CONTRAINDICATIONS / PRECAUTIONS
General Information
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.
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. Health care 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. [46638]
Hypophosphatemia, renal failure, renal impairment
New and worsening renal impairment, including acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been associated with tenofovir use. Assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients prior to initiation and as clinically appropriate during therapy; a dosage adjustment may be necessary. In patients at risk for or with a history of renal dysfunction, also assess serum phosphorus prior to therapy initiation and periodically during therapy. Although no safety or efficacy data are available, the dosing interval should be adjusted in patients with a creatinine clearance less than 50 mL/minute. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent (e.g., non-steroidal anti-inflammatory drugs [NSAIDs]). Cases of acute renal failure, requiring hospitalization and renal replacement therapy, have been reported in patients with HIV at high-risk for renal impairment, who appeared stable on tenofovir, after initiation of high-dose or multiple-dose NSAIDs. Patients at risk for renal dysfunction should be given alternative therapy to NSAIDs if required. Worsening bone pain, pain in extremities, bone fracture, and muscular pain or weakness may be manifestations of proximal renal tubulopathy; promptly evaluate renal function in patients experiencing these symptoms.[28193]
Bone fractures, children, osteomalacia, osteoporosis
Bone mineral density (BMD) monitoring should be considered for patients receiving tenofovir who have a history of pathologic bone fractures or are at substantial risk for osteopenia, osteoporosis, or osteomalacia; osteomalacia has been reported in association with tenofovir administration. Cases of osteomalacia associated with proximal renal tubulopathy have been reported with tenofovir therapy. Worsening bone pain, pain in extremities, fractures, and muscular pain or weakness may also be manifestations of proximal renal tubulopathy; promptly evaluate renal function in patients experiencing these symptoms. Normally, BMD increases rapidly in children and adolescents; however, in studies of tenofovir-treated pediatric patients, bone effects were similar to those noted in adult patients. One study evaluating children aged 2 to 12 years with HIV found total body BMD gains in recipients of tenofovir to be lower than the gains observed in patients receiving either stavudine or zidovudine. Additionally, at treatment week 48, 1 tenofovir-treated patient experienced significant (more than 4%) BMD loss in the lumbar spine; significant BMD losses were not observed in the stavudine or zidovudine treatment groups. In another study involving adolescents aged 12 to 17 years, the mean rate of BMD gain was less in the tenofovir-treated patients compared to the placebo group. Six tenofovir-treated adolescents and 1 placebo-treated adolescent had significant (more than 4%) lumbar spine BMD loss in 48 weeks. Two other studies in pediatric patients 2 to 11 years and 12 to 17 years with chronic hepatitis B also observed smaller gains in lumbar and total body BMD for those patients receiving tenofovir compared to the placebo group. In patients, 2 to 11 years, lumbar and total body BMD gains were +4% and +5%, respectively, in patients who received tenofovir compared with +8% and +9%, respectively, for the placebo group. In patients, 12 to 17 years, lumbar and total body BMD gains were +5% and +3%, respectively, in patients who received tenofovir compared with +8% and +5%, respectively, for the placebo group. After 72 weeks of treatment in the adolescent group, significant (more than 4%) lumbar spine BMD losses occurred in 3 tenofovir patients and 2 placebo patients. In all pediatric studies, the skeletal growth height appeared to be unaffected. The long-term effect of lower spine and total body BMD on skeletal growth in pediatric patients, and in particular, the effects of long-duration exposure in younger children is unknown. Although the effect of supplementation with calcium and vitamin D has not been studied, such supplementation may be considered for HIV-associated osteopenia or osteoporosis. If bone abnormalities are suspected, appropriate consultation should be obtained.[28193]
Geriatric
Geriatric patients are more likely to have decreased renal function and may require dose reduction and special monitoring (see Dosage). Clinical trials of tenofovir did not contain significant numbers of elderly patients to determine if they would respond differently from younger patients.
Alcoholism, females, hepatic disease, hepatotoxicity or lactic acidosis, obesity
Lactic acidosis and hepatomegaly with steatosis, including fatal cases, have been reported following use of tenofovir disoproxil fumarate (DF), both alone and in combination with other antiretroviral medications. Treatment with tenofovir DF 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.
Pregnancy
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 disoproxil fumarate with either emtricitabine or lamivudine as a preferred 2-NRTI backbone in patients who are pregnant or trying to conceive. Available data from the Antiretroviral Pregnancy Registry, which includes more than 4,655 first trimester exposures to tenofovir disoproxil fumarate, have shown no difference in the risk of overall major birth defects when compared to the 2.7% background rate among pregnant women in the US. When tenofovir exposure occurred in the first trimester, the prevalence of defects was 2.5% (95% CI: 2 to 3). Similarly, no difference in risk of congenital anomalies between the tenofovir-containing and placebo arms was identified during an HIV pre-exposure trial involving 431 pregnancies. Finally, data from 3 clinical trials found no increase in adverse pregnancy-related outcomes in 327 pregnant patients with hepatitis B who were exposed to tenofovir from 28 to 32 weeks gestation through 1 to 2 months postpartum. 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 itself 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 of pregnancy 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 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, patients with CD4 count less than 300 cells/mm3, or patients with inconsistent adherence or detectable viral loads. 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 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. 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 the 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 disoproxil fumarate; information about the registry can be obtained at www.apregistry.com or by calling 1-800-258-4263.
Breast-feeding
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; thus, replacement feeding is 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). Limited data on the use of tenofovir in HIV-negative breast-feeding mothers being treated for hepatitis B infection suggest small amounts of tenofovir are excreted during breast-feeding. Exposure of an exclusively breast-fed infant was determined to be equivalent to approximately 4.2 micrograms of tenofovir per day. In a study of 50 breastfeeding mothers on a tenofovir-containing regimen between 1 and 24 weeks postpartum (median 13 weeks), after 7 days of treatment, tenofovir was undetectable in the plasma of most infants; no serious adverse effects were observed. Consider the benefits of breast-feeding, the risk of 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.
Hepatitis B and HIV coinfection, hepatitis B exacerbation
All patients should undergo hepatitis B virus (HBV) screening and HIV antibody testing prior to the initiation of tenofovir to ensure appropriate treatment.[28193] 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 (entecavir should not be considered part of the ARV regimen). Avoid using single-drug therapy to treat HBV (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 HBV 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 HIV and HBV 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, especially in patients with advanced liver disease or cirrhosis, since post-treatment exacerbation may lead to hepatic decompensation and liver failure. 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. [28193] [34362] [46638]
Human immunodeficiency virus (HIV) infection resistance
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. As with all other antiretroviral agents, resistance can develop when tenofovir disoproxil is used either alone or in combination with other agents. Monotherapy with tenofovir is not recommended for treatment of HIV. Clinical studies have demonstrated that regimens that only contain 3 NRTIs are generally less effective than triple drug regimens containing 2 NRTIs in combination with either a NNRTI or a PI. Early virological failure and high rates of resistance have been reported. Triple nucleoside regimens should therefore be used with caution. Patients on a therapy utilizing a triple nucleoside-only regimen should be carefully monitored and considered for treatment modification.
Autoimmune disease, Graves' disease, Guillain-Barre syndrome, immune reconstitution syndrome
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy. During the initial phase of HIV treatment, patients whose immune system responds to tenofovir therapy may develop an inflammatory response to indolent or residual opportunistic infections (such as progressive multifocal leukoencephalopathy (PML), mycobacterium avium complex (MAC), cytomegalovirus (CMV), Pneumocystis carinii pneumonia (PCP), or tuberculosis (TB)), which may necessitate further evaluation and treatment. In addition, autoimmune disease (including Graves' disease, Guillain-Barre syndrome, and polymyositis) may also develop; the time to onset is variable and may occur months after treatment initiation.
Hepatitis C and HIV coinfection
HIV treatment guidelines recommend all patients presenting with HIV infection undergo routine screening for hepatitis C virus (HCV). For HCV seronegative individuals who are at continued high risk of acquiring hepatitis C, specifically men who have sex with men (MSM) or persons who inject drugs, additional HCV screening is recommended annually or as indicated by clinical presentation (e.g., unexplained ALT elevation), risk activities, or exposure. Similarly, the AASLD/IDSA HCV guidelines and the CDC preexposure prophylaxis (PrEP) guidelines recommend HCV serologic testing at baseline and every 12 months for MSM, transgender women, and persons who inject drugs. Use an FDA-approved immunoassay licensed for detection of HCV antibodies (anti-HCV); in settings where acute HCV infection is suspected or in persons with known prior infection that cleared spontaneously or after treatment, use of nucleic acid testing for HCV RNA is recommended. If hepatitis C and HIV coinfection is identified, consider treating both viral infections concurrently. It is recommended to use a fully suppressive antiretroviral therapy and an HCV regimen in all patients with coinfection regardless of CD4 count, as lower CD4 counts do not appear to compromise the efficacy of HCV treatment. In most patients, a simplified pangenotypic HCV regimen (i.e., glecaprevir; pibrentasvir or sofosbuvir; velpatasvir) may be an appropriate choice; however, these regimens are NOT recommended for use in persons with HCV and HIV coinfection who: are treatment-experienced with HCV relapse (reinfection after successful therapy is not an exclusion); have decompensated cirrhosis; on a tenofovir disoproxil fumarate containing regimen with eGFR less than 60 mL/minute; on efavirenz, etravirine, nevirapine, or boosted protease inhibitor; have untreated chronic hepatitis B; are pregnant. Patients with HCV and HIV coinfection who meet these exclusion criteria should be treated for HCV following standard approaches as described in the AASLD/IDSA HCV guidelines. Treatment of HCV infection in children younger than 3 years is not usually recommended; however, treatment should be considered for all children 3 years and older with HCV and HIV coinfection who have no contraindications to treatment. Instruct patients with coinfection to avoid consuming alcohol, limit ingestion of potentially hepatotoxic medications, avoid iron supplementation in the absence of documented iron deficiency, and receive vaccinations against hepatitis A and hepatitis B as appropriate.
DRUG INTERACTIONS
Abrocitinib: (Moderate) Coadministration of tenofovir disoproxil fumarate with abrocitinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and abrocitinib is a P-gp inhibitor.
Acalabrutinib: (Moderate) Coadministration of acalabrutinib and tenofovir disoproxil fumerate may increase may increase the absorption and plasma concentration of tenofovir disoproxil fumerate. Monitor patients for tenofovir-related adverse reactions and discontinue use in patients who experience an adverse reaction. Acalabrutinib is an inhibitor of the breast cancer resistance protein (BCRP) transporter in vitro; it may inhibit intestinal BCRP. Tenofovir disoproxil fumerate is a BCRP substrate.
Acetaminophen; Aspirin, ASA; Caffeine: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Acetaminophen; Aspirin: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Acetaminophen; Aspirin; Diphenhydramine: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Acetaminophen; Ibuprofen: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Acyclovir: (Moderate) Monitor for changes in serum creatinine and phosphorus if tenofovir disoproxil fumarate is administered in combination with nephrotoxic agents, such as acyclovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration with drugs that decrease renal function may increase concentrations of tenofovir. In addition, use with drugs that are also eliminated by active tubular secretion may increase concentrations of the co-administered drug. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate; a majority of the cases occurred in patients who had underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir containing products should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus, and urine glucose and protein.
Adagrasib: (Moderate) Coadministration of tenofovir disoproxil fumarate with adagrasib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and adagrasib is a P-gp inhibitor.
Adefovir: (Major) Avoid coadministration of tenofovir disoproxil fumarate with adefovir. Both tenofovir and adefovir are primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration may increase concentrations of both drugs resulting in additive nephrotoxicity. Additionally, in the treatment of chronic hepatitis B, tenofovir should not be administered in combination with adefovir to avoid multi-drug resistance. If coadministration is necessary, patients should be carefully monitored for changes in serum creatinine and phosphorus, and urine glucose and protein.
Amikacin: (Moderate) 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. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Aminoglycosides: (Moderate) 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. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Aminosalicylate sodium, Aminosalicylic acid: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Amiodarone: (Moderate) Coadministration of tenofovir disoproxil fumarate with amiodarone may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and amiodarone is a P-gp inhibitor.
Amlodipine; Celecoxib: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as clarithromycin. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Amphotericin B lipid complex (ABLC): (Minor) Additive nephrotoxicity can also occur if amphotericin B is given concomitantly with tenofovir. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Amphotericin B liposomal (LAmB): (Minor) Additive nephrotoxicity can also occur if amphotericin B is given concomitantly with tenofovir. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Amphotericin B: (Minor) Additive nephrotoxicity can also occur if amphotericin B is given concomitantly with tenofovir. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Aspirin, ASA: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Aspirin, ASA; Butalbital; Caffeine: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Aspirin, ASA; Caffeine: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Aspirin, ASA; Caffeine; Orphenadrine: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Aspirin, ASA; Carisoprodol: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Aspirin, ASA; Carisoprodol; Codeine: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Aspirin, ASA; Dipyridamole: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Aspirin, ASA; Omeprazole: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Aspirin, ASA; Oxycodone: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Aspirin, ASA; Pravastatin: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Atazanavir: (Moderate) Tenofovir decreases atazanavir AUC and Cmin. If atazanavir and tenofovir, PMPA are to be coadministered, it is recommended that atazanavir 300 mg be given with ritonavir 100 mg and tenofovir 300 mg once per day with food in patients >= 40 kg; atazanavir should not be coadministered with tenofovir without ritonavir. Data are insufficient to recommend atazanavir dosing in children < 40 kg who are also receiving concomitant tenofovir. In three post-marketing clinical trials, atazanavir AUC and Cmin were decreased by approximately 25% and 23 to 40%, respectively, when atazanavir was coadministered with tenofovir, PMPA as compared to atazanavir alone. Coadministration of atazanavir and tenofovir without ritonavir could lead to loss or lack of virologic response and possible resistance to atazanavir. In addition, atazanavir appears to increase tenofovir plasma concentrations, which could lead to adverse effects associated with tenofovir, including renal disorders. Increased tenofovir concentrations have been noted in the following combination regimens: tenofovir with ritonavir 'boosted' atazanavir; tenofovir, atazanavir, and lopinavir; ritonavir. Patients who receive tenofovir with atazanavir and any form/dose of ritonavir should be monitored for tenofovir-associated adverse events, with tenofovir being discontinued in patients who develop such adverse events. Although there are varying results in reports of an interaction between tenofovir and lopinavir; ritonavir, the clinical significance of an interaction is suspected to be insignificant. In treatment-experienced patients >= 40 kg receiving H2-antagonists and tenofovir, atazanavir should be dosed 400 mg with ritonavir 100 mg once daily with food.
Atazanavir; Cobicistat: (Moderate) Tenofovir decreases atazanavir AUC and Cmin. If atazanavir and tenofovir, PMPA are to be coadministered, it is recommended that atazanavir 300 mg be given with ritonavir 100 mg and tenofovir 300 mg once per day with food in patients >= 40 kg; atazanavir should not be coadministered with tenofovir without ritonavir. Data are insufficient to recommend atazanavir dosing in children < 40 kg who are also receiving concomitant tenofovir. In three post-marketing clinical trials, atazanavir AUC and Cmin were decreased by approximately 25% and 23 to 40%, respectively, when atazanavir was coadministered with tenofovir, PMPA as compared to atazanavir alone. Coadministration of atazanavir and tenofovir without ritonavir could lead to loss or lack of virologic response and possible resistance to atazanavir. In addition, atazanavir appears to increase tenofovir plasma concentrations, which could lead to adverse effects associated with tenofovir, including renal disorders. Increased tenofovir concentrations have been noted in the following combination regimens: tenofovir with ritonavir 'boosted' atazanavir; tenofovir, atazanavir, and lopinavir; ritonavir. Patients who receive tenofovir with atazanavir and any form/dose of ritonavir should be monitored for tenofovir-associated adverse events, with tenofovir being discontinued in patients who develop such adverse events. Although there are varying results in reports of an interaction between tenofovir and lopinavir; ritonavir, the clinical significance of an interaction is suspected to be insignificant. In treatment-experienced patients >= 40 kg receiving H2-antagonists and tenofovir, atazanavir should be dosed 400 mg with ritonavir 100 mg once daily with food.
Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Bacitracin: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of 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 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.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Berotralstat: (Moderate) Coadministration of tenofovir disoproxil fumarate with berotralstat may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and berotralstat is a P-gp inhibitor.
Bismuth Subsalicylate: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Brigatinib: (Moderate) Monitor for an increase in tenofovir-related adverse reactions if coadministration with brigatinib is necessary. Tenofovir disoproxil fumarate 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) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
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 disoproxil fumarate with cannabidiol may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Capmatinib: (Moderate) Coadministration of tenofovir disoproxil fumarate with capmatinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-glycoprotein (P-gp) and BCRP substrate and capmatinib is a P-gp and BCRP inhibitor.
Carboplatin: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of 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 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.
Carvedilol: (Moderate) Increased concentrations of tenofovir may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and tenofovir is a P-gp substrate.
Celecoxib: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Celecoxib; Tramadol: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Choline Salicylate; Magnesium Salicylate: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Cidofovir: (Moderate) Tenofovir disoproxil fumarate should be avoided with concurrent or recent use of a nephrotoxic agent, such as cidofovir. If concurrent use is necessary, closely monitor for changes in renal function. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration 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 events. Renal impairment, which may include acute renal failure and hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate.
Cisplatin: (Major) Avoid tenofovir administration with concurrent or recent treatment with cisplatin. Cisplatin can cause nephrotoxicity. Tenofovir is primarily eliminated by the kidneys; drugs that decrease renal function may increase concentrations of tenofovir. Also, cases of acute renal failure after initiation of other nephrotoxic drugs have been reported in HIV-infected patients with risk factors for renal dysfunction who appeared stable on tenofovir treatment; some patients required hospitalization and renal replacement therapy.
Clarithromycin: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as clarithromycin. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Clindamycin: (Moderate) Concomitant use of tenofovir and clindamycin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Clofarabine: (Major) Avoid the concomitant use of clofarabine and tenofovir; coadministration may result in additive nephrotoxicity. Additionally, taking these drugs together may alter clofarabine concentrations; clofarabine and tenofovir are both substrates of OAT1 and OAT3.
Colistimethate, Colistin, Polymyxin E: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of 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 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.
Colistin: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of 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 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.
Conivaptan: (Moderate) Use caution when administering conivaptan and tenofovir concurrently. Conivaptan is an inhibitor of P-glycoprotein (P-gp). Co-administration of conivaptan with P-gp substrates, such as tenofovir, PMPA, can increase tenofovir exposure leading to increased or prolonged therapeutic effects and adverse events.
Cyclosporine: (Major) Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, such as cyclosporine, should be carefully monitored for changes in serum creatinine and phosphorus.
Darolutamide: (Moderate) Caution is advised with the coadministration of darolutamide and tenofovir disoproxil fumarate due to the potential for increased plasma concentrations of tenofovir disoproxil fumarate increasing the risk of adverse effects. Tenofovir disoproxil fumarate is a substrate of breast cancer resistance protein (BCRP) and darolutamide is a BCRP inhibitor.
Darunavir: (Moderate) Pharmacokinetic parameters (AUC, Cmax, Cmin) of tenofovir, PMPA are elevated when administered in combination with darunavir and ritonavir. The clinical significance of this interaction has not been established, and dosage adjustments are not recommended. Monitor the patients closely for tenofovir-related adverse events.
Darunavir; Cobicistat: (Moderate) Pharmacokinetic parameters (AUC, Cmax, Cmin) of tenofovir, PMPA are elevated when administered in combination with darunavir and ritonavir. The clinical significance of this interaction has not been established, and dosage adjustments are not recommended. Monitor the patients closely for tenofovir-related adverse events.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Pharmacokinetic parameters (AUC, Cmax, Cmin) of tenofovir, PMPA are elevated when administered in combination with darunavir and ritonavir. The clinical significance of this interaction has not been established, and dosage adjustments are not recommended. Monitor the patients closely for tenofovir-related adverse events.
Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) substrate, concurrently with inhibitors of P-gp and BCRP, such as ritonavir. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions. (Moderate) Concurrent administration of tenofovir, PMPA with dasabuvir; ombitasvir; paritaprevir; ritonavir may result in elevated tenofovir plasma concentrations. Tenofovir is a substrate for the breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp). Dasabuvir, paritaprevir, and ritonavir are BCRP inhibitors, and ritonavir inhibits P-gp. Caution and close monitoring are advised if these drugs are administered together.
Dextromethorphan; Quinidine: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as quinidine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Dichlorphenamide: (Major) Use of dichlorphenamide and tenofovir disoproxil fumarate 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) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Diclofenac; Misoprostol: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Didanosine, ddI: (Major) HIV guidelines recommend against concurrent use of tenofovir, PMPA and didanosine; however, these medications can be used together, if necessary, in patients with a creatinine clearance 60 mL/min or more if the didanosine dose is reduced; decrease the didanosine dose to 250 mg in patients weighing 60 kg or more and to 200 mg in patients weighing 25 to 59 kg. Concurrent administration of tenofovir, PMPA and didanosine, ddI increases the concentration of both didanosine and its active metabolite (dideoxyadenosine 5-triphosphate) which may cause or worsen didanosine-related clinical toxicities, including pancreatitis, symptomatic hyperlactatemia/lactic acidosis, and peripheral neuropathy. In addition, this combination has been associated with CD4 cell count decline despite viral suppression, high rates of early virologic failure, and rapid selection of resistance mutations. The mechanism of the interaction is not known, but the interaction occurs with both buffered and non-buffered didanosine formulations. When coadministered, tenofovir and didanosine EC may be taken under fasted conditions or with a light meal (under 400 kcal, containing 20% or less fat); coadministration of didanosine buffered tablet formulation with tenofovir should be under fasted conditions. Coadministration of tenofovir and didanosine should be undertaken with caution and patients receiving this combination should be monitored closely for didanosine-associated adverse events. Didanosine therapy should be suspended if signs or symptoms of pancreatitis, symptomatic hyperlactatemia, or lactic acidosis develop.
Diflunisal: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Diphenhydramine; Ibuprofen: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Diphenhydramine; Naproxen: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Dofetilide: (Major) Dofetilide should be co-administered with tenofovir, PMPA 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.
Dronedarone: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as dronedarone. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Elacestrant: (Moderate) Coadministration of tenofovir disoproxil fumarate with elacestrant may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is substrate of BCRP and P-gp; elacestrant is an inhibitor of BCRP and P-gp.
Elexacaftor; tezacaftor; ivacaftor: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as ivacaftor. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Eliglustat: (Moderate) Coadministration of tenofovir, PMPA 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.
Enasidenib: (Moderate) Coadministration of tenofovir disoproxil fumarate with enasidenib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp and BCRP substrate and enasidenib is a P-gp and BCRP inhibitor.
Encorafenib: (Moderate) Coadministration of tenofovir disoproxil fumarate with encorafenib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a BCRP substrate and encorafenib is a BCRP inhibitor.
Erythromycin: (Moderate) Coadministration of tenofovir disoproxil fumarate with erythromycin may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and erythromycin is a P-gp inhibitor.
Ethiodized Oil: (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 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.
Etodolac: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Etravirine: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as etravirine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Fenoprofen: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Flurbiprofen: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Foscarnet: (Moderate) Monitor for changes in serum creatinine and phosphorus if tenofovir is administered in combination with nephrotoxic agents, such as foscarnet. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of tenofovir 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 increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir; a majority of the cases occurred in patients who had underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir containing products should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Fostamatinib: (Moderate) Monitor for tenofovir toxicities that may require tenofovir disoproxil 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 disoproxil 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%.
Futibatinib: (Moderate) Coadministration of tenofovir disoproxil fumarate with futibatinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp and BCRP substrate and futibatinib is a P-gp and BCRP inhibitor.
Ganciclovir: (Moderate) Concurrent use of nephrotoxic agents with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Other nephrotoxic agents include tenofovir.
Gentamicin: (Moderate) 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. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Gilteritinib: (Moderate) Coadministration of tenofovir disoproxil fumarate with gilteritinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate 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) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Ibuprofen: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Ibuprofen; Famotidine: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Ibuprofen; Oxycodone: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Ibuprofen; Pseudoephedrine: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Indomethacin: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Iodixanol: (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 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.
Iohexol: (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 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.
Iomeprol: (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 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.
Iopamidol: (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 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.
Iopromide: (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 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.
Ioversol: (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 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.
Isosulfan Blue: (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 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.
Istradefylline: (Moderate) Monitor for an increase in tenofovir-related adverse reactions if coadministration with istradefylline is necessary as concurrent use may increase tenofovir exposure. Tenofovir is a P-gp substrate and istradefylline is a P-gp inhibitor.
Itraconazole: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) substrate, concurrently with inhibitors of P-gp and BCRP, such as itraconazole. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Ivacaftor: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as ivacaftor. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Ketoconazole: (Moderate) Monitor for an increase in tenofovir-related adverse effects if coadministration with ketoconazole is necessary. Concurrent use may increase tenofovir exposure. Tenofovir disoproxil fumarate is a P-gp substrate and ketoconazole is a P-gp inhibitor.
Ketoprofen: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Ketorolac: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as clarithromycin. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Lansoprazole; Naproxen: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Lapatinib: (Moderate) Monitor for an increase in tenofovir-related adverse reactions if coadministration with lapatinib is necessary. Tenofovir is a P-glycoprotein (P-gp) substrate and lapatinib is a P-gp inhibitor. Increased plasma concentrations of tenofovir may occur.
Lasmiditan: (Moderate) Coadministration of tenofovir disoproxil fumarate with lasmiditan may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Ledipasvir; Sofosbuvir: (Moderate) Closely monitor for tenofovir-associated adverse reactions if ledipasvir is administered with tenofovir disoproxil fumarate. In addition, because safety has not been established, avoid use of ledipasvir in combination with HIV regimens that contain tenofovir disoproxil fumarate and HIV protease inhibitors boosted with ritonavir. Consider use of tenofovir alafenamide in place of tenofovir disoproxil fumarate. If coadministration is deemed necessary, closely monitor for tenofovir adverse effects. Plasma concentrations of tenofovir may increase when administered with ledipasvir. 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.
Leniolisib: (Moderate) Coadministration of tenofovir disoproxil fumarate with leniolisib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a BCRP substrate and leniolisib is a BCRP inhibitor.
Levoketoconazole: (Moderate) Monitor for an increase in tenofovir-related adverse effects if coadministration with ketoconazole is necessary. Concurrent use may increase tenofovir exposure. Tenofovir disoproxil fumarate is a P-gp substrate and ketoconazole is a P-gp inhibitor.
Lonafarnib: (Moderate) Coadministration of tenofovir disoproxil fumarate with lonafarnib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-glycoprotein (P-gp) substrate and lonafarnib is a P-gp inhibitor.
Lopinavir; Ritonavir: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) substrate, concurrently with inhibitors of P-gp and BCRP, such as ritonavir. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions. (Minor) There are varying results in reports of an interaction between tenofovir and lopinavir; ritonavir. In one report, the concurrent administration of tenofovir with lopinavir; ritonavir increased tenofovir Cmax 31%, AUC 34%, and Cmin 29%, with slight (15%) decreases in lopinavir Cmax and AUC; the alterations may be a food effect rather than a drug-drug interaction. In another report, lopinavir; ritonavir (400 mg; 100 mg PO twice daily for 14 days) increased the tenofovir (300 mg/day PO) Cmin 51% and AUC 32%, with no effect seen on lopinavir; ritonavir pharmacokinetics. While the clinical significance of this interaction is unknown, and is suspected to be insignificant, patients receiving lopinavir; ritonavir with tenofovir should be monitored for tenofovir-associated adverse events.
Lumacaftor; Ivacaftor: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as ivacaftor. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Magnesium Salicylate: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Maribavir: (Moderate) Coadministration of tenofovir disoproxil fumarate with maribavir may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp and BCRP substrate and maribavir is a P-gp and BCRP inhibitor.
Meclofenamate Sodium: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Mefenamic Acid: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Mefloquine: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as mefloquine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Meloxicam: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Methenamine; Sodium Salicylate: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Methotrexate: (Major) Avoid concomitant use of methotrexate with tenofovir disoproxil fumarate 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 disoproxil fumarate and methotrexate are both nephrotoxic drugs; methotrexate is also renally eliminated. Coadministration of methotrexate with tenofovir disoproxil fumarate may result in decreased renal function as well as increased methotrexate plasma concentrations.
Midostaurin: (Moderate) Coadministration of tenofovir disoproxil fumarate with midostaurin may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a BCRP substrate and midostaurin is a BCRP inhibitor.
Mitapivat: (Moderate) Coadministration of tenofovir disoproxil fumarate with mitapivat may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and mitapivat is a P-gp inhibitor.
Nabumetone: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Naproxen: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Naproxen; Esomeprazole: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Naproxen; Pseudoephedrine: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Nelfinavir: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as nelfinavir. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Neratinib: (Moderate) Coadministration of tenofovir disoproxil fumarate with neratinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-glycoprotein (P-gp) substrate and neratinib is a P-gp inhibitor.
Nirmatrelvir; Ritonavir: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) substrate, concurrently with inhibitors of P-gp and BCRP, such as ritonavir. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Non-Ionic Contrast Media: (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 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.
Nonsteroidal antiinflammatory drugs: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) substrate, concurrently with inhibitors of P-gp and BCRP, such as ritonavir. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions. (Moderate) Concurrent administration of tenofovir, PMPA with dasabuvir; ombitasvir; paritaprevir; ritonavir may result in elevated tenofovir plasma concentrations. Tenofovir is a substrate for the breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp). Dasabuvir, paritaprevir, and ritonavir are BCRP inhibitors, and ritonavir inhibits P-gp. Caution and close monitoring are advised if these drugs are administered together.
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 disoproxil is a BCRP and P-glycoprotein (P-gp) substrate. Osimertinib is a BCRP and P-gp inhibitor.
Oteseconazole: (Moderate) Coadministration of tenofovir disoproxil fumarate with oteseconazole may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a BCRP substrate and oteseconazole is a BCRP inhibitor.
Oxaliplatin: (Major) Avoid coadministration of oxaliplatin with tenofovir disoproxil fumarate due to the risk of increased oxaliplatin-related adverse reactions. Tenofovir disoproxil fumarate 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) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Pacritinib: (Moderate) Concomitant use of tenofovir disoproxil fumarate with pacritinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp and BCRP substrate; pacritinib is a P-gp and BCRP inhibitor.
Pamidronate: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of 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 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.
Paromomycin: (Moderate) 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. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Piroxicam: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Pirtobrutinib: (Moderate) Coadministration of tenofovir disoproxil fumarate with pirtobrutinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp and BCRP substrate and pirtobrutinib is a P-gp and BCRP inhibitor.
Plazomicin: (Moderate) 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. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Polymyxin B: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of 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 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.
Posaconazole: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as posaconazole. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Pretomanid: (Moderate) Coadministration of tenofovir disoproxil fumarate with pretomanid may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp and BCRP substrate and pretomanid is a P-gp and BCRP inhibitor.
Probenecid: (Moderate) 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. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as probenecid; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Probenecid; Colchicine: (Moderate) 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. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as probenecid; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Propafenone: (Moderate) Coadministration of tenofovir disoproxil fumarate with propafenone may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and propafenone is a P-gp inhibitor.
Quinidine: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as quinidine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Ranolazine: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as ranolazine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Regorafenib: (Moderate) Use caution if coadministration of regorafenib with tenofovir, PMPA is necessary, and monitor for an increase in tenofovir-related adverse reactions. Tenofovir is a BCRP substrate and regorafenib is a BCRP inhibitor. Regorafenib-mediated BCRP inhibition may increase exposure to tenofovir.
Ritonavir: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) substrate, concurrently with inhibitors of P-gp and BCRP, such as ritonavir. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Rolapitant: (Moderate) Use caution if tenofovir, PMPA and rolapitant are used concurrently, and monitor for tenofovir-related adverse effects. Tenofovir is a substrate of the Breast Cancer Resistance Protein (BCRP) and P-glycoprotein (P-gp), where an increase in exposure may significantly increase adverse effects; rolapitant is a BCRP and P-gp inhibitor. The Cmax and AUC of another BCRP substrate, sulfasalazine, were increased by 140% and 130%, respectively, on day 1 with rolapitant, and by 17% and 32%, 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% and 30%, respectively; the Cmax and AUC on day 8 were not studied.
Salicylates: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Salsalate: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Saquinavir: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as saquinavir. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Selpercatinib: (Moderate) Coadministration of tenofovir disoproxil fumarate with selpercatinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and selpercatinib is a P-gp inhibitor.
Simeprevir: (Moderate) Closely monitor for tenofovir-associated adverse reactions if simeprevir is administered with tenofovir, PMPA. Tenofovir is a substrate of the drug transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); simeprevir is an inhibitor of both P-gp and BCRP.
Sodium Phenylbutyrate; Taurursodiol: (Moderate) Coadministration of tenofovir disoproxil fumarate with taurursodiol may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate 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 disoproxil fumarate and velpatasvir due to potential increases in tenofovir serum concentrations. When administered concurrently with velpatasvir, the peak concentration (Cmax), systemic exposure (AUC), and the trough concentration (Cmin) of tenofovir increased by 44%, 40%, and 84%, respectively. Tenofovir is a substrate of the breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp) transporters, while velpatasvir inhibits both BCRP and P-gp. Consider use of tenofovir alafenamide in place of tenofovir disoproxil fumarate.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid concurrent administration of voxilaprevir with tenofovir disoproxil fumarate. Taking these medications together may increase tenofovir plasma concentrations, potentially increasing the risk for adverse events. Tenofovir disoproxil fumarate is a substrate for the drug transporter Breast Cancer Resistance Protein (BCRP). Voxilaprevir is a BCRP inhibitor. (Moderate) Monitor patients for tenofovir-associated adverse reactions, such as renal toxicity, in patients receiving regimens containing tenofovir disoproxil fumarate and velpatasvir due to potential increases in tenofovir serum concentrations. When administered concurrently with velpatasvir, the peak concentration (Cmax), systemic exposure (AUC), and the trough concentration (Cmin) of tenofovir increased by 44%, 40%, and 84%, respectively. Tenofovir is a substrate of the breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp) transporters, while velpatasvir inhibits both BCRP and P-gp. Consider use of tenofovir alafenamide in place of tenofovir disoproxil fumarate.
Sorafenib: (Moderate) Monitor for an increase in tenofovir-related adverse reactions if coadministration with sorafenib is necessary. Tenofovir is a P-glycoprotein (P-gp) substrate and sorafenib inhibits P-gp in vitro. Sorafenib may increase the concentrations of concomitantly administered drugs that are P-gp substrates.
Sotorasib: (Moderate) Coadministration of tenofovir disoproxil fumarate with sotorasib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp and BCRP substrate and sotorasib is a P-gp and BCRP inhibitor.
Sparsentan: (Moderate) Coadministration of tenofovir disoproxil fumarate with sparsentan may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp and BCRP substrate and sparsentan is a P-gp and BCRP inhibitor.
Streptomycin: (Moderate) 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. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Sulindac: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Sumatriptan; Naproxen: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Tacrolimus: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, including tacrolimus.
Tafamidis: (Moderate) Caution is advised with the coadministration of tafamidis and tenofovir disoproxil fumarate due to the potential for increased plasma concentrations of tenofovir disoproxil fumarate increasing the risk of adverse effects. Tenofovir disoproxil fumarate dose adjustment may be needed with coadministration. Tenofovir disoproxil fumarate is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Tedizolid: (Moderate) Coadministration of tenofovir disoproxil fumarate with tedizolid may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a BCRP substrate and tedizolid is a BCRP inhibitor.
Temsirolimus: (Moderate) Monitor for an increase in tenofovir disoproxil fumarate-related adverse reactions if coadministration with temsirolimus is necessary. Tenofovir disoproxil fumarate is a P-glycoprotein (P-gp) substrate and temsirolimus is a P-gp inhibitor. Concomitant use may lead to increased concentrations of tenofovir disoproxil fumarate.
Tepotinib: (Moderate) Coadministration of tenofovir disoproxil fumarate with tepotinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and tepotinib is a P-gp inhibitor.
Tezacaftor; Ivacaftor: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as ivacaftor. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Ticagrelor: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as ticagrelor. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Tipranavir: (Moderate) Concurrent administration of tipranavir and ritonavir with tenofovir, results in decreased tipranavir concentrations. The clinical significance of this interaction has not been established, and no recommendations for tenofovir dosage adjustments are available.
Tobramycin: (Moderate) 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. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Tolmetin: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Trandolapril; Verapamil: (Moderate) Coadministration of tenofovir disoproxil fumarate with verapamil may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and verapamil is a P-gp inhibitor.
Trospium: (Minor) Both trospium and tenofovir are eliminated by active renal tubular secretion; coadministration has the potential to increase serum concentrations of trospium or tenofovir due to competition for the drug elimination pathway. Careful patient monitoring and dosage adjustment of trospium and/or tenofovir, PMPA is recommended.
Tucatinib: (Moderate) Coadministration of tenofovir disoproxil fumarate with tucatinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-glycoprotein (P-gp) substrate and tucatinib is a P-gp inhibitor.
Valacyclovir: (Moderate) Monitor for changes in serum creatinine and phosphorus if tenofovir disoproxil fumarate is administered in combination with nephrotoxic agents, such as valacyclovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration with drugs that decrease renal function may increase concentrations of tenofovir. In addition, use with drugs that are also eliminated by active tubular secretion may increase concentrations of the co-administered drug. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate; a majority of the cases occurred in patients who had underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir containing products should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus, and urine glucose and protein.
Valdecoxib: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment.
Valganciclovir: (Minor) Since tenofovir is primarily eliminated by the kidneys, concurrent administration of tenofovir disoproxil with valganciclovir may increase serum concentrations of tenofovir via competition for renal tubular secretion.
Vancomycin: (Moderate) Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as vancomycin. Patients receiving these drugs together should be carefully monitored for changes in serum creatinine and phosphorus. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir; a majority of cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents.
Vemurafenib: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as vemurafenib. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Verapamil: (Moderate) Coadministration of tenofovir disoproxil fumarate with verapamil may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and verapamil is a P-gp inhibitor.
Voclosporin: (Moderate) Coadministration of tenofovir disoproxil fumarate 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 disoproxil fumarate is a P-gp substrate and voclosporin is a P-gp inhibitor.
Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as clarithromycin. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Zoledronic Acid: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of 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 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.
Zonisamide: (Minor) Caution is advised when administering tenofovir disoproxil fumarate 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, a P-gp substrate. If these medications are administered together, monitor for tenofovir-associated adverse reactions.