Antifungals (polyene antibiotics) .

Amphotericin

Powder in vial.

Powder for injection, amphotericin (as sodium cholesteryl complex) 50 mg (50, 000 units), 100 mg (100,000 units).

Treatment of severe systemic and/ or deep mycoses in cases where toxicity or renal failure precludes the use of conventional amphotericin B in effective doses, and in cases where prior systemic antifungal therapy has failed. Fungal infections successfully treated with Amphocil include disseminated candidiasis and aspergillosis. Amphocil has been used successfully in severely neutropenic patients. Amphocil is not intended for use in common, clinically inapparent fungal diseases diagnosed only by skin tests or serological determinations.

Amphocil 100mg:

Dosage:

Therapy may begin at a daily dose of 1.0 mg/kg of body weight, increasing to the recommended dose of 3.0-4.0 mg/kg as required. Doses as high as 6 mg/kg have been used in patients. Dosage should be adjusted to the individual requirements of each patient. The median cumulative dose in clinical studies was 3.5 g and the median treatment duration was 16 days. Ten percent (10%) of patients received 13 g or more of Amphocil over a period of 27 to 409 days.

Administration:

Amphocil is administered by intravenous infusion at a rate of 1 to 2 mg/kg/hour. If the patient experiences acute reactions or cannot tolerate the infusion volume, the infusion time may be extended. Pre-medication (e.g. paracetamol, antihistamines, antiemetics) may be administered to patients who have previously suffered infusion related adverse reactions.

Paediatric Patients:

A limited number of paediatric patients have been treated with Amphocil at daily doses (mg/kg) similar to those in adults. No unusual adverse events were reported.

Amphocil 50mg:

Dosage:

Therapy may begin at a daily dose of 1.0 mg/kg of body weight, increasing to the recommended dose of 3.0-4.0 mg/kg as required. Doses as high as 6 mg/kg have been used in patients. Dosage should be adjusted to the individual requirements of each patient. The median cumulative dose in clinical studies was 3.5 g and the median treatment duration was 16 days. Ten percent (10%) of patients received 13 g or more of Amphocil over a period of 27 to 409 days.

Administration:

Amphocil is administered by intravenous infusion at a rate of 1 to 2 mg/kg/hour. If the patient experiences acute reactions or cannot tolerate the infusion volume, the infusion time may be extended. Pre-medication (e.g. paracetamol, antihistamines, antiemetics) may be administered to patients who have previously suffered infusion related adverse reactions.

Paediatric Patients:

A limited number of paediatric patients have been treated with Amphocil at daily doses (mg/kg) similar to those in adults. No unusual adverse events were reported

Amphocil 100mg/50mg

A limited number of elderly patients have been treated with Amphocil; available data do not indicate the need for specific dose recommendations or precautions in elderly patients.

Amphocil should not be administered to patients who have documented hypersensitivity to any of its components, unless, in the opinion of the physician, the advantages of using Amphocil outweigh the risks of hypersensitivity.

test dose, which is advisable when commencing all new courses of treatment should immediately precede the first dose; a small amount of drug (e.g. 20 ml of a solution containing 0.1 g per litre) should be infused over 10 minutes and the patient carefully observed for the next 30 minutes.

In the treatment of diabetic patients:

It should be noted that each vial of Amphocil contains lactose monohydrate.

In the treatment of renal dialysis patients:

Amphocil should be administered only at the end of each dialysis period. Serum electrolytes, particularly potassium and magnesium, should be regularly monitored.

There have been no reported interactions between Amphocil and other drugs including cyclosporine. However, caution should be used in patients receiving concomitant therapy with drugs known to interact with conventional amphotericin B such as nephrotoxic drugs (aminoglycosides, cisplatin and pentamidine), corticosteroids and corticotropin (ACTH) that may potentiate hypokalaemia and digitalis glycosides, muscle relaxants and antiarrhythmic agents whose effects may be potentiated in the presence of hypokalaemia.

The use of flucytosine with Amphocil has not been studied. While the synergy between amphotericin B and flucytosine has been reported, amphotericin B may enhance the toxicity of flucytosine by increasing its cellular uptake and impeding its renal excretion.

Acute pulmonary reactions have been noted in patients receiving amphotericin B during or shortly after leukocyte transfusions.

In general, the physician should monitor the patient for any type of adverse event associated with conventional amphotericin B. The appearance of adverse reactions does not generally prevent the patient completing the course of treatment. Caution should be exercised when high doses or prolonged therapy is indicated.

Acute reactions including fever, chills and rigours may occur. Anaphylactoid reactions including hypotension, tachycardia, bronchospasm, dyspnoea, hypoxia and hyperventilation have also been reported. Most acute reactions are successfully treated by reducing the rate of infusion and prompt administration of anti-histamines and adrenal corticosteroids. Serious anaphylactoid effects may necessitate discontinuation of Amphocil and treatment with additional supportive therapy (e.g. adrenaline).

Clinical studies conducted so far have shown Amphocil to be less nephrotoxic than conventional amphotericin B. Serum creatinine levels tend to remain consistent throughout the course of therapy even in patients with renal insufficiency. Patients who developed renal insufficiency during treatment with conventional amphotericin B, were stabilised or improved when Amphocil was substituted. Decreases in renal function attributable to Amphocil treatment were rare. However, as with conventional amphotericin B, renal function should be monitored with particular attention to those patients receiving concomitant therapy with nephrotoxic drugs.

There have been no reports of unequivocal hepatic toxicity of Amphocil. Changes in alkaline phosphatase and bilirubin levels were infrequent.

Changes in coagulation, thrombocytopenia and hypomagnesemia were sometimes observed on Amphocil. Anaemia, which is a very common adverse event during treatment with conventional amphotericin B, developed in only 2.5% of the patients treated with Amphocil.

Other reported events include nausea, vomiting, hypertension, headache, backache, diarrhoea and abdominal pain.

Cambridge Laboratories

(POM)

04 June 2009