Rivastigmin-ET (Transdermal patch) Instructions for Use

Marketing Authorization Holder

Endocrine Technologies, LLC (Russia)

Manufactured By

Moscow Endocrine Plant FSUE (Russia)

ATC Code

N06DA03 (Rivastigmine)

Active Substance

Rivastigmine

Dosage Forms

	Rivastigmine-ET	Transdermal patch 9 mg (4.6 mg/24 h): sachet of 30.
		Transdermal patch 18 mg (9.5 mg/24 h): sachet of 30.
		Transdermal patch 27 mg (13.3 mg/24 h): sachet of 30.

Dosage Form, Packaging, and Composition

Transdermal patch with an area of 10.5 cm², round, on a flesh-colored aluminized backing with an adhesive layer ranging from colorless to light yellow and a transparent removable protective film. The removable protective film matches the size of the patch. A longitudinal cut divides the removable protective film into two parts.

Excipients adhesive layer – polyacrylate adhesive, α-tocopherol; backing – pigmented aluminized polyethylene terephthalate; protective film – silicone-coated polyethylene terephthalate.

1 pc. – sachet (30 pcs.) – cardboard packs (30 pcs.) – By prescription

Transdermal patch with an area of 21 cm², round, on a flesh-colored aluminized backing with an adhesive layer ranging from colorless to light yellow and a transparent removable protective film. The removable protective film matches the size of the patch. A longitudinal cut divides the removable protective film into two parts.

Excipients adhesive layer – polyacrylate adhesive, α-tocopherol; backing – pigmented aluminized polyethylene terephthalate; protective film – silicone-coated polyethylene terephthalate.

1 pc. – sachet (30 pcs.) – cardboard packs (30 pcs.) – By prescription

Transdermal patch with an area of 31.5 cm², round, on a flesh-colored aluminized backing with an adhesive layer ranging from colorless to light yellow and a transparent removable protective film. The removable protective film matches the size of the patch. A longitudinal cut divides the removable protective film into two parts.

Excipients adhesive layer – polyacrylate adhesive, α-tocopherol; backing – pigmented aluminized polyethylene terephthalate; protective film – silicone-coated polyethylene terephthalate.

1 pc. – sachet (30 pcs.) – cardboard packs (30 pcs.) – By prescription

Pharmacotherapeutic Group

Psychoanaleptics; agents for the treatment of dementia; anticholinesterase agents

Pharmacological Action

Selective inhibitor of brain acetylcholinesterase. Inactivation of the enzyme is due to the temporary formation of a complex with a covalent bond.

Slowing the breakdown of acetylcholine, which is released by functionally intact cholinergic neurons, leads to facilitation of cholinergic neurotransmission.

Experimental studies have shown that Rivastigmine selectively increases the acetylcholine content in the cerebral cortex and hippocampus.

Rivastigmine has a positive effect on the cognitive deficits inherent in Alzheimer’s disease that are mediated by cholinergic influences. Furthermore, there are indications that cholinesterase inhibition may slow the formation of amyloid beta-protein precursor (APP) fragments involved in amyloidogenesis and, consequently, the formation of amyloid plaques, which are one of the main pathological features of Alzheimer’s disease.

Rivastigmine has a positive effect on cognitive decline associated with acetylcholine deficiency in dementia associated with Alzheimer’s disease and Parkinson’s disease.

Pharmacokinetics

After oral administration, Rivastigmine is rapidly and completely absorbed from the gastrointestinal tract. C_max in plasma is reached in approximately 1 hour. With topical application (TTS), absorption is slow. After the first dose application, C_max in plasma is reached in 10-16 hours.

Rivastigmine is weakly bound to plasma proteins (about 40%) and easily penetrates the blood-brain barrier.

Rivastigmine is rapidly and extensively metabolized, mainly by hydrolysis by cholinesterase to form a decarbamylated metabolite (NAP226-90). After oral administration, T_1/2 is 1 hour; with topical application, T_1/2 is 3.4 hours after TTS removal.

Rivastigmine is excreted mainly by the kidneys as metabolites; it is not detected unchanged in the urine. More than 90% of the dose is excreted within 24 hours after administration. Less than 1% of the dose is excreted through the intestines. No accumulation of rivastigmine or its decarbamylated metabolite is observed in patients with Alzheimer’s disease.

Indications

Dementia of the Alzheimer’s type. Mild to moderate dementia in Parkinson’s disease (for oral administration).

ICD codes

Dosage Regimen

Apply one transdermal patch to clean, dry, intact, and healthy skin on the upper or lower back, upper arm, or chest. Avoid areas with redness, irritation, or hair. Do not apply to skin folds or under tight clothing.

Select the application site to minimize repeated application to the same area within 14 days. Remove the protective liner and press the patch firmly into place for at least 30 seconds, ensuring full contact, especially around the edges.

Wear the patch continuously for 24 hours. After removal, apply a new patch to a different skin area. If a patch falls off, apply a new one for the remainder of the 24-hour period.

Initiate treatment with the 4.6 mg/24 hours patch. After a minimum of 4 weeks, if the initial dose is well tolerated, increase to the 9.5 mg/24 hours maintenance dose. For patients who demonstrate tolerance but require further efficacy, the dose may be increased to 13.3 mg/24 hours after a minimum of another 4 weeks.

If adverse reactions occur, discontinue treatment until symptoms subside. Restart therapy at the same or a lower dose. For therapy interruptions exceeding 3 days, re-initiate at the lowest dose of 4.6 mg/24 hours to minimize adverse events.

In patients with mild to moderate hepatic impairment or moderate renal impairment, exercise caution during dose titration due to increased drug exposure and a higher risk of adverse reactions. Monitor for gastrointestinal effects, weight loss, and bradycardia.

Adverse Reactions

Infections and infestations urinary tract infections.

Metabolism and nutrition disorders anorexia, decreased appetite; infrequently – dehydration.

Psychiatric disorders: agitation, anxiety, confusion, insomnia, depression, delirium, excitation, nightmares, aggression, restlessness, hallucinations.

Nervous system disorders: headache, syncope, dizziness, drowsiness, psychomotor hyperactivity, extrapyramidal disorders, worsening of Parkinson’s disease symptoms, seizures, tremor.

Cardiac disorders: increased blood pressure, bradycardia, tachycardia, AV block, atrial fibrillation, sick sinus syndrome, angina pectoris, myocardial infarction.

Gastrointestinal disorders nausea, vomiting, diarrhea, decreased appetite, abdominal pain, dyspepsia, gastric and duodenal ulcer, gastrointestinal bleeding, pancreatitis.

Hepatobiliary disorders hepatitis, abnormal liver function tests.

Skin and subcutaneous tissue disorders increased sweating; with topical application at the TTS attachment site – irritation, rash, itching, swelling, erythema, urticaria, allergic dermatitis, generalized allergic dermatitis.

General disorders and administration site conditions increased fatigue, urinary incontinence, asthenia, fever, weight loss, accidental falls, unsteady gait.

Contraindications

Hypersensitivity to rivastigmine, other carbamate derivatives; history of contact allergic dermatitis that occurred during the use of the TTS dosage form; children and adolescents under 18 years of age.

With caution in patients with sick sinus syndrome or severe arrhythmias, increased risk of erosive and ulcerative lesions of the gastrointestinal tract, with urinary tract obstruction, seizures, in patients with a history of bronchial asthma or obstructive airway diseases, in patients with severe hepatic impairment.

Use in Pregnancy and Lactation

The safety of rivastigmine use during human pregnancy has not been established. Use is only possible in cases where the expected treatment benefit for the mother outweighs the potential risk to the fetus.

It is unknown whether Rivastigmine is excreted in human breast milk. If use during lactation is necessary, breastfeeding should be discontinued.

Use in Hepatic Impairment

Due to increased exposure to rivastigmine in patients with mild to moderate hepatic impairment, careful dose titration of rivastigmine is recommended in this category of patients due to the increased risk of dose-dependent adverse events.

Use in Renal Impairment

Due to increased exposure to rivastigmine in patients with moderate renal impairment, careful dose titration of rivastigmine is recommended in this category of patients due to the increased risk of dose-dependent adverse events.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Geriatric Use

Should be used with caution in elderly patients, as higher sensitivity to the effects of rivastigmine in this category of patients cannot be ruled out.

Special Precautions

If treatment is interrupted for more than 3 days, therapy should be resumed with the minimum daily dose to reduce the likelihood of adverse events.

Body weight should be monitored in patients with Alzheimer’s disease, as weight loss may occur in this group of patients when taking cholinesterase inhibitors, including Rivastigmine.

After increasing the dose of rivastigmine, a short-term increase in blood pressure and the occurrence of hallucinations may occur in patients with dementia of the Alzheimer’s type, as well as worsening of extrapyramidal disorders (especially tremor) in patients with dementia in Parkinson’s disease. These symptoms may disappear when the dose is reduced; otherwise, drug therapy should be discontinued. Patients should be regularly assessed to identify these adverse events.

Effect on ability to drive vehicles and operate machinery

Use with caution in patients whose activities require concentration and high speed of psychomotor reactions.

Drug Interactions

Rivastigmine is metabolized mainly by hydrolysis involving esterases. Metabolism involving the major cytochrome P450 isoenzymes occurs to a minimal extent. Therefore, pharmacokinetic interaction with other drugs metabolized by these enzymes is unlikely.

There is a possibility of a cumulative effect of rivastigmine and metoclopramide on the extrapyramidal system. Concurrent use of metoclopramide and rivastigmine is not recommended.

Given the pharmacodynamic characteristics of rivastigmine, simultaneous use with other cholinomimetics should be avoided due to the possibility of their cumulative action. Rivastigmine may affect the action of anticholinergics (e.g., oxybutynin, tolterodine).

During anesthesia, Rivastigmine, being a cholinesterase inhibitor, may enhance the effects of depolarizing muscle relaxants (e.g., suxamethonium salts). Caution should be exercised when choosing an anesthetic agent. If necessary, before anesthesia, it is possible to reduce the dose of rivastigmine or temporarily stop therapy.

When rivastigmine was used concomitantly with beta-blockers (including atenolol), a synergistic interaction was noted, leading to the development of bradycardia, which in turn can cause syncope. Although concomitant use with cardioselective beta-blockers is associated with the greatest risk of such effects, these adverse events have also been observed in patients receiving other drugs in this group.

In patients taking nicotine, an increase in rivastigmine absorption by 23% was observed with oral administration.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.