Produodopa

/ AbbVie

This medical product is administered as a continuous subcutaneous infusion, 24 hours per day.
The recommended starting infusion rate is determined by converting the daytime levodopa intake to levodopa equivalents (LE) and then increasing it to account for a 24-hour administration. The maximum recommended daily dose of foslevodopa is 6000 mg (or 25 ml of this medical product per day equivalent to approximately 4260 mg levodopa per day).

Treatment of advanced levodopa-responsive Parkinson’s disease with severe motor fluctuations and hyperkinesia or dyskinesia when available combinations of Parkinson medicinal products have not given satisfactory results.

* Hypersensitivity to the active substances or to any of the excipients
* Narrow-angle glaucoma
* Severe heart failure
* Acute stroke
* Severe cardiac arrhythmia
* Non-selective MAO inhibitors and selective MAO type A inhibitors are contraindicated for use. These inhibitors must be discontinued at least two weeks prior to initiating therapy with this medical product. It may be administered concomitantly with selectivity for MAO type B.
* Conditions in which medication with adrenergic activity are contraindicated, e.g., pheochromocytoma, hyperthyroidism and Cushing’s syndrome.
* Should not be used in patients with suspicious undiagnosed skin lesions or a history of melanoma.

* As treatment of drug-induced extrapyramidal reactions.
* Severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic, or endocrine disease, or history of peptic ulcer disease or of convulsions, caution is required.
* History of myocardial infarction who have residual atrial nodal or ventricular arrhythmias, cardiac function should be monitored with particular care during the period of initial dosage adjustments.
* All patients should be monitored carefully for the development of mental changes, depression with suicidal tendencies, and other serious mental changes. Patients with past or current psychosis should be treated with caution. Higher frequency of hallucinations can occur in patients treated with dopamine agonists and/or other dopaminergic treatments containing levodopa. Review of treatment is recommended if such symptoms develop.
* Concomitant administration of antipsychotics with dopamine receptor-blocking properties, particularly D2 receptor antagonists, should be carried out with caution, and the patient should be carefully observed for loss of antiparkinsonian effect or worsening of parkinsonian symptoms
* Patients with chronic wide-angle glaucoma may be treated with caution, provided the intra-ocular pressure is well controlled and the patient is monitored carefully for changes in intra-ocular pressure during therapy.
* This medical product may induce orthostatic hypotension. Therefore, it should be given cautiously to patients who are taking other medicinal products which may cause orthostatic hypotension
* Levodopa has been associated with somnolence and episodes of sudden sleep onset in patients with Parkinson’s disease, and caution should, therefore, be exercised when driving and operating machines.
* Patients should be regularly monitored for the development of impulse control disorders. Patients and carers should be made aware that behavioural symptoms of impulse control disorders including pathologic gambling, increased libido and hypersexuality, compulsive spending or buying, binge-eating and compulsive-eating can occur in patients treated with dopamine agonists and/or other dopaminergic treatments containing levodopa. Review of treatment is recommended if such symptoms develop.
* Monitor for melanomas on a regular basis
* Dopamine Dysregulation Syndrome (DDS) is an addictive disorder resulting in excessive use of the product seen in some patients treated with levodopa/carbidopa. Before initiation of treatment, patients and caregivers should be warned of the potential risk of developing DDS.
* The dose may need to be adjusted downwards in order to avoid levodopa induced dyskinesias.
* Periodic evaluation of hepatic, haematopoietic, cardiovascular and renal function is recommended during extended therapy
* This medical product contains hydrazine, a degradation product of foscarbidopa, that can be genotoxic and probably carcinogenic. This includes hydrazine at up to a median exposure of 0.2 mg/day, with a maximum of 0.5 mg/day. The clinical significance of this hydrazine exposure is not known.
* Reduced ability to handle the delivery system can lead to complications.
* A sudden or gradual worsening of bradykinesia may indicate an obstruction in the device for whatever reason and needs to be explored.
* Polyneuropathy has been reported in patients treated with levodopa/carbidopa-containing products. Before starting therapy evaluate patients for history or signs of polyneuropathy and known risk factors, and periodically thereafter.
* Infusion site events, following aseptic techniques while using this medication and frequent rotation of the infusion site are recommended to reduce the risk.
See prescribing information for full details.

The most frequent adverse reactions (≥10%) were infusion site events (infusion site erythema, infusion site nodule, infusion site cellulitis, infusion site oedema, infusion site pain, and infusion site reaction), hallucination, fall, anxiety, and dizziness.
Very common: Infusion site abscess, Infusion site cellulitis, Anxiety, Hallucination, Dizziness, Infusion site erythema, Infusion site reaction, Infusion site nodule, Infusion site oedema ,Infusion site pain, Fall.
Common: Infusion site infection, Anaemia, Decreased appetite, Abnormal dreams, Agitation, Confusional state, Delusion, Depression, Impulse control disorder, Insomnia, Psychotic disorder, Sleep attacks, Sleep disorder, Suicidal ideation, Cognitive disorder, Dizziness postural, Dyskinesia, Dystonia, Headache, Hypoaesthesia, On and off phenomenon, Paraesthesia, Polyneuropathy, Somnolence, Syncope, Tremor, Heart rate irregular, Hypertension, Hypotension, Orthostatic hypotension, Dyspnoea, Abdominal distension, Abdominal pain, Constipation, Diarrhoea, Dry mouth, Dysgeusia, Dyspepsia, Dysphagia, Flatulence, Nausea, Vomiting, Dermatitis contact, Hyperhidrosis, Pruritus, Rash, Muscle spasms, Urinary incontinence, Urinary retention, Asthenia, Fatigue, Infusion site bruising, Infusion site exfoliation, Infusion site extravasation, Infusion site haematoma, Infusion site haemorrhage, Infusion site induration, Infusion site inflammation, Infusion site irritation, Infusion site mass, Infusion site papule, Infusion site pruritus, Infusion site rash, Infusion site swelling, Malaise, Oedema peripheral, Pain, Vitamin B6 decreased
Weight decreased.
See prescribing information for full details

No interaction studies have been performed with this medical product. The following interactions are known from the generic combination of levodopa/carbidopa.
Antihypertensives
Symptomatic postural hypotension has occurred when combinations of levodopa and a decarboxylase inhibitor are added to the treatment of patients already receiving anti-hypertensives. Dosage adjustment of the antihypertensive agent may be required.
COMT inhibitors (e.g., tolcapone, entacapone, opicapone)
Concomitant use of COMT (catechol-O-methyl transferase) inhibitors can increase the bioavailability of levodopa. The dose of this medical product may need to be adjusted.
Other medicinal products
* Dopamine receptor antagonists (some antipsychotics, e.g., phenothiazines, butyrophenones and risperidone and antiemetics, e.g., metoclopramide), benzodiazepines, isoniazid, phenytoin and papaverine can reduce the therapeutic effect of levodopa. Patients taking these medicinal products together with this medical product should be observed carefully for loss of therapeutic response.
* MAO inhibitors are contraindicated, with the exception of MAO-B selective inhibitors. The dose of this medical product may need to be reduced when a MAO inhibitor selective for type B is added.
* Concomitant use of selegiline and levodopa/carbidopa has been associated with serious orthostatic hypotension.
* Amantadine has synergistic effect with levodopa and may increase levodopa related adverse events. An adjustment of the dose of this medical product may be needed.
* Sympathomimetics (e.g., adrenergic drugs not limited to – salbutamol, phenylephrine, isoproterenol, dobutamine) may increase cardiovascular adverse events related to levodopa.
* Foscarbidopa has been identified as a potential inducer of CYP1A2 in vitro. Care should be taken when prescribing this medical product in combination with sensitive CYP1A2 substrates (e.g., fluvoxamine, clozapine, caffeine, theophylline, duloxetine and melatonin). No clinical DDI studies have been conducted to assess the clinical relevance of this finding.
See prescribing information for full details.

Pregnancy: There are no data from the use of this medical product in pregnant women. Studies of levodopa and carbidopa in animals have shown reproduction toxicity.
Lactation: Levodopa and possibly levodopa metabolites are excreted in human milk. There is evidence that lactation is suppressed during treatment with levodopa.

In the event of an overdosage, the infusion should be stopped immediately. The treatment of an acute overdose is the same as that of an acute overdose of levodopa; however, pyridoxine has no effect on the reversal of the action of this medical product. Electrocardiographic monitoring should be used, and the patient observed carefully for the development of cardiac arrhythmias; if necessary, an appropriate antiarrhythmic therapy should be given. Patients must also be monitored for hypotension. The possibility that the patient took other medicinal products should be taken into consideration.

It has a major influence on the ability to drive and use machines. Levodopa and carbidopa may cause dizziness and orthostatic hypotension. Therefore, caution should be exercised when driving or using machines. Patients presenting with somnolence and/or sudden sleep episodes must be advised to refrain from driving or engaging in activities where impaired alertness may put them, or others.