Tenofovir Disoproxil Fumarate Prescribing Information
Severe acute exacerbations of hepatitis B virus (HBV) have been reported in HBV-infected patients who have discontinued anti-hepatitis B therapy, including tenofovir disoproxil fumarate tablets. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in HBV-infected patients who discontinue anti-hepatitis B therapy, including tenofovir disoproxil fumarate tablets. If appropriate, resumption of anti-hepatitis B therapy may be warranted
Discontinuation of anti-HBV therapy, including tenofovir disoproxil fumarate, may be associated with severe acute exacerbations of hepatitis B. Patients infected with HBV who discontinue tenofovir disoproxil fumarate should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment. If appropriate, resumption of anti-hepatitis B therapy may be warranted, especially in patients with advanced liver disease or cirrhosis, since posttreatment exacerbation of hepatitis may lead to hepatic decompensation and liver failure.
Indications and Usage, Chronic Hepatitis B (
Dosage and Administration (
Prior to initiation and during use of tenofovir disoproxil fumarate tablets, on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus
The recommended dosage of tenofovir disoproxil fumarate tablets in adults and pediatric patients weighing at least 35 kg is one 300 mg tablet taken orally once daily without regard to food. The dosage for tenofovir disoproxil fumarate tablet is the same for both HIV and HBV indications.
The recommended dosage of tenofovir disoproxil fumarate tablet in adults and pediatric patients 2 years and older weighing at least 17 kg is 8 mg of tenofovir disoproxil fumarate (TDF) per kg of body weight (up to a maximum of 300 mg) once daily. Dosage for pediatric patients 2 years and older weighing between 17 kg and 35 kg and able to swallow an intact tablet is provided in Table 1. Weight should be monitored periodically and the tenofovir disoproxil fumarate tablets dose adjusted accordingly.
Table 1 Recommended Dosing for Patients 2 Years and Older and Weighing at Least 17 kg Using Tenofovir Disoproxil Fumarate Tablets
Body Weight (kg) | Dosing of Tenofovir Disoproxil Fumarate Tablets |
| 17 to less than 22 | one 150 mg tablet once daily |
| 22 to less than 28 | one 200 mg tablet once daily |
| 28 to less than 35 | one 250 mg tablet once daily |
| at least 35 | one 300 mg tablet once daily |
The recommended dosage of tenofovir disoproxil fumarate tablets in adults and pediatric patients weighing at least 35 kg is one 300 mg tablet taken orally once daily without regard to food. The dosage for tenofovir disoproxil fumarate tablet is the same for both HIV and HBV indications.
The recommended dosage of tenofovir disoproxil fumarate tablet in adults and pediatric patients 2 years and older weighing at least 17 kg is 8 mg of tenofovir disoproxil fumarate (TDF) per kg of body weight (up to a maximum of 300 mg) once daily. Dosage for pediatric patients 2 years and older weighing between 17 kg and 35 kg and able to swallow an intact tablet is provided in Table 1. Weight should be monitored periodically and the tenofovir disoproxil fumarate tablets dose adjusted accordingly.
Table 1 Recommended Dosing for Patients 2 Years and Older and Weighing at Least 17 kg Using Tenofovir Disoproxil Fumarate Tablets
Body Weight (kg) | Dosing of Tenofovir Disoproxil Fumarate Tablets |
| 17 to less than 22 | one 150 mg tablet once daily |
| 22 to less than 28 | one 200 mg tablet once daily |
| 28 to less than 35 | one 250 mg tablet once daily |
| at least 35 | one 300 mg tablet once daily |
Creatinine Clearance (mL/min)a | Hemodialysis Patients | |||
50 or greater | 30–49 | 10–29 | Every 7 days or after a total of approximately 12 hours of dialysisb | |
Recommended 300 mg Dosing Interval | Every 24 hours | Every 48 hours | Every 72 to 96 hours | |
a. Calculated using ideal (lean) body weight.
b. Generally once weekly assuming 3 hemodialysis sessions a week of approximately 4 hours' duration. Tenofovir disoproxil fumarate should be administered following completion of dialysis.
No data are available to make dosage recommendations in patients with creatinine clearance below 10 mL/min who are not on hemodialysis.
No data are available to make dosage recommendations in pediatric patients with renal impairment.
Warnings and Precautions (
Discontinuation of anti-HBV therapy, including tenofovir disoproxil fumarate, may be associated with severe acute exacerbations of hepatitis B. Patients infected with HBV who discontinue tenofovir disoproxil fumarate should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment. If appropriate, resumption of anti-hepatitis B therapy may be warranted, especially in patients with advanced liver disease or cirrhosis, since posttreatment exacerbation of hepatitis may lead to hepatic decompensation and liver failure.
Tenofovir is principally eliminated by the kidney. Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported with the use of tenofovir disoproxil fumarate
Dosing interval adjustment of tenofovir disoproxil fumarate and close monitoring of renal function are recommended in all patients with creatinine clearance below 50 mL/min
Tenofovir disoproxil fumarate should be avoided with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs])
Persistent or worsening bone pain, pain in extremities, fractures and/or muscular pain or weakness may be manifestations of proximal renal tubulopathy and should prompt an evaluation of renal function in patients at risk of renal dysfunction.
In clinical trials in HIV-1 infected adults, tenofovir disoproxil fumarate was associated with slightly greater decreases in bone mineral density (BMD) and increases in biochemical markers of bone metabolism, suggesting increased bone turnover relative to comparators
The effects of tenofovir disoproxil fumarate -associated changes in BMD and biochemical markers on long-term bone health and future fracture risk in adults and pediatric subjects 2 years and older are unknown. The long-term effect of lower spine and total body BMD on skeletal growth in pediatric patients, and in particular, the effects of long-duration exposure in younger children is unknown.
Although the effect of supplementation with calcium and vitamin D was not studied, such supplementation may be beneficial. Assessment of BMD should be considered for adult and pediatric patients who have a history of pathologic bone fracture or other risk factors for osteoporosis or bone loss. If bone abnormalities are suspected, appropriate consultation should be obtained.
Cases of osteomalacia associated with proximal renal tubulopathy, manifested as bone pain or pain in extremities and which may contribute to fractures, have been reported in association with tenofovir disoproxil fumarate use
See Table 12 for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations. Consider the potential for drug interactions prior to and during therapy with tenofovir disoproxil fumarate; review concomitant medications during therapy with tenofovir disoproxil fumarate; and monitor for adverse reactions associated with the concomitant drugs.
Early Virologic Failure
Tenofovir disoproxil fumarate tablets are a nucleotide analog HIV-1 reverse transcriptase inhibitor and an HBV reverse transcriptase inhibitor and is indicated:
• in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients 2 years of age and older weighing at least 10 kg. (
Tenofovir disoproxil fumarate tablets are indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and pediatric patients 2 years of age and older weighing at least 10 kg.
• for the treatment of chronic hepatitis B in adults and pediatric patients 2 years and older weighing at least 10 kg.(
• Testing: Prior to or when initiating tenofovir disoproxil fumarate tablets test for hepatitis B virus infection and HIV-1 infection. Prior to initiation and during use of tenofovir disoproxil fumarate tablets, on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorous. (
Prior to initiation and during use of tenofovir disoproxil fumarate tablets, on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus
• Recommended tablet dosage in adults and pediatric patients weighing at least 35 kg: One tenofovir disoproxil fumarate 300 mg tablet once daily taken orally without regard to food. (
The recommended dosage of tenofovir disoproxil fumarate tablets in adults and pediatric patients weighing at least 35 kg is one 300 mg tablet taken orally once daily without regard to food. The dosage for tenofovir disoproxil fumarate tablet is the same for both HIV and HBV indications.
The recommended dosage of tenofovir disoproxil fumarate tablet in adults and pediatric patients 2 years and older weighing at least 17 kg is 8 mg of tenofovir disoproxil fumarate (TDF) per kg of body weight (up to a maximum of 300 mg) once daily. Dosage for pediatric patients 2 years and older weighing between 17 kg and 35 kg and able to swallow an intact tablet is provided in Table 1. Weight should be monitored periodically and the tenofovir disoproxil fumarate tablets dose adjusted accordingly.
Table 1 Recommended Dosing for Patients 2 Years and Older and Weighing at Least 17 kg Using Tenofovir Disoproxil Fumarate Tablets
Body Weight (kg) | Dosing of Tenofovir Disoproxil Fumarate Tablets |
| 17 to less than 22 | one 150 mg tablet once daily |
| 22 to less than 28 | one 200 mg tablet once daily |
| 28 to less than 35 | one 250 mg tablet once daily |
| at least 35 | one 300 mg tablet once daily |
• Recommended dosage in pediatric patients at least 2 years of age and adults:
o Tablets: For patients weighing at least 17 kg who can swallow an intact tablet, one tenofovir disoproxil fumarate tablet (300 mg based on body weight) once daily taken orally without regard to food. (
The recommended dosage of tenofovir disoproxil fumarate tablets in adults and pediatric patients weighing at least 35 kg is one 300 mg tablet taken orally once daily without regard to food. The dosage for tenofovir disoproxil fumarate tablet is the same for both HIV and HBV indications.
The recommended dosage of tenofovir disoproxil fumarate tablet in adults and pediatric patients 2 years and older weighing at least 17 kg is 8 mg of tenofovir disoproxil fumarate (TDF) per kg of body weight (up to a maximum of 300 mg) once daily. Dosage for pediatric patients 2 years and older weighing between 17 kg and 35 kg and able to swallow an intact tablet is provided in Table 1. Weight should be monitored periodically and the tenofovir disoproxil fumarate tablets dose adjusted accordingly.
Table 1 Recommended Dosing for Patients 2 Years and Older and Weighing at Least 17 kg Using Tenofovir Disoproxil Fumarate Tablets
Body Weight (kg) | Dosing of Tenofovir Disoproxil Fumarate Tablets |
| 17 to less than 22 | one 150 mg tablet once daily |
| 22 to less than 28 | one 200 mg tablet once daily |
| 28 to less than 35 | one 250 mg tablet once daily |
| at least 35 | one 300 mg tablet once daily |
• Recommended dosage in renally impaired adult patients:
o Creatinine clearance (CrCl) 30−49 mL/min: 300 mg every 48 hours. (
Creatinine Clearance (mL/min)a | Hemodialysis Patients | |||
50 or greater | 30–49 | 10–29 | Every 7 days or after a total of approximately 12 hours of dialysisb | |
Recommended 300 mg Dosing Interval | Every 24 hours | Every 48 hours | Every 72 to 96 hours | |
a. Calculated using ideal (lean) body weight.
b. Generally once weekly assuming 3 hemodialysis sessions a week of approximately 4 hours' duration. Tenofovir disoproxil fumarate should be administered following completion of dialysis.
No data are available to make dosage recommendations in patients with creatinine clearance below 10 mL/min who are not on hemodialysis.
No data are available to make dosage recommendations in pediatric patients with renal impairment.
o CrCl 10−29 mL/min: 300 mg every 72 to 96 hours. (2.4)
o Hemodialysis: 300 mg every 7 days or after approximately 12 hours of dialysis. (
Creatinine Clearance (mL/min)a | Hemodialysis Patients | |||
50 or greater | 30–49 | 10–29 | Every 7 days or after a total of approximately 12 hours of dialysisb | |
Recommended 300 mg Dosing Interval | Every 24 hours | Every 48 hours | Every 72 to 96 hours | |
a. Calculated using ideal (lean) body weight.
b. Generally once weekly assuming 3 hemodialysis sessions a week of approximately 4 hours' duration. Tenofovir disoproxil fumarate should be administered following completion of dialysis.
No data are available to make dosage recommendations in patients with creatinine clearance below 10 mL/min who are not on hemodialysis.
No data are available to make dosage recommendations in pediatric patients with renal impairment.
Tenofovir disoproxil fumarate is available as tablets.
300 mg Tablets: 300mg of TDF, which is (equivalent to 245 mg of tenofovir disoproxil). The tablets are blue coloured, oval shaped, biconvex, film coated tablets debossed with 'CL 77' on one side and plain on other side.
Lactation: Breastfeeding in HIV-1 infected mothers is not recommended due to the potential for HIV-1 transmission. (
Based on published data, tenofovir has been shown to be present in human breast milk (
The Centers for Disease Control and Prevention recommend that HIV-1 infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV-1.
Because of the potential for: (1) HIV transmission (in HIV-negative infants); (2) developing viral resistance (in HIV-positive infants); and (3) adverse reactions in a breastfed infant similar to those seen in adults, instruct mothers not to breastfeed if they are taking tenofovir disoproxil fumarate for the treatment of HIV-1.
The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for tenofovir disoproxil fumarate and any potential adverse effects on the breastfed infant from tenofovir disoproxil fumarate or from the underlying maternal condition.
In a study of 50 HIV-uninfected, breastfeeding women on a tenofovir-containing regimen initiated between 1 and 24 weeks postpartum (median 13 weeks), tenofovir was undetectable in the plasma of most infants after 7 days of treatment in mothers. There were no serious adverse events in mothers or infants.