Package Leaflet: Information for the User

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

levodopa/carbidopa monohydrate

Read this leaflet carefully before you start taking 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. Do not give it to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

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

Duodopa is a gel that is delivered through a pump and a catheter to the small intestine. The gel contains two active ingredients:

• Levodopa
• Carbidopa

How Duodopa works

• Levodopa is converted into a substance called 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 cause the symptoms of Parkinson's disease, such as tremors, a feeling of stiffness, slow movement, and balance problems.
• Treatment with levodopa increases the amount of dopamine in the body, which means that these symptoms are reduced.
• Carbidopa improves the effect of levodopa and also reduces the side effects of levodopa.

Do not useDuodopa if

• He is allergic to levodopa, carbidopa, or any of the other components of this medication (listed in section 6).
• Has a narrow-angle glaucoma.
• Has severe heart problems.
• Has a severe irregular heartbeat (arrhythmia).
• Has had a severe stroke.
• Is taking medications for depression called MAO-A inhibitors and non-selective MAO inhibitors such as moclobemide and phenelzine.
• Has a tumor in the adrenal gland (pheochromocytoma).
• Has hormonal problems such as excessive cortisol production (Cushing's syndrome) or very high thyroid hormone levels (hyperthyroidism).
• Has had skin cancer or has any suspicious skin lesions or marks that have not been controlled by your doctor.

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

Warnings and precautions

Consult your doctor before starting to use Duodopa if:

• Has had a heart attack, coronary artery occlusion, or any other heart disease, including cardiac arrhythmias.
• Has a lung problem (such as asthma).
• Has had any hormonal disease.
• Has had depression with suicidal thoughts or any other mental illness.
• Has narrow-angle glaucoma.
• Has had stomach ulcers.
• Has had seizures (convulsions).
• Has had surgery in the upper abdomen (upper abdominal surgery).
• Has progressive weakness, pain, numbness, or loss of sensation in the fingers or toes (polyneuropathy) in patients treated with intestinal gel of levodopa/carbidopa. Your doctor will examine the signs and symptoms of neuropathy before starting with the intestinal gel of levodopa/carbidopa 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 using Duodopa.

Be careful with the following adverse effects

Malignant Neuroleptic Syndrome

Do not interrupt treatment with Duodopa or reduce its dose unless your doctor tells you to. Stopping treatment or suddenly reducing Duodopa may cause a serious condition called "Malignant Neuroleptic Syndrome" (see section 4 "Serious adverse effects").

Feeling dizzy or drowsy

If you find yourself falling asleep suddenly (sleep attacks), if you feel strong drowsiness or if you feel dizzy or disoriented:

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

Skin changes

Inform your doctor, pharmacist, or nurse if you notice that you may develop or worsen any suspicious skin lesions or marks (see section 4 "Possible adverse effects").

Impulse control disorders (changes in behavior)

Inform your doctor if:

• You, your family, or caregiver notice that you are developing impulses or urges to behave in an unusual way for you or you cannot resist the impulse, urge, or temptation to carry out certain activities that may be harmful to you or others. These behaviors are called "impulse control disorders" and include:
• Excessive gaming.
• 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").

Inform your doctor if you, or your family/caregiver, notice that you are developing symptoms similar to addiction, which lead to a desire for large doses of Duodopa and other medications used to treat Parkinson's disease.

Problems with using the pump or catheter

Some problems may occur related to the use of the pump and catheter:

• Experiencing a reduction in the ability to manipulate the pump or catheter, or that your Parkinson's disease symptoms have worsened or that your ability to move has been reduced (bradykinesia). The pump and catheter may not be functioning properly.
• Experiencing abdominal pain, nausea, and vomiting. Inform your doctor immediately if you experience any of these symptoms (see section 4 "Serious adverse effects").
• You may have other adverse effects that affect the intestine and the site where the catheter is inserted (see section 4 "Problems with using the pump or catheter").

Duodopa and cancer

In the body, carbidopa (one of the active principles of Duodopa) breaks down into a substance called "hydrazine". It is possible that hydrazine may cause damage to the genetic material that can cause cancer. However, it is unknown if the amount of hydrazine produced with normal doses of Duodopa can cause it.

Laboratory tests

Your doctor may perform regular blood tests if you are using this medication.

Surgery

If you need to undergo any surgery (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 old.

Other medications and Duodopa

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication. This includes those obtained without a prescription, as well as herbal remedies.

Do not use Duodopa if you are taking:

• Medications 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 medications for:

• Anemia, such as iron tablets.
• Tuberculosis, such as isoniazid.
• Anxiety, such as benzodiazepines.
• Nausea, such as metoclopramide.
• High blood pressure, such as anti-hypertensives.
• Spasms of blood vessels, such as papaverine.
• Seizures (convulsions) or epilepsy, such as phenytoin.
• Parkinson's disease, such as tolcapone, entacapone, and 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 medication that can lower blood pressure. This can cause something called "orthostatic hypotension", which can make you feel dizzy when getting up from a chair or bed. Duodopa may worsen this phenomenon. Always change position slowly.

Use of Duodopa with food and drinks

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

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.
• 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 may cause strong drowsiness, or you may find yourself falling asleep suddenly (sleep attacks).
• Duodopa may lower blood pressure, which can make you feel dizzy or disoriented.

Do not drive or use any tools or machines until you feel completely awake again and no longer feel dizzy or disoriented.

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

About Duodopa Gel and Pump

• Duodopa is a gel that is delivered through a pump and a catheter to your small intestine.
• The gel is presented in a plastic cartridge. The cartridge is connected to a pump.
• The pump is connected to a catheter that is placed in your small intestine.
• The pump administers a small dose continuously throughout the day. This means that the medication level in your blood is constant. This also means that some of the adverse effects on movement are reduced.

How Much to Use

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

If You Use More Duodopa Than You Should

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

• Difficulty opening your eyes.
• Uncontrollable muscle spasms affecting your eyes, head, neck, or body (dystonia).
• Involuntary movements (dyskinesia).
• Unusual, rapid, slow, or irregular heartbeats (arrhythmia).

If You Forget to Use Duodopa

• Activate your pump with your usual dose as soon as possible.
• Do not increase the dose to compensate for the missed dose.

If You Interrupt Treatment with Duodopa or Reduce the Dose

Do not stop using Duodopa or reduce the dose until your doctor tells you to, as sudden interruption or reduction of the Duodopa dose may cause a severe condition called "Neuroleptic Malignant Syndrome". This condition is more likely to occur if you are also taking a medication called "antipsychotic" (see section 4 "Severe Side Effects").

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

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

Severe side effects of Duodopa

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

• Sharp eye pain, headache, blurred vision, nausea, and vomiting. These may be symptoms of closed-angle glaucoma. Rare: may affect up to 1 in 100 patients.
• Fever, throat or mouth inflammation, or difficulty urinating. These may be signs of a blood cell disorder 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 may make it difficult to swallow or breathe; any type of skin irritation. These may 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 side effects:

• Neuroleptic Malignant Syndrome, symptoms may include:

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

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

For more information about Neuroleptic Malignant Syndrome, see section 3 “If you stop taking Duodopa or reduce the dose”.

Other side effects of Duodopa

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

• Falling.
• Weight loss.
• Uncomfortable feeling (nausea), constipation.
• Anxiety, depression, inability to fall asleep (insomnia).
• Uncontrolled movements (dyskinesia), worsening of Parkinson's disease symptoms.
• Dizziness, lightheadedness when standing up or changing position (orthostatic hypotension) due to low blood pressure. Always change position slowly, do not stand up quickly.
• Urinary tract infections.

Common:may affect 1 in 10 patients

• Weight gain.
• Irregular heartbeats.
• Loss of appetite.
• Fatigue, weakness.
• High or low blood pressure.
• Anemia (low iron levels in blood).
• Pain, neck pain, muscle cramps, muscle weakness.
• Sudden onset of sleep (sleep attacks), feeling very drowsy, sleep disorders.
• Increased amino acids or homocysteine in blood, vitamin B6 and B12 deficiency.
• Dizziness, feeling of fainting or fainting (syncope).
• Difficulty swallowing or dry mouth, altered taste (bitter taste).
• Headache.
• Progressive weakness, pain, numbness, or loss of sensation in fingers or feet (polyneuropathy).
• Rashes, itching, increased sweating, swelling caused by excess fluids (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 dizzy (vomiting).
• Sudden or unexpected appearance of Parkinson's disease symptoms, this is called “on-off phenomenon”.
• Reduced sense of touch, involuntary muscle spasms affecting the eyes, head, neck, and body (dystonia), tremors.

Impulse control disorders - changes in behavior.They are common,may affect 1 in 10 patients.

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

• Strong urge to gamble excessively despite severe personal or family consequences.
• Alteration or increase in sexual interest and behavior with great concern for yourself or others, for example, increased sexual desire.
• Uncontrolled or excessive spending.
• Eating too much (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 ifyou, your family, or caregiver notices that you develop any of these behaviors.Your doctor will discuss methods with you to control or reduce these symptoms.

Rare:may affect 1 in 100 patients

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

Rare:may affect 1 in 1,000 patients

• Abnormal thoughts.
• Irregular breathing pattern.
• Prolonged and painful erection that does not go away.
• Moles or suspicious marks on the skin that seem to worsen or skin tumor (malignant melanoma)
• Dark saliva or dark sweat, tongue burning sensation, teeth grinding, hiccups.

Unknown: frequency unknown

• Desire for large doses of Duodopa exceeding the required dose to control motor symptoms, known as dopamine dysregulation syndrome. Some patients experience abnormal involuntary movements (dyskinesias), mood changes, or other side effects after taking large doses of Duodopa.

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

Side effects of the pump and catheter

The following side effects have been reported with the pump and catheter “infusion system”. Inform your doctor or nurse if you experience any of these side effects:

• If you experience a reduction in ability to manipulate the pump or catheter, or if your Parkinson's disease symptoms have worsened or your ability to move has decreased (bradykinesia), the pump and catheter may not be functioning properly.
• If you experience abdominal pain, nausea, and 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, difficulty swallowing, abdominal pain, 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 1 in 10 patients

• Infection at the incision site, post-procedural infection after catheter placement in the intestine.
• Stomach wall inflammation.
• Infection in the intestine or at the site where the catheter enters your abdomen.
• Catheter movement within your abdomen or catheter blockage (resulting in reduced medication absorption).
• Dyspnea, feeling of lack of air, chest infections (pneumonia, including aspiration pneumonia).

Rare:may affect 1 in 100 patients

• Colitis (inflammation of the colon).
• Pancreatitis (inflammation of the pancreas).
• The catheter penetrates the wall of the large intestine.
• Intestinal blockage, bleeding, or ulcer.
• Intestinal invagination (slipping of a part of the intestine into an adjacent part of it).
• Food particles stuck around the catheter causing its blockage.
• Abcess (infection blockage, this may occur after catheter placement in the intestine.

Unknown: frequency unknown

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

Side effects when levodopa and carbidopa are taken orally

The following side effects have been reported when taking oral medications containing levodopa and carbidopa (the same active principles as Duodopa). These side effects may also occur with Duodopa:

Rare:may affect 1 in 1,000 patients

• Anemia, low iron levels in blood.
• A disorder called Horner's syndrome.
• Inability to open the mouth fully (trismus).
• Irritation of the skin with red or purple spots that resemble small bruises (Henoch-Schönlein purpura).
• Neuroleptic Malignant Syndrome (see section 4 “Severe side effects”).
• Prolonged dilation of the pupil (mydriasis), decreased eye movements.

Very rare:may affect 1 in 10,000 patients

• Changes in blood tests.

Reporting side effects

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

You can also report them directly through theSpanish 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 packaging after CAD.
• Store and transport in a 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 after removal from the refrigerator.
• The medication cartridges are for single use. The cartridge should not be used for more than 24 hours, even if there is some gel remaining.

• Do not reuse an opened cartridge.
• The gel may become slightly yellow. This does not affect the medication.
• Medications should not be disposed of through drains or trash. Ask your pharmacist how to dispose of unused packaging and medications. This will help protect the environment.Return used cartridges to the pharmacy, do not reuse them.

Composition of Duodopa

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

Appearance of the product and contents of the packaging

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 off-white or slightly yellow.

Marketing Authorization Holder

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

Responsible for manufacturing

HP Halden Pharma ASSvinesundsveien 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

Last review date of this leaflet: October2023

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