Loading…
Amphotericin B is a brand name for Amphotericin B. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: INDICATIONS AND USAGE Amphotericin B liposome for injection is indicated for the following: Empirical therapy for presumed fungal infection in febrile, neutropenic patients. Treatment of Cryptococcal Meningitis in HIV-infected patients (see DESCRIPTION OF CLINICAL STUDIES) . Treatment of patients with Aspergillus…
Verbatim from this product's FDA label. Tap a section to expand.
DOSAGE AND ADMINISTRATION
Amphotericin B liposome for injection is not interchangeable or substitutable on a mg per mg basis with other amphotericin B products. Different amphotericin B products are not equivalent in terms of pharmacodynamics, pharmacokinetics and dosing.
Amphotericin B liposome for injection should be administered by intravenous infusion, using a controlled infusion device, over a period of approximately 120 minutes. 0 MICRON.
NOTE:
An existing intravenous line must be flushed with 5% Dextrose Injection prior to infusion of amphotericin B liposome for injection. If this is not feasible, amphotericin B liposome for injection must be administered through a separate line.
Infusion time may be reduced to approximately 60 minutes in patients in whom the treatment is well-tolerated. If the patient experiences discomfort during infusion, the duration of infusion may be increased. The recommended initial dose of amphotericin B liposome for injection for each indication for adult and pediatric patients is as follows: Indication Dose (mg/kg/day) Empirical therapy 3 Systemic fungal infections: Aspergillus Candida Cryptococcus 3 to 5 Cryptococcal meningitis in HIV-infected patients (see DESCRIPTION OF CLINICAL STUDIES ) 6 Dosing and rate of infusion should be individualized to the needs of the specific patient to ensure maximum efficacy while minimizing systemic toxicities or adverse events.
Doses recommended for visceral leishmaniasis are presented below:
Visceral Leishmaniasis Dose (mg/kg/day) Immunocompetent patients 3 (days 1 to 5) and 3 on days 14, 21 Immunocompromised patients 4 (days 1 to 5) and 4 on days 10, 17, 24, 31, 38 For immunocompetent patients who do not achieve parasitic clearance with the recommended dose, a repeat course of therapy may be useful.
For immunocompromised patients who do not clear parasites or who experience relapses, expert advice regarding further treatment is recommended. For additional information, see DESCRIPTION OF CLINICAL STUDIES. Directions for Reconstitution, Filtration and Dilution Read This Entire Section Carefully Before Beginning Reconstitution Amphotericin B liposome for injection must be reconstituted using Sterile Water for Injection, USP (without a bacteriostatic agent).
ADVERSE REACTIONS
The following adverse events are based on the experience of 592 adult patients (295 treated with amphotericin B liposome for injection and 297 treated with amphotericin B deoxycholate) and 95 pediatric patients (48 treated with amphotericin B liposome for injection and 47 treated with amphotericin B deoxycholate) in Study 94-0-002, a randomized double-blind, multicenter study in febrile, neutropenic patients.
Amphotericin B liposome for injection and amphotericin B were infused over two hours. 8 Urogenital System Hematuria 14 14 Amphotericin B liposome for injection was well tolerated. Amphotericin B liposome for injection had a lower incidence of chills, hypertension, hypotension, tachycardia, hypoxia, hypokalemia, and various events related to decreased kidney function as compared to amphotericin B deoxycholate.
In pediatric patients (16 years of age or less) in this double-blind study, amphotericin B liposome for injection compared to amphotericin B deoxycholate, had a lower incidence of hypokalemia (37% versus 55%), chills (29% versus 68%), vomiting (27% versus 55%), and hypertension (10% versus 21%).
Similar trends, although with a somewhat lower incidence, were observed in open-label, randomized Study 104-14 involving 205 febrile neutropenic pediatric patients (141 treated with amphotericin B liposome for injection and 64 treated with amphotericin B deoxycholate).
Pediatric patients appear to have more tolerance than older individuals for the nephrotoxic effects of amphotericin B deoxycholate. The following adverse events are based on the experience of 244 patients (202 adult and 42 pediatric patients) of whom 85 patients were treated with amphotericin B liposome for injection 3 mg/kg, 81 patients were treated with amphotericin B liposome for injection 5 mg/kg and 78 patients were treated with amphotericin B lipid complex 5 mg/kg in Study 97-0-034, a randomized, double-blind, multicenter study in febrile, neutropenic patients.
WARNINGS
Anaphylaxis has been reported with amphotericin B deoxycholate and other amphotericin B-containing drugs, including amphotericin B liposome for injection. If a severe anaphylactic reaction occurs, the infusion should be immediately discontinued and the patient should not receive further infusions of amphotericin B liposome for injection.
CONTRAINDICATIONS
Amphotericin B liposome for injection is contraindicated in those patients who have demonstrated or have a known hypersensitivity to amphotericin B deoxycholate or any other constituents of the product unless, in the opinion of the treating physician, the benefit of therapy outweighs the risk.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
Know a brand we are missing in United States of America? Suggest a brand →
Brand names are compiled from public regulatory records for active-ingredient mapping only. Drugvu is not affiliated with any manufacturer. This is not medical advice.
Vials of amphotericin B liposome for injection containing 50 mg of amphotericin B are prepared as follows: Reconstitution 1. Aseptically add 12 mL of Sterile Water for Injection, USP to each amphotericin B liposome for injection vial to yield a preparation containing 4 mg amphotericin B/mL.
CAUTION:
DO NOT RECONSTITUTE WITH SALINE OR ADD SALINE TO THE RECONSTITUTED CONCENTRATION, OR MIX WITH OTHER DRUGS. The use of any solution other than those recommended, or the presence of a bacteriostatic agent in the solution, may cause precipitation of amphotericin B liposome for injection.
2. Immediately after the addition of water, SHAKE THE VIAL VIGOROUSLY for 30 seconds to completely disperse the amphotericin B liposome for injection. Amphotericin B liposome for injection forms a yellow, translucent suspension. Visually inspect the vial for particulate matter and continue shaking until completely dispersed.
Filtration and Dilution 3. Calculate the amount of reconstituted (4 mg/mL) amphotericin B liposome for injection to be further diluted. 4. Withdraw this amount of reconstituted amphotericin B liposome for injection into a sterile syringe.
5. Attach the 5 micron filter provided to the syringe. Inject the syringe contents through the filter, into the appropriate amount of 5% Dextrose Injection (use only one filter per vial of amphotericin B liposome for injection). 6. Amphotericin B liposome for injection must be diluted with 5% Dextrose Injection to a final concentration of 1 mg/mL to 2 mg/mL prior to administration.
5 mg/mL) may be appropriate for infants and small children to provide sufficient volume for infusion. DISCARD PARTIALLY USED VIALS. STORAGE OF AMPHOTERICIN B LIPOSOME FOR INJECTION Unopened vials of lyophilized material are to be stored at temperatures 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].
Storage of Reconstituted Product Concentrate The reconstituted product concentrate may be stored for up to 24 hours at 2°C to 8°C (36°F to 46°F) following reconstitution with Sterile Water for Injection, USP. Do not freeze. Storage of Diluted Product Amphotericin B liposome for injection should commence within 6 hours of dilution with 5% Dextrose Injection.
As with all parenteral drug products, the reconstituted amphotericin B liposome for injection should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use material if there is any evidence of precipitation or foreign matter.
Aseptic technique must be strictly observed in all handling, since no preservative or bacteriostatic agent is present in amphotericin B liposome for injection or in the materials specified for reconstitution and dilution.
Amphotericin B liposome for injection and amphotericin B lipid complex were infused over two hours. 7 mg/kg in Study 94-0-013 a randomized, double-blind, comparative multicenter trial, in the treatment of cryptococcal meningitis in HIV-positive patients.
6 Infusion-Related Reactions In Study 94-0-002, the large, double-blind study of pediatric and adult febrile neutropenic patients, no premedication to prevent infusion-related reaction was administered prior to the first dose of study drug (Day 1).
Amphotericin B liposome for injection-treated patients had a lower incidence of infusion-related fever (17% versus 44%), chills/rigors (18% versus 54%) and vomiting (6% versus 8%) on Day 1 as compared to amphotericin B deoxycholate-treated patients.
0ºC 6 (13%) 22 (47%) 52 (18%) 128 (43%) Patients with chills/rigors 4 (8%) 22 (47%) 59 (20%) 165 (56%) Patients with nausea 4 (8%) 4 (9%) 38 (13%) 31 (10%) Patients with vomiting 2 (4%) 7 (15%) 19 (6%) 21 (7%) Patients with other reactions 10 (21%) 13 (28%) 47 (16%) 69 (23%) †Day 1 body temperature increased above the temperature taken within 1 hour prior to infusion (preinfusion temperature) or above the lowest infusion value (no preinfusion temperature recorded).
, acetaminophen, diphenhydramine, meperidine and hydrocortisone) was lower in amphotericin B liposome for injection-treated patients compared with amphotericin B deoxycholate-treated patients. In the empirical therapy study 97-0-034, on Day 1, where no premedication was administered, the overall incidence of infusion-related events of chills/rigors was significantly lower for patients administered amphotericin B liposome for injection compared with amphotericin B lipid complex.
Fever, chills/rigors and hypoxia were significantly lower for each amphotericin B liposome for injection group compared with the amphotericin B lipid complex group. 2% of patients treated with 5 mg/kg per day amphotericin B liposome for injection.
5%) Day 1 body temperature increased above the temperature taken within 1 hour prior to infusion (preinfusion temperature) or above the lowest infusion value (no preinfusion temperature recorded). Patients were not administered premedications to prevent infusion-related reactions prior to the Day 1 study drug infusion.
In Study 94-0-013, a randomized, double-blind multicenter trial comparing amphotericin B liposome for injection and amphotericin B deoxycholate as initial therapy for cryptococcal meningitis, premedications to prevent infusion-related reactions were permitted.
7 mg/kg/day Total number of patients receiving at least one dose of study drug 86 94 87 Patients with fever increase of >1ºC 6 (7%) 8 (9%) 24 (28%) Patients with chills/rigors 5 (6%) 8 (9%) 42 (48%) Patients with nausea 11 (13%) 13 (14%) 18 (20%) Patients with vomiting 14 (16%) 13 (14%) 16 (18%) Respiratory adverse events 0 1 (1%) 8 (9%) There have been a few reports of flushing, back pain with or without chest tightness, and chest pain associated with amphotericin B liposome for injection administration; on occasion this has been severe.
Where these symptoms were noted, the reaction developed within a few minutes after the start of infusion and disappeared rapidly when the infusion was stopped. The symptoms do not occur with every dose and usually do not recur on subsequent administrations when the infusion rate is slowed.
Toxicity and Discontinuation of Dosing In Study 94-0-002, a significantly lower incidence of grade 3 or 4 toxicity was observed in the amphotericin B liposome for injection group compared with the amphotericin B group. In addition, nearly three times as many patients administered amphotericin B required a reduction in dose due to toxicity or discontinuation of study drug due to an infusion-related reaction compared with those administered amphotericin B liposome for injection.
In empirical therapy study 97-0-034, a greater proportion of patients in the amphotericin B lipid complex group discontinued the study drug due to an adverse event than in the amphotericin B liposome for injection groups. Less Common Adverse Events The following adverse events also have been reported in 2% to 10% of amphotericin B liposome for injection-treated patients receiving chemotherapy or bone marrow transplantation, or who had HIV disease in six comparative, clinical trials: Body as a Whole Abdomen enlarged, allergic reaction, cellulitis, cell-mediated immunological reaction, face edema, graft-versus-host disease, malaise, neck pain, and procedural complication.
Cardiovascular System Arrhythmia, atrial fibrillation, bradycardia, cardiac arrest, cardiomegaly, hemorrhage, postural hypotension, valvular heart disease, vascular disorder, and vasodilatation (flushing). Digestive System Anorexia, constipation, dry mouth/nose, dyspepsia, dysphagia, eructation, fecal incontinence, flatulence, hemorrhoids, gum/oral hemorrhage, hematemesis, hepatocellular damage, hepatomegaly, liver function test abnormal, ileus, mucositis, rectal disorder, stomatitis, ulcerative stomatitis, and veno-occlusive liver disease.
Hemic & Lymphatic System Anemia, coagulation disorder, ecchymosis, fluid overload, petechia, prothrombin decreased, prothrombin increased, and thrombocytopenia. Metabolic & Nutritional Disorders Acidosis, amylase increased, hyperchloremia, hyperkalemia, hypermagnesemia, hyperphosphatemia, hyponatremia, hypophosphatemia, hypoproteinemia, lactate dehydrogenase increased, nonprotein nitrogen (NPN) increased, and respiratory alkalosis.
Musculoskeletal System Arthralgia, bone pain, dystonia, myalgia, and rigors. Nervous System Agitation, coma, convulsion, cough, depression, dysesthesia, dizziness, hallucinations, nervousness, paresthesia, somnolence, thinking abnormality, and tremor.
Respiratory System Asthma, atelectasis, hemoptysis, hiccup, hyperventilation, influenza-like symptoms, lung edema, pharyngitis, pneumonia, respiratory insufficiency, respiratory failure, and sinusitis. Skin & Appendages Alopecia, dry skin, herpes simplex, injection site inflammation, maculopapular rash, purpura, skin discoloration, skin disorder, skin ulcer, urticaria, and vesiculobullous rash.
Special Senses Conjunctivitis, dry eyes, and eye hemorrhage. Urogenital System Abnormal renal function, acute kidney failure, acute renal failure, dysuria, kidney failure, toxic nephropathy, urinary incontinence, and vaginal hemorrhage.
Postmarketing Experience The following infrequent adverse experiences have been reported in postmarketing surveillance, in addition to those mentioned above: angioedema, erythema, urticaria, bronchospasm, cyanosis/hypoventilation, pulmonary edema, agranulocytosis, hemorrhagic cystitis, and rhabdomyolysis.
Clinical Laboratory Values The effect of amphotericin B liposome for injection on renal and hepatic function and on serum electrolytes was assessed from laboratory values measured repeatedly in Study 94-0-002. The frequency and magnitude of hepatic test abnormalities were similar in the amphotericin B liposome for injection and amphotericin B groups.
2 mg/dL. 5 mmol/L any time during treatment. 6%) The effect of amphotericin B liposome for injection (3 mg/kg/day) vs. 6 mg/kg/day) on renal function in adult patients enrolled in this study is illustrated in the following figure: Mean Change in Creatinine Over Time in Study 94-0-002 In empirical therapy study 97-0-034, the incidence of nephrotoxicity as measured by increases of serum creatinine from baseline was significantly lower for patients administered amphotericin B liposome for injection (individual dose groups and combined) compared with amphotericin B lipid complex.
7 mg/dL) pretreatment creatinine concentrations. 5X baseline serum creatinine 30 (35%) 44 (47%) 52 (60%) 2 X baseline serum creatinine 12 (14%) 20 (21%) 29 (33%) spl-figure1 spl-figure2