This is a combination product containing two medications in the form of a gel: levodopa and carbidopa. It is used to treat advanced Parkinson's disease for people who have severe and disabling movement symptoms that cannot be controlled with other available medications. Levodopa–carbidopa intestinal gel is given using a small portable pump and tube that connects directly into the gut. The medication is given throughout the day, which allows a constant amount of medication to be in the blood and decrease the Parkinson's symptoms.

Levodopa helps to control the symptoms of Parkinson's disease by correcting the chemical imbalance in the brain that produces symptoms. The addition of carbidopa lowers the amount of levodopa that is required and may reduce some of the side effects of levodopa, such as nausea and vomiting.

Although levodopa helps relieve symptoms of Parkinson's disease, it does not slow down the progression of the disease.

This medication may be available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms or approved for all of the conditions discussed here. As well, some forms of this medication may not be used for all of the conditions discussed here.

Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor. Do not stop taking this medication without consulting your doctor.

Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it.

Levodopa - carbidopa intestinal gel is given by a small portable pump and tube (called percutaneous endoscopic gastrostomy jejunal tube or PEG-J tube) that connects directly into your gut. The medication itself is contained in hard plastic cassettes. Instructions on how to use the pump as well as how to attach the cassettes to the pump are provided at the end of this section. Your doctor will teach you how to properly use this device and medication.

A minor surgery is needed to place the medication tube into your gut. Before this surgery, your doctor will first give you a trial of the medication by placing a temporary tube through your nose into your gut to see how well you respond to the medication and to adjust the dose. Follow the instructions given by your doctor on how to maintain this tube. If you are also using an extension tube, the extension tube should be removed, capped, and placed in the refrigerator each night.

The usual dose for levodopa - carbidopa intestinal gel is different for each person and you may need regular small adjustments to reach the best dose for your symptoms. Your dose is programmed into your pump by your doctor or nurse and should only be adjusted by a healthcare professional. Once your pump has been programmed, you will learn how to take your various doses throughout the day (up to 16 hours). This medication is not for use by people under 18 years of age.

Usually, a larger dose in the morning is given to quickly reach the correct amount of medication needed in the blood. Afterward, a lower dose is given throughout the day until bedtime. Your doctor may recommend extra doses throughout the day, if needed. If needed, you may give yourself extra doses throughout the day as recommended by your doctor. It is normal that some gel may remain in your cassette at the end of the day or after a 16-hour period. You should never reuse any leftover gel after the 16-hour period. At bedtime, the tube should be disconnected from the pump and flushed daily with room temperature tap water to prevent it from becoming blocked.

Do not suddenly stop or reduce the dose of this medication on your own, as it can result in serious life-threatening problems.

Using the pump: Before using the pump, carefully inspect the tubing and connections for any kinks or blockages that may result in too little or no medication being pumped. Before attaching the cassette to the pump, inspect the cassette tube to ensure that its contents appear milky white, or slightly yellow. Do not use the medication if the contents are not milky white, or slightly yellow, or the container is leaking.

Attaching the cassette to the pump:

1. Insert the cassette hooks into the hinge pins on the pump.
2. Place the pump and cassette upright on a firm, flat surface. Press down so the cassette fits tightly against the pump.
3. Insert a coin into the latch, push in, and turn counter-clockwise until the line on the latch lines up with the arrow on the side of the pump. You should be able to hear and/or feel the latch click into place.
4. Gently twist, push and pull on the cassette to make sure it is firmly attached. You may need to repeat the procedure if the cassette is not secure.

To attach the cassette to the PEG-J tube:

1. Remove the red protective cap from the cassette tube and open any tube clamps.
2. Connect the cassette tube to the intestinal port of the PEG-J tube. Make sure to twist the cassette tube and not the PEG-J tube.

Cleaning the pump: To clean the pump and accessories, dampen a soft, lint-free cloth with soapy water and wipe the exterior surface of the pump. Wipe the surface dry with another soft, lint-free cloth. Allow the pump to dry completely before using it again. Do not immerse the pump in water or cleaning fluid or use any acetone, solvents, or abrasive cleaners.

Cleaning the tubes: Clean the external PEG-J tubing and connectors on a regular basis using warm, soapy water. The intestinal tube should be flushed with tap water every night to prevent blockages.

It is important to only use the PEG-J tube for this medication. Do not use your PEG-J tube to take any substances other than this medication without speaking with your doctor.

During treatment with this medication, the internal and external tubing will periodically require replacement. Your doctor should regularly check to see that it is working properly.

This medication should be stored in a refrigerator and protected from light (i.e., keep the carton of this medication carefully closed).

It is important to use this medication exactly as prescribed by your doctor. Do not change the dose or stop treatment without talking to your doctor. If your symptoms suddenly or slowly become worse, it is possible that a part of the tube is blocked, disconnected, or has moved. If this happens, call your doctor right away.

This medication is available as a ready-to-use intestinal gel contained in a reservoir bag inside a hard plastic cassette. Each cassette contains 100 mL of this medication.

Each mL of white-to-slightly-yellow intestinal gel contains 20 mg of levodopa and 5 mg of carbidopa. Nonmedicinal ingredients: carmellose sodium and purified water.

Do not use levodopa–carbidopa intestinal gel if you:

• are allergic to levodopa, carbidopa, or any ingredients of the medication
• cannot take sympathomimetic amines (e.g., epinephrine, norepinephrine)
• have a history of stomach or pancreas problems such as swelling or obstruction that prevents placement of a PEG tube (a type of tube that connects to the gut in order to use this medication)
• have an active infection of the abdominal space
• have active uncontrolled or severe heart disease, blood-related diseases, endocrine disease, liver disease, lung disease, or kidney disease
• have narrow-angle glaucoma
• have suspicious undiagnosed skin lesions or a history of melanoma
• have or have had a stroke in the last 6 months
• have used an MAO inhibitor (e.g., phenelzine, tranylcypromine) within the past 2 weeks (as an exception, selegiline can be used safely at the recommended dose with levodopa–carbidopa intestinal gel)

Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent.

The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.

As this medication is delivered using a pump-tube delivery system, complications can occur from the surgical procedure required to create the small opening in the stomach wall for the intestinal tube and with long-term use of the intestinal tube. This risk should be discussed with your doctor to determine if this medication is a good choice for your treatment.

The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.

Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.

• constipation
• diarrhea
• dizziness
• loss of appetite
• upset stomach
• vomiting
• weight loss

Although most of these side effects listed below don't happen very often, they could lead to serious problems if you do not seek medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

• abnormal thinking – developing urges to gamble, increased sexual urges, excessive eating or spending, and/or other intense urges that could harm yourself or others
• anxiety
• cold, burning, tingling, prickling sensations in the hands, feet, arms, or legs
• falling asleep without warning
• falls
• feeling lightheaded or faint after standing
• hallucinations
• involuntary movements, muscle cramps
• signs of depression (e.g., poor concentration, changes in weight, changes in sleep, decreased interest in activities, thoughts of suicide)
• signs of lung infection (e.g., pain when breathing, difficulty breathing, cough, fever)
• signs of skin cancer, irregular or new skin lesions
• a sudden return of your Parkinson's disease symptoms (possible sign of tube blockage)
• surgical-procedure-related problems (e.g., abdominal pain, redness or swelling around the surgical wound, infection around the tube, air or gas in the abdomen etc.)
• symptoms of irregular heart beat (e.g., chest pain, dizziness, rapid, pounding heartbeat, shortness of breath)

The following side effects may be caused by the tubing. Check you with your doctor as soon as possible if any of the following occur:

• tube blockages
• dislocation of the tube
• inflammation or infection around the tube leading to swelling or leakage
• stomach pain, nausea, vomiting
• worsening movement (or slow movement)

Seek immediate medical attention if any of the following occur:

• severe abdominal pain which may be associated with fever, vomiting, abdominal tenderness, or swelling of the abdomen
• signs of a serious allergic reaction (e.g., abdominal cramps, difficulty breathing, nausea and vomiting, redness, itching, or swelling of the skin, face and throat)
• vomiting of blood or noticing blood in your stools
• reduced dosing or stopping the medication resulting in a high fever, muscle rigidity, involuntary movements, altered consciousness, mental status changes such as more frequent breathing, sweating, or dizziness

Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.

Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use this medication.

Activities requiring alertness: Levodopa–carbidopa may cause drowsiness or dizziness, affecting your ability to drive or operate machinery. Avoid driving, operating machinery, or performing other potentially hazardous tasks until you have determined how this medication affects you.

There have been reports of sudden onset of sleep by individuals taking levodopa and carbidopa combination. Tell your doctor immediately if any episodes of suddenly falling asleep occur.

Behavioural and mood changes: This medication has been known to cause mood swings, changes in behavior, and symptoms of depression. If you have depression or a history of depression, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. You may notice compulsive behaviour, such as gambling, increased sexual activity, or inappropriate spending. If you experience symptoms of depression such as poor concentration, changes in weight, changes in sleep, or decreased interest in activities, contact your doctor as soon as possible. If you notice compulsive behaviour or signs of depression in a family member, ensure that they see their doctor.

Blood pressure and heart: This medication can cause blood pressure changes, making symptoms of heart conditions worse. If you have an existing heart condition, you should talk to your doctor about how your condition may affect your medication dosage, or how your dosage may affect your medical condition.

Some people taking levodopa–carbidopa experience blood pressure drops when getting up from a sitting or lying position, causing dizziness, lightheadedness, and falls. If you experience this problem, try getting up more slowly. If it persists or if you faint, contact your doctor.

Device-related complications: A sudden decrease in treatment response with increased symptoms of Parkinson's disease may be due to problems with the tubing or pump device, including tube blockages or dislocations. Tell your doctor immediately if this occurs.

Diet:Protein-rich diets such as diets that contain a lot of meat, poultry, or fish may reduce the beneficial effects of levodopa. Discuss appropriate diet options with your doctor.

Glaucoma: This medication may make symptoms of glaucoma worse by increasing the pressure in the eye. If you have chronic wide-angle glaucoma, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Medical conditions: People with epilepsy, peptic ulcer or previous surgery in the upper part of the abdomen, heart disease, lung disease (e.g., asthma), liver disease, kidney disease, or hormonal disturbances, should be frequently monitored by their doctor while taking this medication.

Neuroleptic malignant syndrome (NMS): Very rarely, levodopa–carbidopa can cause a potentially fatal syndrome known as neuroleptic malignant syndrome (NMS). If you notice the symptoms of NMS such as high fever, muscle stiffness, confusion or loss of consciousness, sweating, racing or irregular heartbeat, or fainting, get immediate medical attention.

Neuropathy: This medication can cause you to develop symptoms like numbness, tingling, loss of feeling, weakness or pain in your legs, hands, feet, and other parts of the body. In many cases, this may be related to a medical condition or if your folic acid, vitamin B12, vitamin B6 or other levels are low. If you develop any of these symptoms, let your doctor know. Your doctor will monitor your folic acid, vitamin B12, vitamin B6 and other levels while you’re taking this medication.

Seizures: If you have seizures or a history of seizures, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Skin cancer: People with Parkinson's have been shown to have 2 to 6 times the risk of developing skin cancer compared to the general population. It is unknown if this is caused by the medication or the Parkinson's disease. You should discuss with your doctor regarding regular monitoring of your skin.

Surgeries: Use of anesthesia and this medication together may cause changes in blood pressure or abnormal heart rhythms. Make sure that your doctor and the other members of your health care team are aware that you are using levodopa–carbidopa intestinal gel. Your surgeon or anesthesiologist will tell you how long before surgery you need to stop using this medication.

Pregnancy: The safety and effectiveness of using this medication have not been established for pregnant women. Levodopa–carbidopa intestinal gel should not be used during pregnancy unless the benefits outweigh the risks.

Breast-feeding: Levodopa passes into breast milk. It is not known if carbidopa passes into breast milk. If you are breast-feeding and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.

Children: The safety and effectiveness of levodopa–carbidopa intestinal gel have not been established for use by people less than 18 years of age.

There may be an interaction between levodopa–carbidopa intestinal gel and any of the following:

• aldesleukin
• aliskiren
• alpha-agonists (e.g., clonidine, guanfacine, methyldopa)
• alpha-blockers (e.g., alfuzosin, doxazosin, tamsulosin)
• amiodarone
• angiotensin-converting enzyme inhibitors (ACEIs; captopril, enalapril, ramipril)
• angiotensin receptor blockers (ARBs; e.g., candesartan, irbesartan, losartan)
• antipsychotics (e.g., cariprazine, chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone)
• apomorphine
• barbiturates (e.g., butalbital, phenobarbital)
• beta-adrenergic blockers (e.g., atenolol, propranolol, sotalol)
• bortezomib
• brimonidine
• bromocriptine
• bupropion
• calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
• conivaptan
• diuretics (water pills; e.g., furosemide, hydrochlorothiazide, triamterene)
• duloxetine
• eplerenone
• general anesthetics (medications used to put people to sleep before surgery)
• glycopyrrolate
• iron supplements (e.g., ferrous gluconate, ferrous sulfate)
• isoniazid
• kava kava
• linezolid
• metoclopramide
• monoamine oxidase inhibitors (MAOIs; e.g., moclobemide, phenelzine, rasagiline, selegiline, tranylcypromine)
• morphine
• multivitamins
• nabilone
• nitrates (e.g., isosorbide dinitrate, nitroglycerin)
• obinutuzumab
• other medications containing levodopa
• pentoxifylline
• pergolide
• phenytoin
• phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil, vardenafil)
• pramipexole
• primidone
• pyridoxine
• riociguat
• ropinirole
• rotigotine
• sacubitril
• sapropterin
• spironolactone
• tetrabenazine
• tizanidine
• tretinoin
• tricyclic antidepressants (e.g., amitriptyline, clomipramine, desipramine, trimipramine)

If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

• stop taking one of the medications,
• change one of the medications to another,
• change how you are taking one or both of the medications, or
• leave everything as is.

An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.

Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.