Amphostal

Amphostal

amphotericin b

Manufacturer:

Stallion Labs

Distributor:

Ambica
Full Prescribing Info
Contents
Amphotericin B.
Description
Each vial contains: Amphotericin B. USP 50 mg.
Action
Pharmacology: Pharmacokinetics: An initial intravenous infusion of 1 to 5 mg of Amphotericin B per day, gradually increased to 0.65 mg/kg daily, produces peak plasma concentrations of approximately 2 to 4 mg/L which can persist between doses since the plasma half-life of Amphotericin B is about 24 hours. It has been reported that Amphotericin B is highly bound (more than 90%) to plasma proteins and is poorly dialysable.
Amphotericin B is excreted very slowly by the kidneys with 2 to 5% of a given dose being excreted in biologically active form. After treatment is discontinued the drug can be detected in the urine for at least seven weeks. The cumulative urinary output over a seven day period amounts to approximately 40% of the amount of drug infused. Details of tissue distribution and possible metabolic pathways are not known.
Indications/Uses
Amphotericin B Intravenous should be administered primarily to patients with progressive, potentially fatal infections. This potent drug should not be used to treat the common non-invasive fungal infections such as oral thrush, vaginal candidiasis and oesophageal candidiasis in patients with normal neutrophil counts.
Amphotericin B Intravenous is specifically intended to treat potentially life-threatening fungal infections: cryptococcosis (torulosis); North American blastomycosis; the disseminated forms of moniliasis (candidiasis), coccidioidomycosis and histoplasmosis; mucormycosis (phycomycosis) caused by susceptible species of the genera Mucor, Rhizopus, Absidia, Entomophthora, and Basidiobolus; sporotrichosis (Sporothrix schenckii); aspergillosis (Aspergillus fumigatus).
Amphotericin B may be helpful in the treatment of American mucocutaneous leishmaniasis, but is not the drug of choice in primary therapy.
Dosage/Direction for Use
Amphotericin B should be administered by intravenous infusion over a period of 2-4 hours. Reduction of the infusion rate may reduce the incidence of side-effects. In rare instances infusion times of up to 6 hours may be necessary. Initial daily dose should be 0.25 mg/kg of body weight gradually increasing to a level of 1.0 mg/kg of body weight depending on individual response and tolerance. Within the range of 0.25-1.0 mg/kg the daily dose should be maintained at the highest level which is not accompanied by unacceptable toxicity.
In seriously ill patients the daily dose may be gradually increased up to a total of 1.5 mg/kg. Since Amphotericin B is excreted slowly, therapy may be given on alternate days in patients on the higher dosage schedule. Several months of therapy are usually necessary; a shorter period of therapy may produce an inadequate response and lead to relapse.
When commencing all new courses of treatment, it is advisable to administer a test dose immediately preceding the first dose. A volume of the infusion containing 1 mg (i.e. 10 mL) should be infused over 20-30 minutes and the patient carefully observed for at least a further 30 minutes. It should be noted that patient responses to the test dose may not be predictive of subsequent severe side effects.
Whenever medication is interrupted for a period longer than seven days, therapy should be resumed by starting with the lowest dosage level, i.e. 0.25 mg/kg of body weight and increased gradually.
Safety and effectiveness in paediatric patients have not been established through adequate and well-controlled studies. Systemic fungal infections have been treated in paediatric patients, with reports of side effects similar to those seen in adults. Or as prescribed by the physicians.
Overdosage
Treatment of overdosage should be symptomatic and supportive. Amphotericin B overdoses can result in cardio-respiratory arrest. If an overdose is suspected, discontinue therapy and monitor the patient's clinical status (e.g., cardio respiratory, renal and liver function, hematologic status, serum electrolytes) and administer supportive therapy as required. Amphotericin B is not hemodialyzable. Prior to reinstituting therapy, the patient's condition should be stabilized (including correction of electrolyte deficiencies, etc.).
Contraindications
This product is contra-indicated in patients who have shown hypersensitivity to it unless, in the opinion of the physician, the condition requiring treatment is life-threatening and amenable only to Amphotericin B therapy.
Use in Pregnancy: Safety for use in pregnancy has not been established; therefore, it should be used during pregnancy only if the possible benefits to be derived outweigh the potential risks involved.
Use in Lactation: It is not known whether Amphotericin B is excreted in human milk.
Paediatric Use: Safety and effectiveness in pediatric patients have not been established through adequate and well-controlled studies.
Warnings
This drug should be used primarily for treatment of patients with progressive and potentially fatal fungal infections; it should not be used to treat the common clinically in apparent forms of fungal disease which show only positive skin or serologic tests.
Amphotericin B may be the only effective treatment available for a potentially fatal disease.
In each case, therefore, its possible life saving effect must be balanced against its untoward and dangerous effects.
Special Precautions
Under no circumstances should a total daily dose of 1.5 mg/kg be exceeded. Amphotericin B overdoses can result in potentially fatal cardiac or cardiorespiratory arrest. The recommended concentration for intravenous infusion is 10 mg/100 mL.
Use in Elderly: No specific dosage recommendations or precautions.
Use In Pregnancy & Lactation
Use in Pregnancy: Safety for use in pregnancy has not been established; therefore, it should be used during pregnancy only if the possible benefits to be derived outweigh the potential risks involved.
Use in Lactation: It is not known whether Amphotericin B is excreted in human milk.
Side Effects
The side effects most commonly observed are: General (body as a whole): fever (sometimes accompanied by shaking chills usually occurring within 15 to 20 minutes after initiation of treatment); malaise; loss of mass.
Cardiopulmonary: hypotension, tachypnoea.
Gastrointestinal: anorexia; nausea; vomiting; diarrhoea; dyspepsia; cramping epigastric pain.
Haematologic: normochromic, normocytic anemia.
Local: pain at the injection site with or without phlebitis or thrombophlebitis.
Musculoskeletal: generalized pain, including muscle and joint pains.
Neurologic: headache.
Renal: decreased renal function and renal function abnormalities including: azotemia, increased serum creatinine, hypokalemia, hyposthenuria, renal tubular acidosis, and nephrocalcinosis. These usually improve with interruption of therapy. However, some permanent impairment often occurs, especially in those patients receiving large cumulative amounts (over 5 g) of Amphotericin B.
The following adverse reactions have also been reported: General (body as a whole): flushing.
Allergic: anaphylactoid and other allergic reactions.
Cardiovascular: cardiac arrest; arrhythmias, including ventricular fibrillation; cardiac failure; hypertension; shock.
Dermatologic: rash, in particular maculopapular; pruritis. Less frequent reports of Stevens-Johnson syndrome have been received during post-marketing surveillance.
Gastrointestinal: liver function test abnormalities; jaundice; acute liver failure; haemorrhagic gastroenteritis; melaena.
Haematologic: agranulocytosis; coagulation defects; thrombocytopenia; leukopenia; eosinophilia; leukocytosis.
Neurologic: convulsions; hearing loss; tinnitus; transient vertigo; blurred vision or diplopia; peripheral neuropathy; encephalopathy; other neurologic symptoms.
Pulmonary: dyspnea, bronchospasm; non-cardiac pulmonary edema; hypersensitivity pneumonitis.
Renal: acute renal failure; anuria; oliguria.
Altered serum electrolytes: hypomagnesaemia, hypo- and hyperkalaemia and hypocalcaemia.
Drug Interactions
When administered concurrently, the following drugs may interact with Amphotericin B: Other nephrotoxic medications e.g., cisplatin, pentamidine, aminoglycosides, and cyclosporine, may enhance the potential for renal toxicity, and thus should be used concomitantly only with great caution.
Corticosteroids and Corticotropin (ACTH) may potentiate Amphotericin B induced hypokalemia. Agents whose effects or toxicity may be increased by hypokalemia e.g., digitalis glycosides, skeletal muscle relaxants and antiarrhythmic agents.
Flucytosine concomitant use may increase the toxicity of flucytosine possibly by increasing its cellular uptake and/or impairing its renal excretion.
Leukocyte transfusions though not observed in all studies, acute pulmonary reactions have been observed in patients given Amphotericin B during or shortly after leukocyte transfusions, thus it is advisable to separate these infusions as far as possible and to monitor pulmonary function.
Imidazoles (e.g., Ketoconazole, miconazole, clotrimazole, fluconazole). In vitro studies and animal studies with the combination of Amphotericin B and suggest that imidazoles may induce fungal resistance to Amphotericin B. Combination therapy should be administered with caution, especially in immunocompromised patients.
Caution For Usage
Direction for Reconstitution: Reconstitute as follows: An initial concentrate of 5 mg Amphotericin B per mL is first prepared by rapidly expressing 10 mL sterile water for injection, without a bacteriostatic agent, directly into the lyophilised cake, using a sterile needle (minimum diameter: 20 gauge) and syringe. Shake the vial immediately until the colloidal solution is clear. The infusion solution, providing 10 mg/100 mL is obtained by further dilution (1:50) with 5% Glucose Injection of pH above 4.2. The pH of each container of Glucose Injection should be ascertained before use. Commercial Glucose Injection usually has a pH above 4.2; however, if it is below 4.2 then 1 or 2 mL of buffer should be added to the Glucose Injection before it is used to dilute a concentrated solution of Amphotericin B. The recommended buffer has the following composition: Dibasic sodium phosphate (anhydrous) 1.59 g, Monobasic sodium phosphate (anhydrous) 0.96 g, Water for Injections BP q.s. to 100 mL.
The buffer should be sterilised before it is added to the Glucose Injection, either by filtration through a bacterial filter, or by autoclaving for 30 mins at 15 lb pressure (121°C).
Storage
Store in a refrigerator (2-8°C).
The concentrate (5 mg/mL after reconstitution with 10 mL Sterile Water for Injection) should be stored protected from light. The absence of any antimicrobial preservative and the risk of contamination during reconstitution mean that the product should be stored for no more than 8 hours at room temperature (25°C) or 24 hours in a refrigerator (2-8°C). Should the need arise and a validated aseptic reconstitution technique is applied, the product is chemically stable when stored for 24 hours at room temperature or one week in a refrigerator. It is not intended as a multidose vial. Any unused material should be discarded. Solutions prepared for intravenous infusion (i.e. 10 mg or less Amphotericin B per 100 mL) should be used promptly after preparation.
MIMS Class
ATC Classification
J02AA01 - amphotericin B ; Belongs to the class of antibiotics. Used in the systemic treatment of mycotic infections.
Presentation/Packing
Infusion conc (vial) 50 mg x 10 mL x 1's.
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