Tenofovir alafenamide is a hepatitis B virus (HBV) nucleoside analog reverse transcriptase inhibitor. It is indicated for the treatment of chronic HBV infection in adults and pediatric patients 12 years and older with compensated liver disease. Additionally, HIV treatment guidelines recommend use of tenofovir alafenamide with lamivudine or emtricitabine as preferred 2-NRTI backbones. Similar to tenofovir disoproxil fumarate, the FDA-approved package labeling for tenofovir alafenamide contains a Black Box Warning regarding the potential for acute exacerbations of hepatitis B in patients following treatment discontinuation. Avoid the use of tenofovir alafenamide in patients with an estimated creatinine clearance of less than 15 mL/min who are NOT receiving chronic hemodialysis. For patients on hemodialysis, no dosage adjustment is needed and the drug should be administered after completion of the hemodialysis treatment on dialysis days.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
NOTE: Tenofovir alafenamide monotherapy is NOT recommended for hepatitis B virus and HIV coinfection. Tenofovir alafenamide MUST be used in combination with other antiretroviral agents when treating HIV coinfection.
Route-Specific Administration
Oral Administration
-Administer with food.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with combination antiretroviral therapies that included nucleotide reverse transcriptase inhibitors. A majority of these cases have occurred in women, obese patients, and patients with prolonged nucleoside exposure. If a patient develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity while receiving tenofovir alafenamide, treatment should be discontinued.
Severe acute hepatitis B exacerbation (e.g., hepatic decompensation and hepatic failure) has been observed following discontinue of anti-hepatitis B therapy, including tenofovir. Patients who discontinue use of tenofovir alafenamide must have their hepatic function closely monitored (both clinical and laboratory) for at least several months. If appropriate, reinitiating HBV treatment may be warranted.
The effects of tenofovir alafenamide (TAF) on renal function were compared against tenofovir disoproxil fumarate (TDF) in two 96 week clinical trials involving a total of 1,298 adults with chronic hepatitis B. Pooled data from these trials found that for both treatment groups, the mean increase in serum creatinine was less than 0.1 mg/dL and the median decrease in serum phosphorus was 0.1 mg/dL. However, the median decrease in estimated creatinine clearance (as compared to baseline) was less with TAF (-1.2 mL/minute) than with TDF (-4.8 mL/minute). In patients who remained on treatment beyond 96 weeks, the change from baseline in renal laboratory parameter values in each group at week 120 were similar to those observed at week 96. The long-term significance of these laboratory changes is not known. During postmarketing use of TAF-containing regimens, cases of nephrotoxicity, including acute renal failure, acute renal tubular necrosis, proximal renal tubulopathy, and Fanconi syndrome have been reported. In most cases, potential confounders were identified that may have contributed to the reported renal events; however, it is also possible these factors could have predisposed patients to tenofovir-related adverse events.
Although not as severe as tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) has been associated with reduced bone mineral density (BMD). Pooled data from two 96 week clinical trials in adults found 11% of TAF and 25% of TDF patients experienced an at least 5% decrease in BMD at the lumbar spine. In addition, a 7% decrease in BMD at the femoral neck was observed in 5% of TAF and 13% TDF recipients. The mean percent change in BMD for TAF was -0.7% at the lumbar spine and -0.3% at the total hip, compared to -2.6% at the lumbar spine and -2.5% at the total hip for TDF. Another study compared BMDs in pediatric subjects who received either TAF (n = 37) or placebo (n = 18). In this study, the mean percent change in BMD from baseline to Week 24 was 2.4% and 1.9% for lumbar spine and 1.5% and 1.9% for whole body, respectively. At Week 24, mean changes from baseline BMD Z-scores were -0.03 and -0.09 for lumbar spine, and -0.05 and -0.01 for whole body, for the Cohort TAF and placebo groups, respectively. The long-term significance of these BMD changes are unknown; however, these results increase the concern of developing osteopenia, osteoporosis, and bone fractures.
During clinical trials, hyperamylasemia (more than 2-times upper limit of normal (ULN)) was observed in 3% of tenofovir alafenamide treated patients. In addition, 8 patients with elevated amylase concentrations developed symptoms suggestive of pancreatitis. Of these 8 patients, 2 discontinued treatment due to elevated amylase and lipase concentrations; 1 patient experienced adverse reaction recurrence upon restarting tenofovir alafenamide. Other gastrointestinal adverse events noted during clinical trials included abdominal pain (9%), lower back pain (6%), nausea (6%), diarrhea (5%), dyspepsia (5%), flatulence (less than 5%), and vomiting (less than 5%). Other laboratory abnormalities observed during clinical trials included elevated hepatic enzymes more than 5-time ULN, (ALT, 8%; AST, 3%), elevated creatine kinase of at least 10-times ULN (3%), and glycosuria of 3+ or more (5%). Hypercholesterolemia (fasting LDL more than 190 mg/dL) was observed in 6% of patients. Pooled data from clinical trials found tenofovir alafenamide recipients experienced a +7 point increase in fasting LDL cholesterol, -5 point decrease in fasting HDL cholesterol, and an +13 point increase in fasting triglyceride concentration from baseline by treatment weak 96.
Other adverse events observed during tenofovir alafenamide clinical trials included headache (12%), cough (8%), fatigue (6%), arthralgia (5%), and rash (less than 5%).
Angioedema and urticaria have been reported with tenofovir alafenamide in postmarketing surveillance.
Weight gain (up to 10 kg over 96 weeks) has been associated with the use of tenofovir alafenamide during postmarketing surveillance. Data from an open-label trial found patients who started a tenofovir alafenamide-containing regimen gained more weight than patients who began a regimen containing tenofovir disoproxil fumarate. Additionally, significant weight gain was initially reported in a cohort of patients switching from tenofovir disoproxil fumarate to tenofovir alafenamide. It is unknown whether the increase in weight is reversible upon treatment discontinuation.
During baseline evaluation of people with HIV, discuss risk reduction measures and the need for status disclosure to sexual or needle-sharing partners, especially with untreated patients who are still at high risk of HIV transmission. Include the importance of adherence to therapy to achieve and maintain a plasma HIV RNA less than 200 copies/mL. Maintaining a plasma HIV RNA less than 200 copies/mL, including any measurable value below this threshold, with antiretroviral therapy prevents sexual transmission of HIV to their partners. Patients may recognize this concept as Undetectable = Untransmittable or U=U. Instruct patients to achieve sustained viral suppression (i.e., 2 recorded measurements of plasma viral loads that are below the limits of detection and taken at least 3 months apart) before attempting to conceive a child in order to maximize their health, prevent HIV sexual transmission, and minimize the risk of HIV transmission to the infant once conception occurs. For partners with different HIV status when the person with HIV is on antiretroviral therapy and has achieved sustained viral suppression, sexual intercourse without a condom allows conception without sexual HIV transmission to the person without HIV. Expert consultation is recommended.
Unplanned antiretroviral therapy interruption may be necessary for specific situations, such as serious drug toxicity, intercurrent illness or surgery precluding oral intake (e.g., gastroenteritis or pancreatitis), severe hyperemesis gravidarum unresponsive to antiemetics, or drug non-availability. If short-term treatment interruption (i.e., less than 1 to 2 days) is necessary, in general, it is recommended that all antiretroviral agents be discontinued simultaneously, especially if the interruption occurs in a pregnant patient or is because of a 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; as stopping all simultaneously in a regimen containing drugs with differing half-lives may result in functional monotherapy of the drug with the longest half-life and may increase the risk for resistant mutations. Healthcare providers are advised to reinitiate a complete and effective antiretroviral regimen as soon as possible after an interruption of therapy. 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.
To assure appropriate treatment, test all patients for HIV coinfection prior to initiating tenofovir alafenamide. Patients with hepatitis B and HIV coinfection should be started on a fully suppressive antiretroviral (ARV) regimen with activity against both viruses (regardless of CD4 counts and HBV DNA concentrations). HIV treatment guidelines recommend these patients receive an ARV regimen that contains a dual NRTI backbone of tenofovir alafenamide or tenofovir disoproxil fumarate with either emtricitabine or lamivudine. If tenofovir cannot be used, entecavir should be given in combination with a fully suppressive ARV regimen (note: entecavir should not be considered part of the ARV regimen). Avoid using single-drug therapy to treat hepatitis B virus (i.e., lamivudine, emtricitabine, tenofovir, or entecavir as the only active agent) as this may result in HIV resistant strains. Further, HBV treatment regimens that include adefovir or telbivudine should also be avoided, as these regimens are associated with a higher incidence of toxicities and increased rates of HBV treatment failure. Most coinfected patients should continue treatment indefinitely with the goal of maximal HIV suppression and prevention of hepatitis B relapse. If considering discontinuation of the drug, it is important to note that some patients with coexisting HIV and HBV infection have experienced severe acute hepatitis B exacerbation, including reports of liver decompensation and liver failure, after stopping treatment. Although such flares have not yet been observed in persons without HBV and HIV coinfection, all patients who discontinue tenofovir should have transaminase concentrations monitored every 6 weeks for the first 3 months, and every 3 to 6 months thereafter. If appropriate, resumption of anti-hepatitis B therapy may be warranted. For patients who refuse a fully suppressive ARV regimen, but still require treatment for HBV, consider 48 weeks of peginterferon alfa; do not administer HIV-active medications in the absence of a fully suppressive ARV regimen. Instruct coinfected patients to avoid consuming alcohol, and offer vaccinations against hepatitis A and hepatitis B as appropriate.
Lactic acidosis and hepatomegaly with steatosis, including fatal cases, have been reported following use of tenofovir disoproxil fumarate (another tenofovir prodrug), both alone and in combination with other antiretroviral medications. Treatment with tenofovir alafenamide should be suspended 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 events may occur in any drug recipient, some risk factors include hepatic disease (e.g., alcoholism), obesity, and prolonged nucleoside exposure. In addition, a majority of these cases have been in females; it is unknown if being pregnant augments the incidence of this syndrome in patients receiving nucleoside analogs. However, because being pregnant itself can mimic some of the early symptoms of the lactic acid and hepatic steatosis syndrome or be associated with other significant disorders of liver metabolism, clinicians need to be alert for early diagnosis of this syndrome. Pregnant women receiving nucleoside analogs should have LFTs and serum electrolytes assessed more frequently during the last trimester and any new symptoms should be evaluated thoroughly.
Increased body weight has been observed in antiretroviral-naive patients after starting treatment with tenofovir alafenamide and after switching from tenofovir disoproxil fumarate to tenofovir alafenamide. Predictors and mechanisms for the increase in weight are still unclear; however, the weight gain appears to disproportionately affect females, Hispanic patients, and Black patients (particularly Black women). It is unknown whether the increase in weight is associated with significant cardio-metabolic risks or if it is reversible upon treatment discontinuation.
Tenofovir (the active metabolite of tenofovir alafenamide) is eliminated via the kidneys; therefore, use of tenofovir alafenamide in patients with end-stage renal disease (creatinine clearance less than 15 mL/minute) who are not receiving chronic hemodialysis should be avoided. In addition, tenofovir prodrugs (i.e., tenofovir disoproxil fumarate, tenofovir alafenamide) have been associated with the development of renal toxicity. During postmarketing use of tenofovir alafenamide, cases of renal impairment, including acute renal failure, acute tubular necrosis, proximal renal tubulopathy, and Fanconi syndrome have been reported. In most cases, potential confounders were identified that may have contributed to the reported renal events; however, it is also possible these factors could have predisposed patients to tenofovir-related adverse events. Assess an estimated creatinine clearance, urine glucose, and urine protein in all patients before treatment, and as indicated during treatment. Serum phosphorus concentrations should also be assessed prior to, and periodically during treatment in patients with chronic kidney disease. Discontinue treatment in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. In addition, avoid concurrent use with or recently after a nephrotoxic agent, including high-dose or multiple nonsteroidal anti-inflammatory drugs (NSAIDS), as use of these medications together increases the risk for developing renal-related adverse reactions.
Although not as severe as tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) has been associated with reduced bone mineral density (BMD) at the lumbar spine and femoral neck. The long-term significance of these BMD changes are unknown; therefore, consider BMD monitoring for drug recipients who have a history of pathologic bone fracture or are at substantial risk for osteopenia or osteoporosis. Close monitoring is also recommended for patients experiencing bone pain or pain in the extremities, as these may be signs of osteomalacia. While not reported during TAF clinical trials, cases of osteomalacia secondary to proximal renal tubulopathy have been reported with the TDF. Obtain appropriate consultation if bone abnormalities are suspected. In addition, consider supplementation with calcium and vitamin D for all patients.
Consider patient specific factors, such as preexisting hyperlipidemia (i.e., hypertriglyceridemia or hypercholesterolemia), when selecting an antiretroviral treatment regimen. According to CDC guidelines, lipid concentrations are lower in patients treated with regimens containing tenofovir disoproxil fumarate than in those receiving tenofovir alafenamide. Pooled data from clinical trials found tenofovir alafenamide recipients experienced a +7 point increase in fasting LDL cholesterol, -5 point decrease in fasting HDL cholesterol, and an +13 point increase in fasting triglyceride concentration from baseline by treatment weak 96. If a patient develops hyperlipidemia during treatment, possible interventions include dietary modification, use of lipid lowering agents, or modification of treatment regimen. Obtain a fasting lipid profile at entry of care, initiation or modification of antiretroviral therapy, every 3 months if last test was abnormal, or every 12 months if last test was within normal limits.
Recipients of tenofovir alafenamide may be an increased risk for developing pancreatitis. During clinical trials, 7 patients experienced symptoms of pancreatitis (i.e., abdominal tenderness, lower back pain, nausea) in conjunction with elevated amylase concentrations. Of these 7 patients, 2 required treatment discontinuation; 1 patient experience adverse event recurrence when restarting tenofovir alafenamide.
Antiretroviral therapy should be provided to all patients during pregnancy, regardless of HIV RNA concentrations or CD4 cell count. Using highly active antiretroviral combination therapy (HAART) to maximally suppress viral replication is the most effective strategy to prevent the development of resistance and to minimize the risk of perinatal transmission. Begin HAART as soon as pregnancy is recognized, or HIV is diagnosed. HIV guidelines recommend the use of tenofovir alafenamide with either emtricitabine or lamivudine as a preferred 2-NRTI backbone in patients who are pregnant or trying to become pregnant. Available data from the Antiretroviral Pregnancy Registry, which includes first trimester exposures to tenofovir alafenamide (915 exposures), have shown no statistically significant difference in the risk of overall major birth defects when compared to the 2.7% background rate among pregnant women in the US. When exposure occurred in the first trimester, the prevalence of defects was 3.9% (95% CI: 2.8 to 5.4) for tenofovir alafenamide. Nucleoside reverse transcriptase inhibitors (NRTIs) are known to induce mitochondrial dysfunction. An association of mitochondrial dysfunction in infants and in utero antiretroviral exposure has been suggested, but not established. While the development of severe or fatal mitochondrial disease in exposed infants appears to be extremely rare, more intensive monitoring of hematologic and electrolyte parameters during the first few weeks of life is advised. Nucleoside analogs have been associated with the development of lactic acidosis, especially during pregnancy. It is unclear if pregnancy augments the incidence of lactic acidosis/hepatic steatosis in patients receiving nucleoside analogs. However, because pregnancy can mimic some early symptoms of the lactic acid/hepatic steatosis syndrome or be associated with other significant disorders of liver metabolism, clinicians need to be alert for early diagnosis of this syndrome. Pregnant patients receiving nucleoside analogs should have LFTs and serum electrolytes assessed more frequently during the last trimester, and any new symptoms should be evaluated thoroughly. Regular laboratory monitoring is recommended to determine antiretroviral efficacy. Monitor CD4 counts at the initial visit. Patients who have been on HAART for at least 2 years and have consistent viral suppression and CD4 counts consistently greater than or equal to 300 cells/mm3 do not need CD4 counts monitored after the initial visit during the pregnancy. However, CD4 counts should be monitored every 3 months during pregnancy for patients on HAART less than 2 years and have CD4 counts less than 300 cells/mm3, patients with inconsistent adherence, or patients with detectable viral loads. For patients on HAART less than 2 years but have CD4 counts greater than or equal to 300 cells/mm3, monitor CD4 counts every 6 months. Monitor plasma HIV RNA at the initial visit (with review of prior levels), 2 to 4 weeks after initiating or changing therapy, monthly until undetectable, and then at least every 3 months during pregnancy. Viral load should also be assessed at approximately 36 weeks gestation, or within 4 weeks of planned delivery, to inform decisions regarding mode of delivery and optimal treatment for newborns. Patients whose HIV RNA levels are above the threshold for resistance testing (usually greater than 500 copies/mL but may be possible for levels greater than 200 copies/mL in some laboratories) should undergo antiretroviral resistance testing (genotypic testing, and if indicated, phenotypic testing). Resistance testing should be conducted before starting therapy in treatment-naive patients who have not been previously tested, starting therapy in treatment-experienced patients (including those who have received pre-exposure prophylaxis), modifying therapy in patients who become pregnant while receiving treatment, or modifying therapy in patients who have suboptimal virologic response to treatment that was started during pregnancy. DO NOT delay initiation of antiretroviral therapy while waiting on the results of resistance testing; treatment regimens can be modified, if necessary, once the testing results are known. A first trimester ultrasound is recommended to confirm gestational age and provide an accurate estimation of gestational age at delivery. A second trimester ultrasound can be used for both anatomical survey and determination of gestational age in those patients not seen until later in gestation. Perform standard glucose screening in patients receiving antiretroviral therapy at 24 to 28 weeks gestation, although it should be noted that some experts would perform earlier screening with ongoing chronic protease inhibitor-based therapy initiated prior to pregnancy, similar to recommendations for patients with high-risk factors for glucose intolerance. Liver function testing is recommended within 2 to 4 weeks after initiating or changing antiretroviral therapy, and approximately every 3 months thereafter during pregnancy (or as needed). All pregnant patients should be counseled about the importance of adherence to their antiretroviral regimen to reduce the potential for development of resistance and perinatal transmission. It is strongly recommended that antiretroviral therapy, once initiated, not be discontinued. If a patient decides to discontinue therapy, a consultation with an HIV specialist is recommended. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to tenofovir alafenamide; information about the registry can be obtained at www.apregistry.com or by calling 1-800-258-4263.
HIV treatment guidelines recommend clinicians provide mothers with evidence-based, patient-centered counseling to support shared decision-making regarding infant feeding. Inform patients that use of replacement feeding (i.e., formula or banked pasteurized donor human milk) eliminates the risk of HIV transmission. Advise patients who receive a diagnosis of HIV infection while breast-feeding (acute HIV) to immediately discontinue breast-feeding and switch to replacement feeding in order to reduce the risk of postnatal HIV transmission to the infant. Replacement feeding is also recommended for use when mothers with HIV are not on antiretroviral therapy (ART) or do not have suppressed viral load during pregnancy, as well as at delivery. For patients on ART who have achieved and maintained viral suppression during pregnancy (at minimum throughout the third trimester) and postpartum, the transmission risk from breast-feeding is less than 1%, but not zero. Virologically suppressed mothers who choose to breast-feed should be supported in this decision. If breast-feeding is chosen, counsel the patient about the importance of adherence to therapy and recommend that the infant be exclusively breast-fed for up to 6 months of age, as exclusive breast-feeding has been associated with a lower rate of HIV transmission as compared to mixed feeding (i.e., breast milk and formula). Promptly identify and treat mastitis, thrush, and cracked or bleeding nipples, as these conditions may increase the risk of HIV transmission through breast-feeding. Breast-fed infants should undergo immediate diagnostic and virologic HIV testing. Testing should continue throughout breast-feeding and up to 6 months after cessation of breast-feeding. For expert consultation, healthcare workers may contact the Perinatal HIV Hotline (888-448-8765). Tenofovir alafenamide breast milk transfer has been examined in small studies. In one study, breast milk from 5 patients with HIV identified a breast milk-to-plasma ratio of 4.09 for tenofovir alafenamide and a median estimated infant daily dose of 0.007 mg/kg. Another study in 8 breast-feeding patients with hepatitis B virus infection who received tenofovir alafenamide for at least 4 weeks estimated the breast milk-to-plasma ratio for tenofovir alafenamide and tenofovir to be 0.029 and 2.809, respectively. The relative tenofovir alafenamide dose was estimated at 0.005% of the maternal dose. Use of tenofovir alafenamide in HIV-negative breast-feeding mothers being treated for hepatitis B infection has not been studied; a consensus among healthcare providers regarding the use of tenofovir in this population has not been established. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.
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. The prevalence of transmitted drug resistance (TDR) in high-income countries ranges from 9% to 14% and varies by country. In most TDR surveys, non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance and nucleoside reverse transcriptase inhibitor (NRTI) resistance are the most common mutation class types detected, followed by protease inhibitor (PI) and integrase strand transfer inhibitor (INSTI) resistance mutations, respectively. 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 result kept in the patient's medical record until it becomes 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.
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy for HIV. During the initial phase of HIV treatment, patients whose immune system responds to a tenofovir alafenamide-containing regimen may develop an inflammatory response to indolent or residual opportunistic infections (such as progressive multifocal leukoencephalopathy (PML), mycobacterium avium complex (MAC), cytomegalovirus (CMV), Pneumocystis pneumonia, 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.
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
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.
This drug may also have activity against the following microorganisms: human immunodeficiency virus (HIV)
NOTE: Some organisms may not have been adequately studied during clinical trials; therefore, exclusion from this list does not necessarily negate the drug's activity against the organism.
For the treatment of chronic hepatitis B infection:
Oral dosage:
Adults: 25 mg PO once daily. 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 12 to 17 years: 25 mg PO once daily. 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 the treatment of human immunodeficiency virus (HIV) infection in combination with other anti-retroviral agents*:
NOTE: HIV guidelines recommend consideration be given to avoiding use of tenofovir alafenamide-containing regimens in patients with concurrent tuberculosis infection and receiving a rifamycin.
Initiation of therapy for HIV treatment
-For adults, initiation of treatment immediately (or as soon as possible) after HIV diagnosis is recommended in all patients to reduce the risk of disease progression and to prevent the transmission of HIV, including perinatal transmission and transmission to sexual partners. Starting antiretroviral therapy early is particularly important for patients with AIDS-defining conditions, those with acute or recent HIV infection, and individuals who are pregnant; delaying therapy in these subpopulations has been associated with high risks of morbidity, mortality, and HIV transmission.
-Prior to initiating treatment, obtain baseline plasma HIV RNA (viral load) and CD4 count; results do not need to be available before starting therapy.
-Antiretroviral drug-resistance testing:-Genotypic drug-resistance testing is recommended prior to initiation of therapy and prior to changing therapy for treatment failure.
--Standard genotypic drug-resistance testing in treatment-naive people should focus on testing for mutations in reverse transcriptase (RT) and protease (PR) genes.
-Testing for mutations in the integrase gene should also be performed if integrase strand transfer inhibitor (INSTI) resistance is a concern (e.g., people who acquire HIV after pre-exposure prophylaxis with long-acting cabotegravir).
-Phenotypic resistance testing may be used in conjunction with the genotypic test for patients with known or suspected complex drug-resistance mutation patterns.
-HIV-1 proviral DNA resistance testing is available for use in patients with HIV RNA concentrations below the limits of detection or with low-level viremia (i.e., less than 1,000 copies/mL), where genotypic testing is unlikely to be successful; however, the clinical utility of this assay has not been fully determined.
-It is not necessary to delay treatment until resistance test results are available; however, subsequent modifications to the treatment regimen should be made, if needed, once the test results are available.
-Pediatric guidelines are also available.
Place in therapy for HIV treatment
-For pregnant and non-pregnant patients, tenofovir alafenamide plus lamivudine or emtricitabine are preferred 2-NRTI backbones.
-Pediatric guidelines are also available.
Oral dosage:
Adults: 25 mg PO once daily.
Maximum Dosage Limits:
-Adults
25 mg/day PO.
-Geriatric
25 mg/day PO.
-Adolescents
25 mg/day PO.
-Children
12 years: 25 mg/day PO.
1 to 11 years: Safety and efficacy not established.
-Infants
Safety and efficacy not established.
-Neonates
Safety and efficacy not established.
Patients with Hepatic Impairment Dosing
No dosage adjustments are needed for mild hepatic impairment (Child-Pugh A). Tenofovir alafenamide is not recommended for use in patients with moderate to severe hepatic impairment (Child-Pugh B and C).
Patients with Renal Impairment Dosing
No data are available to make dose recommendations in pediatric patients with renal impairment.
For Adults:
CrCl 15 mL/minute or more: No dosage adjustment needed.
CrCl less than 15 mL/minute not receiving chronic hemodialysis: Use is not recommended.
Intermittent hemodialysis
CrCl less than 15 mL/minute receiving chronic hemodialysis: No dosage adjustment needed. Administer tenofovir alafenamide after completion of hemodialysis treatment on dialysis days.
*non-FDA-approved indication
Abrocitinib: (Moderate) Coadministration of tenofovir alafenamide with abrocitinib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and abrocitinib is a P-gp inhibitor.
Acalabrutinib: (Moderate) Coadministration of acalabrutinib and tenofovir alafenamide may increase the absorption and plasma concentration of tenofovir alafenamide. Acalabrutinib is an inhibitor of the breast cancer resistance protein (BCRP) transporter in vitro; it may inhibit intestinal BCRP. Tenofovir alafenamide is a BCRP substrate.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as salicylates. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Acetaminophen; Aspirin: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as salicylates. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as salicylates. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Acetaminophen; Ibuprofen: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Acyclovir: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as acyclovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Adagrasib: (Moderate) Coadministration of tenofovir alafenamide with adagrasib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and adagrasib is a P-gp inhibitor.
Adefovir: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as adefovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Aldesleukin, IL-2: (Major) Avoid concomitant use of tenofovir alafenamide and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Amikacin: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as aminoglycosides. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Aminoglycosides: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as aminoglycosides. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as salicylates. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Amiodarone: (Moderate) Coadministration of tenofovir alafenamide with amiodarone may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and amiodarone is a P-gp inhibitor.
Amlodipine; Celecoxib: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Coadministration of clarithromycin and tenofovir alafenamide may result in elevated tenofovir concentrations. Clarithromycin is an inhibitor of the drug transporter P-glycoprotein (P-gp). Tenofovir alafenamide is a P-gp substrate. However, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Amphotericin B lipid complex (ABLC): (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as amphotericin B. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Amphotericin B liposomal (LAmB): (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as amphotericin B. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Amphotericin B: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as amphotericin B. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Asciminib: (Moderate) Coadministration of tenofovir alafenamide with asciminib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a BCRP substrate and asciminib is a BCRP inhibitor.
Aspirin, ASA: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as salicylates. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as salicylates. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Aspirin, ASA; Caffeine: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as salicylates. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as salicylates. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as salicylates. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as salicylates. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Aspirin, ASA; Dipyridamole: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as salicylates. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Aspirin, ASA; Omeprazole: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as salicylates. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Aspirin, ASA; Oxycodone: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as salicylates. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Atazanavir: (Moderate) Concurrent use of atazanavir with tenofovir alafenamide may result in elevated tenofovir serum concentrations. Tenofovir alafenamide is a substrate for the drug transporter organic anion transporting polypeptide (OATP1B1/1B3); atazanavir is an OATP1B1 inhibitor. Monitor for increased toxicities if these drugs are given together.
Atazanavir; Cobicistat: (Moderate) Concurrent use of atazanavir with tenofovir alafenamide may result in elevated tenofovir serum concentrations. Tenofovir alafenamide is a substrate for the drug transporter organic anion transporting polypeptide (OATP1B1/1B3); atazanavir is an OATP1B1 inhibitor. Monitor for increased toxicities if these drugs are given together. (Moderate) The plasma concentrations of tenofovir may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects is recommended during coadministration. Cobicistat is an inhibitor of the drug transporters P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and organic anion transport protein (OATP1B1/1B3). Tenofovir alafenamide is a substrate for all three transporters.
Bacitracin: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as bacitracin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Barium Sulfate: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus, and urine glucose and protein.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as salicylates. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Bismuth Subsalicylate: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as salicylates. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as salicylates. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Brigatinib: (Moderate) Monitor for an increase in tenofovir-related adverse reactions if coadministration with brigatinib is necessary. Tenofovir alafenamide is a substrate of P-glycoprotein (P-gp) and BCRP. Brigatinib inhibits both P-gp and BCRP in vitro and may have the potential to increase concentrations of substrates of these transporters.
Bupivacaine; Meloxicam: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as salicylates. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Cabozantinib: (Minor) Monitor for an increase in both cabozantinib- and tenofovir-related adverse reactions if coadministration is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and tenofovir is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib. Cabozantinib is also P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates such as tenofovir. The clinical relevance of either of these interactions is unknown.
Cannabidiol: (Moderate) Coadministration of tenofovir alafenamide with cannabidiol may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Capmatinib: (Moderate) Coadministration of tenofovir alafenamide with capmatinib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-glycoprotein (P-gp) and BCRP substrate and capmatinib is a P-gp and BCRP inhibitor.
Carbamazepine: (Major) Administering tenofovir alafenamide with carbamazepine is not recommended. Consider use of an alternative anticonvulsant. Taking these drugs together is expected to decrease tenofovir plasma concentrations, which may increase the potential for resistance and HIV treatment failure.
Carboplatin: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as carboplatin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Carvedilol: (Minor) Caution is advised when administering tenofovir alafenamide concurrently with carvedilol, as coadministration may result in elevated tenofovir alafenamide plasma concentrations. Inhibitors of the drug transporter P-glycoprotein (P-gp), such as carvedilol, may increase absorption of tenofovir alafenamide, a P-gp substrate. If these medications are administered together, monitor for tenofovir-associated adverse reactions. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Celecoxib: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Celecoxib; Tramadol: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Choline Salicylate; Magnesium Salicylate: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as salicylates. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Cidofovir: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as cidofovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Cisplatin: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as cisplatin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Clarithromycin: (Moderate) Coadministration of clarithromycin and tenofovir alafenamide may result in elevated tenofovir concentrations. Clarithromycin is an inhibitor of the drug transporter P-glycoprotein (P-gp). Tenofovir alafenamide is a P-gp substrate. However, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Clindamycin: (Moderate) Concomitant use of tenofovir alafenamide and clindamycin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Cobicistat: (Moderate) The plasma concentrations of tenofovir may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects is recommended during coadministration. Cobicistat is an inhibitor of the drug transporters P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and organic anion transport protein (OATP1B1/1B3). Tenofovir alafenamide is a substrate for all three transporters.
Colistimethate, Colistin, Polymyxin E: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as colistimethate sodium. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Colistin: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as colistimethate sodium. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Conivaptan: (Moderate) Coadministration of conivaptan and tenofovir alafenamide may result in elevated tenofovir concentrations. Conivaptan is an inhibitor of the drug transporter P-glycoprotein (P-gp). Tenofovir alafenamide is a substrate for P-gp. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Cyclosporine: (Moderate) Cyclosporine therapeutic drug monitoring is recommended when administered concurrently with tenofovir alafenamide. Additionally, monitoring for changes in renal function is advised if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as cyclosporine. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions. Also, tenofovir alafenamide is a substrate of the drug transporters P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and the organic anion transport protein (OATP1B1 and 1B3); cyclosporine is an inhibitor of all three transporters. Inhibition of P-gp, BCRP, and OATP by cyclosporine may further increase tenofovir plasma concentrations. When tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Daclatasvir: (Minor) Caution is advised when administering tenofovir alafenamide concurrently with daclatasvir. Coadministration may result in increased tenofovir alafenamide plasma concentrations. Tenofovir alafenamide is a substrate of the drug transporters P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and the organic anion transport protein (OATP1B1 and 1B3); daclatasvir is an inhibitor all three transporters. If these drugs are administered together, closely monitor for tenofovir-associated adverse reactions. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Daridorexant: (Moderate) Coadministration of tenofovir alafenamide with daridorexant may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and daridorexant is a P-gp inhibitor.
Darolutamide: (Moderate) Caution is advised with the coadministration of darolutamide and tenofovir alafenamide due to the potential for increased plasma concentrations of tenofovir alafenamide increasing the risk of adverse effects. Tenofovir alafenamide is a substrate of breast cancer resistance protein (BCRP) and darolutamide is a BCRP inhibitor.
Darunavir; Cobicistat: (Moderate) The plasma concentrations of tenofovir may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects is recommended during coadministration. Cobicistat is an inhibitor of the drug transporters P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and organic anion transport protein (OATP1B1/1B3). Tenofovir alafenamide is a substrate for all three transporters.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) The plasma concentrations of tenofovir may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects is recommended during coadministration. Cobicistat is an inhibitor of the drug transporters P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and organic anion transport protein (OATP1B1/1B3). Tenofovir alafenamide is a substrate for all three transporters.
Dichlorphenamide: (Major) Use of dichlorphenamide and tenofovir alafenamide is not recommended because of increased tenofovir exposure and a risk of tenofovir-related adverse effects. Monitor closely for signs of drug toxicity if coadministration cannot be avoided. For example, it is important to monitor renal and hepatic function for all patients during treatment with tenofovir, as the drug may cause hepatotoxicity or nephrotoxicity. Increased tenofovir exposure is possible. Tenofovir is a sensitive OAT1 substrate. Dichlorphenamide inhibits OAT1.
Diclofenac: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Diclofenac; Misoprostol: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Diflunisal: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Diphenhydramine; Ibuprofen: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Diphenhydramine; Naproxen: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Dofetilide: (Major) Dofetilide should be co-administered with tenofovir alafenamide with caution since both drugs are actively secreted via cationic secretion and could compete for common renal tubular transport systems. This results in a possible increase in plasma concentrations of either drug. Increased concentrations of dofetilide may increase the risk for side effects including proarrhythmia. Careful patient monitoring and dose adjustment of dofetilide is recommended.
Elacestrant: (Moderate) Coadministration of tenofovir alafenamide with elacestrant may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a substrate of BCRP and P-gp; elacestrant is an inhibitor of BCRP and P-gp.
Elexacaftor; tezacaftor; ivacaftor: (Moderate) Monitor for tenofovir alafenamide-related adverse reactions during coadministration of elexacaftor; tezacaftor; ivacaftor as concurrent use may increase exposure of tenofovir alafenamide. Tenofovir alafenamide is a substrate for the transporters OATP1B1 and OATP1B3; elexacaftor; tezacaftor; ivacaftor may inhibit uptake of OATP1B1 and OATP1B3. (Minor) Use caution when administering ivacaftor and tenofovir alafenamide concurrently. Ivacaftor is an inhibitor of the drug transporter P-glycoprotein (P-gp). Tenofovir alafenamide is a substrate for P-gp. Concurrent use can increase tenofovir exposure leading to adverse events. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Eliglustat: (Major) Coadministration of tenofovir alafenamide and eliglustat may result in increased concentrations of tenofovir. Monitor patients closely for tenofovir-related adverse effects including nausea, diarrhea, headache, asthenia, and nephrotoxicity. Tenofovir is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor. For coadministration with P-gp substrates, eliglustat's product labeling recommends monitoring therapeutic drug concentrations of the P-gp substrate, if possible, or consideration of a dosage reduction and titrating to clinical effect. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) The plasma concentrations of tenofovir may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects is recommended during coadministration. Cobicistat is an inhibitor of the drug transporters P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and organic anion transport protein (OATP1B1/1B3). Tenofovir alafenamide is a substrate for all three transporters.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) The plasma concentrations of tenofovir may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects is recommended during coadministration. Cobicistat is an inhibitor of the drug transporters P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and organic anion transport protein (OATP1B1/1B3). Tenofovir alafenamide is a substrate for all three transporters.
Enasidenib: (Moderate) Coadministration of tenofovir alafenamide with enasidenib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp and BCRP substrate and enasidenib is a P-gp and BCRP inhibitor.
Encorafenib: (Moderate) Coadministration of tenofovir alafenamide with encorafenib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp and BCRP substrate and encorafenib is a BCRP inhibitor.
Erdafitinib: (Moderate) Coadministration of tenofovir alafenamide with erdafitinib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Erythromycin: (Moderate) Coadministration of tenofovir alafenamide with erythromycin may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and erythromycin is a P-gp inhibitor.
Estradiol; Norgestimate: (Moderate) Monitor for norgestimate-related adverse events, such as insulin resistance, dyslipidemia, acne, and venous thrombosis, and consider risks and benefits of coadministration of tenofovir alafenamide in persons who have risk factors for these events. Concomitant use may increase norgestimate concentrations.
Ethiodized Oil: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Etodolac: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Felodipine: (Minor) Caution is advised when administering tenofovir alafenamide concurrently with felodipine, as coadministration may result in elevated tenofovir alafenamide plasma concentrations. Inhibitors of the drug transporter P-glycoprotein (P-gp), such as felodipine, may increase absorption of tenofovir alafenamide, a P-gp substrate. If these medications are administered together, monitor for tenofovir-associated adverse reactions. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Fenoprofen: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Flibanserin: (Minor) Caution is advised when administering tenofovir alafenamide concurrently with flibanserin, as coadministration may result in elevated tenofovir alafenamide plasma concentrations. Inhibitors of the drug transporter P-glycoprotein (P-gp), such as flibanserin, may increase absorption of tenofovir alafenamide, a P-gp substrate. If these medications are administered together, monitor for tenofovir-associated adverse reactions. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Flurbiprofen: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Foscarnet: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as foscarnet. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Fosphenytoin: (Major) Administering tenofovir alafenamide with fosphenytoin is not recommended. Consider use of an alternative anticonvulsant. Taking these drugs together is expected to decrease tenofovir plasma concentrations, which may increase the potential for resistance and HIV treatment failure.
Fostamatinib: (Moderate) Monitor for tenofovir toxicities that may require tenofovir alafenamide dose reduction if given concurrently with fostamatinib. Concomitant use of fostamatinib with a BCRP or P-gp substrate may increase the concentration of the BCRP or P-gp substrate. Fostamatinib is a P-gp inhibitor, and the active metabolite of fostamatinib, R406, is a BCRP inhibitor; tenofovir alafenamide is a substrate for BCRP and P-gp. Coadministration of fostamatinib with another BCRP substrate increased the substrate AUC by 95% and Cmax by 88%. Coadministration of fostamatinib with another P-gp substrate increased the substrate AUC by 37% and Cmax by 70%.
Fostemsavir: (Moderate) Concomitant use of tenofovir alafenamide with fostemsavir may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a BCRP substrate and fostemsavir is a BCRP inhibitor.
Futibatinib: (Moderate) Coadministration of tenofovir alafenamide with futibatinib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp and BCRP substrate and futibatinib is a P-gp and BCRP inhibitor.
Gadobutrol: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Gadoversetamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Ganciclovir: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as ganciclovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Gentamicin: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as aminoglycosides. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Gilteritinib: (Moderate) Coadministration of tenofovir alafenamide with gilteritinib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a substrate of P-gp and BCRP and gilteritinib is a P-gp and BCRP inhibitor.
Grapefruit juice: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as grapefruit juice. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Hydrocodone; Ibuprofen: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as salicylates. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Ibuprofen: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Ibuprofen; Famotidine: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Ibuprofen; Oxycodone: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Ibuprofen; Pseudoephedrine: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Indomethacin: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Iodixanol: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Iohexol: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Iomeprol: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Iopamidol: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Iopromide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Ioversol: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Isavuconazonium: (Minor) Close clinical monitoring for adverse events is advised when administering tenofovir alafenamide with isavuconazonium. Use of these drugs together may result in elevated tenofovir plasma concentrations. Isavuconazonium is an inhibitor of the drug transporter P-glycoprotein (P-gp). Tenofovir alafenamide is a substrate for P-gp. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Administering tenofovir alafenamide with rifampin is not recommended. Taking these drugs together is expected to decrease tenofovir plasma concentrations, which may increase the potential for resistance and HIV treatment failure.
Isoniazid, INH; Rifampin: (Major) Administering tenofovir alafenamide with rifampin is not recommended. Taking these drugs together is expected to decrease tenofovir plasma concentrations, which may increase the potential for resistance and HIV treatment failure.
Isosulfan Blue: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Ivacaftor: (Minor) Use caution when administering ivacaftor and tenofovir alafenamide concurrently. Ivacaftor is an inhibitor of the drug transporter P-glycoprotein (P-gp). Tenofovir alafenamide is a substrate for P-gp. Concurrent use can increase tenofovir exposure leading to adverse events. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Ketoconazole: (Minor) According to the manufacturer, interactions are not expected during coadministration of ketoconazole and tenofovir alafenamide; however based on the metabolic pathways of these medications, monitoring for tenofovir-associated adverse reactions should be considered if these drugs are given together. Ketoconazole is an inhibitor of the drug transporter P-glycoprotein (P-gp). Tenofovir alafenamide is a substrate for P-gp. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Ketoprofen: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Ketorolac: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Coadministration of clarithromycin and tenofovir alafenamide may result in elevated tenofovir concentrations. Clarithromycin is an inhibitor of the drug transporter P-glycoprotein (P-gp). Tenofovir alafenamide is a P-gp substrate. However, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Lasmiditan: (Moderate) Coadministration of tenofovir alafenamide with lasmiditan may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Ledipasvir; Sofosbuvir: (Minor) According to the manufacturer, interactions are not expected during coadministration of ledipasvir; sofosbuvir and tenofovir alafenamide; however based on the metabolic pathways of these medications, monitoring for tenofovir-associated adverse reactions should be considered if these drugs are given together. Tenofovir is a substrate of the drug transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); ledipasvir is an inhibitor of both P-gp and BCRP. Use of these drugs together may increase tenofovir plasma concentrations. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Leniolisib: (Moderate) Coadministration of tenofovir alafenamide with leniolisib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a BCRP substrate and leniolisib is a BCRP inhibitor.
Levoketoconazole: (Minor) According to the manufacturer, interactions are not expected during coadministration of ketoconazole and tenofovir alafenamide; however based on the metabolic pathways of these medications, monitoring for tenofovir-associated adverse reactions should be considered if these drugs are given together. Ketoconazole is an inhibitor of the drug transporter P-glycoprotein (P-gp). Tenofovir alafenamide is a substrate for P-gp. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Lonafarnib: (Moderate) Coadministration of tenofovir alafenamide with lonafarnib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and lonafarnib is a P-gp inhibitor.
Lopinavir; Ritonavir: (Moderate) Concurrent use of lopinavir with tenofovir alafenamide may result in elevated tenofovir serum concentrations. Tenofovir alafenamide is a substrate for the drug transporter organic anion transporting polypeptide (OATP1B1/1B3); lopinavir is an OATP1B1 inhibitor. When 10 mg of tenofovir alafenamide was administered daily with lopinavir; ritonavir (800 mg/200 mg PO daily), the tenofovir Cmax and AUC increased by 2.19-fold and 1.47-fold, respectively. Monitor for increased toxicities if these drugs are given together.
Lumacaftor; Ivacaftor: (Moderate) Concomitant use of lumacaftor; ivacaftor and tenofovir alafenamide could potentially alter the systemic exposure of tenofovir. Tenofovir alafenamide is a substrate of the drug transporter P-glycoprotein (P-gp). In vitro data suggest that lumacaftor; ivacaftor has the potential to both induce and inhibit P-gp. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor. (Minor) Use caution when administering ivacaftor and tenofovir alafenamide concurrently. Ivacaftor is an inhibitor of the drug transporter P-glycoprotein (P-gp). Tenofovir alafenamide is a substrate for P-gp. Concurrent use can increase tenofovir exposure leading to adverse events. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Lumacaftor; Ivacaftor: (Moderate) Concomitant use of lumacaftor; ivacaftor and tenofovir alafenamide could potentially alter the systemic exposure of tenofovir. Tenofovir alafenamide is a substrate of the drug transporter P-glycoprotein (P-gp). In vitro data suggest that lumacaftor; ivacaftor has the potential to both induce and inhibit P-gp. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Magnesium Salicylate: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as salicylates. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Maribavir: (Moderate) Coadministration of tenofovir alafenamide with maribavir may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp and BCRP substrate and maribavir is a P-gp and BCRP inhibitor.
Meclofenamate Sodium: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Mefenamic Acid: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Meloxicam: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Meropenem: (Moderate) Coadministration of tenofovir alafenamide with meropenem may result in decreased tenofovir exposure, which may result in potential loss of virologic control. Tenofovir alafenamide is a P-gp substrate and meropenem is a P-gp inducer.
Meropenem; Vaborbactam: (Moderate) Coadministration of tenofovir alafenamide with meropenem may result in decreased tenofovir exposure, which may result in potential loss of virologic control. Tenofovir alafenamide is a P-gp substrate and meropenem is a P-gp inducer.
Methenamine; Sodium Salicylate: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as salicylates. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Methotrexate: (Major) Avoid concomitant use of methotrexate with tenofovir alafenamide due to the risk of additive nephrotoxicity as well as an increased risk of severe methotrexate-related adverse reactions. If concomitant use is unavoidable, closely monitor for adverse reactions. Tenofovir alafenamide and methotrexate are both nephrotoxic drugs; methotrexate is also renally eliminated. Coadministration of methotrexate with tenofovir alafenamide may result in decreased renal function as well as increased methotrexate plasma concentrations.
Midostaurin: (Moderate) Coadministration of tenofovir alafenamide with midostaurin may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a BCRP substrate and midostaurin is a BCRP inhibitor.
Mitapivat: (Moderate) Coadministration of tenofovir alafenamide with mitapivat may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and mitapivat is a P-gp inhibitor.
Momelotinib: (Moderate) Coadministration of tenofovir alafenamide with momelotinib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a BCRP substrate and momelotinib is a BCRP inhibitor.
Nabumetone: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Naproxen: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Naproxen; Esomeprazole: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Naproxen; Pseudoephedrine: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Neratinib: (Moderate) Coadministration of tenofovir alafenamide with neratinib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-glycoprotein (P-gp) substrate and neratinib is a P-gp inhibitor.
Nitisinone: (Moderate) Monitor for increased tenofovir-related adverse effects if coadministered with nitisinone. Increased tenofovir exposure is possible. Nitisinone inhibits OAT1. Tenofovir is an OAT1 substrate.
Non-Ionic Contrast Media: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Nonsteroidal antiinflammatory drugs: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Norgestimate; Ethinyl Estradiol: (Moderate) Monitor for norgestimate-related adverse events, such as insulin resistance, dyslipidemia, acne, and venous thrombosis, and consider risks and benefits of coadministration of tenofovir alafenamide in persons who have risk factors for these events. Concomitant use may increase norgestimate concentrations.
Omeprazole; Amoxicillin; Rifabutin: (Major) Coadministration is not recommended. Concurrent use may result in significant decreases in the plasma concentrations of tenofovir alafenamide, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance.
Orlistat: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with tenofovir, PMPA. Loss of virological control has been reported in HIV-infected patients taking orlistat with tenofovir disoproxil fumarate and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
Osimertinib: (Moderate) Monitor for an increase in tenofovir-related adverse reactions if coadministration with osimertinib is necessary. Concomitant use may result in increased tenofovir absorption. Tenofovir alafenamide is a BCRP and P-glycoprotein (P-gp) substrate. Osimertinib is a BCRP and P-gp inhibitor.
Oteseconazole: (Moderate) Coadministration of tenofovir alafenamide with oteseconazole may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a BCRP substrate and oteseconazole is a BCRP inhibitor.
Oxaliplatin: (Major) Avoid coadministration of oxaliplatin with tenofovir alafenamide due to the risk of increased oxaliplatin-related adverse reactions. Tenofovir alafenamide is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
Oxaprozin: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Oxcarbazepine: (Major) Administering tenofovir alafenamide with oxcarbazepine is not recommended. Consider use of an alternative anticonvulsant. Taking these drugs together is expected to decrease tenofovir plasma concentrations, which may increase the potential for resistance and HIV treatment failure.
Pacritinib: (Moderate) Concomitant use of tenofovir alafenamide with pacritinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp and BCRP substrate; pacritinib is a P-gp and BCRP inhibitor.
Pamidronate: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as pamidronate. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Paromomycin: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as aminoglycosides. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Phenobarbital: (Major) Administering tenofovir alafenamide with phenobarbital is not recommended. Consider use of an alternative anticonvulsant. Taking these drugs together is expected to decrease tenofovir plasma concentrations, which may increase the potential for resistance and HIV treatment failure.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Administering tenofovir alafenamide with phenobarbital is not recommended. Consider use of an alternative anticonvulsant. Taking these drugs together is expected to decrease tenofovir plasma concentrations, which may increase the potential for resistance and HIV treatment failure.
Phenytoin: (Major) Administering tenofovir alafenamide with phenytoin is not recommended. Consider use of an alternative anticonvulsant. Taking these drugs together is expected to decrease tenofovir plasma concentrations, which may increase the potential for resistance and HIV treatment failure.
Pirfenidone: (Moderate) Close clinical monitoring for adverse events is advised when administering tenofovir alafenamide with pirfenidone. Use of these drugs together may result in elevated tenofovir plasma concentrations. Pirfenidone is an inhibitor of the drug transporter P-glycoprotein (P-gp). Tenofovir alafenamide is a substrate for P-gp. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Piroxicam: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Pirtobrutinib: (Moderate) Coadministration of tenofovir alafenamide with pirtobrutinib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp and BCRP substrate and pirtobrutinib is a P-gp and BCRP inhibitor.
Plazomicin: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as aminoglycosides. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Polymyxin B: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as polymyxin B. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Posaconazole: (Moderate) Close clinical monitoring adverse events are advised when administering tenofovir alafenamide with posaconazole. Use of these drugs together may result in elevated tenofovir alafenamide plasma concentrations. Posaconazole is an inhibitor of the drug transporter P-glycoprotein (P-gp). Tenofovir alafenamide is a substrate for P-gp. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Pretomanid: (Moderate) Coadministration of tenofovir alafenamide with pretomanid may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp and BCRP substrate and pretomanid is a P-gp and BCRP inhibitor.
Primidone: (Moderate) Close clinical monitoring is advised when administering primidone with tenofovir alafenamide due to the potential for treatment failure. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of these drugs. Primidone is an inducer of the drug transporter P-glycoprotein (P-gp). Tenofovir alafenamide is a substrate for P-gp. Coadministration may result in decreased tenofovir serum concentrations and impaired virologic response.
Probenecid: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as probenecid. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Probenecid; Colchicine: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as probenecid. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Propafenone: (Moderate) Coadministration of tenofovir alafenamide with propafenone may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and propafenone is a P-gp inhibitor.
Ranolazine: (Minor) Close clinical monitoring is advised when administering ranolazine with tenofovir alafenamide due to an increased potential for adverse events. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of these drugs. Ranolazine is an inhibitor of the drug transporter P-glycoprotein (P-gp). Tenofovir alafenamide is a substrate for P-gp. Coadministration may result in increased tenofovir plasma concentrations. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Regorafenib: (Moderate) Use caution if coadministration of regorafenib with tenofovir alafenamide is necessary, and monitor for an increase in tenofovir alafenamide-related adverse reactions. Tenofovir alafenamide is a BCRP substrate and regorafenib is a BCRP inhibitor. Regorafenib-mediated BCRP inhibition may increase exposure to tenofovir alafenamide. However, when tenofovir alafenamide is administered in combination with cobicistat, other inhibitors of BCRP are not expected to further increase tenofovir alafenamide concentrations.
Rifabutin: (Major) Coadministration is not recommended. Concurrent use may result in significant decreases in the plasma concentrations of tenofovir alafenamide, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance.
Rifampin: (Major) Administering tenofovir alafenamide with rifampin is not recommended. Taking these drugs together is expected to decrease tenofovir plasma concentrations, which may increase the potential for resistance and HIV treatment failure.
Rifapentine: (Major) Avoid coadministration of tenofovir alafenamide and rifapentine as concurrent use may decrease tenofovir alafenamide exposure leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Additionally, HIV patients treated with rifapentine have a higher rate of TB relapse than those treated with other rifamycin-based regimens; an alternative agent is recommended.
Rivaroxaban: (Minor) Caution is advised when administering tenofovir alafenamide concurrently with rivaroxaban, as coadministration may result in elevated tenofovir alafenamide plasma concentrations. Inhibitors of the drug transporter P-glycoprotein (P-gp), such as rivaroxaban, may increase absorption of tenofovir alafenamide, a P-gp substrate. If these medications are administered together, monitor for tenofovir-associated adverse reactions. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Rolapitant: (Moderate) Coadministration of rolapitant and tenofovir alafenamide may result in elevated tenofovir concentrations. Tenofovir is a substrate of the Breast Cancer Resistance Protein (BCRP) and P-glycoprotein (P-gp); rolapitant is a BCRP and P-gp inhibitor. The Cmax and AUC of another BCRP substrate, sulfasalazine, were increased by 140 percent and 130 percent, respectively, on day 1 with rolapitant, and by 17 percent and 32 percent, respectively, on day 8 after rolapitant administration. When rolapitant was administered with digoxin, a P-gp substrate, the day 1 Cmax and AUC were increased by 70 percent and 30 percent, respectively; the Cmax and AUC on day 8 were not studied.
Salicylates: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as salicylates. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Salsalate: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as salicylates. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Selpercatinib: (Moderate) Coadministration of tenofovir alafenamide with selpercatinib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and selpercatinib is a P-gp inhibitor.
Sodium Phenylbutyrate; Taurursodiol: (Moderate) Coadministration of tenofovir alafenamide with taurursodiol may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp and BCRP substrate and taurursodiol is a P-gp and BCRP inhibitor.
Sofosbuvir; Velpatasvir: (Moderate) Monitor patients for tenofovir-associated adverse reactions, such as renal toxicity, in patients receiving regimens containing tenofovir alafenamide and velpatasvir due to potential increases in tenofovir serum concentrations. Tenofovir alafenamide is a substrate of the breast cancer resistance protein (BCRP),P-glycoprotein (P-gP), OATP1B1, and OATB1B3 transporters, while velpatasvir inhibits these transporters.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Monitor patients for tenofovir-associated adverse reactions, such as renal toxicity, in patients receiving regimens containing tenofovir alafenamide and velpatasvir due to potential increases in tenofovir serum concentrations. Tenofovir alafenamide is a substrate of the breast cancer resistance protein (BCRP),P-glycoprotein (P-gP), OATP1B1, and OATB1B3 transporters, while velpatasvir inhibits these transporters.
Sotorasib: (Moderate) Coadministration of tenofovir alafenamide with sotorasib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp and BCRP substrate. Sotorasib is a P-gp and BCRP inhibitor.
Sparsentan: (Moderate) Coadministration of tenofovir alafenamide with sparsentan may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp and BCRP substrate and sparsentan is a P-gp and BCRP inhibitor.
St. John's Wort, Hypericum perforatum: (Major) Administering tenofovir alafenamide with St. John's wort is not recommended. Taking these drugs together is expected to decrease tenofovir plasma concentrations, which may increase the potential for resistance and HIV treatment failure.
Streptomycin: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as aminoglycosides. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Sulindac: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Sumatriptan; Naproxen: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Tacrolimus: (Moderate) Tacrolimus therapeutic drug monitoring is recommended when administered concurrently with tenofovir alafenamide. Use of these medications together may result in elevated tacrolimus serum concentrations. Additionally, monitoring for changes in renal function is advised if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as tacrolimus. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Tafamidis: (Moderate) Caution is advised with the coadministration of tafamidis and tenofovir alafenamide due to the potential for increased plasma concentrations of tenofovir alafenamide increasing the risk of adverse effects. Tenofovir alafenamide dose adjustment may be needed with coadministration. Tenofovir alafenamide is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Tedizolid: (Moderate) If possible, stop use of tenofovir alafenamide temporarily during treatment with oral tedizolid. If coadministration cannot be avoided, closely monitor for tenofovir-associated adverse events. Tenofovir plasma concentrations may be increased when tenofovir alafenamide is administered concurrently with oral tedizolid. Tenofovir alafenamide is a substrate of the Breast Cancer Resistance Protein (BCRP); oral tedizolid inhibits BCRP in the intestine. When tenofovir alafenamide is administered in combination with cobicistat, other inhibitors of BCRP are not expected to further increase tenofovir concentrations.
Temsirolimus: (Moderate) Monitor for an increase in tenofovir alafenamide-related adverse reactions if coadministration with temsirolimus is necessary. Tenofovir alafenamide is a P-glycoprotein (P-gp) substrate and temsirolimus is a P-gp inhibitor. Concomitant use is likely to lead to increased concentrations of tenofovir alafenamide.
Tepotinib: (Moderate) Coadministration of tenofovir alafenamide with tepotinib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp and BCRP substrate and tepotinib is a P-gp inhibitor.
Tezacaftor; Ivacaftor: (Minor) Use caution when administering ivacaftor and tenofovir alafenamide concurrently. Ivacaftor is an inhibitor of the drug transporter P-glycoprotein (P-gp). Tenofovir alafenamide is a substrate for P-gp. Concurrent use can increase tenofovir exposure leading to adverse events. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Ticagrelor: (Moderate) Coadministration of tenofovir alafenamide with ticagrelor may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and ticagrelor is a P-gp inhibitor.
Tipranavir: (Major) Administering tenofovir alafenamide concurrently with tipranavir boosted with ritonavir is not recommended. Taking these drugs together is expected to decrease tenofovir plasma concentrations, which may increase the potential for resistance and HIV treatment failure. Tenofovir alafenamide is a substrate of P-glycoprotein (P-gp); tipranavir boosted with ritonavir is an inducer of P-gp.
Tobramycin: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as aminoglycosides. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Tolmetin: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Trandolapril; Verapamil: (Moderate) Coadministration of tenofovir alafenamide with verapamil may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and verapamil is a P-gp inhibitor.
Trospium: (Moderate) Tenofovir-containing products should be avoided with concurrent trospium administration as both are eliminated by active renal tubular secretion; coadministration has the potential to increase serum concentrations of either drug due to competition for the elimination pathway and patients should be carefully monitored.
Tucatinib: (Moderate) Coadministration of tenofovir alafenamide with tucatinib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-glycoprotein (P-gp) substrate and tucatinib is a P-gp inhibitor.
Valacyclovir: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as valacyclovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Valganciclovir: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as valganciclovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Valproic Acid, Divalproex Sodium: (Moderate) Caution is advised when administering tenofovir alafenamide with valproic acid, divalproex sodium, as there is a potential for decreased tenofovir plasma concentrations. Valproic acid is an in vitro inducer of P-glycoprotein (P-gp); tenofovir alafenamide is a P-gp substrate. Concurrent use may decrease absorption and alter metabolism of tenofovir.
Vancomycin: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as vancomycin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Vemurafenib: (Moderate) Coadministration of vemurafenib and tenofovir alafenamide may result in elevated tenofovir concentrations. Vemurafenib is an inhibitor of the drug transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Tenofovir alafenamide is a P-gp and BCRP substrate. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Verapamil: (Moderate) Coadministration of tenofovir alafenamide with verapamil may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and verapamil is a P-gp inhibitor.
Voclosporin: (Moderate) Coadministration of tenofovir alafenamide and voclosporin may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Concomitant use may also may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required. Tenofovir alafenamide is a P-gp substrate and voclosporin is a P-gp inhibitor.
Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) Coadministration of clarithromycin and tenofovir alafenamide may result in elevated tenofovir concentrations. Clarithromycin is an inhibitor of the drug transporter P-glycoprotein (P-gp). Tenofovir alafenamide is a P-gp substrate. However, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Zoledronic Acid: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as zoledronic acid. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Zonisamide: (Minor) Caution is advised when administering tenofovir alafenamide concurrently with zonisamide, as coadministration may result in elevated tenofovir plasma concentrations. Inhibitors of the drug transporter P-glycoprotein (P-gp), such as zonisamide, may increase absorption of tenofovir alafenamide, a P-gp substrate. If these medications are administered together, monitor for tenofovir-associated adverse reactions. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Tenofovir alafenamide is a phosphonamidate prodrug of tenofovir. Tenofovir alafenamide is taken up by cells, where it undergoes hydrolysis by cathepsin A to form tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5'-monophosphate. Subsequently, tenofovir is phosphorylated by cellular kinases to form the active metabolite, tenofovir diphosphate. Tenofovir diphosphate acts as a competitive inhibitor of 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, including mitochondrial DNA polymerase-gamma.
The mean EC50 (50% effective concentration) of tenofovir alafenamide against HBV is 86.6 (range, 34.7 to 134.4 nM). No antagonistic activity was observed with the following HBV nucleoside reverse transcriptase inhibitors in cell: entecavir, lamivudine, telbivudine.
Tenofovir alafenamide is administered orally. Plasma protein binding of tenofovir alafenamide is approximately 80%, with a mean blood to plasma ratio of 1. Initially, tenofovir alafenamide is converted to tenofovir via hydrolysis by cathepsin A (in peripheral blood mononuclear cells and macrophages) and by carboxylesterase 1 (in hepatocytes). Subsequently, tenofovir undergoes phosphorylation to its active metabolite, tenofovir diphosphate. Neither tenofovir nor tenofovir diphosphate are substrates for CYP450 hepatic isoenzymes; however, CYP3A enzymes play a minor role in the metabolism of the prodrug, tenofovir alafenamide. Metabolism is the primary mechanism by which tenofovir alafenamide is eliminated (more than 80% of the dose), with excretion via feces and urine accounting for 31.7% and less than 1%, respectively. Elimination of the tenofovir metabolite occurs primarily via the kidneys (70% to 80%) by a combination of glomerular filtration and active tubular secretion. The median terminal plasma half-life of tenofovir alafenamide is 0.51 hours.
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A, P-gp, BCRP, OATP1B1, and OATP1B3
Tenofovir alafenamide is a minor substrate of the hepatic isoenzyme CYP3A, and a substrate for the drug transporters P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporter polypeptide (OATP1B1), and OATP1B3.
-Route-Specific Pharmacokinetics
Oral Route
Peak plasma concentrations are observed approximately 0.5 hours after oral administration. Systemic exposure (AUC) is increased when administered with a high-fat meal (800 kcal; 50% fat).
-Special Populations
Hepatic Impairment
Compared to patients with normal hepatic function, the pharmacokinetics of tenofovir alafenamide and the active metabolite (tenofovir) are similar in patients with mild hepatic impairment (Child-Pugh A).
Renal Impairment
The pharmacokinetics of tenofovir alafenamide (as part of the combination drug elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide 150/150/200/10 mg) were studied in an open-label trial of subjects with HIV and ESRD on chronic hemodialysis (n = 55; CrCl less than 15 mL/minute). Tenofovir alafenamide 10 mg, given in this combination, achieved similar exposures as tenofovir alafenamide 25 mg given alone. In another trial of virologically suppressed patients with HBV, the pharmacokinetics of tenofovir alafenamide 25 mg were evaluated in subjects with severe renal impairment (n = 78; CrCl 15 to 59 mL/min) and ESRD on chronic hemodialysis (n = 15; CrCl less than 15 mL/min). In this trial, exposures to tenofovir alafenamide were similar to exposure observed in patients with normal renal function; however, tenofovir exposures were increased in patients with severe renal impairment and ESRD on chronic hemodialysis as compared to those with normal renal function. Within the chronic hemodialysis population, increased tenofovir exposures were also observed in subjects receiving 25 mg of tenofovir alafenamide for HBV as compared to those treated with 10 mg for HIV; the clinical significance of these higher exposures has not been established. The pharmacokinetics and safety of tenofovir alafenamide have not been evaluated in patients with ESRD not receiving chronic hemodialysis.
Pediatrics
No clinically meaningful differences in the pharmacokinetics of tenofovir alafenamide were observed in pediatric patients between the ages of 12 to less than 18 years when compared to adults.
Other
Pregnancy
The pharmacokinetics of tenofovir alafenamide can differ during pregnancy, depending on the concomitant antiretrovirals administered; however, exposures appear to be adequate in the second and third trimesters based on comparisons to historical data in nonpregnant adults. The pharmacokinetics of tenofovir alafenamide were evaluated as part of the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network in 31 patients taking 10 mg with cobicistat, 27 patients taking 25 mg without a booster, and 29 patients taking 25 mg with a booster. Systemic exposure of tenofovir alafenamide did not differ between pregnancy and postpartum for patients taking 10 mg with cobicistat or 25 mg with a booster. For patients taking 25 mg without a booster, exposures were 33% to 43% lower during pregnancy compared to postpartum, but comparable to exposures observed in nonpregnant adults. The pharmacokinetics of tenofovir alafenamide and tenofovir were also evaluated by the Pharmacokinetics of Newly Developed Antiretroviral Agents in HIV-infected pregnant patients (PANNA) Network in 20 pregnant and postpartum European patients receiving 10 mg with cobicistat or 25 mg without a booster. The results from both dosing combinations were pooled and showed that tenofovir alafenamide and tenofovir exposures were 46% and 33% lower during pregnancy, respectively, than postpartum. Despite these decreases, 94% of pregnant patients remained above the predefined tenofovir alafenamide exposure efficacy target of 53.1 ng x hour/mL.