PRIALT 100 micrograms/ml SOLUTION FOR INFUSION

2. What you need to know before you are given Prialt

You should not be given Prialt

• If you are allergic to ziconotide or any of the other ingredients of this medicine (listed in section 6).
• If you are being given a cancer medicine in the area around the spinal cord.
• If you have a history of attempted suicide or suicidal thoughts with ziconotide.

Warnings and precautions

Patients must undergo neuropsychiatric evaluation before, after starting and during ziconotide intrathecal administration, and immediately if any depressive signs or symptoms appear.

Caregivers should contact a doctor immediately if the patient shows symptoms of a potentially life-threatening adverse event.

Talk to your doctor before you are given Prialt.

• The effects of long-term treatment with Prialt are, to date, uncertain and the possibility of toxic effects on the spinal cord has not been ruled out. If long-term treatment is necessary, monitoring (as decided by your doctor) may be required.
• If you are receiving Prialt through a pump placed outside the body, it is essential that you check once a day for signs of infection at the point where the tube enters the body.
• If you notice any signs of infection around the tube, such as redness of the skin, swelling, pain or discharge, you should inform your doctor immediately and seek treatment for the infection.
• If you experience increased sensitivity in the area around the tube but no signs of infection, you should consult your doctor as soon as possible, as this may be an early sign of infection.
• If you are receiving Prialt with a pump placed outside the body and any part of the infusion system becomes disconnected, you should contact your doctor or nurse immediately.
• If you experience any of the following symptoms: high temperature, headache, stiff neck, tiredness, confusion, feeling unwell, vomiting or occasional seizures, these may be signs of meningitis. If you experience any of these symptoms, you should inform your doctor immediately.
• If you experience any changes in your thoughts, mood or memory, you should talk to your doctor.
• If you are receiving chemotherapy, you should inform your doctor.
• You may experience an increase in blood levels of an enzyme called creatine kinase, and although this usually does not cause any symptoms or problems, your doctor may decide to monitor it. Additionally, you may occasionally experience muscle problems. If this happens, you should inform your doctor immediately, as they may decide to stop treatment with Prialt.
• You should inform your doctor immediately if you experience any of the following symptoms: if you notice sudden wheezing, breathing difficulties, chest pain, swelling of the eyelids, face and lips, skin rash or itching (especially if it affects the whole body). These may be signs of a severe allergic reaction.
• In patients with severe chronic pain, there is a higher risk of suicide and attempted suicide than in the general population. Prialt may also cause depression or worsen it in people who are already susceptible. If you suffer from depression or have a history of depression, you should inform your healthcare professional before starting treatment with Prialt. If, after starting treatment with Prialt, you experience worsening of depression or any other symptoms that affect your mood, you should inform your healthcare professional.
• You may experience drowsiness or may not be fully aware of your surroundings while receiving treatment. If this happens, you should inform your doctor immediately, as they may decide to stop treatment with Prialt.

Children and adolescents

Prialt is not recommended for use in children and adolescents.

Other medicines and Prialt

Tell your doctor if you are using, have recently used or might use any other medicines (e.g. baclofen, used to treat muscle spasticity; clonidine, used to treat high blood pressure; bupivacaine, used for local anaesthesia; morphine, used for pain; propofol, used for general anaesthesia or any other medicine given by injection into the space around the spinal cord and brain). You may experience drowsiness if you use Prialt with certain medicines used to treat pain.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant or plan to become pregnant, you should talk to your doctor before using this medicine.

Prialt is not recommended during pregnancy or in women of childbearing age who are not using contraceptive methods.

Driving and using machines

Prialt has been reported to cause confusion and drowsiness. You should talk to your doctor before driving or using machinery.

Prialt contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per maximum recommended intrathecal dose (21.6 micrograms per day); this is essentially 'sodium-free'.

3. How to use Prialt

Treatment with Prialt should be supervised by a doctor with experience in the administration of medicines into the space around the spinal cord and in the use of internal and external infusion pumps.

The recommended starting dose is no more than2.4 micrograms per day. Your doctor may adjust the dose of Prialt very slowly, depending on the intensity of the pain, adding up to 2.4 micrograms/day. The maximum dose is 21.6 micrograms/day. At the start of treatment, your doctor may increase the dose every one or two days, or more. If the side effects are too severe, the dose may be reduced or the infusion stopped.

Prialt is given as a continuous, very slow injection into the space around the spinal cord (intrathecal route). The medicine will be given continuously through a pump that can be implanted in the abdominal wall or placed outside the body with a belt. Your doctor will discuss with you which type of pump is most suitable for you and inform you when the pump needs to be refilled.

Pain relief may be achieved through a gradual process, adjusting the dose of Prialt very slowly. If you think you still have too much pain despite treatment with Prialt, or if the side effects are too severe, you should inform your doctor.

Before giving you Prialt, your doctor may decide to gradually stop the administration of opioids (other types of pain relief medicines) into the spinal cord and replace them with alternative pain relief medicines.

If you are given more Prialt than you should

If you are given more Prialt than your doctor intended, you may experience signs such as confusion, language problems, difficulty finding words, excessive agitation, dizziness, excessive drowsiness and feeling unwell. If you experience any of these signs, you should talk to your doctor or go to the hospital immediately.

If you have any further questions on the use of this medicine, ask your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Serious side effects

You should tell your doctor immediately if you notice any of the following serious side effects, as you may need urgent medical treatment.

• Meningitis (may affect up to 1 in 100 people): this is an inflammation of the membranes that surround the brain and spinal cord, usually caused by an infection. The symptoms of meningitis are headache, stiff neck, intolerance to light, fever, vomiting, confusion and drowsiness.

• Seizures (may affect up to 1 in 100 people): seizures are sudden, uncontrolled movements of the body. During a seizure, the muscles contract and relax repeatedly and the person may lose consciousness.

• Suicidal thoughts or attempted suicide (may affect up to 1 in 100 people).

• Rhabdomyolysis (may affect up to 1 in 100 people): this is the breakdown of muscle fibres, which can cause kidney damage. The symptoms of rhabdomyolysis are abnormal urine colour (brown), decreased urine output, muscle weakness, muscle pain or muscle tenderness.

• Coma (may affect up to 1 in 100 people): this is a state of unconsciousness with difficulty responding or waking up.

• Anaphylactic reaction (frequency cannot be estimated from the available data): this is a severe allergic reaction, with symptoms such as sudden wheezing, breathing difficulties, chest pain, swelling of the eyelids, face and lips, skin rash or itching (especially if it affects the whole body).

Other side effects

Very common (may affect more than 1 in 10 people)

Confusion, dizziness, blurred vision, headache, rapid eye movements, memory loss or disturbances (absent-mindedness), vomiting, nausea, general weakness and drowsiness.

Common (may affect up to 1 in 10 people)

Decreased appetite, anxiety or worsening anxiety, hallucinations, difficulty sleeping or staying asleep, agitation, disorientation, depression or worsening depression, nervousness, mood changes, mental disorders (abnormal thinking, confusion), paranoia, irritability, worsening confusion, learning difficulties, memory or thinking problems, absence or loss of reflexes, problems expressing or understanding words, stuttering, difficulties with language or loss of ability to speak, laziness, balance or coordination problems, burning sensation, increased abnormal sensations, decreased level of consciousness (unresponsive or nearly unresponsive), sedation, difficulty concentrating, problems with sense of smell, abnormal taste or loss of taste, agitation, tingling, double vision, visual disturbances, light intolerance, tinnitus (ringing in the ears), dizziness or feeling like everything is spinning, fainting or dizziness when standing up, low blood pressure, breathing difficulties, dry mouth, abdominal pain, increased nausea, diarrhoea, constipation, sweating, itching, muscle weakness, muscle spasms, muscle cramps, muscle or joint pain, difficulty or pain when urinating, difficulty starting or controlling urination, feeling restless, falls, pain or increased pain, fatigue, feeling cold, swelling of the face, legs or feet, chest pain, changes in blood biochemistry, mental deterioration and weight loss.

Uncommon (may affect up to 1 in 100 people)

Blood infection, delirium (feeling of mental confusion), psychotic disorder (abnormal thoughts and perceptions), thought disorders, abnormal dreams, incoherence (inability to make sense), loss of consciousness, stupor (unresponsive/difficulty waking up), stroke, encephalopathy (brain disorder), aggression, abnormal heart rhythm, breathing difficulties, indigestion, skin rash, muscle inflammation, back pain, muscle spasms, neck pain, acute kidney failure, abnormal ECG readings, increased body temperature and difficulty walking.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly to the Spanish Medicines Agency at www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Prialt

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the label and carton after EXP. The expiry date is the last day of the month stated.

Store in a refrigerator (between 2°C and 8°C).

Do not freeze.

Keep the vial in the outer packaging to protect it from light.

It has been demonstrated that the product is chemically and physically stable for 60 days at 37°C.

From a microbiological point of view, once the product is diluted, it should be transferred to the infusion pump immediately. If not used immediately, the in-use storage times and conditions are the responsibility of the user and normally should not exceed 24 hours between 2°C and 8°C, unless the dilution has been performed under validated and controlled aseptic conditions.

Do not use this medicine if you notice a change in colour, turbidity or particles.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Content and Additional Information

Prialt Composition

• The active ingredient is ziconotide.
• One milliliter of solution contains 100 micrograms of ziconotide (as acetate).
• Each 1 ml vial contains 100 micrograms; each 2 ml vial contains 200 micrograms; each 5 ml vial contains 500 micrograms.
• The other components (excipients) are methionine, sodium chloride, water for injectable preparations, hydrochloric acid, and sodium hydroxide.

Product Appearance and Container Content

Prialt is a solution for infusion (infusion). The solution is transparent and colorless. Prialt is presented in containers with a single vial of 1 ml, 2 ml, or 5 ml. Only some package sizes may be marketed.

Marketing Authorization Holder:

Esteve Pharmaceuticals GmbH

Hohenzollerndamm 150-151

14199 Berlin

Germany

Manufacturer:

HWI pharma services GmbH

Straßburger Straße 77

77767 Appenweier

Germany

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Prospectus:{MM/AAAA}

Other Sources of Information

Detailed information about this medication is available on the European Medicines Agency website: http://www.ema.europa.eu. There are also links to other websites about rare diseases and orphan medicines.

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This information is intended only for healthcare professionals:

Instructions for Use and Handling

Prialt is presented as a transparent and colorless solution, in single-use vials. Before administration, a visual inspection must be performed to detect the presence of particles and color changes. The solution should not be used if it has changed color or appears turbid, or if particles are observed.

For single use. The disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.

If dilution of the product is necessary, the dilution of Prialt should be performed before use and in an aseptic manner with a 9 mg/ml (0.9%) sodium chloride injectable solution without preservatives. The concentration of the solution used in the infusion pump should not be less than 5 μg/ml of ziconotide in an external pump and 25 μg/ml in an internal pump.

During the preparation and handling of the infusion solution and filling of the pump, rigorous aseptic procedures should be used. The patient and healthcare personnel should be familiar with the handling of external or internal infusion systems and be aware of the need to avoid infections.

The specific instructions for the use of the pumps provided by the manufacturers should be followed.

Prialt has been shown to be chemically and physically compatible with the Synchromed implantable pump and the CADD-Micro external pump, at the concentrations mentioned above. Chemical and physical stability has been demonstrated for 14 days at 37°C in the Synchromed pump when the pump has not previously been in contact with the medication. Therefore, the initial load should be replaced after 14 days.

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

Technical data are provided for informational purposes only and should not limit the choice of healthcare professionals. For the administration of ziconotide, pumps with a CE mark equivalent to Synchromed and CADD-Micro should be used.

Pumps previously used to administer other medications should be washed three times with a 9 mg/ml (0.9%) sodium chloride injectable solution (without colorants) before loading with ziconotide. It is essential to minimize the amount of air introduced into the pump reservoir or cartridge, as oxygen can degrade ziconotide.

Before starting treatment, internal pumps should be rinsed three times with 2 ml of the solution at concentrations of 25 μg/ml. The concentration of Prialt in an unused pump may decrease due to absorption by the device surfaces or dilution by the device's residual space. For this reason, after the first use of Prialt, the reservoir should be emptied and reloaded after 14 days. Subsequently, the empty pump will be reloaded every 60 days.