Package Insert: Information for the Patient

Prialt 100 micrograms/mL Infusion Solution

Ziconotide

Read this entire package insert carefully before you receive this medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor or pharmacist.
• If you experience any adverse effects, consult your doctor, even if they are not listed in this package insert. See section 4.

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Prialt contains the active ingredient ziconotide, which belongs to a group of medications called analgesics or "pain medications". Prialt is used for the treatment of severe chronic pain in adults who require a pain medication administered via intrathecal injection (injection into the space surrounding the spinal cord and brain).

Do not administer Prialt

• If you are allergic to ziconotide or any of the other components of this medication (listed in section 6).
• If you are receiving chemotherapy in the area around the spinal cord.
• If you have a history of suicidal attempts or suicidal ideation with ziconotide.

Warnings and precautions

Patients must undergo a neuropsychiatric evaluation before, after initiating, and during the administration of intrathecal ziconotide, and immediately if any depressive symptoms appear.

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

Consult your doctor before receiving Prialt.

• The effects of prolonged treatment with Prialt are, to date, uncertain and the possibility of spinal cord toxicity has not been ruled out. If prolonged treatment is necessary, monitoring may be required (as decided by your doctor).
• If you are receiving Prialt through a pump placed outside the body, it is essential to check once a day for signs of infection at the entry point of the tube in the body.
• If you notice any signs of infection around the tube, such as redness of the skin, swelling, pain, or discharge, you must inform your doctor immediately and request treatment for the infection.
• If increased sensitivity appears in the area around the tube but there are no signs of infection, you should consult your doctor as soon as possible, as it may be an early sign of infection.
• If you are receiving Prialt with a pump placed outside the body and disconnect any part of the infusion system, you must contact your doctor or nurse immediately.
• If you experience any of the following symptoms: high temperature, headache, neck stiffness, fatigue, confusion, feeling unwell, vomiting, or occasional seizures, they may be signs of meningitis. If you experience any of the above symptoms, you must inform your doctor immediately.
• If you experience any change in your thoughts, mood, or memory, consult your doctor.
• If you are receiving chemotherapy, 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 monitor it. You may also experience occasional muscle problems. If this is the case, you must inform your doctor immediately, as they may decide to suspend treatment with Prialt.
• You must inform your doctor immediately if you experience any of the following symptoms: sudden onset of wheezing (sudden wheezing), difficulty breathing, chest pain, swelling of the eyelids, face, and lips, skin rash, or itching (especially if it affects the entire body). These may be signs of a severe allergic reaction.
• In patients with severe chronic pain, there is a higher probability of suicide and suicide attempts than in the general population. Prialt may also cause depression or worsen it in people who are susceptible. If you experience depression or have a history of depression, inform your healthcare professional before starting treatment with Prialt. If you experience a worsening of depression or any other symptom that affects your mood after starting treatment with Prialt, inform your healthcare professional.
• You may experience drowsiness or may not be fully aware of your surroundings while receiving treatment. If this occurs, you must inform your doctor immediately, as they may decide to suspend treatment with Prialt.

Children and adolescents

Prialt is not recommended for use in children and adolescents.

Other medications and Prialt

Inform your doctor if you are using, have used recently, or may need to use any other medication (for example, baclofen, which is used to treat muscle spasticity; clonidine, which is used to treat high blood pressure; bupivacaine, which is used for local anesthesia; morphine, which is used for pain; propofol, which is used for general anesthesia, or any other medication administered intrathecally [injection in the space around the spinal cord and brain]). You may experience drowsiness if you use Prialt with certain medications used to treat pain.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, or plan to become pregnant, consult your doctor before using this medication.

Prialt is not recommended during pregnancy, nor in women of childbearing age who are not using contraceptive methods.

Driving and operating machinery

It has been reported that the use of Prialt may cause confusion and drowsiness. Consult your doctor before driving or operating machinery.

Prialt contains sodium

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

Prialt treatment should be controlled by a doctor with experience in administering medications 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 gradually adjust the Prialt dose, depending on the intensity of the pain, by adding a maximum of 2.4 micrograms/day. The maximum dose is 21.6 micrograms/day. At the beginning of treatment, the doctor may increase the dose every one or two days, or more. If adverse effects are too severe, the dose may be reduced or the injection stopped.

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

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

Before giving you Prialt, your doctor may decide to gradually discontinue the administration of opioids (other types of medications used to treat pain) in the spinal cord and replace them with alternative analgesic medications.

If you receive more Prialt than you should

If you receive more Prialt than your doctor intended to administer, you may experience symptoms such as confusion, language problems, difficulty finding words, excessive agitation, dizziness, excessive drowsiness, and a feeling of discomfort. If you experience any of these symptoms, consult your doctor or the hospital immediately.

If you have any other questions about the use of this medication, ask your doctor.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

Severe side effects

You must inform your doctor immediately if you observe the following severe side effects, as you may need urgent medical treatment.

• Meningitis (may affect up to 1 in 100 people): it 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, aversion to bright light, fever, vomiting, confusion, and drowsiness.

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

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

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

• Anaphylactic reaction (frequency cannot be estimated from available data): it is a severe allergic reaction, whose symptoms are sudden, high-pitched breathing sounds (sudden wheezing), difficulty breathing, chest pain, swelling of the eyelids, face, and lips, skin rash, or itching (especially if it affects the entire body).

Other side effects

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

Confusion, dizziness, blurred vision, headache, rapid eye movements from side to side, loss or disturbances of memory (blackouts), vomiting, nausea, general weakness, and drowsiness.

Common (may affect up to 1 in 10 people)

Decreased appetite, anxiety or worsening of anxiety, hallucinations, difficulty falling asleep or staying asleep, agitation, disorientation, depression or worsening of depression, nervousness, mood changes, mental disorders (abnormal thinking, confusion), paranoia, irritability, worsening of confusion, difficulties with learning, memory, or thinking, absence or deterioration of reflexes, problems expressing or understanding words, stuttering speech, difficulties with language or loss of ability to speak, lethargy, alterations in balance or coordination, burning sensation, increased abnormal sensations, decreased level of consciousness (does not respond or almost unconscious), sedation, difficulty concentrating, problems with sense of smell, strange or absent taste, agitation, paresthesia, double vision, visual disturbances, light intolerance, tinnitus (ringing in the ears), dizziness or feeling that everything is spinning, lipotimia or dizziness when standing, hypotension, difficulty breathing, dry mouth, abdominal pain, increased nausea, diarrhea, constipation, sweating, pruritus, muscle weakness, muscle spasms, muscle cramps, muscle or joint pain, difficulty or pain urinating, difficulty initiating or controlling urination, feeling of restlessness, falls, pain or increased pain, fatigue, feeling cold, facial swelling, leg or foot swelling, chest pain, alterations in blood chemistry, mental deterioration, and weight loss.

Rare (may affect up to 1 in 100 people)

Bloodstream 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 (does not respond/difficulty waking up), stroke, encephalopathy (brain disorder), aggression, abnormal heart rhythm, difficulty breathing, indigestion, skin rash, muscle inflammation, back pain, muscle spasms, neck pain, acute renal failure, abnormal ECG tracing, increased body temperature, and difficulty walking.

Reporting side effects

If you experience any type of side effect, consult your doctor, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the label and the box after CAD. The expiration date is the last day of the month indicated.

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

Do not freeze.

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

Stability of use has been demonstrated both chemically and physically for 60 days at 37°C.

From a microbiological point of view, once the product is diluted, it should be passed to the infusion pump immediately. If it is not used immediately, the useful storage times and conditions before use are the responsibility of the user and should not usually be greater than 24 hours at 2°C to 8°C, unless the dilution has been made in validated and controlled aseptic conditions.

Do not use this medication if you observe a change in color, turbidity, or particles.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of Prialt

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

Appearance of the product and contents of the package

Prialt is a perfusion solution (infusion). The solution is transparent and colorless. Prialt is presented in single-use vials of 1 ml, 2 ml, or 5 ml. Only some package sizes may be commercially available.

Marketing Authorization Holder:

Esteve Pharmaceuticals GmbH

Hohenzollerndamm 150-151

14199 Berlin

Germany

Responsible for manufacturing:

HWI pharma services GmbH

Straßburger Straße 77

77767 Appenweier

Germany

For more information about this medication, please contact the local representative of the marketing authorization holder:

Last review date of this leaflet:{MM/AAAA}

Other sources of information

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

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This information is intended solely for healthcare professionals:

Instructions for use and handling

Prialt is a clear, colorless solution for infusion. Before administration, a visual inspection should be performed to detect the presence of particles and changes in color.The solution should not be used if it has changed color or appears turbid, or if particles are visible.

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

If dilution is necessary, Prialt should be diluted before use and in an aseptic manner with sodium chloride 9 mg/ml (0.9%) 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 the 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 pumps and be aware of the need to prevent 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 external CADD-Micro 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 come into contact with the medication. Therefore, the initial loading should be replaced after 14 days.

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

The technical data provided are 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 sodium chloride 9 mg/ml (0.9%) solution (without dyes) before loading them 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 flushed 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 pump surfaces or dilution by the residual space in the pump. Therefore, after the first use of Prialt, the pump reservoir should be emptied and reloaded after 14 days. Subsequently, the empty pump should be reloaded every 60 days.