Pexola 0.25 Mg 100 Tablets ingredient pramipexole equivalent of mirapex and parcopa

4. CLINICAL FEATURES

4.1. Therapeutic indications

PEXOLA ER extended release tablet is indicated for the treatment of signs and symptoms of idiopathic Parkinson's disease in adults. It can be used alone (without levodopa), or in the course of the disease, when late effects of levodopa have begun to decrease, or when the therapeutic effect fluctuates (fluctuations in the end of dose or on / off), as the effect of the change becomes apparent Available in the form.

4.2. Posology and method of administration

Posology / frequency and duration of administration:

PEXOLA ER is an oral release formulation of pramipexole once daily.

Initial treatment: As

shown below, the dose should be increased incrementally from the initial dose of 0.375 mg salt (0.26 mg base) per day, and the dose increments should be made at intervals of 5-7 days. Dose titration should be performed in such a way that maximum therapeutic effect can be achieved unless undesirable adverse effects are observed in patients.

If the dose is to be increased further, the daily dose should be increased to a dose of 0.75 mg of salt (0.52 mg base) at weekly intervals, to a maximum daily dose of 4.5 mg salt (3.15 mg base). However, it should be kept in mind that the incidence of somnolence increases when the daily doses of 1.5 mg salt (1.05 mg base) are exceeded (see 4.8).

Patients who are currently taking PEXOLA tablets may switch to the PEXOLA ER extended release tablet at the same daily dose starting the following morning. After switching to the PEXOLA ER extended release tablet, the drug dose can be adjusted according to the patient's response to treatment (see 5.1).

Maintenance therapy:

Daily individual doses should be in the range of 0.375 mg salt (0.26 mg base) and a maximum of 4.5 mg salt (3.15 mg base). In pivotal trials, during dose increase, efficacy was observed from 1.5 mg daily salt (1.05 mg base) daily. Further dose adjustments should be made according to clinical response and adverse effects. In clinical trials, approximately 5% of patients were treated with doses lower than 1.5 mg salt (1.05 mg base). In advanced Parkinson's disease, doses higher than 1.5 mg salt (1.05 mg base) daily may be beneficial when the dose of levodopa is planned to be lowered. With the PEXOLA ER, it is recommended to reduce the dose of levodopa during the dose increase and maintenance treatment, according to the patient's reactions (see 4.5).

Forgotten doses:missed

If a dose is missed, the PEXOLA ER extended release tablet should be taken within 12 hours of the time that thedose should be taken. If more than 12 hours have passed, the missed dose should be skipped and the next dose should be used at the next day.

Termination of treatment:

Sudden discontinuation of dopaminergic treatment may lead to the development of neuroleptic malignant syndrome.

Pramipexole daily dose is reduced to 0.75 mg salt (0.52 mg base) per day, down to 0.375 mg salt (0.26 mg base) daily. style (see section 4.4).

Application:

Extended release (ER) tablets should be swallowed as a whole with water, not chewed, broken or crushed. Extended release tablets can be taken with or without food. It should be taken at the same time every day.

Additional information on specific populations:

Renal failure:

Elimination of pramipexole is dependent on renal function. The following dose scheme is recommended: In

patients with creatinine clearance greater than 50 ml / min, it is not necessary to reduce the daily dose or the frequency of dosing.

In patients with creatinine clearance between 30 and 50 ml / min, treatment should be started every day with 0.35 mg of salt (0.26 mg base) PEXOLA ER extended release tablet. After one week, the dose should be cautious before the dose is increased to the daily dose of administration and the therapeutic response and tolerability should be carefully evaluated. If the dose is to be increased further, the daily dose should be increased by weekly doses to a maximum daily dose of 2.25 mg salt (1.57 mg base) with a dosage of 0.375 mg of pramipexole salt (0.26 mg base).

Since there is no data on the treatment of patients with creatinine clearance below 30 ml / min with PEXOLA ER extended release tablet, the use of PEXOLA ER extended release tablets is not recommended in this patient group. PEXOLA tablets should be considered in these patients.

If the kidney function decreases during maintenance therapy, the above recommendations should be followed.

Hepatic impairment: Since

approximately 90% of the absorbed active substance is excreted by the kidneys, dose adjustment in patients with hepatic impairment will probably not be necessary. However, the potential effect of liver failure on PEXOLA pharmacokinetics has not been investigated.

Pediatric population: The

effectiveness and safety of the PEXOLA ER extended release tablet in children under 18 years of age has not been established. The PEXOLA ER extended release tablet has no use in the pediatric population in Parkinson's disease.

The

elimination half-life of the PEXOLA ER extended release tablet is longer in the elderly (see 5.2).

4.3. Contraindications Contraindicated in

case of hypersensitivity to the active substance or to any component of the product (see 6.1).

4.4. Special warnings and precautions for use

A Parkinson's patient with renal failure should be prescribed PEXOLA ER prolonged release tablet while a dose reduction is recommended as described in the section ete Posology and mode of administration EX (see 4.2).

Halüsinasvon with

hallucinations, it is known that a side effect of dopamine agonists or levodopa therapy. Patients should be warned that hallucinations (mostly visual) may occur.

Dyskinesia In

advanced Parkinson's disease, combination therapy with levodopa may cause dyskinesia during initial titration of PEXOLA ER. If dyskinesia occurs, the dose of levodopa should be reduced.

Suddenly falling asleep and somnolence

Pramipexole was associated with somnolence and sudden onset falling asleep, especially in patients with Parkinson's disease. Sudden onset of sleep seizures occurring during daily living activities and in some cases without any symptoms of symptoms have been reported to be uncommon; this may occur in some cases without awareness or without any stimulatory symptoms. Patients should be warned about this issue and it should be advised to be careful during the use of this medicine, especially in the use of vehicles and machines. Patients who experience somnolence and / or sudden sleep seizures should avoid using tools and machinery. It may also be considered to reduce the dose or terminate the treatment. Due to possible additive effects, patients should be cautioned that they should be careful when taking other sedative drugs or alcohol during use of a drug containing prmipeksol (see 4.5, 4.7 and 4.8).

Impulse control

disorder Patients should be regularly monitored for the possibility of developing impulse control disorders. Individuals interested in the care and treatment of patients and patients should be cautioned about the behavioral symptoms of impulse control disorders such as pathological gambling, increased libido, hypersexuality, compulsive spending or shopping, obstructive eating and over-eating in patients treated with dopamine agonists, including PEXOLA. If such symptoms develop, the dose should be reduced or stepped down in steps.

Mania and delirvum

Patients should be monitored regularly for the risk of mania and delirium development. Patients and those who are caring for the patient should be warned that mania and delirium may occur in patients treated with pramipexole. If such symptoms develop, discontinuation of the drug by dose reduction / dose reduction should be considered.

Patients withwith

psychotic disorders Treatment with dopamine agonists in patientspsychotic disorders should only be performed if the potential benefit from treatment is higher than the potential risk. The simultaneous use of pramipexole and antipsychotic drugs should be avoided (see 4.5).

Ophthalmological monitoring In case of

regular or visual abnormalities, ophthalmological monitoring is recommended.

Severe cardiovascular disease

Care should be taken in case of severe cardiovascular disease. Due to the risk of postural hypotension associated with dopaminergic therapy, it is recommended to monitor blood pressure, especially at the beginning of treatment.

Nnrolepthic syndrome With

sudden discontinuation of dopaminergic therapy, symptoms suggestive of neuroleptic malignant syndrome have been reported (see 4.2).

Stool remnants

Some patients have reported residues in their feces that resemble intact PEXOLA ER tablets. If the patient reports such an observation, the doctor should re-evaluate the patient's response to treatment.

4.5. Interactions with other medicinal products and other forms of interaction

Linking to

plasma proteins Pramipexole is bound to plasma proteins at a very low level (<20%) and a low biotransformation is seen in humans. Therefore, interaction with other drugs that affect binding to plasma proteins or which are effective on elimination by biotransformation is not expected. Because anticholinergic drugs are mainly eliminated by biotransformation, the potential for interaction is low. However, the interaction with anticholinergics has not been studied. It does not show a pharmacokinetic interaction with selegiline and levodopa.

Active renal elimination pathway inhibitors / competitors

Cimetidine reduced the renal clearance of pramipexole by about 34%, possibly by inhibiting the cationic secretory transport system in the renal tubules. Thus, drugs such as cimetidine, amantadine, mexiletine, zidovudine, cisplatin, quinine and procainamide, which inhibit or inhibit this active renal elimination pathway, may interact with pramipexole and lead to a decrease in pramipexole clearance. If these drugs are used concurrently with the PEXOLA ER extended release tablet, the reduction of pramipexole dose should be considered.

Combination with levodopa If the

PEXOLA ER extended release tablet is administered concurrently with levodopa, it is recommended to reduce the dose of levodopa and increase the dose of PEXOLA ER prolonged release tablet while keeping doses of other antiparkinsonian drugs constant.

Because of the likelihood of additive effects, patients should be warned to be careful when taking other sedating drugs or alcohol with PEXOLA extended release tablets (see 4.4, 4.7 and 4.8).

Antipsychotic drugs

Antipsychotic drugs should be avoided in combination with pramipexole (see 4.4), in which case antagonistic effects can be expected.

4.6. Pregnancy and lactation

General recommendation

Pregnancy category is C.

Women with childbearing potential / Contraception The

women with childbearing potential should use contraceptive methods that are considered to be medically effective during treatment.

The

effects of pregnancy and lactation on pregnancy are not investigated in humans.

Pramipexole did not show teratogenic effects in rats and rabbits, but showed embryotoxic effects in rats with matemotoxic doses (see 5.3).

PEXOLA ER should not be used unless explicitly necessary during pregnancy, it should be used only if its potential benefits outweigh the potential risk on the fetus.

Lactation An

inhibition of lactation is expected because pramipexole therapy inhibits prolactin secretion in humans. It has not been studied whether pramipexole has passed into milk in women. In rats, the concentration of active substance-associated radioactivity in milk was higher than in plasma.

PEXOLA should not be used during breastfeeding due to lack of data on humans. However, if its use cannot be avoided, breastfeeding should be discontinued.

Fertility

Human fertility has not been studied. Pramipexole influenced oestrus cycles in animal studies and led to a decrease in female fertility as expected from a dopamine agonist. These studies did not show any direct or indirect adverse effects on male fertility.

4.7. Effects ondrive and use machines The

ability toPEXOLA extended release tablet can have major effects on the ability to drive and use machines.

Hallucinations or somnolence may occur.

Patients who are treated with PEXOLA ER and who have somnolence and / or sudden episodes of sleep should avoid cautionary activities, such as driving a car and machine until these problems are eliminated, or be warned that there is a risk of serious injury or death to himself or others, due to impaired eye. (see 4.4, 4.5 and 4.8).

8.4. Undesirable effects

Expected adverse reactions The

following adverse reactions are expected during PEXOLA use; abnormal dreams, amnesia; behavioral symptoms of impulse control disorders and compulsions, such as overeating, compulsive shopping, hypersexuality and pathological gambling; heart failure, confusion, constipation, delirium, delusion, dizziness, dyskinesia, dyspnea, exhaustion, hallucinations, headache, hiccup, hyperkinesia, hyperphagia, hypotension, inappropriate antidiuretic hormone release, insomnia, libido disorders, mania, nausea, paranoia, peripheral edema, pneumonia; itching, rash and other hypersensitivity reactions; restlessness, somnolence, sudden falling asleep, syncope; visual disturbances, including diplopia, blurred vision and decreased visual acuity; Vomiting, decreased appetite, weight loss, weight gain.

Based on the pooled analysis of placebo-controlled studies involving 1,778 patients with Parkinson's disease who received pramipexole therapy and 1,277 patients with placebo, adverse effects were reported frequently in both groups. At least one adverse effect has been reported in 67% of patients receiving pramipexole and 54% of the placebo group.

The adverse drug effects reported below are events that are seen in 0.1% or more of patients treated with pramipexole, and are reported to be clinically important, or have been reported to be clinically significant, in patients receiving pramipexole. The majority of adverse drug reactions are mild to moderate, usually in the early stages of treatment and tend to disappear in the continuation of treatment.

Adverse reactions are reported in the following system-organ classes using the following frequency categories (Number of patients who are expected to have an adverse reaction):

Very common Common

Uncommon Uncommon Rare Very rare Unknown

> 1/10

> 1/100 to <1/10

> 1 / 1,000 to <1/100

> 1 / 10,000 to <1 / 1,000 <1 / 10,000

cannot be estimated with the data in hand.

The most common adverse drug reactions reported as the most common (> 5%) in patients with Parkinson's disease and more common with placebo are the treatment of pramipexole; nausea, dyskinesia, hypotension, dizziness, somnolans, insomnia, constipation, hallucinations, headaches and exhaustion. The incidence of somnolans increases at a dose higher than 1.5 mg pramipexole salt per day (see 4.2). A more commonly reported adverse effect in combination with levodopa is dyskinesia. At the beginning of the treatment, especially if the pramipexole titration is done very quickly, hypotension may occur.

Infections and infestations

Uncommon pneumonia

Endocrine disorders

Uncommon:Inappropriate antidiuretic hormone release1

Psychiatric disorders

Common: Abnormal dreams, impulse control disorders and kompulsiyonl that reflects

behavioral symptoms, confusion, hallucinations, insomnia Uncommon: Tıkanırcas on eatingone,compulsive shopping, delusion , hyperphagia1,

hypersexuality, libido disorders, paranoia, pathological gambling, restlessness delirium Rare: Mania

Nervous system diseases

Very common: dizziness, dyskinesia, somnolence

Common:

Uncommon:

Headache

Amnesia, hyperkinesis, sudden sleep collapse, syncope

Ophthalmology

Common: Diplopia, blurred vision and visualincluding visual

disturbances,impairment

Cardiac diseases:

Uncommon: Cardiac failure1