Truvada

TRUVADA tablets are fixed-dose combination tablets containing emtricitabine and tenofovir DF. Emtricitabine is a synthetic nucleoside analog of cytidine. Tenofovir DF is converted in vivo to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5′-monophosphate. Both emtricitabine and tenofovir exhibit inhibitory activity against HIV-1 reverse transcriptase.

Emtricitabine

The chemical name of emtricitabine is 5-fluoro-1-(2R,5S)-[2(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine. Emtricitabine is the (-) enantiomer of a thio analog of cytidine, which differs from other cytidine analogs in that it has a fluorine in the 5-position.

It has a molecular formula of C8H10FN3O3S and a molecular weight of 247.24. It has the following structural formula:

Emtricitabine is a white to off-white crystalline powder with a solubility of approximately 112 mg/mL in water at 25 °C. The partition coefficient (log p) for emtricitabine is −0.43 and the pKa is 2.65.

Tenofovir DF

Tenofovir DF is a fumaric acid salt of the bisisopropoxycarbonyloxymethyl ester derivative of tenofovir. The chemical name of tenofovir DF is 9-[(R)-2 [[bis[[(isopropoxycarbonyl)oxy]methoxy]phosphinyl]methoxy]propyl]adenine fumarate (1:1). It has a molecular formula of C19H30N5O10P • C4H4O4 and a molecular weight of 635.52. It has the following structural formula:

Tenofovir DF is a white to off-white crystalline powder with a solubility of 13.4 mg/mL in water at 25 °C. The partition coefficient (log p) for tenofovir disoproxil is 1.25 and the pKa is 3.75. All dosages are expressed in terms of tenofovir DF except where otherwise noted.

TRUVADA tablets are for oral administration, and are available in the following strengths:

• Film-coated tablet containing 200 mg of emtricitabine and 300 mg of tenofovir DF (which is equivalent to 245 mg of tenofovir disoproxil) as active ingredients
• Film-coated tablet containing 167 mg of emtricitabine and 250 mg of tenofovir DF (which is equivalent to 204 mg of tenofovir disoproxil) as active ingredients
• Film-coated tablet containing 133 mg of emtricitabine and 200 mg of tenofovir DF (which is equivalent to 163 mg of tenofovir disoproxil) as active ingredients
• Film-coated tablet containing 100 mg of emtricitabine and 150 mg of tenofovir DF (which is equivalent to 123 mg of tenofovir disoproxil) as active ingredients

All strengths of TRUVADA tablets also include the following 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.

You should not take this medication if you are allergic to emtricitabine (Emtriva) or tenofovir (Viread). Do not take emtricitabine and tenofovir if you also take other medicines that contain emtricitabine, tenofovir, lamivudine, or adefovir (this includes Atripla, Combivir, Complera, Emtriva, Epivir, Epzicom, Hepsera, Trizivir, and Viread).

If you use emtricitabine and tenofovir to reduce your risk of HIV infection: You must have a negative HIV test immediatly before you start taking the medicine. An HIV test is also required every 3 months during treatment.

Do not take emtricitabine and tenofovir to reduce infection risk if you are HIV-positive, if have been exposed to HIV within the past month, or if you had any symptoms (such as fever, night sweats, swollen glands, diarrhea, body aches).

To make sure you can safely take emtricitabine and tenofovir, tell your doctor if you have other medical conditions, especially:

• liver or kidney disease;
• osteopenia (low bone mineral density); or
• if you also have hepatitis B infection.

Some people develop a life-threatening condition called lactic acidosis while taking emtricitabine and tenofovir. You may be more likely to develop lactic acidosis if you are overweight or have liver disease, if you are a woman, or if you have taken HIV or AIDS medications for a long time. Talk with your doctor about your individual risk.

FDA pregnancy category B. Emtricitabine and tenofovir is not expected to be harmful to an unborn baby. However, HIV can be passed to your baby if you are not properly treated during pregnancy. Take all of your HIV medicines as directed to control your infection. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

If you are pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of emtricitabine and tenofovir on the baby.

You should not breast-feed while you are using this medication to treat or prevent HIV. Women with HIV or AIDS should not breast-feed a baby. Even if your baby is born without HIV, the virus may be passed to the baby in your breast milk.

This medication should not be given to a child younger than 12 years old, or weighing less than 77 pounds.

The following adverse reactions are discussed in other sections of the labeling:

• Severe Acute Exacerbations of Hepatitis B [see BOX WARNING, WARNINGS AND PRECAUTIONS].
• New Onset or Worsening Renal Impairment [see WARNINGS AND PRECAUTIONS].
• Lactic Acidosis/Severe Hepatomegaly with Steatosis [see WARNINGS AND PRECAUTIONS].
• Bone Effects of Tenofovir DF [see WARNINGS AND PRECAUTIONS].
• Immune Reconstitution Syndrome [see WARNINGS AND PRECAUTIONS].

Adverse Reactions From Clinical Trials Experience In HIV-1 Infected Subjects

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The most common adverse reactions (incidence greater than or equal to 10%, any severity) occurring in Study 934, an active-controlled clinical trial of efavirenz, emtricitabine, and tenofovir DF, include diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash. See also Table 3 for the frequency of treatment-emergent adverse reactions (Grades 2–4) occurring in greater than or equal to 5% of subjects treated in any treatment group in this trial.

Skin discoloration, manifested by hyperpigmentation on the palms and/or soles, was generally mild and asymptomatic. The mechanism and clinical significance are unknown.

Study 934 –Treatment Emergent Adverse Reactions

In Study 934, 511 antiretroviralnaïve subjects received either VIREAD + EMTRIVA administered in combination with efavirenz (N=257) or zidovudine/lamivudine administered in combination with efavirenz (N=254) for 144 weeks. Subjects had a mean age of 40 years (range 20 to 73 years) and were predominantly male (88%). Overall, 65% were White, 17% were Black, and 13% were Hispanic. Adverse reactions observed in this trial were generally consistent with those seen in other trials in treatment-experienced or treatment-naïve subjects receiving VIREAD and/or EMTRIVA (Table 3).

Table 3 Selected Treatment-Emergent Adverse Reactionsa (Grades 2–4) Reported in ≥5% in Any Treatment Group in Study 934 (0–144 Weeks)

In addition to the events described above for Study 934, other adverse reactions that occurred in at least 5% of subjects receiving EMTRIVA or VIREAD with other antiretroviral agents in clinical trials include anxiety, arthralgia, increased cough, dyspepsia, fever, myalgia, pain, abdominal pain, back pain, paresthesia, peripheral neuropathy (including peripheral neuritis and neuropathy), pneumonia, and rhinitis.

Laboratory Abnormalities

Laboratory abnormalities observed in this trial were generally consistent with those seen in other trials of VIREAD and/or EMTRIVA (Table 4).

Table 4 Significant Laboratory Abnormalities Reported in ≥1% of Subjects in Any Treatment Group in Study 934 (0–144 Weeks)

In addition to the laboratory abnormalities described above for Study 934, Grades 3−4 laboratory abnormalities of increased bilirubin (>2.5 × ULN), increased pancreatic amylase (>2.0 × ULN), increased or decreased serum glucose (<40 or >250 mg/dL), and increased serum lipase (>2.0 × ULN) occurred in up to 3% of subjects treated with EMTRIVA or VIREAD with other antiretroviral agents in clinical trials.

Emtricitabine

In addition to the adverse reactions reported in adults, anemia and hyperpigmentation were observed in 7% and 32%, respectively, of pediatric subjects (3 months to less than 18 years of age) who received treatment with EMTRIVA in the larger of two open-label, uncontrolled pediatric trials (N=116). For additional information, consult the EMTRIVA prescribing information.

Tenofovir DF

In pediatric clinical trials (Studies 352 and 321) conducted in 184 HIV-1 infected subjects 2 to less than 18 years of age, the adverse reactions observed in pediatric subjects who received treatment with VIREAD were consistent with those observed in clinical trials of VIREAD in adults.

Eighty-nine pediatric subjects (2 to less than 12 years of age) received VIREAD in Study 352 for a median exposure of 104 weeks. Of these, 4 subjects discontinued from the trial due to adverse reactions consistent with proximal renal tubulopathy. Three of these 4 subjects presented with hypophosphatemia and also had decreases in total body or spine BMD Z score [see WARNINGS AND PRECAUTIONS]. For additional information, consult the VIREAD prescribing information.

Adverse Reactions From Clinical Trial Experience In HIV-1 Uninfected Adult Subjects

No new adverse reactions to TRUVADA were identified from two randomized placebo-controlled clinical trials (iPrEx, Partners PrEP), in which 2,830 HIV-1 uninfected adults received TRUVADA once daily for pre-exposure prophylaxis. Subjects were followed for a median of 71 weeks and 87 weeks, respectively. These trials enrolled HIV-negative individuals ranging in age from 18 to 67 years. The iPrEx trial enrolled only men or transgender women of Hispanic/Latino (72%), White (18%), Black (9%), and Asian (5%) race. The Partners PrEP trial enrolled both men (61−64% across treatment groups) and women in Kenya and Uganda. Table 5 provides a list of all adverse events that occurred in 2% or more of subjects in any treatment group in the iPrEx and Partners PrEP trials.

Table 6 provides a list of laboratory abnormalities observed in both trials. Six subjects in the TDF-containing arms of the Partners PrEP trial discontinued participation in the study due to an increase in blood creatinine compared with no discontinuations in the placebo group. One subject in the TRUVADA arm of the iPrEx trial discontinued from the study due to an increase in blood creatinine and another due to low phosphorous.

In addition to the laboratory abnormalities described above, Grade 1 proteinuria (1+) occurred in 6% of subjects receiving TRUVADA in the iPrEx trial. Grades 2−3 proteinuria (2–4+) and glycosuria (3+) occurred in less than 1% of subjects treated with TRUVADA in the iPrEx trial and Partners PrEP trial.

Table 5 Selected Adverse Events (All Grades) Reported in ≥2% in Any Treatment Group in the iPrEx Trial and Partners PrEP Trial

Table 6 Laboratory Abnormalities (Highest Toxicity Grade) Reported for Each Subject in the iPrEx Trial and Partners PrEP Trial

Changes In Bone Mineral Density

In clinical trials of HIV-1 uninfected individuals, decreases in BMD were observed. In the iPrEx trial, a substudy of 503 subjects found mean changes from baseline in BMD ranging from –0.4% to –1.0% across total hip, spine, femoral neck, and trochanter in the TRUVADA group compared with the placebo group, which returned toward baseline after discontinuation of treatment. Thirteen percent of subjects receiving TRUVADA versus 6% of subjects receiving placebo lost at least 5% of BMD at the spine during treatment. Bone fractures were reported in 1.7% of the TRUVADA group compared with 1.4% in the placebo group. No correlation between BMD and fractures was noted [see Clinical Studies]. The Partners PrEP trial found similar fracture rates between treatment and placebo groups (0.8% and 0.6%, respectively); no BMD evaluations were performed during this trial [see Clinical Studies].

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of VIREAD. No additional adverse reactions have been identified during postapproval use of EMTRIVA. Because postmarketing reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

allergic reaction, including angioedema

lactic acidosis, hypokalemia, hypophosphatemia

dyspnea

pancreatitis, increased amylase, abdominal pain

hepatic steatosis, hepatitis, increased liver enzymes (most commonly AST, ALT gamma GT)

rash

rhabdomyolysis, osteomalacia (manifested as bone pain and which may contribute to fractures), muscular weakness, myopathy

acute renal failure, renal failure, acute tubular necrosis, Fanconi syndrome, proximal renal tubulopathy, interstitial nephritis (including acute cases), nephrogenic diabetes insipidus, renal insufficiency, increased creatinine, proteinuria, polyuria

asthenia

The following adverse reactions, listed under the body system headings above, may occur as a consequence of proximal renal tubulopathy: rhabdomyolysis, osteomalacia, hypokalemia, muscular weakness, myopathy, hypophosphatemia.

Read the entire FDA prescribing information for Truvada (Emtricitabine and Tenofovir Disoproxil Fumarate)

Tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• have kidney, bone or liver problems (including hepatitis B infection). Be sure and tell your doctor if you are undergoing kidney dialysis treatment.
• are pregnant or breastfeeding

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. 

Emtricitabine and tenofovir are antiviral medicines that prevent human immunodeficiency virus (HIV) from multiplying in your body.

Emtricitabine and tenofovir is a combination medicine used to treat HIV, the virus that can cause acquired immunodeficiency syndrome (AIDS). This medicine is not a cure for HIV or AIDS, but it can be used to treat HIV in adults and children who are at least 12 years old and weigh at least 17 kilograms (37 pounds).

The Truvada brand of this medicine may be used together with safer-sex practices to reduce the risk of becoming infected with HIV. You must be HIV-negative and an adult to use Truvada for this purpose. Truvada may not provide protection from disease in every person.

Emtricitabine and tenofovir may also be used for purposes not listed in this medication guide.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Upset stomach.
• Loose stools (diarrhea).
• Not able to sleep.
• Dizziness.
• Headache.
• Strange or odd dreams.
• Feeling tired or weak.

For HIV negative patients taking this medicine to lower the chance of getting HIV through sex:

• Weight loss.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time Truvada is refilled. If you have any questions about this medicine, please talk with the doctor, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Truvada (emtricitabine and tenofovir disoproxil fumarate) or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Truvada. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

HBV Infection

It is recommended that all individuals be tested for the presence of chronic hepatitis B virus (HBV) before initiating Truvada. Truvada is not approved for the treatment of chronic HBV infection, and the safety and efficacy of Truvada have not been established in patients infected with HBV. Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV-1 and have discontinued Truvada. In some patients infected with HBV and treated with EMTRIVA, the exacerbations of hepatitis B were associated with liver decompensation and liver failure. Patients who are infected with HBV should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment with Truvada. If appropriate, initiation of anti-hepatitis B therapy may be warranted. HBV-uninfected individuals should be offered vaccination.

New Onset or Worsening Renal Impairment

Emtricitabine and tenofovir are principally eliminated by the kidney. Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported with the use of VIREAD [see Adverse Reactions (6.3)].

It is recommended that estimated creatinine clearance be assessed in all individuals prior to initiating therapy and as clinically appropriate during therapy with Truvada. In patients at risk of renal dysfunction, including patients who have previously experienced renal events while receiving HEPSERA®, it is recommended that estimated creatinine clearance, serum phosphorus, urine glucose, and urine protein be assessed prior to initiation of Truvada, and periodically during Truvada therapy.

Truvada should be avoided with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.4)]. 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 tenofovir DF. Some patients required hospitalization and renal replacement therapy. 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 at-risk patients.

Treatment of HIV-1 Infection

Dosing interval adjustment of Truvada and close monitoring of renal function are recommended in all patients with estimated creatinine clearance 30–49 mL/min [see Dosage and Administration (2.4)]. No safety or efficacy data are available in patients with renal impairment who received Truvada using these dosing guidelines, so the potential benefit of Truvada therapy should be assessed against the potential risk of renal toxicity. Truvada should not be administered to patients with estimated creatinine clearance below 30 mL/min or patients requiring hemodialysis.

Pre-exposure Prophylaxis

Truvada for a PrEP indication should not be used if estimated creatinine clearance is less than 60 mL/min. If a decrease in estimated creatinine clearance is observed in uninfected individuals while using Truvada for PrEP, evaluate potential causes and re-assess potential risks and benefits of continued use [see Dosage and Administration (2.4)].

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 tenofovir DF and emtricitabine, components of Truvada, alone or in combination with other antiretrovirals. Treatment with Truvada should be suspended in any patient or uninfected individual 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).

Coadministration with Other Products

Truvada is a fixed-dose combination of emtricitabine and tenofovir DF. Do not coadminister Truvada with other drugs containing emtricitabine, tenofovir DF, or tenofovir alafenamide, including ATRIPLA, COMPLERA, DESCOVY, EMTRIVA, GENVOYA, ODEFSEY, STRIBILD, VEMLIDY, or VIREAD. Due to similarities between emtricitabine and lamivudine, do not coadminister Truvada with other drugs containing lamivudine, including Combivir (lamivudine/zidovudine), Dutrebis (lamivudine/raltegravir), Epivir or Epivir-HBV (lamivudine), Epzicom (abacavir sulfate/lamivudine), Triumeq (abacavir sulfate/dolutegravir/lamivudine), or Trizivir (abacavir sulfate/lamivudine/zidovudine).

Do not coadminister Truvada with HEPSERA (adefovir dipivoxil).

Bone Effects of Tenofovir DF

Bone Mineral Density

In clinical trials in HIV-1 infected adults and in a clinical trial of HIV-1 uninfected individuals, tenofovir DF 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 [see Adverse Reactions (6.2) and VIREAD prescribing information]. Serum parathyroid hormone levels and 1,25 Vitamin D levels were also higher in subjects receiving tenofovir DF.

Clinical trials evaluating tenofovir DF in pediatric and adolescent subjects were conducted. 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 tenofovir DF 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. In all pediatric trials, skeletal growth (height) appeared to be unaffected. For more information, consult the VIREAD prescribing information.

The effects of tenofovir DF-associated changes in BMD and biochemical markers on long-term bone health and future fracture risk are unknown. Assessment of BMD should be considered for adult and pediatric patients who have a history of pathologic bone fracture or other risk factors for osteoporosis or bone loss. Although the effect of supplementation with calcium and vitamin D was not studied, such supplementation may be beneficial. If bone abnormalities are suspected then appropriate consultation should be obtained.

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 the use of tenofovir DF [see Adverse Reactions (6.3)]. 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 products containing tenofovir DF [see Warnings and Precautions (5.2)].

Immune Reconstitution Syndrome

Immune reconstitution syndrome has been reported in HIV-1 infected patients treated with combination antiretroviral therapy, including Truvada. During the initial phase of combination antiretroviral treatment, HIV-1 infected 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, and Guillain-Barré syndrome) 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.

Early Virologic Failure

Clinical trials in HIV-1 infected subjects have demonstrated that certain regimens that only contain three nucleoside reverse transcriptase inhibitors (NRTIs) are generally less effective than triple drug regimens containing two NRTIs in combination with either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a HIV-1 protease inhibitor. In particular, early virologic failure and high rates of resistance substitutions have been reported. Triple nucleoside regimens should therefore be used with caution. Patients on a therapy utilizing a triple nucleoside-only regimen should be carefully monitored and considered for treatment modification.

Comprehensive Management to Reduce the Risk of Acquiring HIV-1

Use Truvada for pre-exposure prophylaxis only as part of a comprehensive prevention strategy that includes other prevention measures, such as safer sex practices, because Truvada is not always effective in preventing the acquisition of HIV-1 [See Clinical Studies (14.2 and 14.3)].

• Counsel uninfected individuals about safer sex practices that include consistent and correct use of condoms, knowledge of their HIV-1 status and that of their partner(s), and regular testing for other sexually transmitted infections that can facilitate HIV-1 transmission (such as syphilis and gonorrhea).
• Inform uninfected individuals about and support their efforts in reducing sexual risk behavior.

Use Truvada to reduce the risk of acquiring HIV-1 only in individuals confirmed to be HIV-negative. HIV-1 resistance substitutions may emerge in individuals with undetected HIV-1 infection who are taking only Truvada, because Truvada alone does not constitute a complete treatment regimen for HIV-1 treatment [see Microbiology (12.4)]; therefore, care should be taken to minimize drug exposure in HIV-infected individuals.

• Many HIV-1 tests, such as rapid tests, detect anti-HIV antibodies and may not identify HIV-1 during the acute stage of infection. Prior to initiating Truvada for a PrEP indication, evaluate seronegative individuals for current or recent signs or symptoms consistent with acute viral infections (e.g., fever, fatigue, myalgia, skin rash) and ask about potential exposure events (e.g., unprotected, or condom broke during, sex with an HIV-1 infected partner) that may have occurred within the last month.
  • If clinical symptoms consistent with acute viral infection are present and recent (<1 month) exposures are suspected, delay starting PrEP for at least one month and reconfirm HIV-1 status or use a test approved by the FDA as an aid in the diagnosis of HIV-1 infection, including acute or primary HIV-1 infection.
• While using Truvada for a PrEP indication, HIV-1 screening tests should be repeated at least every 3 months. If symptoms consistent with acute HIV-1 infection develop following a potential exposure event, PrEP should be discontinued until negative infection status is confirmed using a test approved by the FDA as an aid in the diagnosis of HIV-1, including acute or primary HIV-1 infection.

Counsel uninfected individuals to strictly adhere to the recommended Truvada dosing schedule. The effectiveness of Truvada in reducing the risk of acquiring HIV-1 is strongly correlated with adherence as demonstrated by measurable drug levels in clinical trials [see Clinical Studies (14.2 and 14.3)].

If overdose occurs, the patient must be monitored for evidence of toxicity, and standard supportive treatment applied as necessary.

Emtricitabine: Limited clinical experience is available at doses higher than the therapeutic dose of EMTRIVA. In one clinical pharmacology trial, single doses of emtricitabine 1200 mg were administered to 11 subjects. No severe adverse reactions were reported.

Hemodialysis treatment removes approximately 30% of the emtricitabine dose over a 3-hour dialysis period starting within 1.5 hours of emtricitabine dosing (blood flow rate of 400 mL/min and a dialysate flow rate of 600 mL/min). It is not known whether emtricitabine can be removed by peritoneal dialysis.

Tenofovir DF: Limited clinical experience at doses higher than the therapeutic dose of VIREAD 300 mg is available. In one trial, 600 mg tenofovir DF was administered to 8 subjects orally for 28 days, and no severe adverse reactions were reported. The effects of higher doses are not known.

Tenofovir is efficiently removed by hemodialysis with an extraction coefficient of approximately 54%. Following a single 300 mg dose of VIREAD, a four-hour hemodialysis session removed approximately 10% of the administered tenofovir dose.

NDC 61958-0703-1

Truvada®
(emtricitabine and tenofovir
disoproxil fumarate)
Tablets

100 mg/150 mg

30 tablets
Rx only

DISPENSER: Each time Truvada® is dispensed
give the patient the attached Medication Guide.

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

Truvada is sometimes used to reduce the risk of becoming infected with HIV. You must be HIV-negative to use Truvada for this purpose.

Truvada may cause a serious condition called lactic acidosis. Get emergency medical help if you have even mild symptoms such as: muscle pain or weakness, numb or cold feeling in your arms and legs, trouble breathing, stomach pain, nausea with vomiting, fast or uneven heart rate, dizziness, or feeling very weak or tired.

If you have hepatitis B you may develop liver symptoms after you stop taking this medicine, even months after stopping.

Take Truvada exactly as prescribed by your doctor. Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

You may take this medicine with or without food.

Use Truvada regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

While using Truvada, you may need frequent blood tests. Your kidney and liver function, or bone mineral density may also need to be checked.

If you have hepatitis B you may develop liver symptoms after you stop taking this medication, even months after stopping. Your doctor may want to check your liver function for several months after you stop using Truvada.

HIV/AIDS is usually treated with a combination of drugs. Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice. Every person with HIV or AIDS should remain under the care of a doctor.

Store in the original container at room temperature, away from moisture and heat. Keep the bottle tightly closed when not in use.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• chemotherapy, injected antibiotics, injectable osteoporosis medications, medicine for bowel disorders, medicine to prevent organ transplant rejection;

• antiviral medicine to treat hepatitis C - ledipasvir, sofosbuvir, velpatasvir;

• other HIV medications - atazanavir, darunavir, didanosine, lopinavir, ritonavir; or

• some pain or arthritis medicines - aspirin, Tylenol, Advil, and Aleve.

This list is not complete. Other drugs may interact with emtricitabine and tenofovir, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Applies to emtricitabine / tenofovir: oral tablet

Along with its needed effects, emtricitabine / tenofovir may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking emtricitabine / tenofovir:

• Blisters under the skin
• body aches or pain
• difficulty in breathing
• ear and nasal congestion
• fever and chills
• loss of voice
• pain or tenderness around the eyes and cheekbones
• rash with flat lesions or small raised lesions on the skin
• redness of the skin
• runny nose
• sore throat
• spots on your skin resembling a blister or pimple
• unusual tiredness or weakness

• Blindness or vision changes
• burning of the face or mouth
• burning, crawling, itching, numbness, painful, prickling, "pins and needles", or tingling feelings in the hands, arms, feet, or legs
• chest pain
• clumsiness or unsteadiness
• stabbing pain
• weakness in the hands or feet

• Agitation
• bloating
• bloody or cloudy urine
• bone pain
• change in how much or how often you urinate
• coma
• confusion
• constipation
• cough
• darkened urine
• difficult or painful urination
• difficulty in swallowing
• fast heartbeat
• fast, shallow breathing
• general feeling of discomfort
• increased blood pressure
• increased thirst
• indigestion
• irritability
• itching skin, hives, welts
• lethargy
• loss of appetite
• lower back or side pain
• muscle pain or cramping
• muscle twitching
• pains in the stomach, side, or abdomen, possibly radiating to the back
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• rapid weight gain
• seizures
• sleepiness
• stomach pain
• stupor
• sudden decrease in the amount of urine
• swelling of the face, fingers, hands, lower legs, or ankles
• tightness in the chest
• yellow eyes or skin

Some side effects of emtricitabine / tenofovir may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Depression
• diarrhea
• nausea

• Acidic or sour stomach
• anxiety
• back pain
• belching
• difficulty in moving
• heartburn
• joint pain
• lack or loss of strength
• pain
• passing of gas
• stomach upset
• stuffy nose
• sweating
• swollen joints
• tiredness
• trouble sleeping
• vomiting
• weight loss