AMPHOTERICIN B Deoxycholate
(conventional amphotericin)

Fungizone®

Amphotericin B X-Gen®

Reviewed by Brenda Hughes(Pharmacy),
Dr Lesley Voss & Dr Elizabeth Wilson (ID Starship)
June 2015
Administration Newborn Drug Protocol Index Newborn Services Home Page

Dose and Administration

Intravenous1

1 mg/kg/dose every 24 hours (Maximum 1.5 mg/ kg/ dose if given on alternate days)

NB

  1. Administer the first dose over 4 hours or more, then if tolerated administer subsequent doses over 1 - 2 hours or more (the exact time may vary using a drug library on pump so ensure the full dose is given).
  2. Use the first 30 minutes of the first dose as a “test dose” to observe for adverse reactions
  3. Incremental treatment is inappropriate.
  4. Amphotericin must be used under close clinical supervision. Toxicity occurs commonly – see Adverse Effects and Monitoring (“Special Considerations”)
  5. May need to treat for 4-6 weeks.

Indications Indications

  1. Systemic candidiasis.
  2. Congenital candidiasis.
  3. Other systemic fungal infections.
  4. For all indications, ID Team approval is required prior to starting therapy.

Contraindications and Precautions

  1. Hypersensitivity to amphotericin B.
  2. Minor, superficial fungal infections.
  3. Caution in preterm infants, especially extreme immaturity.

Clinical Pharmacology

Amphotericin B is a polyene antifungal antibiotic that is active against a wide range of yeasts and yeast-like fungi including Candida albicans. The mechanism of action depends on its binding to a sterol moiety, ergosterol, present in the membrane of sensitive fungi. May be fungicidal or fungistatic, depending on the drug concentration obtained and the sensitivity of the fungus.

Absorption from the gastrointestinal tract is negligible, even with very large doses. After IV administration only a small percentage of the drug remains in the plasma compartment. High binding (> 90%) to human plasma protein. CSF concentrations of amphotericin B are only 2-4% of the serum concentrations. Drug may accumulate in tissues to a significant concentration and be excreted renally for months.

Dosage schedules for amphotericin B have been devised following observations of toxicity with large doses and other clinical experiences. No objective data exists regarding the appropriate length of therapy required, although most infants have been treated for an average of 40 days (range 14-70 days). Amphotericin is frequently used in combination with flucytosine.

Possible Adverse Effects

Amphotericin B deoxycholate is rarely used in children and adults due to toxicity, but neonates seem to tolerate this drug better with fewer side effects. However any neonate receiving this drug still needs close monitoring for adverse effects.

  1. Cardiotoxicity – more common with rapid infusion rates or high doses
  2. Nephrotoxicity – assess sodium status and correct deficiency at start of and during treatment if necessary. Ensure adequate hydration.
  3. Hypokalaemia and hypomagnesaemia - monitor both electrolytes, especially potassium, and correct deficiencies.
  4. Abnormal liver function tests (stop therapy) and hyperbilirubinaemia.
  5. Anaphylaxis
  6. Anaemia
  7. Venous irritation, pain and thrombophlebitis at injection site. Extravasation may cause tissue damage.
  8. Fever, vomiting, hypotension. For other adverse effects contact the ward pharmacist.

Interactions

  1. Loop diuretics (eg. frusemide), and thiazide diuretics – potential for hypokalemia..
  2. Nephrotoxic drugs eg. Gentamicin, amikacin, vancomycin, frusemide – renal toxicity risk.
  3. Digoxin - digitalis toxicity with hypokalaemia.
  4. Flucytosine - synergistic effect and risk of flucytosine toxicity. (Monitor flucytosine levels).

Special Considerations

  1. Amphotericin B should be used primarily for treatment of infants with progressive and potentially fatal fungal infections.
  2. Concommitant administration of sodium chloride at 4 mmol/kg/day reduces the risk of nephrotoxicity3.

Monitor