Tenofovir Disoproxil Fumarate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Powder, Oral, as disoproxil fumarate:

Viread: 40 mg/g (60 g)

Tablet, Oral, as disoproxil fumarate:

Viread: 150 mg, 200 mg, 250 mg

Viread: 300 mg [contains fd&c blue #2 aluminum lake]

Generic: 300 mg

Pharmacology

Mechanism of Action

Tenofovir disoproxil fumarate (TDF), a nucleotide reverse transcriptase inhibitor, is an analog of adenosine 5'-monophosphate; it interferes with the HIV viral RNA dependent DNA polymerase resulting in inhibition of viral replication. TDF is first converted intracellularly by hydrolysis to tenofovir and subsequently phosphorylated to the active tenofovir diphosphate. Tenofovir inhibits replication of HBV by inhibiting HBV polymerase.

Pharmacokinetics/Pharmacodynamics

Distribution

V_d: 1.2 to 1.3 L/kg

Metabolism

Tenofovir disoproxil fumarate (TDF) is converted intracellularly by hydrolysis (by non-CYP enzymes) to tenofovir, then phosphorylated to the active tenofovir diphosphate

Excretion

Urine (70% to 80%) via filtration and active secretion, primarily as unchanged tenofovir within 72 hours; after multiple oral doses (administered with food): 32% ± 10% is excreted in the urine within 24 hours

Clearance: Total body clearance is decreased in patients with renal impairment

Time to Peak

Serum: Fasting: 36 to 84 minutes; With high-fat meal: 96 to 144 minutes

Half-Life Elimination

Serum: 17 hours; intracellular: 10 to 50 hours

Protein Binding

<7% to serum proteins

Use in Specific Populations

Special Populations: Renal Function Impairment

In patients with CrCl <50 mL/minute or with ESRD requiring dialysis, C_max and AUC of tenofovir were increased.

Use: Labeled Indications

Chronic hepatitis B: Treatment of chronic hepatitis B virus (HBV) in patients ≥2 years of age weighing ≥10 kg

HIV-1 infection, treatment: Treatment of HIV-1 infection in patients ≥2 years of age weighing ≥10 kg, in combination with other antiretroviral agents.

Use: Off Label

HIV-1 nonoccupational postexposure prophylaxisyes

Based on the Centers for Disease Control and Prevention, US Department of Health and Human Services updated guidelines for antiretroviral postexposure prophylaxis after sexual, injection drug use, or other nonoccupational exposure to HIV, tenofovir is effective and recommended (in conjunction with other antiretrovirals) as postexposure prophylaxis of HIV-1 infection following nonoccupational exposure (nPEP) in individuals exposed to blood, genital secretions, or other potentially infectious body fluids that may contain HIV when that exposure represents a substantial risk for HIV transmission.

HIV-1 occupational postexposure prophylaxisyes

Based on the US Public Health Service updated guidelines for the management of occupational exposures to human immunodeficiency virus and recommendations for postexposure prophylaxis, tenofovir (in combination with emtricitabine and raltegravir) is effective and recommended for postexposure prophylaxis of HIV-1 infection in health care personnel following occupational exposure (oPEP) to blood and/or other body fluids that may contain HIV.

Contraindications

There are no contraindications listed in the manufacturer's US labeling.

Canadian labeling: Additional contraindications (not in the US labeling): Hypersensitivity to tenofovir or any component of the formulation

Dosage and Administration

Dosing: Adult

Hepatitis B infection: Oral: 300 mg once daily

Note: Concurrent use with adefovir and/or tenofovir combination products should be avoided.

Treatment duration (AASLD practice guidelines): Treatment duration for nucleos(t)ide analog-based therapy (eg, tenofovir) is variable and influenced by HBeAg status, duration of HBV suppression, and presence of cirrhosis/decompensation (AASLD [Terrault 2016]):

Patients without cirrhosis:

Hepatitis B e antigen (HBeAg) positive immune-active chronic hepatitis: Treat until HBeAg seroconversion; after seroconversion, prolonged duration of therapy is often required in patients treated with nucleos(t)ide analogues,. Optimal duration is unknown; however, consolidation therapy is generally a minimum of 12 months of persistently normal ALT and undetectable serum HBV DNA levels after HBeAg seroconversion

HBeAg-negative immune-active chronic hepatitis: Indefinite antiviral therapy is suggested unless there is competing rationale for discontinuation (risk/benefit decision); treatment discontinuation may be considered in patients with loss of HBsAg; however, there is insufficient evidence to guide decisions in these patients.

Patients with cirrhosis:

HBeAg-positive immune-active chronic hepatitis: In patients who seroconvert on therapy, continue antiviral therapy indefinitely due to concerns with decompensation and death, unless there is a strong competing rationale for discontinuation.

HBeAg-negative immune-active chronic hepatitis: Treatment discontinuation is not recommended due to potential for decompensation and death (limited data).

HIV-1 infection, treatment: Oral: 300 mg once daily (in combination with other antiretrovirals). Note: Tenofovir is a component of recommended initial regimens in treatment-naive patients (when coadministered with emtricitabine plus dolutegravir or with emtricitabine plus raltegravir; lamivudine may be substituted for emtricitabine in either of these regimens) (HHS [adult] 2018).

HIV-1 nonoccupational postexposure prophylaxis (nPEP) (off-label use): Oral: 300 mg once daily for 28 days (in combination with other antiretroviral agents). Initiate therapy within 72 hours of exposure. Note: The fixed dose emtricitabine and tenofovir disoproxil fumarate combination product is recommended for these components of the 3-drug regimen (HHS [nPEP] 2016)

HIV-1 occupational postexposure, prophylaxis (oPEP) (off-label use): Oral: 300 mg once daily in combination with emtricitabine and raltegravir; initiate therapy as soon as possible after occupational exposure (and within 72 hours) and continue for 4 weeks. Note: The fixed dose emtricitabine and tenofovir disoproxil fumarate combination product is recommended for these components of the 3-drug regimen (Kuhar 2013)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

HIV-1 infection, treatment: Note: Gene mutation and antiretroviral (ARV) resistance patterns should be evaluated (refer to https://www.iasusa.org/ for more information) when necessary.

Weight-directed dosing: Children ≥2 years weighing ≥10 kg and Adolescents: Oral: 8 mg/kg/dose once daily; maximum daily dose: 300 mg/day

Dosage form specific fixed dosing:

Oral powder: Children ≥2 years weighing ≥10 kg and Adolescents: Oral:

Note: Only measure with the provided scoop. One level scoop = 40 mg tenofovir disoproxil fumarate

10 to <12 kg: 80 mg (2 scoops) once daily

12 to <14 kg: 100 mg (2.5 scoops) once daily

14 to <17 kg: 120 mg (3 scoops) once daily

17 to <19 kg: 140 mg (3.5 scoops) once daily

19 to <22 kg: 160 mg (4 scoops) once daily

22 to <24 kg: 180 mg (4.5 scoops) once daily

24 to <27 kg: 200 mg (5 scoops) once daily

27 to <29 kg: 220 mg (5.5 scoops) once daily

29 to <32 kg: 240 mg (6 scoops) once daily

32 to <34 kg: 260 mg (6.5 scoops) once daily

34 to <35 kg: 280 mg (7 scoops) once daily

≥35 kg: 300 mg (7.5 scoops) once daily

Oral tablets: Children ≥2 years weighing ≥17 kg and Adolescents: Oral:

17 to <22 kg: 150 mg once daily

22 to <28 kg: 200 mg once daily

28 to <35 kg: 250 mg once daily

≥35 kg: 300 mg once daily

HIV-1 nonoccupational postexposure prophylaxis (nPEP) (HHS [nPEP] 2016):

Children ≥2 years: Oral: Age- and weight-appropriate dosing (see HIV-1 infection, treatment above) for 28 days in combination with other antiretroviral agents. Initiate therapy within 72 hours of exposure.

Adolescents: The combination product is recommended (see Emtricitabine and Tenofovir Disoproxil Fumarate monograph)

Hepatitis B infection, chronic: Children ≥2 years weighing ≥10 kg and Adolescents: Oral: 8 mg/kg/dose once daily; maximum daily dose: 300 mg/day; see HIV treatment dosing for product-specific dosing. In trials, oral antivirals were continued for 1 to 4 years; Hepatitis B e antigen (HBeAg) seroconversion has been suggested as a therapeutic endpoint followed by an additional 12 months of consolidation (AASLD [Terrault 2016]).

Administration

Tablets may be administered without regard to meals. Powder should be mixed with 2 to 4 ounces of soft food (applesauce, baby food, yogurt) and swallowed immediately (avoids bitter taste); do not mix in liquid (powder may float on top of the liquid even after stirring). Measure powder using only the supplied dosing scoop.

Dietary Considerations

Consider calcium and vitamin D supplementation.

Storage

Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Dispense only in original container.

Drug Interactions

Acyclovir-Valacyclovir: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Acyclovir-Valacyclovir. Monitor therapy

Adefovir: May diminish the therapeutic effect of Tenofovir Products. Adefovir may increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Adefovir. Avoid combination

Aminoglycosides: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Aminoglycosides. Monitor therapy

Atazanavir: Tenofovir Disoproxil Fumarate may decrease the serum concentration of Atazanavir. Atazanavir may increase the serum concentration of Tenofovir Disoproxil Fumarate. Management: Must use boosted atazanavir in adults; give combo (atazanavir/ritonavir or atazanavir/cobicistat with tenofovir) as a single daily dose with food. Pediatric patients, pregnant patients, and users of H2-blockers require other dose changes. Consider therapy modification

Cabozantinib: MRP2 Inhibitors may increase the serum concentration of Cabozantinib. Monitor therapy

Cidofovir: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Cidofovir. Monitor therapy

Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Avoid combination

Cobicistat: May enhance the adverse/toxic effect of Tenofovir Products. More specifically, cobicistat may impair proper tenofovir monitoring and dosing. Monitor therapy

Darunavir: Tenofovir Disoproxil Fumarate may increase the serum concentration of Darunavir. Darunavir may increase the serum concentration of Tenofovir Disoproxil Fumarate. Monitor therapy

Diclofenac (Systemic): May enhance the nephrotoxic effect of Tenofovir Products. Management: Seek alternatives to this combination whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose. Consider therapy modification

Didanosine: Tenofovir Disoproxil Fumarate may diminish the therapeutic effect of Didanosine. Tenofovir Disoproxil Fumarate may increase the serum concentration of Didanosine. Management: Avoid concomitant treatment with tenofovir disoproxil fumarate and didanosine. Consider altering even existing, stable treatment to avoid this combination. Avoid combination

Ganciclovir-Valganciclovir: Tenofovir Products may increase the serum concentration of Ganciclovir-Valganciclovir. Ganciclovir-Valganciclovir may increase the serum concentration of Tenofovir Products. Monitor therapy

Ledipasvir: May increase the serum concentration of Tenofovir Disoproxil Fumarate. Management: Avoidance of this combination is recommended under some circumstances. Refer to full monograph for details. Consider therapy modification

Lopinavir: May enhance the nephrotoxic effect of Tenofovir Disoproxil Fumarate. Lopinavir may increase the serum concentration of Tenofovir Disoproxil Fumarate. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May enhance the nephrotoxic effect of Tenofovir Products. Management: Seek alternatives to these combinations whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose. Consider therapy modification

Orlistat: May decrease the serum concentration of Antiretroviral Agents. Monitor therapy

Simeprevir: Tenofovir Disoproxil Fumarate may decrease the serum concentration of Simeprevir. Simeprevir may increase the serum concentration of Tenofovir Disoproxil Fumarate. Monitor therapy

Tipranavir: Tenofovir Disoproxil Fumarate may decrease the serum concentration of Tipranavir. Tipranavir may decrease the serum concentration of Tenofovir Disoproxil Fumarate. Monitor therapy

Velpatasvir: May increase the serum concentration of Tenofovir Disoproxil Fumarate. Monitor therapy

Voxilaprevir: Tenofovir Disoproxil Fumarate may increase the serum concentration of Voxilaprevir. Voxilaprevir may increase the serum concentration of Tenofovir Disoproxil Fumarate. Monitor therapy

Adverse Reactions

Includes data from both treatment-naive and treatment-experienced HIV patients and in chronic hepatitis B.

>10%:

Central nervous system: Insomnia (3% to 18%), headache (5% to 14%), pain (12% to 13%), dizziness (8% to 13%), depression (4% to 11%)

Dermatologic: Skin rash (includes maculopapular, pustular, or vesiculobullous rash; pruritus; or urticaria: 5% to 18%), pruritus (16%)

Endocrine & metabolic: Hypercholesterolemia (19% to 22%), increased serum triglycerides (1% to 4%)

Gastrointestinal: Abdominal pain (4% to 22%), nausea (8% to 20%), diarrhea (9% to 16%), vomiting (2% to 13%)

Neuromuscular & skeletal: Decreased bone mineral density (28%; ≥5% at spine or ≥7% at hip), increased creatine phosphokinase (2% to 12%), weakness (6% to 11%)

Miscellaneous: Fever (4% to 11%)

1% to 10%:

Cardiovascular: Chest pain (3%)

Central nervous system: Fatigue (9%), anxiety (6%), peripheral neuropathy (1% to 5%)

Dermatologic: Diaphoresis (3%)

Endocrine & metabolic: Weight loss (2% to 4%), glycosuria (grades 3/4: ≤3%), hyperglycemia (grades 3/4: 2% to 3%), lipodystrophy (1%)

Gastrointestinal: Increased serum amylase (grades 3/4: 4% to 9%), anorexia (3% to 4%), dyspepsia (3% to 4%), flatulence (3% to 4%)

Genitourinary: Hematuria (≤ grades 3/4: 3% to 7%)

Hematologic & oncologic: Neutropenia (3%)

Hepatic: Increased serum ALT (2% to 10%), increased serum AST (3% to 5%), increased serum transaminases (2% to 5%), increased serum alkaline phosphatase (1%)

Neuromuscular & skeletal: Back pain (4% to 9%), arthralgia (5%), myalgia (4%)

Renal: Increased serum creatinine (9%), renal failure (7%)

Respiratory: Sinusitis (8%), upper respiratory tract infection (8%), nasopharyngitis (5%), pneumonia (2% to 5%)

Postmarketing and/or case reports: Angioedema, dyspnea, exacerbation of hepatitis B (following discontinuation), Fanconi's syndrome, hepatitis, hypersensitivity reaction, hypokalemia, hypophosphatemia, immune reconstitution syndrome, increased gamma-glutamyl transferase, interstitial nephritis, lactic acidosis, myasthenia, myopathy, nephrogenic diabetes insipidus, nephrotoxicity, osteomalacia, pancreatitis, polyuria, proteinuria, proximal tubular nephropathy, renal insufficiency, renal tubular necrosis, rhabdomyolysis, severe hepatomegaly with steatosis

Warnings/Precautions

Concerns related to adverse effects:

• Decreased bone mineral density: In clinical trials, use has been associated with decreases in bone mineral density in HIV-1 infected adults and increases in bone metabolism markers. Serum parathyroid hormone and 1,25 vitamin D levels were also higher. Decreases in bone mineral density have also been observed in clinical trials of HIV-1 infected pediatric patients. Observations in chronic hepatitis B infected pediatric patients were similar. In all pediatric clinical trials, skeletal growth (height) appears unaffected. Effects on long-term bone health and future fracture risk in adult and pediatric patients, including long-term effects on skeletal growth in pediatric patients and effects of extended duration in younger children, is unknown. Consider monitoring of bone density in adult and pediatric patients with a history of pathologic fractures or with other risk factors for bone loss or osteoporosis. Consider calcium and vitamin D supplementation for all patients; effect of supplementation has not been studied but may be beneficial. If abnormalities are suspected, expert assessment is recommended.
• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves’ disease, polymyositis, Guillain-Barré syndrome) later in therapy; further evaluation and treatment may be required.
• Lactic acidosis/hepatomegaly: Lactic acidosis and severe hepatomegaly with steatosis, sometimes fatal, have been reported with the use of nucleoside analogs, alone or in combination with other antiretrovirals. Suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (marked transaminase elevation may/may not accompany hepatomegaly and steatosis).
• Osteomalacia and renal dysfunction: May cause osteomalacia with proximal renal tubulopathy. Bone pain, extremity pain, fractures, arthralgias, weakness and muscle pain have been reported. In patients at risk for renal dysfunction, persistent or worsening bone or muscle symptoms should be evaluated for hypophosphatemia and osteomalacia.
• Renal toxicity: May cause renal toxicity (acute renal failure and/or Fanconi syndrome); avoid use with concurrent or recent nephrotoxic therapy (including high dose or multiple NSAID use). Acute renal failure has occurred in HIV-infected patients with risk factors for renal impairment who were on a stable tenofovir regimen to which a high dose or multiple NSAID therapy was added. Consider alternatives to NSAIDS in patients taking tenofovir disoproxil fumarate and at risk for renal impairment. Assess serum creatinine, estimated creatinine clearance (CrCl), urine protein, and urine glucose prior to initiation of therapy and during therapy; in patients with chronic kidney disease, also assess serum phosphorus. Dosage adjustment required in patients with CrCl <50 mL/minute. IDSA guidelines recommend discontinuing tenofovir (and substituting with alternative antiretroviral therapy) in HIV-infected patients who develop a decline in GFR (a >25% decrease in GFR from baseline and to a level of <60 mL/minute/1.73 m²) during use, particularly in presence of proximal tubular dysfunction (eg, euglycemic glycosuria, increased urinary phosphorus excretion and hypophosphatemia, proteinuria [new onset or worsening]) (IDSA [Lucas 2014]).

Disease-related concerns:

• Chronic hepatitis B: [US Boxed Warning]: Severe, acute exacerbation of hepatitis B may occur upon discontinuation. Monitor hepatic function several months after discontinuing treatment; reinitiation of antihepatitis B therapy may be required. Posttreatment hepatitis B exacerbation may lead to hepatic decompensation and hepatic failure, especially in patients with advanced hepatic disease or cirrhosis. Treatment of HBV in patients with unrecognized/untreated HIV may lead to HIV resistance; patients should be tested for presence of HIV infection prior to initiating therapy
• Hepatic impairment: Use with caution in patients with hepatic impairment. Limited data supporting treatment of chronic hepatitis B in patients with decompensated liver disease; observe for increased adverse reactions, including renal dysfunction.
• Renal impairment: Use with caution in patients with renal impairment (CrCl <50 mL/minute); dosage adjustment required. IDSA guidelines recommend avoiding tenofovir in HIV patients with preexisting kidney disease (CrCl <50 mL/minute and not on hemodialysis or GFR <60 mL/minute/1.73 m²) when other effective HIV treatment options exist because data suggest risk of chronic kidney disease (CKD) is increased (IDSA [Lucas 2014]).

Concurrent drug therapy issues:

• Concomitant therapy: Do not use in combination with other tenofovir disoproxil fumarate or tenofovir alafenamide products, or with adefovir.
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Appropriate use: Hepatitis B coinfection: In patients coinfected with HIV and HBV, an appropriate antiretroviral combination should be selected due to HIV resistance potential; these patients should receive tenofovir dosed for HIV therapy.

Monitoring Parameters

Manufacturer’s labeling:

Patients with HIV: CBC with differential, reticulocyte count, creatine kinase, CD4 count, HIV RNA plasma levels, serum phosphorus (baseline and as clinically indicated in patients with chronic kidney disease); serum creatinine, urine glucose, urine protein (baseline and as clinically indicated during therapy); hepatic function tests; bone density (patients with a history of bone fracture or have risk factors for bone loss); testing for HBV is recommended prior to the initiation of antiretroviral therapy; weight (children).

Patients with HBV: HIV status (prior to initiation of therapy); serum phosphorus (baseline and as clinically indicated in patients with chronic kidney disease); serum creatinine, urine glucose, urine protein (baseline and as clinically indicated during therapy); bone density (patients with a history of bone fracture or have risk factors for bone loss); LFTs every 3 months during therapy and for several months following discontinuation of tenofovir; signs/symptoms of HBV relapse/exacerbation following discontinuation of therapy.

Patients with HIV and HBV coinfection should be monitored for several months following tenofovir discontinuation.

Alternate recommendations: Patients with chronic hepatitis B: HBV DNA and ALT (HBV DNA usually done every 3 months until undetectable and then every 3 to 6 months thereafter); HBeAg; anti-HBe (in patients who are HBeAg-positive to monitor for seroconversion); HBsAg; creatinine clearance (baseline); if at risk for renal impairment, creatinine clearance, serum phosphate, urine glucose, and urine protein at baseline and at least annually; in patients with a history of fracture or risks for osteopenia, consider a bone density study (baseline and during treatment); consider lactic acid levels if clinical concern for lactic acidosis; following discontinuation, monitor for recurrent viremia, ALT flares, seroreversion, and clinical decompensation every 3 months for at least 1 year (AASLD [Terrault 2016). As antivirals do not eliminate the risk of hepatocellular carcinoma, continued monitoring for this complication is recommended in at-risk patients.

Pregnancy

Pregnancy Considerations

Tenofovir has a high level of transfer across the human placenta following maternal use of tenofovir disoproxil fumarate.

No increased risk of overall birth defects has been observed following first trimester exposure according to data collected by the antiretroviral pregnancy registry. Maternal antiretroviral therapy (ART) may be associated with adverse pregnancy outcomes, including preterm delivery, stillbirth, low birth weight, and small-for-gestational-age infants. Actual risks may be influenced by maternal factors such as disease severity, gestational age at initiation of therapy, and specific ART regimen; therefore, close fetal monitoring is recommended. Because there is clear benefit to appropriate treatment, maternal ART should not be withheld due to concerns for adverse neonatal outcomes. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children without HIV but who were exposed to ART in utero and develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential mitochondrial dysfunction. Cases of lactic acidosis and hepatic steatosis have been reported in pregnant women with use of nucleoside reverse transcriptase inhibitors (NRTIs).

The Health and Human Services (HHS) perinatal HIV guidelines consider tenofovir disoproxil fumarate a preferred NRTI for pregnant females living with HIV who are antiretroviral naive, who have had ART therapy in the past but are restarting, who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen), and who are not yet pregnant but are trying to conceive. In addition, females who become pregnant while taking tenofovir disoproxil fumarate may continue if viral suppression is effective and the regimen is well tolerated. Maternal exposure is modestly decreased during the third trimester; dose adjustments are not needed.

The HHS perinatal HIV guidelines consider tenofovir disoproxil fumarate in combination with emtricitabine or lamivudine to be preferred dual NRTI backbone for initial therapy in antiretroviral-naive pregnant females. The guidelines also consider tenofovir disoproxil fumarate plus emtricitabine or lamivudine as recommended dual NRTI backbone for HIV/hepatitis B virus coinfected pregnant females. Hepatitis B flare may occur if tenofovir disoproxil fumarate is discontinued. Tenofovir disoproxil fumarate is also a preferred component of a regimen when acute HIV infection is detected during pregnancy.

In general, ART is recommended for all pregnant females living with HIV to keep the viral load below the limit of detection and reduce the risk of perinatal transmission. Therapy should be individualized following a discussion of the potential risks and benefits of treatment during pregnancy. Monitoring of pregnant females is more frequent than in nonpregnant adults. ART should be continued postpartum for all females living with HIV and can be modified after delivery.

Tenofovir disoproxil fumarate is one of the agents recommended for pre-exposure prophylaxis in couples with differing HIV status who are planning a pregnancy. The partner without HIV should begin therapy 1 month prior to attempting conception and continue therapy for 1 month after attempting conception (HHS [perinatal] 2019).

In hepatitis B-infected women (not coinfected with HIV), the American Association for the Study of Liver Disease (AASLD) chronic hepatitis B treatment guidelines suggest antiviral therapy to reduce the risk of perinatal transmission of hepatitis B in HBsAg-positive pregnant women with an HBV DNA >200,000 units/mL. There are limited data on the level of HBV DNA for when antiviral therapy is routinely recommended (>200,000 units/mL is a conservative recommendation); however, the AASLD recommends against antiviral therapy to reduce the risk of perinatal transmission in HBsAg-positive pregnant women with an HBV DNA ≤200,000 units/mL. Tenofovir is one of the antivirals that has been studied in pregnant women (and may be the preferred agent); with most studies initiating antiviral therapy at 28 to 32 weeks' gestation and discontinuing antiviral therapy between birth to 3 months postpartum (monitor for ALT flares every 3 months for 6 months following discontinuation). There are insufficient long-term safety data in infants born to mothers who took antiviral agents during pregnancy (AASLD [Terrault 2016]). The safety profile of tenofovir disoproxil fumarate, when administered during the third trimester to females with chronic hepatitis B infection, is similar to nonpregnant adults.

Health care providers are encouraged to enroll pregnant females exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or http://www.APRegistry.com). Health care providers caring for pregnant females living with HIV and their infants may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation (HHS [perinatal] 2019).

Patient Education

What is this drug used for?

• It is used to treat HIV infection.
• It is used to treat hepatitis B infection.

Frequently reported side effects of this drug

• Headache
• Dizziness
• Nausea
• Vomiting
• Diarrhea
• Pain
• Abdominal pain
• Trouble sleeping
• Anxiety
• Loss of strength and energy

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.
• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain.
• Lactic acidosis like fast breathing, fast heartbeat, abnormal heartbeat, vomiting, fatigue, shortness of breath, severe loss of strength and energy, severe dizziness, feeling cold, or muscle pain or cramps.
• Depression
• Bone pain
• Muscle pain
• Muscle weakness
• Painful extremities
• Burning or numbness feeling
• Infection
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.