The first antifungal, amphotericin B deoxycholate, was introduced in 1958. It offers potent, broad-spectrum antifungal activity but is associated with significant renal toxicity and infusion reactions. Lipid-based amphotericin B formulations were introduced in the 1990s and maintain the potent, broad-spectrum activity of the deoxycholate formulation with less toxicity. Side-effects, including renal failure, electrolyte abnormalities, and infusion reactions, often limit its use.
Spectrum of Activity
A single agent, amphotericin B, is available in multiple formulations. The deoxycholate formulation was initially developed and 3 lipid-based formulations have been developed to limit toxicity and improve tolerability [Liposomal amphotericin B (L-AmB) and amphotericin B lipid complex (ABLC) are two available lipid formulations, Note >> Amphotericin B colloidal dispersion (ABCD), is not currently being manufactured.]
Amphotericin B exerts its activity through hydrophobic interactions with cell membrane ergosterol, subsequently disrupting membrane function. Pores formation allows the efflux of potassium, leading to cell death.
|Conventional Ampho-B dosing Guidelines (0.7-1 mg/kg/day)||Remarks|
If fluid overload is not a problem in patient prehydration with 500 ml NS + 1 amp KCL (20meq) is to be given as prehydration over 2 hours. (Plan to give it between 8-10 am so that Ampho-B can be infused from 10 am to 2 pm)
|Reduces the risk of renal toxicity and hypokalaemia.
Renal toxicity is mediated by both direct tubular damage and rapid vasoconstriction via tubuloglomerular feedback from osmotic changes.
Coadministration of Corticosteroids: Increased risk of hypokalemia
Less kidney toxicity has been reported with liposomal formulations and it has become preferred in patients with preexisting renal injury.
|Premedication (15-30 min before Ampho-B infusion)
Injection Avil (Pheniramine 22.75mg) 1 amp/Febrinil 1 amp 15-30 minutes before starting Ampho-B
Note > Intravenous hydrocortisone should not be given routinely, although it may be necessary for patients who experience severe reactions; dosages of between 25 and 50 mg are usually adequate for this purpose.
Meperidine can be added as premedication if patients develops severe chills and rigors with infusion.
|Infusion related side effects include fever, shaking chills, hypotension, anorexia, nausea, vomiting, headache, and tachypnea are common 1 to 3 hours after starting an intravenous infusion.
Severe infusion reactions can be managed by addition of Hydrocort/Meperidine 25-50 mg/slowing rate of infusion.
|The co-administration of Amiloride (10 mg daily) has been shown to reduce potassium loss via the kidneys and hypokalaemia and is beneficial to patients who are able to tolerate oral medication.||Reduction of Hypokalemia.|
|Infusion of Ampho-B
Dose = 0.7-1 mg/kg/day (Single daily dose must not excede 1.5 mg/kg/day)
Prepration: Drug concentration = 0.1 mg/ml or 1 mg/10 ml of D5 (pH of soln should be >4.2)
Administration: In not less than 4 hours (4-6 hours)
|The Amphotericin B should NEVER be mixed with Normal Saline or Half Normal Saline as it will precipitate.
The line that is used for Amphotericin-B should not be used for administering any other drugs including TPN. (Separate line should be used for TPN)
Rapid intravenous infusion has been associated with hypotension, hypokalemia, arrhythmias, and shock and should, therefore, be avoided.
|Special precaution: Since acute pulmonary reactions have been reported in patients given amphotericin B during or shortly after leukocyte (Granulocyte) transfusions, it is advisable to temporarily separate these infusions as far as possible and to monitor pulmonary function. (4-6 hours separation should be maintained)|
During Infusion: Hypotension and infusion reactions
Monitor Electrolytes: K+/Mg2+
Monitor LFT: Hepatic dysfunction including liver failure documented.
Renal Function: Lipid formulations or Other renosafe antifungals to be used
- Renal impairment following a cumulative amphotericin B dosage of less than 4 g is almost always reversible.
- The concomitant administration of other potentially nephrotoxic drugs, such as loop diuretics and aminoglycosides, should be avoided wherever possible.
- The potassium-depleting effect of amphotericin B may potentiate the actions of neuromuscular-blocking agents and increase the toxicity of cardiac glycosides.
- The concurrent administration of corticosteroids may enhance potassium loss due to amphotericin B.
Administration dose > 3-6 mg/kg/day
Administer 1st dose over 2 hours then can be reduced to 1 hour in patients who tolerate 2 hour dosing well or 4 hours if patient experiences discomfort.
Prepration >> Only compatible in D5W, not in NS. Drug Concentration > must be diluted with 5% Dextrose Injection to a final concentration of 1 to 2 mg/mL prior to administration. Lower concentrations (0.2 to 0.5 mg/mL) may be appropriate for infants and small children to provide sufficient volume for infusion.
Hydration: 500 mL NS IV given pre- and post-infusion, If fluid overloaded, use 250 mL pre/post or skip post-hydration.
Unopened vials of lyophilized material are to be stored at temperatures up to 25° C.
Storage of Reconstituted Product Concentrate : The reconstituted product concentrate may be stored for up to 24 hours at 2º-8º C (36º-46º F) following reconstitution with Sterile Water for Injection, USP. Do not freeze.
Storage of Diluted Product: Injection of AmBisome should commence within 6 hours of dilution with 5% Dextrose Injection.