DBL CISPLATIN INJECTION 1 MG/ML [SIN00762P]

Product Info

DBL CISPLATIN INJECTION 1 MG/ML

[SIN00762P]

4.1 Therapeutic indications

DBL Cisplatin Injection is indicated for the palliative treatment of metastatic non-seminomatous germ cell carcinoma, advanced-stage refractory ovarian carcinoma, advanced-stage refractory bladder carcinoma and refractory squamous cell carcinoma of the head and neck. It may be used as a single agent or in combination with other chemotherapeutic agents. It may be employed, in appropriate circumstances, in addition to other modalities, e.g., radiotherapy or surgery.

4.2 Dose and method of administration

Dosage

A variety of doses and schedules are used. To obtain optimum therapeutic results with minimum adverse effects, the dosage of cisplatin must be based on the clinical, renal and haematologic status of the patient.

The usual dose in adults and children when used as single agent therapy is 50–100 mg/m² as a single IV infusion every 3–4 weeks, or 15–20 mg/m² as a daily IV infusion for 5 days every 3–4 weeks.

Dosage adjustment

Dosage should be reduced in patients with depressed bone marrow function.

Subsequent treatment with cisplatin

A repeat course of cisplatin should not be given until:

• the serum creatinine is below 140 micromol/L and/or the plasma urea is below 9 mmol/L and

• circulating blood elements are at an acceptable level (platelets at least 100,000/mm³, WBC at least 4000/mm³).

A base line audiogram should be taken and the patient monitored periodically for auditory deterioration (see section 4.4 Special warnings and precautions for use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Hepatic impairment

Human studies show a high uptake of cisplatin in the liver. An elevated aspartate aminotransferase (AST) and alkaline phosphatase (ALP) with clinical signs of liver toxicity have been reported in some cases. The adult dosage should be used with caution in patients with pre-existing hepatic dysfunction.

Renal impairment

Cisplatin displays high tissue uptake in the kidneys, exhibits dose related and cumulative nephrotoxicity, and is excreted mainly in the urine. In addition, the plasma elimination half-life of cisplatin is prolonged in renal failure.

Caution should be exercised in patients with pre-existing renal dysfunction. Cisplatin is contraindicated in patients with serum creatinine levels greater than 0.2 mmol/L. Repeat courses are not advised until serum creatinine is below 0.14 mmol/L and/or blood urea below 9 mmol/L.

Administration

1. Pre-treatment hydration: Patients should be adequately hydrated before and for 24 hours after administration of cisplatin to ensure good urinary output and minimise nephrotoxicity. Hydration may be achieved by IV infusion of 2 litres of either sodium chloride IV infusion 0.9% or glucose-saline (e.g., glucose 4% in one-fifth sodium chloride IV infusion 0.9%) over a 2-hour period. During the last 30 minutes of the pre-treatment hydration or after the hydration, 375 mL of 10% mannitol injection may be administered via a side-arm drip.

2. Preparation of cisplatin infusion: DBL Cisplatin Injection should be added to 1 litre of sodium chloride IV infusion 0.9%.

   Aluminium-containing equipment should not be used for administration of cisplatin (see section 6.2 Incompatibilities – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

3. Treatment: Following prehydration, administer the cisplatin infusion over 1–2 hours. It has been proposed that a longer infusion time of 6–8 hours may decrease gastrointestinal and renal toxicities.

   The IV flask should be covered to preclude light.

4. Post-treatment hydration: Adequate hydration and urinary output must be maintained during the 24 hours following infusion. It has been suggested that IV hydration continue after treatment with the aim to administer 2 litres of sodium chloride IV infusion 0.9% or glucose-saline over a period of 6–12 hours.

The product and its admixtures contain no antimicrobial agent. In order to reduce microbiological hazards, it is recommended that further dilution be effected immediately prior to use and infusion commenced as soon as practicable after preparation of the admixture. Infusion should be completed within 24 hours of preparation and the residue discarded.

Handling precautions

As with all antineoplastic agents, trained personnel should prepare DBL Cisplatin Injection. This should be performed in a designated area (preferably a cytotoxic laminar flow cabinet). Care should be taken to prevent inhaling particles and exposing the skin to cisplatin. Protective gown, mask, gloves and appropriate eye protection should be worn while handling cisplatin. In the event of contact with the eyes, wash with water or saline; where solution accidentally contacts skin or mucosa, the affected area should be immediately washed thoroughly with soap and water and in both cases seek medical advice. Seek immediate medical attention if the drug is ingested or inhaled. It is recommended that pregnant personnel not handle cytotoxic agents such as cisplatin.

Luer-Lock fitting syringes and giving sets to avoid leakage are recommended. Large bore needles are recommended to minimise pressure and possible formation of aerosols. Aerosols may also be reduced by using a venting needle during preparation.

Items used to prepare cisplatin, or articles associated with body waste should be disposed of by placing in a double sealed polythene bag, and incinerating at 1100°C.

Spills and disposal

If spills occur, restrict access to the affected area. Wear two pairs of gloves (latex rubber), a respirator mask, a protective gown and safety glasses. Limit the spread of the spill by covering with a suitable material such as absorbent towel or adsorbent granules. Spills may also be treated with 5% sodium hypochlorite. Collect up absorbent/adsorbent material and other debris from spill and place in a leak proof plastic container and label accordingly.

Cleanse the remaining spill area with copious amounts of water.

4.3 Contraindications

Use of cisplatin is contraindicated in the following conditions:

• Renal impairment (refer to Section 4.2 Dose and method of administration)

• Hearing disorders (refer to Section 4.4 Special warnings and precautions for use, Ototoxicity – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information)

• Bone marrow depression

• Generalised infections

• During pregnancy or lactation

• In patients with a history of hypersensitivity to cisplatin or platinum-containing compounds.