The package insert of the drug Prometax

the package insert of the medicine Prometax. Active principles Hydroxypropylmethylcellulose, Microcrystalline Cellulose, Iron Oxide Yellow and Gelatin. Sale under medical prescription.

what For?

Treatment of patients with dementia, mild to moderately severe of the Alzheimer’s type,
also known as Alzheimer’s Disease or probable Alzheimer’s Disease.

Pharmacokinetics

How it works?

Absorption: rivastigmine is absorbed rapidly and completely. Plasma concentrations
highs are reached in approximately 1 hour. As a result
the interaction of the drug with the enzyme-target, the increase in availability is around
1.5 times greater than that expected by the increase of the dose. The absolute bioavailability
after a dose of 3 mg is about 36%. The administration of capsules of rivastigmine
with food delays absorption (tmax) by 90 min and lowers Cmax and
increases AUC by approximately 30%. Distribution: rivastigmine has a low binding to plasma proteins
(approximately 40%). She crosses rapidly the blood brain barrier and
has an apparent volume of distribution in the range of 1.8 – 2,7 L/kg. Metabolism: rivastigmine is rapidly and extensively metabolised (half-life
the plasma approximately 1 hour), primarily via hydrolysis mediated by
cholinesterase to the metabolite descarbamilado. In vitro, this metabolite shows a
inhibition minimum of acetylcholinesterase (90%) in 24 hours. Less
1% of the administered dose is excreted in the stool. There is no accumulation of rivastigmine
neither of the metabolite descarbamilado in patients with Alzheimer’s Disease.

safety Data pre-clinical acute Toxicity values oral LD50 estimated in mice that were
The 5.6 mg/kg (males) and 13.8 mg/kg (females). The values of oral LD50 in rats
were 8.1 mg/kg (males) and 13.8 mg/kg (females). Dose toxicity multiple: Studies in rats, mice, dogs and monkeys (doses
maximum 3.8; 6,3; 2,5 and 6,3 mg/kg/day, respectively) showed evidence
stimulation cholinergic of the central and peripheral nervous system. The tolerability
in vivo to rivastigmine proved to be variable between species, the dog being the kind
the more sensitive. Was not observed toxicity in a target organ or changes to pathology
clinic in any of the species, although effects gastrointestinal have been
prominent in dogs. Mutagenicity: rivastigmine was not mutagenic in tests of mutation
genetic testing, damage of DNA primary nor in chromosomal changes in
alive. In tests of chromosomal changes in vitro, a small increase in the number
of cells with chromosomal aberrations occurred at concentrations
very, very high. However, as there is no evidence of activity clastogênica
Format: 212 x 165 mm
Color: Black
in the tests, in vivo chromosome aberration more relevant, it is more likely that
the results in vitro have configured the observations of false-positive. Carcinogenicity: has Not been observed any evidence of carcinogenicity in
studies conducted at dose levels up to 1.1 mg/kg/day in rats and 1.6 mg/kg/
day in mice. Reproductive toxicity: Studies oral in rats and rabbits pregnant with levels of
dose of up to 2.3 mg/kg/day showed no indications of potential teratogenic
related to rivastigmine. In the same way, was not demonstrated evidence of
adverse effects of rivastigmine on fertility, reproductive function or growth
in utero or post-natal in rats that received dose levels up to 1.1 mg/kg/day.

Contraindications

When should I not use?

The use of PROMETAX (rivastigmine) is contraindicated in patients with known
hypersensitivity to rivastigmine, to other derivatives of carbamate-or any
component of the formula (see “Composition – Excipients”).

PROMETAX (rivastigmine) is contraindicated in patients with hepatic insufficiency
severe not to have been studied in this population.

Dosage

How to use?

Administration: PROMETAX (rivastigmine) should be administered two times a
day, with meals morning and evening. Initial Dose: 1.5 mg two times a day. Patients who are known to be
sensitive to the effects of drugs cholinergic should start the treatment with dose
1 mg two times a day.

Adjust dose: The initial dose is 1.5 mg twice a day. If this dose is well
tolerated after at least 2 weeks of treatment, the same may be increased
to 3 mg two times a day. Increases subsequent to 4.5 mg and then for 6
mg twice a day should also be based on good tolerability of the dose
current and can be considered after a minimum of 2 weeks of treatment
at that dose level.

If adverse effects are observed (for ex.: nausea, vomiting, or abdominal pain
loss of appetite or decrease in weight during the treatment period, these should be
resolved with the omission of one or more doses. If adverse effects persist,
the daily dose should be reduced to the previous dose that had a good tolerability. Maintenance Dose: 1.5 to 6 mg twice a day; to achieve the therapeutic benefit
maximum, patients should be maintained on the dose well tolerated, the most high. Dose maximum recommended daily: 6 mg two times a day.

Restart of therapy: The incidence and severity of adverse reactions generally
increase with higher doses. If the treatment is stopped for a period of
some days, should be restarted with the lowest dose daily and adjusted as described
above.

Use in the elderly The bioavailability of rivastigmine is greater in healthy volunteers
the elderly than in young volunteers; however, studies in patients with Disease
Alzheimer’s between the ages of 50 and 92 years showed no changes in bioavailability
as a function of age.

Use in patients with renal or hepatic insufficiency – it is Not necessary to perform
dose adjustment in patients with renal or hepatic insufficiency (see “Counter-
Indications”).

Side Effects

What are the evils that can cause me?

The adverse reactions reported most commonly are gastrointestinal including nausea
(38%) and vomiting (23%), especially during titration. The patients of the
clinical studies were most likely adverse reactions gastrointestinal and loss
weight.

The following adverse reactions, listed in Table 1 below, have been accumulated the
from clinical studies with PROMETAX® (rivastigmine), and since its introduction
in the market.

Table 1*
Infections and infestations
Urinary tract infection Very rare
Psychiatric disorders
Agitation Common
Confusion Common
Insomnia Unusual
Depression Unusual
Hallucinations Very rare
Disorders of the Nervous System
Vertigo is Very common
Headache Common
Drowsiness Common
Tremor Common
Syncope Uncommon
Seizures Rare
Heart disorders
Cardiac arrhythmia (e.g. bradycardia, lock
atrioventricular, atrial fibrillation and tachycardia) Very rare
Angina pectoris Rare
Vascular disorders
Hypertension Very rare
Disorders gastrointestinal
Nausea Very common
Vomiting is Very common
Diarrhea: Very common
Loss of appetite is Very common
Abdominal pain and dyspepsia Common
Ulcers gastric and duodenal Rare
Bleeding gastrointestinal Very rare
Pancreatitis rims Very rare
Disorders of skin and subcutaneous
Increased sweating Common
Skin rash Rare
Disorders general
Fatigue and asthenia Common
If you feel unwell, Common
Accidentally dropping Unusual
Investigations
Weight loss Common
* The adverse reactions are classified according to their titles, frequency,
the most frequent first, using the following convention: Very common (>1/
10); common (> 1/100, 1/1000 < 1/100); rare (>1/10.000 < 1/1000);
very common (>1/10.000), including isolated reports.

Warnings and Precautions

what should I know before using?

as Well as other colinomiméticos, care should be taken when using PROMETAX
(rivastigmine) in patients with disease of the sinus node or defects in the driving
(block sino-atrial, atrioventricular block) (see “backlash”).

The stimulation cholinergic can cause increased secretion of acid gastric and can
exacerbate obstructions, urinary tract and precipitate seizures. Caution is recommended
when treating patients predisposed to these pathologies.

As with other colinomiméticos, PROMETAX (rivastigmine) should be used
with caution in patients with a history of asthma or obstructive pulmonary disease.

treatment should always be started with the dose of 1.5 mg, twice a day, and
be adjusted to the maintenance dose of the patient. If treatment is stopped
for several days, should be restarted with the lowest daily dose in order to minimize
the possibility of adverse reactions (for example, vomiting, severe) (see “Dose”).

Titration of the dose: As with theother colinomiméticos, adverse effects were observed
soon after increasing the dose, and these may respond to a reduction of the
dose. In other cases, Exelon has been discontinued (see Adverse Reactions).

The sodium benzoate is one of the excipients of PROMETAX (rivastigmine) solution
oral. The benzoic acid is very irritating to skin, eyes and mucous membranes.

Overdose

what to do if someone use a larger amount than is recommended?

Symptoms: most cases of overdose accidental has not been associated with
The no sign or clinical symptom, and almost all the patients involved continued
The treatment with prometax (rivastigmine). in the cases that have occurred
Symptoms, these included nausea, vomiting, diarrhoea, hypertension and hallucinations.

Due to the known effect vagotônico of the inhibitors of cholinesterase about the
The heart, bradycardia and/or syncope may also occur.

The ingestion of 46 mg occurred in one case; following conservative treatment, the patient
If completely recovered in 24 hours. treatment: as rivastigmine has a half-life in plasma of about
1 hour and duration of inhibition of the acetylcholinesterase of about 9 hours, it is recommended to
That, in cases of overdose asymptomatic, no dose of prometax
(rivastigmine) should be administered for the next 24 hours. in cases
In overdose accompanied by vomiting and nausea severe, the use of antiemetics
Should be considered. symptomatic treatment for other adverse events should
Be performed, if necessary.

In overdose-severe, atropine may be used. the recommended dose
The initial i. v. of 0.03 mg/kg of sulphate of atropine, with subsequent doses based
In the clinical response. it is not recommended the use of scopolamine as an antidote.

Attention: this product is a new drug and, although the research
Conducted have indicated effectiveness and security when
Correctly indicated, may occur adverse reactions unpredictable
Not yet described or known. in the case of a suspected
Of adverse reaction, the doctor should be notified.