Introduction

Antiretroviral; HIV nucleotide reverse transcriptase inhibitor; also has antiviral activity against HBV.

Uses for Tenofovir Disoproxil Fumarate

Treatment of HIV Infection

Treatment of HIV-1 infection in adults, adolescents, and pediatric patients; used in conjunction with other antiretrovirals.

Single-entity tenofovir DF used with another NRTI (dual NRTIs) in conjunction with an HIV integrase strand transferase inhibitor (INSTI), HIV nonnucleoside reverse transcriptase inhibitor (NNRTI), or HIV protease inhibitor (PI) in INSTI-, NNRTI-, or PI-based regimens. Also commercially available in various fixed combinations containing tenofovir DF and emtricitabine with or without a third antiretroviral; these fixed combinations used in certain patient groups to decrease pill burden and improve compliance.

For initial treatment in HIV-infected adults and adolescents, experts state that tenofovir DF and emtricitabine or tenofovir DF and lamivudine are recommended dual NRTI options for use in most INSTI-, NNRTI-, and PI-based regimens.

For initial treatment in antiretroviral-naive pediatric patients, experts state that tenofovir DF and emtricitabine or tenofovir DF and lamivudine are alternative dual NRTI options in adolescents ≥12 years of age at sexual maturity rating (SMR) 3, but should be used in children ≥2 years of age or adolescents at SMR 1 or 2 only in special circumstances after weighing potential risks versus benefits.

Because all 3 drugs have activity against both HIV and HBV, tenofovir DF and emtricitabine or tenofovir DF and lamivudine are preferred dual NRTI options for antiretroviral regimens in HIV-infected patients coinfected with HBV.

Emtricitabine/tenofovir DF fixed combination (Truvada) can be used in adults, adolescents, and children weighing ≥17 kg; used in conjunction with other antiretrovirals for treatment of HIV-1.

Efavirenz/emtricitabine/tenofovir DF fixed combination (Atripla) can be used in adults and adolescents ≥12 years of age weighing ≥40 kg; used alone as a complete treatment regimen or used in conjunction with other antiretrovirals.

Emtricitabine/rilpivirine/tenofovir DF fixed combination (Complera) can be used alone as a complete treatment regimen in antiretroviral-naive adults and adolescents ≥12 years of age weighing ≥35 kg with baseline plasma HIV-1 RNA levels ≤100,000 copies/mL; also can be used to replace a stable antiretroviral regimen in antiretroviral-experience patients who are virologically suppressed (i.e., plasma HIV-1 RNA levels <50 copies/mL) on their current regimen for ≥6 months, are currently receiving only their first or second antiretroviral regimen, have no history of treatment failure, and have no current evidence or history of resistance to the components of the fixed combination.

Preexposure Prophylaxis for Prevention of HIV-1 Infection (PrEP)

Emtricitabine/tenofovir DF (Truvada) used for preexposure prophylaxis (PrEP) in conjunction with safer sex practices to reduce the risk of sexually acquired HIV-1 in HIV-1-negative adults at high risk.

Adults at high risk include those with partner(s) known to be infected with HIV-1 or those engaging in sexual activity within a high prevalence area or social network and with ≥1 of the following factors: inconsistent or no condom use, diagnosis of sexually transmitted infections, exchange of sex for commodities (e.g., money, food, shelter, drugs), use of illicit drugs, alcohol dependence, incarceration, or partner(s) of unknown HIV-1 status with any of these risk factors.

PrEP with emtricitabine/tenofovir DF not always effective in preventing acquisition of HIV-1 infection; must be used as part of a comprehensive prevention strategy that includes safer sex practices. (See Precautions Related to HIV-1 Preexposure Prophylaxis under Cautions.)

Postexposure Prophylaxis following Occupational Exposure to HIV (PEP)

Postexposure prophylaxis of HIV infection following occupational exposure^{† [off-label]} (PEP) in health-care personnel and others exposed via percutaneous injury (e.g., needlestick, cut with sharp object) or mucous membrane or nonintact skin (e.g., chapped, abraded, dermatitis) contact with blood, tissue, or other body fluids that might contain HIV. Used in conjunction with other antiretrovirals.

USPHS recommends 3-drug regimen of raltegravir in conjunction with emtricitabine and tenofovir DF as the preferred regimen for PEP following occupational exposures to HIV. Several alternative regimens that include an INSTI, NNRTI, or PI and 2 NRTIs (dual NRTIs) also recommended. Preferred dual NRTI option for PEP regimens is emtricitabine and tenofovir DF (may be given as emtricitabine/tenofovir DF; Truvada); alternative dual NRTIs are tenofovir DF and lamivudine, lamivudine and zidovudine (may be given as lamivudine/zidovudine; Combivir), or zidovudine and emtricitabine.

Management of occupational exposures to HIV is complex and evolving; consult infectious disease specialist, clinician with expertise in administration of antiretroviral agents, and/or National Clinicians’ Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) whenever possible. Do not delay initiation of PEP while waiting for expert consultation.

Postexposure Prophylaxis following Nonoccupational Exposure to HIV (nPEP)

Postexposure prophylaxis of HIV infection following nonoccupational exposure^{† [off-label]} (nPEP) in individuals exposed to blood, genital secretions, or other potentially infectious body fluids that might contain HIV when the exposure represents a substantial risk for HIV transmission. Used in conjunction with other antiretrovirals.

When nPEP indicated in adults and adolescents ≥13 years of age with normal renal function, CDC states preferred regimen is either raltegravir or dolutegravir used in conjunction with emtricitabine and tenofovir DF (given as emtricitabine/tenofovir DF; Truvada); alternative recommended in these patients is ritonavir-boosted darunavir used in conjunction with emtricitabine/tenofovir DF (Truvada).

Consult infectious disease specialist, clinician with expertise in administration of antiretroviral agents, and/or the National Clinicians’ Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) if nPEP indicated in certain exposed individuals (e.g., pregnant women, children, those with medical conditions such as renal impairment) or if considering a regimen not included in CDC guidelines, source virus is known or likely to be resistant to antiretrovirals, or healthcare provider is inexperienced in prescribing antiretrovirals. Do not delay initiation of nPEP while waiting for expert consultation.

Chronic HBV Infection

Treatment of chronic HBV infection in adults and adolescents ≥12 years of age.

Used in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative adults with compensated liver disease who had not previously received a nucleoside antiviral (nucleoside-naive) and in treatment-experienced adults with documented resistance to lamivudine.

Only limited data in patients with decompensated liver disease.

Insufficient data in patients with adefovir-associated substitutions at baseline.

Do not use for treatment of chronic HBV infection in HIV-infected individuals who are not currently receiving antiretroviral therapy.

Treatment of chronic HBV infection is complex and evolving; consult specialized references. Information from the American Association for the Study of Liver Diseases (AASLD) regarding management of chronic HBV infection is available at [Web].

Tenofovir Disoproxil Fumarate Dosage and Administration

Administration

Oral Administration

Tenofovir DF (Viread): Administer orally once daily without regard to meals. Use in conjunction with other antiretrovirals for treatment of HIV-1 infection; can be used alone for treatment of chronic HBV infection.

Emtricitabine/tenofovir DF (Truvada): Administer orally once daily without regard to meals. Use in conjunction with other antiretrovirals for treatment of HIV-1; use alone as a complete regimen for PrEP for prevention of sexually transmitted HIV-1.

Efavirenz/emtricitabine/tenofovir DF (Atripla): Administer orally once daily on an empty stomach, preferably at bedtime. Use alone as a complete regimen or in conjunction with other antiretrovirals for treatment of HIV-1.

Emtricitabine/rilpivirine/tenofovir DF (Complera): Administer orally once daily with a meal. Use alone as a complete treatment regimen.

Because antiretrovirals contained in the fixed combinations also may be available in single-entity or other fixed-combination preparations, take care to ensure that therapy is not duplicated if a fixed combination is used in conjunction with other antiretrovirals. (See Precautions Related to Use of Fixed Combinations under Cautions.)

Oral Powder (Viread)

Measure dosage using only the scoop provided by the manufacturer.

Mix required number of scoops of oral powder with 2–4 ounces of soft food that can be swallowed without chewing (e.g., applesauce, baby food, yogurt); immediately ingest entire mixture to avoid a bitter taste.

Do not administer the powder in liquid since powder may float to the top, even after stirring.

Dosage

Available as tenofovir DF; dosage expressed in terms of tenofovir DF.

Dosage of tenofovir DF (Viread) oral powder is expressed as number of scoops of powder. The oral powder contains 40 mg of tenofovir DF per g; scoop provided by the manufacturer delivers 1 g of powder for each level scoop.

Pediatric Patients

Treatment of HIV Infection

Oral

Tenofovir DF (Viread) in children ≥2 to <12 years of age: 8 mg/kg (up to 300 mg) once daily as a tablet or oral powder. In those weighing ≥17 kg who can reliably swallow tablets, use a single tablet containing appropriate dosage (see Table 1). When oral powder is used, use required number of scoops of powder (see Table 2).

Tenofovir DF (Viread) in adolescents ≥12 years of age weighing ≥35 kg: 300 mg (one 300-mg tablet) once daily. In those unable to swallow the tablet, use 300 mg once daily as the oral powder (7.5 scoops of powder).

Emtricitabine/tenofovir DF (Truvada) in children weighing ≥35 kg: 1 tablet (emtricitabine 200 mg and tenofovir DF 300 mg) once daily.

Emtricitabine/tenofovir DF in children weighing 17 to <35 kg: Base dosage on weight and use a low-strength fixed-combination tablet. (See Table 3.)

Efavirenz/emtricitabine/tenofovir DF (Atripla) in adolescents ≥12 years of age weighing ≥40 kg: 1 tablet (efavirenz 600 mg, emtricitabine 200 mg, and tenofovir DF 300 mg) once daily.

Emtricitabine/rilpivirine/tenofovir DF (Complera) in adolescents ≥12 years of age weighing ≥35 kg: 1 tablet (emtricitabine 200 mg, rilpivirine 25 mg, and tenofovir DF 300 mg) once daily.

Chronic HBV Infection

Oral

Tenofovir DF (Viread) in adolescents ≥12 years of age weighing ≥35 kg: 300 mg once daily. Optimal duration of treatment unknown.

Adults

Treatment of HIV Infection

Oral

Tenofovir DF (Viread): 300-mg tablet once daily. Alternatively, in those unable to swallow tablets, 7.5 scoops of oral powder (300 mg) once daily.

Emtricitabine/tenofovir DF (Truvada): 1 tablet (emtricitabine 200 mg and tenofovir DF 300 mg) once daily.

Efavirenz/emtricitabine/tenofovir DF (Atripla): 1 tablet (efavirenz 600 mg, emtricitabine 200 mg, and tenofovir DF 300 mg) once daily.

Emtricitabine/rilpivirine/tenofovir DF (Complera): 1 tablet (emtricitabine 200 mg, rilpivirine 25 mg, and tenofovir DF 300 mg) once daily.

Preexposure Prophylaxis for Prevention of HIV-1 Infection (PrEP)

HIV-1-negative Adults at High Risk

Emtricitabine/tenofovir DF (Truvada): 1 tablet (emtricitabine 200 mg and tenofovir DF 300 mg) once daily.

Use PrEP only in high-risk adults confirmed to be HIV-1-negative; do not initiate if signs or symptoms of acute HIV-1 infection are present and recent (<1 month) exposure to HIV-1 is suspected. (See Precautions Related to HIV-1 Preexposure Prophylaxis [PrEP] under Cautions.)

Postexposure Prophylaxis following Occupational Exposure to HIV (PEP)† [off-label]

Oral

Tenofovir DF (Viread): 300 mg once daily. Use in conjunction with other antiretrovirals (see Postexposure Prophylaxis following Occupational Exposure to HIV under Uses).

Emtricitabine/tenofovir DF (Truvada): 1 tablet (emtricitabine 200 mg and tenofovir DF 300 mg) once daily. Use in conjunction with a recommended INSTI, NNRTI, or PI (see Postexposure Prophylaxis following Occupational Exposure to HIV [PEP] under Uses).

Emtricitabine/rilpivirine/tenofovir DF (Complera): 1 tablet (emtricitabine 200 mg, rilpivirine 25 mg, and tenofovir DF 300 mg) once daily. Use as a complete regimen for PEP.

Initiate PEP as soon as possible following occupational exposure to HIV (preferably within hours); continue for 4 weeks, if tolerated.

Postexposure Prophylaxis following Nonoccupational Exposure to HIV (nPEP)† [off-label]

Oral

Tenofovir DF (Viread): 300 mg once daily. Usually used in conjunction with emtricitabine and a preferred or alternative INSTI, NNRTI, or PI (see Postexposure Prophylaxis following Nonoccupational Exposure to HIV [nPEP] under Uses).

Emtricitabine/tenofovir DF (Truvada): 1 tablet (emtricitabine 200 mg and tenofovir DF 300 mg) once daily. Use in conjunction with a preferred or alternative INSTI, NNRTI, or PI.

Emtricitabine/rilpivirine/tenofovir DF (Complera): 1 tablet (emtricitabine 200 mg, rilpivirine 25 mg, and tenofovir DF 300 mg) once daily. Use as a complete regimen for nPEP.

Initiate nPEP as soon as possible (within 72 hours) following nonoccupational exposure that represents a substantial risk for HIV transmission and continue for 28 days.

nPep not recommended if exposed individual seeks care >72 hours after exposure.

Chronic HBV Infection

Oral

Tenofovir DF (Viread): 300 mg once daily.

Optimal duration of treatment unknown.

Special Populations

Hepatic Impairment

Treatment of HIV Infection

Oral

Tenofovir DF (Viread): Dosage adjustments not needed.

Emtricitabine/tenofovir DF (Truvada): Not studied in hepatic impairment.

Efavirenz/emtricitabine/tenofovir DF (Atripla): Use usual dosage in patients with mild hepatic impairment; caution advised. Not recommended in those with moderate or severe hepatic impairment.

Emtricitabine/rilpivirine/tenofovir DF (Complera): Use usual dosage in patients with mild or moderate hepatic impairment (Child-Pugh class A or B); not studied in those with severe hepatic impairment (Child-Pugh class C).

Treatment of Chronic HBV Infection

Oral

Tenofovir DF (Viread): Dosage adjustments not needed.

Renal Impairment

Treatment of HIV Infection

Oral

Tenofovir DF (Viread): Reduce dosage in adults with Cl_cr <50 mL/minute (see Table 4). Dosage adjustments not needed in those with Cl_cr 50–80 mL/minute; however, monitor calculated Cl_cr, serum phosphorus, urine glucose, and urine protein. Dosage recommendations not available for patients with Cl_cr <10 mL/minute who are not undergoing hemodialysis.

Emtricitabine/tenofovir DF (Truvada): Use usual dosage in adults with Cl_cr 50–80 mL/minute; however, monitor calculated Cl_cr, serum phosphorus, urine glucose, and urine protein. In adults with Cl_cr 30–49 mL/minute, reduce dosage to 1 tablet (emtricitabine 200 mg and tenofovir DF 300 mg) once every 48 hours; monitor clinical response and renal function since dosage not evaluated clinically. Do not use in adults with Cl_cr <30 mL/minute (including hemodialysis patients). Data insufficient to make dosage recommendations for treatment of HIV-1 infection in pediatric patients with renal impairment.

Efavirenz/emtricitabine/tenofovir DF (Atripla): Use usual dosage in patients with Cl_cr ≥50 mL/minute; do not use in those with estimated Cl_cr< 50 mL/minute.

Emtricitabine/rilpivirine/tenofovir DF (Complera): Do not use in moderate, severe, or end-stage renal impairment (estimated Cl_cr <50 mL/minute) or if dialysis required.

Preexposure Prophylaxis for Prevention of HIV-1 Infection

Oral

Emtricitabine/tenofovir DF (Truvada): Use usual dosage in adults with Cl_cr ≥60 mL/minute; however, monitor calculated Cl_cr, serum phosphorus, urine glucose, and urine protein. If Cl_cr decreases, evaluate potential causes and reassess potential risks and benefits of continued use. Do not use if Cl_cr <60 mL/minute.

Treatment of Chronic HBV Infection

Oral

Tenofovir DF (Viread): Adjust dosage if Cl_cr <50 mL/minute (see Table 4). Dosage adjustments not needed in adults with Cl_cr 50–80 mL/minute; however, monitor calculated Cl_cr, serum phosphorus, urine glucose, and urine protein. Dosage recommendations not available for adults with Cl_cr <10 mL/minute who are not undergoing hemodialysis.

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Contraindications

• Tenofovir DF: Manufacturer states none.

• Emtricitabine/tenofovir DF: Do not use alone for treatment of HIV-1 infection; do not use for preexposure prophylaxis of HIV-1 infection in individuals with unknown or positive HIV-1 status. (See Precautions Related to HIV-1 Preexposure Prophylaxis [PrEP] under Cautions.)

• Efavirenz/emtricitabine/tenofovir DF (Atripla): History of clinically important hypersensitivity reaction (e.g., Stevens-Johnson syndrome, erythema multiforme, toxic skin eruption) to efavirenz; concomitant use with voriconazole contraindicated (because of efavirenz component).

• Emtricitabine/rilpivirine/tenofovir DF (Complera): Concomitant use with certain drugs that induce CYP3A or elevate gastric pH contraindicated (because of rilpivirine component); substantially decreased plasma concentrations of rilpivirine may occur and may result in loss of virologic response and development of resistance to rilpivirine and/or class resistance to HIV NNRTIs.

• Fixed combinations containing tenofovir DF: Consider contraindications associated with each drug in the fixed combination.

Warnings/Precautions

Warnings

Lactic Acidosis and Severe Hepatomegaly with Steatosis

Lactic acidosis and severe hepatomegaly with steatosis (sometimes fatal) reported in patients receiving HIV NRTIs, including tenofovir DF, in conjunction with other antiretrovirals. Reported mostly in women; obesity and long-term NRTI therapy also may be risk factors. Cases reported in patients with no known risk factors.

Use tenofovir DF (single entity or fixed combinations) with caution in patients with known risk factors for liver disease.

Discontinue if there are clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (e.g., hepatomegaly and steatosis even in the absence of marked increases in serum aminotransferase concentrations).

Individuals with HBV Infection

Test all HIV-infected patients for presence of HBV before initiating antiretroviral therapy.

Test all HBV-infected patients for HIV before initiating tenofovir DF.

Use tenofovir DF with other highly active antiretroviral agents in individuals coinfected with HBV and HIV.

Severe acute exacerbations of HBV reported following discontinuance of HBV therapy in patients with HBV infection. HBV exacerbations have been associated with hepatic decompensation and hepatic failure.

If tenofovir DF (single entity or fixed combinations) used in patients coinfected with HIV and HBV, closely monitor hepatic function (using both clinical and laboratory follow-up) for at least several months after tenofovir DF or fixed combinations containing tenofovir DF are discontinued. If appropriate, initiation or resumption of HBV treatment may be warranted.

Precautions Related to HIV-1 Preexposure Prophylaxis

Use emtricitabine/tenofovir DF (Truvada) for HIV-1 PrEP only in HIV-1-negative adults at high risk.

Confirm a negative HIV-1 test immediately prior to initiating PrEP and screen for HIV-1 infection at least once every 3 months during PrEP. Also test for HBV prior to initiating PrEP. (See Individuals with HBV Infection under Cautions.)

Emtricitabine/tenofovir DF PrEP not always effective in preventing acquisition of HIV-1 infection.

Must be used as part of a comprehensive HIV prevention strategy that includes other prevention measures (e.g., safer sex practices). (See REMS.) Counsel all uninfected individuals about safer sex practices that include consistent and correct use of condoms, knowledge of their own HIV-1 status and that of their partner(s), and regular testing for other sexually transmitted infections that can facilitate HIV-1 transmission (e.g., syphilis, gonorrhea). Inform and support uninfected individuals regarding efforts to reduce sexual risk behavior.

Because emtricitabine/tenofovir DF alone does not constitute a complete antiretroviral regimen for treatment of HIV-1 infection, HIV-1 resistance-associated mutations may emerge if emtricitabine/tenofovir DF PrEP is used in individuals with undetected HIV-1 infection. Drug-resistant HIV-1 variants have been identified in such individuals.

Many HIV-1 tests (e.g., rapid tests) detect anti-HIV antibodies and may not identify HIV-1 during the acute stage of infection. Prior to initiating PrEP, evaluate HIV-negative individuals for current or recent signs or symptoms consistent with acute viral infections (e.g., fever, fatigue, myalgia, rash) and ask about any potential exposure events within the last month (e.g., unprotected sex, condom broke during sex with HIV-infected partner).

If symptoms consistent with acute viral infection are present and recent (<1 month) exposures to HIV-1 are suspected, delay initiating PrEP for at least 1 month and reconfirm HIV-1 status or use a test approved by FDA as an aid in the diagnosis of HIV-1 infection, including acute or primary HIV-1 infection.

During PrEP, if symptoms consistent with acute HIV-1 infection develop following a potential exposure event, discontinue the drugs until negative infection status is confirmed using a test approved by FDA as an aid in the diagnosis of HIV-1 infection, including acute or primary HIV-1 infection.

Counsel uninfected individuals to strictly adhere to recommended emtricitabine/tenofovir DF dosage schedule. (See Preexposure Prophylaxis [PrEP] for Prevention of HIV-1 Infection under Dosage and Administration.) Effectiveness in reducing risk of acquiring HIV-1 is strongly correlated with adherence.

Adverse effects similar to those reported in HIV-infected patients receiving the drugs for treatment of HIV-1 infection.

Other Warnings/Precautions

Renal Toxicity

Renal impairment, including acute renal failure and Fanconi syndrome (renal tubular injury with hypophosphatemia) reported with tenofovir DF.

Calculate Cl_cr in all patients prior to and as clinically indicated during therapy. Routinely monitor calculated Cl_cr, serum phosphorus, urine glucose, and urine protein prior to and periodically during therapy in all patients at risk for renal impairment, including those who had adverse renal effects while receiving adefovir.

Avoid tenofovir DF or fixed combinations containing tenofovir DF in patients who are receiving or recently received nephrotoxic drugs (e.g., high-dose or multiple nonsteroidal anti-inflammatory agents [NSAIAs]). In patients at risk for renal dysfunction, promptly evaluate renal function if manifestations of proximal renal tubulopathy are present (i.e., persistent or worsening bone pain, pain in extremities, fractures, and/or muscular pain or weakness).

Bone Effects

Decreases from baseline in bone mineral density (BMD) at lumbar spine and hip, increases in biochemical markers of bone metabolism, increased serum parathyroid hormone, and increased 1,25 vitamin D levels reported in adults receiving tenofovir DF with lamivudine and efavirenz. Similar effects observed in pediatric patients with HIV-1 or HBV infection; however, skeletal growth appeared to be unaffected.

Clinical importance of tenofovir DF-associated changes in BMD and biochemical markers on long-term bone health and fracture risk are unknown. Consider BMD monitoring in adults and pediatric patients with history of pathologic bone fracture or other risk factors for osteoporosis or bone loss. Effect of calcium and vitamin D supplementation not studied, but may be beneficial for all patients. If bone abnormalities suspected, obtain appropriate consultation.

Osteomalacia associated with proximal renal tubulopathy, which may contribute to fractures, reported; arthralgias and muscle pain or weakness also reported in patients with proximal renal tubulopathy. Consider hypophosphatemia and osteomalacia secondary to proximal renal tubulopathy in patients at risk of renal dysfunction who present with persistent or worsening bone or muscle symptoms.

Early Virologic Failure in HIV Infection

Triple NRTI regimens associated with early virologic failure and high rates of resistance. Use with caution; closely monitor and consider modifying the regimen.

Precautions Related to Use of Fixed Combinations

Emtricitabine/tenofovir DF, efavirenz/emtricitabine/tenofovir DF, emtricitabine/rilpivirine/tenofovir DF: Consider cautions, precautions, contraindications, and interactions associated with each drug in the fixed combination. Consider cautionary information applicable to specific populations (e.g., pregnant or nursing women, individuals with hepatic or renal impairment, geriatric patients) for each drug.

Because the antiretrovirals contained in the fixed-combination preparations also may be available in single-entity or other fixed-combination preparations, take care to ensure that therapy is not duplicated if a fixed combination is used in conjunction with other antiretrovirals.

Do not use multiple tenofovir DF-containing preparations concomitantly.

Do not use preparations containing tenofovir DF concomitantly with adefovir dipivoxil. In addition, because of similarities between emtricitabine and lamivudine, do not use any preparations containing emtricitabine (single entity or fixed combinations) concomitantly with any preparation containing lamivudine.

Adipogenic Effects

Possible redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement (“buffalo hump”), peripheral wasting, facial wasting, breast enlargement, and general cushingoid appearance.

Mechanisms and long-term consequences of adipogenic effects unknown; causal relationship not established.

Immune Reconstitution Syndrome

During initial treatment, HIV-infected patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jirovecii [formerly P. carinii]); this may necessitate further evaluation and treatment.

Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome) also reported in the setting of immune reconstitution; time to onset is more variable and can occur many months after initiation of antiretroviral therapy.

Specific Populations

Pregnancy

Tenofovir DF (Viread): Category B.

Emtricitabine/tenofovir DF (Truvada): Category B.

Efavirenz/emtricitabine/tenofovir DF (Atripla): Category D.

Emtricitabine/rilpivirine/tenofovir DF (Complera): Category B.

Antiretroviral Pregnancy Registry at 800-258-4263 or [Web].

Experts state that tenofovir DF and either emtricitabine or lamivudine is a preferred dual NRTI option for use in conjunction with an INSTI, NNRTI, or PI for initial treatment of HIV-1 infection in antiretroviral-naive pregnant women, and is a preferred dual NRTI option in pregnant HIV-1-infected women coinfected with HBV.

Experts state that the dual NRTI option of tenofovir DF and emtricitabine in conjunction with the fixed combination of lopinavir and ritonavir (lopinavir/ritonavir) is a preferred regimen for treatment of HIV type 2 (HIV-2) infection^{† [off-label]} in pregnant women.

If HIV-negative woman receiving emtricitabine/tenofovir DF (Truvada) for HIV-1 PrEP becomes pregnant, carefully consider whether PrEP regimen should be continued, taking into account the potential increased risk of HIV-1 infection during pregnancy.

Lactation

Tenofovir distributed into human milk in low concentrations.

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.

Pediatric Use

Tenofovir DF (Viread): Safety and efficacy for treatment of HIV-1 infection not established in children <2 years of age. Safety and efficacy for treatment of HBV infection not established in children <12 years of age or weighing <35 kg.

Emtricitabine/tenofovir DF (Truvada): Safety and efficacy for treatment of HIV-1 not established in pediatric patients weighing <17 kg; safety and efficacy for HIV-1 PrEP not established in pediatric patients.

Efavirenz/emtricitabine/tenofovir DF (Atripla): Do not use in pediatric patients <12 years of age or weighing <40 kg.

Emtricitabine/rilpivirine/tenofovir DF (Complera): Safety and efficacy not established in pediatric patients <12 years of age or weighing <35 kg.

Geriatric Use

Insufficient experience in those ≥65 years of age to determine whether they respond differently to tenofovir DF (single entity or fixed combinations) than younger adults; select dosage with caution.

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Hepatic Impairment

Tenofovir DF (Viread): Limited data indicate dosage adjustments not needed in patients with hepatic impairment. (See Hepatic Impairment under Dosage and Administration.)

Emtricitabine/tenofovir DF (Truvada): Not studied in patients with hepatic impairment.

Efavirenz/emtricitabine/tenofovir DF (Atripla): Not recommended in those with moderate or severe hepatic impairment.

Emtricitabine/rilpivirine/tenofovir DF (Complera): Not studied in patients with severe hepatic impairment (Child-Pugh class C).

Renal Impairment

Tenofovir DF (Viread): Principally eliminated by kidneys; pharmacokinetics likely to be affected. Monitor Cl_cr and serum phosphorus in patients with mild renal impairment. Adjust dosage in those with moderate or severe renal impairment. (See Renal Impairment under Dosage and Administration.)

Emtricitabine/tenofovir DF (Truvada): Do not use for treatment of HIV-1 in patients with Cl_cr <30 mL/minute or patients with end stage renal disease requiring dialysis. Do not use for PrEP in HIV-1 uninfected adults with Cl_cr <60 mL. If Cl_cr decreases during emtricitabine/tenofovir DF (Truvada) PrEP, evaluate potential causes and reassess potential risks and benefits of continued use.

Efavirenz/emtricitabine/tenofovir DF (Atripla): Do not use in those with estimated Cl_cr <50 mL/minute.

Emtricitabine/rilpivirine/tenofovir DF (Complera): Do not use in those with moderate, severe, or end-stage renal impairment (estimated Cl_cr <50 mL/minute) or if dialysis required.

Common Adverse Effects

HIV-1 infection: Nausea, diarrhea, rash, headache, pain, depression, asthenia.

HBV infection: GI effects (abdominal pain, nausea, vomiting, diarrhea), headache, insomnia, dizziness, fatigue, rash, pruritus, nasopharyngitis, back pain, fever.

Administration

Oral Administration

Tenofovir DF (Viread): Administer orally once daily without regard to meals. Use in conjunction with other antiretrovirals for treatment of HIV-1 infection; can be used alone for treatment of chronic HBV infection.

Emtricitabine/tenofovir DF (Truvada): Administer orally once daily without regard to meals. Use in conjunction with other antiretrovirals for treatment of HIV-1; use alone as a complete regimen for PrEP for prevention of sexually transmitted HIV-1.

Efavirenz/emtricitabine/tenofovir DF (Atripla): Administer orally once daily on an empty stomach, preferably at bedtime. Use alone as a complete regimen or in conjunction with other antiretrovirals for treatment of HIV-1.

Emtricitabine/rilpivirine/tenofovir DF (Complera): Administer orally once daily with a meal. Use alone as a complete treatment regimen.

Because antiretrovirals contained in the fixed combinations also may be available in single-entity or other fixed-combination preparations, take care to ensure that therapy is not duplicated if a fixed combination is used in conjunction with other antiretrovirals. (See Precautions Related to Use of Fixed Combinations under Cautions.)

Oral Powder (Viread)

Measure dosage using only the scoop provided by the manufacturer.

Mix required number of scoops of oral powder with 2–4 ounces of soft food that can be swallowed without chewing (e.g., applesauce, baby food, yogurt); immediately ingest entire mixture to avoid a bitter taste.

Do not administer the powder in liquid since powder may float to the top, even after stirring.

Dosage

Available as tenofovir DF; dosage expressed in terms of tenofovir DF.

Dosage of tenofovir DF (Viread) oral powder is expressed as number of scoops of powder. The oral powder contains 40 mg of tenofovir DF per g; scoop provided by the manufacturer delivers 1 g of powder for each level scoop.

Pediatric Patients

Treatment of HIV Infection

Oral

Tenofovir DF (Viread) in children ≥2 to <12 years of age: 8 mg/kg (up to 300 mg) once daily as a tablet or oral powder. In those weighing ≥17 kg who can reliably swallow tablets, use a single tablet containing appropriate dosage (see Table 1). When oral powder is used, use required number of scoops of powder (see Table 2).

Tenofovir DF (Viread) in adolescents ≥12 years of age weighing ≥35 kg: 300 mg (one 300-mg tablet) once daily. In those unable to swallow the tablet, use 300 mg once daily as the oral powder (7.5 scoops of powder).

Emtricitabine/tenofovir DF (Truvada) in children weighing ≥35 kg: 1 tablet (emtricitabine 200 mg and tenofovir DF 300 mg) once daily.

Emtricitabine/tenofovir DF in children weighing 17 to <35 kg: Base dosage on weight and use a low-strength fixed-combination tablet. (See Table 3.)

Efavirenz/emtricitabine/tenofovir DF (Atripla) in adolescents ≥12 years of age weighing ≥40 kg: 1 tablet (efavirenz 600 mg, emtricitabine 200 mg, and tenofovir DF 300 mg) once daily.

Emtricitabine/rilpivirine/tenofovir DF (Complera) in adolescents ≥12 years of age weighing ≥35 kg: 1 tablet (emtricitabine 200 mg, rilpivirine 25 mg, and tenofovir DF 300 mg) once daily.

Chronic HBV Infection

Oral

Tenofovir DF (Viread) in adolescents ≥12 years of age weighing ≥35 kg: 300 mg once daily. Optimal duration of treatment unknown.

Adults

Treatment of HIV Infection

Oral

Tenofovir DF (Viread): 300-mg tablet once daily. Alternatively, in those unable to swallow tablets, 7.5 scoops of oral powder (300 mg) once daily.

Emtricitabine/tenofovir DF (Truvada): 1 tablet (emtricitabine 200 mg and tenofovir DF 300 mg) once daily.

Efavirenz/emtricitabine/tenofovir DF (Atripla): 1 tablet (efavirenz 600 mg, emtricitabine 200 mg, and tenofovir DF 300 mg) once daily.

Emtricitabine/rilpivirine/tenofovir DF (Complera): 1 tablet (emtricitabine 200 mg, rilpivirine 25 mg, and tenofovir DF 300 mg) once daily.

Preexposure Prophylaxis for Prevention of HIV-1 Infection (PrEP)

HIV-1-negative Adults at High Risk

Emtricitabine/tenofovir DF (Truvada): 1 tablet (emtricitabine 200 mg and tenofovir DF 300 mg) once daily.

Use PrEP only in high-risk adults confirmed to be HIV-1-negative; do not initiate if signs or symptoms of acute HIV-1 infection are present and recent (<1 month) exposure to HIV-1 is suspected. (See Precautions Related to HIV-1 Preexposure Prophylaxis [PrEP] under Cautions.)

Postexposure Prophylaxis following Occupational Exposure to HIV (PEP)† [off-label]

Oral

Tenofovir DF (Viread): 300 mg once daily. Use in conjunction with other antiretrovirals (see Postexposure Prophylaxis following Occupational Exposure to HIV under Uses).

Emtricitabine/tenofovir DF (Truvada): 1 tablet (emtricitabine 200 mg and tenofovir DF 300 mg) once daily. Use in conjunction with a recommended INSTI, NNRTI, or PI (see Postexposure Prophylaxis following Occupational Exposure to HIV [PEP] under Uses).

Emtricitabine/rilpivirine/tenofovir DF (Complera): 1 tablet (emtricitabine 200 mg, rilpivirine 25 mg, and tenofovir DF 300 mg) once daily. Use as a complete regimen for PEP.

Initiate PEP as soon as possible following occupational exposure to HIV (preferably within hours); continue for 4 weeks, if tolerated.

Postexposure Prophylaxis following Nonoccupational Exposure to HIV (nPEP)† [off-label]

Oral

Tenofovir DF (Viread): 300 mg once daily. Usually used in conjunction with emtricitabine and a preferred or alternative INSTI, NNRTI, or PI (see Postexposure Prophylaxis following Nonoccupational Exposure to HIV [nPEP] under Uses).

Emtricitabine/tenofovir DF (Truvada): 1 tablet (emtricitabine 200 mg and tenofovir DF 300 mg) once daily. Use in conjunction with a preferred or alternative INSTI, NNRTI, or PI.

Emtricitabine/rilpivirine/tenofovir DF (Complera): 1 tablet (emtricitabine 200 mg, rilpivirine 25 mg, and tenofovir DF 300 mg) once daily. Use as a complete regimen for nPEP.

Initiate nPEP as soon as possible (within 72 hours) following nonoccupational exposure that represents a substantial risk for HIV transmission and continue for 28 days.

nPep not recommended if exposed individual seeks care >72 hours after exposure.

Chronic HBV Infection

Oral

Tenofovir DF (Viread): 300 mg once daily.

Optimal duration of treatment unknown.

Special Populations

Hepatic Impairment

Treatment of HIV Infection

Oral

Tenofovir DF (Viread): Dosage adjustments not needed.

Emtricitabine/tenofovir DF (Truvada): Not studied in hepatic impairment.

Efavirenz/emtricitabine/tenofovir DF (Atripla): Use usual dosage in patients with mild hepatic impairment; caution advised. Not recommended in those with moderate or severe hepatic impairment.

Emtricitabine/rilpivirine/tenofovir DF (Complera): Use usual dosage in patients with mild or moderate hepatic impairment (Child-Pugh class A or B); not studied in those with severe hepatic impairment (Child-Pugh class C).

Treatment of Chronic HBV Infection

Oral

Tenofovir DF (Viread): Dosage adjustments not needed.

Renal Impairment

Treatment of HIV Infection

Oral

Tenofovir DF (Viread): Reduce dosage in adults with Cl_cr <50 mL/minute (see Table 4). Dosage adjustments not needed in those with Cl_cr 50–80 mL/minute; however, monitor calculated Cl_cr, serum phosphorus, urine glucose, and urine protein. Dosage recommendations not available for patients with Cl_cr <10 mL/minute who are not undergoing hemodialysis.

Emtricitabine/tenofovir DF (Truvada): Use usual dosage in adults with Cl_cr 50–80 mL/minute; however, monitor calculated Cl_cr, serum phosphorus, urine glucose, and urine protein. In adults with Cl_cr 30–49 mL/minute, reduce dosage to 1 tablet (emtricitabine 200 mg and tenofovir DF 300 mg) once every 48 hours; monitor clinical response and renal function since dosage not evaluated clinically. Do not use in adults with Cl_cr <30 mL/minute (including hemodialysis patients). Data insufficient to make dosage recommendations for treatment of HIV-1 infection in pediatric patients with renal impairment.

Efavirenz/emtricitabine/tenofovir DF (Atripla): Use usual dosage in patients with Cl_cr ≥50 mL/minute; do not use in those with estimated Cl_cr< 50 mL/minute.

Emtricitabine/rilpivirine/tenofovir DF (Complera): Do not use in moderate, severe, or end-stage renal impairment (estimated Cl_cr <50 mL/minute) or if dialysis required.

Preexposure Prophylaxis for Prevention of HIV-1 Infection

Oral

Emtricitabine/tenofovir DF (Truvada): Use usual dosage in adults with Cl_cr ≥60 mL/minute; however, monitor calculated Cl_cr, serum phosphorus, urine glucose, and urine protein. If Cl_cr decreases, evaluate potential causes and reassess potential risks and benefits of continued use. Do not use if Cl_cr <60 mL/minute.

Treatment of Chronic HBV Infection

Oral

Tenofovir DF (Viread): Adjust dosage if Cl_cr <50 mL/minute (see Table 4). Dosage adjustments not needed in adults with Cl_cr 50–80 mL/minute; however, monitor calculated Cl_cr, serum phosphorus, urine glucose, and urine protein. Dosage recommendations not available for adults with Cl_cr <10 mL/minute who are not undergoing hemodialysis.

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Tenofovir DF and tenofovir are not substrates of CYP enzymes; tenofovir does not inhibit CYP3A4, 2D6, 2C9, or 2E1, but may have a slight inhibitory effect on CYP1A.

Substrate of P-glycoprotein (P-gp) transport system.

Substrate of breast cancer resistance protein (BCRP).

The following drug interactions are based on studies using tenofovir DF. Interaction studies also have been performed using efavirenz/emtricitabine/tenofovir DF or emtricitabine/rilpivirine/tenofovir DF. When a fixed combination containing tenofovir DF is used, consider interactions associated with each drug in the fixed combination.

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

CYP inhibitors or substrates: Pharmacokinetic interactions unlikely.

Drugs Affecting P-glycoprotein Transport System

P-gp inhibitors: Concomitant use may increase absorption of tenofovir DF.

Drugs Affecting Breast Cancer Resistance Protein

BCRP inhibitors: Concomitant use may increase absorption of tenofovir DF.

Nephrotoxic Drugs or Drugs Eliminated by Renal Excretion

Drugs that reduce renal function or compete for active tubular secretion: Potential increased concentrations of tenofovir and/or concomitant drug.

Specific Drugs