Amphotericin B Liposome

Drug overview for AMPHOTERICIN B LIPOSOME (amphotericin b liposome):

Generic name: AMPHOTERICIN B LIPOSOME (AM-foe-TER-i-sin/LIP-id)
Drug class: Antifungals-Systemic
Therapeutic class: Anti-Infective Agents

Amphotericin B, a macrocyclic polyene, is an antifungal agent.

Conventional IV amphotericin B (formulated with sodium desoxycholate) is used for the treatment of potentially life-threatening fungal infections including aspergillosis, blastomycosis, systemic candidiasis, coccidioidomycosis, cryptococcosis, histoplasmosis, paracoccidioidomycosis+, sporotrichosis, and zygomycosis. The drug also has been used IV for empiric antifungal therapy in febrile neutropenic patients+ or for prevention of fungal infections in other immunocompromised individuals+ (e.g., cancer patients, bone marrow or solid organ transplant recipients). In addition, conventional IV amphotericin B is used for the treatment of certain protozoal infections, including leishmaniasis and primary amebic meningoencephalitis caused by Naegleria fowleri+.

Conventional IV amphotericin B should be used principally in patients with progressive, potentially life-threatening fungal infections and should not be used to treat noninvasive fungal infections (e.g., oral thrush, vaginal candidiasis, esophageal candidiasis) in immunocompetent patients with normal neutrophil counts. When necessary, conventional amphotericin B has been administered intrathecally+ or intraventricularly+ (either alone or in conjunction with systemic antifungal therapy) for the treatment of CNS infections caused by susceptible fungi. Conventional amphotericin B also has been administered by bladder irrigation+ for the treatment of Candida cystitis, administered intraperitoneally+ for the treatment of fungal peritonitis, and given intrabronchially+ or by nebulization+ for the treatment or prophylaxis of pulmonary fungal infections.

Amphotericin B lipid complex (Abelcet(R)) is labeled for the treatment of invasive fungal infections in patients who are refractory to or intolerant of conventional IV amphotericin B. Amphotericin B liposomal (AmBisome(R)) is labeled for the treatment of infections caused by Aspergillus, Candida, or Cryptococcus that are refractory to conventional IV amphotericin B and for the treatment of these infections in patients who cannot receive conventional amphotericin B because of renal impairment or unacceptable toxicity. Amphotericin B liposomal also is labeled for the treatment of cryptococcal meningitis in patients with human immunodeficiency virus (HIV) infection, for empiric therapy of presumed fungal infections in febrile, neutropenic patients, and for the treatment of visceral leishmaniasis.

IV amphotericin B is considered a drug of choice for the treatment of many systemic infections caused by susceptible fungi, especially for initial treatment in patients with severe infections. Although clinical experience with lipid formulations of amphotericin B (amphotericin B lipid complex, amphotericin B liposomal) has been obtained principally from small, open-label studies and case reports, the lipid formulations of amphotericin B generally appear to be better tolerated (e.g., lower incidence of acute infusion reactions and adverse hematologic and renal effects) and may be preferred for some infections. Additional study is needed to determine the relative efficacy of these lipid formulations of amphotericin B compared with conventional IV amphotericin B for the treatment of severe, potentially life-threatening fungal infections.

DRUG IMAGES

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The following indications for AMPHOTERICIN B LIPOSOME (amphotericin b liposome) have been approved by the FDA:

Indications:
Candida peritonitis
Candidal meningitis
Candidal septicemia
Candidemia
Candidiasis
Cryptococcal meningitis
Cryptococcal septicemia
Cryptococcosis
Disseminated candidiasis
Febrile neutropenic patient presumed infection treatment
Fungal sepsis
Refractory aspergillosis
Visceral leishmaniasis

Professional Synonyms:
Assam fever
Black fever - visceral leishmaniasis
Black sickness
Burdwan fever
Busse-Buschke disease
Cachectic fever
Cachexial fever
Candida species peritonitis
Candida spp. peritonitis
Candidal infection
Candidal sepsis
Candidosis
Cryptococcal infection
Cryptococcal sepsis
Disseminated candidosis
Disseminated moniliasis
Dumdum fever
Empiric therapy in febrile neutropenia
Empiric therapy of infection in febrile neutrophilic leukocytopenia
Empiric therapy of infection in febrile neutrophilopenia
Fungal septicemia
Infection with Cryptococcus neoformans
Intractable aspergillosis
Kala-Azar
Meningeal Candidiasis
Meningeal Moniliasis
Moniliasis
Mycotic sepsis
Mycotic septicemia
Presumed infection in febrile neutropenic patient
Septic Candidiasis
Septic Moniliasis
Torulosis
Tropical splenomegaly

Dosing information for AMPHOTERICIN B LIPOSOME
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
AMPHOTERICIN B LIPOSOME 50 MG	Maintenance	Adults infuse 4 mg/kg over 60-120 minute(s) by intravenous route once daily

Generic dosing information for AMPHOTERICIN B LIPOSOME
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
AMPHOTERICIN B LIPOSOME 50 MG	Maintenance	Adults infuse 4 mg/kg over 60-120 minute(s) by intravenous route once daily

The following drug interaction information is available for AMPHOTERICIN B LIPOSOME (amphotericin b liposome):

Contraindicated
Severe
Moderate

There are 2 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
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

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

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 7 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
Digitalis Glycosides/Amphotericin B SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Amphotericin B may cause hypokalemia which can predispose patients to digitalis toxicity. CLINICAL EFFECTS: Possible potentiation of digitalis effects. Symptoms of digoxin toxicity can include anorexia, nausea, vomiting, headache, fatigue, malaise, drowsiness, generalized muscle weakness, disorientation, hallucinations, visual disturbances, and arrhythmias. PREDISPOSING FACTORS: Low body weight, advanced age, impaired renal function, hypokalemia, hypercalcemia, and/or hypomagnesemia may increase the risk of digoxin toxicity. PATIENT MANAGEMENT: Monitor potassium levels carefully in patients using these agents concomitantly. Correct potassium deficits promptly. DISCUSSION: Amphotericin B induced hypokalemia is a well known drug side effect.	DIGITEK, DIGOXIN, DIGOXIN MICRONIZED, LANOXIN, LANOXIN PEDIATRIC
Cyclosporine/Amphotericin B SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Additive nephrotoxicity is most likely mechanism. CLINICAL EFFECTS: May observe enhanced nephrotoxicity of one or both drugs. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Administer this combination cautiously. Monitoring of renal function is indicated. A decrease in cyclosporine dose will result in rapid reversal of cyclosporine-induced increases in creatinine. Holding the cyclosporine dose until serum levels are less than 150 ng/ml may reduce the likelihood of renal toxicity. DISCUSSION: Documentation is lacking; however, if an interaction occurs, the consequences could be severe.	CYCLOSPORINE, CYCLOSPORINE MODIFIED, GENGRAF, NEORAL, SANDIMMUNE
Amphotericin B/Corticosteroids; Corticotropin (ACTH) SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Corticosteroids and corticotropin may potentiate potassium excretion and overload salt and water retention.(1) CLINICAL EFFECTS: Concurrent use of amphotericin b with corticosteroids or corticotropin may potentiate amphotericin b-induced hypokalemia, thereby predisposing patients to cardiac dysfunction.(1-2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of amphotericin b states that concurrent use of corticosteroids or corticotropin should be avoided unless absolutely necessary to avoid side effects. If concurrent use is necessary, serum electrolytes and cardiac function must be monitored closely.(1) DISCUSSION: There are four case reports of cardiac enlargement, hypokalemia, and hypernatremia from concurrent use of amphotericin b and corticosteroids.(2)	ACTHAR, ACTHAR SELFJECT, ADRENOCORTICOTROPHIC HORMONE, AGAMREE, ALKINDI SPRINKLE, ANUCORT-HC, ANUSOL-HC, BECLOMETHASONE DIPROPIONATE, BETA 1, BETALOAN SUIK, BETAMETHASONE ACETATE MICRO, BETAMETHASONE ACETATE-SOD PHOS, BETAMETHASONE DIPROPIONATE, BETAMETHASONE SOD PHOS-ACETATE, BETAMETHASONE SOD PHOS-WATER, BETAMETHASONE SODIUM PHOSPHATE, BETAMETHASONE VALERATE, BSP 0820, BUDESONIDE, BUDESONIDE DR, BUDESONIDE EC, BUDESONIDE ER, BUDESONIDE MICRONIZED, BUPIVACAINE-DEXAMETH-EPINEPHRN, CELESTONE, CLOBETASOL PROPIONATE MICRO, CORTEF, CORTENEMA, CORTICOTROPHIN, CORTIFOAM, CORTISONE ACETATE, CORTROPHIN, DEFLAZACORT, DEPO-MEDROL, DESONIDE MICRONIZED, DESOXIMETASONE, DEXABLISS, DEXAMETHASONE, DEXAMETHASONE ACETATE, DEXAMETHASONE ACETATE MICRO, DEXAMETHASONE INTENSOL, DEXAMETHASONE ISONICOTINATE, DEXAMETHASONE MICRONIZED, DEXAMETHASONE SOD PHOS-WATER, DEXAMETHASONE SODIUM PHOSPHATE, DEXAMETHASONE-0.9% NACL, DMT SUIK, DOUBLEDEX, EMFLAZA, EOHILIA, FLUNISOLIDE, FLUOCINOLONE ACETONIDE, FLUOCINOLONE ACETONIDE MICRO, FLUOCINONIDE MICRONIZED, FLUTICASONE PROPIONATE, FLUTICASONE PROPIONATE MICRO, HEMADY, HEMMOREX-HC, HEXATRIONE, HYDROCORTISONE, HYDROCORTISONE ACETATE, HYDROCORTISONE SOD SUCCINATE, HYDROCORTISONE-PRAMOXINE, KENALOG-10, KENALOG-40, KENALOG-80, LIDOCIDEX-I, MAS CARE-PAK, MEDROL, MEDROLOAN II SUIK, MEDROLOAN SUIK, METHYLPREDNISOLONE, METHYLPREDNISOLONE AC MICRO, METHYLPREDNISOLONE ACETATE, METHYLPREDNISOLONE SODIUM SUCC, MILLIPRED, MILLIPRED DP, MOMETASONE FUROATE, ORAPRED ODT, ORTIKOS, PEDIAPRED, PREDNISOLONE, PREDNISOLONE ACETATE MICRONIZE, PREDNISOLONE MICRONIZED, PREDNISOLONE SODIUM PHOS ODT, PREDNISOLONE SODIUM PHOSPHATE, PREDNISONE, PREDNISONE INTENSOL, PREDNISONE MICRONIZED, PRO-C-DURE 5, PRO-C-DURE 6, PROCTOCORT, RAYOS, SOLU-CORTEF, SOLU-MEDROL, TAPERDEX, TARPEYO, TRIAMCINOLONE, TRIAMCINOLONE ACETONIDE, TRIAMCINOLONE DIACETATE, TRIAMCINOLONE DIACETATE MICRO, TRILOAN II SUIK, TRILOAN SUIK, UCERIS, VERIPRED 20, ZCORT, ZILRETTA
Deferiprone/Selected Myelosuppressive Agents SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis may increase the frequency or risk for severe toxicity.(1) CLINICAL EFFECTS: Concurrent use of deferiprone and myelosuppressive agents may result in severe neutropenia or agranulocytosis, which may be fatal. PREDISPOSING FACTORS: Agranulocytosis may be less common in patients receiving deferiprone for thalassemia, and more common in patients treated for other systemic iron overload conditions (e.g. myelodysplastic syndromes, sickle cell disease).(2,3) Inadequate monitoring appears to increase the risk for severe outcomes. Manufacturer post market surveillance found that in all fatal cases of agranulocytosis reported between 1999 and 2005, data on weekly white blood count (WBC) monitoring was missing. In three fatal cases, deferiprone was continued for two to seven days after the detection of neutropenia or agranulocytosis.(2) PATIENT MANAGEMENT: If possible, discontinue one of the drugs associated with risk for neutropenia or agranulocytosis. If alternative therapy is not available, documentation and adherence to the deferiprone monitoring protocol is essential. Baseline absolute neutrophil count (ANC) must be at least 1,500/uL prior to starting deferiprone. Monitor ANC weekly during therapy. If infection develops, interrupt deferiprone therapy and monitor ANC more frequently. If ANC is less than 1,500/uL but greater than 500/uL, discontinue deferiprone and any other drugs possibly associated with neutropenia. Initiate ANC and platelet counts daily until recovery (i.e. ANC at least 1,500/uL). If ANC is less than 500/uL, discontinue deferiprone, evaluate patient and hospitalize if appropriate. Do not resume deferiprone unless potential benefits outweigh potential risks.(1) DISCUSSION: Drugs linked to this monograph have an FDA Boxed Warning for risk of neutropenia, agranulocytosis, or pancytopenia, or have > 5% risk for neutropenia and/or warnings describing risk for myelosuppression in manufacturer prescribing information.(1-25) In pooled clinical studies submitted to the FDA, 6.1% of deferiprone patients met criteria for neutropenia and 1.7% of patients developed agranulocytosis.(1) The time to onset of agranulocytosis was highly variable with a range of 65 days to 9.2 years (median, 161 days).(3)	DEFERIPRONE, DEFERIPRONE (3 TIMES A DAY), FERRIPROX, FERRIPROX (2 TIMES A DAY), FERRIPROX (3 TIMES A DAY)
Clozapine/Selected Myelosuppressive Agents SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Clozapine and other myelosuppressive agents may be associated with neutropenia or agranulocytosis.(2) CLINICAL EFFECTS: Moderate neutropenia, even if due to combination therapy, may require abrupt discontinuation of clozapine resulting in decompensation of the patient's psychiatric disorder (e.g. schizophrenia). The disease treated by the myelosuppressive agent may be compromised if myelosuppression requires dose reduction, delay, or discontinuation of the myelosuppressive agent. Undetected severe neutropenia or agranulocytosis may be fatal. PREDISPOSING FACTORS: Low white blood counts prior to initiation of the myelosuppressive agent may increase risk for clinically significant neutropenia. PATIENT MANAGEMENT: If a patient stabilized on clozapine therapy requires treatment with a myelosuppressive agent, the clozapine prescriber should consult with prescriber of the myelosuppressive agent (e.g. oncologist) to discuss treatment and monitoring options.(2) More frequent ANC monitoring or treatment alternatives secondary to neutropenic episodes may need to be considered. Clozapine is only available through a restricted distribution system which requires documentation of the absolute neutrophil count (ANC) prior to dispensing.(1-2) For most clozapine patients, clozapine treatment must be interrupted for a suspected clozapine-induced ANC < 1000 cells/microliter. For patients with benign ethnic neutropenia (BEN), treatment must be interrupted for suspected clozapine-induced neutropenia < 500 cells/microliter.(2) DISCUSSION: Clozapine is only available through a restricted distribution system which requires documentation of the ANC prior to dispensing.(1) Agents linked to this interaction generally have > 5% risk for neutropenia and/or warnings describing risk for myelosuppression in manufacturer prescribing information.(3-26)	CLOZAPINE, CLOZAPINE ODT, CLOZARIL, VERSACLOZ
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
Sodium Iodide I 131/Myelosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Sodium iodide I 131 can cause depression of the hematopoetic system. Myelosuppressives and immunomodulators also suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of sodium iodide I 131 with agents that cause bone marrow depression, including myelosuppressives or immunomodulators, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of sodium iodide I 131 states that concurrent use with bone marrow depressants may enhance the depression of the hematopoetic system caused by large doses of sodium iodide I 131.(1) Sodium iodide I 131 causes a dose-dependent bone marrow suppression, including neutropenia or thrombocytopenia, in the 3 to 5 weeks following administration. Patients may be at increased risk of infections or bleeding during this time. Monitor complete blood counts within one month of therapy. If results indicate leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide I 131 activity.(1) DISCUSSION: Hematologic disorders including death have been reported with sodium iodide I 131. The most common hematologic disorders reported include anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia.(1)	HICON, SODIUM IODIDE I-131

There are 4 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
Gentamicin, Amikacin, Tobramycin/Amphotericin SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The ototoxic or nephrotoxic effects of gentamicin, amikacin, or tobramycin may be additive with those of amphotericin. CLINICAL EFFECTS: The concurrent administration of gentamicin, amikacin, or tobramycin with amphotericin may result in additive ototoxic or nephrotoxic effects.(1) PREDISPOSING FACTORS: Preexisting renal impairment, sepsis, extended duration of aminoglycoside therapy, greater than one aminoglycoside dose per day, or concomitant use of additional nephrotoxic agents such as iodinated contrast media or vancomycin appear to increase the risk for nephrotoxicity and ototoxicity.(1-6). Patients carrying certain variants in the MT-RNR1 gene (m.1555A>G, m.1095T>C, and m.1494C>T) are at increased risk of developing ototoxicity. An additional risk factor includes patients with a maternal relative known to have a clinically relevant MT-RNR1 variant. The risk of ototoxicity can occur at standard recommended doses of aminoglycosides.(7) PATIENT MANAGEMENT: The Australian manufacturer of gentamicin, amikacin, and tobramycin state that the concurrent use of gentamicin, amikacin, or tobramycin and amphotericin should be avoided.(1,4,5) DISCUSSION: The Australian and U.K. manufacturers of gentamicin, amikacin, and tobramycin state that since the ototoxic or nephrotoxic effects of gentamicin, amikacin, or tobramycin may be additive, avoid concurrent or sequential use of other neurotoxic and/or nephrotoxic agents including amphotericin.(1,3,4,5)	AMIKACIN SULFATE, ARIKAYCE, BETHKIS, GENTAMICIN SULFATE, GENTAMICIN SULFATE IN NS, KITABIS PAK, TOBI, TOBI PODHALER, TOBRAMYCIN, TOBRAMYCIN SULFATE
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)	BIKTARVY, CIMDUO, COMPLERA, DELSTRIGO, DESCOVY, EFAVIRENZ-EMTRIC-TENOFOV DISOP, EFAVIRENZ-LAMIVU-TENOFOV DISOP, EMTRICITABINE-TENOFOVIR DISOP, GENVOYA, ODEFSEY, STRIBILD, SYMFI, SYMFI LO, SYMTUZA, TENOFOVIR DISOPROXIL FUMARATE, TRUVADA, VEMLIDY, VIREAD
Selected Nephrotoxic Agents/Adefovir SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Recommended doses of adefovir have been associated with delayed nephrotoxicity.(1-4) Concurrent administration of other nephrotoxic agents may result in additive or synergistic effects on renal function.(1) CLINICAL EFFECTS: Concurrent use of adefovir with nephrotoxic agents such as intravenous aminoglycosides, amphotericin B, cyclosporine, tacrolimus,tenofovir, vancomycin, voclosporin and non-steroidal anti-inflammatory agents may result in renal toxicity.(1) Other nephrotoxic agents include capreomycin, cisplatin, gallium nitrate, high-dose methotrexate, intravenous pentamidine, and streptozocin. PREDISPOSING FACTORS: Patients with pre-existing renal impairment(1,2) or receiving multiple nephrotoxic agents appear to be at greater risk for nephrotoxicity. PATIENT MANAGEMENT: 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. Weigh the risks and benefits of concurrent therapy in patients with treatment-emergent nephrotoxicity. DISCUSSION: Because of the known risks for adefovir nephrotoxicity, particularly at higher than recommended doses, the safety of adefovir has not been studied in patients receiving other known potentially nephrotoxic agents.	ADEFOVIR DIPIVOXIL, HEPSERA
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

Severe List
Hypokalemia
Hypomagnesemia
Systemic mastocytosis

Moderate List
Kidney disease with reduction in glomerular filtration rate (GFr)

The following adverse reaction information is available for AMPHOTERICIN B LIPOSOME (amphotericin b liposome):

Overview
Severe
Less Severe

Adverse reaction overview.

No enhanced Common Adverse Effects information available for this drug.

There are 21 severe adverse reactions.

More Frequent	Less Frequent
Chills Dyspnea Fever Hypokalemia	Back pain Chest pain Hypertension Hypotension Increased alanine transaminase Increased aspartate transaminase Jaundice Skin rash Urine discoloration

Rare/Very Rare
Acute renal failure Agranulocytosis Anaphylaxis Angioedema Hemorrhagic cystitis Hypoventilation Pulmonary edema Rhabdomyolysis

There are 16 less severe adverse reactions.

More Frequent	Less Frequent
Acute abdominal pain Diarrhea Headache disorder Insomnia Nausea Vomiting	Acute cognitive impairment Cough Hematuria Peripheral edema

Rare/Very Rare
Abnormal vaginal bleeding Dysuria Erythema Kidney disease with reduction in glomerular filtration rate (GFr) Urinary incontinence Urticaria

The following precautions are available for AMPHOTERICIN B LIPOSOME (amphotericin b liposome):

Pediatric
Pregnant
Lactation
Geriatric

No enhanced Pediatric Use information available for this drug.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

Safe use of amphotericin B during pregnancy has not been established. Conventional IV amphotericin B has been used to treat systemic fungal infections or visceral leishmaniasis in a limited number of pregnant women without obvious adverse effects to the fetus. While reproduction studies in rats and rabbits using conventional amphotericin B, amphotericin B lipid complex, or amphotericin B liposomal have not revealed evidence of harm to the fetus, rabbits receiving amphotericin B liposomal dosages equivalent to 0.5-2

times the usual human dosage experienced a higher rate of spontaneous abortions than the control group. However, animal reproduction studies are not always predictive of human response. There are no adequate or controlled studies to date using any amphotericin B formulation in pregnant women, and these drugs should be used during pregnancy only when clearly needed.

It is not known whether amphotericin B is distributed into human milk. Because many drugs are distributed into human milk and because of the potential for serious adverse reactions to amphotericin B in nursing infants if it were distributed, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

No enhanced Geriatric Use information available for this drug.

The following icd codes are available for AMPHOTERICIN B LIPOSOME (amphotericin b liposome)'s list of indications:

Candida peritonitis
B37.89	Other sites of candidiasis
K65.0	Generalized (acute) peritonitis
T85.71	Infection and inflammatory reaction due to peritoneal dialysis catheter
T85.71xA	Infection and inflammatory reaction due to peritoneal dialysis catheter, initial encounter
Candidal meningitis
B37.5	Candidal meningitis
Candidal septicemia
B37.7	Candidal sepsis
Candidemia
B37.7	Candidal sepsis
Candidiasis
B37	Candidiasis
B37.0	Candidal stomatitis
B37.1	Pulmonary candidiasis
B37.2	Candidiasis of skin and nail
B37.3	Candidiasis of vulva and vagina
B37.31	Acute candidiasis of vulva and vagina
B37.32	Chronic candidiasis of vulva and vagina
B37.4	Candidiasis of other urogenital sites
B37.41	Candidal cystitis and urethritis
B37.42	Candidal balanitis
B37.49	Other urogenital candidiasis
B37.5	Candidal meningitis
B37.6	Candidal endocarditis
B37.7	Candidal sepsis
B37.8	Candidiasis of other sites
B37.81	Candidal esophagitis
B37.82	Candidal enteritis
B37.83	Candidal cheilitis
B37.84	Candidal otitis externa
B37.89	Other sites of candidiasis
B37.9	Candidiasis, unspecified
P37.5	Neonatal candidiasis
Cryptococcal meningitis
B45.1	Cerebral cryptococcosis
Cryptococcal septicemia
B45.7	Disseminated cryptococcosis
Cryptococcosis
B45	Cryptococcosis
B45.0	Pulmonary cryptococcosis
B45.1	Cerebral cryptococcosis
B45.2	Cutaneous cryptococcosis
B45.3	Osseous cryptococcosis
B45.7	Disseminated cryptococcosis
B45.8	Other forms of cryptococcosis
B45.9	Cryptococcosis, unspecified
Disseminated candidiasis
B37.5	Candidal meningitis
B37.6	Candidal endocarditis
B37.7	Candidal sepsis
B37.89	Other sites of candidiasis
Febrile neutropenic patient presumed infection treatment
D70.1	Agranulocytosis secondary to cancer chemotherapy
D70.2	Other drug-induced agranulocytosis
D70.3	Neutropenia due to infection
D70.8	Other neutropenia
D70.9	Neutropenia, unspecified
R50.81	Fever presenting with conditions classified elsewhere
Fungal sepsis
B37.7	Candidal sepsis
B44.7	Disseminated aspergillosis
Refractory aspergillosis
B44	Aspergillosis
B44.0	Invasive pulmonary aspergillosis
B44.1	Other pulmonary aspergillosis
B44.2	Tonsillar aspergillosis
B44.7	Disseminated aspergillosis
B44.89	Other forms of aspergillosis
B44.9	Aspergillosis, unspecified
Visceral leishmaniasis
B55.0	Visceral leishmaniasis