Apomorphine For Parkinson’s Disease

Injection Sites Can Become Sore And Irritated

The areas of skin where the needle goes in can become sore. This can happen when a pump is used. Youll need to change where you put the needle each day to reduce the risk of this happening.

Lumps might appear under the skin where the needle is inserted, but these can be treated using ultrasound. You can prevent them by making sure the place where the needle is inserted is clean, changing the injection site every day, and gently rubbing your skin once youve taken the needle out.

One advantage of a pen is that it’s less likely to irritate your skin than a continuous infusion using a pump. This is because you can change where you inject each time.

Clinical Outcomes And Adverse Events

Gamma knife thalamotomy has been shown to improve motor function in patients with PD. The radiation dose used in GK thalamotomy ranges from 120 to 180Gy, and it appears that doses less than 120Gy do not provide clinical benefits . In a prospective study of unilateral gamma knife thalamotomy for patients with PD and essential tremor , Ohye et al. reported an improvement in tremor scores , with 81.1% of patients evaluated as having good or excellent results at 24-month follow-up . A more recent prospective, single-blind study of unilateral GK thalamotomy for patients PD and ET reported a 54.2% improvement in the upper limb tremor score . GK pallidotomy has also been performed to treat PD, although only a few reports have described the procedure . The GPi is considered a high-risk target for GK radiosurgery due to its proximity to the optic tract and the risk of optic neuropathy . Likewise, the STN is not an advised target due to the risk of neurologic complications including hemiparesis, dysarthria, and gait disturbances .

Parkinson’s Diseaseinfusion Pump And Apomorphine Therapy

The disease is named after James Parkinson, a 19th century London surgeon, who was the first to describe its symptoms in a book: âA Treatise on Agitating Paralysisâ. Parkinson’s disease is characterised by the slow but progressive degeneration of the nerve structures that make up the extrapyramidal system.

The first symptoms of Parkinson’s disease emerge when the production of dopamine is considerably reduced, and the main motor disorders are characterised by: tremor at rest, stiffness, slow movement and balance.

Parkinson’s disease generally affects individuals over the age of fifty, the causes of which are not yet fully known.

Currently, there is no cure to completely recover from Parkinson’s disease, but there are treatments to improve the quality of life of those living with this disease. Attack therapy for the treatment of Parkinson’s disease aims to replace dopamine through the administration of levodopa or oral dopamine agonists. While it is true that oral therapy for the treatment of Parkinson’s disease can significantly improve the clinical characteristics for several years, up to 80% of patients develop complications to the motor response, characterised by motor fluctuations such as an end-of-dose effect and dyskinesias.

Subcutaneous administration of apomorphine, using a portable infusion pump, has been shown to be effective in controlling the complications of the disease.

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How To Store Apomorphine

• Keep all medicines out of the reach and sight of children.
• Store in a cool, dry place, away from direct heat and light.
• Each APO-go® Pen can be used for up to 48 hours. Do not use any ‘opened’ pens after this time.
• Discard your used pens, syringes or needles in a ‘sharps bin’ after use and arrange for safe disposal. Speak with your doctor or pharmacist for advice on local disposal schemes.

Clinical Outcomes And Adverse Events Of Rf

Ventral intermediate

Ablation of the ventral intermediate nucleus of the thalamus has been shown to significantly improve tremors in patients with tremor-dominant Parkinson’s disease . A retrospective study by Jankovic et al. demonstrated that 86% of patients with PD experienced moderate to complete tremor improvement at a mean follow-up of 53 months . Most AEs with RF thalamotomy are transient and due to the perilesional edema that resolves with time. However, persistent adverse effects may occur, including ataxia, gait disturbances, dysarthria, and motor/sensory deficits . While RF thalamotomy can be performed bilaterally, the risk of dysarthria is significantly higher with bilateral lesions, so the procedure is generally only performed unilaterally .

Globus pallidus internus

Subthalamic nucleus

Ablation of the subthalamic nucleus has been explored for treating the motor symptoms of PD. A 43%52% improvement in off-medication UPDRS-III scores has been reported in more recent trials of RF subthalamotomy. Adverse effects include contralateral dyskinesias and transient hemiballism .

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Conventional Oral Treatment Vs Apomorphine

The quality of the response to oral levodopa is indistinguishable from the quality of the response to apomorphine1111. Hagell P Odin P. Apomorphine in Parkinson’s disease. 3rd ed. Bremen: UNI-MED 2014.,1616. Lees AJ. Dopamine agonists in Parkinson’s disease: a look at apomorphine. Fundam Clin Pharmacol. 1993 7:121-8. https://doi.org/10.1111/j.1472-8206.1993.tb00226.x. Apomorphine, however, produces a shorter motor response, supporting the idea that the integrity of the postsynaptic receptors is the key factor that determines the dopamine response in Parkinson’s disease treatment. In other words, the clinical responses to the drugs are the same although they have different mechanisms of action1111. Hagell P Odin P. Apomorphine in Parkinson’s disease. 3rd ed. Bremen: UNI-MED 2014.,1616. Lees AJ. Dopamine agonists in Parkinson’s disease: a look at apomorphine. Fundam Clin Pharmacol. 1993 7:121-8. https://doi.org/10.1111/j.1472-8206.1993.tb00226.x.

When Is Apomorphine Used

Apomorphine is usually used for more advanced Parkinson’s when other treatments no longer work well to control Parkinson’s symptoms on their own. It is used if you have sudden and unpredictable changes in your symptoms or have severe off periods.

On/off refers to movement fluctuations, usually caused by levodopa medication becoming less effective before the next dose is due. On is when your symptoms are controlled and when you feel at your most capable. Being off is when your Parkinsons symptoms recur and affect you the most.

Apomorphine is often prescribed with other medicines such as levodopa to help it work better. Apomorphine works within 510 minutes, which means it can act as a rescue treatment if your other medicines havent taken effect. The effects of apomorphine generally wear off after 40 minutes, but by this time your other medicines may have started to work.

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Patient Considerations For Dbs

The nonlesional and adjustable nature of DBS is among the advantages offered over other methods for neuromodulation . While many advantages exist, several patient-specific and ethical considerations must also be examined. DBS is a minimally invasive surgery with low incidences of infection and symptomatic hemorrhage. Additionally, DBS incurs large capital costs and requires a multidisciplinary expert team to provide optimal programming and troubleshooting for the patient. DBS can also be problematic for some in that it commits patients to a lifelong implant requiring subsequent battery changes . However, due to advancing technology, battery life continues to increase and patients have the option of a rechargeable battery, thus decreasing the number of battery replacement surgeries. Patients who travel far to receive DBS surgery also now have the option to have DBS programmed remotely . Ideal PD candidates for DBS are those with motor fluctuations and/or TSD without having other red flags for an alternative diagnosis. Patients with neuropsychiatric issues and multiple comorbidities may be poor candidates. Many centers exclude patients older than 70 years from DBS surgeries, although an age limit for DBS has not been defined .

Is Injection Or Infusion Right For Me

No one method is right for everyone. Your choice will depend on:

• how often you need to take apomorphine
• how well you can use your hands
• whether you have anyone to help you if you need it

For each option, the dose can be adjusted to suit you. Talk to your specialist or Parkinsons nurse about what might be best for you.

Yes. Because apomorphine has to be taken by injection or infusion, you and your family member or carer will learn how to do this.

You will usually start apomorphine in hospital. This will mean a Parkinson’s nurse or specialist will be able to check you’re not experiencing any problems. It can take one day or a few days to do this. You can also be trained at home in some cases.

If you, your carer or family member are unable to insert the needle or set up the equipment, a district nurse may be able to come daily to do this. They can set up the infusion in the morning and then come back in the evening to take it out. Or, the device so it can be left in and removed by the nurse the next day.

Britannia and EVER Pharma, the companies that make apomorphine products, have specially trained apomorphine nurses who can also start you on treatment. They are registered nurses with specialist experience in apomorphine injections and infusions, as well as the general management of Parkinsons. Apomorphine nurses can support you with home visits and telephone contact if you need it.

Try not to spill the drug as it can leave a blue or green stain on your clothes.

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Continuous Subcutaneous Apomorphine Infusion

Apomorphine is a dopamine agonist with a mixed affinity for D1 and D2 receptors and an affinity for serotonergic and alpha-adrenergic receptors . While the motor efficacy of apomorphine is similar to that of levodopa, apomorphine cannot be administered orally due to its low oral bioavailability . Subcutaneous infusions have a similar pharmacokinetic profile to the intravenous route. Compared with intermittent subcutaneous injections, CSAI has a longer apparent plasma half-life and simulates the physiological stimulation of striatal neurons .

Clinical outcomes of CSAI

In the OPTIPUMP cohort study, the efficacy and safety of CSAI were assessed. The total UPDRS score showed significant improvement in all patients at 6 months. UPDRS-III decreased in the on-medication state by 16.3% . In the first prospective, randomized, placebo-controlled trial to investigate the efficacy and safety of apomorphine subcutaneous infusion in PD patients, a daily off time reduction of 1.89h from a baseline of 6.69h was seen in treated patients, while there was an increase of 1.97h in on time without TSD from a baseline of 8.52h . In a retrospective study, 230 patients were treated with CSAI over 10 years. In this cohort, the daily off hours were reduced from 5.4 to 1.2h .

Safety of CSAI

Patient considerations for CSAI

What Are The Symptoms Of End

In addition to needing help with daily tasks, symptoms of stage 5 Parkinsons include:

• Inability to rise from sitting or lying down without assistance
• Inability to walk or stand due to leg stiffness or freezing
• Possible hallucinations and/or delusions

People with end-stage Parkinsons can have a variety of severe motor and nonmotor symptoms including:

• Personality changes

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Apomorphine Injection May Cause Side Effects Tell Your Doctor If Any Of These Symptoms Are Severe Or Do Not Go Away:

• painful erection that does not go away
• tiredness, chest pain, shortness of breath

Some laboratory animals that were given apomorphine injection developed eye disease. It is not known if apomorphine injection increases the risk of eye disease in humans. Talk to your doctor about the risks of using this medication.

Apomorphine may cause other side effects. Call your doctor if you have any unusual problems while using this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration’s MedWatch Adverse Event Reporting program online or by phone .

How To Use Apomorphine

• Always use apomorphine exactly as your doctor tells you to. It is only available as an injection.
• Treatment with apomorphine will be started while you are in hospital or in a specialist clinic. This is because you will need to be supervised closely at first. Your doctor or nurse will administer apomorphine for you to begin with. You will then be taught how to inject apomorphine yourself. It is injected under the skin on your lower abdomen or on the outer part of a thigh, as soon as you begin to feel an ‘off’ episode.
• Your doctor will tell you how much to use for each injection, and how often to give the injections. It is usual to use 3-30 mg daily, divided into several doses. The maximum dose per injection will be 10 mg, and the maximum dose in any 24-hour period will be 100 mg.
• Before you use an injection, check to make sure that the liquid is clear and doesn’t contain any floating ‘bits’. Do not use the injection if the solution is cloudy, contains particles or has turned a green colour.

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Efficacy Of Intermittent Apomorphine Injections

Chronic treatment of PD with levodopa is compromised by the development of motor fluctuations despite optimized oral dopaminergic therapy . This lack of a stable response to therapy has a significant negative impact on quality of life because of the many motor and non-motor disabilities associated with the off state and reduced autonomy in planning activities because of the unpredictability of off phases. A large observational study in 1000 patients with PD experiencing off episodes despite best medical management showed that they had to live with an average of 23 h of off time per day .

Numerous studies have assessed the efficacy of apomorphine injections in patients with PD with fluctuations .2). These studies consistently reported a marked reduction in the number of daily off periods and other off-related phenomena such as early morning dystonia, urinary disfunction and pain.

Alternative Apomorphine Delivery Strategies

To date, the main administration route for apomorphine in PD has been subcutaneous, either as a continuous infusion or as an intermittent pen injection. This route has proven effective, but skin reactions are among the most common adverse events and can complicate treatment or lead to withdrawal. For some patients, this delivery may also be problematic because of needle phobia for others, the pen injection may prove challenging for resolving an acute off phase because of bradykinesia and tremor. Despite its remarkable efficacy, apomorphine suffers from the lack of an easier and less invasive delivery system. Several alternative delivery routes have therefore been tested, and some are in active clinical development.

Oral apomorphine is considered infeasible because of the almost complete first-pass hepatic metabolism of the molecule . However, the administration of apomorphine and its prodrug via oral lipid-based formulations has recently been reported in animal models of PD. This formulation is still in the preclinical phase but may have the potential to achieve steady dopaminergic stimulation because of its sustained drug release .

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Patient Considerations For Srs

A major benefit of GK radiosurgery is that it allows for precise intracranial treatment without cranial opening, eliminating the surgical risk of hemorrhage as it does not require the creation of burr holes or puncturing of brain tissue. A major drawback to GK radiosurgery for treating movement disorders is that there are often significant delays before any symptom improvement is appreciated. In previous reports, a delay of 36 months was noted prior to the onset of tremor suppression . Additionally, the radiation response after GK radiosurgery can be variable. Approximately 10% of patients exhibited excess reactions, demonstrated by a high signal zone in the thalamus and surrounding area on MR images, even when the administered radiation dose was uniform . The delayed effect, exposure to ionizing radiation, and lack of intraoperative feedback are all disadvantages that must be considered when utilizing GK radiosurgery as a treatment for advanced PD . GK radiosurgery remains a good option for patients with significant medical comorbidities who cannot undergo more invasive procedures like DBS or RF .

Can Apomorphine Cause Problems

Along with their useful effects, most medicines can cause unwanted side-effects although not everyone experiences them. The table below contains some of the most common ones associated with apomorphine. You will find a full list in the manufacturer’s information leaflet supplied with your medicine. The unwanted effects often improve as your body adjusts to the new medicine, but speak with your doctor or pharmacist if any of the following continue or become troublesome.

Important: speak with your doctor as soon as possible if you notice any of the following:

• Changes in your behaviour, such as a desire to gamble or an increased sex drive.
• Falling asleep suddenly.

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What Are The Ingredients In Apomorphine

Active ingredient: apomorphine hydrochloride, USP

Inactive ingredients:

Apomorphine injection : sodium metabisulfite, NF, benzyl alcohol, NF, water for injection, USP. It may also contain sodium hydroxide, NF and/or hydrochloric acid, NF.

Apomorphine sublingual film : disodium EDTA dihydrate, FD& C Blue #1, glycerol, glyceryl monostearate, hydroxyethyl cellulose, hydroxypropyl cellulose, maltodextrin, -menthol, pyridoxine hydrochloride, sodium hydroxide, sodium metabisulfite, sucralose, and white ink.

Apomorphine injection is distributed under the brand name Apokyn by MDD US Operations, LLC, Rockville, MD 20850. TruPharmac, LLC also produces a generic version of apomorphine injection

Apomorphine sublingual film is manufactured under the brand name Kynmobi for Sunovion Pharmaceuticals Inc. Marlborough, Massachusetts 01752 USA.

Apomorphine In Parkinsons Disease: Practical Considerations

CSAI is administered via a portable pump system that delivers a continuous dose, with the possibility of releasing a rescue bolus if needed. The duration of infusion is normally 1216 h , but a 24-h regimen can also be programmed for patients experiencing nocturnal hypokinesia . Patients with PD who have off periods no longer controlled with optimized oral therapy or who need apomorphine rescue doses too frequently are suitable candidates for CSAI. The pump can also be an alternative to surgical therapy or to enteral levodopa infusion . For patients starting CSAI in the inpatient setting, domperidone 10 mg three times daily from 1 day before initiation to 37 days in total is strongly recommended to prevent nausea . On the first day, apomorphine treatment is started at a dose of 0.5 or 1 mg/h. Uptitration is usually with 0.5 or 1 mg/h daily increments, and the optimal infusion rate ranges from 4 to 7 mg/h for most patients. Concomitantly, oral dopamine agonists and other antiparkinsonian drugs are gradually discontinued. During the titration phase, levodopa is also usually reduced, and discontinued if possible in patients with dyskinesia . The same uptitration protocol should be used for outpatients but with a slower increase in infusion rates.

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