TENOFOVIR DISOPROXIL FUMARATE (Generic for VIREAD)

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Oral Administration
Oral Solid Formulations
-Tablets: May be administered with or without food.
-Oral powder: Using the dosing scoop provided, measure the number of scoops prescribed (each level scoop delivers 40 mg). To ensure accurate dosing, use the flat edge of a clean knife to make the powder even with the top of the scoop. Mix the powder into 2-4 ounces (1/4 to 1/2 cup) of soft food that does not require chewing, such as applesauce, baby food, or yogurt. Do not mix with liquid; the powder will not disperse. To avoid bitter taste, administer the entire dose immediately after mixing. Clean the scoop after each administration.

Adverse events observed in pediatric tenofovir trials were consistent with those observed in clinical trials in adults. The most common adverse events that occurred in adult patients receiving tenofovir disoproxil with other antiretrovirals during clinical trials were mild to moderate gastrointestinal events, including nausea (8% to 11%), vomiting (2% to 7%), diarrhea (9% to 16%), flatulence (3% to 4%), abdominal pain (4% to 7%), dyspepsia (3% to 4%), and anorexia (3% to 4%) with weight loss (2% to 4%). The incidence of abdominal pain (22%), nausea (20%), and vomiting (13%) was higher in a separate study that involved 45 chronic hepatitis B and decompensated liver disease patients randomized to receive tenofovir for 48 weeks.

Adverse events observed in pediatric tenofovir trials were consistent with those observed in clinical trials in adults. During adult clinical trials, 2% of patients developed hyperglycemia (more than 250 mg/dL), while up to 3% experienced glycosuria (3+ or more). Hyperamylasemia (more than 175 units/L) has been noted in 4% to 9% of patients during clinical trials. There have been postmarketing reports of pancreatitis.

Adverse events observed in pediatric tenofovir trials were consistent with those observed in clinical trials in adults. Musculoskeletal adverse events experienced by adult patients receiving treatment with tenofovir during clinical trials included arthralgia (5%), back pain (3% to 9%), chest pain (unspecified) (3%), and myalgia (3% to 4%). Elevations in creatine kinase (male: more than 990 units/L; female: more than 845 units/L) were also observed in 2% to 12% during clinical trials. Rhabdomyolysis, myopathy, and muscular weakness have been noted during postmarketing surveillance. Worsening bone pain, pain in extremities, fractures and/or muscular pain or weakness (myasthenia) may also be manifestations of proximal renal tubulopathy; promptly evaluate renal function in patients experiencing these symptoms.


Adverse events observed in pediatric tenofovir trials were consistent with those observed in clinical trials in adults. Hypertriglyceridemia (more than 750 mg/dL) and hypercholesterolemia (more than 240 mg/dL) have been reported in 1% to 11% and 19% to 22%, respectively, of adult patients receiving tenofovir during clinical trials.

Lactic acidosis and severe hepatomegaly with steatosis, sometimes fatal, have been reported with the concomitant use of nucleoside reverse transcriptase inhibitors, including tenofovir, and other antiretroviral agents. Adult females appear to be at a higher risk for lactic acidosis; it is not clear whether this increased risk also applies to pediatric females. Tenofovir should be discontinued if a patient develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity, including hepatomegaly and steatosis even in the absence of marked elevated transaminases. During clinical trials, 2% to 10% of patients receiving tenofovir developed elevated hepatic enzymes (AST Male: more than 180 units/L; AST Female: more than 170 units/L; ALT Male: more than 215 units/L; ALT Female: more than 170 units/L). There have been reports of acute, severe hepatitis B exacerbation in patients after discontinuation of tenofovir therapy; close monitoring of clinical signs and symptoms, including laboratory monitoring, is recommended for several months after discontinuation. If appropriate, resumption of anti-hepatitis B therapy may be warranted, especially in patients with advanced liver disease or cirrhosis, since post-treatment exacerbation may lead to hepatic decompensation and liver failure.

Allergic reaction (unspecified), angioedema, and dyspnea have been noted during the postmarketing period with tenofovir.


Dermatologic adverse events may develop following treatment with tenofovir. Adverse events observed in pediatric trials were consistent with those observed in clinical trials in adults. Skin rash and diaphoresis were reported in 5% to 18% and 3%, respectively, of adult patients during clinical trials. Reports of rash included pruritus, exfoliative rash, macular rash, maculopapular rash, urticaria, bullous rash, vesicular rash, pruritic rash, and pustular rash.

During one clinical trial in adult patients, lipodystrophy, as described by the investigators and not a protocol defined syndrome, was reported in 1% of tenofovir disoproxil fumarate treated patients.

Renal impairment and renal failure (unspecified), which may include hypophosphatemia and acute interstitial nephritis, have been reported with the use of tenofovir. Assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients prior to initiating therapy, and as indicated during treatment. Additionally, patients at risk for or with a history of renal dysfunction should have serum phosphorus assessed prior to therapy initiation and periodically during therapy. In pediatric trials (n = 89), 4 patients discontinued therapy due to proximal renal tubulopathy; 3 of these patients presented with hypophosphatemia. Tenofovir should be avoided in those patients with concurrent or recent use of nephrotoxic agents (e.g., non-steroidal anti-inflammatory drugs [NSAIDs]). Cases of acute renal failure, requiring hospitalization and renal replacement therapy, have been reported in HIV-infected patients at high-risk for renal impairment, who appeared stable on tenofovir, after initiation of high-dose or multiple dose NSAIDs. Hematuria was noted in 3% to 7% of adult patients during HIV clinical trials. In a clinical trial involving 45 adults with chronic hepatitis B and decompensated liver disease, 4 patients (9%) experienced increase in serum creatinine of 0.5 mg/dL, 1 patient (2.2%) had a confirmed serum phosphorous less than 2 mg/dL, and 3 patients (6.7%) developed renal failure. Other adverse reactions that have been reported during the postmarketing period include elevated serum creatinine, Fanconi syndrome (with associated renal tubular acidosis (RTA)), hypophosphatemia, hypokalemia, nephrogenic diabetes insipidus, proteinuria, proximal renal tubulopathy, acute renal failure, renal insufficiency, interstitial nephritis, polyuria, and acute renal tubular necrosis. Health care providers are advised that worsening bone pain, pain in extremities, fractures and/or muscular pain or weakness may also be manifestations of proximal renal tubulopathy; promptly evaluate renal function in patients experiencing these symptoms.

Tenofovir has been associated with the development of adverse reactions that affect the nervous system and the body as a whole. Adverse events observed in pediatric trials were consistent with those observed in clinical trials in adults. During adult HIV clinical trials, patients treated with tenofovir in combination with other antiretrovirals reported experiencing the following symptoms: headache (5% to 14%), pain (7% to 13%), depression (4% to 11%), asthenia (6% to 11%), fatigue (9%), fever (2% to 8%), dizziness (1% to 8%), anxiety (6%), insomnia (3% to 5%), and peripheral neuropathy (including peripheral neuritis) (1% to 5%). In a separate study involving 45 adult patients with chronic hepatitis B and decompensated liver disease receiving tenofovir for 48 weeks the incidences of dizziness (13%), pyrexia or fever (11%), and insomnia (18%) were all higher than those reported for HIV treated patients.

Greater decreases in bone mineral density (BMD) have been associated with tenofovir relative to comparators in clinical studies. Normally, BMD increases rapidly in pediatric patients; however, in studies of tenofovir-treated pediatric patients, bone effects were similar to those noted in adult patients, suggesting increased bone turnover. Assessment of BMD is recommended in patients with a history of bone fractures or other risk factors for osteoporosis or bone loss. Although the effect of supplementation with calcium and vitamin D has not been studied, such supplementation may be considered for HIV-associated osteopenia or osteoporosis. If bone abnormalities are suspected, appropriate consultation should be obtained. One study evaluating HIV-infected children aged 2 to 12 years found total body BMD gains in recipients of tenofovir to be lower than the gains observed in patients receiving either stavudine or zidovudine. Additionally, at treatment week 48, 1 tenofovir-treated patient experienced significant (more than 4%) BMD loss in the lumbar spine; significant BMD losses were not observed in the stavudine or zidovudine treatment groups. In another study involving adolescents aged 12 to 17 years, the mean rate of BMD gain was less in the tenofovir-treated patients compared to the placebo group. Six tenofovir-treated adolescents and 1 placebo-treated adolescent had significant (more than 4%) lumbar spine BMD loss at 48 weeks. Two other studies in pediatric patients 2 to 11 years and 12 to 17 years with chronic hepatitis B also observed smaller gains in lumbar and total body BMD for those patients receiving tenofovir compared to the placebo group. In patients 2 to 11 years, lumbar and total body BMD gains were +4% and +5%, respectively, in patients who received tenofovir compared with +8% and +9%, respectively, for the placebo group. In patients 12 to 17 years, lumbar and total body BMD gains were +5% and +3%, respectively, in patients who received tenofovir compared with +8% and +5%, respectively, for the placebo group. After 72 weeks of treatment in the adolescent group, significant (more than 4%) lumbar spine BMD losses occurred in 3 tenofovir patients and 2 placebo patients. In all pediatric studies, the skeletal growth height appeared to be unaffected. Osteomalacia has also been reported with tenofovir use in postmarketing surveillance, including cases associated with proximal renal tubulopathy. Worsening pain in bones or extremities, bone fractures and/or muscular pain or weakness may also be manifestations of proximal renal tubulopathy; promptly evaluate renal function in patients experiencing these symptoms.

Adverse reactions observed in pediatric tenofovir clinical trials were consistent with those observed in adult trials. Neutropenia, defined as a neutrophil count less than 750 cells/mm3, was observed in 1% to 3% of adult patients during clinical trials. Additionally, 2% to 8% of adult patients developed an infection during these trials. Specific infection sites included upper respiratory tract infection (8%), sinusitis (8%), naso-pharyngitis (5%), and pneumonia (2% to 5%).

Unplanned tenofovir therapy interruption may be necessary in specific situations, such as serious drug toxicity, intercurrent illness or surgery precluding oral intake (e.g., gastroenteritis or pancreatitis), or drug non-availability. If short-term treatment interruption is necessary (i.e., less than 1 to 2 days), in general, it is recommended that all antiretroviral agents be discontinued simultaneously, especially if the interruption is because of serious toxicity. However, if a short-term treatment interruption is anticipated in the case of elective surgery, the pharmacokinetic properties and food requirements of specific drugs should be considered. When the antiretroviral regimen contains drugs with differing half-lives, stopping all drugs simultaneously may result in functional monotherapy of the drug with the longest half-life. For example, after discontinuation, the duration of detectable drug concentrations of efavirenz and nevirapine ranges from < 1 week to > 3 weeks. Simultaneously stopping all drugs in a regimen containing these agents may result in functional monotherapy with the NNRTI and may increase the risk of NNRTI-resistant mutations. Planned long-term treatment interruptions are not recommended due to the potential for HIV disease progression (i.e., declining CD4 counts, viral rebound, acute viral syndrome), development of minor HIV-associated manifestations or serious non-AIDS complications, development of drug resistance, increased risk of HIV transmission, and increased risk for opportunistic infections. If therapy must be discontinued, counsel patient on the potential risks and closely monitor for any clinical or laboratory abnormalities.

New and worsening renal impairment, including acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been associated with tenofovir use, including in children. Assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients prior to initiation and as clinically appropriate during therapy; a dosage adjustment may be necessary. In patients at risk for or with a history of renal dysfunction, also assess serum phosphorus prior to therapy initiation and periodically during therapy. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent (e.g., non-steroidal anti-inflammatory drugs [NSAIDs]). Cases of acute renal failure, requiring hospitalization and renal replacement therapy, have been reported in HIV-infected patients at high-risk for renal impairment, who appeared stable on tenofovir, after initiation of high-dose or multiple dose NSAIDs. Patients at risk for renal dysfunction should be given alternative therapy to NSAIDs, if required. Worsening bone pain, pain in extremities, bone fracture, and/or muscular pain or weakness may be manifestations of proximal renal tubulopathy; promptly evaluate renal function in patients experiencing these symptoms.

Bone mineral density (BMD) monitoring should be considered for patients receiving tenofovir who have a history of pathologic bone fractures or are at substantial risk for osteopenia, osteoporosis, or osteomalacia; osteomalacia has been reported in association with tenofovir administration. Cases of osteomalacia associated with proximal renal tubulopathy have been reported with tenofovir therapy. Worsening bone pain, pain in extremities, fractures and/or muscular pain or weakness may also be manifestations of proximal renal tubulopathy; promptly evaluate renal function in patients experiencing these symptoms. Normally, BMD increases rapidly in children and adolescents; however, in studies of tenofovir-treated pediatric patients, bone effects were similar to those noted in adult patients. One study evaluating HIV-infected children aged 2 to 12 years found total body BMD gains in recipients of tenofovir to be lower than the gains observed in patients receiving either stavudine or zidovudine. Additionally, at treatment week 48, 1 tenofovir-treated patient experienced significant (more than 4%) BMD loss in the lumbar spine; significant BMD losses were not observed in the stavudine or zidovudine treatment groups. In another study involving adolescents aged 12 to 17 years, the mean rate of BMD gain was less in the tenofovir-treated patients compared to the placebo group. Six tenofovir-treated adolescents and 1 placebo-treated adolescent had significant (more than 4%) lumbar spine BMD loss in 48 weeks. Two other studies in pediatric patients 2 to 11 years and 12 to 17 years with chronic hepatitis B also observed smaller gains in lumbar and total body BMD for those patients receiving tenofovir compared to the placebo group. In patients 2 to 11 years, lumbar and total body BMD gains were +4% and +5%, respectively, in patients who received tenofovir compared with +8% and +9%, respectively, for the placebo group. In patients 12 to 17 years, lumbar and total body BMD gains were +5% and +3%, respectively, in patients who received tenofovir compared with +8% and +5%, respectively, for the placebo group. After 72 weeks of treatment in the adolescent group, significant (more than 4%) lumbar spine BMD losses occurred in 3 tenofovir patients and 2 placebo patients. In all pediatric studies, the skeletal growth height appeared to be unaffected. The long-term effect of lower spine and total body BMD on skeletal growth in pediatric patients, and in particular, the effects of long-duration exposure in younger children is unknown. Although the effect of supplementation with calcium and vitamin D has not been studied, such supplementation may be considered for HIV-associated osteopenia or osteoporosis. If bone abnormalities are suspected, appropriate consultation should be obtained.

Lactic acidosis and hepatotoxicity with steatosis, including fatal cases, have been reported after use of tenofovir disoproxil fumarate (DF), both alone and in combination with other antiretroviral medications. Suspend treatment with tenofovir DF in any patient who develops clinical or laboratory findings suggestive of hepatotoxicity or lactic acidosis, which may include hepatomegaly and steatosis even in the absence of marked elevated hepatic enzymes. Although these adverse reactions may occur in any drug recipient, some risk factors include hepatic disease (e.g., alcoholism), obesity, and prolonged nucleoside exposure. In addition, adult females appear to be at a higher risk for lactic acidosis; it is not clear whether this increased risk applies to pediatric females.

All patients should undergo hepatitis B virus (HBV) screening and HIV antibody testing prior to initiation of tenofovir to ensure appropriate treatment. Patients with hepatitis B and HIV coinfection who require treatment for either infection should be started on a fully suppressive antiretroviral regimen that contains NRTIs with activity against both viruses. Avoid using single-drug therapy to treat HBV (i.e., lamivudine, emtricitabine, or tenofovir as the only active agent) due to the risk of developing resistant strains of HIV. The HIV guidelines recommend that coinfected pediatric patients 2 years and older receive an antiretroviral regimen that contains tenofovir in combination with either lamivudine or emtricitabine as the dual NRTI backbone. If tenofovir cannot be used, another agent with anti-HBV activity should be used in combination with lamivudine or emtricitabine to assure adequate treatment of HBV infection. Management of HIV should be continued with the goal of maximal virus suppression. After discontinuation of tenofovir in patients with coexisting HBV and HIV infection, some patients have experienced severe acute hepatitis B exacerbation. In patients co-infected with HBV and HIV who discontinue tenofovir, closely monitor hepatic function with both clinical and laboratory follow-up for at least several months. If appropriate, resumption of anti-hepatitis B therapy may be warranted, especially in patients with advanced liver disease or cirrhosis, since post-treatment exacerbation may lead to hepatic decompensation and liver failure.

Testing for human immunodeficiency virus (HIV) infection resistance is recommended in all antiretroviral treatment-naive patients at the time of HIV diagnosis, regardless of whether treatment will be initiated. Additionally, perform resistance testing prior to initiating or changing any HIV treatment regimen. Transmission of drug-resistant HIV strains has been both well documented and associated with suboptimal virologic response to initial antiretroviral therapy. Therefore, resistance testing at baseline can help optimize treatment and, thus, virologic response. In the absence of therapy, resistant viruses may decline over time to less than the detection limit of standard resistance tests, but may still increase the risk of treatment failure when therapy is eventually initiated. Thus, if therapy is deferred, resistance testing should still be performed during acute HIV infection with the genotypic resistance test results kept in the patient's medical record until they become clinically useful. Additionally, because of the possibility of acquisition of another drug-resistant virus before treatment initiation, repeat resistance testing at the time therapy is initiated would be prudent. As with all other antiretroviral agents, resistance can develop when tenofovir is used either alone or in combination with other agents. Monotherapy with tenofovir is not recommended.

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy. During the initial phase of HIV treatment, patients whose immune system responds to tenofovir therapy may develop an inflammatory response to indolent or residual opportunistic infections (such as mycobacterium avium complex (MAC), cytomegalovirus (CMV), Pneumocystis jirovecii pneumonia (PCP), or tuberculosis (TB)), which may necessitate further evaluation and treatment. In addition, autoimmune disease (including Graves' disease, Guillain-Barre syndrome, and polymyositis) may also develop; the time to onset is variable and may occur months after treatment initiation.

Perform hepatitis C virus (HCV) screening in any child whose mother is known to have HCV infection and all HIV-infected adolescents. Treatment of HCV infection in children < 3 years is not usually recommended; however, treatment should be considered for all children >= 3 years and adolescents with hepatitis C and HIV coinfection who have no contraindications to treatment. For antiretroviral-naive adolescent patients with CD4 counts > 500 cells/mm3, consideration may be given to deferring ARV therapy until the hepatitis C treatment regimen has been completed. Conversely, for adolescent patients with CD4 counts < 200 cells/mm3, consider delaying initiation of the hepatitis C treatment regimen until the patient is stable on a fully suppressive ARV regimen. All HIV-infected children and adolescents, regardless of HIV and HCV status, should receive standard vaccination with hepatitis A and B vaccines. Additionally, HIV/HCV-coinfected adolescents should be counseled to avoid alcohol.

Description: Tenofovir (also known as PMPA) is an acyclic nucleotide analog and is available as an ester prodrug, tenofovir disoproxil fumarate (tenofovir DF). Tenofovir exhibits activity against HIV-1 viruses with reduced sensitivity to nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitors (PIs), and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Tenofovir's activity is additive or synergistic when combined with other antiretroviral agents. It also inhibits hepatitis B virus (HBV) and is indicated for chronic HBV infection. The FDA-approved package labeling has a Black Box warning that acute exacerbations of hepatitis B have been reported in patients after discontinuation of the drug. If treatment for HIV infection is discontinued in a patient co-infected with HBV, the patient should be closely monitored for several months for signs and symptoms of worsening hepatitis infection. Decreases in bone mineral density (BMD) have been reported in children receiving tenofovir. Tenofovir is FDA-approved in pediatric patients as young as 2 years.

Initiation of HIV therapy
-Antiretroviral drug resistance testing (preferably genotypic testing) is recommended prior to initiation of therapy in antiretroviral treatment (ART)-naive patients and prior to changing therapy for treatment failure.
-Initiation of treatment immediately or within days after HIV diagnosis is recommended in all pediatric patients, except for patients with cryptococcal meningitis, disseminated Mycobacterium avium complex disease, or Mycobacterium tuberculosis disease. In these patients, initiate treatment for the opportunistic infection first, ahead of ART initiation. The urgency of rapid treatment initiation is especially critical for all patients younger than 1 year, who carry the highest risk of rapid disease progression and mortality. If therapy is deferred for certain circumstances, closely monitor the patient's virologic, immunologic, and clinical status at least every 3 to 4 months. If therapy is deferred, initiate treatment when HIV RNA concentrations increase, CD4 count or percentage values decline (i.e., approaching CDC Stage 2 or 3), the patient develops new HIV-related clinical symptoms, or the ability of the caregiver and patient to adhere to the prescribed regimen has improved.

Place in therapy for HIV
-Tenofovir disoproxil fumarate is one of the preferred nucleoside reverse transcriptase inhibitors (NRTIs) to be included as a part of a 2-NRTI backbone regimen in treatment-naive adolescents with Sexual Maturity Rating (SMR) of 4 or 5. The 2-NRTI backbone should be used in combination with an integrase strand transfer inhibitor (INSTI), which is the preferred regimen, or in combination with a protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) in certain clinical situations.
-Due to decreases in bone mineral density that may occur, tenofovir disoproxil fumarate is considered an alternative option as part of a 2-NRTI backbone regimen in children 2 to 12 years.

Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: hepatitis B virus, human immunodeficiency virus (HIV)
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.

For the treatment of human immunodeficiency virus (HIV) infection in combination with other anti-retroviral agents:
Oral dosage (oral powder):
Children and Adolescents 2 to 17 years weighing at least 10 kg: 8 mg/kg/dose PO once daily (Max: 300 mg/dose) with 2 to 4 ounces of soft food. Round dose to the nearest 20-mg increment (i.e., 80 mg, 100 mg, 120 mg, 140 mg, etc.), as each scoop of oral powder provides 40 mg of tenofovir (i.e., doses given as whole or half scoop).
Oral dosage (tablets):
Children 2 to 12 years weighing 17 to 21 kg: 150 mg PO once daily.
Children 2 to 12 years weighing 22 to 27 kg: 200 mg PO once daily.
Children and Adolescents weighing 28 to 34 kg: 250 mg PO once daily.
Children and Adolescents weighing 35 kg or more: 300 mg PO once daily.

For treatment of chronic hepatitis B infection:
Oral dosage (oral powder):
Children and Adolescents 2 to 17 years weighing at least 10 kg: 8 mg/kg/dose (Max: 300 mg/dose) PO once daily. Round dose to the nearest 20-mg increment. Therapy is generally continued for at least 12 months, although the optimal treatment duration is unknown, and often longer treatment is necessary. Children with HBeAg-positive chronic HBV infection who have complete viral suppression and HBeAg seroconversion should receive at least 6 months of consolidation therapy; however, the optimal treatment duration has not been established. Indefinite treatment may be required in persons with HBeAg-negative chronic HBV infection. Tenofovir is recommended for use as part of a fully suppressive antiretroviral regimen with lamivudine or emtricitabine to treat HBV in conjunction with HIV. Tenofovir added to a lamivudine-containing HIV regimen has been found to decrease HBV DNA in persons with lamivudine-resistant HBV. When treating both HIV and HBV, tenofovir and lamivudine or tenofovir and emtricitabine (at appropriate HIV treatment doses and in combination with other antiretroviral agents) are appropriate first-line treatment options. When treating HBV and not HIV, avoid the use of emtricitabine, lamivudine, or tenofovir without a full HAART regimen because of the rapid development of drug-resistant HIV mutations. Most persons on HAART should receive HBV therapy indefinitely.
Oral dosage (tablets):
Children 2 to 12 years weighing 17 to 21 kg: 150 mg PO once daily. Therapy is generally continued for at least 12 months, although the optimal treatment duration is unknown, and often longer treatment is necessary. Children with HBeAg-positive chronic HBV infection who have complete viral suppression and HBeAg seroconversion should receive at least 6 months of consolidation therapy; however, the optimal treatment duration has not been established. Indefinite treatment may be required in persons with HBeAg-negative chronic HBV infection. Tenofovir is recommended for use as part of a fully suppressive antiretroviral regimen with lamivudine or emtricitabine to treat HBV in conjunction with HIV. Tenofovir added to a lamivudine-containing HIV regimen has been found to decrease HBV DNA in persons with lamivudine-resistant HBV. When treating both HIV and HBV, tenofovir and lamivudine or tenofovir and emtricitabine (at appropriate HIV treatment doses and in combination with other antiretroviral agents) are appropriate first-line treatment options. When treating HBV and not HIV, avoid the use of emtricitabine, lamivudine, or tenofovir without a full HAART regimen because of the rapid development of drug-resistant HIV mutations. Most persons on HAART should receive HBV therapy indefinitely.
Children 2 to 12 years weighing 22 to 27 kg: 200 mg PO once daily. Therapy is generally continued for at least 12 months, although the optimal treatment duration is unknown, and often longer treatment is necessary. Children with HBeAg-positive chronic HBV infection who have complete viral suppression and HBeAg seroconversion should receive at least 6 months of consolidation therapy; however, the optimal treatment duration has not been established. Indefinite treatment may be required in persons with HBeAg-negative chronic HBV infection. Tenofovir is recommended for use as part of a fully suppressive antiretroviral regimen with lamivudine or emtricitabine to treat HBV in conjunction with HIV. Tenofovir added to a lamivudine-containing HIV regimen has been found to decrease HBV DNA in persons with lamivudine-resistant HBV. When treating both HIV and HBV, tenofovir and lamivudine or tenofovir and emtricitabine (at appropriate HIV treatment doses and in combination with other antiretroviral agents) are appropriate first-line treatment options. When treating HBV and not HIV, avoid the use of emtricitabine, lamivudine, or tenofovir without a full HAART regimen because of the rapid development of drug-resistant HIV mutations. Most persons on HAART should receive HBV therapy indefinitely.
Children and Adolescents weighing 28 to 34 kg: 250 mg PO once daily. Therapy is generally continued for at least 12 months, although the optimal treatment duration is unknown, and often longer treatment is necessary. Children with HBeAg-positive chronic HBV infection who have complete viral suppression and HBeAg seroconversion should receive at least 6 months of consolidation therapy; however, the optimal treatment duration has not been established. Indefinite treatment may be required in persons with HBeAg-negative chronic HBV infection. Tenofovir is recommended for use as part of a fully suppressive antiretroviral regimen with lamivudine or emtricitabine to treat HBV in conjunction with HIV. Tenofovir added to a lamivudine-containing HIV regimen has been found to decrease HBV DNA in persons with lamivudine-resistant HBV. When treating both HIV and HBV, tenofovir and lamivudine or tenofovir and emtricitabine (at appropriate HIV treatment doses and in combination with other antiretroviral agents) are appropriate first-line treatment options. When treating HBV and not HIV, avoid the use of emtricitabine, lamivudine, or tenofovir without a full HAART regimen because of the rapid development of drug-resistant HIV mutations. Most persons on HAART should receive HBV therapy indefinitely.
Children and Adolescents weighing 35 kg or more: 300 mg PO once daily. Therapy is generally continued for at least 12 months, although the optimal treatment duration is unknown, and often longer treatment is necessary. Children with HBeAg-positive chronic HBV infection who have complete viral suppression and HBeAg seroconversion should receive at least 6 months of consolidation therapy; however, the optimal treatment duration has not been established. Indefinite treatment may be required in persons with HBeAg-negative chronic HBV infection. Tenofovir is recommended for use as part of a fully suppressive antiretroviral regimen with lamivudine or emtricitabine to treat HBV in conjunction with HIV. Tenofovir added to a lamivudine-containing HIV regimen has been found to decrease HBV DNA in persons with lamivudine-resistant HBV. When treating both HIV and HBV, tenofovir and lamivudine or tenofovir and emtricitabine (at appropriate HIV treatment doses and in combination with other antiretroviral agents) are appropriate first-line treatment options. When treating HBV and not HIV, avoid the use of emtricitabine, lamivudine, or tenofovir without a full HAART regimen because of the rapid development of drug-resistant HIV mutations. Most persons on HAART should receive HBV therapy indefinitely.

For human immunodeficiency virus (HIV) prophylaxis* after nonoccupational exposure to HIV, including sexual assault:
NOTE: Higher risk exposures for which prophylaxis is recommended include exposure of vagina, rectum, eye, mouth, or other mucous membrane, nonintact skin, or percutaneous contact with blood, semen, vaginal secretions, rectal secretions, breast milk, or any body fluid that is visibly contaminated with blood when the source is known to be HIV-positive. Exposures to a source patient with unknown HIV status should be assessed on a case-by-case basis.
Oral dosage (oral powder):
Children 2 to 12 years: 8 mg/kg/dose PO once daily (Max: 300 mg/dose) in combination with emtricitabine and raltegravir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in children 2 years and older. Round dose to the nearest 20-mg increment (i.e., 80 mg, 100 mg, 120 mg, 140 mg, etc.), as each scoop of oral powder provides 40 mg of tenofovir (i.e., doses given as whole or half scoop). Tenofovir in combination with emtricitabine and lopinavir/ritonavir or darunavir/ritonavir (children 3 years and older) is an alternative regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.
Adolescents: 8 mg/kg/dose PO once daily (Max: 300 mg/dose) in combination with emtricitabine and raltegravir or dolutegravir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in adolescents. Round dose to the nearest 20-mg increment (i.e., 80 mg, 100 mg, 120 mg, 140 mg, etc.), as each scoop of oral powder provides 40 mg of tenofovir (i.e., doses given as whole or half scoop). Tenofovir in combination with emtricitabine and darunavir/ritonavir is an alternative regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.
Oral dosage (tablets):
Children 2 years and older weighing 17 to 21 kg: 150 mg PO once daily in combination with emtricitabine and raltegravir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in children 2 years and older. Tenofovir in combination with emtricitabine and lopinavir/ritonavir or darunavir/ritonavir (children 3 years and older) is an alternative regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.
Children 2 years and older weighing 22 to 27 kg: 200 mg PO once daily in combination with emtricitabine and raltegravir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in children 2 years and older. Tenofovir in combination with emtricitabine and lopinavir/ritonavir or darunavir/ritonavir (children 3 years and older) is an alternative regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.
Children weighing 28 to 34 kg: 250 mg PO once daily in combination with emtricitabine and raltegravir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in children 2 years and older. Tenofovir in combination with emtricitabine and lopinavir/ritonavir or darunavir/ritonavir is an alternative regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.
Children weighing 35 kg or more: 300 mg PO once daily in combination with emtricitabine and raltegravir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in children 2 years and older. Tenofovir in combination with emtricitabine and lopinavir/ritonavir or darunavir/ritonavir is an alternative regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.
Adolescents weighing 28 to 34 kg: 250 mg PO once daily in combination with emtricitabine and raltegravir or dolutegravir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in adolescents. Tenofovir in combination with emtricitabine and darunavir/ritonavir is an alternative regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.
Adolescents weighing 35 kg or more: 300 mg PO once daily in combination with emtricitabine and raltegravir or dolutegravir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in adolescents. Tenofovir in combination with emtricitabine and darunavir/ritonavir is an alternative regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

Maximum Dosage Limits:
-Neonates
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Children
1 year: Safety and efficacy have not been established.
2 to 12 years weighing less than 10 kg: Safety and efficacy have not been established.
2 to 12 years weighing 10 to 16 kg: 8 mg/kg/day PO for the powder; safety and efficacy of the tablets have not been established.
2 to 12 years weighing 17 kg or more: 8 mg/kg/day PO (Max: 300 mg/day).
-Adolescents
8 mg/kg/day PO (Max: 300 mg/day).

Patients with Hepatic Impairment Dosing
No dosage adjustment required. However, due to the risk of hepatotoxicity, use caution when administering to patients with hepatic disease.

Patients with Renal Impairment Dosing
There are no recommendations for pediatric patients. Renal adjustment recommendations for adults are listed below:
CrCl 50 mL/minute or more: No dosage adjustment needed.
CrCl 30 to 49 mL/minute: 300 mg PO every 48 hours.
CrCl 10 to 29 mL/minute: 300 mg PO every 72 to 96 hours.
CrCl less than 10 mL/minute: Not recommended for patients with a CrCl less than 10 mL/minute not receiving hemodialysis.

Intermittent hemodialysis
There are no recommendations for pediatric patients. In adults, tenofovir is administered every 7 days after routine dialysis (assuming 3 hemodialysis sessions per week of approximately 4 hours duration); administer after completion of dialysis.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Tenofovir inhibits viral reverse transcriptase and acts as a DNA chain terminator. Tenofovir disoproxil fumarate (tenofovir DF) is an acyclic nucleoside phosphonate (nucleotide) diester analog of adenosine monophosphate. Tenofovir DF requires initial diester hydrolysis for conversion to tenofovir. Tenofovir is then taken up by cells and undergoes phosphorylation to form tenofovir diphosphate (PMPApp). Tenofovir diphosphate competitively inhibits RNA- and DNA-directed reverse transcriptase. Tenofovir diphosphate competes with the natural substrate deoxyadenosine 5'-triphosphate (dATP) and, since it lacks a 3' hydroxyl group, causes premature DNA termination. Tenofovir diphosphate is a weak inhibitor of mammalian DNA polymerase alpha, beta, and mitochondrial DNA polymerase-gamma.

Pharmacokinetics: Tenofovir disoproxil fumarate (tenofovir DF) is administered orally. The in vitro binding to human plasma and serum proteins is < 0.7% and 7.2%, respectively. Intracellularly, tenofovir undergoes phosphorylation to its active metabolite, tenofovir diphosphate (PMPApp). In vitro studies indicate that neither tenofovir DF nor tenofovir are substrates of cytochrome P450 enzymes. After IV administration of tenofovir, 70-80% of the dose is recovered in the urine as unchanged drug within 72 hours. After multiple oral doses of tenofovir DF (300 mg once daily), 32 +/- 10% of the administered dose is recovered in urine over 24 hours. After a single, orally administered dose, the terminal elimination half-life of tenofovir is approximately 17 hours in adults. Tenofovir is eliminated by a combination of glomerular filtration and active renal tubular secretion; there may be competition for elimination with other compounds that are also renally eliminated.

Affected cytochrome P450 isoenzymes or drug transporters: P-gp, BCRP
Tenofovir is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters. Administration with inhibitors of these transporters may result in increased absorption of tenofovir.


-Route-Specific Pharmacokinetics
Oral Route
Oral bioavailability is 25% in the fasted state. Administration of tenofovir DF after a high-fat meal (roughly 700-1000 kcal containing 40-50% fat) increases the oral bioavailability with approximate increases of 40% in AUC and 14% in Cmax. Administration with a light meal, however, does not have a significant effect on the pharmacokinetic profile when compared to administration in a fasted state. Food delays the time to Cmax by approximately 1 hour. In a single-dose study in healthy adult volunteers, mean AUCs after administration of the tablet and powder formulations were comparable when administered under fed conditions; however, the mean Cmax was 26% lower in oral powder recipients compared to those who received the tablet.


-Special Populations
Pediatrics
Children >= 2 years and Adolescents
Steady-state pharmacokinetics of tenofovir were evaluated in 31 HIV-infected pediatric patients (ages 2 to < 18 years). Patients received either 8 mg/kg of the oral powder (up to 300 mg) or a 300 mg tablet. The exposure (AUC) in these pediatric patients was similar to that observed in adults receiving a 300 mg oral daily dose. Exposures in 52 pediatric patients (12-17 years) with hepatitis B (HBV) were similar to those achieved in HIV-infected adults and adolescents. Renal clearance is approximately 1.5-fold higher in children than in adults with a half-life of approximately 12.5 hours (range, 8-18 hours). Clearance increases with body weight in pediatric patients.

Hepatic Impairment
No substantial pharmacokinetic changes have been noted in patients with moderate to severe hepatic impairment, after a single dose of tenofovir 300 mg, and no change in dosage is required in patients with hepatic impairment.

Renal Impairment
When administered to patients with renal impairment or end-stage renal disease (ESRD) requiring dialysis, the tenofovir Cmax and AUC were significantly increased. The hemodialysis extraction coefficient is 54% and approximately 10% of the dose is removed in a 4 hour hemodialysis session.