Apomorphine belongs to a class of drugs called dopamine agonists. It is used to treat a progressive nervous system disorder that affects movement called Parkinson's disease.

Dopamine agonist, such as apomorphine, are medications that mimic the action of dopamine. Dopamine is produced by the brain and acts as a messenger or neurotransmitter sending information between nerve cells (neurons).

Apomorphine works to help treat Parkinson's disease by binding to dopamine receptors in the brain and acting like natural dopamine. Low levels of dopamine are thought to cause the symptoms of Parkinson's disease.

Apomorphine comes in the form of a:

• Subcutaneous injection - an injection that you inject under your skin. This form of the drug is available under the brand name Apokyn and a generic version is also available.
• Sublingual film - a film you put under your tongue. This form of the drug is available under the brand name Kynmobi. Generic versions of a sublingual film have not been approved.

Apomorphine was approved by the US Food and Drug Administration (FDA) in 2004.

What is apomorphine used for?

Apomorphine injection is a prescription medicine used to treat acute, intermittent episodes of poor mobility called " off " episodes (end-of-dose wearing "off" or unpredictable "on - off" episodes) in people with advanced Parkinson's disease.

Apomorphine sublingual film is a prescription medicine used to treat short-term (acute), intermittent “off” episodes in people with Parkinson's disease.

It is not known if apomorphine is safe and effective in children.

• Read the Instructions for Use that come with your apomorphine injection or sublingual film about the right way to use apomorphine.
• Use apomorphine exactly as your healthcare provider tells you to use it.
• Your healthcare provider will tell you how much apomorphine to use and teach you the right way to use it.
• Your healthcare provider may change your dose if needed.
• Do not change your dose of apomorphine or use it more often than prescribed unless your healthcare provider has told you to.
• Do not stop taking apomorphine unless you are told to do so by your healthcare provider.
• Do not give another dose of apomorphine sooner than 2 hours after the last dose.
• Your healthcare provider may prescribe another medicine for nausea called an antiemetic to take while you are taking apomorphine. Antiemetic medicines help to decrease the symptoms of nausea and vomiting that can happen when you take apomorphine.
• Additional instructions for people using apomorphine injection:
  • Your healthcare provider will prescribe apomorphine injection that comes in prefilled glass cartridges, for single-patient-use, that are used with a special pen injector.
  • Your apomorphine injection pen is dosed in milliliters (mL), not milligrams (mg). Make sure your prescription tells you how many milliliters (mL) to use.
  • Inject apomorphine injection under your skin (subcutaneously). Do not inject it into a vein.
  • Keep a record of how much apomorphine you have used each time you inject or your care partner gives you an injection.
  • Use a new needle with each injection. Never reuse a needle.
  • Apomorphine injection is a clear and colorless liquid. Do not use apomorphine injection if it appears cloudy, colored, or to contain particles, and call your pharmacist.
• Additional instructions for people using apomorphine sublingual film:
  • Do not take more than 1 dose of apomorphine sublingual film to treat an "off" episode.
  • Do not take apomorphine sublingual film more than 5 times a day.
  • Do not cut, chew, or swallow apomorphine sublingual film

Apomorphine injection

• For subcutaneous use only
• The starting dose of apomorphine is 0.2 mL (2 mg). The first dose will be given under medical supervision. The dose will be adjusted depending on how well it works and how well you tolerate it. The maximum recommended dose is 0.6 mL.
• Treatment with a concomitant antiemetic, e.g., trimethobenzamide, is recommended, starting 3 days prior to the first dose. Treatment with trimethobenzamide should only be continued as long as necessary to control nausea and vomiting, and generally no longer than two months.
• Apomorphine doses must be separated by at least 2 hours.
• If you have renal impairment the test dose will be reduced. A starting dose to 0.1 mL (1 mg) is recommended.

Apomorphine sublingual film

• For sublingual administration only
• The first time you take a dose it should be supervised by a healthcare provider.
• Treatment with a concomitant antiemetic, e.g. trimethobenzamide, is recommended, beginning 3 days prior to initial dose.
• The dose range for apomorphine sublingual film is 10 mg to 30 mg per dose, administered sublingually, as needed.
• Apomorphine sublingual film doses should be separated by at least 2 hours.
• Maximum of 5 doses per day; maximum single dose is 30 mg.

Do not take apomorphine if you are:

• taking certain medicines to treat nausea called 5HT 3 antagonists including, ondansetron, granisetron, dolasetron, palonosetron, and alosetron. People taking ondansetron together with apomorphine have had very low blood pressure and lost consciousness or "blacked out."
• allergic to apomorphine hydrochloride or to any of the ingredients in the injection or sublingual film and experience hives, itching, rash, or swelling (e.g., eyes, tongue, etc.). Apomorphine also contains a sulfite called sodium metabisulfite. Sulfites can cause severe, life-threatening allergic reactions in some people. An allergy to sulfites is not the same as an allergy to sulfa. People with asthma are more likely to be allergic to sulfites. Call your healthcare provider if you have hives, itching, rash, swelling of the eyes, tongue, lips, redness of your face (flushin), throat tightness, chest pain or trouble breathing or swallowing.
  
  See the end of this leaflet for a complete list of ingredients apomorphine injection and sublingual film.

What should I tell my doctor before using apomorphine?

Before you start using apomorphine, tell your healthcare provider if you:

• have difficulty staying awake during the daytime
• have dizziness
• have fainting spells
• have low blood pressure
• have asthma
• are allergic to any medicines containing sulfites
• have liver problems
• have kidney problems
• have heart problems
• have had a stroke or other brain problems
• have a mental problem called a major psychotic disorder
• drink alcohol

If you take too much apomorphine injection, call your healthcare provider. If you experience severe or serious side effects such as chest pain or prolonged erection lasting more than 4 hours, go to the nearest hospital emergency room.

• Do not drink alcohol while you are using apomorphine. It can increase your chance of developing serious side effects.
• Do not take medicines that make you sleepy while you are using apomorphine.
• Do not drive, operate machinery, or do other dangerous activities until you know how apomorphine affects you.
• Do not change your body position too fast. Get up slowly from sitting or lying. Apomophine can lower your blood pressure and cause dizziness or fainting.

Side effects of apomorphine injection

Apomorphine injection may cause serious side effects. Call your healthcare provider right away if you have any of the serious side effects, including:

• allergic reaction. An allergic reaction with side effects of hives, itching, rash, swelling (e.g., eyes, tongue, etc.); trouble breathing and/or swallowing may occur after injecting apomorphine.
• blood clots. Injecting apomorphine into a vein (intravenous) can cause blood clots. Do not inject it in your vein.
• nausea and vomiting. Severe nausea and vomiting can happen with apomorphine injection. Your healthcare provider may prescribe a medicine called trimethobenzamide (Tigan) to help prevent nausea and vomiting. Some patients can stop taking Tigan after using this medication for several months. Some patients may need to keep taking Tigan to help prevent nausea and vomiting. Talk to your healthcare provider before you stop taking Tigan.
• sleepiness or falling asleep during the day. Some people treated with apomorphine injection may get sleepy during the day or fall asleep without warning while doing everyday activities such as talking, eating, or driving a car.
• dizziness. Apomorphine injection can lower your blood pressure and cause dizziness. Dizziness can happen when apomorphine injection treatment is started or when the dose is increased. Do not get up too fast from sitting or after lying down, especially if you have been sitting or lying down for a long period of time.
• falls. The changes that can happen with Parkinson's disease, and the effects of some Parkinson's disease medicines, can increase the risk of falling. Apomoprhine injection may also increase your risk of falling.
• hallucinations or psychotic-like behavior. Apomorphine injection can cause or worsen psychotic-like behavior including hallucinations (seeing or hearing things that are not real), confusion, excessive suspicion, aggressive behavior, agitation, delusional beliefs (believing things that are not real), and disorganized thinking.
• sudden uncontrolled movements (dyskinesias). Some people with Parkinson's disease may get sudden, uncontrolled movements after treatment with some Parkinson's disease medicines. Apomorphine injection can cause or make dyskinesias worse.
• intense urges. Some people with Parkinsion's disease have reported new or increased gambling urges, increased sexual urges, and other intense urges, while taking Parkinson's disease medicines, including apomorphine injection.
• heart problems. If you have shortness of breath, fast heartbeat, or chest pain while taking apomorphine injection, call your healthcare provider or get emergency help right away.
• serious heart rhythm changes (QT prolongation). Tell your healthcare provider right away if you have a change in your heartbeat (a fast or irregular heartbeat), or if you faint.
• injection site problems. Bruising, swelling, and itching can happen at the site where you inject apomorphine.
• fever and confusion. This can happen in some people when their Parkinson's disease medicine is stopped or there is a fast decrease in the dose of their Parkinson's disease medicine.
• tissue changes (fibrotic complications). Some people have had changes in the tissues of their pelvis, lungs, and heart valves when taking medicines called non-ergot derived dopamine agonists like apomorphine injection.
• prolonged painful erections (priaprism). Apomorphine injection may cause prolonged, painful erections in some people. If you have an erection that lasts more than 4 hours you should call your healthcare provider or go to the nearest hospital emergency room right away.
• swelling of ankles/legs. Apomorphine injection may cause swelling, especially in the ankles or legs. Tell your healthcare provider if you notice any swelling.

Other common side effects of apomorphine injection include:

• yawning
• runny nose
• confusion
• swelling of your hands, arms, legs, and feet

Side effects of apomorphine sublingual film

Apomorphine sublingual film can cause serious side effects, including:

• nausea and vomiting. Nausea is a common side effect of apomorphine sublingual film. Nausea and vomiting can happen with apomorphine sublingual film. Your healthcare provider may prescribe a medicine called an antiemetic, such as trimethobenzamide, to help prevent nausea and vomiting. Some patients can stop taking trimethobenzamide after using apomorphine sublingual film, when advised by your healthcare provider. Some patients may need to keep taking trimethobenzamide to help treat nausea and vomiting. Talk to your healthcare provider before you stop taking trimethobenzamide.
• sleepiness or falling asleep during the day. Sleepiness is a serious and common side effect of apomorphine sublingual film. Some people treated with this medication may get sleepy during the day or fall asleep without warning while doing everyday activities such as talking, eating, or driving a car.
• allergic reactions. See the “Who should not use apomorphine” above.
• dizziness. Dizziness is a serious and common side effect of apomorphine sublingual film. It may lower your blood pressure and cause dizziness. Dizziness can happen when apomorphine sublingual film treatment is started or when the dose is increased. Do not get up too fast from sitting or after lying down, especially if you have been sitting or lying down for a long period of time.
• mouth (oral) irritation. Mouth (oral) irritation is a common side effect of apomorphine sublingual film. You should call your healthcare provider if you develop any of these signs or symptoms:
  • redness
  • swelling
  • mouth sores (ulceration)
  • pain
  • dryness of the mouth, lips, or tongue
  • pain with swallowing

These signs and symptoms may go away if apomorphine sublingual film treatment is stopped.

• falls. The changes that can happen with Parkinson's disease, and the effects of some Parkinson's disease medicines, can increase the risk of falling. Apomorphine sublingual film may also increase your risk of falling.
• hallucinations or psychotic-like behavior. Apomorphine sublingual film may cause or make psychotic-like behavior worse, including hallucinations (seeing or hearing things that are not real), confusion, excessive suspicion, aggressive behavior, agitation, delusional beliefs (believing things that are not real), and disorganized thinking.
• strong (intense) urges. Some people with Parkinson's disease have reported new or strong uncontrollable urges to gamble, increased sexual urges, increased urges to spend money (compulsive shopping), and other intense urges, while taking Parkinson's disease medicines, including apomorphine sublingual film. If you or your family members notice that you have strong urges, talk to your healthcare provider. The strong urges may go away if your dose is lowered or stopped.
• high fever and confusion. Apomorphine sublingual film may cause a problem that can happen in people who suddenly lower their dose, stop using, or change their dose. Symptoms include:
  • very high fever
  • stiff muscles
  • confusion
  • changes in breathing and heartbeat

Do not stop taking apomorphine sublingual film or change your dose unless you are told to do so by your healthcare provider.

• heart problems. If you have shortness of breath, fast heartbeat, chest pain, or feel like you are going to pass out (faint) while taking apomorphine sublingual film, call your healthcare provider or get emergency help right away.
• tissue changes (fibrotic complications). Some people have had changes in the tissues of their pelvis, lungs, and heart valves when taking medicines called non-ergot-derived dopamine agonists like apomorphine sublingual film.
• prolonged painful erections (priapism). Apomorphine sublingual film may cause prolonged, painful erections in some people. If you have a prolonged and painful erection you should call your healthcare provider or go to the nearest hospital emergency room right away.

If you have any of these symptoms, stop taking apomorphine sublingual film and call your healthcare provider right away before taking another dose.

The most common side effects of apomorphine sublingual film include:

• nausea
• sleepiness
• dizziness
• mouth swelling, pain, or sores

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of apomorphine. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

You may also report side effects to MDD US Operations, LLC at 1-877-727-6596.

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

Using apomorphine with certain other medicines may affect each other. Using apomorphine with other medicines can cause serious side effects.

If you take nitroglycerin under your tongue while using apomorphine, your blood pressure may decrease and cause dizziness. After taking nitroglycerin, you should lie down and try to continue lying down for at least 45 minutes. You should avoid standing for 45 minutes after taking nitroglycerin.

Know the medicines you take. Keep a list of them to show your healthcare provider or pharmacist when you get a new medicine.