DUODOPA 20 mg/ml + 5 mg/ml INTESTINAL GEL

Introduction

Package Leaflet: Information for the User

Duodopa 20 mg/ml + 5 mg/ml Intestinal Gel

levodopa/carbidopa monohydrate

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What Duodopa is and what it is used for
2. What you need to know before you use Duodopa
3. How to use Duodopa
4. Possible side effects
5. Storage of Duodopa
6. Contents of the pack and other information

1. What Duodopa is and what it is used for

Duodopa belongs to a group of medicines for Parkinson's disease.

Duodopa is a gel that is administered through a pump and a tube into your small intestine. The gel contains two active substances:

• Levodopa
• Carbidopa

How Duodopa works

• Levodopa is converted into a substance called dopamine in the body. This adds to the dopamine already present in your brain and spinal cord. Dopamine helps to transmit signals between nerve cells.
• Low dopamine levels cause Parkinson's disease symptoms such as tremors, stiffness, slow movement, and balance problems.
• Treatment with levodopa increases the amount of dopamine in your body, which reduces these symptoms.
• Carbidopa improves the effect of levodopa and also reduces the side effects of levodopa.

2. What you need to know before you use Duodopa

Do not useDuodopa if

• You are allergic to levodopa, carbidopa, or any of the other ingredients of this medicine (listed in section 6).
• You have a severe eye disorder called "narrow-angle glaucoma".
• You have severe heart problems.
• You have a severe irregular heartbeat (arrhythmia).
• You have had a severe stroke.
• You are taking medicines for depression called non-selective MAO-A inhibitors and selective MAO inhibitors such as moclobemide and phenelzine.
• You have a tumor in the adrenal gland (pheochromocytoma).
• You have hormonal problems such as an overproduction of cortisol (Cushing's syndrome) or your thyroid hormones are very high (hyperthyroidism).
• You have had skin cancer or have any suspicious moles or marks on your skin that have not been checked by your doctor.

Do not use Duodopa in any of the above cases. If you are not sure, consult your doctor before using Duodopa.

Warnings and precautions

Consult your doctor before starting to use Duodopa if:

• You have had a heart attack, blockage of the blood vessels in your heart, or any other heart disease, including arrhythmias.
• You have a lung problem (such as asthma).
• You have had a hormonal disorder.
• You have had depression with suicidal thoughts or any other mental illness.
• You have an eye disorder called "open-angle glaucoma".
• You have had a stomach ulcer.
• You have had seizures (convulsions).
• You have had surgery in the upper part of your abdomen (upper abdominal surgery).
• Progressive weakness, pain, numbness, or loss of sensation in your fingers or toes (polyneuropathy) has been reported in patients treated with intestinal gel of levodopa/carbidopa. Your doctor will examine you for signs and symptoms of neuropathy before starting and periodically during treatment with intestinal gel of levodopa/carbidopa. 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 using Duodopa.

Be careful with the following side effects

Malignant Neuroleptic Syndrome

Do not stop treatment with Duodopa or reduce your dose unless your doctor tells you to. Stopping treatment or suddenly reducing Duodopa can cause a serious disorder called "Malignant Neuroleptic Syndrome" (see section 4 "Serious side effects").

Feeling dizzy or drowsy

If you find yourself falling asleep suddenly (sleep attacks), feeling very drowsy, or feeling dizzy:

• Do not drive or use tools or machines until you feel fully awake again and are no longer dizzy (see section 2 "Driving and using machines").

Changes in the skin

Tell your doctor, pharmacist, or nurse if you notice any new or worsening suspicious marks or moles on your skin (see section 4 "Possible side effects").

Impulse control disorders (changes in behavior)

Tell your doctor if you, your family, or caregiver notice that you are developing impulses or urges to behave in unusual ways 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:

• Compulsive gambling.
• 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 discuss with you methods to control or reduce these symptoms (see section 4 "Impulse control disorders - changes in behavior").

Tell your doctor if you, or your family/caregiver, notice that you are developing symptoms similar to addiction, leading to a desire for high doses of Duodopa and other medicines used to treat Parkinson's disease.

Problems with the pump or tube

Some problems may occur related to the use of the pump and tube

• Experiencing a reduction in the ability to handle the pump or tube, that your Parkinson's disease symptoms have worsened, or that your movement ability is reduced (bradykinesia). The pump and tube may not be working properly.
• Experiencing abdominal pain, nausea, and vomiting, inform your doctor immediately if you experience any of these symptoms (see section 4 "Serious side effects").
• You may have other side effects that affect the intestine and the site where the tube is inserted (see section 4 "Problems with the pump or tube").

Duodopa and cancer

In the body, carbidopa (one of the active substances of Duodopa) breaks down into a substance called "hydrazine". It is possible that hydrazine may cause damage to genetic material that can cause cancer. However, it is not known if the amount of hydrazine produced with normal doses of Duodopa can cause this.

Lab tests

Your doctor may regularly perform blood tests if you are using this medicine.

Surgical procedures

If you need to undergo any surgical procedure (including dental surgery), inform your doctor (or dentist) that you are using Duodopa.

Children and adolescents

Duodopa should not be administered to children or adolescents under 18 years of age.

Other medicines and Duodopa

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines. This includes medicines obtained without a prescription, as well as herbal medicines.

Do not use Duodopa if you are taking:

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

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

• Anemia, such as iron tablets.
• Tuberculosis, such as isoniazid.
• Anxiety, such as benzodiazepines.
• Nauses, such as metoclopramide.
• High blood pressure, such as antihypertensives.
• Vasospasm, such as papaverine.
• Seizures (convulsions) or epilepsy, such as phenytoin.
• Parkinson's disease, such as tolcapone, entacapone, amantadine.
• Mental disorders, antipsychotics such as phenothiazines, butyrophenones, and risperidone.
• Severe allergic reactions, asthma, chronic bronchitis, heart disease, and low blood pressure, such as anticholinergics and sympathomimetics.
• If you are taking a medicine that may lower your blood pressure. This can cause a condition called "orthostatic hypotension", which can make you feel dizzy when standing up from a chair or bed. Duodopa may worsen this phenomenon. Always change positions slowly.

Using Duodopa with food and drinks

In some patients, Duodopa may not work properly if taken with, or shortly after, foods high in protein such as meat, fish, dairy products, seeds, and nuts. Consult your doctor to see if you might be one of them.

Pregnancy and breastfeeding

• If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before using this medicine.
• Do not use Duodopa if you are breastfeeding.

Driving and using machines

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

• Duodopa can make you feel very drowsy or cause you to fall asleep suddenly (sleep attacks).
• Duodopa can lower your blood pressure, which can make you feel dizzy.

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

3. How to use Duodopa

Follow exactly the administration instructions of this medicine given by your doctor, pharmacist, or nurse. If you are unsure, consult your doctor or pharmacist again.

About the Duodopa gel and its pump

• Duodopa is a gel that is administered through a pump and a tube into your small intestine.
• The gel comes in a plastic cartridge. The cartridge is connected to a pump.
• The pump is connected to a tube that is inserted into your small intestine.
• The pump gives you a small dose continuously throughout the day. This means that the level of medicine in your blood is constant. This also means that some of the movement-related side effects are reduced.

How much to use

• Your doctor will decide how much Duodopa you will receive and for how long.
• Usually, a higher morning dose called "bolus dose" will be administered. This allows you to quickly reach the correct level of medicine in your blood. After this dose, a continuous dose ("maintenance dose") will be administered.
• If needed, you may receive an extra dose, which will be indicated by your doctor.

If you use more Duodopa than you should

If you have been administered a higher dose of Duodopa than you should, contact your doctor or go to a hospital immediately. Bring the pack with you. The following effects may occur:

• Difficulty opening your eyes.
• Uncontrollable muscle spasms that affect your eyes, head, neck, or body (dystonia).
• Involuntary movements (dyskinesia).
• Unusual heartbeats, fast, slow, or unexpected (arrhythmia).

If you forget to use Duodopa

• Activate your pump with your usual dose as soon as possible.
• Do not increase the dose to make up for the forgotten dose.

If you stop treatment with Duodopa or reduce the dose

Do not stop using Duodopa or reduce your dose unless your doctor tells you to, as stopping treatment or suddenly reducing the dose of Duodopa can cause a serious disorder called "Malignant Neuroleptic Syndrome". This disorder is more likely to occur if you are also taking a medicine called "antipsychotic" (see section 4 "Serious side effects").

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Severe Adverse Effects of Duodopa

Stop using Duodopa and consult your doctor if you notice any of the following severe adverse effects. You may need urgent medical treatment:

• Acute eye pain, headache, blurred vision, nausea, and vomiting. These can be symptoms of acute angle-closure glaucoma. Uncommon: may affect up to 1 in 100 patients.
• Fever, inflammation of the throat or mouth, or problems urinating. These can be signs of a blood cell problem called "agranulocytosis". Your doctor will take a blood sample to check for it. Very rare (may affect up to 1 in 10,000 patients).
• Swelling of the face, tongue, or throat that can make it difficult to swallow or breathe; any type of skin irritation. These can be symptoms of a severe allergic reaction (anaphylactic reaction). Frequency not known. Cannot be estimated from available data.

Inform your doctor immediately if you notice any of the following severe adverse effects:

• Neuroleptic Malignant Syndrome, symptoms may include:

• Rapid heartbeat, changes in blood pressure, and sweating, followed by fever.
• Rapid breathing, muscle stiffness, loss of consciousness, and coma.
• Elevated levels of a protein in the blood (an enzyme called "creatine phosphokinase"). Your doctor will measure this.

Uncommon: may affect up to 1 in 1,000 patients.

For more information about Neuroleptic Malignant Syndrome, see section 3 "If you stop treatment with Duodopa or reduce the dose".

Other Adverse Effects of Duodopa

Inform your doctor, pharmacist, or nurse if you notice any of the following adverse effects:

Very Common:may affect more than 1 in 10 patients

• Falls.
• Weight loss.
• Discomfort (nausea), constipation.
• Anxiety, depression, inability to stay asleep (insomnia).
• Uncontrolled movements (dyskinesia), worsening of Parkinson's disease symptoms.
• Dizziness when standing up or changing posture (orthostatic hypotension) due to a drop in blood pressure. Always change posture slowly, do not stand up quickly.
• Urinary tract infections

Common:may affect up to 1 in 10 patients

• Weight gain.
• Irregular heartbeats.
• Loss of appetite.
• Fatigue, weakness.
• High blood pressure or low blood pressure.
• Anemia (low iron levels in the blood).
• Pain, neck pain, muscle cramps, muscle weakness.
• Sudden sleepiness (sleep attacks), feeling very sleepy, sleep disorders.
• Increased amino acids or homocysteine in the blood, deficiency of vitamins B6 and B12.
• Feeling dizzy, feeling faint, or fainting (syncope).
• Difficulty swallowing or dry mouth, alteration of taste (bitter taste).
• Headache.
• Progressive weakness or pain, or numbness or loss of sensation in the fingers or toes (polyneuropathy).
• Rashes, itching, increased sweating, swelling caused by excess fluid (edema).
• Difficulty urinating (urinary retention) or inability to control urine flow (incontinence).
• Seeing, hearing, or feeling things that do not exist (hallucinations), confusion, abnormal dreams, feeling agitated, impulsive behavior, psychotic disorder.
• Abdominal distension, diarrhea, gas (flatulence), indigestion (dyspepsia), feeling nauseous (vomiting).
• Sudden and unexpected appearance of Parkinson's disease symptoms, this is called "on-off phenomenon".
• Reduced sense of touch, uncontrolled muscle spasms affecting the eyes, head, neck, and body (dystonia), tremors.

Impulse Control Disorders - Changes in Behavior.These are common, may affect up to 1 in 10 patients.

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

• Strong impulse to gamble excessively despite serious personal or family consequences.
• Alteration or increased interest and sexual behavior with great concern for you or others, for example, increased sexual impulse.
• Uncontrolled or excessive shopping or spending.
• Eating excessively (eating large amounts of food in a short period) or compulsive eating (eating more food than normal and more than necessary to satisfy hunger).

Inform your doctor if you, your family, or caregiver notice that you develop any of these behaviors. Your doctor will discuss methods to control or reduce these symptoms with you.

Uncommon:may affect up to 1 in 100 patients

• Dark urine.
• Hoarseness, chest pain.
• Hair loss, skin redness, rash.
• Unusual increase in salivation.
• Swelling of the veins (phlebitis).
• Changes in gait.
• Suicidal intentions (suicide).
• Feeling tired or not feeling well in general.
• Rapid and irregular heartbeats (palpitations).
• Abnormally low white blood cell count that can lead to bleeding.
• Disorientation, euphoria, increased sexual desire, nightmares, dementia, fears.
• Difficulty controlling movements and violent involuntary contraction.
• Difficulty opening the eyes, double vision, blurred vision, damage to the optic nerve (ischemic optic neuropathy).

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

• Abnormal thoughts.
• Irregular breathing pattern.
• Prolonged and painful erection that does not disappear.
• Moles or suspicious skin marks that seem to worsen or skin tumor (malignant melanoma)
• Dark saliva or dark sweat, feeling of tongue tingling, teeth grinding, hiccups.

Frequency Not Known(cannot be estimated from available data)

Desire for large doses of Duodopa higher than those required to control motor symptoms, known as dopamine dysregulation syndrome. Some patients experience severe abnormal involuntary movements (dyskinesias), mood changes, or other adverse effects after taking large doses of Duodopa.

Inform your doctor, pharmacist, or nurse if you notice any of the adverse effects mentioned.

Adverse Effects of the Pump and Catheter

The following adverse effects have been reported with the pump and catheter "catheter administration system". Inform your doctor or nurse if you experience any of these adverse effects.

• If you experience a reduction in your ability to manipulate the pump or catheter, that your Parkinson's disease symptoms have worsened, or that your movement ability is reduced (bradykinesia), the pump and catheter may not be functioning properly.
• If you have abdominal pain, feel sick (nausea), and are sick (vomiting), inform your doctor immediately if you experience any of these symptoms, you may have a problem with the pump or catheter.

Very Common:may affect more than 1 in 10 patients

• Abdominal pain.
• Infection at the site where the catheter enters your abdomen as a result of surgery.
• Thickening of the scar at the site where the catheter enters your abdomen.

• Problems related to catheter placement, such as mouth or throat pain, swelling, difficulty swallowing, abdominal discomfort, pain or swelling, throat, mouth, or stomach injuries, bleeding, vomiting, gas (flatulence), anxiety.
• Problems at the site where the catheter enters your abdomen, red skin, sores, secretions, pain, or irritation.

Common:may affect up to 1 in 10 patients

• Infection at the incision site, post-procedural infection after catheter placement in the intestine.
• Inflammation of the stomach wall.
• Infection in the intestine or at the site where the catheter enters your abdomen.
• Movement of the catheter inside your abdomen or blockage of the catheter (which causes a decrease in drug absorption).
• Pain when breathing, feeling short of breath, chest infections (pneumonia, including aspiration pneumonia).

Uncommon:may affect up to 1 in 100 patients

• Inflammation of the colon (colitis).
• Inflammation of the pancreas (pancreatitis).
• The catheter perforates the wall of the large intestine.
• Blockage (obstruction), bleeding, or intestinal ulcer.
• Slippage of a part of the intestine into an adjacent part of it (intestinal intussusception).
• Food getting stuck around the catheter causing blockage.
• Abscess (infection blockage, this can occur after catheter placement in the intestine.

Unknown: Frequency Not Known

• Decreased blood flow in the small intestine.
• The catheter perforates the wall of the stomach or small intestine.
• Blood infection (sepsis).

Adverse Effects When Levodopa and Carbidopa Are Taken Orally

The following adverse effects have been reported when levodopa and carbidopa medicines were taken orally (the same active ingredients as Duodopa). These adverse effects may also occur with Duodopa:

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

• Anemia, low iron levels in the blood.
• An eye disorder called "Horner's syndrome".
• Inability to open the mouth completely (trismus).
• Skin irritation of a red or purple color that resembles small bruises (Henoch-Schönlein purpura).
• Neuroleptic Malignant Syndrome (see section 4 "Severe Adverse Effects").
• Prolonged pupil dilation (mydriasis), decreased eye movements.

Very Rare:may affect up to 1 in 10,000 patients

• Changes in blood tests.

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet.

You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Duodopa

• Keep this medicine out of sight and reach of children.
• Do not use this medicine after the expiration date stated on the packaging after EXP.
• Store and transport in the refrigerator (2°C to 8°C). Keep the cartridge in the box to protect it from light.
• The gel cartridges must be used within 24 hours of removal from the refrigerator.
• The medicine cartridges are for single use. The cartridge must not be used for more than 24 hours, even if some gel remains.

• Do not reuse an opened cartridge.
• The gel may turn slightly yellow. This does not affect the medicine.
• Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment. Return used cartridges to the pharmacy, do not reuse them.

6. Package Contents and Additional Information

Composition of Duodopa

• The active ingredients are levodopa and carbidopa monohydrate. 1 ml of gel contains 20 mg of levodopa and 5 mg of carbidopa monohydrate.
• The other ingredients are sodium carmellose and purified water.

Appearance of the Product and Package Contents

Duodopa is presented in cartridges (PVC plastic bags with a hard plastic protective cover) containing 100 ml, with 7 cartridges in each package. The gel is white or slightly yellow.

Marketing Authorization Holder

AbbVie Spain, S.L.U. Avenida de Burgos, 91. 28050 Madrid

Manufacturer

HP Halden Pharma AS, Svinesundsveien 80, NO-1788 Halden, Norway

AbbVie Logistics B.V.

Zuiderzeelaan 53

8017 JV Zwolle

Netherlands

This medicine is authorized in all Member States of the European Economic Area with the following name:

Duodopa

Date of Last Revision of this Leaflet: October 2023

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