LECIGON

6). The dose should be titrated to achieve the optimal clinical response in the individual patient, which involves maximising the functional ON-time during the day by minimising the number and duration of OFF episodes (bradykinesia) and minimising ON-time with disabling dyskinesia.

The total dose/day of Lecigon is composed of three individually adjusted doses: the morning bolus dose, the continuous maintenance dose, and extra bolus doses. Treatment is usually limited to the patient's awake period. If medically justified, Lecigon can be administered up to 24 hours/day.

4). During the maintenance dose, the plasma concentration/time profile of levodopa has a somewhat different appearance, with a gradually increasing levodopa concentration in plasma over the course of the day, than previously observed from intestinal gel with levodopa/carbidopa alone.

2. If individual needs exist, the pump can be preprogrammed to provide up to three maintenance doses over the course of the day/24-hour period. In case of dyskinesias in the latter part of the day, reductions of 10–20% during the middle of the day may be relevant.

All maintenance doses should be titrated until the desired clinical effect is reached. The multiple maintenance dose function may also be useful, for example, in patients with persistent dyskinesias or stiffness with recurring need of extra doses in the latter part of the day, or for patients with 24-hour treatment who need a reduction of the maintenance dose during the night.

Morning dose The morning dose is administered by the pump to rapidly achieve the therapeutic dose level (within 30 minutes). 1 ml (2 mg). The total morning dose is usually 5–10 ml, corresponding to 100–200 mg levodopa. The total morning dose should not exceed 15 ml (300 mg levodopa).

Continuous maintenance dose The continuous maintenance dose is administered by the pump to maintain the therapeutic dose level. 1 ml/hour). 0 ml/hour (15–100 mg levodopa/hour). The maximum recommended daily dose is 100 ml (2000 mg levodopa).

Extra bolus doses Extra doses are given as required if the patient becomes hypokinetic. The extra dose is normally less than 3 ml but is adjusted individually. An increase in the continuous maintenance dose should be considered if the need for extra doses exceeds 5 doses per day.

Titration during transition from levodopa/carbidopa to Lecigon Lecigon contains entacapone, which enhances the effect of levodopa. It may therefore be necessary to reduce the total daily intake of Lecigon by, on average, 20–35% compared to the patient's previous dose of levodopa and carbidopa without catechol- O-methyl transferase (COMT) inhibitors.

Because the effect of entacapone on levodopa is dose dependent, a larger dose reduction is expected in high-dose patients. The initial dose setting is based on the patient's daily levodopa intake. The size of the morning dose should be the same as the previous levodopa morning intake, to reach a therapeutic plasma concentration as quickly as possible, plus the volume required to fill the tube.

The continuous maintenance dose should be based on the patient's daily levodopa intake (excluding the morning dose) and initially reduced to 65% of the previous daily levodopa intake. The doses are then titrated gradually, based on clinical symptoms, until the desired effect is achieved.

6 ml/hour Titration during transition from levodopa/benserazide to Lecigon Entacapone increases the bioavailability of levodopa from standard preparations of levodopa/benserazide slightly more (5–10%) than from standard preparations of levodopa/carbidopa.

The transition from levodopa/benserazide to Lecigon has not been studied. Titration during transition from levodopa/carbidopa/entacapone to Lecigon The initial dose setting is based on the patient's daily levodopa intake. The initial size of the morning dose should be the same as the previous levodopa morning intake plus the volume required to fill the tube.

The continuous maintenance dose is converted 1:1 and is based on the patient's daily levodopa intake (excluding the morning dose). The doses are then titrated gradually, based on clinical symptoms, until the desired effect is achieved.

Transition from combination therapy with levodopa/DDC inhibitor/tolcapone to Lecigon has not been studied. Transition from dopamine agonist therapy to Lecigon When transitioning from dopamine agonist therapy to Lecigon monotherapy, the risk of dopamine agonist withdrawal symptoms should be taken into consideration and abrupt dopamine agonist discontinuation should be avoided.

Monitoring of treatment After initial titration, the morning dose and maintenance dose are fine-tuned over the course of a few weeks. Lecigon is initially given as monotherapy. 3 and […]

Summary of the safety profile The expected safety profile for Lecigon is based on available data from clinical trials and post-marketing experience of levodopa/carbidopa intestinal gel and oral levodopa/carbidopa/entacapone. Drug-related undesirable effects that occur frequently with levodopa/carbidopa intestinal gel and could therefore occur with Lecigon include nausea and dyskinesia.

Device and procedure-related undesirable effects that occur frequently with levodopa/carbidopa intestinal gel and could therefore occur with Lecigon include abdominal pain, complications of tube insertion, excessive granulation tissue, incision site erythema, postoperative wound infection, post-procedural discharge, procedure- related pain, and incision site reaction.

Most of these adverse reactions were reported early in the studies, subsequent to the percutaneous endoscopic gastrostomy procedure, and occurred during the first 28 days. The most commonly reported adverse reactions with oral levodopa/carbidopa/entacapone are dyskinesias (affecting approximately 19% of patients); gastrointestinal symptoms including nausea and diarrhoea (affecting approximately 15% and 12% of patients respectively); muscle and connective tissue disorders (affecting approximately 12% of patients); and harmless maroon discolouration of urine (chromaturia) (affecting approximately 10% of patients).

Serious adverse reactions for gastrointestinal haemorrhage (uncommon) and angioedema (rare) have been identified from clinical trials with oral levodopa/carbidopa/entacapone or entacapone in combination with levodopa/DDC inhibitor.

Serious hepatitis with mainly cholestatic elements, rhabdomyolysis and neuroleptic malignant syndrome may occur with oral levodopa/carbidopa/entacapone, although no case has been identified from clinical trials. A pharmacokinetic study with Lecigon that included 11 patients with advanced Parkinson's disease was performed.

Adverse reactions considered to be associated with Lecigon were headache, nausea and dizziness. No serious adverse reactions were reported in this 2-day study. No adverse reactions were considered to be associated with the pump during administration of Lecigon.

Table of adverse reactions Adverse reactions related to the medicinal product, device and procedure-related adverse reactions observed in clinical trials and during post-marketing use of levodopa/carbidopa intestinal gel and oral levodopa/carbidopa/entacapone are summarised in Table 1 below by system organ class and frequency.

For oral levodopa/carbidopa/entacapone, the adverse reactions listed in Table 1 have been compiled from double-blind clinical trials and data collected during post- marketing use of entacapone for combination therapy with levodopa/DDC inhibitor.

Table 1. Adverse reactions from clinical trials and post-marketing experience of levodopa/carbidopa intestinal gel and/or oral levodopa/carbidopa/entacapone. g. g. 3) Angioedema Musculoskeleta l and connective tissue disorders Pain in muscles and tissues, and musculoskel etal pain Arthralgia, Muscle spasms, Neck pain Rhabdomyolysi s Renal and urinary disorders Chromaturia Urinary incontinence, Urinary retention- Reproductive system and breast disorders Priapism General […]

4. If treatment is discontinued, the patient should receive an alternative treatment. Method of administration Lecigon is a gel for continuous intestinal delivery (delivery to the duodenum or upper jejunum). Only pump Crono LECIG (CE 0476) may be used for the administration of Lecigon.

A manual with instructions for using the portable pump is supplied with the pump. A temporary nasoduodenal/nasojejunal tube should be considered to determine if the patient responds favourably to this method of treatment before a permanent percutaneous endoscopic gastrostomy with jejunal tube (PEG-J) is placed.

In cases where the physician considers this assessment is not necessary, the nasojejunal test phase may be waived and treatment initiated directly with placement of the PEG-J. For long-term administration, the gel should be administered with a portable pump directly into the duodenum or upper jejunum by a permanent tube via percutaneous endoscopic gastrostomy with an outer transabdominal tube and an inner intestinal tube.

Alternatively, a radiological gastrojejunostomy may be considered if percutaneous endoscopic gastrostomy is not suitable for any reason. The surgery and dose adjustment should be carried out in association with a neurological clinic.

Cartridge replacement In order to use a new cartridge, it should be attached to the portable pump and the system connected to the tube for administration, according to the instructions given. The cartridge is for single use only and should not be used for more than 24 hours.

The dosing pump with installed cartridge can be worn close to the body for up to 16 hours. During overnight treatment, the pump should not be worn next to the body but can, for example, be kept on the bedside table. e. up to 24 hours after it was first opened.

The cartridge is removed from the pump after 24 hours of use or when used up, whichever occurs first. The gel may become slightly yellow/reddish by the end of the shelf life. This does not influence the concentration of the medicine or the effect of treatment.

1. • Narrow-angle glaucoma. • Severe heart failure. • Severe cardiac arrhythmia. • Acute stroke. • Severe hepatic impairment. • Administration of non-selective MAO inhibitors and selective MAO type A inhibitors are contraindicated for use with Lecigon.

These inhibitors must be discontinued at least two weeks prior to initiating therapy with Lecigon. g. 5). g. pheochromocytoma, hyperthyroidism and Cushing's syndrome. • Previous neuroleptic malignant syndrome (NMS) and/or non-traumatic rhabdomyolysis.

• Suspected undiagnosed skin lesions or a history of melanoma (levodopa could activate malignant melanoma). 4 Special warnings and precautions for use Lecigon is not recommended for the treatment of drug-induced extrapyramidal reactions.

Lecigon should be administered with caution to patients with ischaemic heart disease, severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease, or history of peptic ulcer disease or of convulsions.

In patients with a 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 treated with Lecigon 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. Concomitant administration of antipsychotics with dopamine receptor blocking properties, particularly D2 receptor antagonists, should be carried out with caution, and the patient carefully observed for loss of antiparkinsonian effect or worsening of parkinsonian symptoms; see section

3. Renal impairment The dosage of Lecigon is individually adjusted by titration to the dose that provides optimal effect (which corresponds to individually optimised plasma exposure to levodopa, carbidopa and entacapone). Thus, any effects of renal impairment on levodopa, carbidopa and entacapone exposure are taken into account in the dose titration.

Renal impairment does not affect the pharmacokinetics of entacapone. There are no specific pharmacokinetic studies of levodopa and carbidopa in patients with renal impairment. 2). Interruption of therapy Treatment with Lecigon can be interrupted at any time by removing the tube and allowing the wound to heal.

Patients should be carefully observed in case a sudden reduction of the dose is required or if it becomes necessary to discontinue treatment with Lecigon, particularly if the patient is receiving antipsychotics; see section