Prospecto: information for the user

Duodopa 240mg/ml + 12mg/ml infusion solution

levodopa/carbidopa

Read this prospectus carefully before starting to use this medication, as it contains important information for you.

• Keep this prospectus, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist, or nurse.

-This medication has been prescribed only to you, and you should not give it to other people even if they have the same symptoms as you, as it may harm them.

• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this prospectus. See section4.

1.What is Duodopa infusion solution and for what it is used

2.What you need to know before starting to use Duodopa infusion solution

3.How to use Duodopa infusion solution

4.Possible adverse effects

1. Storage of Duodopa infusion solution
2. Contents of the package and additional information
3. Instructions for using Duodopa infusion solution with the Vyafuser pump

This medication contains two active principles, levodopa and carbidopa, and is used to treat Parkinson's disease.

How Duodopa infusion solution works

• Levodopa is transformed into "dopamine" in the body. This is added to the dopamine that is already present in the brain and spinal cord. Dopamine helps to transmit signals between nerve cells.
• Low levels of dopamine are the cause of the symptoms of Parkinson's disease, such as tremor, sensation of stiffness, slow movement, and balance disorders.
• Treatment with levodopa increases the amount of dopamine in the body. This means that it reduces these symptoms.
• Carbidopa improves the effect of levodopa. It also reduces the adverse effects of levodopa.

Do not use Duodopa infusion solution if

• You are allergic to levodopa, carbidopa or any of the other ingredients of this medicine (listed in section6)
• You have a eye disorder called “narrow-angle glaucoma”
• You have severe heart problems
• You have a serious irregular heartbeat (arrhythmia)
• You have had an acute stroke
• You are taking depression medications called MAO-A inhibitors and non-selective MAO inhibitors such as moclobemide and phenelzine. You must stop taking these medications at least two weeks before starting Duodopa infusion solution
• You have an adrenal gland tumor (pheochromocytoma)
• You have hormonal problems such as excessive cortisol production (Cushing's syndrome) or your thyroid hormones are very high (hyperthyroidism)
• You have had skin cancer or have any suspicious skin marks that have not been controlled by your doctor

Do not use Duodopa infusion solution in any of the above cases. If you are unsure, consult your doctor before using this medicine.

Warnings and precautions

Consult your doctor, pharmacist or nurse before starting to use Duodopa infusion solution and during your treatment if:

• You have had a heart attack, blood vessel blockage or any other heart disease, including irregular heartbeat (arrhythmia),
• You have a lung problem (such as asthma),
• You have had any hormonal disorder,
• You have had depression with suicidal thoughts or any other mental disorder,
• You have a eye disorder called “open-angle glaucoma”,
• You have had stomach ulcers,
• You have had seizures,
• You have kidney or liver disease,
• You are following a low-sodium diet (see “Duodopa infusion solution contains sodium”),
• You experience any changes in the skin at the infusion site, such as redness, heat, swelling, pain or color change when pressure is applied to the area,
• You have progressive weakness, pain, numbness or loss of sensation in your fingers or feet (peripheral neuropathy). Your doctor will examine these signs and symptoms before starting treatment with Duodopa infusion solution and periodically thereafter. Inform your doctor if you already have neuropathy or a health problem associated with neuropathy.

If you are in any of the above situations or are unsure, consult your doctor or pharmacist before starting treatment with Duodopa infusion solution.

Inform your doctor if you notice involuntary and uncontrollable movements in your limbs, back, neck or chin (dyskinesias) or an increase in stiffness or slowness of movements. It may be necessary to adjust your daily dose, or the device may be clogged.

Malignant neuroleptic syndrome

Do not stop using Duodopa infusion solution unless your doctor tells you to. Stopping treatment or suddenly reducing Duodopa infusion solution can cause a serious condition called “malignant neuroleptic syndrome”. The signs may include:

• rapid heartbeat, changes in blood pressure and sweating, followed by fever,
• rapid breathing, muscle rigidity, decreased consciousness and coma,
• higher levels of a protein in the blood (an enzyme called “creatine phosphokinase”). Your doctor will take care of measuring it.

Impulse control disorders (changes in your behavior)

Inform your doctor if you, your family or caregiver notice that you develop impulses or urges to behave in an unusual way for you, or you cannot resist the impulse, drive or temptation to carry out certain activities that may be harmful to you or others. These behaviors are called “impulse control disorders” and include:

• gambling addiction,
• excessive eating or spending,
• abnormal increase in sexual desire or increase in sexual thoughts or feelings.

Your doctor may need to review your treatments. They will talk to you about methods to control or reduce these symptoms (see section4 “Impulse control disorders - changes in your behavior”).

Dopamine dysregulation syndrome

Inform your doctor if you, your family or caregiver notice that you develop symptoms similar to addiction, leading to a desire for large doses of Duodopa infusion solution and other medications used to treat Parkinson's disease.

Infusion site infections

Inform your doctor if you notice any changes in the skin at the infusion site, such as redness, heat, swelling, pain or color change when pressure is applied to the area. You must always follow aseptic techniques (sterile) while using this medicine and change the infusion site regularly (at least every three days) using a new infusion device. Make sure the new infusion site is at least 2.5cm away from the site used in the last 12days. You may need to change the infusion site more frequently than every 3days if you notice any of the above changes.

Duodopa infusion solution and cancer

In the body, carbidopa (a component of Duodopa infusion solution) breaks down into a substance called “hydrazine”. It is possible that hydrazine may cause damage to the genetic material, which can cause cancer. However, it is unknown if the amount of hydrazine produced with normal doses of Duodopa infusion solution can cause it.

Children and adolescents

Duodopa infusion solution is not recommended for children and adolescents under 18years of age. This is because the medicine has not been studied in this age group.

Other medicines and Duodopa infusion solution

Inform your doctor or pharmacist if you are taking, have taken recently or may need to take any other medicine. This includes those obtained without a prescription, as well as herbal remedies.

Consult your doctor or pharmacist before starting to use Duodopa infusion solution if you are taking other medicines for:

• tuberculosis, such as isoniazid;
• anxiety, such as benzodiazepines;
• nausea or vomiting, such as metoclopramide;
• high blood pressure, such as antihypertensives;
• blood vessel spasms, such as papaverine;
• seizures or epilepsy, such as phenytoin;
• psychiatric disorders, such as antipsychotics, including phenothiazines, butyrophenones and risperidone;
• Parkinson's disease, such as tolcapone, entacapone, opicapone and amantadine;
• depression, such as tricyclic antidepressants that include amoxapine and trimipramine.

Inform your doctor or pharmacist if you are taking a COMT inhibitor (catechol-O-methyltransferase), as it may increase the amount of levodopa in your blood. Your doctor may need to adjust the dose of these medications.

Inform your doctor if you are taking medications called sympathomimetics, such as salbutamol, phenylephrine, isoproterenol, dobutamine for low blood pressure. Sympathomimetics and levodopa may increase the risk of high blood pressure (hypertension) or irregular heartbeat (arrhythmia).

Inform your doctor or pharmacist if you are taking medications that are eliminated by the action of an enzyme called ‘CYP1A2’. For example:

• caffeine (helps to stay alert)
• melatonin (helps to regulate sleep)

• fluvoxamine, duloxetine (antidepressants that improve mood)
• clozapine (to control schizophrenia)
• theophylline (helps with asthma)

Certain medications (such as selegiline) you may be taking can lower blood pressure, making you feel dizzy when getting up from a chair or bed (orthostatic hypotension). Duodopa infusion solution may worsen this feeling of dizziness. Moving slowly when lying down or sitting may make you feel less dizzy.

Do not use Duodopa infusion solution if you are taking

• medicines for depression called MAO-A inhibitors and non-selective MAO inhibitors, such as moclobemide or phenelzine.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor before using this medicine.

This medicine should not be used during pregnancy or in women of childbearing age who are not using contraceptive methods unless the benefits for the mother outweigh the possible risks to the fetus.

It is unknown if Duodopa infusion solution is excreted in breast milk.You should stop breastfeeding during treatment withDuodopa infusion solution.

Driving and using machines

Do not drive or use tools or machines until you are sure how Duodopa infusion solution affects you.

• Duodopa infusion solution may make you feel a strong drowsiness, or you may find yourself falling asleep suddenly (sleep attacks).
• Duodopa infusion solution may lower blood pressure, making you feel dizzy or lightheaded.

Do not drive or use any tool or machine until you feel completely active again or do not feel dizzy or lightheaded.

Duodopa infusion solution contains sodium

Consult your doctor or pharmacist if you need 9ml or more of Duodopa infusion solution daily for a prolonged period, especially if you have been recommended a low-sodium diet (sodium).

Follow exactly the administration instructions of this medication as indicated by your doctor, nurse, or pharmacist. In case of doubt, consult your doctor or pharmacist again.

How to use Duodopa infusion solution

• Before starting treatment, you or your caregiver will receive training on how to handle the product and the infusion pump.
• Duodopa infusion solution is a solution administered under the skin (known as "subcutaneous infusion"), more frequently in the abdomen, using an infusion pump. You should avoid using the infusion pump in a circular area of 5 cm around the navel.
• Your doctor or nurse will adjust the pump parameters to adjust the dose to your needs.
• The pump administers the medication continuously for 24 hours. You may need to recharge the pump with a new syringe within a 24-hour period to ensure that you administer sufficient medication in the blood to control your symptoms.

How much medication to use

• Follow exactly the administration instructions of this medication as indicated by your doctor.
• Your doctor will decide how much Duodopa infusion solution you will receive and for how long. Generally, a continuous maintenance dose will be administered.

• If necessary, you may receive additional doses (an option available on your pump) to treat sudden "OFF" symptoms that may appear during continuous infusion; this will be decided by your doctor.
• In case of interruptions exceeding 3 hours, you will also need to self-administer a loading dose (an option available on your pump) before resuming continuous infusion to quickly restore control of symptoms.

See section 7, "Instructions for use of Duodopa infusion solution with the Vyafuser pump" before using Duodopa infusion solution.

If you use more Duodopa infusion solution than you should

If a higher dose of Duodopa infusion solution has been administered than should be, stop the infusion immediately and contact your doctor, call the Toxicological Information Service, phone 91 562 04 20, indicating the medication and the amount administered, or go to a hospital immediately. Bring the medication with you. The following effects may occur:

• unusual rapid, slow, or irregular heartbeats (arrhythmia).
• low blood pressure (hypotension).

If you forgot to use or interrupt treatment with Duodopa infusion solution

If you forgot to use Duodopa infusion solution, activate your pump with your usual dose as soon as possible.

Duodopa infusion solution administration can be interrupted for brief periods, for example, when showering. Make sure to change the infusion equipment (tubes and cannula) and change to a different administration site if the infusion is interrupted for more than 1 hour. In case of interruptions exceeding 3 hours, you will also need to self-administer a loading dose to quickly restore control of symptoms. The loading dose option is available on your pump as established by your doctor or nurse.

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

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

Stop using Duodopa infusion solution and inform your doctor immediately if you notice any of the following serious side effects. You may need urgent medical treatment:

• angle-closure glaucoma (sudden eye pain, headache, blurred vision, nausea, and vomiting),
• swelling of the face, tongue, or throat that may make it difficult to swallow or breathe, or skin rash of the type known as urticaria. These may be signs of a severe allergic reaction (anaphylactic reaction). Frequency not known. Cannot be estimated from available data.

Your doctor will decide if you can continue using Duodopa infusion solution.

Other side effects

Inform your doctor, pharmacist, or nurse if you notice any of the following side effects.

Very common:may affect more than 1 in 10 patients

• infection at the infusion site (cellulitis at the infusion site) (see section2),
• anxiety,
• seeing, hearing, or perceiving things that do not exist (hallucinations),
• depression,
• reactions at the infusion site (redness, swelling, inflammation, and pain),
• falls,
• urinary tract infections.

Common:may affect up to 1 in 10 patients

• reactions at the infusion site (hematomas, skin peeling, leakage of the medicine, bleeding, inflammation, irritation, swelling, protuberance, itching, and hives),
• abscesses at the infusion site,
• loss of appetite,
• confusion,
• false beliefs (delusions),
• paranoia,
• thoughts of self-harm (suicidal thoughts),
• problems with thinking, learning, and remembering (cognitive disorder),
• involuntary movements (dyskinesia),
• uncontrollable muscle spasms affecting the eyes, head, neck, or body (dystonia)
• headache,
• reduced sense of touch, tingling, or numbness, burning or itching sensation in the hands, arms, legs, or feet (hypoaesthesia, paresthesia),
• progressive weakness, pain, numbness, or loss of sensitivity in the fingers or feet (polyneuropathy),
• sudden onset or sudden appearance of Parkinson's disease symptoms, known as "ON/OFF" phenomenon,
• sudden falls asleep (sleep attacks), excessive sleepiness, sleep disorders,
• high or low blood pressure,
• sensation of dizziness,
• dizziness, lightheadedness, or fainting due to low blood pressure. Always change position slowly, do not get up quickly,
• fainting,
• abdominal pain,
• constipation,
• dry mouth,
• nausea, diarrhea, or vomiting,
• inability to control urination (incontinence),
• difficulty urinating (urinary retention),
• lack of energy, feeling weak (fatigue),
• swelling of the ankles and hands due to excess fluid (peripheral edema)
• psychotic disorder,
• very low levels of vitamin B6 in the body,
• very low levels of vitamin B12 in the body,
• increase in amino acid levels, small molecules that form proteins in the body,
• increase in homocysteine levels in the blood, which contributes to protein formation in the body,
• throat pain,
• weight gain,
• weight loss,
• difficulty sleeping (insomnia),
• eruptions, itching, increased sweating,
• muscle spasms,
• difficulty breathing,
• general feeling of discomfort,
• anemia,
• abnormal dreams,
• agitation,
• having a bloated stomach (abdominal distension), gas (flatulence), indigestion (dyspepsia)
• having pain,
• having neck pain,
• difficulty swallowing or change in taste (bitter taste),
• irregular heartbeat.

Cognitive impulse control disorders (changes in behavior)are common and may affect 1 in 10 patients.

Some people are unable to resist the urge to perform an action that could be harmful to themselves or others. This may include

• a strong urge to gamble excessively despite severe personal or family consequences,
• alteration or increase in sexual interest and behavior with great concern for you or others. This may include an increase in sexual urge,
• uncontrolled excessive spending or excessive spending,
• eating excessively (eating large amounts of food in a short period of time), or compulsive eating (eating more food than normal and more than needed to satisfy hunger).

Inform your doctor if you, your family, or caregiver notice any of these behaviors. Your doctor may need to review your treatment. They will discuss methods with you to control or reduce these symptoms.

Uncommon:may affect up to 1 in 100 patients

• desire for large doses of Duodopa infusion solution beyond those required to control motor symptoms, known as dopamine dysregulation syndrome,
• dark urine,
• hoarse voice, chest pain,
• hair loss, red skin, hives,
• excessive salivation,
• change in gait,
• attempting to end or end their own life, suicide,
• low white blood cell count or changes in blood cell counts, which may cause bleeding,
• elevated mood (euphoric mood), increased sexual interest, dementia, fear sensation,
• problems controlling movements and making sudden, uncontrollable movements
• problems opening the eyes, double vision, blurred vision, damage to the optic nerve (ischemic optic neuropathy),
• irregular heartbeat that you can feel (palpitations),
• confusion,
• nightmares,
• swelling of a vein.

Rare:may affect up to 1 in 1,000 patients

• grinding of teeth
• painful erection that does not go away,
• suspicious marks or moles on the skin that appear or worsen, or skin tumors (malignant melanoma),
• dark saliva or sweat, burning sensation in the tongue, hiccups,
• unusual thoughts,
• abnormal breathing.

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is not listed in this leaflet. You can also report them directly through theSistema Español de Farmacovigilancia de Medicamentos de Uso Humano:www.notificaRAM.es. By reporting side effects, you can contribute to providing more informationon the safety of this medicine.

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

Store the vials in the outer packaging to prevent breakage.

Do not use this medication after the expiration date shown on the vial label and the packaging. The expiration date is the last day of the month indicated.

• Do not freeze.
• Store and transport refrigerated (between 2°C and 8°C).
• The vials can be stored at room temperature, up to a maximum of 30°C, for a single period of a maximum of 28 days.
• The packaging includes a space to record the day the medication was removed from the refrigerator.

• After storing the medication at room temperature, do not return it to the refrigerator.
• Discard the medication if it is not used within the 28-day period at room temperature.
• Transfer the entire contents of the vial to the syringe at once for administration.
• Do not reuse an opened vial; vials are for single use only.
• Once opened: use immediately. Use Duodopa solution for infusion within 24 hours after transferring from the vial to the syringe.
• Medicines should not be disposed of through drains or trash. Ask your pharmacist how to dispose of empty packaging and unused medications. This will help protect the environment.
• Discard the vial after transferring the medication to the syringe.
• Discard the syringe and any unused medication remaining in the syringe after the medication has been in the syringe for 24 hours.

Composition of Duodopa solution for infusion

• The active principles are levodopa and carbidopa. 1 ml contains 240 mg of levodopa and 12 mg of carbidopa.
• 1 vial of 10 ml contains 2,400 mg of levodopa and 120 mg of carbidopa.
• The other components are sodium hydroxide 10 N (to adjust the pH), concentrated hydrochloric acid (to adjust the pH) and water for injection.

Appearance of the product and contents of the package

Duodopa solution for infusion is a transparent to slightly opalescent solution, without particles, which is provided in a transparent and colorless glass vial with a grey rubber stopper and a turquoise plastic cap. The color of the solution may vary from colorless to yellow or brown and may have a purple or red tint. Variations in color are expected and do not affect the quality of the medication. The solution may darken after piercing the vial stopper or while in the syringe.

Each package contains 7 vials of 10 ml each.

The sterile infusion components of single use (syringe, infusion equipment and vial adapter) suitable for use are provided separately, consulting your doctor or pharmacist. The Vyafuser pump is supplied separately.

Marketing Authorization Holder

AbbVie Spain, S.L.U.

Avenida de Burgos 91,

28050 Madrid, Spain

Manufacturers

AbbVie S.r.I

S.R. 148 Pontina Km 52 snc

04011 Campoverde di Aprilia (LT)

Italy

Last review date of this leaflet: December 2023

Other sources of information

The detailed information of this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/)

7.Instructions for useofDuodopa solution for infusionwith the Vyafuser pump

Read the entire following section before using Duodopa solution for infusion.

Important information

Read carefully the following instructions: these instructions explain how to prepare and use Duodopa solution for infusion.

How to prepare your medication

• Do not dilute the Duodopa solution for infusion or fill the syringe with any other solution.
• The medication must be at room temperature before infusion. If it has been refrigerated before use, remove the vial from the refrigerator and let it reach room temperature away from direct sunlight for 30 minutes. If the medication has been refrigerated, do not heat it (neither in the vial nor in the syringe) in any way other than letting it reach room temperature. For example, do not heat it in the microwave or in hot water.

1. Preparation

Follow the following steps each time you need to fill your pump with Duodopa solution for infusion.

• Wash your hands with soap and water and dry them.
• Make sure the smooth surface is clean. This will help prevent contamination when preparing the syringe.
• On a smooth surface, place
• • Syringe (inside its package)
  • Vial ofDuodopa solution for infusion
  • Vial adapter (in its package). A new vial adapter must be used with each new vial of Duodopa solution for infusion.
  • Alcohol wipes (not provided with the medication)
• Check the expiration date of the vial, vial adapter and syringe and that the sterile packages are not damaged.
• • Do notuse the vial, vial adapter or syringe if their respective sterile packages are damaged.
  • Do notuse the Duodopa solution for infusion, vial adapter or syringe if the expiration date has passed.
  • Do notuse if the Duodopa solution for infusion is cloudy or contains scales or particles.

2. Prepare the vial of solution

3. Prepare the subcutaneous infusion of Duodopa solution for infusion

4. Choose and prepare the infusion site

5. Start the subcutaneous infusion of Duodopa solution for infusion

6. After use

• Used vials of solution with the vial adapter still attached must be disposed of according to local regulations or as indicated by your doctor, pharmacist or nurse.