Lamivudine; tenofovir disoproxil fumarate is an oral 2-drug combination of a nucleoside reverse transcriptase inhibitor (NRTI) and an acyclic nucleoside analog (i.e., nucleotide reverse transcriptase inhibitor) approved for use with other antiretroviral medications to treat human immunodeficiency virus type 1 (HIV-1) in adult and pediatric patients weighing at least 35 kg. This combination product allows for once-daily dosing. Although lamivudine and tenofovir disoproxil fumarate both exhibit activity against hepatitis B virus (HBV), this drug is not indicated to treat HBV. The FDA approved package labeling has a Black Box Warning stating that severe, acute exacerbations of hepatitis B have been reported in patients who are co-infected with HBV and HIV and have discontinued either lamivudine or tenofovir. If treatment for HIV with lamivudine; tenofovir disoproxil fumarate is discontinued in a patient coinfected with HBV, the patient should be closely monitored for several months for signs and symptoms of worsening hepatitis infection. Due to the similarities between emtricitabine and lamivudine, lamivudine containing products are not likely to be effective in individuals who display antimicrobial resistance to emtricitabine.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Administer with or without food.
In a study comparing tenofovir disoproxil fumarate with stavudine (each given in combination with lamivudine and efavirenz) in treatment-naive patients, decreases in bone mineral density (BMD) from baseline were seen at the lumbar spine and hip regions in both treatment groups. At 144 weeks, percent decreases (mean +/- SD) in BMD from baseline at the lumbar spine were greater in patients receiving tenofovir (-2.2% +/- 3.9) compared with patients receiving stavudine (-1% +/- 4.6); percent decreases from baseline at the hip were similar in between both treatment groups (tenofovir, -2.8% +/- 3.5; stavudine -2.4% +/- 4.5). In both groups, the majority of the reduction in BMD occurred in the first 24 to 48 weeks of treatment and was sustained. There was a higher proportion of patients who met a protocol-defined value of BMD loss (5% decrease in spine or 7% decrease in hip) in the tenofovir group (28%) compared to the stavudine group (21%). In addition, there were significant increases in levels of biochemical markers of bone metabolism (serum bone-specific alkaline phosphatase, serum osteocalcin, serum C-telopeptide, and urinary N-telopeptide) in the tenofovir group compared to the stavudine group, suggesting increase bone turnover. Except for bone-specific alkaline phosphatase, these changes resulted in values that remained within normal range. At week 144, clinically relevant bone fractures (excluding fingers and toes) were reported in 4 patients in the tenofovir group (1.3%) compared with 6 patients in the stavudine group (2%). In studies of pediatric patients with HIV, bone effects were similar to those noted in adult patients. Normally, BMD increases rapidly as children and adolescents age; however, in a study of patients ages 12 to 17 years, gains in BMD were found to be lower in tenofovir-treated patients than in patients receiving placebo. Additionally, 7 tenofovir-treated patients and 1 placebo-treated patient had significant (more than 4%) lumbar spine BMD loss in 48 weeks. Of note, skeletal growth height appeared to be unaffected by tenofovir treatment. Additionally, osteomalacia has been reported with postmarketing use of tenofovir. These results also increase the concern of developing osteopenia and osteoporosis. Assessment of BMD is recommended in patients with a history of bone fractures or other risk factors for osteoporosis or bone loss. Although the effect of supplementation with calcium and vitamin D has not been studied, such supplementation may be considered for HIV-associated osteopenia or osteoporosis. If bone abnormalities are suspected, appropriate consultation should be obtained.
Musculoskeletal adverse events reported by patients receiving lamivudine; tenofovir disoproxil fumarate during clinical trials include arthralgia (5%), back pain (9%), generalized pain (13%), and myalgia (3%). In addition, 12% of drug recipients experienced increases in creatine kinase (Males: greater than 990 units/L; Females: greater than 845 units/L). Cases of rhabdomyolysis and muscle weakness have been noted during postmarketing use of lamivudine. Use of tenofovir disoproxil fumarate during the postmarketing period has been associated with rhabdomyolysis, muscle weakness, and myopathy. Some of these adverse events may occur due to proximal renal tubulopathy and include rhabdomyolysis, osteomalacia, bone pain and fractures, hypokalemia, muscular weakness, myopathy, and hypophosphatemia; promptly evaluate renal function in patients experiencing these symptoms.
Elevated hepatic enzymes were observed in patients treated with lamivudine; tenofovir disoproxil fumarate during clinical trials. Grade 3 to 4 increases in ALT and AST were identified in 4% and 5% of the 299 drug recipients, respectively. Postmarketing reports of hepatitis and elevated gamma GT have also been reported with tenofovir disoproxil fumarate.
Pneumonia (infection) was reported 5% of patients during lamivudine; tenofovir disoproxil fumarate during clinical trials. Fever was noted in 8% of drug recipients and neutropenia (neutrophils less than 750 cells/mm3) were observed in 3% of patients.
Severe acute hepatitis B exacerbation has been reported in patients coinfected with HIV and the hepatitis B virus (HBV) who have discontinued treatment with lamivudine or tenofovir disoproxil fumarate. If use of efavirenz; lamivudine; tenofovir disoproxil fumarate is stopped in a coinfected patient, closely monitor hepatic function with both clinical and laboratory follow-up for at least several months. If appropriate, treatment for hepatitis B infection may be warranted. Prior to initiating antiretroviral therapy for the treatment of HIV, it is recommended that all patients be tested for the presence of chronic HBV.
Renal impairment and renal failure (unspecified), which may include hypophosphatemia, have been reported with the use of tenofovir disoproxil fumarate. The majority of the reported cases occurred in patients with underlying systemic or renal disease, or in patients taking nephrotoxic agents. Postmarketing cases of interstitial nephritis (including acute cases), acute renal failure, renal failure, acute renal tubular necrosis, Fanconi syndrome, proximal renal tubulopathy, nephrogenic diabetes insipidus, renal insufficiency, increased creatinine, proteinuria, and polyuria have all been reported in patients receiving tenofovir disoproxil fumarate.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported during postmarketing use of nucleoside and nucleotide reverse transcriptase inhibitors, including lamivudine and tenofovir disoproxil fumarate. Many of these cases have occurred in women, obese patients, and patients with prolonged nucleoside exposure. If a patient develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity while receiving lamivudine; tenofovir disoproxil fumarate, treatment should be discontinued.
A rash event was reported in 18% of patients during clinical trials with lamivudine; tenofovir disoproxil fumarate. These include rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash (vesicular rash/bullous rash), and pustular rash. Additional postmarketing adverse events noted with lamivudine include anaphylaxis (anaphylactoid reactions) and alopecia. Allergic reaction and angioedema were reported postmarketing with tenofovir disoproxil fumarate.
Hypercholesterolemia and hypertriglyceridemia were observed in patients treated with lamivudine; tenofovir disoproxil fumarate during clinical trials. Grade 3 to 4 included 19% of patients had fasting cholesterol higher than 240 mg/dL and 1% had fasting triglycerides higher than 750 mg/dL.
Pancreatitis, which has been fatal in some cases, has been observed in antiretroviral-experienced pediatric patients receiving lamivudine alone and in combination with other antiretroviral agents. Cases of pancreatitis have also been observed during postmarketing use of tenofovir disoproxil fumarate. During lamivudine; tenofovir disoproxil fumarate clinical trials, serum amylase concentrations greater than 175 units/L were observed in 9% of drug recipients.
While more commonly associated with protease inhibitor therapy, a lipodystrophy syndrome consisting of redistribution or accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, accumulation of facial fat, lipomas, breast enlargement, gynecomastia, and other cushingoid features has been reported in patients receiving long-term highly active antiretroviral therapy (HAART). The mechanism by which nucleoside analogues may cause body fat changes is not known. It has been suggested that nucleoside analogs may damage the mitochondria of adipocytes. An increased incidence of body fat changes is noted in those patients receiving long-term nucleoside therapy and in female patients. Lipodystrophy was observed in 1% of patients treated with lamivudine; tenofovir disoproxil fumarate during clinical trials.
Gastrointestinal adverse events reported by patients receiving lamivudine; tenofovir disoproxil fumarate during clinical trials include abdominal pain (7%), diarrhea (11%), dyspepsia (4%), nausea (8%), and vomiting (5%).
Asthenia was reported by 6% of patients treated with lamivudine; tenofovir disoproxil fumarate during clinical trials.
Nervous system adverse events reported with lamivudine; tenofovir disoproxil fumarate during clinical trials include headache (14%), depression (11%), insomnia (5%), dizziness (3%), anxiety (6%), and peripheral neuropathy (1%), which includes peripheral neuritis and neuropathy.
Hematuria (more than 100 RBC/HPF) was observed in 7% of patients treated with lamivudine; tenofovir disoproxil fumarate during clinical trials.
Dyspnea has been noted during the postmarketing use of tenofovir disoproxil fumarate.
Hyperglycemia and case of anemia (including pure red cell aplasia and severe anemias progressing on therapy) have been noted during the postmarketing use of lamivudine.
During baseline evaluation of people with HIV, discuss risk reduction measures and the need for status disclosure to sexual or needle-sharing partners, especially with untreated patients who are still at high risk of HIV transmission. Include the importance of adherence to therapy to achieve and maintain a plasma HIV RNA less than 200 copies/mL. Maintaining a plasma HIV RNA less than 200 copies/mL, including any measurable value below this threshold, with antiretroviral therapy prevents sexual transmission of HIV to their partners. Patients may recognize this concept as Undetectable = Untransmittable or U=U. Instruct patients to achieve sustained viral suppression (i.e., 2 recorded measurements of plasma viral loads that are below the limits of detection and taken at least 3 months apart) before attempting to conceive a child in order to maximize their health, prevent HIV sexual transmission, and minimize the risk of HIV transmission to the infant once conception occurs. For partners with different HIV status when the person with HIV is on antiretroviral therapy and has achieved sustained viral suppression, sexual intercourse without a condom allows conception without sexual HIV transmission to the person without HIV. Expert consultation is recommended.
Unplanned antiretroviral therapy interruption may be necessary for specific situations, such as serious drug toxicity, intercurrent illness or surgery precluding oral intake (e.g., gastroenteritis or pancreatitis), severe hyperemesis gravidarum unresponsive to antiemetics, or drug non-availability. If short-term treatment interruption (i.e., less than 1 to 2 days) is necessary, in general, it is recommended that all antiretroviral agents be discontinued simultaneously, especially if the interruption occurs in a pregnant patient or is because of a serious toxicity. However, if a short-term treatment interruption is anticipated in the case of elective surgery, the pharmacokinetic properties and food requirements of specific drugs should be considered; as stopping all simultaneously in a regimen containing drugs with differing half-lives may result in functional monotherapy of the drug with the longest half-life and may increase the risk for resistant mutations. Healthcare providers are advised to reinitiate a complete and effective antiretroviral regimen as soon as possible after an interruption of therapy. Planned long-term treatment interruptions are not recommended due to the potential for HIV disease progression (i.e., declining CD4 counts, viral rebound, acute viral syndrome), development of minor HIV-associated manifestations or serious non-AIDS complications, development of drug resistance, increased risk of HIV transmission, and increased risk for opportunistic infections. If therapy must be discontinued, counsel patient on the potential risks and closely monitor for any clinical or laboratory abnormalities.
Lamivudine; tenofovir disoproxil fumarate is not indicated for the treatment of chronic hepatitis B virus (HBV) infection; however, both the lamivudine and tenofovir components are active against the hepatitis B virus. Perform hepatitis B virus (HBV) screening in any patient who presents with HIV infection to assure appropriate treatment. 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 used in combination with a fully suppressive ARV regimen (note: entecavir should not be considered part of the ARV regimen). Avoid using single-drug therapy to treat 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. Patients with coexisting HBV and HIV infections who discontinue lamivudine or tenofovir may experience severe acute hepatitis B exacerbation with some cases resulting in hepatic decompensation and hepatic failure. Therefore, close monitoring of transaminase concentrations (every 6 weeks for the first 3 months, and every 3 to 6 months thereafter) is recommended in coinfected patients who discontinue NRTI therapy. If appropriate, resumption of anti-hepatitis B treatment may be required, especially in patients with advanced liver disease or cirrhosis, since posttreatment exacerbation of hepatitis 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 patients to avoid consuming alcohol, and offer vaccinations against hepatitis A and hepatitis B as appropriate.
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. If lamivudine; tenofovir disoproxil fumarate is to be used in combination with interferon alfa with or without ribavirin, closely monitored the patient for treatment-associated toxicities (especially hepatic decompensation). In vitro studies have shown antiretroviral use with ribavirin can reduce the phosphorylation of pyrimidine nucleoside analogs, such as lamivudine. Although no evidence of pharmacokinetic or pharmacodynamic interactions were observed, some patients who received these drugs concurrently experienced fatal hepatic decompensation. If adverse events are identified, consider treatment discontinuation or ribavirin and interferon alfa dose reductions as medically appropriate. 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.
Lactic acidosis and hepatomegaly with steatosis, including fatal cases, have been reported following use of lamivudine and tenofovir disoproxil fumarate (DF), both alone and in combination with other antiretroviral medications. Treatment with lamivudine; 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 impaired hepatic function (hepatic disease), 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.
Tenofovir disoproxil fumarate is principally eliminated by the kidney; use of lamivudine; tenofovir should be avoided in patients with impaired renal function (i.e., creatinine clearance less than 50 mL/min) and in patients with end-stage renal disease requiring hemodialysis. Renal impairment, including acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been associated with tenofovir disoproxil fumarate administration. The majority of such cases occurred in patients with underlying systemic or renal disease, or in patients taking nephrotoxic agents; some cases, however, occur in patients with no identifiable risk factors. The manufacturer recommends that an estimated creatinine clearance, serum creatinine, urine glucose, and urine protein be assessed in all patients prior to treatment, and as clinically appropriate during treatment. In patients with chronic kidney diseases, serum phosphorous should also be assessed. In addition, closely evaluate the renal function of patients who experience persistent or worsening bone pain, pain in extremities, bone fractures, and muscle pain or weakness while receiving the drug as these may be manifestations of proximal renal tubulopathy. Avoid use of the drug concurrently with or recently after administration of a nephrotoxic agent, including high-dose or multiple non-steroidal antiinflammatory drugs (NSAIDS), as cases of acute renal failure requiring hospitalization and renal replacement therapy have been reported.
There appears to be a significant risk of pancreatitis in pediatric patients treated with lamivudine-containing regimens. Administer lamivudine; tenofovir disoproxil fumarate with caution to children with a history of prior antiretroviral nucleoside exposure, pancreatitis, or other significant risk factors for pancreatitis. Stop treatment immediately if clinical signs, symptoms, or laboratory abnormalities suggestive of pancreatitis occur.
Bone mineral density (BMD) monitoring should be considered for patients with HIV who have a history of pathologic bone fracture or are at substantial risk for osteopenia, osteoporosis, or osteomalacia. Cases of osteomalacia associated with proximal renal tubulopathy have been reported in association with the use of tenofovir disoproxil fumarate. In a postmarketing study comparing tenofovir with stavudine (each given in combination with lamivudine and efavirenz), decreases from baseline in BMD were seen at the lumbar spine and hip regions in both arms of the study. The clinical significance of the changes in BMD is unknown. Normally, BMD increases rapidly in pediatric patients; however, in studies of tenofovir-treated pediatric patients, bone effects were similar to those noted in adult patients. One study evaluating children with HIV aged 2 to 12 years found total body BMD gains in recipients of tenofovir to be lower than the gains observed in patients receiving either stavudine or zidovudine. Additionally, at treatment week 48, 1 tenofovir-treated patient experienced significant (more than 4%) BMD loss in the lumbar spine; significant BMD losses were not observed in the stavudine or zidovudine treatment groups. In another study involving adolescents aged 12 to 17 years, the mean rate of BMD gain was less in the tenofovir-treated patients compared to the placebo group. Six tenofovir-treated adolescents and 1 placebo-treated adolescent had significant (greater than 4%) lumbar spine BMD loss in 48 weeks. In both studies, skeletal growth height appeared to be unaffected. Although the effect of supplementation with calcium and vitamin D was not studied, such supplementation may be considered for all patients. If bone abnormalities are suspected, appropriate consultation should be obtained.
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. Lamivudine will not likely be effective in individuals who display antimicrobial resistance to emtricitabine, due to the similarities between the 2 drugs. Clinicians should not expect patients with the M184 mutation associated with emtricitabine to benefit from a lamivudine containing regimen. The M184 mutation confers high-level resistance, and lamivudine, like emtricitabine, selects for the M184 mutation. It is important that persons with detectable viral load who plan to switch therapy from emtricitabine to lamivudine have genotypic testing performed to determine whether the M184 mutation is present. A patient's treatment history is also extremely important; if emtricitabine has failed in the past, the 184 is archived, thus rendering lamivudine ineffective in this patient population. 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.
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 lamivudine; 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 jirovecii pneumonia (PCP), or tuberculosis (TB)), which may necessitate further evaluation and treatment. In addition, autoimmune disease (including Graves' disease, Guillain-Barre syndrome, and polymyositis) may also develop; the time to onset is variable and may occur months after treatment initiation.
Patients with peripheral neuropathy can experience exacerbations during treatment with lamivudine-containing regimens.
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 lamivudine; tenofovir disoproxil fumarate (DF) as a preferred 2-NRTI backbone in patients who are pregnant or trying to conceive. Available data from the Antiretroviral Pregnancy Registry (APR), which includes 5,613 first trimester exposures to lamivudine and 4,840 first trimester exposures to tenofovir DF, 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 exposure occurred in the first trimester, the prevalence of birth defects was 3.1% (95% CI: 2.6 to 3.6) for lamivudine and 2.6% (95% CI: 2.2 to 3.1) for tenofovir DF. Nucleoside reverse transcriptase inhibitors (NRTIs) are known to induce mitochondrial dysfunction. An association of mitochondrial dysfunction in infants and in-utero antiretroviral exposure has been suggested, but not established. While the development of severe or fatal mitochondrial disease in exposed infants appears to be extremely rare, more intensive monitoring of hematologic and electrolyte parameters during the first few weeks of life is advised. Nucleoside analogs have been associated with the development of lactic acidosis, especially during pregnancy. It is unclear if pregnancy augments the incidence of lactic acidosis/hepatic steatosis in patients receiving nucleoside analogs. However, because pregnancy 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 or equal to 300 cells/mm3 do not need CD4 counts monitored after the initial visit during the pregnancy. However, CD4 counts should be monitored every 3 months during pregnancy for patients on HAART less than 2 years and have CD4 counts less than 300 cells/mm3, patients with inconsistent adherence, or patients with detectable viral loads. For patients on HAART less than 2 years but have CD4 counts greater than or equal to 300 cells/mm3, monitor CD4 counts every 6 months. Monitor plasma HIV RNA at the initial visit (with review of prior levels), 2 to 4 weeks after initiating or changing therapy, monthly until undetectable, and then at least every 3 months during pregnancy. Viral load should also be assessed at approximately 36 weeks gestation, or within 4 weeks of planned delivery, to inform decisions regarding mode of delivery and optimal treatment for newborns. Patients whose HIV RNA levels are above the threshold for resistance testing (usually greater than 500 copies/mL but may be possible for levels greater than 200 copies/mL in some laboratories) should undergo antiretroviral resistance testing (genotypic testing, and if indicated, phenotypic testing). Resistance testing should be conducted before starting therapy in treatment-naive patients who have not been previously tested, starting therapy in treatment-experienced patients (including those who have received pre-exposure prophylaxis), modifying therapy in patients who become pregnant while receiving treatment, or modifying therapy in patients who have suboptimal virologic response to treatment that was started during pregnancy. DO NOT delay initiation of antiretroviral therapy while waiting on the results of resistance testing; treatment regimens can be modified, if necessary, once the testing results are known. 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 lamivudine; tenofovir disoproxil fumarate; information about the registry can be obtained at www.apregistry.com or by calling 1-800-258-4263; fax 1-800-800-1052.
HIV treatment guidelines recommend clinicians provide mothers with evidence-based, patient-centered counseling to support shared decision-making regarding infant feeding. Inform patients that use of replacement feeding (i.e., formula or banked pasteurized donor human milk) eliminates the risk of HIV transmission. Advise patients who receive a diagnosis of HIV infection while breast-feeding (acute HIV) to immediately discontinue breast-feeding and switch to replacement feeding in order to reduce the risk of postnatal HIV transmission to the infant. Replacement feeding is also recommended for use when mothers with HIV are not on antiretroviral therapy (ART) or do not have suppressed viral load during pregnancy, as well as at delivery. For patients on ART who have achieved and maintained viral suppression during pregnancy (at minimum throughout the third trimester) and postpartum, the transmission risk from breast-feeding is less than 1%, but not zero. Virologically suppressed mothers who choose to breast-feed should be supported in this decision. If breast-feeding is chosen, counsel the patient about the importance of adherence to therapy and recommend that the infant be exclusively breast-fed for up to 6 months of age, as exclusive breast-feeding has been associated with a lower rate of HIV transmission as compared to mixed feeding (i.e., breast milk and formula). Promptly identify and treat mastitis, thrush, and cracked or bleeding nipples, as these conditions may increase the risk of HIV transmission through breast-feeding. Breast-fed infants should undergo immediate diagnostic and virologic HIV testing. Testing should continue throughout breast-feeding and up to 6 months after cessation of breast-feeding. For expert consultation, healthcare workers may contact the Perinatal HIV Hotline (888-448-8765). Both drug components have been shown to pass into human breast milk. Lamivudine was found to be secreted in human breast milk during a study involving 20 breast-feeding mothers with HIV who were administered either 300 mg of lamivudine twice daily as a single agent (n = 10) or lamivudine 150 mg twice daily in combination with zidovudine (n = 10). The mean breast milk concentrations of lamivudine in the respective groups were similar at 1.22 mg/L (range less than 0.5 to 6.09 mg/L) and 0.9 mg/L (range less than 0.5 to 8.2 mg/L). In another study, tenofovir exposure in exclusively breast-fed infants was found to be equivalent to approximately 4.2 micrograms per day. Other antiretroviral medications whose passage into human breast milk have been evaluated include nevirapine, zidovudine, and nelfinavir.
HIV guidelines recommend consideration be given to avoiding use of tenofovir disoproxil fumarate-containing regimens in patients with renal disease and osteoporosis.
Initiation of therapy for HIV treatment:
-For adults, initiation of treatment immediately (or as soon as possible) after HIV diagnosis is recommended in all patients to reduce the risk of disease progression and to prevent the transmission of HIV, including perinatal transmission and transmission to sexual partners. Starting antiretroviral therapy early is particularly important for patients with AIDS-defining conditions, those with acute or recent HIV infection, and individuals who are pregnant; delaying therapy in these subpopulations has been associated with high risks of morbidity, mortality, and HIV transmission.
-Prior to initiating treatment, obtain baseline plasma HIV RNA (viral load) and CD4 count; results do not need to be available before starting therapy.
-Antiretroviral drug-resistance testing:-Genotypic drug-resistance testing is recommended prior to initiation of therapy and prior to changing therapy for treatment failure.
--Standard genotypic drug-resistance testing in treatment-naive people should focus on testing for mutations in reverse transcriptase (RT) and protease (PR) genes.
-Testing for mutations in the integrase gene should also be performed if integrase strand transfer inhibitor (INSTI) resistance is a concern (e.g., people who acquire HIV after pre-exposure prophylaxis with long-acting cabotegravir).
-Phenotypic resistance testing may be used in conjunction with the genotypic test for patients with known or suspected complex drug-resistance mutation patterns.
-HIV-1 proviral DNA resistance testing is available for use in patients with HIV RNA concentrations below the limits of detection or with low-level viremia (i.e., less than 1,000 copies/mL), where genotypic testing is unlikely to be successful; however, the clinical utility of this assay has not been fully determined.
-It is not necessary to delay treatment until resistance test results are available; however, subsequent modifications to the treatment regimen should be made, if needed, once the test results are available.
-Pediatric guidelines are also available.
Place in therapy for HIV treatment:
-For pregnant and non-pregnant adults and adolescents, lamivudine; tenofovir disoproxil fumarate is a preferred 2-NRTI backbone.
-Pediatric guidelines are also available.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: human immunodeficiency virus (HIV)
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
For use in combination with other antiretroviral medications to treat human immunodeficiency virus (HIV) infection:
Oral dosage:
Adults weighing 35 kg or more: 1 tablet (lamivudine 300 mg; tenofovir disoproxil fumarate 300 mg) PO once daily.
Children and Adolescents weighing 35 kg or more: 1 tablet (lamivudine 300 mg; tenofovir disoproxil fumarate 300 mg) PO once daily.
Maximum Dosage Limits:
-Adults
35 kg or more: 1 tablet (lamivudine 300 mg; tenofovir disoproxil fumarate 300 mg) PO daily.
Less than 35 kg: Use not recommended.
-Geriatric
35 kg or more: 1 tablet (lamivudine 300 mg; tenofovir disoproxil fumarate 300 mg) PO daily.
Less than 35 kg: Use not recommended.
-Adolescents
35 kg or more: 1 tablet (lamivudine 300 mg; tenofovir disoproxil fumarate 300 mg) PO daily.
Less than 35 kg: Use not recommended.
-Children
35 kg or more: 1 tablet (lamivudine 300 mg; tenofovir disoproxil fumarate 300 mg) PO daily.
Less than 35 kg: Use not recommended.
-Infants
Use not recommended.
-Neonates
Use not recommended.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
CrCl 50 mL/min or greater: No dosage adjustment is needed.
CrCl less than 50 mL/min: Not recommended.
Hemodialysis
Hemodialysis removes tenofovir from the blood, but is not expected to significantly remove lamivudine. Avoid use in patient with end-stage renal disease requiring hemodialysis.
*non-FDA-approved indication
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. (Major) Patients who are concurrently taking adefovir with antiretrovirals (i.e., anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs)) are at risk of developing lactic acidosis and severe hepatomegaly with steatosis. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with antiretrovirals. A majority of these cases have been in women; obesity and prolonged nucleoside exposure may also be risk factors. Particular caution should be exercised when administering nucleoside analogs to any patient with known risk factors for hepatic disease; however, cases have also been reported in patients with no known risk factors. Suspend adefovir in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).
Aldesleukin, IL-2: (Major) Avoid concomitant use of tenofovir disoproxil and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Alogliptin; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
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.
Amiloride: (Moderate) Drugs that are actively secreted via cationic tubular secretion, such as amiloride, should be co-administered with caution with lamivudine since they could increase lamivudine plasma concentrations, and therefore lamivudine associated adverse reactions, via potential competition for renal cationic secretion.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Drugs that are actively secreted via cationic tubular secretion, such as amiloride, should be co-administered with caution with lamivudine since they could increase lamivudine plasma concentrations, and therefore lamivudine associated adverse reactions, via potential competition for renal cationic secretion.
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.
Asciminib: (Moderate) Coadministration of tenofovir disoproxil fumarate with asciminib 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 asciminib is a BCRP inhibitor.
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; 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.
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.
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.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
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.
Bortezomib: (Minor) Monitor patients for the development of peripheral neuropathy when receiving bortezomib in combination with other drugs that can cause peripheral neuropathy like lamivudine; the risk of peripheral neuropathy may be additive.
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. (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with lamivudine is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and lamivudine is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown.
Canagliflozin; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
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.
Danicopan: (Moderate) Coadministration of tenofovir disoproxil fumarate with danicopan 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 danicopan is a P-gp and BCRP inhibitor.
Dapagliflozin; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Daridorexant: (Moderate) Coadministration of tenofovir disoproxil fumarate with daridorexant 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 daridorexant is a P-gp inhibitor.
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: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine. (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.
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. (Moderate) Drugs that are actively secreted via cationic secretion, such as lamivudine, should be co-administered with dofetilide with caution since they could increase dofetilide plasma concentrations via potential competition for renal tubular secretion.
Donepezil; Memantine: (Moderate) Memantine is excreted in part by renal tubular secretion. Competition of memantine for excretion with other drugs that are also eliminated by tubular secretion, such as lamivudine, could result in elevated serum concentrations of one or both drugs.
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.
Echinacea: (Moderate) Use Echinacea sp. with caution in patients taking medications for human immunodeficiency virus (HIV) infection. Some experts have suggested that Echinacea's effects on the immune system might cause problems for patients with HIV infection, particularly with long-term use. There may be less risk with short-term use (less than 2 weeks). A few pharmacokinetic studies have shown reductions in blood levels of some antiretroviral medications when Echinacea was given, presumably due to CYP induction. However, more study is needed for various HIV treatment regimens. Of the agents studied, the interactions do not appear to be significant or to require dose adjustments at the time of use. Although no dose adjustments are required, monitoring drug concentrations may give reassurance during co-administration. Monitor viral load and other parameters carefully during therapy.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
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.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Empagliflozin; Linagliptin; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Empagliflozin; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Emtricitabine: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Emtricitabine; Tenofovir alafenamide: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
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.
Erdafitinib: (Moderate) Coadministration of tenofovir disoproxil fumarate with erdafitinib 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 erdafitinib is a P-gp inhibitor.
Ertugliflozin; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
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.
Glipizide; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Glyburide; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
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.
Interferon Alfa-2b: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6).
Interferon Alfa-n3: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6).
Interferon Beta-1a: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6).
Interferon Beta-1b: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6).
Interferon Gamma-1b: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6).
Interferons: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6).
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.
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.
Linagliptin; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
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.
Memantine: (Moderate) Memantine is excreted in part by renal tubular secretion. Competition of memantine for excretion with other drugs that are also eliminated by tubular secretion, such as lamivudine, could result in elevated serum concentrations of one or both drugs.
Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Metformin; Repaglinide: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Metformin; Saxagliptin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Metformin; Sitagliptin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
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.
Momelotinib: (Moderate) Coadministration of tenofovir disoproxil fumarate with momelotinib 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 momelotinib is a BCRP 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.
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. (Moderate) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, 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.
Peginterferon Alfa-2a: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6).
Peginterferon Alfa-2b: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6).
Peginterferon beta-1a: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6).
Pioglitazone; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
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.
Procainamide: (Moderate) Cationic drugs that are eliminated by renal tubular secretion such as procainamide may compete with lamivudine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of the response to lamivudine and/or procainamide is recommended to individualize dosage. In selected individuals, procainamide serum concentration monitoring may be appropriate.
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.
Ribavirin: (Moderate) Use lamivudine with ribavirin and interferon with caution and closely monitor for hepatic decompensation and anemia. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh greater than 6). Hepatic decompensation (some fatal) has occurred in HCV/HIV coinfected patients who received both ribavirin/interferon and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) therapies. In addition, ribavirin has been shown in cell culture to inhibit phosphorylation of lamivudine, which could lead to decreased antiretroviral activity; however, while ribavirin inhibits the phosphorylation reactions required to activate lamivudine, no evidence of a pharmacokinetic or pharmacodynamic interaction has been observed.
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.
Ropeginterferon alfa-2b: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6).
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.
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.
Sorbitol: (Major) Avoid coadministration of lamivudine oral solution and sorbitol if possible due to sorbitol dose-dependent reduction in lamivudine exposure. An all-tablet regimen should be used when possible to avoid a potential interaction with sorbitol. Consider more frequent monitoring of viral load when treating with lamivudine oral solution. In a drug interaction study in 16 healthy adult patients, coadministration of a single 300 mg dose of lamivudine oral solution with sorbitol 3.2 g, 10.2 g, or 13.4 g resulted in dose-dependent decreases of 20%, 39%, and 44% in the AUC24 and 28%, 52%, and 55% in the Cmax of lamivudine.
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: (Moderate) Trospium is eliminated by active tubular secretion and has the potential for pharmacokinetic interactions with other drugs that are eliminated by active tubular secretion including lamivudine. In theory, coadministration of trospium with lamivudine may increase the serum concentrations of trospium or lamivudine due to competition for the drug elimination pathway. (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.
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.
Lamivudine is a nucleoside reverse transcriptase inhibitor (NRTI) and tenofovir disoproxil fumarate is a nucleotide reverse transcriptase inhibitor (although sometimes classified with the NRTIs). Combination therapy targets different points in the life cycle of HIV, reducing viral capacity to mutate to drug-resistant strains.
Lamivudine: Lamivudine inhibits viral reverse transcriptase in both HIV-1 and HBV. When used in combination with efavirenz and tenofovir, it is used specifically for its activity against HIV. Lamivudine is a synthetic nucleoside analog of cytosine and is phosphorylated by cellular enzymes to its active 5'-triphosphate metabolite, lamivudine triphosphate. Lamivudine triphosphate inhibits the activity of HIV-1 reverse transcriptase by competing with the deoxycytidine 5'-triphosphate and by being incorporated into nascent viral DNA, resulting in chain termination.
HIV-1 resistance to lamivudine is predominately due to a methionine to valine or isoleucine (M184V/I) substitution in reverse transcriptase. Cross-resistance is expected with abacavir, didanosine, and emtricitabine.
Tenofovir disoproxil fumarate: Tenofovir inhibits viral reverse transcriptase in both HIV-1 and HBV. Tenofovir disoproxil fumarate (tenofovir DF) is an acyclic nucleoside phosphonate (nucleotide) diester analog of adenosine monophosphate. Tenofovir DF requires initial diester hydrolysis for conversion to tenofovir. Tenofovir is then taken up by cells and undergoes phosphorylation to form tenofovir diphosphate (PMPApp). Tenofovir diphosphate competes with the natural substrate deoxyadenosine 5'-triphosphate (dATP) for incorporation into the DNA. Once incorporated, tenofovir diphosphate, which lacks a 3' hydroxyl group, causes premature DNA chain termination.
HIV-1 isolates that express a K65R amino acid substitutions in reverse transcriptase show a 2- to 4-fold reduction in the susceptibility to tenofovir. In addition, a K70E substitution in HIV-1 reverse transcriptase has been selected by tenofovir and results in reduced susceptibility. The K70E substitution selected clinically by tenofovir results in reduced susceptibility to abacavir, didanosine, emtricitabine, and lamivudine. HIV-1 isolates with the K65R substitution also show reduced susceptibility to lamivudine and emtricitabine.
Lamivudine; tenofovir disoproxil fumarate is administered orally.
Lamivudine: Lamivudine exhibits low plasma protein binding (less than 36%). Within 12 hours after a single dose, approximately 5% of the dose is excreted in the urine as the trans-sulfoxide metabolite. The majority of the dose is eliminated unchanged in the urine by active organic cationic secretion. The observed mean elimination half-life ranges from 5 to 7 hours.
Tenofovir disoproxil fumarate: Protein binding of tenofovir is negligible (less than 0.7%) and binding is independent of concentration over the range of 0.01 to 25 mcg/mL. Intracellularly, tenofovir undergoes phosphorylation to its active metabolite, tenofovir diphosphate (PMPApp). Tenofovir and tenofovir diphosphate have a prolonged intracellular half-life (15 to 50 hours). In vitro studies indicate that neither tenofovir disoproxil fumarate nor tenofovir are substrates of cytochrome P450 enzymes. Approximately 70% to 80% of the dose is recovered as unchanged drug in the urine. Tenofovir is eliminated by a combination of glomerular filtration and active renal tubular secretion; there may be competition for elimination with other compounds that are also renally eliminated. The terminal elimination half-life is approximately 17 hours.
Affected cytochrome P450 isoenzymes and transporters: P-gp, BRCP
Tenofovir disoproxil fumarate is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters. Administration with inhibitors of these transporters may result in increased absorption of tenofovir.
-Route-Specific Pharmacokinetics
Oral Route
Lamivudine: Following oral administration, the absolutes bioavailability of lamivudine is approximately 86%. Drug exposure (AUC) and the maximum plasma concentration (Cmax) increase in proportion to the dose over a range from 0.25 to 10 mg/kg.
Tenofovir disoproxil fumarate: The bioavailability in a fasting state is 25%; when given with either a high fat or light meal, tenofovir AUC and Cmax increase by 35% and 15%, respectively.
-Special Populations
Hepatic Impairment
Lamivudine: Lamivudine pharmacokinetic parameters are not altered by diminishing hepatic function. Safety and efficacy of lamivudine have not been established in the presence of decompensated hepatic disease.
Tenofovir disoproxil fumarate: No substantial pharmacokinetic changes have been noted following tenofovir disoproxil fumarate administration in patients with moderate to severe hepatic impairment (Child-Pugh B and C).
Renal Impairment
Lamivudine: The pharmacokinetic parameters of lamivudine are altered in patients with renal impairment. A single dose study involving patients with varying degrees of renal dysfunction, found patients with moderate and severe renal impairment had significant increases in lamivudine exposure (AUC) and maximum plasma concentration (Cmax) when compared to patients with normal renal function.
Tenofovir disoproxil fumarate: The pharmacokinetic parameters of tenofovir disoproxil fumarate are altered in patients with renal impairment. A single dose study involving patients with varying degrees of renal dysfunction, found patients with CrCl less than 50 mL/min or with end-stage renal disease requiring dialysis had increases in tenofovir exposure (AUC) and maximum plasma concentration (Cmax) when compared to patients with normal renal function.
Gender Differences
There are no significant or clinically relevant gender differences in the pharmacokinetics of lamivudine and tenofovir disoproxil fumarate.
Ethnic Differences
Lamivudine: There are no significant or clinically relevant racial differences in lamivudine concentrations.
Tenofovir disoproxil fumarate: There were insufficient numbers from racial and ethnic groups other than Caucasian to adequately determine potential pharmacokinetic differences among these populations.
Obesity
Pregnancy
Lamivudine: Although population pharmacokinetic modeling suggests the oral clearance of lamivudine is increased by 22% during pregnancy, limited data from 2 studies involving 36 pregnant women (16 at 36 weeks, 20 at 38 weeks gestation) found the pharmacokinetic parameters of lamivudine to be similar to those observed in non-pregnant and postpartum adults. No change in dose is indicated. In addition, placental transfer of lamivudine results in drug concentrations that are 2-times greater than maternal serum levels.
Tenofovir disoproxil fumarate: Pregnancy alters the pharmacokinetic parameters of tenofovir. In 1 study, a 30% increase in the clearance of tenofovir was observed in 34 pregnant women with HIV. In addition, the drug exposure (AUC), peak (Cmax), and trough (Cmin) obtained during the 3rd trimester were 23% (p less than 0.001), 19% (p = 0.001) and 21% (p = 0.003) lower, respectively, than those obtained postpartum. Despite these reductions, most women maintain a therapeutic AUC of at least 2 mg x hour/L throughout pregnancy; thus, dosage adjustments are not required. Changes in the pharmacokinetics of tenofovir are theorized to be a result of increased renal clearance, expanded plasma volume, and reduced gastrointestinal absorption. Tenofovir has a high placental transfer to the fetus.