(1997; 132 pages) [French] [Spanish]
Oral suspension, 100 mg/ml
Lozenge, 10 mg
Powder for injection, 50 mg in vial
Amphotericin B is a lipophilic polyene antibiotic that is active against many yeasts and yeast-like fungi, including Candida albicans. It is presumed to alter membrane permeability by binding with sterols in the fungal cell wall. Since it is poorly absorbed from the gastrointestinal tract, it must be administered parenteally.
It is extensively bound to plasma lipoproteins, but it enters serous cavities and crosses the placental barrier. The plasma half-life is about 24 hours. It is excreted very slowly by the kidneys and can be detected in the plasma and the urine for several weeks after discontinuation of treatment.
• oral and perioral candidosis
• progressive, potentially fatal systemic fungal infections with skin involvement, including disseminated candidosis.
Dosage and administration
Amphotericin B is a highly toxic substance that should be used only under experienced medical supervision.
All doses are suitable for adults and children.
Oral and perioral candidosis:
1 ml of oral suspension or one lozenge (10 mg) orally four times daily after food until symptoms have resolved (maximum 2 g daily). The suspension should be retained in the mouth for as long as possible before swallowing. Lozenges should be retained as close to major lesions as possible and allowed to dissolve in the mouth.
0.25-1.0 mg/kg by i.v. infusion daily for 10-14 days. Higher doses, up to a maximum of 1.5 mg/kg daily, may be required in disseminated candidosis.
An initial dose of 1 mg in 50 ml of 5% dextrose should be administered over 30 minutes. If this is well tolerated the dosage should be increased over a period of 2 days to a level of 0.25-1.0 mg/kg.
Infusion fluids should be freshly prepared by dissolving 50 mg in 10 ml of water for injection and making up the volume to 500 ml with 5% glucose to give a final concentration of amphotericin B of 100 μg/ml. Solutions containing electrolytes or preservatives are incompatible since they promote precipitation. The required dosages should be administered by slow intravenous infusion, when possible via a central venous catheter. An oral dose of 5 mg of hydrocortisone sodium succinate given 1 hour before infusion may reduce the severity of chills, fever and vomiting. Acetylsalicylic acid, pethidine, antihistamines or antiemetics may also be of value.
Known hypersensitivity to amphotericin B.
Close medical supervision in a hospital setting is required throughout systemic treatment.
Renal function and serum potassium concentrations should be closely monitored when high doses are administered. Impairment of renal function, which may be only partially reversible, is common when the cumulative dosage reaches 5 g, and may necessitate a reduction in dosage or interruption of treatment. If treatment is interrupted for more than 7 days, it is important to revert to the initial starting dose.
A high fluid intake should be maintained. Potassium supplements may be required to compensate for urinary losses. Dosage must be reduced if renal function deteriorates substantially and particularly if serum creatinine levels rise by over 50%. Infusions of an osmotic diuretic such as mannitol may then be of value.
The blood count should be monitored at weekly intervals since bone-marrow depression supervenes frequently. Occasionally blood transfusion is required.
Use in pregnancy
Safe use during pregnancy has not been established. Amphotericin B should be used only when the need of the mother outweighs the risk of harm to the fetus.
Chills, fever and vomiting are frequent during infusion. Anaphylaxis, flushing, muscle and joint pains, headache and anorexia may also occur. These effects are often most marked in the first days of treatment. Maculopapular rash, pruritus and haemorrhagic gastroenteritis are less common.
Deterioration of renal function, which may be only partially reversible, must be anticipated.
Progressive normochromic anaemia is indicative of bone-marrow depression. Selective leukopenia and thrombocytopenia are less common.
Nerve palsies, impaired vision, tinnitus, hearing loss, convulsions and difficult micturition have also been reported.
Cardiotoxic effects, including dysrhythmias, cardiac arrest and changes in blood pressure, occur rarely.
Concomitant administration of other nephrotoxic drugs should be avoided.
Corticosteroids may worsen hypokalaemia due to amphotericin B.
The action of flucytosine is potentiated.
Large doses can result in anuria, dysrhythmias, cardiac arrest, hypotension, visual disturbances and convulsions. Treatment is symptomatic. Amphotericin B cannot be removed by haemodialysis.
Vials of powder for injection should be kept in tightly closed containers below 4°C, protected from light. Oral suspension and lozenges should be stored in tightly closed containers.