada to treat HIV-1, the amount of virus in your blood may increase if you stop the medicine even for a short time, and the virus may develop resistance and become harder to treat.

If you miss a dose, talk to your healthcare provider or pharmacist about what to do. Do not take a double dose to make up for a missed one.

When your Truvada supply starts to run low, get more from your healthcare provider or pharmacy.

If you take too much Truvada, call your healthcare provider, go to the nearest hospital emergency room, or call the Poison Help line at 1-800-222-1222.

If an overdose happens, you will be monitored for signs of toxicity and given supportive treatment as needed. Hemodialysis removes about 30% of an emtricitabine dose over a 3-hour session and about 10% of a tenofovir disoproxil fumarate dose over a 4-hour session.

Sometimes it is not safe to use certain medicines at the same time. Some drugs can affect your blood levels of other drugs you use, which may increase side effects or make the medicines less effective.

Medicines that can affect your kidneys

Emtricitabine and tenofovir are cleared from the body by the kidneys. Taking Truvada with other medicines that are cleared the same way can raise the levels of either medicine. Examples include acyclovir, adefovir dipivoxil, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycoside antibiotics such as gentamicin, and high-dose or multiple NSAIDs (including Advil, Motrin, and Aleve). Cases of sudden kidney failure have been reported after starting high-dose or multiple NSAIDs in people with HIV who had risk factors for kidney problems. If you are at risk of kidney problems, your healthcare provider may suggest an alternative to NSAIDs.

Interactions that may need a dose change or extra monitoring

This list is not complete, and many other drugs may interact with emtricitabine and tenofovir. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.

Store Truvada at 25 degrees C (77 degrees F). Short periods between 15 degrees C and 30 degrees C (59 degrees F and 86 degrees F) are allowed.

• Keep the container tightly closed.
• Keep Truvada in its original container.
• Keep out of reach of children.

All Truvada tablets are blue and film-coated. They come in bottles of 30 tablets with a child-resistant closure.

Active ingredients: emtricitabine and tenofovir disoproxil fumarate. The tenofovir disoproxil fumarate content is equivalent to 245 mg, 204 mg, 163 mg, and 123 mg of tenofovir disoproxil in the 200 mg/300 mg, 167 mg/250 mg, 133 mg/200 mg, and 100 mg/150 mg tablets, respectively.

Inactive ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and pregelatinized starch (gluten-free). The 200 mg/300 mg strength tablets are coated with Opadry II Blue Y-30-10701, which contains FD&C Blue #2 aluminum lake, hypromellose 2910, lactose monohydrate, titanium dioxide, and triacetin. The 167 mg/250 mg, 133 mg/200 mg, and 100 mg/150 mg strength tablets are coated with Opadry II Blue, which contains FD&C Blue #2 aluminum lake, hypromellose 2910, lactose monohydrate, titanium dioxide, and triacetin.

Truvada (emtricitabine/tenofovir disoproxil fumarate) is manufactured for and distributed by Gilead Sciences, Inc., which is based in Foster City, California, USA.