Tenofovir Disoproxil Fumarate

Drug overview for TENOFOVIR DISOPROXIL FUMARATE (tenofovir disoproxil fumarate):

Generic name: tenofovir disoproxil fumarate (ten-OF-oh-vir)
Drug class: Antiviral-HIV(Antiretroviral) Nucleoside/-tide RT Inhibitors
Therapeutic class: Anti-Infective Agents

Tenofovir disoproxil fumarate (tenofovir DF), an antiretroviral agent, is a human immunodeficiency virus (HIV) nucleotide reverse transcriptase inhibitor that is active against HIV and hepatitis B virus (HBV).

No enhanced Uses information available for this drug.

DRUG IMAGES

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The following indications for TENOFOVIR DISOPROXIL FUMARATE (tenofovir disoproxil fumarate) have been approved by the FDA:

Indications:
Chronic hepatitis B
HIV infection

Professional Synonyms:
Chronic hepatitis B virus infection
Chronic hepatitis due to HBV
Human immunodeficiency virus disease
Human immunodeficiency virus infection

The following dosing information is available for TENOFOVIR DISOPROXIL FUMARATE (tenofovir disoproxil fumarate):

Dosing
Administration
TENOFOVIR DISOPROXIL FUMARATE
TENOFOVIR DISOPROXIL FUMARATE

Although tenofovir DF is a prodrug that requires metabolism for activation, dosage of the drug is expressed in terms of the prodrug diester (i.e., tenofovir DF).

Dosage of tenofovir DF oral powder containing 40 mg/g is expressed as the number of scoops of powder.

Single-entity tenofovir DF is commercially available as tablets or oral powder. Tenofovir DF tablet is administered orally once daily without regard to meals. Tenofovir DF oral powder is administered once daily.

Measure the appropriate dosage of the oral powder using only the scoop provided by the manufacturer. One level scoop delivers 1 g of powder, which contains 40 mg of tenofovir DF. Mix the required number of scoops of the powder with 2-4 ounces of soft food that can be swallowed without chewing (e.g., applesauce, baby food, yogurt), and ingest the entire mixture immediately to avoid a bitter taste.

Do not administer the oral powder in a liquid since the powder may float to the top of the liquid, even after stirring. Store tenofovir DF oral power and tablets at 25oC (excursions permitted to 15-30oC). Dispense in the original container, and keep the container tightly closed.

Dosing information for TENOFOVIR DISOPROXIL FUMARATE
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
TENOFOVIR DISOP FUM 300 MG TB	Maintenance	Adults take 1 tablet (300 mg) by oral route once daily with a meal

Generic dosing information for TENOFOVIR DISOPROXIL FUMARATE
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
TENOFOVIR DISOP FUM 300 MG TB	Maintenance	Adults take 1 tablet (300 mg) by oral route once daily with a meal

The following drug interaction information is available for TENOFOVIR DISOPROXIL FUMARATE (tenofovir disoproxil fumarate):

Contraindicated
Severe
Moderate

There are 3 contraindications. These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.

Drug Interaction	Drug Names
Selected Nephrotoxic Agents/Cidofovir SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Cidofovir is nephrotoxic. Concurrent administration of other nephrotoxic agents may result in additive or synergistic effects on renal function.(1-3) CLINICAL EFFECTS: Concurrent use of cidofovir with nephrotoxic agents such as adefovir, intravenous aminoglycosides, amphotericin B, foscarnet, intravenous pentamidine, tenofovir, vancomycin, voclosporin and non-steroidal anti-inflammatory agents may result in renal toxicity.(1-3) Other nephrotoxic agents include capreomycin, cisplatin, gallium nitrate, high-dose methotrexate, and streptozocin. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The Australian,(1) UK,(2) and US(3) manufacturers of cidofovir state that concurrent administration of potentially nephrotoxic agents such as adefovir, intravenous aminoglycosides, amphotericin B, foscarnet, intravenous pentamidine, tenofovir, vancomycin, voclosporin and non-steroidal anti-inflammatory agents may result in renal toxicity.(1-3) Other nephrotoxic agents include capreomycin, cisplatin, gallium nitrate, high-dose methotrexate, and streptozocin. These agents should be discontinued at least 7 days before the administration of cidofovir. DISCUSSION: The safety of cidofovir has not been studied in patients receiving other known potentially nephrotoxic agents. Renal impairment is the major toxicity of cidofovir.(1-3)	CIDOFOVIR
Adefovir/Tenofovir SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: The mechanism involves competition for active tubular secretion sites in the kidney.(1-4) CLINICAL EFFECTS: Concurrent use of adefovir and tenofovir in the treatment of hepatitis B may result in elevated levels of tenofovir or adefovir. PREDISPOSING FACTORS: Renal impairment or use of concurrent renally excreted drugs. PATIENT MANAGEMENT: The US manufacturer of adefovir(1) and the UK(2) and US(3) manufacturers of tenofovir state that adefovir and tenofovir should be not be administered together. DISCUSSION: Tenofovir is eliminated principally by renal tubular secretion and any competitive inhibition of excretion of tenofovir by adefovir increases the likelihood of increased serum concentrations of tenofovir and resultant toxicity.(1-4)	ADEFOVIR DIPIVOXIL, HEPSERA
Selected Nephrotoxic Agents/Bacitracin SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Bacitracin may cause renal failure due to glomerular and tubular necrosis. Concurrent administration of other nephrotoxic agents may result in additive renal toxicity.(1-3) CLINICAL EFFECTS: Concurrent use of bacitracin with other potentially nephrotoxic agents may result in renal toxicity.(1-3) PREDISPOSING FACTORS: Dehydration and high-dose bacitracin may predispose to adverse renal effects.(1) PATIENT MANAGEMENT: Health Canada states that bacitracin is contraindicated in patients with renal impairment, including those taking other nephrotoxic drugs.(1) The Canadian and US manufacturers of bacitracin state that concomitant use of bacitracin with other potentially nephrotoxic agents should be avoided.(2,3) DISCUSSION: Renal impairment is a major toxicity of bacitracin. Cases of nephrotoxicity have been reported when bacitracin was used off-label.(1-3)	BACITRACIN, BACITRACIN MICRONIZED, BACITRACIN ZINC

There are 8 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
Colistimethate/Selected Nephrotoxic Agents SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Colistimethate can cause nephrotoxicity.(1,2) Concurrent administration of other nephrotoxic agents may result in an increased risk of nephrotoxicity.(1) It is suspected that cephalothin interferes with the excretion of colistimethate resulting in enhanced nephrotoxicity.(2,3) CLINICAL EFFECTS: Concurrent use of colistimethate with other nephrotoxic agents may result in additive nephrotoxic effects. PREDISPOSING FACTORS: Factors predisposing to nephrotoxicity include higher cumulative doses of colistimethate, longer treatment duration, hypovolemia, and critical illness. PATIENT MANAGEMENT: Concurrent use of potentially nephrotoxic agents with colistimethate should be avoided.(1,2) If concurrent use is necessary, it should be undertaken with great caution.(1) DISCUSSION: In a case control study of 42 patients on intravenous colistimethate sodium, NSAIDs were identified as an independent risk factor for nephrotoxicity (OR 40.105, p=0.044).(4) In 4 case reports, patients developed elevated serum creatinine and blood urea nitrogen following concurrent colistimethate and cephalothin (3 patients) or when colistimethate followed cephalothin therapy (1 patient).(3) A literature review found that individual nephrotoxic agents, including aminoglycosides, vancomycin, amphotericin, IV contrast, diuretics, ACE inhibitors, ARBs, NSAIDs, and calcineurin inhibitors, were not consistently associated with additive nephrotoxicity when used with colistimethate. However, when multiple agents (at least 2 additional potential nephrotoxins) were used concurrently, there was a significant correlation to colistimethate nephrotoxicity.(5)	COLISTIMETHATE, COLISTIMETHATE SODIUM, COLY-MYCIN M PARENTERAL
Selected Nephrotoxic Agents/Foscarnet SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Foscarnet is nephrotoxic. Concurrent administration of other nephrotoxic agents may result in additive or synergistic effects on renal function.(1) Concurrent intravenous pentamidine may also result in hypocalcemia.(1) CLINICAL EFFECTS: Concurrent use of foscarnet with nephrotoxic agents such as acyclovir, adefovir, intravenous aminoglycosides, amphotericin B, cyclosporine, methotrexate, non-steroidal anti-inflammatory agents, intravenous pentamidine, tacrolimus, tenofovir, vancomycin and voclosporin may result in renal toxicity.(1) Other nephrotoxic agents include capreomycin, cisplatin, gallium nitrate, high-dose methotrexate, and streptozocin. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of foscarnet state that concurrent administration of potentially nephrotoxic agents such as acyclovir, intravenous aminoglycosides, amphotericin B, cyclosporine, methotrexate, tacrolimus, and intravenous pentamidine should be avoided.(1) Other nephrotoxic agents include adefovir, capreomycin, cisplatin, gallium nitrate, high-dose methotrexate, non-steroidal anti-inflammatory agents, streptozocin, tenofovir, vancomycin and voclosporin. If concurrent therapy is warranted, monitor renal function closely. In patients receiving concurrent foscarnet and pentamidine, also monitor serum calcium levels and instruct patients to report severe muscle spasms, mental/mood changes, and/or seizures.(1) DISCUSSION: The safety of foscarnet has not been studied in patients receiving other known potentially nephrotoxic agents. Renal impairment is the major toxicity of foscarnet.(1)	FOSCARNET SODIUM, FOSCAVIR
Cobicistat/Tenofovir disoproxil SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The exact mechanism is unknown. CLINICAL EFFECTS: Coadministration of cobicistat with tenofovir disoproxil increases the risk of new onset or worsening renal impairment including acute renal failure and Fanconi syndrome.(1-10) PREDISPOSING FACTORS: Patients with impaired baseline renal function or who are receiving concomitant nephrotoxic agents may have an increased risk of renal-related adverse events.(1-10) PATIENT MANAGEMENT: The Canadian, UK, and US manufacturers of atazanavir/cobicistat, cobicistat and darunavir/cobicistat do not recommend coadministration with tenofovir disoproxil fumarate (DF) in patents with a creatinine clearance (CrCl) below 70 ml/min or with concomitant or recent use of an additional nephrotoxic agent.(2-10) In patients receiving concurrent therapy, check glucose and urine protein at baseline and routinely monitor CrCl, urine glucose, urine protein, and serum phosphorus. Discontinue concurrent therapy if CrCl decreases below 70 ml/min.(2-10) DISCUSSION: Renal toxicity has been documented with coadministration of cobicistat with tenofovir disoproxil fumarate (DF) but not tenofovir alafenamide (AF). Monitoring of renal function is prudent and discontinuation is recommended when CrCl decreases below 70 ml/min to avoid renal impairment.(1-10)	EVOTAZ, PREZCOBIX, TYBOST
Orlistat/Selected Antiretrovirals SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The exact mechanism is unknown. Orlistat may reduce the absorption of lipophilic antiretroviral HIV drugs by retention in the gastrointestinal tract or reduced gastrointestinal tract transit time. CLINICAL EFFECTS: The concurrent administration of orlistat and atazanavir, efavirenz, emtricitabine, maraviroc, ritonavir, or tenofovir may result in a decrease in the levels and clinical effects of the antiretroviral, including loss of virological control.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: HIV RNA levels should be frequently monitored in patients taking orlistat while being treated for HIV infection. If there is a confirmed increase in HIV viral load, orlistat should be discontinued.(1) DISCUSSION: Loss of virological control has been reported in HIV-infected patients taking orlistat concomitantly with lipophilic antiretroviral drugs.(1) There are three case reports of patients having an increased HIV viral load after taking orlistat concomitantly with their HIV therapy.(2-4) Antiretrovirals included in this monograph are atazanavir, efavirenz, emtricitabine, maraviroc, ritonavir, and tenofovir.	ORLISTAT, XENICAL
Betibeglogene Autotemcel/Anti-Retrovirals; Hydroxyurea SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Betibeglogene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. Hydroxyurea may interfere with hematopoietic stem cell (HSC) mobilization of CD34+ cells.(1) CLINICAL EFFECTS: Use of hydroxyurea before mobilization may result in unsuccessful stem cell mobilization. Use of antiretrovirals before mobilization and apheresis may interfere with the production of betibeglogene autotemcel. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discontinue antiretrovirals and hydroxyurea for at least one month prior to mobilization and until all cycles of apheresis are completed. If a patient requires antiretrovirals for HIV prophylaxis, then confirm a negative HIV test before beginning mobilization and apheresis of CD34+ cells. DISCUSSION: Antiretroviral medications and hydroxyurea may interfere with the manufacturing of betibeglogene autotemcel therapy.(1)	ZYNTEGLO
Elivaldogene Autotemcel/Anti-Retrovirals SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Elivaldogene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. CLINICAL EFFECTS: Use of antiretrovirals before mobilization and apheresis may interfere with the production of elivaldogene autotemcel. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discontinue antiretrovirals for at least one month prior to mobilization and until all cycles of apheresis are completed. If a patient requires antiretrovirals for HIV prophylaxis, then confirm a negative HIV test before beginning mobilization and apheresis of CD34+ cells. DISCUSSION: Antiretroviral medications may interfere with the manufacturing of elivaldogene autotemcel therapy.(1)	SKYSONA
Lovotibeglogene Autotemcel/Anti-Retrovirals SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Lovotibeglogene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. CLINICAL EFFECTS: Use of antiretrovirals before mobilization and apheresis may interfere with the production of lovotibeglogene autotemcel.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discontinue antiretrovirals for at least one month prior to mobilization and until all cycles of apheresis are completed.(1) There are some long-acting antiretroviral medications that may require a longer duration of discontinuation for elimination of the medication. If a patient is taking anti-retrovirals for HIV prophylaxis, confirm a negative test for HIV before beginning mobilization and apheresis of CD34+ cells.(1) DISCUSSION: Antiretroviral medications may interfere with the manufacturing of lovotibeglogene autotemcel therapy.(1)	LYFGENIA
Atidarsagene Autotemcel/Anti-Retrovirals SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Atidarsagene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. CLINICAL EFFECTS: Use of antiretrovirals before mobilization and apheresis may interfere with the production of atidarsagene autotemcel. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discontinue antiretrovirals for at least one month prior to mobilization (or the expected duration of time needed for elimination of the medication) until all cycles of apheresis are completed. If a patient requires antiretrovirals for HIV prophylaxis, then confirm a negative HIV test before beginning mobilization and apheresis of CD34+ cells. DISCUSSION: Antiretroviral medications may interfere with the manufacturing of atidarsagene autotemcel therapy.(1)	LENMELDY

There are 3 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
Atazanavir/Tenofovir disoproxil SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Tenofovir disoproxil may induce the metabolism of atazanavir.(1) It is unknown how atazanavir increases tenofovir disoproxil levels.(2) CLINICAL EFFECTS: Concurrent use of atazanavir and tenofovir disoproxil without concurrent ritonavir or cobicistat may result in decreased levels and effectiveness of atazanavir.(1-3) Concurrent use of atazanavir may result in increased levels and toxicity from tenofovir disoproxil.(2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of atazanavir states that patients on concurrent tenofovir disoproxil 300 mg daily should receive atazanavir 300 mg and ritonavir 100 mg once daily all as a single daily dose with food. Treatment-experienced patients on both tenofovir disoproxil and a H-2 antagonist should have their atazanavir dose increased to 400 mg with ritonavir 100 mg daily. Treatment-experienced pregnant patients in the second or third trimester on concurrent tenofovir disoproxil should also have their atazanavir dose increased to 400 mg with ritonavir 100 mg daily.(1) Atazanavir should not be administered with tenofovir disoproxil without concurrent ritonavir in adults or pediatric patients of at least 13 years of age and weighing at least 40 kg.(1-3) There are no data to recommend a dose of atazanavir with tenofovir disoproxil in pediatric patients weighing less than 40 kg.(1) Patients receiving concurrent therapy should be monitored for tenofovir associated adverse events and tenofovir should be discontinued in patients who experience adverse events.(1-2) The combination product containing efavirenz/emtricitabine/tenofovir disoproxil is not recommended for use in patients receiving atazanavir.(4) No dosage adjustment is required with the use of tenofovir alafenamide.(5) DISCUSSION: In a study in healthy subjects, concurrent atazanavir (400 mg daily) with tenofovir disoproxil fumarate (300 mg daily) decreased atazanavir area-under-curve (AUC), maximum concentration (Cmax), and minimum concentration (Cmin) by 25%, 21%, and 40%, respectively. The AUC, Cmax, and Cmin of tenofovir increased by 24%, 14%, and 22%, respectively.(1,2) In another study, atazanavir AUC, Cmax, and Cmin decreased by 25%, 28%, and 23%, respectively, when atazanavir (300 mg daily), ritonavir (100 mg daily), and tenofovir disoproxil fumarate (300 mg daily) were coadministered, when compared to the administration of atazanavir and ritonavir alone. However, these decreased levels were approximately 2.3-fold and 4-fold higher that the respective values for atazanavir (400 mg daily) alone.(1,2) Interim data suggests that rate of moderate or severe adverse effects is similar between atazanavir-treated patients and unboosted atazanavir-treated patients.(1) In a study of 12 subjects, the AUC, Cmax and Cmin of tenofovir disoproxil fumarate (300 mg daily) increased 37%, 34% and 29% respectively, when given with atazanavir (300 mg daily) and ritonavir (100 mg daily).(1) Because both efavirenz and tenofovir disoproxil decrease atazanavir concentrations and the effect of taking both on atazanavir pharmacokinetics has not been studied, the use of atazanavir with the combination product efavirenz/emtricitabine/tenofovir disoproxil is not recommended.(4)	ATAZANAVIR SULFATE, REYATAZ
Tenofovir/Selected Nephrotoxic Agents SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Tenofovir and other nephrotoxic agents may result in additive or synergistic effects on renal function and increase nephrotoxicity risk.(1) CLINICAL EFFECTS: Concurrent use of tenofovir and other nephrotoxic agents may result in renal toxicity and acute renal failure.(1) Reports of acute renal failure and Fanconi syndrome have been reported with tenofovir use.(2,3) However, this has been reported in 3 case reports and the renal failure may have been complicated by other pre-existing conditions.(2) PREDISPOSING FACTORS: Pre-existing renal dysfunction, long duration of use, low body weight, concomitant use of drugs that may increase tenofovir levels may increase the risk of nephrotoxicity.(1) PATIENT MANAGEMENT: The US prescribing information for tenofovir recommends avoiding concurrent or recent use of a nephrotoxic agent.(3) Evaluate renal function prior to initiation of concurrent therapy and continue renal function monitoring during therapy. Dose adjustments may be required for impaired renal function. Tenofovir should be avoided with high-dose or multiple NSAIDs. Alternatives to NSAIDs should be considered in patients at risk for renal dysfunction.(3) Patients receiving concurrent NSAIDs with tenofovir should be monitored for possible renal toxicity.(1,2) The dosing interval should be adjusted in patients with a baseline creatinine clearance of less than 50 ml/min.(1-3) DISCUSSION: From March 18, 2003 to December 1, 2005, Health Canada received 10 reports of nephrotoxic reactions with tenofovir. Three of these occurred following the addition of a NSAID to tenofovir therapy. In the first report, a patient maintained on tenofovir for 29 months developed acute renal failure and acute tubular necrosis requiring dialysis 5 days after beginning indomethacin (100 mg rectally twice daily). In the second report, a patient maintained on tenofovir for 7 months developed acute renal failure and acute tubular necrosis after taking 90 tablets of naproxen (375 mg) over 2 months. The patient died. In the third report, a patient maintained on tenofovir for over a year developed acute renal failure and nephrotic syndrome after 2 months of valdecoxib (20 mg daily) therapy. Symptoms subsided following discontinuation of valdecoxib.(1)	ABELCET, ACYCLOVIR, ACYCLOVIR SODIUM, ACYCLOVIR SODIUM-0.9% NACL, AFINITOR, AFINITOR DISPERZ, AMBISOME, AMIKACIN SULFATE, AMPHOTERICIN B, AMPHOTERICIN B LIPOSOME, ANAPROX DS, ANJESO, ARTHROTEC 50, ARTHROTEC 75, ASTAGRAF XL, BROMFENAC SODIUM, BUPIVACAINE-KETOROLAC-KETAMINE, CALDOLOR, CELEBREX, CELECOXIB, CISPLATIN, COMBOGESIC, COMBOGESIC IV, CONSENSI, COXANTO, CYCLOSPORINE, CYCLOSPORINE MODIFIED, DAYPRO, DICLOFENAC, DICLOFENAC POTASSIUM, DICLOFENAC SODIUM, DICLOFENAC SODIUM ER, DICLOFENAC SODIUM MICRONIZED, DICLOFENAC SODIUM-MISOPROSTOL, EC-NAPROSYN, ELYXYB, ENVARSUS XR, ETODOLAC, ETODOLAC ER, EVEROLIMUS, FELDENE, FENOPROFEN CALCIUM, FENOPRON, FLURBIPROFEN, FYARRO, GANCICLOVIR SODIUM, GENGRAF, GENTAMICIN SULFATE, GENTAMICIN SULFATE IN NS, HYDROCODONE-IBUPROFEN, IBU, IBUPAK, IBUPROFEN, IBUPROFEN LYSINE, IBUPROFEN-FAMOTIDINE, INDOCIN, INDOMETHACIN, INDOMETHACIN ER, INFLAMMACIN, INFLATHERM(DICLOFENAC-MENTHOL), KANAMYCIN SULFATE, KEMOPLAT, KETOPROFEN, KETOPROFEN MICRONIZED, KETOROLAC TROMETHAMINE, KIPROFEN, LODINE, LOFENA, LUPKYNIS, MECLOFENAMATE SODIUM, MEFENAMIC ACID, MELOXICAM, METHOTREXATE, METHOTREXATE SODIUM, NABUMETONE, NABUMETONE MICRONIZED, NALFON, NAPRELAN, NAPROSYN, NAPROTIN, NAPROXEN, NAPROXEN SODIUM, NAPROXEN SODIUM CR, NAPROXEN SODIUM ER, NAPROXEN-ESOMEPRAZOLE MAG, NEOMYCIN SULFATE, NEOPROFEN, NEORAL, OXAPROZIN, PENTAM 300, PENTAMIDINE ISETHIONATE, PHENYLBUTAZONE, PIROXICAM, PROGRAF, R.E.C.K.(ROPIV-EPI-CLON-KETOR), RELAFEN DS, ROPIVACAINE-CLONIDINE-KETOROLC, ROPIVACAINE-KETOROLAC-KETAMINE, SANDIMMUNE, SIROLIMUS, SPRIX, STREPTOMYCIN SULFATE, SULINDAC, SUMATRIPTAN SUCC-NAPROXEN SOD, SYMBRAVO, TACROLIMUS, TACROLIMUS XL, TEMSIROLIMUS, TOBRAMYCIN, TOBRAMYCIN SULFATE, TOLECTIN 600, TOLMETIN SODIUM, TORISEL, TORONOVA II SUIK, TORONOVA SUIK, TORPENZ, TOXICOLOGY SALIVA COLLECTION, TRESNI, TREXIMET, VALACYCLOVIR, VALACYCLOVIR HCL, VALCYTE, VALGANCICLOVIR HCL, VALTREX, VANCOMYCIN, VANCOMYCIN HCL, VANCOMYCIN HCL-0.9% NACL, VANCOMYCIN HCL-D5W, VIMOVO, VIVLODEX, XIFYRM, ZANOSAR, ZIPSOR, ZORTRESS, ZORVOLEX, ZOVIRAX, ZYNRELEF
Selected Nephrotoxic Agents/Immune Globulin IV (IGIV) SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Immune Globulin Intravenous (IGIV) products, particularly those containing sucrose, can cause renal dysfunction, acute renal failure, osmotic nephrosis, and/or death. Concurrent administration of other nephrotoxic agents may result in additive or synergistic effects on renal function.(1-4) CLINICAL EFFECTS: Concurrent use of Immune Globulin Intravenous (IGIV) products with nephrotoxic agents such as adefovir, intravenous aminoglycosides, amphotericin B, non-steroidal anti-inflammatory agents, tenofovir, and vancomycin may result in renal toxicity.(1-4) Other nephrotoxic agents include capreomycin, gallium nitrate, and streptozocin. PREDISPOSING FACTORS: Patients at risk of acute renal failure include those with any degree of pre-existing renal insufficiency, diabetes mellitus, advanced age (above 65 years of age), volume depletion, sepsis, paraproteinemia, or receiving known nephrotoxic drugs.(1-4) Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV products containing sucrose.(3-4) PATIENT MANAGEMENT: For patients at risk of renal dysfunction or renal failure, the US manufacturers of Immune Globulin Intravenous (IGIV) products recommends administration at the minimum dose and infusion rate practicable; ensure adequate hydration in patients before administration; and monitor renal function and urine output with assessment of blood urea nitrogen (BUN) and serum creatinine before initial infusion and at regular intervals during therapy.(1-3) Concurrent administration of potentially nephrotoxic agents should be avoided.(1) Review prescribing information for IGIV product to be administered for sucrose content. If concurrent therapy is warranted, monitor renal function closely. In high risk patients, consider selecting an IGIV product that does not contain sucrose. DISCUSSION: The safety of Immune Globulin Intravenous (IGIV) has not been studied in patients receiving other known potentially nephrotoxic agents. Renal impairment is a major toxicity of IGIV products.(1-3) A review of the FDA renal adverse events (RAEs) (i.e. acute renal failure or insufficiency) from June 1985 to November 1998 identified 120 reports worldwide associated with IGIV administration. In the US, the FDA received 88 reports of cases with clinical and/or laboratory findings consistent with RAE (i.e. increased serum creatinine, oliguria, and acute renal failure). Patient cases involved a median age of 60.5 years and 55% were male. Of the 54 patients who developed acute renal failure, 65% were greater than 65 years, 56% had diabetes, and 26% had prior renal insufficiency; 59% had one, 35% had two, and 6% had three of these conditions. Upon review of the IGIV product received, 90% of cases received sucrose-containing IGIV products with the remaining patients receiving either maltose- or glucose-containing products. Approximately 40% of affected patients required dialysis and RAE may have contributed to death in 15% of patients.(4)	ALYGLO, BIVIGAM, CUTAQUIG, CUVITRU, FLEBOGAMMA DIF, GAMMAGARD LIQUID, GAMMAGARD S-D, GAMMAKED, GAMMAPLEX, GAMUNEX-C, HIZENTRA, HYQVIA, HYQVIA IG COMPONENT, OCTAGAM, PANZYGA, PRIVIGEN, XEMBIFY

The following contraindication information is available for TENOFOVIR DISOPROXIL FUMARATE (tenofovir disoproxil fumarate):

Overview
Contraindicated
Severe
Moderate

Drug contraindication overview.

*None.

There are 1 contraindications. Absolute contraindication.

Contraindication List
Lactic acidosis

There are 8 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Acute renal failure
Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
Chronic kidney disease stage 5 (failure) GFr<15 ml/min
Fanconi syndrome
Hypophosphatemia
Osteomalacia
Pathological fracture

There are 2 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
Osteopenia

The following adverse reaction information is available for TENOFOVIR DISOPROXIL FUMARATE (tenofovir disoproxil fumarate):

Overview
Severe
Less Severe

Adverse reaction overview.

The most common adverse effects (incidence >=10%; grades 2-4) in HIV-infected patients receiving tenofovir DF are rash, diarrhea, headache, pain, depression, asthenia, and nausea. The most common adverse effect (all grades) in HBV-infected patients with compensated liver disease was nausea (9%). The most common adverse effects (incidence >=10%; all grades) in HBV-infected patients with decompensated liver disease were abdominal pain, nausea, vomiting, pruritus, insomnia, dizziness, and pyrexia. Adverse reactions in pediatric patients were consistent with those observed in adults.

There are 27 severe adverse reactions.

More Frequent	Less Frequent
Depression	Hypercholesterolemia Increased alanine transaminase Increased aspartate transaminase Osteopenia Pneumonia

Rare/Very Rare
Abnormal hepatic function tests Acute renal failure Angioedema Dyspnea Fanconi syndrome Graves' disease Guillain-barre syndrome Hepatitis Hypokalemia Hypophosphatemia Interstitial nephritis Kidney disease with reduction in glomerular filtration rate (GFr) Lactic acidosis Nephrogenic diabetes insipidus Osteomalacia Pancreatitis Peripheral neuropathy Polymyositis Renal tubular necrosis Rhabdomyolysis Steatosis of liver

Rare/Very Rare

Abnormal hepatic function tests
Acute renal failure
Angioedema
Dyspnea
Fanconi syndrome
Graves' disease
Guillain-barre syndrome
Hepatitis
Hypokalemia
Hypophosphatemia
Interstitial nephritis
Kidney disease with reduction in glomerular filtration rate (GFr)
Lactic acidosis
Nephrogenic diabetes insipidus
Osteomalacia
Pancreatitis
Peripheral neuropathy
Polymyositis
Renal tubular necrosis
Rhabdomyolysis
Steatosis of liver

There are 33 less severe adverse reactions.

More Frequent	Less Frequent
Acute abdominal pain Back pain Cough Diarrhea Dizziness Dyspepsia Fatigue Fever General weakness Headache disorder Insomnia Nausea Pain Pruritus of skin	Anorexia Arthralgia Chest pain Elevated serum amylase Elevated serum lipase Flatulence Myalgia Pharyngitis Polyuria Proteinuria Sinusitis Skin rash Vomiting Weight loss

Rare/Very Rare
Hyperhidrosis Hypertriglyceridemia Muscle weakness Myopathy Urticaria

The following precautions are available for TENOFOVIR DISOPROXIL FUMARATE (tenofovir disoproxil fumarate):

Pediatric
Pregnant
Lactation
Geriatric

Safety and efficacy of tenofovir DF for treatment of HIV-1 infection in pediatric patients 2 to <18 years of age are supported by data from 2 randomized controlled trials. Peak plasma concentrations and AUC of tenofovir in HIV-1-infected pediatric patients 2 to <18 years of age receiving 8 mg/kg of tenofovir DF (up to 300 mg) once daily as oral powder or receiving 300 mg once daily as tablets were similar to peak plasma concentrations and AUC reported in adults receiving 300 mg once daily. Safety and efficacy of tenofovir DF for treatment of HIV-1 infection have not been established in children <2 years of age weighing <10 kg.

In HBV-infected pediatric patients 12 to <18 years of age receiving tenofovir DF 300 mg once daily as tablets, and pediatric patients 2 to <12 years of age receiving 8 mg/kg of tenofovir DF (up to 300 mg) once daily as tablets or oral powder, tenofovir exposures were similar to those reported in HIV-1-infected adults receiving identical doses. Safety and efficacy of tenofovir DF for treatment of chronic HBV infection have not been established in children <2 years of age weighing <10 kg.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

The Antiretroviral Pregnancy Registry (APR) monitors pregnancy outcomes in women exposed to tenofovir DF during pregnancy. Clinicians are encouraged to register patients in the APR by calling 1-800-258-4263 or visiting https://www.apregistry.com/.

Based on prospective data from the APR, the prevalence of birth defects in live births was 2.3% and 2.1% following first and second/third trimester exposure, respectively, to tenofovir DF-containing regimens.

The overall risk of birth defects with first-trimester exposure for tenofovir DF was not markedly different compared to the background rate for major birth defects of 2.7% in the United States reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP). Limitations of using an external comparator (the MACDP) include differences in populations and methodology, and confounding due to the underlying disease.

The rate of miscarriage is not reported in the APR. Tenofovir crosses the human placenta. In published studies that included HBV-infected pregnant women treated with tenofovir DF, an increased risk of adverse pregnancy-related outcomes was not observed with use of tenofovir DF during the third trimester.

Two stillbirths were identified, and there was 1 major birth defect (talipes) and 1 occurrence of multiple congenital abnormalities (not further specified) in infants exposed to tenofovir DF. No clinically relevant drug-related safety findings were found in infants exposed to tenofovir DF during late gestation. Animal reproduction studies did not find any adverse developmental effects when tenofovir DF was administered at doses >=14 (tenofovir DF) and exposures 2.7 (tenofovir) times the recommended daily dose of tenofovir DF in humans.

Tenofovir is distributed into human milk in low concentrations. In a study of breast-feeding women (not infected with HIV) who were on a tenofovir-containing regimen started between 1-24 weeks postpartum, tenofovir was undetectable in the plasma of most infants after 7 days of treatment in mothers. No serious adverse events were reported in mothers or infants.

It is not known whether tenofovir DF affects human milk production or has effects on the breast-fed infant. The HHS perinatal HIV transmission guideline provides updated recommendations on infant feeding. The guideline states that patients with HIV should receive evidence-based, patient-centered counseling to support shared decision making about infant feeding.

During counseling, patients should be informed that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates the risk of postnatal HIV transmission to the infant. Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces the risk of breastfeeding HIV transmission to <1%, but does not completely eliminate the risk. Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery. If using tenofovir DF for the treatment of HBV infection, consider the developmental and health benefits of breast-feeding and the importance of tenofovir DF to the mother along with the potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.

Clinical studies did not include sufficient numbers of patients >=65 years of age to determine whether they respond differently to tenofovir DF than younger adults. Select dosage in geriatric patients with caution because of the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease or drug therapy. Pharmacokinetic studies have not been conducted in patients >=65 years of age.

The following icd codes are available for TENOFOVIR DISOPROXIL FUMARATE (tenofovir disoproxil fumarate)'s list of indications:

Chronic hepatitis B
B18.0	Chronic viral hepatitis B with delta-agent
B18.1	Chronic viral hepatitis B without delta-agent
HIV infection
B20	Human immunodeficiency virus [HIv] disease
B97.35	Human immunodeficiency virus, type 2 [HIV 2] as the cause of diseases classified elsewhere
O98.7	Human immunodeficiency virus [HIv] disease complicating pregnancy, childbirth and the puerperium
O98.71	Human immunodeficiency virus [HIv] disease complicating pregnancy
O98.711	Human immunodeficiency virus [HIv] disease complicating pregnancy, first trimester
O98.712	Human immunodeficiency virus [HIv] disease complicating pregnancy, second trimester
O98.713	Human immunodeficiency virus [HIv] disease complicating pregnancy, third trimester
O98.719	Human immunodeficiency virus [HIv] disease complicating pregnancy, unspecified trimester
O98.72	Human immunodeficiency virus [HIv] disease complicating childbirth
O98.73	Human immunodeficiency virus [HIv] disease complicating the puerperium
Z21	Asymptomatic human immunodeficiency virus [HIv] infection status