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

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

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

foslevodopa/foscarbidopa

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.

• If you have any questions, ask your doctor, pharmacist or nurse.

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

  • If you experience any adverse reactions, consult your doctor, pharmacist or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the leaflet

1. What Duodopa solution for infusion is and what it is used for
2. What you need to know before you start using Duodopa solution for infusion
3. How to use Duodopa solution for infusion
4. Possible side effects
   1. Storage of Duodopa solution for infusion
   2. Contents of the pack and other information
   3. Instructions for use of Duodopa solution for infusion with the Vyafuser pump

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

This medicinal product contains two active substances, foslevodopa and foscarbidopa, and is used to treat Parkinson's disease.

How Duodopa infusion solution works

• Foslevodopa is converted into "dopamine" in the body. This adds to the dopamine already present in your brain and spinal cord. Dopamine helps transmit signals between nerve cells.
• Low levels of dopamine are responsible for the symptoms of Parkinson's disease, such as tremor, feelings of stiffness, slowness of movement, and balance disorders.
• Treatment with foslevodopa increases the amount of dopamine in your body, thereby reducing these symptoms.
• Foscarbidopa enhances the effect of foslevodopa and also reduces the adverse effects of foslevodopa.

2. What you need to know before using Duodopa infusion solution

Do not use Duodopa infusion solution if

• you are allergic to foslevodopa, foscarbidopa, or any of the other ingredients of this medicine (listed in section 6)
• you have a type of eye disorder called “narrow-angle glaucoma”
• you have severe heart problems
• you have a serious irregular heartbeat (arrhythmia)
• you have an acute stroke
• you are taking antidepressant medicines known as selective MAO-A inhibitors or non-selective MAO inhibitors such as moclobemide and phenelzine. You must stop treatment with these medicines at least two weeks before starting Duodopa infusion solution
• you have a tumour of the adrenal gland (phaeochromocytoma)
• you have hormonal problems such as excess cortisol production (Cushing’s syndrome) or very high thyroid hormone levels (hyperthyroidism)
• you have ever had skin cancer or have any suspicious skin mark or mole that has not been checked by your doctor.

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

Warnings and precautions

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

• you have ever had a heart attack, blood vessel blockage, or any other heart disease, including an irregular heartbeat (arrhythmia)
• you have a lung problem (such as asthma)
• you have ever had a hormonal disorder
• you have ever had depression with suicidal thoughts or any other mental illness
• you have a type of eye disorder called “open-angle glaucoma”
• you have had a stomach ulcer
• you have ever had seizures (fits)
• you have kidney or liver disease
• you are on a sodium-controlled diet (see “Duodopa infusion solution contains sodium”)
• you notice any skin changes at the infusion site, such as redness, warmth, swelling, pain, or colour change when pressure is applied to the area
• you experience progressive weakness, pain, numbness, or loss of sensation in your fingers or feet (polyneuropathy). Your doctor will examine for these signs and symptoms before you start treatment with Duodopa infusion solution and periodically thereafter. Inform your doctor if you already have neuropathy or a medical condition associated with neuropathy.

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

Inform your doctor if you experience involuntary and uncontrollable movements in your limbs, back, neck, or jaw (dyskinesias), or an increase in stiffness or slowness of movement. Your daily dose may need adjustment, or the device may be blocked.

Malignant neuroleptic syndrome

Do not stop using Duodopa infusion solution unless your doctor tells you to. Stopping treatment or a sudden reduction in Duodopa infusion solution may cause a serious condition called “malignant neuroleptic syndrome.” Signs may include:

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

Impulse control disorders (changes in your behaviour)

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

• gambling addiction
• excessive eating or spending
• abnormally increased sex drive or increased sexual thoughts or feelings.

Your doctor may need to review your treatment. They will discuss methods to manage or reduce these symptoms with you (see section 4 “Impulse control disorders – changes in your behaviour”).

Dopamine dysregulation syndrome

Inform your doctor if you, your family, or caregiver notice symptoms resembling addiction, leading to a desire for high doses of Duodopa infusion solution and other medicines used to treat Parkinson’s disease.

Infections at the infusion site

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

Duodopa infusion solution and cancer

In the body, foscarbidopa (a component of Duodopa infusion solution) breaks down into a substance called “hydrazine.” Hydrazine may damage genetic material and potentially cause cancer. However, it is unknown whether the amount of hydrazine produced by normal doses of Duodopa infusion solution is sufficient to cause cancer.

Children and adolescents

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

Other medicines and Duodopa infusion solution

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

Talk to your doctor or pharmacist before starting Duodopa infusion solution if you are taking 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 (fits) 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 including amoxapine and trimipramine.

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

Inform your doctor if you are taking medicines called sympathomimetic drugs, such as salbutamol, phenylephrine, isoprenaline, or dobutamine for low blood pressure. Sympathomimetic drugs and levodopa may increase the risk of high blood pressure (hypertension) or irregular heartbeats (arrhythmia).

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

• caffeine (helps keep the mind alert)

• melatonin (helps regulate sleep)

• fluvoxamine, duloxetine (antidepressants that improve mood)

• clozapine (used to control schizophrenia)

• theophylline (helps with asthma)

Certain medicines (such as selegiline) you may be taking can lower blood pressure, which may make you feel dizzy when standing up from a chair or bed (orthostatic hypotension). Duodopa infusion solution may worsen this dizziness. Moving slowly when getting up from lying or sitting positions may reduce dizziness.

Do not use Duodopa infusion solution if you are taking

• antidepressant medicines known as selective MAO-A inhibitors or non-selective MAO inhibitors, such as moclobemide or phenelzine.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become 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 contraception unless the benefits to the mother outweigh the potential risks to the foetus.

It is unknown whether Duodopa infusion solution is excreted in breast milk. Breastfeeding must be discontinued during treatment with Duodopa 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 very sleepy, or you may suddenly fall asleep (sleep attacks).
• Duodopa infusion solution may lower your blood pressure, which may make you feel lightheaded or dizzy.

Do not drive or use any tools or machines until you feel fully alert and no longer feel lightheaded or dizzy.

Duodopa infusion solution contains sodium

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

3. How to use Duodopa infusion solution

Follow exactly the instructions for administering this medicine as given by your doctor, nurse, or pharmacist. If in 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 (called “subcutaneous infusion”), most often into the abdomen, using an infusion pump. You must avoid using the infusion pump within a 5 cm circular area around the navel.
• Your doctor or nurse will adjust the pump settings to tailor the dosage to your needs.
• The pump continuously delivers the medicine over 24 hours. You may need to refill the pump with a new syringe within a 24-hour period to ensure sufficient medicine enters your bloodstream to control your symptoms.

How much medicine to use

• Follow exactly the instructions for administering this medicine as given 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 needed, you may receive additional doses (an option available on your pump) to treat sudden “OFF” symptoms that may occur during continuous infusion; this will be decided by your doctor.

• In case of interruptions longer than 3 hours, you should also self-administer a loading dose (an option available on your pump) before resuming continuous infusion to rapidly re-establish symptom control.

Refer to 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 you have administered a higher dose of Duodopa infusion solution than you should, stop the infusion immediately and contact your doctor, call the Toxicology Information Service at telephone 91 562 04 20 stating the medicine and amount administered, or go to a hospital immediately. Take the medicine with you. The following effects may occur:

• unusually fast, slow, or irregular heartbeat (arrhythmia).
• low blood pressure (hypotension).

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

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

Administration of Duodopa infusion solution may be interrupted for short periods, for example, while showering. Make sure to change the infusion set (tubes and cannula) and switch to a different administration site if the infusion is interrupted for more than 1 hour. In case of interruptions longer than 3 hours, you should also self-administer a loading dose to rapidly re-establish symptom control. The loading dose option is available on your pump as established by your doctor or nurse.

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

4. Possible side effects

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

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

• closed-angle glaucoma (acute eye pain, headache, blurred vision, nausea and vomiting),
• swelling of the face, tongue or throat which may make swallowing or breathing difficult, or skin rash resembling hives. These may be signs of a severe allergic reaction (anaphylactic reaction). Frequency not known. Cannot be estimated from available data.

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

Other side effects

Tell your doctor, pharmacist or nurse if you experience 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 section 2),
• anxiety,
• seeing, hearing or sensing things that are not there (hallucinations),
• depression,
• reactions at the infusion site (redness, lump, swelling and pain),
• falls,
• urinary tract infections.

Common: may affect up to 1 in 10 patients

• reactions at the infusion site (bruising, peeling of the skin in fine layers, leakage of medication, bleeding, inflammation, irritation, lump, bump, itching, rash),
• abscesses at the infusion site,
• loss of appetite,
• confusion,
• false beliefs (delusions),
• paranoia,
• thoughts of suicide (suicidal thoughts),
• problems with thinking, learning and memory (cognitive disorder),
• involuntary movements (dyskinesia),
• uncontrolled muscle spasms affecting the eyes, head, neck or body (dystonia),
• headache,
• reduced sense of touch, tingling or numbness, burning or stinging sensations in the hands, arms, legs or feet (hypoesthesia, paresthesia),
• progressive weakness or pain, numbness or loss of sensation in fingers or feet (polyneuropathy),
• sudden or unexpected onset of Parkinson's disease symptoms, known as “ON/OFF phenomenon”,
• sudden episodes of falling asleep (sleep attacks), excessive drowsiness, sleep disorders,
• high or low blood pressure,
• dizziness,
• dizziness when standing up or changing position (orthostatic hypotension) due to low blood pressure. Always change positions slowly; do not stand up quickly,
• fainting,
• abdominal pain,
• constipation,
• dry mouth,
• nausea, diarrhoea or vomiting,
• inability to control urine (incontinence),
• difficulty urinating (urinary retention),
• lack of energy, feeling weak (fatigue),
• swelling of the calves and hands due to fluid retention (peripheral oedema),
• psychotic disorder,
• very low levels of vitamin B6 in the body,
• very low levels of vitamin B12 in the body,
• increased levels of amino acids, small molecules that make up the body's proteins,
• increased levels of homocysteine in the blood, which contributes to protein formation in the body,
• sore throat,
• weight gain,
• weight loss,
• difficulty sleeping (insomnia),
• rashes, itching, increased sweating,
• muscle spasms,
• difficulty breathing,
• general feeling of discomfort,
• anaemia,
• abnormal dreams,
• restlessness,
• bloated stomach (abdominal distension), gas (flatulence), indigestion (dyspepsia),
• pain,
• neck pain,
• difficulty swallowing or change in taste (bitter taste),
• irregular heartbeat.

Impulse control disorders (changes in behaviour) These are common and may affect up to 1 in 10 patients.

Some people are unable to resist the impulse to carry out an action that could be harmful to themselves or others. This may include:

• a strong urge to gamble excessively despite serious personal or family consequences,
• altered or increased interest in and engagement in sexual behaviour, causing concern to you or others. This may include increased sexual drive,
• excessive or uncontrolled shopping or spending,
• overeating (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 behaviours. Your doctor may need to review your treatment. They will discuss with you ways to manage or reduce these symptoms.

Uncommon: may affect up to 1 in 100 patients

• desire for high doses of Duodopa infusion solution beyond those required to control motor symptoms, known as dopamine dysregulation syndrome,
• dark urine,
• hoarseness, chest pain,
• hair loss, red skin, hives,
• excessive salivation,
• change in walking pattern,
• attempting or completing suicide,
• low white blood cell count or changes in blood cell counts, which may lead to bleeding,
• elevated mood (euphoric mood), increased sexual interest, dementia, feeling of fear,
• difficulty controlling movements and making sudden, uncontrollable movements,
• difficulty opening the eyes, double vision, blurred vision, damage to the optic nerve (ischaemic 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

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

Reporting of side effects

If you experience any side effect, talk to your doctor, pharmacist or nurse, including any side effects not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicinal Products: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Duodopa infusion solution

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

Store the vials in their outer packaging to protect them from breakage.

Do not use this medicine after the expiry date stated on the label of the vial and on the carton. The expiry date refers to the last day of the month indicated.

• Do not freeze.

• Store and transport refrigerated (between 2 °C and 8 °C).

• The vials may be kept at room temperature, up to a maximum of 30 °C, for a single period of up to 28 days.

• The carton includes a space to record the date on which the medicine was removed from the refrigerator.

• Once the medicine has been stored at room temperature, it must not be returned to the refrigerator.

• Discard the medicine if not used within the 28-day period at room temperature.

• The entire contents of the vial should be transferred to the syringe at once for administration.

• Do not reuse an opened vial; vials are for single use only.

• After opening: use immediately. Duodopa infusion solution must be used within 24 hours after transfer from the vial to the syringe.

• Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging no longer required. This helps protect the environment.

• Dispose of the vial after transferring the medicine to the syringe.

• Dispose of the syringe and any unused medicine remaining in the syringe after the medicine has been in the syringe for 24 hours.

6. Contents of the pack and other information

Composition of Duodopa infusion solution

• The active substances are foslevodopa and foscarbidopa. 1 ml contains 240 mg of foslevodopa and 12 mg of foscarbidopa.
• 1 vial of 10 ml contains 2,400 mg of foslevodopa and 120 mg of foscarbidopa.
• The other components are sodium hydroxide 10 N (to adjust pH), concentrated hydrochloric acid (to adjust pH) and water for injections.

Appearance of the product and contents of the pack

Duodopa infusion solution is a clear to slightly opalescent solution, free from particles, supplied in a colourless transparent glass vial with a grey rubber stopper and a turquoise plastic cap. The solution may vary in colour from colourless to yellow or brown and may have a purple or red tint. Colour variations are expected and do not affect the quality of the medicine. The solution may darken after piercing the vial stopper or while in the syringe.

Each pack contains 7 vials of 10 ml each.

Sterile, single-use infusion components (syringe, infusion set and vial adapter) suitable for use are provided separately; consult 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

or

AbbVie Deutschland GmbH & Co. KG

Knollstrasse

67061 Ludwigshafen Am Rhein

Germany

Date of the most recent revision of this leaflet: December 2023

Other sources of information

Detailed information on this medicine is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/)

7. Instructions for use of Duodopa infusion solution with the Vyafuser pump

Read the entire section below before using Duodopa infusion solution.

Important information

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

• Duodopa infusion solution is administered by subcutaneous infusion using the Vyafuser pump and its infusion components (syringe, infusion set and vial adapter).

• The components of your infusion set are available separately; consult your doctor or pharmacist.

• You should also read carefully the complete instructions before using Duodopa infusion solution:

  • Instructions for use of the vial adapter
  • Instructions for use of the infusion set
  • Instructions for use of the Vyafuser pump for patients.

• Your doctor or nurse will set up the pump for you so that you always receive the correct dose.

• Your doctor or nurse will instruct you on how to administer the medicine and how to handle the pump before starting treatment.

• If in doubt, consult your doctor or nurse.

How to prepare your medication

• Do not dilute Duodopa infusion solution or fill the syringe with any other solution.
• The medicine should be at room temperature before infusion. If refrigerated before use, remove the vial from the refrigerator and allow it to reach room temperature, protected from direct sunlight, for 30 minutes. If the medicine is refrigerated, do not heat it (neither in the vial nor in the syringe) by any method other than allowing it to warm to room temperature. For example, do not heat it in a microwave or in hot water.

1. Preparation

• Follow the steps below each time you need to refill your pump with Duodopa infusion solution.*

• Wash your hands with soap and water and dry them thoroughly.

• Ensure the work surface is clean. This will help prevent contamination when preparing the syringe.

• On a flat surface, place:

  • Syringe (inside its packaging)
  • Vial of Duodopa infusion solution
  • Vial adapter (in its packaging). A new vial adapter must be used with each new vial of Duodopa infusion solution.
  • Alcohol wipes (not supplied with the medicine)

• Check the expiry date of the vial, vial adapter and syringe, and ensure the packaging is undamaged.

  • Do not use the vial, vial adapter or syringe if their sterile packaging is damaged.
  • Do not use the Duodopa infusion solution, vial adapter or syringe if past the expiry date.
  • Do not use if the Duodopa infusion solution is cloudy or contains flakes or particles.

1. Prepare the solution vial

1. Prepare the subcutaneous infusion of Duodopa infusion solution

1. Choose and prepare the infusion site

1. Begin subcutaneous infusion of Duodopa solution for infusion

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