Apomorphine stimulates the postsynaptic D2 receptors and is indicated for the treatment of hypomobility "off" episodes in patients with advanced Parkinson's disease. It is never used as monotherapy and administered with other concomitant antiparkinson medications such as levodopa-carbidopa, ropinirole, amantadine, and rasagiline. 

Apomorphine dose in adults:

Patients should be initiated on antiemetic therapy at least three days prior to the treatment. Treatment may be continued for as long as two months and not more than two months. It should be used with other antiparkinson medications.

Apomorphine dose in the treatment of Parkinson disease, “off” episode:

• An initial test dose of 0.2 mL (2 mg) is administered subQ under medical supervision.
• If the patient tolerates the test dose and responds to the treatment, a starting dose of 0.2 mL (2 mg) may be administered as needed.
• The dose may be increased in 0.1 mL (1 mg) increments every few days to the maximum dose of 0.6 mL (6 mg).
• If the patient tolerates the test dose of 0.2 ml (2 mg) but does not respond, a second test dose of 0.4 mL (4 mg) should be administered.
• After the second test dose, if the patient tolerates and responds to a 0.4 mL (4 mg) test dose, a starting dose of 0.3 mL (3 mg) may be administered as needed for “off” episodes.
• The dose may be increased in 0.1 mL (1 mg) increments every few days to the maximum dose of 0.6 mL (6 mg).
• If the patient does not tolerate a 0.4 mL (4 mg) test dose, a third test dose of 0.3 mL (3 mg) should be administered.
• If the patient tolerates 0.3 mL (3 mg) test dose, a starting dose of 0.2 mL (2 mg) as needed for “off” episodes should be administered. The dose may be increased after a few days to 3 mg.

• If the treatment is interrupted for more than a week, restart at 0.2 mL (2 mg) and gradually titrate the dose.

Note:

• For all the test doses administered, the patient should be supervised with standing and supine blood pressure monitoring before the dose and at 20, 40, and 60 minutes after the dose
• If subsequent doses are required and the patient develops hypotension after 60 minutes, the next dose should be administered after 2 or more hours.
• The next test dose should be timed with another "off" episode. If a single dose is ineffective for a particular “off” episode, then a second dose should not be given.

Apomorphine Dose in Children

It is not recommended for use in children.

Pregnancy Risk Factor C

• It has not yet been tested in pregnant women.

Use of apomorphine while breastfeeding

• It is unknown if the drug will be excreted into breastmilk.
• Manufacturer suggests weighing the risks for the neonate against the benefits of continuing drug therapy in the lactating mom.

Apomorphine dose in Kidney disease:

• Mild to moderate impairment

  • Initial test dose is 1 mg (0.1mL).
  • As needed, the usual starting dose is 0.1mL (1 mg).

• Severe impairment

  • For those with severe kidney disease, it is not advised.

Apomorphine dose in liver disease:

• Mild to moderate impairment

  • Although no modifications are required, it is advised that these patients be handled carefully.

• Severe impairment

  • For those with severe kidney disease, it is not advised.

Common Side Effects of Apomorphine include:

• Cardiovascular:

  • Angina pectoris
  • Chest pain
  • Chest pressure

• Central nervous system:

  • Drowsiness
  • Dizziness
  • Orthostatic hypotension

• Gastrointestinal:

  • Nausea
  • Vomiting

• Neuromuscular & skeletal:

  • Dyskinesia
  • Falling

• Respiratory:

  • Yawning
  • Rhinorrhea

Less Common Side Effects of Apomorphine Include:

• Cardiovascular:

  • Edema
  • Vasodilatation
  • Hypotension
  • Syncope
  • Cardiac failure

• Central nervous system:

  • Confusion
  • Hallucinations
  • Anxiety
  • Depression
  • Fatigue
  • Headache
  • Insomnia
  • Pain

• Dermatologic:

  • Bruise

• Endocrine & metabolic:

  • Dehydration

• Gastrointestinal:

  • Constipation
  • Diarrhea

• Local:

  • Injection site reaction

• Neuromuscular & skeletal:

  • Arthralgia
  • Weakness

• Miscellaneous:

  • Diaphoresis

Contraindication to Apomorphine Include:

• Allergy reactions to apomorphine and any component of the formulation
• Use with vasodilators and 5-HT3 antagonists in conjunction.
• Grave liver and renal disease.

Warnings and precautions

• GI effects

  • Apomorphine can cause severe nausea and vomiting. Antiemetics should be administered at least three days before the patient begins treatment.
  • You can continue antiemetics for as long as you need, but no longer than two months.
  • It is important to note that antiemetics can increase the chance of falls, dizziness, somnolence, and dizziness.
  • Avoid antidopaminergic antiemetic drugs such as promethazine and prochlorperazine , phenytomazine , metoclopramide and haloperidol.

• Hallucinations, psychosis and hallucinations:

  • It can cause hallucinations, psychotic-like behavior, thoughts, aggression, delusions and paranoia.
  • Patients with severe psychotic disorders should avoid it.

• Hypersensitivity

  • Avoid its use if you have an allergic reaction.

• Disorders of impulse control:

  • It has been linked to compulsive behavior such as binge eating and pathological gambling.
  • Patients may need to reduce the dosage or discontinue using the drug completely.

• Melanoma

  • Patients with Parkinson's disease should have a skin exam every other day. The risk of developing melanoma in this group is higher.

• Orthostatic hypotension, syncope

  • It could lead to orthostatic hypotension.
  • Orthostatic hypotension is more common among patients who have taken higher doses of antihypertensive and vasodilator medications, patients with pre-existing cerebrovascular disease and cardiovascular diseases.
  • Parkinson's patients have a reduced ability to respond to hypotension posturally.
  • Patients should avoid ethanol, and signs and symptoms of hypotension should also be monitored. Dose escalation should be used to treat these conditions.

• Retroperitoneal and pleural fibrosis

  • It is important to monitor patients for signs and symptoms of fibrosis.
  • Dopamine antagonists generated from ergot have been associated with fibrotic side effects such as retroperitoneal fibrosis, pleural thickening, and cardiac valvulopathy.

• Priapism

  • This can lead to a prolonged erection, which may need medical attention, especially if it lasts longer than four hours.

• Somnolence

  • You should not use it with hypnotic or sedative drugs. It can cause somnolence.
  • Without warning signs, patients may fall asleep.
  • Monitoring patients for sleepiness during the day is important.
  • People who are required to be alert for mental tasks, such as operating heavy machinery, should be aware that the drug is not recommended.

• Cardiovascular disease

  • Hypotension can result, which could cause coronary ischemia.
  • Preexisting coronary artery disease should not be treated with this medication.

• Cerebrovascular disease

  • Hypotension can result, which could cause cerebral ischemia.
  • Preexisting cerebrovascular diseases should not be treated with this medication.

• Dyskinesias

  • This medication can exacerbate dyskinesia that has already been present and should be avoided in such patients.

• Hepatic impairment

  • Patients with liver disease should be cautious.

•   Renal impairment

  • Patients with kidney disease should be cautious.

Apomorphine: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring Parameters:

• Blood pressure, including postural hypotension.
• Before each dose, pulse at 20, 40, 60 and 60 minutes after the last dose.
• Monitor for changes in mental status, drowsiness, or sleepiness.
• Be on the lookout for behavioral changes
• Regular skin examinations are recommended to check for melanoma.

How to administer Apomorphine?

• This product is only for SubQ use. 
• It should not be administered intravenously as it can crystallize, and there is a higher risk of thrombus formation that could lead to pulmonary embolism.
• The anterior abdominal wall, upper arms, and thighs should all be injected. 
• Each time, the injection site should be changed.
• The injection pen can deliver 10 mg (1 ml), of the drug in increments of 0.02 ml (0.25 mg).

Mechanism of action of Apomorphine:

It is found in the caudate-putamen area of the brain, and stimulates postsynaptic D2-type nerves. It is a fast growing industry.

The beginning of actionSubcutaneous administration is recommended. It is subcutaneously administered.

Eliminating half-lifeapproximately 40 minutes, and the time it takes to get therePeak serum concentrationIt takes between 10 and 60 minutes.   

Apomorphine Brand Names (International):

• Apo-Go
• APOgo
• Apofin
• Apokinon
• Apomine
• Apskyn
• Dacepton
• Ixense
• Li Ke Ji
• Movapo
• NOC
• Noc
• Taluvian
• Uprima

Apomorphine brand names in Pakistan:

No brands are available in Pakistan.