Amphotericin B is an antifungal antibiotic derived from a strain of streptomyces nodosus. It is available as a crystalline powder which is soluble in water. Therefore the drug is solubilized by the addition of sodium desoxycholate to form a mixture that provides a colloidal dispersion for parenteral use.
Indications of Amphotericin B
The drug shows a high order of in vitro activity against a number of fungi species. A concentration of 0.03 to 1.0 mcg/ml inhibits;
- Histoplasma capsulatum
- Cryptococcus neoformans,
- Candida species,
- Blastomyces dermatitidis,
- Rhodotorula and
- Sporotrichum schenchi.
Amphotericin B can also be used in the treatment of Leishmaniasis when its conventional treatment has failed.
Mechanism of Action of Amphotericin B
In concentrations obtainable in body fluids, Amphotericin B is fungistatic. It acts by binding to sterols in the fungal cell membrane with a resultant change in membrane permeability which allows leakage of intracellular components.
Mammalian cell membranes also contain sterols and it has been suggested that the damage to human cells and fungal cells may share the common mechanisms.
The initial intravenous infusion of 1-5 mg per day followed by a gradual increase ranging from 0.37 to 0.65 mg/kg daily produces peak blood levels of 1.8 to 3.5 mcg/ml.
Concentrations from 0.5 to 1.5 mcg/ml remain 20 hours after the infusion has been discontinued.
In the treatment of Leishmaniasis, Amphotericin B is given intravenously over several hours starting with a dose of 5-10 mg which is then gradually increased by 5-10 mg daily until the desired dose of 0.5-1.0 mg/kg. Treatment continues until a total dose of 1 to 3 grams has been given.
The drug is excreted slowly via the kidneys. The cumulative urinary output over 7 days period is about 40% of the drug-infused.
Indication of Amphotericin B
Amphotericin B should only be used in serious progressive potentially fatal infections
It is specifically intended for the treatment of cryptococcosis (tolurosis); North American blastomycosis and disseminated forms of moniliasis coccidiomycosis and histoplasmosis.
Like we have mentioned above it can be used for the treatment of Americal mucocutaneous leishmaniasis and Kala-azar when the conventional treatment fails.
Amphotericin B is contraindicated in patients who have shown hypersensitivity towards the drug.
Usage in pregnancy
Safety for usage in pregnancy has not yet been established. Therefore use the drug in pregnancy if only the possible benefits outweigh the risks.
Since the treatment course of Amphotericin B is usually long, there are high chances that unwanted effects will rise. Therefore the treatment should take place in a hospital or under close supervision by medically trained personnel.
Corticosteroids should not be used concomitantly unless they are necessary to control drug reactions.
Other nephrotoxic drugs such as antineoplastics like nitrogen mustard should not be given concomitantly.
Lab facility must be available to perform blood urea nitrogen and serum creatinine or endogenous creatinine clearance weekly.
If BUN exceeds 40 mg/10 ml or serum creatinine exceeds 3.0 per 100 ml the drug should be discontinued of the dose reduced until renal function has improved.
Weekly full hemogram and serum potassium levels should be performed.
Whenever the medication has been interrupted for over 7 days, the therapy should be resumed starting with the lowest dosage level ie 0.25 mg/kg and then increased gradually.
Intolerance may be experienced in some patients who are taking the drug. This can be counteracted by giving aspirin or antihistamines.
Administration of the drug in alternate days may reduce phlebitis and anorexia.
Iv administration of small doses of adrenal corticosteroids may reduce febrile reactions.
Adding a small dose of heparin to the infusion may reduce the incidence of thrombophlebitis.
The most common associated effects are;
Fever, headache, anorexia, weight loss, nausea and vomiting, malaise, muscle, and joint pains, dyspepsia, cramping, diarrhea, epigastric pain, phlebitis at the injection site, thrombophlebitis, normochromic normocytic anemia, and hypokalemia.
Abnormal liver function tests which usually improve upon the termination of the drug.
Dose and Administration
Amphotericin B for injection should be administered as a slow intravenous infusion over a period of approximately 4-6 hours.
The recommended concentration for intravenous infusion is 0.1 mg/cc (1 mg/10 ml).
The dose of Amphotericin B must be adjusted for each client because tolerance to the drug varies for each individual.
The therapy is usually instituted with a daily dose of 0.25 mg/kg body weight and gradually increased as per tolerance permits.
The total daily dose may range up to 1.0 mg/kg of body weight with alternate day dosages ranging up to 1.5 mg/ kg body weight. Several weeks of therapy are usually required.
A total daily dose of more than 1.5 mg/kg should never be exceeded under any circumstances!
The dry powder should be reconstituted as follows:
The initial concentration of 5 mg/ml is prepared by adding 10 ml of sterile water for injection without a bacteriostatic agent to the vial and shake until the solution id clear. The infusion containing 0.1 mg/ml is then obtained by adding 5% dextrose injection USP of pH above 4.2. The pH of a container of dextrose should be ascertained before use.
Aseptic technique must be observed strictly in all handling because there is no preservative or bacteriostatic agent is present in the antibiotic or in the materials used to prepare it. All entries to the vial must be made with a sterile needle and
DO NOT reconstitute with a normal saline solution.
The use of any diluent other than the one recommended or the presence of bacteriostatic agent (e.g, Benzyl alcohol) in the diluent it may cause precipitation of the antibiotic.
Amphotericin B powder should be stored in a refrigerator and protected from light. The reconstituted concentrate of 5 mg Amphotericin B per ml may be stored in a dark room for 24 hours or at a refrigerator for a week with minimal loss of potency.
The solution prepared for intravenous infusion ( 0.1 mg /ml) should be used promptly after preparation and should be protected from light during administration.