Amphotericin B lipid formulations are discussed in a separate monograph.
Amphotericin B is a parenteral antifungal antibiotic produced as a fermentation by-product of Streptomyces nodosus, a soil actinomycete. Amphotericin B is an older drug of the polyene class similar to nystatin. Amphotericin B is named for its amphoteric properties, which are acquired from a carboxyl group on the main ring and a primary amino group on mycosamine. These groups confer improved aqueous solubility in acidic and basic environments. Despite having many well-known side effects and toxicities and the introduction of several antifungal agents of the imidazole class, amphotericin B remains the drug of choice for many serious systemic fungal infections. Amphotericin B is available as an injection, oral suspension, ointment, lotion, and cream. In the 1990s, lipid formulations of amphotericin B became available (see separate monograph). Intranasal amphotericin B is being studied for treatment of chronic rhinosinusitis (CRS). Phase III studies with amphotericin B for CRS are underway with SinuNase (amphotericin B suspension nasal lavage, 100 mcg/mL), an investigational product by Accentia Biopharmaceuticals.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
NOTE: Amphotericin B intravenous products are not interchangeable. Conventional amphotericin B dosing is substantially different from lipid formulations.
Route-Specific Administration
Oral Administration
NOTE: Amphotericin B is not approved by the FDA for oral administration.
Oral Liquid Formulations
NOTE: The oral suspension (100 mg/1 mL) is no longer available as a commercial product in the United States.
-Administer the oral suspension or solution between meals to permit prolonged contact with the oral lesions.
-Place the suspension or solution directly on the tongue with a dropper and swish in the mouth for as long as possible before swallowing or spitting. Alternatively, apply to lesions with a nonabsorbent swab.
Oral Suspension:
-Wet amphotericin B 50 mg bulk powder with glycerin, mix with 3% flavoring, and make sufficient quantity with simple syrup to a dilution of 100 mg/5 mL.
-Shake well prior to administering.
Oral Solution:
-Dilute amphotericin B 50 mg bulk powder with 500 mL of sterile water to a dilution of 0.1 mg/mL solution. Flavor with cherry syrup if desired.
-Dilute amphotericin B 50 mg bulk powder with equal parts sterile water and saliva substitute (50% glycerin and 50% deionized water) to a dilution of 0.2 mg/mL or 1 mg/mL. Add 2 drops of lemon flavoring if desired.
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
-Significant controversy and confusion exist regarding the optimum duration of intravenous infusion. Many clinicians infuse amphotericin B over 4-6 hours in an effort to reduce adverse reactions. Although a small study comparing 45 minute infusions with 4 hour infusions showed that rigors and meperidine requirements were higher in the rapid infusion group, shorter infusions of 1-2 hours have been routinely used without sequelae, except in patients with renal insufficiency. While it has been reported that a 45-minute infusion led to severe hyperkalemia and ventricular fibrillation in a 19-year old patient, this patient was anuric and the dose, when expressed as mg/kg, was relatively large.
-Test dose: A 1 mg test dose (in 20 mL of 5% dextrose solution) administered over 20 to 30 minutes is suggested by the manufacturer; the test dose should be given 2-4 hours prior to the first therapeutic dose. The test dose is used as a means of determining hypersensitivity reactions and patients prone to excessive infusion-related reactions. Overt hypersensitivity reactions are extremely rare with limited case reports in the literature; however, infusion-related reactions are not dose- or time-related; therefore, in susceptible individuals, the clinical reaction will occur regardless of dose size. NOTE: Amphotericin B used to be less pure. Some authors suggest that the recommendation of giving a test dose stems from when amphotericin B was less pure.
-Pre-medication for fever, chills, or rigor: The manufacturer suggests that aspirin, antipyretics (e.g. acetaminophen), antihistamines, antiemetics, meperidine, or small doses of steroids given prior to amphotericin B administration may decrease infusion-related reactions. Of note, steroids should be used cautiously due to the potentiation of hypokalemia (see Drug Interactions). The only dosage regimen recommended by the manufacturer is meperidine 25-50 mg IV to reduce chills and fever. Large prospective trials to evaluate the efficacy of pre-medications to prevent or reduce infusion-related reactions do not exist. Most data are derived from case reports or small series of patients. Case reports and series have described pre-medication regimens that include various combinations including steroids (e.g., hydrocortisone 25 to 100 mg IV), ibuprofen (10 mg/kg PO), diphenhydramine (50 mg IV/PO), acetaminophen (650 mg PO), and/or meperidine (25 to 50 mg IV). Of note, 1 one case series of 9 patients used a mean meperidine dose of 45 mg IV (range, 25-60 mg).
-Pre-medication for nephrotoxicity prophylaxis: The manufacturer suggests that hydration and sodium repletion/sodium loading prior to amphotericin B administration may reduce the risk of nephrotoxicity. Additionally, the manufacturer suggests that supplemental alkali medication may decrease renal tubular acidosis; the suggested alkali medications have not been described. Large prospective trials to evaluate the efficacy of sodium loading to reduce or reverse amphotericin B-associated nephrotoxicity do not exist. Evidence is limited to case reports and smaller trials. Studies have reviewed sodium doses of 85-600 mEq/day, given mostly IV. Most experience is with IV infusions of 150 mEq/day (1 L of 0.9% sodium chloride) over the usual sodium intake; administer as an IV bolus or continuous IV infusion.
Intravenous infusion:
-Rapid IV injection (< 1 hour) should be avoided because severe adverse effects may occur (see Adverse Reactions).
-Reconstitute 50 mg with 10 mL of sterile water for injection without bacteriostatic agent to give a concentration of 5 mg/mL. FURTHER DILUTION IS REQUIRED.
-For infusion, dilute reconstituted product with 500 mL of 5% Dextrose solution which must have a pH greater than 4.2. Maximum recommended concentration for infusion is 0.1 mg/mL.
-Follow test dose protocol (See above). Infuse IV over 2-6 hours. An inline membrane filter may be used if mean pore diameter is >= 1 micrometer. Protect drug from light during infusion.
Intrathecal Administration
NOTE: Amphotericin B is not approved by the FDA for intrathecal administration.
-Reconstitute 50 mg of the lyophilized powder with 200 mL of sterile water for injection without bacteriostatic agent to give a concentration of 0.25 mg/mL.
-0.1 mL (0.025 mg) of the reconstituted solution is diluted with 10-20 mL of cerebral spinal fluid (CSF) and administered by barbotage.
Topical Administration
NOTE: The amphotericin B topical preparation is no longer available as a commercial product in the United States.
NOTE: Amphotericin B is not approved by the FDA for topical administration.
-Apply sparingly to affected area.
-In the treatment of cutaneous candida infection, ointments and occlusive dressings should be avoided since these provide favorable conditions for yeast growth.
Inhalation Administration
NOTE: Amphotericin B is not approved by the FDA for inhalational administration.
-Reconstitute lyophilized powder for injection with sterile water for injection without a bacteriostatic agent. Further dilute with sterile water to a total volume of 5 mL. Most nebulizers generate particles with a diameter of < 5 micro-m, which is necessary for pulmonary deposition. Aerosols generated by ultra-sonic devices contain a greater number of large particles.
-Administer via a face mask nebulizer.
Intranasal Inhalation Administration
NOTE: Amphotericin B is not approved by the FDA for intranasal administration.
-Dissolve enough of the amphotericin B intravenous preparation (50 mg/vial) in sterile water to create a solution containing 100 mcg/mL.
-Using a bulb syringe, administer the appropriate dosage of the solution by gently pointing the tip of the bulb syringe toward the middle meatus region. Bend head laterally to the side being irrigated to treat the maxillary sinus.
Ophthalmic Administration
NOTE: Amphotericin B is not approved by the FDA for ophthalmic administration.
Topical ophthalmic administration:
-Reconstitute lyophilized powder for injection with sterile water for injection without bacteriostatic agent to a strength of 0.5-1.5 mg/mL. More concentrated solutions (3-5 mg/mL) were used initially; however, reports suggest that these concentrations cause ocular irritation.
-Refrigerate the solution in a dark bottle.
-Instruct patient on proper instillation of eye solution.
-Do not to touch the tip of the dropper to the eye, fingertips, or other surface.
Ophthalmic injection:
-No information is available for the preparation of intravitreal or anterior chamber doses based on the case reports of use.
-For intracameral injection 2 mcg dose: Reconstitute 50 mg vial with 5% dextrose in water for a final concentration that provides 2 mcg per 0.1 mL.
-For intracameral injection 5 mcg dose: Reconstitute 50 mg vial with 10 mL of 5% dextrose in water for a 5 mg/1 mL solution. Then further dilute 0.5 mg/0.1 mL of the solution with 10 mL 5% dextrose in water for a final concentration that provides 5 mcg per 0.1 mL.
-For intracameral injection 10 mcg dose: Reconstitute 50 mg vial for a final concentration that provides 10 mcg per 0.1 mL.
Amphotericin B lipid formulations are discussed in a separate monograph.
Nephrotoxicity, often reversible, may occur in up to 80% of patients receiving conventional IV amphotericin B. Nephrotoxicity is manifest in many forms including azotemia, hypokalemia, hyposthenuria, nephrolithiasis (specifically nephrocalcinosis), renal tubular acidosis (RTA), and frank renal failure. Renal tubular acidosis may be present without concurrent systemic acidosis. Although the exact mechanism of renal toxicity has not been defined, amphotericin B can cause a decrease in glomerular filtration rate (GFR) and renal blood flow. A proposed mechanism may involve the effects on membrane permeability as pathological changes of tubular lesions were observed in a study (n=26). Another proposed mechanism is amphotericin B-induced activation of an intrarenal mechanism called tubuloglomerular feedback (TGF); TGF regulates proximal and distal tubule delivery of ions resulting in afferent arteriolar vasoconstriction. TGF can be blocked by sodium loading or with the administration of furosemide or theophylline. However, single-nephron studies suggest that the theory involving TGF may be questionable. Other possible mechanisms include direct toxic effects to the afferent arterioles and tubules and direct renal and systemic vasoconstriction, which may be related to inhibition of nitric oxide or atrial natriuretic peptide systems or potentially to enhanced adenosine release in the kidneys. Vasoconstriction may be calcium-dependent. Other factors that may increase the risk of nephrotoxicity include elevations in daily dose , abnormal baseline renal function, and bone marrow transplantation. In addition to hypokalemia, other electrolyte abnormalities include hypomagnesemia, hypocalcemia, and hyperkalemia. Other adverse renal effects include acute renal failure (unspecified), anuria, decreased renal function, elevated serum creatinine, and oliguria. Cases of nephrogenic diabetes insipidus have been reported during post-marketing use. Health care providers are advised to closely monitor patents' renal function and electrolytes (particularly potassium and magnesium) during therapy. In some patients, hydration and sodium repletion prior to administration may reduce the risk of developing nephrotoxicity.
A normocytic, normochromic anemia occurs in most patients receiving conventional IV amphotericin B. This reaction is believed to be caused by a suppressive effect on erythropoietin production. Usually, this condition does not require transfusions and generally returns to baseline within several months following discontinuation of therapy. Anemia has also been reported rarely in patients receiving amphotericin B lipid formulations. Other hematologic effects, including agranulocytosis, coagulopathy, eosinophilia, leukopenia, leukocytosis, and thrombocytopenia have been reported in patients receiving conventional IV amphotericin B. Health care providers are advised to monitor patients' blood counts and hemoglobin concentrations during therapy.
Gastrointestinal adverse reactions, such as anorexia, cramping, diarrhea, dyspepsia, epigastric or abdominal pain, hemorrhagic gastroenteritis, melena, nausea and vomiting, and weight loss, have occurred in some patients receiving treatment with conventional IV amphotericin B.
Intravenous administration of conventional amphotericin B can cause an injection site reaction including inflammation and pain at the injection site. Phlebitis or thrombophlebitis has also been reported with conventional amphotericin B. The manufacturer of conventional amphotericin B suggests that the addition of 1000 units of heparin to the IV infusion, alternate-day therapy, or use of a scalp-vein needle may decrease these reactions. Extravasation of amphotericin B causes local irritation.
Infusion-related reactions (i.e., reactions occurring during or 1-3 hours after the infusion) develop in 8-54% of conventional IV amphotericin B recipients and include: headache, chills (30-65%), fever (16%), tachypnea, flushing, decreased blood pressure, decreased appetite, and nausea/vomiting. With subsequent doses, the intensity of these reactions usually decreases. Amphotericin B has been shown to stimulate prostaglandin synthesis, which may account for the infusion-related reactions. Although several medications frequently are prescribed to suppress these reactions prior to administration, only hydrocortisone, meperidine, and ibuprofen have been shown to be effective. The manufacturer recommendations for managing acute infusion-related reactions include avoiding rapid infusion rates and pretreatment with aspirin, antipyretics, antihistamines, antiemetics, meperidine, and corticosteroids therapies.
Elevated hepatic enzymes, hyperbilirubinemia, and increased alkaline phosphatase and gamma-glutamyl transpeptidase (GGT) have been reported in patients receiving conventional IV amphotericin B. Rarely, acute hepatic failure, hepatitis, and jaundice have also been reported. Health care providers are advised to monitor patients' hepatic function during amphotericin B therapy.
Adverse neurologic reactions have been reported in patients receiving conventional IV amphotericin B. Specific reactions experienced by recipients of conventional IV amphotericin B include diplopia, encephalopathy, hearing loss, leukoencephalopathy, malaise, peripheral neuropathy, seizures or convulsions, tinnitus, transient vertigo, and visual impairment. Headache has also occurred in some patients and is associated with acute infusion-related reactions.
Anaphylaxis or anaphylactoid reactions, bronchospasm, dyspnea, and wheezing have been reported in patients receiving conventional IV amphotericin B. If severe respiratory distress, anaphylaxis or an anaphylactoid reaction occurs, the drug should be discontinued immediately and the patient given appropriate therapy as indicated. Less frequent adverse effects associated with conventional IV amphotericin B consist of hypersensitivity pneumonitis, pulmonary edema, and shock. Acute pulmonary reactions have occurred in patients receiving amphotericin B during or shortly after leukocyte transfusions; it is recommended to temporarily separate these infusions and to monitor pulmonary function.
Dermatologic adverse events have developed in patients receiving treatment with conventional IV amphotericin B. Specific reactions include rash (unspecified), maculopapular rash, and pruritus. Cases of skin exfoliation, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported during the post-marketing period. Due to the voluntary nature of post-marketing reports, neither a frequency nor a definitive causal relationship can be established.
Intrathecal amphotericin B can cause blurred vision and, in some cases, difficulty in urination. Polyneuropathy and/or paresthesias can occur in some patients, which are exhibited by numbness, tingling, pain, or weakness. Arachnoiditis is also possible.
Musculoskeletal adverse events experienced by recipients of conventional IV amphotericin B include generalized pain, arthralgia, and myalgia.
Nebulized amphotericin B has been associated with cough, dysgeusia (altered taste), nausea/vomiting, wheezing and dysphagia. Patients with a history of asthma have experienced significant decreases in peak flow values as compared to non-asthmatic patients who received nebulized amphotericin B.
Cardiovascular adverse effects associated with conventional IV amphotericin B consist of cardiac arrest (primarily in cases when infusion is too rapid), arrhythmia exacerbation (including ventricular fibrillation), heart failure, hypertension, and hypotension. Assure the appropriate amphotericin B product has been selected. Liposomal amphotericin B product doses are generally higher than conventional amphotericin B doses; therefore, verify the product name and dose prior to drug administration, especially if the conventional amphotericin B dose prescribed exceeds 1.5 mg/kg. Caution is warranted to prevent an inadvertent overdose (based on product selection) that can result in potentially fatal cardiac or cardiorespiratory arrest. Cardiac enlargement with congestive heart failure occurred in a few patients receiving conventional IV amphotericin B with 20-40 mg of hydrocortisone sodium succinate added to each infusion. Congestive heart failure was considered to be due to amphotericin B-induced hypokalemic cardiopathy and corticosteroid-induced salt and fluid retention. Following discontinuance of hydrocortisone and administration of oral potassium supplements, cardiac status returned to normal although conventional amphotericin B therapy was continued.
Amphotericin B lipid formulations are discussed in a separate monograph.
Anaphylaxis has been reported with amphotericin B products. If severe respiratory distress occurs during administration of amphotericin B products, the drug should be immediately discontinued and the patient should not receive further doses of amphotericin B.
Acute pulmonary toxicity has been reported in patients receiving intravenous amphotericin B and leukocyte transfusions simultaneously. When administering systemic amphotericin B, exercise caution to prevent inadvertent overdose; verify product name and dosage if dose exceeds 1.5 mg/kg.
Although dose adjustment is not routinely necessary when administering amphotericin B to patients with renal failure, the drug should be used cautiously in patients with preexisting renal disease because it can cause additional renal impairment. Factors that may increase the risk of nephrotoxicity include concurrent nephrotoxic medications (i.e. diuretics, aminoglycoside, cisplatin), elevations in daily dose duration of therapy , abnormal baseline renal function, and bone marrow transplantation. Hydration and sodium repletion prior to amphotericin B administration may reduce the risk of developing nephrotoxicity in some patients. Supplemental alkali medication may decrease renal tubular acidosis complications. When administering systemic amphotericin B, exercise caution to prevent inadvertent overdose; verify product name and dosage if dose exceeds 1.5 mg/kg.
Amphotericin B intravenous is classified as pregnancy risk category B. There have been no well controlled studies in pregnant women; however, a small number of case reports have documented use during pregnancy without obvious effects to the fetus. The drug should be used during pregnancy only when the benefits clearly outweigh the risks.
Intravenous amphotericin B has been used effectively to treat systemic fungal infections in pediatric patients. However, safety and efficacy have not been established in neonates, infants, children, and adolescents through adequate and well-controlled trials. No unusual adverse effects have been reported in pediatric patients. The manufacturer states that the lowest effective dosage should be used whenever conventional IV amphotericin B is administered to pediatric patients, but does not give a specific dosage recommendation.
Use caution when administering amphotericin B to patients with electrolyte imbalance including hypokalemia, hypomagnesemia, hypocalcemia, and hyponatremia. Significant renal electrolyte loss (especially potassium) may occur with administration of amphotericin B. In addition, pre-existing electrolyte imbalance may increase the risk of amphotericin-associated renal toxicity. Ideally, correct electrolyte imbalances prior to initiating amphotericin therapy. Monitor serum electrolytes carefully during amphotericin B treatment and replace as appropriate. When administering systemic amphotericin B, exercise caution to prevent inadvertent overdose; verify product name and dosage if dose exceeds 1.5 mg/kg.
Data are limited regarding the use of amphotericin B during breast-feeding, and it is not known whether it is excreted into breast milk. According to the manufacturer, because many drugs are excreted in human milk and because of the potential for serious adverse reactions in breast-fed neonates and infants, a decision should be made whether to discontinue breast-feeding or to discontinue the drug, taking into account the importance of the drug to the mother. Fluconazole and ketoconazole may be potential alternatives to consider during breast-feeding. However, site of infection, local susceptibility patterns, and specific microbial susceptibility should be assessed before choosing an alternative agent. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested or administered drug, health care providers are encouraged to report the adverse effect to the FDA.
There is a potential for overdose or poisoning with conventional intravenous amphotericin B due to confusion with the dosing of the various amphotericin B products. Liposomal amphotericin B product doses are generally higher than conventional amphotericin B doses; therefore, verify the product name and dose prior to drug administration, especially if the conventional amphotericin B dose prescribed exceeds 1.5 mg/kg. Caution is warranted to prevent an inadvertent overdose (based on product selection) that can result in potentially fatal cardiac or cardiorespiratory arrest.
Use amphotericin B with caution in patients with hematological disease including patients with preexisting anemia, leukopenia, or thrombocytopenia; amphotericin B use has been associated with anemia, leukopenia, and thrombocytopenia and may worsen pre-existing blood cell count abnormalities. Monitor CBC and platelets during amphotericin B therapy.
Intravenous amphotericin B is associated with infusion-related reactions that can be severe. Acute reactions may include fever, chills, rigors, hypotension, anorexia, nausea, vomiting, headache, and tachypnea and often occur within 1 to 3 hours after beginning the infusion. Although these reactions are typically most severe during the first few doses, monitor patients carefully during all amphotericin infusions. Slowing the infusion rate may help reduce infusion-related reactions; pre-medication with antipyretics, anti-histamines, meperidine (for rigors), and/or corticosteroids may prevent or minimize the reaction in some patients. Rapid administration must be strictly avoided; serious hypotension, hypokalemia, arrhythmias, and shock have occurred with rapid infusion rates. Amphotericin B is also irritating to the veins. Slowing the infusion rate may also help alleviate injection site reactions.
General dosing information:
Initiation of therapy
-A test dose (0.1 mg/kg/dose; Max: 1 mg/dose) may be given prior to therapy and is suggested in the FDA-approved labeling. The test dose should be given 2 to 4 hours prior to the first therapeutic dose. Many clinicians do not utilize a test dose; true hypersensitivity reactions to amphotericin B are rare. Some authors suggest that the recommendation of giving a test dose stems from when amphotericin B products were less pure compared to formulations available today. Test dosing is not recommended in neonates as immediate adverse reactions are not common in this group and the benefit of attaining therapeutic concentrations as soon as possible is often desirable.
-Some clinicians initiate amphotericin B therapy with a lower initial dose (i.e., 0.25 to 0.5 mg/kg/day, increased by 0.25 mg/kg/day increments to the goal dose). Others initiate therapy with the full dose. Most guidelines recommend initiating therapy with the full dose. In addition, lower initial doses are not recommended in neonates as immediate adverse reactions are not common in this group and the benefit of attaining therapeutic concentrations faster outweighs potential risks.
Pre-medication regimens
-Fever, chills, or rigor: To decrease infusion-related reactions, premedication regimens including antipyretics (e.g., acetaminophen), antihistamines (e.g., diphenhydramine), meperidine, and steroids have been used. Of note, steroids should be used cautiously due to the potentiation of hypokalemia.
-Nephrotoxicity prophylaxis: Hydration and sodium repletion/sodium loading prior to amphotericin B administration may reduce the risk of nephrotoxicity. Supplemental alkali medication may decrease renal tubular acidosis; the suggested alkali medications have not been described. Evidence on the efficacy of sodium loading to reduce or reverse amphotericin B-associated nephrotoxicity are lacking in children. One study suggested a sodium intake more than 4 mEq/kg/day in extremely low birth weight infants receiving amphotericin B.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Absidia sp., Aspergillus fumigatus, Aspergillus sp., Basidiobolus sp., Blastomyces dermatitidis, Candida albicans, Candida sp., Coccidioides immitis, Conidiobolus sp., Cryptococcus neoformans, Cryptococcus sp., Histoplasma capsulatum, Leishmania braziliensis, Leishmania donovani, Leishmania infantum, Leishmania mexicana, Leishmania sp., Leishmania tropica, Mucor mucedo, Mucor sp., Rhizopus sp., Rhodotorula sp., Sporothrix schenckii
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
This drug may also have activity against the following microorganisms: Acanthamoeba castellanii, Acanthamoeba polyphaga, Acremonium sp., Entomophthora sp., Naegleria fowleri, Naegleria sp., Paracoccidioides brasiliensis, Talaromyces marneffei
NOTE: Some organisms may not have been adequately studied during clinical trials; therefore, exclusion from this list does not necessarily negate the drug's activity against the organism.
For the treatment of CNS infections, including meningitis:
NOTE: For CNS infections caused by Cryptococcus, see Cryptococcus meningitis.
-for the treatment of CNS infections due to Candida sp.:
Intravenous dosage:
Adults: Conventional amphotericin B is not recommended as routine therapy for invasive Candida infections; liposomal amphotericin B is the preferred treatment. The FDA-approved dosage is 0.25 to 0.3 mg/kg/dose IV daily with doses increased by 5 to 10 mg/day to reach a full dose of 0.5 to 0.7 mg/kg/dose IV once daily. Doses up to 1 mg/kg/day or 1.5 mg/kg/dose given every other day may be warranted.
Infants*, Children*, and Adolescents*: Conventional amphotericin B is not recommended as routine therapy for invasive Candida infections; liposomal amphotericin B is the preferred treatment.
Neonates*: 1 mg/kg/dose IV every 24 hours until all signs and symptoms and cerebrospinal fluid (CSF) and radiologic abnormalities have resolved. Remove intraventricular devices. Guidelines recommend amphotericin B deoxycholate as preferred therapy. Concomitant flucytosine therapy is not routinely recommended but may be considered as salvage therapy for those who do not respond to amphotericin B alone.
Intrathecal dosage*:
Neonates: Very limited data are available; not routinely recommended. In a case report of a single term infant (birth weight = 2.9 kg) 0.05 mg/dose intrathecally followed by a second dose 3 days later.
-for treatment of CNS infections due to Coccidioides sp.:
Intravenous dosage:
Adults: 0.25 to 0.3 mg/kg/dose IV every 24 hours with doses increased by 5 to 10 mg/day to reach a full dose of 0.5 to 0.7 mg/kg/dose IV every 24 hours. Doses up to 1 mg/kg/day or 1.5 mg/kg/dose given every other day may be warranted. Utility of intravenous amphotericin B in clinical cases of coccidioidal meningitis is unclear; reserve for treatment of refractory cases.
Adolescents*: 0.7 to 1 mg/kg/dose IV every 24 hours. Utility of intravenous amphotericin B in clinical cases of coccidioidal meningitis is unclear; reserve for treatment of refractory cases.
Infants* and Children*: 0.5 to 1 mg/kg/dose IV every 24 hours. Guidelines for opportunistic infections in persons living with HIV recommend intravenous amphotericin B plus intrathecal amphotericin B as an alternative regimen for infections unresponsive to fluconazole. Continue with fluconazole or itraconazole for lifelong suppressive therapy. Guidelines for the treatment of Coccidioides sp. recommend reserving intravenous amphotericin B for refractory cases.
Intrathecal dosage*:
Adults: 0.01 to 1.5 mg intrathecally 1 to 3 times weekly, depending on method of administration. For lumbar delivery by barbotage or by mixing drug with 5 mL of 10% Dextrose Injection, 0.01 to 0.025 mg initially and increase as tolerated to target dose of 0.5 mg. For cisternal therapy, 0.25 mg or less in 0.5 mL or smaller volumes. Maintenance doses of 0.01 to 1.5 mg have been used. For ventricular administration by an Omaya reservoir, 0.01 mg initially and increase to maintenance dose of 1.5 mg. The frequency of dosing and duration of therapy are generally 3 times per week for the first 3 months, then 1 to 2 times per week for several months, then once every several weeks, depending on the cerebrospinal fluid (CSF) cell count. Guidelines for opportunistic infections in persons living with HIV suggest intrathecal amphotericin B when triazole antifungals are not effective. Fluconazole is the preferred therapy. Guidelines for the treatment of Coccidioides sp. suggest intrathecal amphotericin B for immunocompetent patients experiencing failure with initial IV fluconazole therapy or pregnant females in their first trimester. After the first pregnancy trimester, a triazole may be used or intrathecal amphotericin B may be continued.
Adolescents: 0.01 to 1.5 mg intrathecally 1 to 3 times weekly, depending on method of administration. For lumbar delivery by barbotage or by mixing drug with 5 mL of 10% Dextrose Injection, 0.01 to 0.025 mg initially and increase as tolerated to target dose of 0.5 mg. For cisternal therapy, 0.25 mg or less in 0.5 mL or smaller volumes. Maintenance doses of 0.01 to 1.5 mg have been used. For ventricular administration by an Omaya reservoir, 0.01 mg initially and increase to maintenance dose of 1.5 mg. The frequency of dosing and duration of therapy are generally 3 times per week for the first 3 months, then 1 to 2 times per week for several months, then once every several weeks, depending on the cerebrospinal fluid (CSF) cell count. Guidelines for opportunistic infections in persons living with HIV suggest intrathecal amphotericin B when triazole antifungals are not effective. Fluconazole is the preferred therapy. Guidelines for the treatment of Coccidioides sp. suggest intrathecal amphotericin B for immunocompetent patients experiencing failure with initial IV fluconazole therapy or pregnant females in their first trimester. After the first pregnancy trimester, a triazole may be used or intrathecal amphotericin B may be continued.
Infants and Children: 0.01 to 0.05 mg/dose intrathecally followed by a gradual dose escalation (0.025 to 0.1 mg/day) until appearance of patient intolerance. Most patients tolerate a maximum dose of approximately 0.5 mg/treatment and many tolerate only a maximum of 0.2 mg/treatment. Initial frequency is often daily, followed by a reduction in intervals after cerebrospinal fluid (CSF) improvement (i.e., few times weekly, then weekly, then every few weeks). In a study in 6 children (19 to 74 months), intrathecal doses were initiated at 0.05 mg/day and increased to patient tolerance; however, no doses exceeded 0.25 mg/day per site. Guidelines for opportunistic infections in persons living with HIV recommend intravenous amphotericin B plus intrathecal amphotericin B as an alternative regimen for infections unresponsive to fluconazole. Guidelines for the treatment of Coccidioides sp. suggest intrathecal amphotericin B for immunocompetent patients experiencing failure with initial IV fluconazole therapy.
-for the treatment of meningitis due to Sporothrix schenckii*:
Intravenous dosage:
Adults: 0.7 to 1 mg/kg/dose IV every 24 hours for at least 4 to 6 weeks. Continue step-down therapy with itraconazole to complete a total of at least 12 months of therapy. The FDA-approved dosage is 0.25 to 0.3 mg/kg/dose IV every 24 hours; may increase dose by 5 to 10 mg/day to a final dose of 0.5 to 0.7 mg/kg/day. Doses up to 1 mg/kg/day or 1.5 mg/kg given every other day may be warranted. Guidelines recommend amphotericin B deoxycholate as an alternative to liposomal amphotericin B.
For the treatment of candidemia and invasive candidiasis (non-CNS):
NOTE: For CNS disease, see meningitis indication.
Intravenous dosage:
Adults: 0.25 to 0.3 mg/kg/dose IV every 24 hours; may increase dose by 5 to 10 mg/day to a final dose of 0.5 to 0.7 mg/kg/day. Doses up to 1 mg/kg/day or 1.5 mg/kg/dose given every other day may be warranted. Guidelines do not include amphotericin B deoxycholate for invasive candidiasis infections. A lipid formulation amphotericin B is preferred.
Infants*, Children*, and Adolescents*: 1 mg/kg/dose IV every 24 hours as an alternative. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
Neonates*: 1 mg/kg/dose IV every 24 hours as first-line therapy. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
For the treatment of fluconazole-refractory oropharyngeal candidiasis (thrush):
NOTE: Amphotericin B deoxycholate should not be used in noninvasive infections, such as oropharyngeal candidiasis (thrush), in patients with normal neutrophil counts.
Intravenous dosage:
Adults: 0.3 mg/kg/dose IV every 24 hours for up to 28 days as an alternative.
Infants*, Children*, and Adolescents*: 0.3 mg/kg/dose IV every 24 hours for up to 28 days as an alternative.
Oral dosage*:
Adults: 100 mg PO 4 times daily for up to 28 days as an alternative. Patients should swish the suspension for as long as reasonably possible before swallowing or spitting. If swabbing the lesion is the desired method of application, a nonabsorbent swab should be used.
Infants, Children, and Adolescents: 100 mg PO 4 times daily for up to 28 days as an alternative. There are limited data in children; however, a study in 63 children (premature infants to 12 years of age) with oropharyngeal candidiasis reported an excellent or good response in 86% of patients who received amphotericin B oral suspension. Patients should swish the suspension for as long as reasonably possible before swallowing or spitting. If swabbing the lesion is the desired method of application, a nonabsorbent swab should be used.
Neonates: 100 mg PO 4 times daily for up to 28 days as an alternative. There are limited data in neonates; however, a study in 63 children (premature infants to 12 years of age) with oropharyngeal candidiasis reported an excellent or good response in 86% of patients who received amphotericin B oral suspension. Bioavailability is poor after oral administration, and swabbing the lesion with a nonabsorbent swab or applying directly to the lesion using a dropper are the preferred methods of application for neonates. Therefore, significant systemic exposure is not expected.
For the treatment of esophageal candidiasis, including fluconazole-refractory disease:
NOTE: Amphotericin B deoxycholate should not be used in noninvasive infections, such as esophageal candidiasis, in patients with normal neutrophil counts.
-for the treatment of esophageal candidiasis in persons without HIV:
Intravenous dosage:
Adults: 0.3 to 0.7 mg/kg/dose IV every 24 hours for 14 to 21 days as an alternative for patients who cannot tolerate oral therapy or for fluconazole-refractory disease.
Infants*, Children*, and Adolescents*: 0.3 to 0.7 mg/kg/dose IV every 24 hours for 14 to 21 days as an alternative for patients who cannot tolerate oral therapy or for fluconazole-refractory disease.
-for the treatment of esophageal candidiasis in persons living with HIV:
Intravenous dosage:
Adults: 0.6 mg/kg/dose IV every 24 hours for 14 to 21 days as an alternative.
Adolescents*: 0.6 mg/kg/dose IV every 24 hours for 14 to 21 days as an alternative.
Infants* and Children*: 0.3 to 0.7 mg/kg/dose IV every 24 hours for 14 to 21 days as an alternative.
For the treatment of Candida respiratory infections (i.e., pneumonia):
Intravenous dosage:
Adults: Growth of Candida sp. from the respiratory tract typically reflects colonization and rarely requires antifungal therapy. In cases where pneumonia is associated with disseminated infection, 0.25 to 0.3 mg/kg/dose IV every 24 hours; may increase dose by 5 to 10 mg/day to a final dose of 0.5 to 0.7 mg/kg/day. Doses up to 1 mg/kg/day or 1.5 mg/kg given every other day may be warranted. Clinical practice guidelines do not include amphotericin B deoxycholate for invasive candidiasis infections. A lipid formulation amphotericin B is preferred.
Infants*, Children*, and Adolescents*: Growth of Candida sp. from the respiratory tract typically reflects colonization and rarely requires antifungal therapy. Clinical practice guidelines do not include amphotericin B deoxycholate for invasive candidiasis infections. A lipid formulation amphotericin B is preferred.
Neonates*: Growth of Candida sp. from the respiratory tract typically reflects colonization and rarely requires antifungal therapy. Restrict treatment to pneumonia associated with disseminated infection. 1 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest amphotericin B deoxycholate as the preferred therapy for neonatal candidiasis.
For the treatment of intraabdominal infections due to candidiasis, including neonatal necrotizing enterocolitis* and peritoneal dialysis-related peritonitis*:
-for the treatment of intraabdominal candidiasis:
Intravenous dosage:
Adults: 0.25 to 0.3 mg/kg/dose IV every 24 hours; may increase dose by 5 to 10 mg/day to a final dose of 0.5 to 0.7 mg/kg/day. Doses up to 1 mg/kg/dose IV every 24 hours or 1.5 mg/kg/dose IV every 48 hours may be warranted. Guidelines do not include amphotericin B deoxycholate for invasive candidiasis infections.
Infants*, Children*, and Adolescents*: 1 mg/kg/dose IV every 24 hours. Guidelines do not include amphotericin B deoxycholate for invasive candidiasis infections.
Neonates*: 1 mg/kg/dose IV every 24 hours. Amphotericin B deoxycholate is the preferred therapy for neonatal candidiasis, including necrotizing enterocolitis.
-for the treatment of peritoneal dialysis-related peritonitis*:
Intravenous dosage:
Adults: 0.1 mg/kg/dose IV every 24 hours; increase dose over 4 days to a final dose of 0.75 to 1 mg/kg/dose IV every 24 hours. Treat for at least 14 days after catheter removal.
For the treatment of Candida bone and joint infections, including osteomyelitis and infectious arthritis:
Intravenous dosage:
Adults: 0.25 to 0.3 mg/kg/dose IV every 24 hours; may increase dose by 5 to 10 mg/day to a final dose of 0.5 to 0.7 mg/kg/day. Doses up to 1 mg/kg/day or 1.5 mg/kg given every other day may be warranted. Clinical practice guidelines do not include amphotericin B deoxycholate for invasive candidiasis infections. A lipid formulation amphotericin B is preferred.
Infants*, Children*, and Adolescents*: Clinical practice guidelines do not include amphotericin B deoxycholate for invasive candidiasis infections. A lipid formulation amphotericin B is preferred.
Neonates*: 1 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest amphotericin B deoxycholate as the preferred therapy for neonatal candidiasis. Treat for at least 2 weeks followed by fluconazole for 6 to 12 months for osteomyelitis or 4 weeks for infectious arthritis. Surgical debridement may be helpful in some cases of osteomyelitis and is recommended for all cases of septic arthritis. For infection involving a prosthetic device, device removal in addition to antifungal therapy is recommended.
For the treatment of asymptomatic candiduria* and Candida urinary tract infection (UTI)*, including cystitis* and pyelonephritis*:
-for the treatment of asymptomatic candiduria* in very low-birth-weight infants (weighing less than 1.5 kg):
Intravenous dosage:
Neonates: 1 mg/kg/dose IV every 24 hours for 14 days as first-line therapy. Candiduria may be the only microbiological documentation of disseminated candidiasis in very-low-birth-weight infants; therefore, candiduria should be treated as disseminated candidiasis in these patients.
-for the treatment of asymptomatic candiduria* in persons undergoing urologic procedures:
Intravenous dosage:
Adults: 0.3 to 0.6 mg/kg/dose IV every 24 hours for several days before and after the urologic procedure.
Infants, Children, and Adolescents: 0.3 to 0.6 mg/kg/dose IV every 24 hours for several days before and after the urologic procedure.
Neonates: 1 mg/kg/dose IV every 24 hours for several days before and after the urologic procedure.
-for the treatment of cystitis*:
Intravenous dosage:
Adults: 0.3 to 0.6 mg/kg/dose IV every 24 hours for 1 to 7 days for C. glabrata or C. krusei.
Infants, Children, and Adolescents: 0.3 to 0.6 mg/kg/dose IV every 24 hours for 1 to 7 days for C. glabrata or C. krusei.
Neonates: 1 mg/kg/dose IV every 24 hours for 14 days as first-line therapy.
Intravesicular dosage (bladder irrigation):
Adults: 50 mg per 1 L of Sterile Water for Irrigation as bladder irrigation once daily for 5 days. May administer by continuous bladder irrigation (i.e., 40 mL/hour continuously). Alternately, dilute 20 to 60 mg in Sterile Water for Irrigation to yield 100 to 200 mcg/mL. Instill 200 to 300 mL into the bladder; clamp the catheter for 60 to 120 minutes then drain bladder. Irrigate bladder 3 to 4 times daily for 2 to 5 days. Guidelines suggest amphotericin B deoxycholate bladder irrigation may be useful for symptomatic cystitis due to fluconazole-resistant species, such as C. glabrata and C. krusei.
Infants, Children, and Adolescents: Data are limited. Various regimens have been used and range from continuous irrigation to intermittent instillation up to 4 times daily. 50 mg per 1 L of Sterile Water for Irrigation administered by continuous bladder irrigation for 5 days has been used. A rate of 40 mL/hour has been used in adults; however, this rate must be individualized to an appropriate rate for the patient's age or size. Alternately, dilute 20 to 60 mg in Sterile Water for Irrigation to yield 100 to 200 mcg/mL. Instill an appropriate volume for the size of the patient's bladder; clamp the catheter for 60 to 120 minutes then drain bladder. Irrigate bladder 3 to 4 times daily for 2 to 5 days. Estimating bladder capacity in pediatric patients, particularly infants and young children, must be individualized. A study of infants younger than 12 months (mean age, 8.2 months) found a mean bladder capacity of 46.8 mL. The following equations have been recommended to estimate bladder capacity: for children younger than 2 years, bladder capacity (ounces) = (2 x age [years]) + 2, and for children 2 years and older, bladder capacity (ounces) = (age [years] / 2) + 6. However, some data suggest that the equation for children younger than 2 years overestimates bladder capacity for infants. Guidelines suggest amphotericin B deoxycholate bladder irrigation may be useful for symptomatic cystitis due to fluconazole-resistant species, such as C. glabrata and C. krusei.
Neonates: Data are limited. 50 mcg/mL solution in Sterile Water for Irrigation as a continuous or intermittent irrigation has been recommended. For intermittent irrigation, instill an appropriate volume for the patient's size into the bladder; clamp catheter for 1 to 2 hours then drain bladder. Repeat 3 to 4 times daily for 2 to 7 days or until cultures are negative. The bladder capacity of neonates is variable, and a standard method of calculating bladder capacity in this population has not been validated. One neonatal reference states that bladder capacity is approximately 5 to 10 mL/kg. A retrospective study of infants younger than 1 year, found a mean bladder capacity of approximately 30 mL (range, 10 to 100 mL) for neonates (gestational ages not reported). A review of free voiding studies found a median bladder capacity in preterm infants (32 weeks gestation) of 12 mL and 52 mL in term infants at 3 months of age. Guidelines suggest amphotericin B deoxycholate bladder irrigation may be useful for symptomatic cystitis due to fluconazole-resistant species, such as C. glabrata and C. krusei.
-for the treatment of ascending pyelonephritis*:
Intravenous dosage:
Adults: 0.3 to 0.6 mg/kg/dose IV every 24 hours for 1 to 7 days for C. glabrata or C. krusei. Consider adding flucytosine for C. glabrata.
Infants, Children, and Adolescents: 0.3 to 0.6 mg/kg/dose IV every 24 hours for 1 to 7 days for C. glabrata or C. krusei. Consider adding flucytosine for C. glabrata.
Neonates: 1 mg/kg/dose IV every 24 hours for 14 days as first-line therapy.
-for the treatment of urinary fungal balls*:
Intravenous dosage:
Adults: 0.3 to 0.6 mg/kg/dose IV every 24 hours for 1 to 7 days.
Infants, Children, and Adolescents: 0.3 to 0.6 mg/kg/dose IV every 24 hours for 1 to 7 days.
Neonates: 1 mg/kg/dose IV every 24 hours for 14 days as first-line therapy.
Local renal irrigation dosage (irrigation of renal pelvis):
Adults: 25 to 50 mg in 200 to 500 mL of Sterile Water for Irrigation as irrigation through nephrostomy tubes.
Infants, Children, and Adolescents: 25 to 50 mg in 200 to 500 mL of Sterile Water for Irrigation as irrigation through nephrostomy tubes.
Neonates: Data are very limited. Two case reports describe the use of amphotericin B irrigation at a concentration of 50 mcg/mL through nephrostomy catheters. A 3-month-old infant (30 week gestational age at birth with 2-month NICU stay) was treated with amphotericin B deoxycholate irrigation through percutaneous nephrostomy catheters for obstructive bilateral fungal balls caused by C. albicans. In addition to systemic therapy, amphotericin B deoxycholate was administered by slow, continuous irrigation or as intermittent doses given every 5 hours. In a second case, a 3-week-old neonate with bladder exstrophy was treated with amphotericin B deoxycholate irrigation through nephrostomy catheters 3 times daily in addition to various systemic antifungal treatments for bilateral aspergilloma. 25 to 50 mg in 200 to 500 mL of Sterile Water for Irrigation as irrigation through nephrostomy tubes.
For the treatment of invasive aspergillosis:
Intravenous dosage:
Adults: 0.25 to 0.3 mg/kg/dose IV every 24 hours; may increase dose by 5 to 10 mg/day to a final dose of 0.5 to 0.7 mg/kg/day. Doses up to 1 mg/kg/day or 1.5 mg/kg/dose given every other day may be warranted. Guidelines do not include amphotericin B deoxycholate for invasive aspergillosis infections. Voriconazole is recommended as primary therapy with a lipid formulation amphotericin B as alternative or salvage therapy.
Infants*, Children*, and Adolescents*: 1 to 1.5 mg/kg/dose IV every 24 hours is the general dosage recommended by the American Academy of Pediatrics (AAP). Guidelines do not include amphotericin B deoxycholate for invasive aspergillosis infections. Voriconazole is recommended as primary therapy with a lipid formulation amphotericin B as alternative or salvage therapy.
Neonates*: 1 to 1.5 mg/kg/dose IV every 24 hours is the general dosage recommended by the American Academy of Pediatrics (AAP). Although specific neonatal recommendations are not available, guidelines do not include amphotericin B deoxycholate for invasive aspergillosis infections. Voriconazole is recommended as primary therapy with a lipid formulation amphotericin B as alternative or salvage therapy.
For the treatment of allergic bronchopulmonary aspergillosis*:
Respiratory (Inhalation) dosage:
Adults: 10 mg inhaled by nebulizer twice daily.
Children and Adolescents: Limited data are available. Case reports and small case series have described 5 to 10 mg inhaled by nebulizer twice daily in persons with cystic fibrosis (CF) with refractory allergic bronchopulmonary aspergillosis (ABPA). A case series of 7 patients with CF (younger than 18 years; n = 4) reports the use of 25 mg inhaled by nebulizer 3 times weekly; 5 of 7 patients were able to successfully wean from systemic steroids without ABPA relapse for at least 12 months.
For the treatment of ocular fungal infections*, including endophthalmitis*, chorioretinitis*, and fungal keratitis*, caused by susceptible fungal organisms:
Topical ophthalmic dosage:
Adults: 1 drop (0.5 to 1.5 mg/mL solution) to the conjunctival sac of affected eye(s) every 30 minutes to 1 hour. In a case, the frequency was decreased at night to every 2 to 3 hours. Altough small numbers of patients, improved response has been reported between 46% to 100%. More concentrated solutions (3 to 5 mg/mL) have been used; however, these concentrations may cause ocular irritation.
Intracameral injection dosage:
Adults: 2 to 10 mcg by intracameral injection to the affected eye(s) using a tuberculin syringe for patients unresponsive to systemic or topical ophthalmic therapy. One patient, who received intermittent 2 mcg amphotericin B in 0.1 mL of 5% Dextrose Injection by intracameral injection plus anterior chamber irrigation for 8 months, clinically recovered. In a series of 3 cases, amphotericin B 10 mcg/0.1 mL intracameral injection was given in 1 or 2 doses at 3 to 6 days apart. A case series of 4 patients describes 5 mcg amphotericin B in 0.1 mL of 5% Dextrose Injection by intracameral injection between 3 to 13 times with doses given 1 to 5 days apart. All patients showed clinical improvement.
Anterior chamber injection dosage:
Adults: 5 to 50 mcg by anterior chamber injection to the affected eye(s). In a case series of 86 patients with postsurgical fungal endophthalmitis, 17 eyes received intraocular amphotericin B injections into either the anterior chamber, vitreous cavity, or into both areas of the eye. Most patients received 5 to 10 mcg per dose; however, 1 patient received 50 mcg into the anterior chamber. Patients received 1 to 6 injections, with most requiring 3 injections or less during the treatment course. All patients also required surgical intervention. All patients in the study who achieved visual acuity scores of 20/200 or better received at least 1 intraocular injection of amphotericin B. In a case report, a patient with metastatic coccidioidal endophthalmitis received 2 doses of amphotericin B 25 mcg by anterior chamber injection 20 days apart. Amphotericin B was diluted with Sterile Water for Injection to a concentration of 25 mcg/1 mL. The eye was eventually removed; however the orbit was found to be free of disease.
Intravitreal injection dosage:
Adults: 5 to 10 mcg given by intravitreal injection to the affected eye(s); doses up to 20 mcg have been administered. If repeat doses were given, the timing between doses ranged from 2 days to 6 weeks, with an average interval of 1 week if reported. In these case reports, intravitreal injection of amphotericin B was often administered in conjunction with surgical intervention and/or systemic therapy; therefore, it is difficult to delineate clinical improvement based on local injection alone. In many case reports, a single dose of intravitreal amphotericin B was given after surgical intervention, including par plana vitrectomy.
-for the treatment of Aspergillus endophthalmitis*:
Intravitreal dosage:
Adults: 5 to 10 mcg by intravitreal injection to the affected eye(s). Clinical practice guidelines suggest intravitreal amphotericin B deoxycholate in combination with systemic therapy for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement.
Infants, Children, and Adolescents: 5 to 10 mcg by intravitreal injection to the affected eye(s). Clinical practice guidelines suggest intravitreal amphotericin B deoxycholate in combination with systemic therapy for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement.
-for the treatment of Candida endophthalmitis* and chorioretinitis*:
Intravenous dosage:
Neonates: 1 mg/kg/dose IV every 24 hours. Clinical practice guidelines suggest amphotericin B deoxycholate as the preferred therapy for neonatal candidiasis. Treat for at least 4 to 6 weeks, with duration depending on stabilization or resolution of lesions.
Intravitreal injection dosage:
Adults: 5 to 10 mcg/0.1 mL Sterile Water for Injection by intravitreal injection to the affected eye(s) for at least 4 to 6 weeks, with duration depending on stabilization or resolution of lesions. Clinical practice guidelines suggest intravitreal amphotericin B deoxycholate in combination with systemic therapy for chorioretinitis macular involvement or vitritis.
Infants, Children, and Adolescents: 5 to 10 mcg/0.1 mL Sterile Water for Injection by intravitreal injection to the affected eye(s) for at least 4 to 6 weeks, with duration depending on stabilization or resolution of lesions. Clinical practice guidelines suggest intravitreal amphotericin B deoxycholate in combination with systemic therapy for chorioretinitis macular involvement or vitritis.
Neonates: 5 to 10 mcg/0.1 mL Sterile Water for Injection by intravitreal injection to the affected eye(s) for at least 4 to 6 weeks, with duration depending on stabilization or resolution of lesions. Clinical practice guidelines suggest intravitreal amphotericin B deoxycholate in combination with systemic therapy for chorioretinitis macular involvement or vitritis.
For the treatment of cardiovascular system infections, including endocarditis, myocarditis, pericarditis, suppurative thrombophlebitis*, and infected pacemaker*, implantable cardiac defibrillator (ICD)*, or ventricular assist devices (VAD)*:
-for the treatment of Aspergillus cardiovascular system infections:
Intravenous dosage:
Adults: 0.25 to 0.3 mg/kg/dose IV every 24 hours; may increase dose by 5 to 10 mg/day to a final dose of 0.5 to 0.7 mg/kg/day. Doses up to 1 mg/kg/day or 1.5 mg/kg/dose given every other day may be warranted. Endocarditis guidelines recommend amphotericin B as primary therapy for fungal endocarditis in addition to valve replacement. Treat for more than 6 weeks, followed by lifelong suppressive therapy with an oral azole. Aspergillosis guidelines do not include amphotericin B deoxycholate for invasive aspergillosis infections. Voriconazole is recommended as primary therapy with a lipid formulation amphotericin B as alternative or salvage therapy.
Infants*, Children*, and Adolescents*: 1 mg/kg/dose IV every 24 hours with or without flucytosine for 4 to 6 weeks and surgical resection is recommended by endocarditis guidelines. Aspergillosis guidelines do not include amphotericin B deoxycholate for invasive aspergillosis infections. Voriconazole is recommended as primary therapy with a lipid formulation amphotericin B as alternative or salvage therapy.
Neonates*: 1 to 1.5 mg/kg/dose IV every 24 hours is the general dosage recommended by the American Academy of Pediatrics (AAP). Although specific neonatal recommendations are not available, guidelines do not include amphotericin B deoxycholate for invasive aspergillosis infections. Voriconazole is recommended as primary therapy with a lipid formulation amphotericin B as alternative or salvage therapy.
-for the treatment of Candida cardiovascular system infections:
Intravenous dosage:
Adults: 0.25 to 0.3 mg/kg/dose IV every 24 hours; may increase dose by 5 to 10 mg/day to a final dose of 0.5 to 0.7 mg/kg/day. Doses up to 1 mg/kg/day or 1.5 mg/kg/dose given every other day may be warranted. Endocarditis guidelines recommend amphotericin B as primary therapy for fungal endocarditis in addition to valve replacement. Treat for more than 6 weeks, followed by lifelong suppressive therapy with an oral azole. Candidiasis guidelines do not include amphotericin B deoxycholate for invasive candidiasis infections. A lipid formulation amphotericin B is preferred. For endocarditis, treat for at least 6 weeks after valve replacement. For infected cardiac hardware, treat for at least 4 to 6 weeks after hardware removal. When valve replacement or hardware removal is not possible or for prosthetic valve endocarditis, chronic suppressive therapy with fluconazole is recommended after initial treatment. Treat suppurative thrombophlebitis for at least 2 weeks after candidemia (if present) has cleared.
Infants*, Children*, and Adolescents*: 1 mg/kg/dose IV every 24 hours with or without flucytosine for 4 to 6 weeks and surgical resection is recommended by endocarditis guidelines. Candidiasis guidelines do not include amphotericin B deoxycholate for invasive candidiasis infections. A lipid formulation amphotericin B is preferred. For endocarditis, treat for at least 6 weeks after valve replacement. For infected cardiac hardware, treat for at least 4 to 6 weeks after hardware removal. When valve replacement or hardware removal is not possible or for prosthetic valve endocarditis, chronic suppressive therapy with fluconazole is recommended after initial treatment. Treat suppurative thrombophlebitis for at least 2 weeks after candidemia (if present) has cleared.
Neonates*: 1 mg/kg/dose IV every 24 hours. Guidelines suggest amphotericin B deoxycholate as the preferred therapy for neonatal candidiasis. For endocarditis, treat for at least 6 weeks after valve replacement. For infected cardiac hardware, treat for at least 4 to 6 weeks after hardware removal. When valve replacement or hardware removal is not possible or for prosthetic valve endocarditis, chronic suppressive therapy with fluconazole is recommended after initial treatment. Treat suppurative thrombophlebitis for at least 2 weeks after candidemia (if present) has cleared.
For empirical therapy for presumed fungal infection in patients with febrile neutropenia*:
Intravenous dosage:
Adults: 0.6 to 1.2 mg/kg/dose IV every 24 hours. In neutropenic patients with cancer, empiric antifungal therapy is suggested for patients with persistent or recurrent fever after 4 to 7 days of antibiotics and whose overall duration of neutropenia is expected to be more than 7 days. If already receiving antifungal prophylaxis, consider switching to a different class of mold active agent.
Infants, Children, and Adolescents: 0.6 to 1.2 mg/kg/dose IV every 24 hours. In neutropenic patients with cancer, empiric antifungal therapy is suggested for patients with persistent or recurrent fever after 4 to 7 days of antibiotics and whose overall duration of neutropenia is expected to be more than 7 days. If already receiving antifungal prophylaxis, consider switching to a different class of mold active agent. Caspofungin or liposomal amphotericin B is a preferred agent for empiric antifungal therapy in children with cancer and/or undergoing hematopoietic stem cell transplantation.
For fungal prophylaxis* (e.g., candidiasis prophylaxis*, aspergillosis prophylaxis*) in immunosuppressed patients:
Intravenous dosage:
Infants, Children, and Adolescents: Various regimens have been used. 0.5 mg/kg/dose IV 3 times/week was compared to oral voriconazole for fungal prophylaxis in patients 15 years and younger with acute leukemia undergoing induction therapy (n = 100). A significant difference in efficacy was not found between the regimens, and oral voriconazole was thought to be more convenient. In another study, 0.2 mg/kg/dose (Max: 10 mg/dose) IV was compared to fluconazole in patients (ages 4 to 63 years) undergoing hematopoietic stem cell transplantation. No significant difference was found between the groups in regard to proven or suspected fungal infections, survival at 100 days post-transplant, or death attributable to fungal infection.
Nebulized dosage:
Adolescents: Data are limited. Doses of 5 to 10 mg (diluted in 5 to 10 mL of Sterile Water for Injection) administered by nebulizer over 10 to 20 minutes and given 1 to 3 times daily have been used in patients after lung transplantation and neutropenic patients after bone marrow transplantation or intensive chemotherapy. In a retrospective study (n = 611) of older adolescent and adult stem cell transplant recipients, 25 mg by nebulizer once daily was used. Most studies have found a reduction in invasive fungal infections with nebulized amphotericin B deoxycholate ; however, some data have shown no benefit.
For the treatment of moderately severe to severe blastomycosis:
NOTE: For CNS disease, see meningitis indication.
-for the treatment of moderately severe to severe pulmonary blastomycosis:
Intravenous dosage:
Adults: 0.7 to 1 mg/kg/dose IV every 24 hours for 1 to 2 weeks or until improvement is noted. Continue step-down therapy with itraconazole to complete a total of 6 to 12 months of therapy. The FDA-approved dosage is 0.25 to 0.3 mg/kg/dose IV every 24 hours; may increase dose by 5 to 10 mg/day to a final dose of 0.5 to 0.7 mg/kg/day. Doses up to 1 mg/kg/day or 1.5 mg/kg given every other day may be warranted.
Infants*, Children*, and Adolescents*: 0.7 to 1 mg/kg/dose IV every 24 hours for 1 to 2 weeks or until improvement is noted. Continue step-down therapy with itraconazole to complete a total of 12 months of therapy.
Neonates*: 1 mg/kg/dose IV every 24 hours for 1 to 2 weeks or until improvement is noted.
-for the treatment of moderately severe to severe disseminated extrapulmonary blastomycosis, including osteoarticular blastomycosis:
Intravenous dosage:
Adults: 0.7 to 1 mg/kg/dose IV every 24 hours for 1 to 2 weeks or until improvement is noted. Continue step-down therapy with itraconazole to complete a total of at least 12 months of therapy. The FDA-approved dosage is 0.25 to 0.3 mg/kg/dose IV every 24 hours; may increase dose by 5 to 10 mg/day to a final dose of 0.5 to 0.7 mg/kg/day. Doses up to 1 mg/kg/day or 1.5 mg/kg given every other day may be warranted.
Infants*, Children*, and Adolescents*: 0.7 to 1 mg/kg/dose IV every 24 hours for 1 to 2 weeks or until improvement is noted. Continue step-down therapy with itraconazole to complete a total of 12 months of therapy.
Neonates*: 1 mg/kg/dose IV every 24 hours for 1 to 2 weeks or until improvement is noted.
-for the treatment of blastomycosis in immunosuppressed patients:
Intravenous dosage:
Immunosuppressed Adults: 0.7 to 1 mg/kg/dose IV every 24 hours for 1 to 2 weeks or until improvement is noted. Continue step-down therapy with itraconazole to complete a total of at least 12 months of therapy. Lifelong suppressive therapy may be required.
Immunosuppressed Infants*, Children*, and Adolescents*: 0.7 to 1 mg/kg/dose IV every 24 hours for 1 to 2 weeks or until improvement is noted. Continue step-down therapy with itraconazole to complete a total of at least 12 months of therapy. Lifelong suppressive therapy may be required.
For the treatment of severe pulmonary or nonmeningeal, extrapulmonary coccidioidomycosis:
NOTE: For CNS disease, see meningitis.
-for the treatment of severe pulmonary or nonmeningeal, extrapulmonary coccidioidomycosis in persons without HIV:
Intravenous dosage:
Adults: 0.25 to 0.3 mg/kg/dose IV every 24 hours; may increase dose by 5 to 10 mg/day to a final dose of 0.5 to 0.7 mg/kg/day. Doses up to 1 mg/kg/day or 1.5 mg/kg given every other day may be warranted. Follow with fluconazole or itraconazole after clinical improvement. Duration of treatment varies with disease location and depends on clinical response; treatment may be necessary for 12 months or longer.
Adolescents*: 0.7 to 1 mg/kg/dose IV every 24 hours until clinical improvement, followed by fluconazole or itraconazole. Duration of treatment varies with disease location and depends on clinical response; treatment may be necessary for 12 months or longer.
Infants* and Children*: 0.5 to 1 mg/kg/dose IV every 24 hours until clinical improvement, followed by fluconazole or itraconazole. Duration of treatment varies with disease location and depends on clinical response; treatment may be necessary for 12 months or longer.
-for the treatment of severe pulmonary or nonmeningeal, extrapulmonary coccidioidomycosis in persons living with HIV:
Intravenous dosage:
Adults: 0.7 to 1 mg/kg/dose IV every 24 hours until clinical improvement, followed by fluconazole or itraconazole for at least 12 months then long-term suppressive therapy; discontinuation is dependent on clinical and serological response. Some experts will also add an azole to amphotericin B during the acute phase of treatment.
Adolescents*: 0.7 to 1 mg/kg/dose IV every 24 hours until clinical improvement, followed by fluconazole or itraconazole for at least 12 months then long-term suppressive therapy; discontinuation is dependent on clinical and serological response. Some experts will also add an azole to amphotericin B during the acute phase of treatment.
Infants* and Children*: 0.5 to 1 mg/kg/dose IV every 24 hours until clinical improvement, followed by fluconazole or itraconazole for at least 12 months then long-term suppressive therapy. Some experts will also add an azole to amphotericin B during the acute phase of treatment.
For the treatment of CNS cryptococcal infections, including cryptococcal meningitis and cerebral cryptococcomas:
-Persons living with HIV:
Intravenous dosage:
Adults: 0.7 to 1 mg/kg/dose IV every 24 hours in combination with flucytosine for at least 2 weeks as a preferred induction therapy. In resource-limited settings, amphotericin B deoxycholate with flucytosine for 1 week followed by high-dose fluconazole for 1 week is recommended as the preferred induction regimen. Alternatively, amphotericin B deoxycholate may be given as a single agent or with high-dose fluconazole for patients unable to tolerate flucytosine. For treatment failure or relapse, continue induction therapy until clinical response. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy. The FDA-approved dosage is 0.25 to 0.3 mg/kg/dose IV every 24 hours; may increase dose by 5 to 10 mg/day to a final dose of 0.5 to 0.7 mg/kg/day. Doses up to 1 mg/kg/day or 1.5 mg/kg every other day may be warranted.
Adolescents*: 0.7 to 1 mg/kg/dose IV every 24 hours in combination with flucytosine for at least 2 weeks as a preferred induction therapy. In resource-limited settings, amphotericin B deoxycholate with flucytosine for 1 week followed by high-dose fluconazole for 1 week is recommended as the preferred induction regimen. Alternatively, amphotericin B deoxycholate may be given as a single agent or with high-dose fluconazole for patients unable to tolerate flucytosine. For treatment failure or relapse, continue induction therapy until clinical response. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
Infants* and Children*: 1 mg/kg/dose IV every 24 hours in combination with flucytosine for at least 2 weeks as a preferred induction therapy. In resource-limited settings, amphotericin B deoxycholate with flucytosine for 1 week followed by high-dose fluconazole for 1 week is recommended as the preferred induction regimen. Alternatively, amphotericin B deoxycholate 1 to 1.5 mg/kg/dose IV every 24 hours may be given as a single agent or with high-dose fluconazole for patients unable to tolerate flucytosine. For treatment failure or relapse, continue induction therapy until clinical response. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
Neonates*: 1 mg/kg/dose IV every 24 hours in combination with flucytosine for at least 2 weeks as a preferred induction therapy. Alternatively, amphotericin B deoxycholate 1 to 1.5 mg/kg/dose IV every 24 hours may be given as a single agent or with high-dose fluconazole for patients unable to tolerate flucytosine. For treatment failure or relapse, continue induction therapy until clinical response. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
-Organ transplant recipients:
Intravenous dosage:
Adults: 0.7 mg/kg/dose IV every 24 hours for 4 to 6 weeks as an alternative single agent induction therapy for patients unable to tolerate flucytosine. For cerebral cryptococcomas, give induction therapy for at least 6 weeks. For persistence or relapse of cryptococcal infection, reinstate induction therapy for 4 to 10 weeks. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy. The FDA-approved dosage is 0.25 to 0.3 mg/kg/dose IV every 24 hours; may increase dose by 5 to 10 mg/day to a final dose of 0.5 to 0.7 mg/kg/day. Doses up to 1 mg/kg/day or 1.5 mg/kg every other day may be warranted.
Infants*, Children*, and Adolescents*: 1 mg/kg/dose IV every 24 hours for 4 to 6 weeks as an alternative single agent induction therapy for patients unable to tolerate flucytosine. For cerebral cryptococcomas, give induction therapy for at least 6 weeks. For persistence or relapse of cryptococcal infection, reinstate induction therapy for 4 to 10 weeks. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
Neonates*: 1 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, guidelines suggest amphotericin B deoxycholate for 4 to 6 weeks as an alternative single agent induction therapy for patients unable to tolerate flucytosine. For cerebral cryptococcomas, give induction therapy for at least 6 weeks. For persistence or relapse of cryptococcal infection, reinstate induction therapy for 4 to 10 weeks. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
-Non-HIV, nontransplant patients:
Intravenous dosage:
Adults: 0.7 to 1 mg/kg/dose IV every 24 hours in combination with flucytosine for at least 4 weeks as a preferred induction therapy. For patients at low risk for therapy failure, consider induction therapy for only 2 weeks. If amphotericin B deoxycholate is given as a single agent, consider lengthening induction therapy for at least 2 weeks. In patients with neurological complications or cerebral cryptococcomas, give induction therapy for at least 6 weeks. For persistence or relapse of cryptococcal infection, reinstate induction therapy for 4 to 10 weeks. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy. The FDA-approved dosage is 0.25 to 0.3 mg/kg/dose IV every 24 hours; may increase dose by 5 to 10 mg/day to a final dose of 0.5 to 0.7 mg/kg/day. Doses up to 1 mg/kg/day or 1.5 mg/kg every other day may be warranted.
Infants*, Children*, and Adolescents*: 1 mg/kg/dose IV every 24 hours in combination with flucytosine for at least 4 weeks as a preferred induction therapy. For patients at low risk for therapy failure, consider induction therapy for only 2 weeks. If amphotericin B deoxycholate is given as a single agent, consider lengthening induction therapy for at least 2 weeks. In patients with neurological complications or cerebral cryptococcomas, give induction therapy for at least 6 weeks. For persistence or relapse of cryptococcal infection, reinstate induction therapy for 4 to 10 weeks. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
Neonates*: 1 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, guidelines suggest amphotericin B deoxycholate in combination with flucytosine for at least 4 weeks as a preferred induction therapy. For patients at low risk for therapy failure, consider induction therapy for only 2 weeks. If amphotericin B deoxycholate is given as a single agent, consider lengthening induction therapy for at least 2 weeks. In patients with neurological complications or cerebral cryptococcomas, give induction therapy for at least 6 weeks. For persistence or relapse of cryptococcal infection, reinstate induction therapy for 4 to 10 weeks. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
For the treatment of disseminated (nonmeningeal) or pulmonary cryptococcosis:
NOTE: For the treatment of CNS infections, see cryptococcal meningitis.
-Persons living with HIV:
Intravenous dosage:
Adults: 0.7 to 1 mg/kg/dose IV every 24 hours in combination with flucytosine for at least 2 weeks as a preferred induction therapy. In resource-limited settings, amphotericin B deoxycholate with flucytosine for 1 week followed by high-dose fluconazole for 1 week is recommended as the preferred induction regimen. Alternatively, amphotericin B deoxycholate may be given as a single agent or with high-dose fluconazole for patients unable to tolerate flucytosine. For treatment failure or relapse, continue induction therapy until clinical response. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy. The FDA-approved dosage is 0.25 to 0.3 mg/kg/dose IV every 24 hours; may increase dose by 5 to 10 mg/day to a final dose of 0.5 to 0.7 mg/kg/day. Doses up to 1 mg/kg/day or 1.5 mg/kg every other day may be warranted.
Adolescents*: 0.7 to 1 mg/kg/dose IV every 24 hours in combination with flucytosine for at least 2 weeks as a preferred induction therapy. In resource-limited settings, amphotericin B deoxycholate with flucytosine for 1 week followed by high-dose fluconazole for 1 week is recommended as the preferred induction regimen. Alternatively, amphotericin B deoxycholate may be given as a single agent or with high-dose fluconazole for patients unable to tolerate flucytosine. For treatment failure or relapse, continue induction therapy until clinical response. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
Infants* and Children*: 0.7 to 1 mg/kg/dose IV every 24 hours with or without flucytosine. Duration of therapy dependent on site and severity of infection and clinical response.
Neonates*: 0.7 to 1 mg/kg/dose IV every 24 hours with or without flucytosine. Duration of therapy dependent on site and severity of infection and clinical response.
-Organ transplant recipients:
Intravenous dosage:
Adults: 0.7 mg/kg/dose IV every 24 hours for 4 to 6 weeks as an alternative single agent induction therapy for patients unable to tolerate flucytosine. For persistence or relapse of cryptococcal infection, reinstate induction therapy for 4 to 10 weeks. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy. The FDA-approved dosage is 0.25 to 0.3 mg/kg/dose IV every 24 hours; may increase dose by 5 to 10 mg/day to a final dose of 0.5 to 0.7 mg/kg/day. Doses up to 1 mg/kg/day or 1.5 mg/kg every other day may be warranted.
Infants*, Children*, and Adolescents*: 1 mg/kg/dose IV every 24 hours for 4 to 6 weeks as an alternative single agent induction therapy for patients unable to tolerate flucytosine. For persistence or relapse of cryptococcal infection, reinstate induction therapy for 4 to 10 weeks. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
Neonates*: 1 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, guidelines suggest amphotericin B deoxycholate for 4 to 6 weeks as an alternative single agent induction therapy for patients unable to tolerate flucytosine. For persistence or relapse of cryptococcal infection, reinstate induction therapy for 4 to 10 weeks. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
-Non-HIV, nontransplant patients:
Intravenous dosage:
Adults: 0.7 to 1 mg/kg/dose IV every 24 hours in combination with flucytosine for at least 4 weeks as a preferred induction therapy. For patients at low risk for therapy failure, consider induction therapy for only 2 weeks. If amphotericin B deoxycholate is given as a single agent, consider lengthening induction therapy for at least 2 weeks. For persistence or relapse of cryptococcal infection, reinstate induction therapy for 4 to 10 weeks. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy. The FDA-approved dosage is 0.25 to 0.3 mg/kg/dose IV every 24 hours; may increase dose by 5 to 10 mg/day to a final dose of 0.5 to 0.7 mg/kg/day. Doses up to 1 mg/kg/day or 1.5 mg/kg every other day may be warranted.
Infants*, Children*, and Adolescents*: 1 mg/kg/dose IV every 24 hours in combination with flucytosine for at least 4 weeks as a preferred induction therapy. For patients at low risk for therapy failure, consider induction therapy for only 2 weeks. If amphotericin B deoxycholate is given as a single agent, consider lengthening induction therapy for at least 2 weeks. For persistence or relapse of cryptococcal infection, reinstate induction therapy for 4 to 10 weeks. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
Neonates*: 1 mg/kg/dose IV every 24 hours. Although specific neonatal recommendations are not available, guidelines suggest amphotericin B deoxycholate in combination with flucytosine for at least 4 weeks as a preferred induction therapy. For patients at low risk for therapy failure, consider induction therapy for only 2 weeks. If amphotericin B deoxycholate is given as a single agent, consider lengthening induction therapy for at least 2 weeks. For persistence or relapse of cryptococcal infection, reinstate induction therapy for 4 to 10 weeks. Follow induction therapy with consolidation therapy with fluconazole for at least 8 weeks, and then chronic suppressive therapy.
For the treatment of moderately severe to severe disseminated (nonmeningeal) or pulmonary histoplasmosis:
-for the treatment of pulmonary histoplasmosis:
Intravenous dosage:
Adults: 0.25 to 0.3 mg/kg/dose IV every 24 hours; may increase dose by 5 to 10 mg/day to a final dose of 0.5 to 0.7 mg/kg/day. Doses up to 1 mg/kg/day or 1.5 mg/kg given every other day may be warranted. Alternately, clinical practice guidelines suggest 0.7 to 1 mg/kg/dose IV every 24 hours for 1 to 2 weeks followed by itraconazole for a total of 12 weeks as an alternative to a lipid formulation amphotericin B in patients who are at a low risk for nephrotoxicity.
Infants*, Children*, and Adolescents*: 1 mg/kg/dose IV every 24 hours for 1 to 2 weeks followed by itraconazole for a total of 12 weeks. Clinical practice guidelines suggest amphotericin B deoxycholate as the preferred treatment.
Neonates*: 1 mg/kg/dose IV every 24 hours for 1 to 2 weeks followed by itraconazole for a total of 12 weeks. Clinical practice guidelines suggest amphotericin B deoxycholate as the preferred treatment.
-for the treatment of disseminated (nonmeningeal) histoplasmosis:
Intravenous dosage:
Adults: 0.25 to 0.3 mg/kg/dose IV every 24 hours; may increase dose by 5 to 10 mg/day to a final dose of 0.5 to 0.7 mg/kg/day. Doses up to 1 mg/kg/day or 1.5 mg/kg given every other day may be warranted. Alternately, clinical practice guidelines suggest 0.7 to 1 mg/kg/dose IV every 24 hours for 1 to 2 weeks followed by itraconazole for a total of 12 weeks as an alternative to a lipid formulation amphotericin B in patients who are at a low risk for nephrotoxicity. For HIV-infected patients, treat for at least 2 weeks or until clinically improved followed by itraconazole for at least 12 months. Longer treatment may be required in patients with persistent immunodeficiency. Clinical practice guidelines suggest liposomal amphotericin B as a preferred treatment.
Adolescents*: 0.7 to 1 mg/kg/dose IV every 24 hours for 1 to 2 weeks followed by itraconazole for a total of 12 weeks as an alternative to a lipid formulation amphotericin B in patients who are at a low risk for nephrotoxicity. For HIV-infected patients, treat for at least 2 weeks or until clinically improved followed by itraconazole for at least 12 months. Longer treatment may be required in patients with persistent immunodeficiency. Clinical practice guidelines suggest liposomal amphotericin B as a preferred treatment.
Infants* and Children*: 1 mg/kg/dose IV every 24 hours for 4 to 6 weeks, or alternately, for 2 to 4 weeks followed by itraconazole for a total of 12 weeks. Longer treatment may be required in patients with persistent immunodeficiency. Treat for at least 2 weeks or longer if clinical improvement is delayed followed by itraconazole for 12 months, or alternately, for 4 to 6 weeks for HIV-infected children. While liposomal amphotericin B is preferred treatment in HIV-infected children, clinical practice guidelines suggest amphotericin B deoxycholate as the preferred treatment in non-HIV-infected children.
Neonates*: 1 mg/kg/dose IV every 24 hours for 4 to 6 weeks, or alternately, for 2 to 4 weeks followed by itraconazole for a total of 12 weeks. Longer treatment may be required in patients with persistent immunodeficiency. Treat for at least 2 weeks or longer if clinical improvement is delayed followed by itraconazole for 12 months, or alternately, for 4 to 6 weeks for HIV-infected children. While liposomal amphotericin B is preferred treatment in HIV-infected children, clinical practice guidelines suggest amphotericin B deoxycholate as the preferred treatment in non-HIV-infected children.
For the treatment of leishmaniasis:
-for the treatment of cutaneous leishmaniasis:
Intravenous dosage:
Adults: 0.5 to 1 mg/kg/dose IV every 24 hours or every other day for a cumulative total of 15 to 30 mg/kg is recommended by guidelines. The FDA-approved dosage is 0.25 to 0.3 mg/kg/dose IV every 24 hours; may increase dose by 5 to 10 mg/day to a final dose of 0.5 to 0.7 mg/kg/day. Doses up to 1 mg/kg/day or 1.5 mg/kg given every other day may be warranted. Amphotericin B deoxycholate may be of some benefit in American mucocutaneous leishmaniasis, but it is not the preferred therapy.
Infants*, Children*, and Adolescents*: 0.5 to 1 mg/kg/dose IV every 24 hours or every other day for a cumulative total of 15 to 30 mg/kg.
-for the treatment of mucosal leishmaniasis:
Intravenous dosage:
Adults: 0.5 to 1 mg/kg/dose IV every 24 hours or every other day for a cumulative total of 20 to 45 mg/kg is recommended by guidelines. The FDA-approved dosage is 0.25 to 0.3 mg/kg/dose IV every 24 hours; may increase dose by 5 to 10 mg/day to a final dose of 0.5 to 0.7 mg/kg/day. Doses up to 1 mg/kg/day or 1.5 mg/kg given every other day may be warranted. Amphotericin B deoxycholate may be of some benefit in American mucocutaneous leishmaniasis, but it is not the preferred therapy.
Infants*, Children*, and Adolescents*: 0.5 to 1 mg/kg/dose IV every 24 hours or every other day for a cumulative total of 20 to 45 mg/kg.
-for the treatment of visceral leishmaniasis*:
Intravenous dosage:
Adults: 1 mg/kg/dose IV every 24 hours or every other day for a cumulative total of 15 to 20 doses as an alternative to liposomal amphotericin B. A total dose of 1.5 to 2 g, then chronic maintenance therapy with a lipid formulation amphotericin B, or alternately, pentavalent antimony is suggested for HIV-infected patients. For patients who do not clear parasites or who experience relapses, expert advice regarding further treatment is recommended. Amphotericin B deoxycholate is not recommended when there are contraindications to or toxicity with liposomal amphotericin B except in patients who develop liposome-induced complement activation-related pseudoallergy (CARPA).
Adolescents: 1 mg/kg/dose IV every 24 hours or every other day for a cumulative total of 15 to 20 doses as an alternative to liposomal amphotericin B. A total dose of 1.5 to 2 g, then chronic maintenance therapy with a lipid formulation amphotericin B, or alternately, pentavalent antimony is suggested for HIV-infected patients. For patients who do not clear parasites or who experience relapses, expert advice regarding further treatment is recommended. Amphotericin B deoxycholate is not recommended when there are contraindications to or toxicity with liposomal amphotericin B except in patients who develop liposome-induced complement activation-related pseudoallergy (CARPA).
Infants and Children: 1 mg/kg/dose IV every 24 hours or every other day for a cumulative total of 15 to 20 doses as an alternative to liposomal amphotericin B. Amphotericin B deoxycholate is not recommended when there are contraindications to or toxicity with liposomal amphotericin B except in patients who develop liposome-induced complement activation-related pseudoallergy (CARPA).
For the treatment of mucormycosis (phycomycosis):
Intravenous dosage:
Adults: 0.25 to 0.3 mg/kg/dose IV every 24 hours; may increase dose by 5 to 10 mg/day to a final dose of 0.5 to 0.7 mg/kg/day. Doses up to 1 mg/kg/day or 1.5 mg/kg given every other day may be warranted.
Infants*, Children*, and Adolescents*: 1 to 1.5 mg/kg/dose IV every 24 hours. In case reports, treatment typically continued for 6 weeks.
-for rhinocerebral phycomycosis:
Intravenous dosage:
Adults: 0.25 to 0.3 mg/kg/dose IV every 24 hours; may increase dose by 5 to 10 mg/day to a final dose of 0.5 to 0.7 mg/kg/day. Doses up to 1 mg/kg/day or 1.5 mg/kg given every other day may be warranted. A total dose of at least 3 g is suggested.
Infants*, Children*, and Adolescents*: 1 to 1.5 mg/kg/dose IV every 24 hours. In case reports, treatment typically continued for 6 weeks.
For the treatment of sporotrichosis:
NOTE: For CNS disease, see meningitis indication.
Intravenous dosage:
Adults: 0.7 to 1 mg/kg/dose IV every 24 hours until favorable response. Continue step-down therapy with itraconazole to complete a total of at least 12 months of therapy. The FDA-approved dosage is 0.25 to 0.3 mg/kg/dose IV every 24 hours; may increase dose by 5 to 10 mg/day to a final dose of 0.5 to 0.7 mg/kg/day. Doses up to 1 mg/kg/day or 1.5 mg/kg given every other day may be warranted. Therapy with amphotericin B deoxycholate has ranged up to 9 months with a total dose up to 2.5 g. Guidelines recommend amphotericin B deoxycholate as alternative therapy for osteoarticular, severe or life-threatening pulmonary, or disseminated disease.
Infants*, Children*, and Adolescents*: 0.7 mg/kg/dose IV every 24 hours for visceral or disseminated disease. After favorable response, continue step-down therapy with itraconazole to complete a total of at least 12 months of therapy.
For the treatment of talaromycosis* in HIV-infected patients:
Intravenous dosage:
Adults: 0.7 mg/kg/day IV for 2 weeks as alternative therapy, then itraconazole for consolidation therapy and chronic suppressive therapy.
Adolescents: 0.7 mg/kg/day IV for 2 weeks as alternative therapy, then itraconazole for consolidation therapy and chronic suppressive therapy.
Maximum Dosage Limits:
Maximum dosage is generally dependent on route of administration and the indication for use. General IV maximum dosage guidelines follow.
-Adults
1-1.5 mg/kg/day IV.
-Elderly
1-1.5 mg/kg/day IV.
-Adolescents
1-1.5 mg/kg/day IV.
-Children
Generally 1 mg/kg/day IV; occasional short term use of 1.5 mg/kg/day IV may be permissible in specific situations.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that dosage adjustments are not needed.
Patients with Renal Impairment Dosing
Use with caution in patients with renal impairment as amphotericin B is nephrotoxic. Specific guidelines for dosage adjustments in renal impairment are not available; it appears that dosage adjustments are not needed. However, a dosage interval of 24 to 36 hours has been recommended in patients with a GFR < 10 mL/min.
Intermittent hemodialysis
Amphotericin B is not efficiently removed by hemodialysis; do not time amphotericin B administration on hemodialysis schedule.
*non-FDA-approved indication
Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Acetaminophen; Aspirin: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Acetaminophen; Aspirin; Diphenhydramine: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Acetaminophen; Ibuprofen: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Acetazolamide: (Moderate) Acetazolamide can potentiate hypokalemia and therefore can increase the risk of hypokalemia caused by amphotericin B.
Acyclovir: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including acyclovir, may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Dosage reduction may be necessary if renal impairment occurs.
Albuterol; Budesonide: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Aldesleukin, IL-2: (Major) Avoid concomitant use of amphotericin B and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Amikacin: (Major) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with aminoglycosides (e.g., gentamicin, tobramycin, or amikacin). Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Aminosalicylate sodium, Aminosalicylic acid: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Amlodipine; Celecoxib: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Aprotinin: (Moderate) The manufacturer recommends using aprotinin cautiously in patients that are receiving drugs that can affect renal function, such as the aprotinin, as the risk of renal impairment may be increased.
Arsenic Trioxide: (Major) Because electrolyte abnormalities increase the risk of QT interval prolongation and serious arrhythmias, avoid the concomitant use of arsenic trioxide with drugs that may cause electrolyte abnormalities, particularly hypokalemia and hypomagnesemia. Examples of drugs that may cause electrolyte abnormalities include amphotericin B. If concomitant drug use is unavoidable, frequently monitor serum electrolytes (and replace as necessary) and electrocardiograms. Torsade de pointes was reported in 1 patient who received arsenic trioxide during induction therapy for relapsed acute promyelocytic leukemia; this patient was also receiving amphotericin B.
Aspirin, ASA: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Aspirin, ASA; Butalbital; Caffeine: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Aspirin, ASA; Caffeine: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Aspirin, ASA; Caffeine; Orphenadrine: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Aspirin, ASA; Carisoprodol; Codeine: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Aspirin, ASA; Dipyridamole: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Aspirin, ASA; Omeprazole: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Aspirin, ASA; Oxycodone: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Atenolol; Chlorthalidone: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Atracurium: (Moderate) Monitor serum potassium concentrations with concomitant use of neuromuscular blockers and amphotericin B. Amphotericin B-induced hypokalemia may prolong neuromuscular blockade.
Auranofin: (Minor) Both amphotericin and gold compounds can cause nephrotoxicity. Auranofin has been reported to cause a nephrotic syndrome or glomerulonephritis with proteinuria and hematuria. Monitor renal function carefully during concurrent therapy.
Azelastine; Fluticasone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Azilsartan; Chlorthalidone: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Bacillus Calmette-Guerin Vaccine, BCG: (Moderate) Administration of amphotericin B [lipid complex (ABLC), cholesteryl sulfate complex (ABCD), and liposomal (LAmB)] with antineoplastic agents may increase the potential for nephrotoxicity, bronchospasm, and hypotension. Amphotericin B-induced hypokalemia can result in interactions with other drugs.
Bacitracin: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents, such as amphoteracin B; when possible, avoid concomitant administration. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, should not be given with other drugs that have a nephrotoxic potential.
Bacitracin; Hydrocortisone; Neomycin; Polymyxin B: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents, such as amphoteracin B; when possible, avoid concomitant administration. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, should not be given with other drugs that have a nephrotoxic potential.
Bacitracin; Polymyxin B: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents, such as amphoteracin B; when possible, avoid concomitant administration. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, should not be given with other drugs that have a nephrotoxic potential.
Beclomethasone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Beractant: (Major) Some surfactant-anti-infective mixtures have been shown to affect the in vivo activity of exogenous pulmonary surfactants when they are administered via inhalation. Surfactants should not be mixed with anti-infectives that are commonly administered via nebulization such as amphotericin B.
Betamethasone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as amphotericin B. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Bismuth Subsalicylate: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Budesonide: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Budesonide; Formoterol: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Bumetanide: (Moderate) Amphotericin B-induced hypokalemia can result in interactions with other drugs. Concurrent use of amphotericin B with loop diuretics can cause additive hypokalemia or hypomagnesemia due to renal potassium and magnesium wasting. It is prudent to monitor renal function parameters and serum electrolyte concentrations during co-therapy with loop diuretics and drugs which induce hypokalemia.
Bupivacaine; Meloxicam: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Butalbital; Aspirin; Caffeine; Codeine: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Calfactant: (Major) Some surfactant-anti-infective mixtures have been shown to affect the in vivo activity of exogenous pulmonary surfactants when they are administered via inhalation. Surfactants should not be mixed with anti-infectives that are commonly administered via nebulization such as amphotericin B.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Capreomycin: (Major) Since capreomycin is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including amphotericin B, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Cardiac glycosides: (Moderate) Amphotericin B-induced hypokalemia can potentiate the cardiac toxicity of cardiac glycosides (e.g., digoxin). If used concomitantly, closely monitor serum electrolytes and cardiac function.
Celecoxib: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Celecoxib; Tramadol: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Chlorothiazide: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Chlorthalidone: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Choline Salicylate; Magnesium Salicylate: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Ciclesonide: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Cidofovir: (Contraindicated) The administration of cidofovir and other potentially nephrotoxic agents, such amphotericin B is contraindicated. Amphotericin B should be discontinued at least 7 days prior to beginning cidofovir.
Cisapride: (Major) Amphotericin B- induced electrolyte imbalances can result in significant interactions with other drugs. Hypokalemia or hypomagnesemia can potentiate the cardiac toxicity of cisapride. Electrolytes should be monitored in patients who are taking cisapride prior to and during amphoteracin B treatment. Cisapride is contraindicated for use in patients with known serum electrolyte imbalances; cisapride should be discontinued if such imbalances occur while these medications are taken concurrently.
Cisatracurium: (Moderate) Monitor serum potassium concentrations with concomitant use of neuromuscular blockers and amphotericin B. Amphotericin B-induced hypokalemia may prolong neuromuscular blockade.
Cisplatin: (Moderate) Closely monitor renal function if concomitant use with cisplatin and amphotericin B is necessary. Both drugs can cause nephrotoxicity, which may be additive when used together.
Clindamycin: (Moderate) Concomitant use of amphotericin B and clindamycin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Colistimethate, Colistin, Polymyxin E: (Major) Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including amphotericin B and the amphotericin B lipid formulations, may increase serum concentrations of either drug. Chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
Colistin: (Major) Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including amphotericin B and the amphotericin B lipid formulations, may increase serum concentrations of either drug. Chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
Corticosteroids: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Cortisone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Cyclophosphamide: (Moderate) Monitor renal function if cyclophosphamide is used concomitantly with amphotericin B as there may be an increased risk of nephrotoxicity.
Cyclosporine: (Moderate) Cyclosporine should be used cautiously with nephrotoxic drugs, such as amphotericin B, as cyclosporine itself can cause structural kidney damage. Additive nephrotoxicity can occur if these drugs are administered together. Monitor renal function and fluid status carefully.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as amphotericin B. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Daunorubicin Liposomal; Cytarabine Liposomal: (Minor) Amphotericin B can reduce cell resistance to daunorubicin, thus enhancing its activity. Amphotericin B can alter cell membranes, which could otherwise impede daunorubicin's entry into the cell. How this may affect liposomal delivery of daunorubicin is not known.
Deflazacort: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Dexamethasone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Dichlorphenamide: (Moderate) Use dichlorphenamide and antifungals together with caution. Dichlorphenamide increases potassium excretion and can cause hypokalemia and should be used cautiously with other drugs that may cause hypokalemia including antifungals. Measure potassium concentrations at baseline and periodically during dichlorphenamide treatment. If hypokalemia occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy. In addition, both dichlorphenamide and some amphotericin B products (i.e., amphotericin B cholesteryl sulfate complex (ABCD), amphotericin B lipid complex (ABLC), amphotericin B liposomal (LAmB)) can cause metabolic acidosis. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
Diclofenac: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Diclofenac; Misoprostol: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Diflunisal: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Digoxin: (Moderate) Amphotericin B-induced hypokalemia can potentiate the cardiac toxicity of cardiac glycosides (e.g., digoxin). If used concomitantly, closely monitor serum electrolytes and cardiac function.
Diphenhydramine; Ibuprofen: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Diphenhydramine; Naproxen: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Dofetilide: (Major) Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs, such as amphotericin B, increasing the potential for dofetilide-induced torsade de pointes. Potassium levels should be within the normal range prior and during administration of dofetilide.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Minor) Additive nephrotoxicity can also occur if amphotericin B is given concomitantly with tenofovir. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Dronabinol: (Major) Use caution if coadministration of dronabinol with amphotericin B is necessary, and monitor for an increase in amphotericin-related adverse reactions. Dronabinol is also highly bound to plasma proteins and may displace and increase the free fraction of other concomitantly administered protein-bound drugs such as amphotericin B.
Droperidol: (Moderate) Caution is advised when using droperidol in combination with amphoterecin B, which may cause hypokalemia or hypomagnesemia. Using these drugs together may increase the risk for QT prolongation or cardiac arrhythmias.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Minor) Additive nephrotoxicity can also occur if amphotericin B is given concomitantly with tenofovir. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Minor) Additive nephrotoxicity can also occur if amphotericin B is given concomitantly with tenofovir. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as amphotericin B. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Minor) Additive nephrotoxicity can also occur if amphotericin B is given concomitantly with tenofovir. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as amphotericin B. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Minor) Additive nephrotoxicity can also occur if amphotericin B is given concomitantly with tenofovir. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as amphotericin B. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Minor) Additive nephrotoxicity can also occur if amphotericin B is given concomitantly with tenofovir. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Entecavir: (Moderate) Entecavir is primarily eliminated by the kidneys and amphotericin B can affect renal function; concurrent administration may increase the serum concentrations of entecavir and adverse events. The manufacturer of entecavir recommends monitoring for adverse effects when these drugs are coadministered.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Ethacrynic Acid: (Moderate) Amphotericin B-induced hypokalemia can result in interactions with other drugs. Concurrent use of amphotericin B with loop diuretics can cause additive hypokalemia or hypomagnesemia due to renal potassium and magnesium wasting. It is prudent to monitor renal function parameters and serum electrolyte concentrations during co-therapy with loop diuretics and drugs which induce hypokalemia.
Ethiodized Oil: (Moderate) Because the use of other nephrotoxic drugs, including amphotericin B, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
Etodolac: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Fenoprofen: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Fluconazole: (Moderate) In vitro and in vivo animal studies of the combination of amphotericin B and imidazoles suggest that imidazole antifungal agents may induce fungal resistance to amphotericin B. Combination therapy should be administered with caution, especially in immunocompromised patients.
Flucytosine: (Minor) Amphotericin B may increase the toxicity of flucytosine by possibly increasing flucytosine cellular uptake and/or impairing flucytosine renal excretion. However, flucytosine can have synergistic effects when used with amphotericin B, and these two drugs frequently are used together to treat cryptococcal infections. This combination may allow for a reduction in the total daily dose of amphotericin B. However, amphotericin B-induced reductions in renal function can increase bone marrow toxicity from flucytosine.
Fludrocortisone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Flunisolide: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Flurbiprofen: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Fluticasone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Fluticasone; Salmeterol: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Fluticasone; Umeclidinium; Vilanterol: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Fluticasone; Vilanterol: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Formoterol; Mometasone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Foscarnet: (Major) The risk of renal toxicity may be increased if foscarnet is used in conjunction with other nephrotoxic agents such as amphotericin B. Avoid concurrent use, unless the potential benefits outweigh the risks to the patient.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Furosemide: (Moderate) Amphotericin B-induced hypokalemia can result in interactions with other drugs. Concurrent use of amphotericin B with loop diuretics can cause additive hypokalemia or hypomagnesemia due to renal potassium and magnesium wasting. It is prudent to monitor renal function parameters and serum electrolyte concentrations during co-therapy with loop diuretics and drugs which induce hypokalemia.
Ganciclovir: (Moderate) Use caution and monitor renal function when ganciclovir is coadministered with amphotericin B because of the potential increase in serum creatinine. Acute renal failure may occur in patients concomitantly receiving potential nephrotoxic drugs.
Gentamicin: (Major) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with aminoglycosides (e.g., gentamicin, tobramycin, or amikacin). Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Gold: (Minor) Both amphotericin and gold compounds can cause nephrotoxicity. Auranofin has been reported to cause a nephrotic syndrome or glomerulonephritis with proteinuria and hematuria. Monitor renal function carefully during concurrent therapy.
Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like amphotericin B. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Hydrocodone; Ibuprofen: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Hydrocortisone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Ibuprofen: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Ibuprofen; Famotidine: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Ibuprofen; Oxycodone: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Ibuprofen; Pseudoephedrine: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Immune Globulin IV, IVIG, IGIV: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like amphotericin B. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Indapamide: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics (indapamide) are coadministered with other drugs with a significant risk of hypokalemia (e.g., amphotericin B).
Indomethacin: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Inotersen: (Moderate) Use caution with concomitant use of inotersen and amphotericin B due to the risk of glomerulonephritis and nephrotoxicity.
Iodixanol: (Moderate) Because the use of other nephrotoxic drugs, including amphotericin B, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
Iohexol: (Moderate) Because the use of other nephrotoxic drugs, including amphotericin B, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
Iomeprol: (Moderate) Because the use of other nephrotoxic drugs, including amphotericin B, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
Iopamidol: (Moderate) Because the use of other nephrotoxic drugs, including amphotericin B, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
Iopromide: (Moderate) Because the use of other nephrotoxic drugs, including amphotericin B, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
Ioversol: (Moderate) Because the use of other nephrotoxic drugs, including amphotericin B, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Isoproterenol: (Moderate) Both isoproterenol and amphotericin B have the potential to cause potassium-wasting or magnesium-wasting. Use of these drugs together may increase the risk of developing arrhythmias by reducing potassium or magnesium serum concentrations.
Isosulfan Blue: (Moderate) Because the use of other nephrotoxic drugs, including amphotericin B, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
Itraconazole: (Moderate) In vitro and in vivo animal studies of the combination of amphotericin B and imidazoles suggest that imidazole antifungal agents may induce fungal resistance to amphotericin B. Combination therapy should be administered with caution, especially in immunocompromised patients.
Ketoconazole: (Moderate) In vitro and in vivo animal studies of the combination of amphotericin B and imidazoles suggest that imidazole antifungal agents may induce fungal resistance to amphotericin B. Combination therapy should be administered with caution, especially in immunocompromised patients.
Ketoprofen: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Ketorolac: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Lamivudine; Tenofovir Disoproxil Fumarate: (Minor) Additive nephrotoxicity can also occur if amphotericin B is given concomitantly with tenofovir. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Levoketoconazole: (Moderate) In vitro and in vivo animal studies of the combination of amphotericin B and imidazoles suggest that imidazole antifungal agents may induce fungal resistance to amphotericin B. Combination therapy should be administered with caution, especially in immunocompromised patients.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Loop diuretics: (Moderate) Amphotericin B-induced hypokalemia can result in interactions with other drugs. Concurrent use of amphotericin B with loop diuretics can cause additive hypokalemia or hypomagnesemia due to renal potassium and magnesium wasting. It is prudent to monitor renal function parameters and serum electrolyte concentrations during co-therapy with loop diuretics and drugs which induce hypokalemia.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Magnesium Salicylate: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Mannitol: (Major) Avoid use of mannitol and amphotericin, if possible. Concomitant administration of nephrotoxic drugs, such as amphotericin, increases the risk of renal failure after administration of mannitol.
Meclofenamate Sodium: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Mefenamic Acid: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Meloxicam: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Methazolamide: (Moderate) Amphotericin B may increase the risk of hypokalemia if used concurrently with methazolamide. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy.
Methenamine; Sodium Salicylate: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Methotrexate: (Major) Avoid concomitant use of methotrexate with amphotericin B due to the risk of additive nephrotoxicity as well as an increased risk of severe methotrexate-related adverse reactions. If concomitant use is unavoidable, closely monitor for adverse reactions. Amphotericin B and methotrexate are both nephrotoxic drugs; methotrexate is also renally eliminated. Coadministration of methotrexate with amphotericin B may result in decreased renal function as well as increased methotrexate plasma concentrations.
Methylprednisolone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Metolazone: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Mometasone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Nabumetone: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Naproxen: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Naproxen; Esomeprazole: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Naproxen; Pseudoephedrine: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Neomycin: (Minor) Because the systemic absorption of neomycin is minimal, the risk of this interaction is expected to be low; however, the combined use of amphotericin B and systemic neomycin may increase the risk of nephrotoxicity or ototoxicity. Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Neomycin; Polymyxin B; Bacitracin: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents, such as amphoteracin B; when possible, avoid concomitant administration. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, should not be given with other drugs that have a nephrotoxic potential.
Neuromuscular blockers: (Moderate) Monitor serum potassium concentrations with concomitant use of neuromuscular blockers and amphotericin B. Amphotericin B-induced hypokalemia may prolong neuromuscular blockade.
Nilotinib: (Moderate) Administration of amphotericin B [lipid complex (ABLC), cholesteryl sulfate complex (ABCD), and liposomal (LAmB)] with antineoplastic agents may increase the potential for nephrotoxicity, bronchospasm, and hypotension. Amphotericin B-induced hypokalemia can result in interactions with other drugs.
Non-Ionic Contrast Media: (Moderate) Because the use of other nephrotoxic drugs, including amphotericin B, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
Nonsteroidal antiinflammatory drugs: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Olopatadine; Mometasone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Oxaprozin: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Pancuronium: (Moderate) Monitor serum potassium concentrations with concomitant use of neuromuscular blockers and amphotericin B. Amphotericin B-induced hypokalemia may prolong neuromuscular blockade.
Paromomycin: (Minor) Because the systemic absorption of paromomycin is minimal, the risk of this interaction is expected to be low; however, the combined use of amphotericin B and systemic paromomycin may increase the risk of nephrotoxicity or ototoxicity. Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Pentamidine: (Moderate) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with pentamidine. Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Pimozide: (Major) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as amphotericin B. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia.
Piroxicam: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Polymyxin B: (Major) Systemic polymyxin B should not be used concurrently or sequentially with other drugs that have the potential for nephrotoxicity or neurotoxicity such as amphotericin B. Topical products containing polymyxin B, especially when they are applied over a large body surface area, should be used cautiously.
Poractant Alfa: (Major) Some surfactant-anti-infective mixtures have been shown to affect the in vivo activity of exogenous pulmonary surfactants when they are administered via inhalation. Surfactants should not be mixed with anti-infectives that are commonly administered via nebulization such as amphotericin B.
Posaconazole: (Moderate) In vitro and in vivo animal studies of the combination of amphotericin B and imidazoles suggest that imidazole antifungal agents may induce fungal resistance to amphotericin B. Combination therapy should be administered with caution, especially in immunocompromised patients.
Prednisolone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Prednisone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Rocuronium: (Moderate) Monitor serum potassium concentrations with concomitant use of neuromuscular blockers and amphotericin B. Amphotericin B-induced hypokalemia may prolong neuromuscular blockade.
Saccharomyces boulardii: (Major) Because Saccharomyces boulardii is an active yeast, it would be expected to be inactivated by any antifungals. The manufacturer does not recommend taking in conjunction with any antifungal agents. Patients should avoid use of this probiotic yeast until the fungal or yeast infection is completely treated.
Salicylates: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Salsalate: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Sodium Stibogluconate: (Major) Avoid use of amphotericin B within 2 weeks of sodium stibogluconate. There have been reports of cardiac arrhythmias and sudden death when amphotericin B has been administered soon after sodium stibogluconate for retreatment of visceral leishmaniasis. Allowing a 2 week washout period between sodium stibogluconate and amphotericin B may reduce this risk.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Streptomycin: (Major) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with aminoglycosides such as streptomycin. Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Succinylcholine: (Moderate) Monitor serum potassium concentrations with concomitant use of neuromuscular blockers and amphotericin B. Amphotericin B-induced hypokalemia may prolong neuromuscular blockade.
Sulindac: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Sumatriptan; Naproxen: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Surfactants: (Major) Some surfactant-anti-infective mixtures have been shown to affect the in vivo activity of exogenous pulmonary surfactants when they are administered via inhalation. Surfactants should not be mixed with anti-infectives that are commonly administered via nebulization such as amphotericin B.
Tacrolimus: (Moderate) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with tacrolimus. Amphotericin B and/or tacrolimus dosage reduction may be necessary if renal impairment occurs.
Telavancin: (Moderate) Concurrent or sequential use of telavancin with other potentially nephrotoxic drugs such as amphotericin B may lead to additive nephrotoxicity. Closely monitor renal function and adjust telavancin doses based on calculated creatinine clearance.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as amphotericin B. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as amphotericin B. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Tenofovir Disoproxil Fumarate: (Minor) Additive nephrotoxicity can also occur if amphotericin B is given concomitantly with tenofovir. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Thiazide diuretics: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Tobramycin: (Major) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with tobramycin. Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Tolmetin: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Torsemide: (Moderate) Amphotericin B-induced hypokalemia can result in interactions with other drugs. Concurrent use of amphotericin B with loop diuretics can cause additive hypokalemia or hypomagnesemia due to renal potassium and magnesium wasting. It is prudent to monitor renal function parameters and serum electrolyte concentrations during co-therapy with loop diuretics and drugs which induce hypokalemia.
Triamcinolone: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Valacyclovir: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including valacyclovir, may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Dosage reduction may be necessary if renal impairment occurs.
Valganciclovir: (Moderate) Use caution and monitor renal function when valganciclovir is coadministered with amphotericin B because of the potential increase in serum creatinine. Acute renal failure may occur in patients concomitantly receiving potential nephrotoxic drugs.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Vancomycin: (Moderate) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as Amphotericin B, can lead to additive nephrotoxicity. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Vecuronium: (Moderate) Monitor serum potassium concentrations with concomitant use of neuromuscular blockers and amphotericin B. Amphotericin B-induced hypokalemia may prolong neuromuscular blockade.
Voclosporin: (Moderate) Concomitant use of voclosporin and amphotericin B may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Voriconazole: (Moderate) In vitro and in vivo animal studies of the combination of amphotericin B and imidazoles suggest that imidazole antifungal agents may induce fungal resistance to amphotericin B. Combination therapy should be administered with caution, especially in immunocompromised patients.
Amphotericin B is a polyene antifungal and binds to sterols in the cell membranes of both fungal and human cells. It is usually fungistatic in vivo but can have fungicidal activity at high concentrations or against extremely susceptible organisms. Its higher affinity for ergosterol, the sterol found in fungal cell membranes, over cholesterol, the sterol found in human cell membranes, allows amphotericin B to be used systemically. As a result of this binding, membrane integrity is impaired, causing the loss of intracellular potassium and other cellular contents.
Some adverse reactions to amphotericin B, such as electrolyte loss and nephrotoxicity, are an extension of its pharmacologic action, while infusion-related reactions may be related to stimulation and release of prostaglandin synthesis as amphotericin B is a potent inducer of prostaglandin E2 synthesis in vitro. Anemia may be secondary to an inhibition of erythropoietin production or may be due to renal toxicity. Although the exact mechanism of renal toxicity has not been defined, amphotericin B can cause a decrease in glomerular filtration rate (GFR) and renal blood flow. A proposed mechanism may involve the effects of amphotericin B on membrane permeability as pathological changes of tubular lesions were observed in a study (n=26). Another proposed mechanism is amphotericin B-induced activation of an intrarenal mechanism called tubuloglomerular feedback (TGF); TGF regulates proximal and distal tubule delivery of ions, which results in afferent arteriolar vasoconstriction. TGF can be blocked by sodium loading or with the administration of furosemide or theophylline. However, single-nephron studies suggest that the theory involving TGF may be questionable. Other possible mechanisms include direct toxic effects to the afferent arterioles and tubules and direct renal and systemic vasoconstriction, which may be a relate to inhibition of nitric oxide or atrial natriuretic peptide systems or potentially to enhanced adenosine release in the kidneys. Vasoconstriction due to amphotericin B may also be calcium-dependent.
Amphotericin B may be given orally, by inhalation, and intravenously. Distribution is believed to be multicompartmental. Low concentrations are achieved in aqueous humor, pleural, pericardial, peritoneal, and synovial fluids. Amphotericin B is 90-95% protein-bound, primarily to lipoproteins.
Metabolism of amphotericin B is unknown. Small amounts of drug are excreted through the biliary system. Approximately 2-5% of a dose is eliminated renally at an extremely slow rate, with 40% being eliminated over 7 days. The elimination half-life in adults with normal renal function averages 24 hours, but after prolonged administration, elimination half-life can be as long as 15 days, possibly due to slow release of the drug from peripheral compartments.
Affected cytochrome P450 isoenzymes: none
-Route-Specific Pharmacokinetics
Oral Route
Amphotericin B is poorly absorbed from the GI tract. High doses of amphotericin B oral suspension produce inconsistent and low blood concentrations. In both pediatric and adult patients the average serum concentration following amphotericin B oral suspension 100 mg PO four times daily was 0.05 mcg/mL. There is no evidence of accumulation of amphotericin B after 2 weeks or more of therapy.
Intravenous Route
Parenteral administration is required to treat systemic fungal infections. Intravenous administration of 30 mg of amphotericin B over several hours produces average peak serum concentrations of about 1 mcg/mL. Doses of 50 mg over the same time period produce average peak serum concentrations of about 2 mcg/mL.
Amphotericin B can be detected for up to 4 weeks in blood and 4-8 weeks in urine after discontinuation of intravenous therapy.
Intramuscular Route
Amphotericin B cannot be given intramuscularly.
Inhalation Route
Following inhalation of 4 mg amphotericin B radiolabelled with technetium-99m inhaled over 10 minutes, between 3.5% and 4% of the total activity of radiolabelled amphotericin B was delivered to the lungs. As a suspension of amphotericin B without desoxycholate was used, the actual distribution cannot be determined. However, since particles of amphotericin B desoxycholate suspension are smaller than the radiolabelled particles, a greater percentage of amphotericin B delivered to the lungs would be expected with this formulation.
Other Route(s)
Intrathecal Route
Amphotericin B must be given intrathecally to achieve fungistatic concentrations within the cerebral spinal fluid (CSF) because CSF concentrations are approximately 3% of those in serum. Arachnoid villi remove amphotericin B from the CSF, and the drug is stored in the extracellular compartment of the brain, which may act as a reservoir for the drug.
-Special Populations
Renal Impairment
Amphotericin B is poorly hemodialyzable.
Pediatrics
Neonates
Amphotericin pharmacokinetics are highly variable in neonates. Unlike older populations, penetration into the CSF is relatively good (40 to 90% of serum concentrations). The following pharmacokinetic parameters have been reported from small studies of neonates (total n = 18; majority of patients were premature; weight 580 to 3325 g) :
half-life: 14.8 to 22.1 hours (median)
volume of distribution (Vd): 1.5 to 2.49 L/kg (median)
clearance: 12 to 18 mL/minute/1.73 m2 (median)
Infants, Children, and Adolescents
Similar to neonates, amphotericin pharmacokinetics are highly variable in infants and children. Clearance of amphotericin B significantly decreases with increasing age. In a study of 12 pediatric patients (mean age, 6.6 years (range, 4 months to 14 years), mean total clearance was 0.57 mL/kg/minute in children 8 months to 9 years of age compared to 0.25 mL/kg/minute in children 9 years and older. The following pharmacokinetic parameters were reported for the overall study group :
half-life: 11.9 to 33.2 hours (range)
volume of distribution (Vd): 0.23 to 1.91 L/kg (range)
clearance: 0.22 to 0.79 mL/minute/kg (range; NOTE: units are per kg, not per standardized BSA)