Duodopa

Package leaflet: Information for the user

Duodopa, 20 mg/ml + 5 mg/ml, intestinal gel
levodopum/carbidopum
Please read all of this leaflet carefully before 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 a specific individual. Do not pass it on to others. It may harm them even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of the leaflet

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. How to store 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 used in Parkinson's disease.
Duodopa is a gel which is administered via a pump through a tube directly into the small intestine.
The gel contains two active substances:

• levodopa,
• carbidopa.

How Duodopa works

• In the body, levodopa is converted into a substance called dopamine, thereby replenishing dopamine levels in the brain and spinal cord. Dopamine facilitates the transmission of nerve impulses between nerve cells.
• A lack of dopamine causes the symptoms of Parkinson's disease, such as tremor, stiffness, slowness of movement and balance problems.
• Treatment with levodopa increases dopamine levels in the body and thus reduces the severity of symptoms.
• Carbidopa enhances the therapeutic effect of levodopa and also reduces its side effects.

2. Important information before using Duodopa

When not to use Duodopa

• if the patient is allergic to levodopa, carbidopa, or any of the other ingredients of this medicine (listed in section 6),
• if the patient has a condition of the eye called narrow-angle glaucoma,
• if the patient has severe heart problems,
• if the patient has an irregular heartbeat (severe arrhythmia),
• if the patient has had a severe stroke,
• if the patient is taking medicines for depression called selective MAO-A inhibitors or non-selective MAO inhibitors, such as moclobemide or phenelzine,
• if the patient has a tumour of the adrenal gland (pheochromocytoma),
• if the patient has hormonal disorders, such as excessive production of cortisol (Cushing's syndrome) or too high levels of thyroid hormones (hyperthyroidism),
• if the patient has ever had skin cancer or has atypical moles ("spots") or skin changes that have not been examined by a doctor.

Do not use Duodopa if any of the above apply to the patient. If in doubt, consult a doctor before starting treatment with Duodopa.

Warnings and precautions

Before starting treatment with Duodopa, discuss with your doctor if:

• the patient has ever had a heart attack, blocked blood vessels in the heart, or other heart conditions, including heart rhythm disorders (arrhythmias),
• the patient has a lung condition such as asthma,
• the patient has ever had a hormonal disorder,
• the patient has ever had depression with suicidal thoughts or any other psychiatric disorders,
• the patient has been diagnosed with a condition of the eye called open-angle glaucoma,
• the patient has ever had a stomach ulcer,
• the patient has ever had seizures (convulsions),
• the patient has ever undergone abdominal surgery in the upper abdomen,
• patients treated with intestinal gel containing levodopa and carbidopa have experienced worsening weakness, pain, numbness, or loss of sensation in fingers or feet (polyneuropathy). Before starting treatment with intestinal gel containing levodopa and carbidopa, the doctor will examine whether the patient has symptoms of neuropathy and will perform periodic examinations. Consult your doctor if the patient already has neuropathy or conditions related to neuropathy.

If any of the above apply to the patient (or if the patient is unsure), inform the doctor before using Duodopa.

Be aware of the following adverse effects

Neuroleptic malignant syndrome

Do not stop or reduce the dose of Duodopa unless instructed by a doctor. Abruptly stopping or rapidly reducing the dose of Duodopa may cause a serious condition called neuroleptic malignant syndrome (see section 4 "Serious adverse effects").

Drowsiness or dizziness

If the patient suddenly falls asleep (sleep attacks), feels excessively sleepy, has a sensation of emptiness in the head, or experiences dizziness:

• the patient should not drive, use tools, or operate machinery until fully awake or until the sensation of emptiness in the head or dizziness has resolved (see section 2 "Driving and use of machines").

Skin changes

Inform the doctor, pharmacist, or nurse if the patient notices the appearance of atypical skin changes or moles ("spots") or worsening of existing ones (see section 4 "Other adverse effects").

Impulse control disorders – changes in patient behaviour

Inform the doctor if the patient, family members, or caregivers notice the emergence of impulses or irresistible urges to engage in behaviours that are unusual for the patient, or if the patient is unable to resist impulsive urges or temptations to perform certain actions that may be harmful to themselves or others. These behaviours are called impulse control disorders and include:

• gambling addiction,
• compulsive eating or spending,
• increased sexual drive or intense sexual thoughts or feelings.

The doctor may need to reassess the ongoing treatment. The doctor will discuss with the patient ways to manage these symptoms or reduce their intensity (see section 4 "Impulse control disorders – changes in patient behaviour").

Dopaminergic dysregulation syndrome

If the patient or their family (caregiver) notices symptoms resembling addiction, leading to a desire to take high doses of Duodopa or other medicines used in the treatment of Parkinson's disease, inform the doctor.

Problems with pump or catheter

Problems may occur related to the use of the pump and catheter:

• The patient begins to have difficulty using the pump and catheter, Parkinson's disease symptoms worsen, or there is a deterioration in movement ability (bradykinesia) – possibly the pump and catheter are not working properly.
• The patient experiences abdominal pain, nausea, and vomiting – inform the doctor immediately (see section 4 "Serious adverse effects").
• Other adverse effects may also occur at the intestine and at the catheter insertion site (see section 4 "Adverse effects related to the use of the pump or catheter").

Duodopa and cancer

In the body, carbidopa (the active substance in Duodopa) breaks down into a substance called hydrazine. Hydrazine may potentially damage genetic material, which could lead to cancer development. However, it is not known whether the amount of hydrazine produced during the administration of the correct dose of Duodopa could cause this.

Laboratory tests

During treatment with Duodopa, the doctor may request certain blood tests.

Surgical procedures

Before any surgical procedure (including dental procedures), inform the doctor (or dentist) that the patient is using Duodopa.

Children and adolescents

Duodopa should not be used in children and adolescents under 18 years of age.

Duodopa and other medicines

Inform the doctor or pharmacist about all medicines currently used or recently used, as well as any medicines the patient plans to take. This includes over-the-counter medicines and herbal remedies.

Do not use Duodopa if:

• the patient is taking medicines for depression called selective MAO-A inhibitors or non-selective MAO inhibitors, such as moclobemide or phenelzine.

Before starting treatment with Duodopa, inform the doctor or pharmacist if the patient is taking medicines for:

• anaemia – such as iron preparations,
• tuberculosis – such as isoniazid,
• anxiety – such as benzodiazepine derivatives,
• nausea – such as metoclopramide,
• high blood pressure – such as antihypertensive medicines,
• blood vessel spasms – such as papaverine,
• seizures (convulsions) or epilepsy – such as phenytoin,
• Parkinson's disease – such as tolcapone, entacapone, amantadine,
• psychiatric disorders – such as antipsychotics, including phenothiazine derivatives, butyrophenone derivatives, and risperidone,
• severe allergic reactions, asthma, chronic bronchitis, heart conditions, and low blood pressure – such as anticholinergic and sympathomimetic medicines,
• if the patient is taking a medicine that may cause low blood pressure. This may lead to a condition called orthostatic hypotension – causing dizziness when the patient stands up from a chair or bed. Duodopa may worsen this. Always change body positions slowly.

Duodopa with food and drink

In some patients, Duodopa may not work effectively if taken with a high-protein meal or shortly after eating (such as meat, fish, dairy products, grains, and nuts). Inform the doctor if the patient suspects this may affect them.

Pregnancy and breastfeeding

• If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a baby, she should consult a doctor before starting treatment with Duodopa.
• Duodopa should not be used during breastfeeding.

Driving and use of machines

Do not drive, use tools, or operate machinery until the patient knows how Duodopa affects them.

• Duodopa may cause significant drowsiness or, occasionally, sudden sleep attacks (sleep episodes).
• Duodopa may lower blood pressure, which may cause a sensation of emptiness in the head or dizziness. Do not drive, use tools, or operate machinery until fully awake or until the sensation of emptiness in the head or dizziness has resolved.

3. How to use Duodopa

This medicine should always be used exactly as directed by your doctor, pharmacist, or nurse. If in
doubt, consult your doctor or pharmacist.
Information about Duodopa gel and the pump

• Duodopa is a gel which is delivered via a pump through a tube into the small intestine.
• The gel is contained in a plastic cassette. The cassette is connected to the pump.
• The pump is connected to the tube placed in the small intestine.
• The patient receives a small, continuous dose of medicine throughout the day via the pump. This maintains a constant level of medicine in the blood, thereby reducing the severity of certain movement-related side effects.

How much medicine to use

• Your doctor will decide how much Duodopa to use and for how long.
• Usually, a higher morning dose (called a "bolus dose") is given in the morning to rapidly achieve the appropriate medicine concentration in the blood. After this, a continuous maintenance dose is administered.
• If necessary, additional doses may be given. This decision will be made by your doctor.

Use of more than the recommended dose of Duodopa
If more Duodopa than recommended is used, contact your doctor immediately or go to the
nearest hospital without delay. Bring the medicine packaging with you. The following symptoms may
occur:

• difficulty opening the eyes,
• uncontrolled muscle spasms of the eyes, head, neck, and body (dystonia),
• involuntary movements (dyskinesia),
• abnormally fast, slow, or irregular heartbeat (arrhythmia).

Missed dose of Duodopa

• Restart the pump as soon as possible and take the next usual dose.
• Do not increase the dose to make up for a missed dose.

Stopping or reducing the dose of Duodopa
Do not stop or reduce the dose of Duodopa unless instructed by your doctor.
Suddenly stopping or reducing the dose of Duodopa may cause a serious condition called
neuroleptic malignant syndrome. The risk of developing this condition is higher if you are also
taking a medicine known as an antipsychotic medicine (see section 4, "Serious side effects").
If you have any further questions about the use of this medicine, consult your doctor, pharmacist,
or nurse.

4. Possible adverse effects

Like any medicine, this medicine can cause adverse effects, although not everyone will experience them.

Serious adverse effects of Duodopa

If any of the following serious adverse effects occur, stop using Duodopa immediately and contact your doctor. The patient may require immediate medical attention:

• Acute eye pain, headache, blurred vision, nausea, and vomiting. These may be symptoms of acute angle-closure glaucoma. Uncommon: may occur in up to 1 in 100 patients.
• Fever, sore throat or mouth, or problems with urination. These may be signs of a serious blood disorder affecting white blood cells called agranulocytosis. Your doctor will take a blood sample to check for this. Very rare: may occur in up to 1 in 10,000 patients.
• Swelling of the face, tongue, or throat, which may make swallowing and breathing difficult, or skin rash such as hives. These may be signs of a severe allergic reaction (anaphylactic reaction). Frequency unknown: cannot be estimated from available data.

Contact your doctor immediately if any of the following serious adverse effects occur:

• Neuroleptic malignant syndrome – signs may include:
  • Rapid heartbeat, changes in blood pressure, excessive sweating, followed by fever,
  • Rapid breathing, muscle rigidity, reduced consciousness, and coma,
  • Increased levels of certain proteins in the blood (an enzyme called creatine kinase), which your doctor will assess with a blood test. Rare: may occur in up to 1 in 1,000 patients. For more information about neuroleptic malignant syndrome, see section 3 “Discontinuation or reduction of Duodopa dosage”.

Other adverse effects of Duodopa

If any of the following adverse effects occur, contact your doctor, pharmacist, or nurse immediately.

Very common: may affect more than 1 in 10 patients

• Fainting,
• Weight loss,
• Nausea, constipation,
• Restlessness, depression, inability to sleep (insomnia),
• Involuntary movements (dyskinesia), worsening of Parkinson’s disease symptoms,
• Dizziness upon standing or changing position (orthostatic hypotension) due to low blood pressure. Always change body position slowly – do not stand up too quickly,
• Urinary tract infections.

Common: may affect up to 1 in 10 patients

• Weight gain,
• Irregular heartbeat,
• Loss of appetite,
• Feeling of fatigue or weakness,
• High or low blood pressure,
• Anaemia – low iron levels in the blood,
• Pain, neck pain, muscle cramps, reduced muscle strength,
• Sudden sleep attacks (sleep attacks), excessive daytime sleepiness, sleep disturbances,
• Increased levels of amino acids or increased homocysteine levels in blood, vitamin B and B deficiency,
• Dizziness or feeling faint or fainting,
• Difficulty swallowing or dry mouth, taste disturbances (bitter taste),
• Headache,
• Progressive weakness, pain, numbness, or loss of sensation in fingers or feet (peripheral neuropathy),
• Skin rash, itching, excessive sweating, fluid retention causing swelling,
• Difficulty urinating (urinary retention) or inability to control urination (urinary incontinence),
• Seeing, hearing, or sensing things or events that are not real (hallucinations), confusion, abnormal dreams, feeling of agitation, impulsive behaviour, psychotic disorder,
• Abdominal distension, diarrhoea, bloating with gas release, indigestion (dyspeptic symptoms), vomiting,
• Sudden and unpredictable return of Parkinson’s disease symptoms – known as the “ON/OFF phenomenon”,
• Reduced touch sensation, uncontrolled muscle contractions of the eyes, head, neck, and body (dystonia), tremor.

Impulse control disorders – changes in patient behaviour.
Common (may affect up to 1 in 10 patients)
Some individuals may be unable to resist impulses that could be harmful to themselves or others. These include:

• Strong impulse towards pathological gambling, despite serious consequences for the patient or their family,
• Changes or increase in sexual thoughts and behaviours, which may be very distressing for the patient or others, such as increased libido,
• Uncontrolled excessive shopping or spending,
• Binge eating – consuming large amounts of food in a short time, or compulsive overeating – eating more food than normal and more than the body needs.

Inform your doctor if the patient, their family, or caregiver notice any of these behaviours. The doctor may need to reassess the treatment. The doctor will discuss ways to manage or reduce the severity of these symptoms.

Uncommon: may affect up to 1 in 100 patients

• Dark urine,
• Hoarseness, chest pain,
• Hair loss, skin redness, hives,
• Increased salivation,
• Vein swelling (phlebitis),
• Change in gait,
• Suicidal thoughts or suicide attempts,
• Feeling of fatigue or general malaise,
• Rapid and irregular heartbeat (palpitations),
• Low white blood cell count or changes in blood cells that may cause bleeding,
• Disorientation, elevated mood (euphoria), increased interest in sex, nightmares, dementia, feeling of anxiety,
• Difficulty controlling movements and making sudden, uncontrolled movements,
• Difficulty opening the eyes, double vision, blurred vision, damage to the optic nerve (ischaemic optic neuropathy).

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

• Abnormal thinking,
• Irregular breathing rate and depth,
• Painful erection that does not resolve,
• Appearance of new or worsening skin changes or moles (spots), or development of skin cancer (malignant melanoma),
• Dark discoloration of saliva or sweat, burning sensation of the tongue, teeth grinding, hiccups.

Not known: frequency cannot be estimated from available data

• Desire to take high doses of Duodopa, higher than necessary to control motor symptoms, known as dopamine dysregulation syndrome. In some patients, taking high doses of Duodopa may lead to severe adverse effects such as involuntary movements (dyskinesias), mood swings, or other adverse effects.

If any of the above adverse effects occur in the patient, inform the doctor, pharmacist, or nurse.

Adverse effects related to the use of the pump or catheter

The following adverse effects have been reported in connection with the pump and catheter (drug delivery system). If any of these occur, inform your doctor or nurse.

• If the patient begins to have difficulty managing the pump and catheter, Parkinson’s symptoms worsen, or movement ability deteriorates (bradykinesia) – the pump and catheter may not be working properly.
• If the patient experiences abdominal pain, nausea, and vomiting – contact the doctor immediately, as this may indicate 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 was inserted into the abdominal cavity – may result from the surgical procedure,
• Thick scar tissue at the site where the catheter was inserted into the abdominal cavity,
• Complications related to catheter placement – pain or swelling of the mouth and/or throat, difficulty swallowing, discomfort in the abdominal cavity, pain or swelling, damage to the throat, mouth, or stomach, bleeding, vomiting, bloating with gas release, restlessness,
• Complications at the site of catheter insertion into the abdominal cavity – redness or skin abrasion, pressure sores, discharge, 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 abdominal wall,
• Infection in the intestine or at the catheter insertion site,
• Catheter displacement in the intestine or catheter blockage – which may result in reduced drug absorption,
• Pain during breathing, feeling of breathlessness, lower respiratory tract infections (pneumonia, including aspiration pneumonia).

Uncommon: may affect up to 1 in 100 patients

• Colitis (inflammation of the colon),
• Pancreatitis,
• Perforation of the colon wall by the catheter,
• Intestinal obstruction, bleeding, or ulcer,
• Intussusception – telescoping of one part of the intestine into another,
• Food debris adhering to the catheter causing blockage,
• Localized infection (abscess) – may develop after catheter insertion into the abdominal cavity.

Frequency unknown: frequency cannot be determined from available data

• Reduced blood flow to the small intestine,
• Perforation of the stomach or small intestine wall by the catheter,
• Blood infection (sepsis).

Adverse effects of oral medicines containing levodopa and carbidopa

The following adverse effects have been reported with oral medicines containing levodopa and carbidopa (the same active substances as in Duodopa). These adverse effects may also occur with the use of Duodopa.

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

• Anaemia – low iron levels in the blood,
• Eye disorder called Horner’s syndrome,
• Inability to fully open the mouth (trismus),
• Red or purple rash resembling small bruises (Henoch-Schönlein purpura),
• Neuroleptic malignant syndrome (see section 4. “Serious adverse effects”),
• Prolonged pupil dilation, reduced eye movement.

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

• Changes in blood test results.

Reporting of adverse effects

If any adverse effects occur, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse effects can also be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
PL-02 222 Warsaw
Tel: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorization holder.

Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Duodopa

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the outer carton after EXP.
• Store and transport in a refrigerated condition (2°C - 8°C). The cassette should be kept in its outer packaging to protect it from light.
• The gel cassette must be used within 24 hours after removal from the refrigerator.
• Medicine cassettes are for single use only. A cassette should not be used for longer than 24 hours, even if some gel remains.
• Opened cassettes must not be reused.
• The gel may turn slightly yellowish; this does not affect the medicine.
• Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures help protect the environment. Used cassettes must not be reused; they should be returned to the nearest pharmacy.

6. Contents of the pack and other information

What Duodopa contains

• The active substances are: levodopa and carbidopa (in monohydrate form). 1 ml of gel contains 20 mg of levodopa and 5 mg of carbidopa (in monohydrate form).
• Other ingredients include: sodium carmellose and purified water.

What Duodopa looks like and contents of the pack
Duodopa is available in cassettes (a plastic bag made of PVC placed in a hard plastic cassette) containing 100 ml of gel, with 7 cassettes in each package. The gel is white to slightly yellowish in colour.
Marketing Authorisation Holder
AbbVie Sp. z o.o.
ul. Postępu 21B
02-676 Warsaw
Poland
Manufacturer
HP Halden Pharma AS
Svinesundsveien 80
NO-1788 Halden
Norway
AbbVie Logistics B.V.
Zuiderzeelaan 53
8017 JV Zwolle
The Netherlands
For further information, please contact your doctor or pharmacist, or contact the Marketing Authorisation Holder:
AbbVie Sp. z o.o.
ul. Postępu 21B
02-676 Warsaw
Poland
tel. +48 22 372 78 00
This medicinal product is authorised in the European Economic Area under the following
names:
Duodopa
Other sources of information
Detailed information on this medicinal product is available on the website of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products http://urpl.gov.pl