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Tenofovir Disoproxil Fumarate

Class: HIV Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
- Nucleotide Analog Reverse Transcriptase Inhibitors
- NtRTIs
VA Class: AM800
Chemical Name: Bis(1-methyl-ethyl)ester-(R)-5-[[2-(6-Amino-9H-purin-9-yl)-1-methylethoxy]methyl]-2,4,6,8-tetraoxa-5-phosphanonanedioic acid 5-oxide (E)-2-butenedioate
Molecular Formula: C9H14N5O4P•H2O
CAS Number: 202138-50-9
Brands: Viread

Tenofovir Disoproxil Fumarate is also contained as an ingredient in the following combinations:
Efavirenz, Emtricitabine, and Tenofovir Disoproxil Fumarate
Emtricitabine and Tenofovir Disoproxil Fumarate
Emtricitabine, Rilpivirine Hydrochloride, and Tenofovir Disoproxil Fumarate

Medically reviewed by Drugs.com on Aug 25, 2020. Written by ASHP.

Warning

    Lactic Acidosis and Hepatomegaly with Steatosis
  • Lactic acidosis and severe hepatomegaly with steatosis, including fatalities, reported in patients receiving HIV nucleoside reverse transcriptase inhibitors (NRTIs) in conjunction with other antiretrovirals. (See Lactic Acidosis and Severe Hepatomegaly with Steatosis under Cautions.)

    HBV Infection
  • Fixed combinations containing tenofovir disoproxil fumarate (tenofovir DF) not labeled by FDA for treatment of chronic HBV infection; safety and efficacy not established in HIV-infected patients coinfected with HBV.

  • Severe, acute exacerbations of HBV reported following discontinuance of preparations containing tenofovir DF in patients coinfected with HIV-1 and HBV. Monitor hepatic function closely with both clinical and laboratory follow-up for at least several months after tenofovir DF or fixed combination containing tenofovir DF and emtricitabine is discontinued in coinfected patients. If appropriate, initiation or resumption of HBV treatment may be warranted.

    HIV-1 Preexposure Prophylaxis (PrEP)
  • Prescribe emtricitabine/tenofovir DF (Truvada) for HIV-1 PrEP only for individuals confirmed to be HIV-1-negative immediately prior to initiation of PrEP; confirm HIV-1-negative status periodically (at least every 3 months) during PrEP.

  • Drug-resistant HIV-1 variants have been identified when emtricitabine/tenofovir DF PrEP was used following undetected acute HIV-1 infection. Do not initiate if signs or symptoms of acute HIV-1 infection are present, unless negative infection status is confirmed. (See Precautions Related to HIV-1 Preexposure Prophylaxis [PrEP] under Cautions.)

Risk Evaluation and Mitigation Strategy (REMS):

FDA approved a REMS for tenofovir DF to ensure that the benefits outweigh the risks. The REMS may apply to one or more preparations of tenofovir DF and consists of the following: elements to assure safe use. See https://www.accessdata.fda.gov/scripts/cder/rems/.

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 (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 (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).

Table 1. Tenofovir DF Dosage (Viread Tablets) for Treatment of HIV-1 Infection in Pediatric Patients ≥2 Years of Age Weighing ≥17 kg1

Weight (kg)

Dosage (as Tablets) Once Daily

17 to <22

150 mg

22 to <28

200 mg

28 to <35

250 mg

≥35

300 mg

Table 2. Tenofovir DF Dosage (Viread Oral Powder) for Treatment of HIV-1 Infection in Pediatric Patients ≥2 Years of Age

Weight (kg)

Dosage (as Oral Powder) Once Daily (40 mg of Tenofovir DF per Scoop)

10 to <12

80 mg (2 scoops)

12 to <14

100 mg (2.5 scoops)

14 to <17

120 mg (3 scoops)

17 to <19

140 mg (3.5 scoops)

19 to <22

160 mg (4 scoops)

22 to <24

180 mg (4.5 scoops)

24 to <27

200 mg (5 scoops)

27 to <29

220 mg (5.5 scoops)

29 to <32

240 mg (6 scoops)

32 to <34

260 mg (6.5 scoops)

34 to <35

280 mg (7 scoops)

≥35

300 mg (7.5 scoops)

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.)

Table 3. Emtricitabine/Tenofovir DF (Truvada) Dosage for Treatment of HIV-1 Infection in Children Weighing ≥17 kg230

Weight (kg)

Dosage of Emtricitabine/Tenofovir DF Given Once Daily

17 to <22 kg

1 tablet (emtricitabine 100 mg and tenofovir DF 150 mg)

22 to <28 kg

1 tablet (emtricitabine 133 mg and tenofovir DF 200 mg)

28 to <35 kg

1 tablet (emtricitabine 167 mg and tenofovir DF 250 mg)

≥35 kg

1 tablet (emtricitabine 200 mg and tenofovir DF 300 mg)

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
Oral

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

Table 4. Tenofovir DF (Viread) Dosage for Treatment of HIV-1 Infection in Adults with Renal Impairment1

Clcr (mL/minute)

Dosage

30–49

300 mg once every 48 hours

10–29

300 mg once every 72–96 hours

Hemodialysis patients

300 mg once every 7 days or after a total of approximately 12 hours of hemodialysis (assuming 3 hemodialysis sessions/week each lasting approximately 4 hours); give dose after hemodialysis

Emtricitabine/tenofovir DF (Truvada): Use usual dosage in adults with Clcr 50–80 mL/minute; however, monitor calculated Clcr, serum phosphorus, urine glucose, and urine protein. In adults with Clcr 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 Clcr <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 Clcr ≥50 mL/minute; do not use in those with estimated Clcr< 50 mL/minute.

Emtricitabine/rilpivirine/tenofovir DF (Complera): Do not use in moderate, severe, or end-stage renal impairment (estimated Clcr <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 Clcr ≥60 mL/minute; however, monitor calculated Clcr, serum phosphorus, urine glucose, and urine protein. If Clcr decreases, evaluate potential causes and reassess potential risks and benefits of continued use. Do not use if Clcr <60 mL/minute.

Treatment of Chronic HBV Infection
Oral

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

Cautions for Tenofovir Disoproxil Fumarate

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 Clcr in all patients prior to and as clinically indicated during therapy. Routinely monitor calculated Clcr, 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 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 Clcr 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 Clcr <30 mL/minute or patients with end stage renal disease requiring dialysis. Do not use for PrEP in HIV-1 uninfected adults with Clcr <60 mL. If Clcr 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 Clcr <50 mL/minute.

Emtricitabine/rilpivirine/tenofovir DF (Complera): Do not use in those with moderate, severe, or end-stage renal impairment (estimated Clcr <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.

Interactions for Tenofovir Disoproxil Fumarate

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

Drug

Interaction

Comments

Abacavir

No clinically important effect on abacavir pharmacokinetics

No in vitro evidence of antagonistic antiretroviral effects

Acyclovir, valacyclovir

Possible increased tenofovir and/or acyclovir concentrations

Avoid concomitant use

Adefovir

Possible increased tenofovir and/or adefovir concentrations

Do not use concomitantly

Aminoglycosides (gentamicin)

Gentamicin: Possible increased tenofovir and/or aminoglycoside concentrations

Avoid concomitant use

Atazanavir

Ritonavir-boosted, cobicistat-boosted, or unboosted atazanavir: Decreased atazanavir concentrations and AUC; increased tenofovir concentrations and AUC and possible increased risk of tenofovir-associated adverse effects, including renal disorders

No in vitro evidence of antagonistic antiretroviral effects

Unboosted atazanavir: Do not use concomitantly with tenofovir DF

Ritonavir-boosted atazanavir: Use atazanavir 300 mg, ritonavir 100 mg, and tenofovir DF 300 mg once daily with food; monitor for tenofovir toxicity; discontinue tenofovir DF if tenofovir-associated adverse effects occur

Ritonavir-boosted atazanavir used concomitantly with tenofovir DF and a histamine H2-receptor antagonist in antiretroviral-experienced adults: Use atazanavir 400 mg, ritonavir 100 mg, and tenofovir DF 300 mg once daily with food; monitor for tenofovir toxicity

Cobicistat-boosted atazanavir: Use atazanavir 300 mg, cobicistat 150 mg, and tenofovir DF 300 mg once daily with food; not recommended if estimated Clcr <70 mL/minute; monitor for tenofovir toxicity

Cobicistat-boosted atazanavir used concomitantly with tenofovir DF and an H2-receptor antagonist in antiretroviral-experienced adults: Use atazanavir 400 mg, cobicistat 150 mg, and tenofovir DF 300 mg once daily with food; monitor for tenofovir toxicity

Buprenorphine

No clinically important pharmacokinetic interactions

Dosage adjustments not needed

Cidofovir

Possible increased tenofovir and/or cidofovir concentrations

Avoid concomitant use

Daclatasvir

No clinically important pharmacokinetic interactions

Darunavir

Ritonavir-boosted darunavir: Increased tenofovir concentrations and AUC; increased darunavir concentrations and AUC

Cobicistat-boosted darunavir: Possible increased tenofovir concentrations

No in vitro evidence of antagonistic antiretroviral effects

Clinical importance unknown; monitor for tenofovir toxicity

Ritonavir-boosted darunavir: Experts state clinical importance unknown; monitor for tenofovir toxicity; manufacturer of darunavir states usual dosage of ritonavir-boosted darunavir and tenofovir DF can be used

Cobicistat-boosted darunavir: Not recommended if estimated Clcr <70 mL/minute; monitor for tenofovir toxicity

Delavirdine

No in vitro evidence of antagonistic antiretroviral effects

Didanosine

Buffered or delayed-release didanosine: Increased didanosine concentrations and AUC; no effect on tenofovir pharmacokinetics

Early virologic failure, rapid selection of resistant mutations, potential for immunologic nonresponse or decline in CD4+ T-cell counts reported; possible increased risk of didanosine-associated adverse effects (e.g., pancreatitis, lactic acidosis, neuropathy)

No in vitro evidence of antagonistic antiretroviral effects

Avoid concomitant use; experts state do not use concomitantly at any time

If used concomitantly, manufacturers state use caution and reduced didanosine dosage; closely monitor for didanosine-associated adverse effects and discontinue didanosine if such effects occur

In adults or adolescents weighing ≥60 kg with Clcr ≥60 mL/minute, reduce didanosine dosage to 250 mg once daily; in those weighing <60 kg with Clcr ≥60 mL/minute, reduce didanosine dosage to 200 mg once daily

If using didanosine delayed-release capsules, administer didanosine and tenofovir DF at same time without food or with a light meal; if using didanosine pediatric oral solution, administer didanosine and tenofovir DF at same time without food or administer didanosine on an empty stomach (i.e., ≥30 minutes before or 2 hours after food) if tenofovir DF is taken with food

Dolutegravir

No clinically important effect on tenofovir or dolutegravir pharmacokinetics

Dosage adjustments not needed

Efavirenz

No effect on concentrations or AUCs of either drug

No in vitro evidence of antagonistic antiretroviral effects

Dosage adjustments not needed

Elbasvir and grazoprevir

Fixed combination of elbasvir and grazoprevir (elbasvir/grazoprevir): No clinically important pharmacokinetic interactions

Dosage adjustments not needed

Emtricitabine

No clinically important pharmacokinetic interactions

In vitro evidence of additive to synergistic antiretroviral effects

No in vitro evidence of antagonistic antiviral effects against HBV

Entecavir

No evidence of clinically important pharmacokinetic interaction

No in vitro evidence of antagonistic antiviral effects against HBV

Estrogens/progestins

Hormonal contraceptives: No clinically important pharmacokinetic interaction

Etravirine

Decreased etravirine concentrations and AUC; no clinically important effect on tenofovir concentrations and AUC

No in vitro evidence of antagonistic antiretroviral effects

Dosage adjustments not needed for either drug

Ganciclovir, valganciclovir

Possible increased tenofovir and/or ganciclovir concentrations

Avoid concomitant use; if used concomitantly, monitor for dose-related toxicities

Histamine H2-receptor antagonists

Alterations in atazanavir concentrations possible with concomitant use of an H2-receptor antagonist, tenofovir DF, and atazanavir (with or without ritonavir)

If used concomitantly with atazanavir and an H2-receptor antagonist in treatment-experienced patients, a regimen of atazanavir 400 mg, tenofovir DF 300 mg, and ritonavir 100 mg once daily with food is recommended

Indinavir

Slight increase in tenofovir concentrations and decrease in indinavir concentrations; no effect on AUC of either drug

No in vitro evidence of antagonistic antiretroviral effects

Lamivudine

No clinically important pharmacokinetic interactions

No in vitro evidence of antagonistic antiretroviral effects

No in vitro evidence of antagonistic antiviral effects against HBV

Ledipasvir and sofosbuvir

Fixed combination of ledipasvir and sofosbuvir (ledipasvir/sofosbuvir): Increased tenofovir exposure

Use alternative HCV treatment that does not contain ledipasvir/sofosbuvir or use alternative antiretroviral regimen that does not contain tenofovir DF

If concomitant use necessary, monitor for tenofovir-associated adverse effects

Lopinavir/ritonavir

Increased tenofovir concentrations and AUC; no clinically important effect on lopinavir concentrations and AUC

Clinical importance unknown

Monitor for tenofovir toxicity; discontinue tenofovir DF if such effects occur

Maraviroc

No effect on maraviroc pharmacokinetics

No in vitro evidence of antagonistic antiretroviral effects

Methadone

No clinically important pharmacokinetic interactions

Dosage adjustments not needed

Nelfinavir

No effect on pharmacokinetics of either drug

No in vitro evidence of antagonistic antiretroviral effects

Nevirapine

No in vitro evidence of antagonistic antiretroviral effects

Nonnucleoside reverse transcriptase inhibitors (NNRTIs)

No evidence of pharmacokinetic interaction with efavirenz

No in vitro evidence of antagonistic antiretroviral effects with delavirdine, efavirenz, or nevirapine

NSAIAs

High-dose or multiple NSAIAs: Possible increased concentrations of tenofovir and/or the NSAIAs

Avoid tenofovir DF in patients who are receiving or have recently received a nephrotoxic drug (e.g., high-dose or multiple NSAIAs)

Ombitasvir, paritaprevir, and ritonavir

Fixed combination of ombitasvir, paritaprevir and ritonavir (ombitasvir/paritaprevir/ritonavir) with or without dasabuvir: No clinically important pharmacokinetic interactions

Ombitasvir/paritaprevir/ritonavir with or without dasabuvir: Dosage adjustments not needed

Raltegravir

Increased raltegravir concentrations and AUC; no clinically important effect on tenofovir concentrations

In vitro evidence of additive to synergistic antiretroviral effects

Not considered clinically important; dosage adjustments not needed

Ribavirin

No clinically important pharmacokinetic interactions

Rilpivirine

Increased tenofovir concentrations and AUC; no clinically important effect on rilpivirine concentrations or AUC

No in vitro evidence of antagonistic antiretroviral effects

Dosage adjustments not needed

Ritonavir

No in vitro evidence of antagonistic antiretroviral effects

Saquinavir

Ritonavir-boosted saquinavir (saquinavir 1 g twice daily and ritonavir 100 mg twice daily): No clinically important change in saquinavir concentrations with tenofovir DF 300 mg once daily

No in vitro evidence of antagonistic antiretroviral effects

Ritonavir-boosted saquinavir: Dosage adjustments not needed

Simeprevir

No clinically important effect on tenofovir pharmacokinetics; slightly decreased simeprevir concentrations and AUC

Dosage adjustments not needed for either drug

Sofosbuvir

No clinically important effect on tenofovir or sofosbuvir pharmacokinetics

Dosage adjustments not needed for either drug

Sofosbuvir and velpatasvir

Fixed combination of sofosbuvir and velpatasvir (sofosbuvir/velpatasvir): Possible increased tenofovir concentrations

Sofosbuvir/velpatasvir: Monitor for tenofovir-associated adverse effects

Stavudine

No in vitro evidence of antagonistic antiretroviral effects

Tacrolimus

No evidence of clinically important pharmacokinetic interaction

Telbivudine

No in vitro evidence of antagonistic antiviral effects against HBV

Tipranavir

Ritonavir-boosted tipranavir: Decreased tenofovir concentrations and AUC; possible decreased tipranavir concentrations and AUC

In vitro evidence of additive antiretroviral effects

Dosage adjustments not needed

Zidovudine

No in vitro evidence of antagonistic antiretroviral effects

Tenofovir Disoproxil Fumarate Pharmacokinetics

Absorption

Bioavailability

Pharmacokinetics in healthy individuals similar to those in individuals with HIV-1 infection.

Tenofovir DF is a diester prodrug of tenofovir.

Oral bioavailability of tenofovir from tenofovir DF is approximately 25%; peak plasma concentrations attained in about 1 hour in fasting HIV-infected patients.

Peak plasma concentrations and AUC in pediatric patients 2 to <12 years of age receiving 8 mg/kg (up to 300 mg) once daily as an oral powder or in pediatric patients 12 to <18 years of age receiving 300 mg once daily as tablets were similar to peak plasma concentrations and AUC reported in adults receiving 300 mg once daily. Exposures in HBV-infected pediatric patients 12 to <18 years of age receiving 300 mg once daily as tablets were similar to those in HIV-1-infected adults and adolescents receiving 300 mg once daily.

In nonfasting individuals, mean peak plasma concentrations were 26% lower when administered as an oral powder compared with administration as tablets; mean AUC was similar with both preparations.

Fixed-combination tablet containing efavirenz 600 mg, emtricitabine 200 mg, and tenofovir DF 300 mg (efavirenz/emtricitabine/tenofovir DF; Atripla) is bioequivalent to a 600-mg efavirenz tablet, 300-mg tenofovir DF tablet, and 200-mg emtricitabine capsule given simultaneously.

Fixed-combination tablet containing emtricitabine 200 mg, rilpivirine 25 mg, and tenofovir DF 300 mg (emtricitabine/rilpivirine/tenofovir DF; Complera) taken with a meal is bioequivalent to a 200-mg emtricitabine capsule, 25-mg rilpivirine tablet, and 300-mg tenofovir DF tablet taken simultaneously with a meal.

Fixed-combination tablet containing emtricitabine 200 mg and tenofovir DF 300 mg (emtricitabine/tenofovir DF; Truvada) is bioequivalent to a 200-mg emtricitabine capsule and 300-mg tenofovir DF tablet given simultaneously.

Food

Food delays time to peak plasma tenofovir concentrations by approximately 1 hour. Administration with a high-fat meal increases oral bioavailability of tenofovir (14% increase in peak plasma concentrations; 40% increase in AUC); pharmacokinetics not appreciably affected by administration with a light meal.

Distribution

Extent

Tenofovir distributed into semen and vaginal tissue and cervicovaginal fluid in low concentrations following oral administration. Very low concentrations may be distributed into saliva.

Tenofovir crosses human placenta.

Tenofovir distributed into human milk in low concentrations.

Plasma Protein Binding

In vitro binding to plasma or serum proteins is <0.7 or 7.2%, respectively, over tenofovir concentrations of 0.01–25 mcg/mL.

Elimination

Metabolism

Tenofovir DF requires initial diester hydrolysis for conversion to tenofovir and subsequent phosphorylation by cellular enzymes to form the active tenofovir diphosphate.

Tenofovir and its prodrug are not substrates of CYP enzymes.

Elimination Route

Tenofovir eliminated principally by kidneys using glomerular filtration and active tubular secretion; approximately 32% of an oral dose eliminated in urine within 24 hours.

Tenofovir removed by hemodialysis.

Half-life

Approximately 17 hours.

Special Populations

No substantial changes in tenofovir pharmacokinetics in individuals with moderate to severe hepatic impairment compared with those with normal hepatic function.

Moderate to severe renal impairment results in increased tenofovir plasma concentrations and AUC. (See Renal Impairment under Dosage and Administration.)

Stability

Storage

Oral

Powder

Tenofovir DF (Viread): 25°C (may be exposed to 15–30°C).

Tablets

Tenofovir DF (Viread): 25°C (may be exposed to 15–30°C).

Emtricitabine/tenofovir DF (Truvada), efavirenz/emtricitabine/tenofovir DF (Atripla), emtricitabine/rilpivirine/tenofovir DF (Complera): 25°C (may be exposed to 15–30°C). Store in original container; keep tightly closed.

Actions and Spectrum

  • Tenofovir DF is an HIV NRTI. Prodrug that is inactive until hydrolyzed in vivo to tenofovir which is then phosphorylated to the active metabolite (tenofovir diphosphate).

  • Active in vitro and in vivo against HIV-1 and HBV; some activity against HIV-2.

  • Inhibits replication of retroviruses, including HIV-1, by interfering with viral RNA-directed DNA polymerase (reverse transcriptase).

  • Inhibits HBV replication through competitive inhibition of viral reverse transcriptase.

  • Weak inhibitor of mammalian DNA α- and β-polymerases and mitochondrial DNA γ-polymerase. Low potential to induce mitochondrial toxicity.

  • HIV-1 resistant to tenofovir can be selected in vitro and have been reported in clinical isolates. HIV-1 strains with reduced susceptibility to tenofovir have K65R and K70E substitutions in reverse transcriptase.

  • HIV resistant to tenofovir may be cross-resistant to some NRTIs. Cross-resistance with HIV PIs or NNRTIs unlikely.

  • May be active against HBV resistant to adefovir and/or lamivudine. Some adefovir-, entecavir-, lamivudine-, or telbivudine-resistant HBV may have reduced susceptibility to tenofovir.

Advice to Patients

  • Critical nature of compliance with HIV therapy and importance of remaining under the care of a clinician. Importance of taking as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinician.

  • Importance of using tenofovir DF (Viread) or emtricitabine/tenofovir DF (Truvada) in conjunction with other antiretrovirals for treatment of HIV-1—not for monotherapy.

  • Efavirenz/emtricitabine/tenofovir DF (Atripla) or emtricitabine/rilpivirine/tenofovir DF (Complera) can be used alone as a complete treatment regimen.

  • Antiretroviral therapy is not a cure for HIV infection; opportunistic infections and other complications of HIV disease may still occur.

  • Advise HIV-infected patients that effective antiretroviral treatment regimens can decrease HIV-1 concentrations in blood and genital secretions and strict adherence to such regimens in conjunction with risk-reduction measures may decrease, but cannot absolutely eliminate, the risk of secondary transmission of HIV to others. Importance of continuing to practice safer sex (e.g., using latex or polyurethane condoms to minimize sexual contact with body fluids), never sharing personal items that can have blood or body fluids on them (e.g., toothbrushes, razor blades), and never reusing or sharing needles.

  • Emtricitabine/tenofovir DF (Truvada) medication guide must be provided to and reviewed with all HIV-negative individuals each time emtricitabine/tenofovir DF is dispensed for HIV-1 PrEP. (See REMS.) Advise such individuals of the importance of confirming that they are HIV-1-negative before starting PrEP, importance of regular HIV-1 testing (at least every 3 months) during PrEP, importance of strictly adhering to recommended dosage schedule and not missing any doses, and importance of using a complete prevention strategy that also includes other measures (e.g., consistent condom use, testing for other sexually transmitted infections such as syphilis and gonorrhea that may facilitate HIV-1 transmission, reducing sexual risk behavior). Advise uninfected individuals that emtricitabine/tenofovir DF PrEP does not protect all individuals from acquiring HIV-1 and to report any symptoms of acute HIV-1 infection (e.g., fever, headache, fatigue, arthralgia, vomiting, myalgia, diarrhea, pharyngitis, rash, night sweats, cervical and inguinal adenopathy) immediately to a clinician.

  • Importance of reading patient information provided by the manufacturer.

  • Redistribution/accumulation of body fat may occur; cause and long-term health effects unknown.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products, as well as concomitant medical problems such as renal or hepatic impairment.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. Advise HIV-infected women not to breast-feed.

  • Importance of advising patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Tenofovir Disoproxil Fumarate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Powder

40 mg per g

Viread

Gilead

Tablets, film-coated

150 mg

Viread

Gilead

200 mg

Viread

Gilead

250 mg

Viread

Gilead

300 mg

Viread

Gilead

Tenofovir Disoproxil Fumarate Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

150 mg with Emtricitabine 100 mg

Truvada

Gilead

200 mg with Emtricitabine 133 mg

Truvada

Gilead

250 mg with Emtricitabine 167 mg

Truvada

Gilead

300 mg with Emtricitabine 200 mg

Truvada

Gilead

300 mg with Emtricitabine 200 mg and Efavirenz 600 mg

Atripla

Bristol-Myers Squibb and Gilead

300 mg with Emtricitabine 200 mg and Rilpivirine Hydrochloride 25 mg (of rilpivirine)

Complera

Gilead

300 mg with Emtricitabine 200 mg, Elvitegravir 150 mg, and Cobicistat 150 mg

Stribild

Gilead

AHFS DI Essentials™. © Copyright 2021, Selected Revisions September 4, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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