Index of drugs

Symptomatic treatment of mild to moderately severe Alzheimer's dementia. Symptomatic treatment of mild to moderately severe dementia in patients with idiopathic Parkinson's disease.

1 kaps or 1 tabl. orally disintegrating contains 1.5 mg, 3 mg, 4.5 mg or 6 mg of rivastigmine in the form of hydrogen tartrate. Table. those that disintegrate in the mouth contain sorbitol.

Rivastigmine is an inhibitor of acetyl- and butyrylcholinesterase from the group of carbamates, facilitating cholinergic neurotransmission, by slowing down the process of acetylcholine decomposition released by functionally efficient cholinergic neurons. Thus, rivastigmine may have a positive effect on cognitive deficits related to cognitive processes in patients with dementia associated with Alzheimer's disease and Parkinson's disease. Rivastigmine exerts an inhibitory action against cholinesterases, forming a complex with them by means of a covalent linkage, which causes their inactivation temporarily. Rivastigmine is absorbed quickly and completely, reaching a peak plasma concentration after about 1 hour. Due to the effect of rivastigmine on its target enzyme, the increase in bioavailability is about 1.5 times higher than would result from increased dose. The absolute bioavailability at a dose of 3 mg is approximately 36% ± 13%. Administration of rivastigmine with food delays the absorption of the drug by 90 minutes, decreases the C value_max and increases the AUC by approximately 30%. Rivastigmine is associated with proteins in approximately 40%. It easily penetrates the blood-brain barrier. It is rapidly and extensively metabolised (T._0,5 in the plasma is about 1 hour) mainly in the hydrolysis, by means of cholinesterase, to the decarbamylated metabolite. The resulting metabolite shows in vitroonly a small inhibitory activity against acetylcholinesterase (<10%). researchin vitro and animal studies have shown that the major cytochrome P450 isoenzymes play only a minor role in rivastigmine metabolism. No unchanged rivastigmine was found in the urine. Excretion of metabolites in urine is the main route of elimination. Fewer than 1% of the administered dose is excreted in the faeces. No accumulation of rivastigmine or its major metabolite was found in patients with Alzheimer's disease. Use of nicotine increases oral clearance of rivastigmine by 23% in patients with Alzheimer's disease after oral administration of rivastigmine capsules. Rivastigmine in the form of tabl. disintegrating in the mouth is bioequivalent to rivastigmine in the form of a capsule, showing a similar rate and extent of absorption.

Hypersensitivity to the active substance, other carbamates or to any of the excipients. Previous reactions at the site of administration, indicative of allergic contact dermatitis after application of a rivastigmine patch.

No studies have been performed in patients with severe hepatic impairment - close monitoring is recommended when using rivastigmine in this patient group. Rivastigmine has not been studied in patients with very advanced dementia in Alzheimer's disease or in Parkinson's disease, other types of dementia or other types of memory impairment (eg age-related cognitive impairment), and therefore rivastigmine is not recommended in this patient group. Use with caution in patients with sinus node syndrome or conduction disorders (sinoatrial block, atrioventricular block); in patients with active gastric or duodenal ulcer disease, as well as in patients prone to these diseases; in patients with a history of bronchial asthma or obstructive pulmonary disease; in patients with tendencies to urinary tract obstruction and seizures. Like other cholinomimetics, rivastigmine may exacerbate or induce extrapyramidal symptoms (including motor retardation, dyskinesias, gait disturbances, tremor), especially in patients with dementia associated with Parkinson's disease - patients should be monitored for these side effects.The body weight of the patient should be monitored during treatment with rivastigmine. Preparation in the form of tabl. disintegrating in the mouth contains sorbitol - should not be used in patients with rare inherited disorders associated with fructose intolerance. The use of rivastigmine in children and adolescents is not appropriate for the treatment of Alzheimer's dementia.

It must not be used during pregnancy unless clearly necessary. It is not known whether rivastigmine is excreted in breast milk, therefore patients on rivastigmine should not breast-feed.

Gastrointestinal disorders such as nausea, vomiting and diarrhea are dose related and may occur especially at the beginning of treatment and / or during dose escalation and are more common in women.Patients with Alzheimer's dementia. Very often: lack of appetite, dizziness, nausea, vomiting, diarrhea. Common: decreased appetite, agitation, confusion, anxiety, headache, drowsiness, tremor, abdominal pain, dyspepsia, excessive sweating, fatigue, asthenia, malaise, weight loss. Uncommon: insomnia, depression, fainting, increased values ​​of liver function tests, fall. Rare: convulsions, angina, gastric and duodenal ulcer, rash. Very rare: urinary tract infection, hallucinations, extrapyramidal symptoms (including deterioration in patients with Parkinson's disease), arrhythmias (eg bradycardia, atrioventricular block, atrial fibrillation, tachycardia), hypertension, gastrointestinal bleeding, inflammation of the pancreas. Not known: dehydration, aggression, restlessness, sick sinus syndrome, some cases of severe vomiting associated with esophageal rupture, hepatitis, pruritus, disseminated hypersensitivity reactions.Patients with dementia associated with Parkinson's disease. Very often: tremor, nausea, vomiting, fall. Common: reduced appetite, dehydration, insomnia, anxiety, anxiety, visual hallucinations, depression, dizziness, drowsiness, headache, worsening of Parkinson's disease, slowness of movement, dyskinesia, hypokinesis, "toothed" stiffness, bradycardia, hypertension, diarrhea, abdominal pain and indigestion, excessive salivation, excessive sweating, fatigue and asthenia, gait disturbances, parkinsonian gait. Uncommon: dystonia, atrial fibrillation, atrioventricular block, hypotension. Not known: aggression, sick sinus syndrome, hepatitis, allergic dermatitis (sclerosis). Side effects (eg hypertension, hallucinations in patients with dementia found in Alzheimer's disease and exacerbation of extrapyramidal symptoms, especially tremor in patients with dementia associated with Parkinson's disease) have been observed shortly after increasing the dose. These effects may resolve after dose reduction; in the remaining cases, rivastigmine was discontinued.

Orally. Adults. Treatment should be initiated and supervised by a physician experienced in the diagnosis and treatment of Alzheimer's dementia or dementia associated with Parkinson's disease. The starting dose is 1.5 mg 2 times a day. If the dose is well tolerated, it can be increased to 3 mg 2 times a day after at least 2 weeks of treatment. Subsequent titration up to 4.5 mg, and then up to 6 mg twice daily is possible with good tolerability of the current dose and may be considered after at least 2 weeks of treatment with the previous dose. Adverse reactions (eg nausea, vomiting, abdominal pain or loss of appetite), weight loss or exacerbation of extrapyramidal symptoms (eg tremor) in patients with dementia associated with Parkinson's disease, occurring during treatment, may resolve if one or several doses are missed . If side effects persist, the daily dose should be temporarily reduced to the previous well-tolerated dose or treatment should be discontinued. The therapeutic dose is 3-6 mg twice daily; for maximum therapeutic effect, patients should continue treatment using the highest, well-tolerated dose. The recommended maximum daily dose is 6 mg 2 times a day. Maintenance treatment can be continued as long as the therapeutic effect persists.Therefore, the therapeutic effect of the medicine should be regularly reassessed, particularly in patients treated with doses lower than 3 mg twice daily. If there is no beneficial change in the relief of dementia after 3 months of treatment, treatment should be discontinued. Discontinuation of treatment should also be considered in the absence of signs of therapeutic effect. Therapy was not investigated in placebo-controlled clinical trials lasting longer than 6 months. If treatment was discontinued for more than a few days, treatment should be resumed at 1.5 mg twice daily. Determination of the optimal dose should then take place as described above.Special groups of patients. No dose adjustment is required in patients with mild to moderate renal or hepatic impairment. However, due to the increase in exposure in these populations, the dose should be carefully determined depending on the individual tolerance (the possibility of increasing the dose-related adverse effects). In patients with severe hepatic impairment, rivastigmine may be used only if closely monitored.
Way of giving. Rivastigmine should be taken twice a day, with morning and evening meals. The capsule should be swallowed whole. The orodispersible tablet should be placed in the mouth where it disintegrates quickly in the saliva and then swallowed easily. Removing the intact orodispersible tablet from the mouth is difficult. Because tabl. disintegrating in the mouth is delicate, it should be taken immediately after opening the blister.