ETOPOPHOS

What it is

Etoposide phosphate is a water-soluble prodrug of etoposide (VP-16-213), a semi-synthetic derivative of podophyllotoxin, is an anti-neoplastic drug for intravenous use, which can be used alone or in combination with other oncolytic drugs. ETOPOPHOS is available in single use vials each containing 113.6 mg of etoposide phosphate (equivalent to 100 mg etoposide) as a lyophilised powder for injection. ETOPOPHOS injection is also available in pharmacy bulk vials containing either 568 mg of etoposide phosphate (equivalent to 500 mg etoposide) or 1136 mg of etoposide phosphate (equivalent to 1 g etoposide).

Approved indications —

Small cell carcinoma of the lung. — Acute monocytic and myelomonocytic leukaemia. — Hodgkin's disease. — Non-Hodgkin's lymphoma. — Testicular tumours.

Dosing overview

ETOPOPHOS is administered by slow intravenous infusion and should not be given by rapid intravenous injection. The usual dose for etoposide is 50 to 100 mg/m²/day, days 1 to 5 or 100–150 mg/m²/day, days 1, 3 and 5 every 3 to 4 weeks in combination with other agents approved for use in the disease to be treated. ETOPOPHOS may be infused over 5–210 minutes. Dosage should be modified to take into account the myelosuppressive effects of other medications in the combination or the effects of prior X-ray therapy or chemotherapy which may have compromised bone marrow reserve.

Key safety warnings

Severe myelosuppression with resulting infection or bleeding may occur. Fatal myelosuppression has been reported following etoposide administration. Patients being treated with ETOPOPHOS must be observed for myelosuppression carefully and frequently both during and after therapy. Dose limiting bone marrow suppression is the most significant toxicity associated with ETOPOPHOS therapy. Physicians should be aware of the possible occurrence of an anaphylactic reaction manifested by chills, fever, tachycardia, bronchospasm, dyspnoea and hypotension, which can be fatal. The administration should be terminated immediately, followed by the administration of pressor agents, corticosteroids, antihistamines, or volume expanders at the discretion of the physician. Tumour lysis syndrome (sometimes fatal) has been reported following the use of etoposide in association with other chemotherapeutic drugs. Close monitoring of patients is needed to detect early signs of tumour lysis syndrome, especially in patients with risk factors such as bulky treatment-sensitive tumours, and renal insufficiency. The occurrence of acute leukaemia, which can occur with or without a myelodysplastic syndrome, has been described in patients that were treated with VEPESID in association with other antineoplastic drugs. Neither the cumulative risk, nor the predisposing factors related to the development of secondary leukaemia are known. Another characteristic that has been associated with secondary leukaemia in patients who have received epipodophyllotoxins appears to be a short latency period, with average median time to development of leukaemia being approximately 32 months.

Contraindications

ETOPOPHOS is contraindicated in patients with severe hepatic or renal dysfunction or in those patients who have demonstrated a previous hypersensitivity to etoposide, etoposide phosphate or any component of the formulation. ETOPOPHOS is contraindicated in severe bone marrow failure (WBC less than 2000 cells/mm³ or platelet count less than 75000 cells/mm³) not due to malignant disease. ETOPOPHOS must not be given by intra-cavity injection.

Regulatory history

ETOPOPHOS (etoposide phosphate 113.6 mg, equivalent to 100 mg etoposide) powder for injection vial was first listed on the ARTG on 18 December 1996. Two additional presentations—500 mg and 1 g vials—were subsequently added to the ARTG on 29 January 2001.