PRIALT Solution for infusion Ref.[9283] Active ingredients: Ziconotide

Treatment with ziconotide should only be undertaken by physicians experienced in intrathecal (IT) administration of medicinal products.

Posology

Adults (including the elderly ≥65 years of age)

Dosing of ziconotide should be initiated at 2.4 μg/day and titrated on an individual patient basis according to the patient’s analgesic response and adverse reactions. Patients should be titrated in dose increments of ≤2.4 μg/day, up to a maximum dose of 21.6 μg/day. The minimalinterval between dose increases is 24 hours; the recommended interval, for safety reasons, is 48 hours or more. If necessary the dose can be decreased by any amount (including stopping the infusion) for the management of adverse reactions. Approximately 75% of patients who respond satisfactorily to treatment require a dose of ≤9.6 μg/day.

Renal impairment

Studies have not been conducted in patients with impaired renal function. Caution should be exercised when ziconotide is administered to patients with impaired renal function.

Hepatic impairment

Studies have not been conducted in patients with impaired hepatic function. Caution should be exercised when ziconotide is administered to patients with impaired hepatic function.

Paediatric population

The safety and efficacy of ziconotide in children aged 0 to 18 years have not been established.

No data are available.

Method of administration

Intrathecal use.

Ziconotide must be administered as a continuous infusion via an intrathecal catheter, using an external or internally implanted mechanical infusion pump capable of delivering an accurate infusion volume. As the risk of meningitis secondary to prolonged catheterisation of the intrathecal space is greater with an external catheter infusion system, internal systems are recommended to administer ziconotide for prolonged periods (see section 4.4). An external catheter system should only be used when an internal system cannot be implanted.

When low doses of ziconotide are required, for example when initiating titration, ziconotide must be diluted before use with preservative-free sodium chloride 9 mg/ml (0.9%) solution for injection.

For instructions on dilution of the medicinal product before administration, see section 6.6.

In intravenous infusion studies, healthy male volunteers received ziconotide at doses of up to70,000 μg/day or 3,200 times the maximum recommended daily intrathecal infusion dose. Postural hypotension was observed in almost all subjects who received high intravenous doses of ziconotide.

The maximum recommended intrathecal dose is 21.6 μg/day. The maximum intended intrathecal dose of ziconotide in clinical trials was 912 μg/day following upward titration over 7 days.

Symptoms

In one clinical study a male cancer patient received an accidental IT ziconotide overdose of 744 μg over a 24-hour period (31 μg/hour) and resumed treatment at the intended dose after experiencing a reduction in Visual Analog Scale of Pain Intensity (VASPI) from 82 to 2.5 mm. In some patients who received intrathecal doses greater than the maximum recommended dose, exaggerated pharmacological effects, e.g., ataxia, nystagmus, dizziness, stupor, depressed level of consciousness, muscle spasms, confusional state, sedation, hypotension, aphasia, speech disorder, nausea and vomiting were observed. There was no indication of respiratory depression. Most patients under observation recovered within 24 hours of withdrawal of the medicinal product.

Management

General medical supportive measures should be administered to patients who receive an overdose until the exaggerated pharmacological effects of the medicinal product have resolved.

Shelf life: 4 years.

In-use shelf-life (diluted product): Chemical and physical in use stability has been demonstrated for 60 days at 37°C.

From a microbiological point of view, if the product is diluted it should be transferred to the infusion pump immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C–8°C, unless dilution has taken place in controlled and validated aseptic conditions.

Store in a refrigerator (2°C-8°C). Do not freeze. Keep the vial in the outer carton in order to protect from light.

For storage conditions after dilution of the medicinal product, see section 6.3.

Type I glass vials with butyl rubber stoppers coated with fluorinated polymer.

Each vial contains 20 ml solution for infusion.

One vial per carton.

If dilution is required, Prialt must be diluted aseptically with preservative-free sodium chloride 9 mg/ml (0.9%) solution for injection before use. The concentration of the solution used in the infusion pump must be no lower than 5 μg/ml ziconotide in an external pump and 25 μg/ml in an internal pump.

Strict aseptic procedures must be used during the preparation and handling of the solution for infusion and refilling of the pump. The patient and health-care providers must be familiar with the handling of the external or internal infusion system and be aware of the need to guard against infection.

Specific instructions for using the pumps must be obtained from the manufacturer.

Prialt has been shown to be chemically and physically compatible with the implantable Synchromed pump and the external CADD-Micro pump at the concentration levels indicated above. Chemical and physical in-use stability has been demonstrated for 14 days at 37ºC in the Synchromed pump when the pump has not previously been exposed to the medicinal product. The initial fill must therefore be replaced after 14 days.

Prialt was stable for 60 days at 37°C in the Synchromed pump previously exposed to the medicinal product. Stability has been demonstrated for 21 days at room temperature in the CADD-Micro pump.

The technical data are given only for information and should not limit health-care providers' choice. CE marked pumps equivalent to the Synchromed and CADD-Micro pump should be used to deliver Prialt.

Pumps previously used to deliver other medicinal products must be washed out three times with sodium chloride 9 mg/ml (0.9%) solution for injection (preservative-free) before being filled with Prialt. The introduction of air into the pump reservoir or cartridge should be minimized, as oxygen can degrade ziconotide.

Prior to initiation of therapy, an internal pump must be rinsed three times with 2 ml of Prialt at 25 μg/ml. The concentration of Prialt in a naïve pump may be reduced due to adsorption onto the surfaces of the device, and/or dilution by the residual space of the device. Because of this, after the first use of Prialt, the reservoir should be emptied and refilled after 14 days. Subsequently the pump should be emptied and refilled every 60 days.

Prialt should be inspected visually for particulate matter and discolouration prior to administration. The solution should not be used if discoloured or cloudy or if particulate matter is observed.

For single use only. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.