AMPHOTERICIN B conventional injectable

Prescription under medical supervision

Therapeutic action

– Antifungal

Indications

– Cryptococcal meningitis (induction phase), in combination with flucytosine or fluconazole
– Severe histoplasmosis or penicilliosis

Forms and strengths, route of administration

– Powder for injection, in 50 mg vial, to be dissolved in 10 ml of water for injection, to obtain a concentrated solution containing 5 mg/ml. The concentrated solution must be diluted in 500 ml of 5% glucose to obtain a solution containing 0.1 mg/ml, for slow IV infusion.

Dosage

– Child and adult: 0.7 to 1 mg/kg once daily over 4 to 6 hours depending on tolerance

Duration

– Cryptococcal meningitis: one week if in combination with flucytosine; 2 weeks if in combination with fluconazole
– Histoplasmosis: 1 to 2 weeks; penicilliosis: 2 weeks

Contra-indications, adverse effects, precautions

– Administer with caution to patients with renal impairment.
– May cause:
• intolerance reactions during administration: fever, chills, headache, nausea, vomiting, hypotension; local reaction: pain and thrombophlebitis at injection site; allergic reactions;
• muscle or joint pain, cardiovascular disorders (arrhythmias, heart failure, hypertension, cardiac arrest), neurologic (seizures, blurred vision, dizziness), haematological or hepatic disorders;
• disturbances in renal function (reduced glomerular filtration, hypokalaemia, hypo magnesiemia).
– Avoid combination with: drugs causing hypokalaemia (furosemide, corticosteroids), nephrotoxic drugs (amikacin, ciclosporine); digoxin, zidovudine, tenofovir.
– To prevent renal toxicity, administer 500 ml to 1 litre of 0.9% sodium chloride or Ringer lactate prior to each amphotericin B infusion.
– In adults, as soon as the patient can swallow, give supplements of potassium (2 tab of 8 mmol 2 times daily) and magnesium (500 mg 2 times daily) until the end of amphotericin treatment.
– In the event of intolerance, stop infusion, give paracetamol or an antihistamine then, resume administration reducing infusion rate by half.
– Monitor serum creatinine levels, and if possible, serum potassium levels (1 to 2 times weekly) throughout treatment.
– If serum creatinine levels rise by over 50%, increase preventive hydration (1 litre every 8 hours) or stop treatment. Then, after improvement, resume amphotericin at the lowest effective dose or on alternate days.
– Use liposomal amphotericin B if serum creatinine levels increase again or if clearance is < 30 ml/minute or in patients with pre-existing severe renal failure.
– Pregnancy: check for renal dysfunction in the newborn if administered during the last month of pregnancy.
– Breast-feeding: avoid, except if vital

Remarks

– Only use 5% glucose for administration (incompatible with other infusion fluids). Do not use the preparation if there is visible precipitation (the glucose solution is too acid).
– Do not add other drugs in the infusion bottle or bag.
– Protect infusion bottle from light during administration (wrap in dark paper).
– Storage
• Vial of powder: must be kept refrigerated (between 2 °C and 8 °C); in the absence of a refrigerator, 7 days maximum, below 25 °C.
• Concentrated solution (5 mg/1 ml): may be kept refrigerated 24 hours (between 2 °C and 8 °C).
• Solution for infusion (0.1 mg/ml): must be used immediately.