Amphotret (Amphotericin B for Injection) is a freeze dried preparation of Amphotericin B for intravenous injection. Amphotret is a yellow coloured cake which is required to be reconstituted with sterile water for Injection before administration.
Amphotericin B is a polyene macrolide antifungal antibiotic obtained from a strain of Streptomyces nodosus. Amphotericin B is insoluble in water at neutral pH and hence formulated as a colloidal dispersion using sodium deoxycholate as a solubiliser.
Pharmacology: Clinical activity of Amphotericin B has been shown against Candida species, Cryptococcus neoformans, Blastomyces dermatitidis, Histoplasma capsulatum, Torulopsis glabrata, Coccidioides immitis, Pracoccidioides braziliensis, Aspergillus species and species causing mucomycosis. Amphotericin B remains the anti-fungal of choice for progressive and potentially fatal infections with susceptible organisms. Depending on the concentration achieved in the body fluids and the susceptibility of the fungus, Amphotericin B acts as either fungicidal or fungistatic.
Amphotret should be administered primarily to patients with progressive, potentially life-threatening fungal infections. Amphotret should not be administered to treat non-invasive fungal infections such as oral thrush, vaginal candidiasis and oesophageal candidiasis in patients having normal neutrophil counts. Amphotret is specifically indicated in the treatment of fungal infections susceptible to amphotericin B such as the one caused by Candida spp., Aspergillus spp., Cryptococcus neoformans, Mucor spp., Rhodotorula spp., Absidia spp., Blastomyces dermatitidis.
Dosage: The determination of Amphotericin B doses is largely empirical and is influenced by therapeutic response data, nephrotoxicity and patient tolerance. The usual daily maintenance dose of Amphotret is equivalent to 0.5 to 1 mg/kg of Amphotericin B; the administration of higher daily dosage hose been documented. At any given time of administration, a total dose of 1.5mg/kg should never be exceeded. Amphotericin B overdoses can result in cardiorespiratory arrest. Most susceptible fungi are inhibited in vitro by less than 2 ug of Amphotericin B / mL and this drug concentration can be achieved with administration of a dose equivalent to 50 to 70 mg of Amphotericin B. Poor correlation exists between therapeutic outcome and in vitro susceptibility. Amphotret can be administered daily or on alternate days. Alternate day administration of twice daily dose of Amphotericin B will provide a predictably higher peak plasma concentration.
Tolerance is improved with alternate day therapy because of less frequent administration and consequently less frequent infusion related adverse events.
Test Dose: A test dose will identify patients who are prone to hyperpyretic reactions or exaggerated rigor and chills. A volume of the initial dose that will deliver 1 mg of Amphotericin B may be infused over 10-30 minutes without administration of premedication. The patient should then be observed for possible severe adverse effects up to 3 hours. Therapy should not be delayed in patients who are acutely ill or immunocompromised.
Initiation with Partial or Full Dose: Therapy with Amphotret is normally initiated with gradual, incremental increases in the Amphotericin B dose until the desired maintenance dose is achieved. The rationale is to improve patients tolerance with respect to infusion related adverse events. This approach may actually be detrimental if it delays the administration of therapeutic doses of Amphotericin B for up to several days after the decision to start Amphotret therapy. Except in very debilitated patients, these adverse events should not cause severe sequelae. A therapeutic dosage of Amphotericin B (0.25 to 0.3 mg/kg/day) should not be delayed in an attempt to avoid infusion related adverse events. Also maintenance doses of Amphotret should not be delayed in patients with immune suppression or acute illness.
In a randomised controlled trial to study the effects of rate of administration of Amphotericin B deoxycholate over a period of 4 hours and 24 hours, it was observed that slow infusion (over 24 hours) of Amphotericin B deoxycholate reduced overall mortality, side effects and nephrotoxicity when compared to rapid infusion (over 4 hours). Slow intravenous infusion of Amphotericin B is indicated in anuric patients and individuals with impaired potassium excretion. The co-administration of 500 to 1000 mL of diluent 5% Dextrose Injection every 24 to 48 hours is recommended when Amphotret is diluted to a concentration of Amphotericin B not exceeding 0.1 mg/mL.
Administration: Reconstitute the content of Amphotret adding 10 mL of Sterile Water for Injection into the vial, shaking the contents till a visibly clear solution is obtained. The solution for infusion is prepared by diluting further with 5% Dextrose Injection (of pH above 4.2). Since Amphotret contains no preservative or a bacteriostatic agent, aseptic techniques must be strictly observed during handling and administration of Amphotret.
Discard the solution on reconstitution if the solution is not clear or contains evidence of foreign particles. In-line microbial membrane filter with pore size 1µ or more may be used for intravenous administration of Amphotret.
Amphotret overdoses may result in cardiorespiratory arrest. Discontinue the therapy, monitor the patient providing supportive therapy are required.
Amphotret is contraindicated in those patients who are hypersensitive to Amphotericin B or any of the component in the formulation.
Amphotret therapy is required to be initiated under close clinical observation by a qualified medical personnel. Acute reactions which are common include fever, chills, headache, nausea and vomiting.
The adverse effects related to the intravenous administration of amphotericin B include nephrotoxicity, anemia, infusion related adverse events and phlebitis. Nephrotoxicity is a major dose limiting organ toxicity. One manifestation is tubular necrosis. Signs of nephrotoxicity include elevated serum creatinine and blood urea nitrogen, hypokalemia and hypomagnesemia. Amphotericin B nephrotoxicity tends to be reversible, although there is evidence that doses exceeding 4 to 5g place at risk for irreversible changes in renal function.
Store at a temperature not exceeding 8°C preferably in a refrigerator. Protect vials from direct sunlight. The reconstituted solution is stable up to 7 days when stored at 2°C - 8°C.
J02AA01 - amphotericin B ; Belongs to the class of antibiotics. Used in the systemic treatment of mycotic infections.
Amphotret lyophilized powd for inj 50 mg
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