Chondroitine may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Chondroitin Polysulfate is reported as an ingredient of Chondroitine in the following countries:
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Betametasona L.D.A. may be available in the countries listed below.
Betamethasone 17α-valerate (a derivative of Betamethasone) is reported as an ingredient of Betametasona L.D.A. in the following countries:
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Tvindal may be available in the countries listed below.
Cefuroxime sodium salt (a derivative of Cefuroxime) is reported as an ingredient of Tvindal in the following countries:
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Fertifol may be available in the countries listed below.
Folic Acid is reported as an ingredient of Fertifol in the following countries:
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Cloxacilina IPS may be available in the countries listed below.
Cloxacillin sodium salt (a derivative of Cloxacillin) is reported as an ingredient of Cloxacilina IPS in the following countries:
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In some countries, this medicine may only be approved for veterinary use.
Bacitracin zinc salt (a derivative of Bacitracin) is reported as an ingredient of Bac Neo Poly in the following countries:
Neomycin sulfate (a derivative of Neomycin) is reported as an ingredient of Bac Neo Poly in the following countries:
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Mainvate may be available in the countries listed below.
Dexamethasone 17α,21-dipropionate (a derivative of Dexamethasone) is reported as an ingredient of Mainvate in the following countries:
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Irinotecan Zyo may be available in the countries listed below.
Irinotecan hydrochloride trihydrate (a derivative of Irinotecan) is reported as an ingredient of Irinotecan Zyo in the following countries:
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Telsan may be available in the countries listed below.
Telmisartan is reported as an ingredient of Telsan in the following countries:
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Pivmecillinam Hydrochloride may be available in the countries listed below.
Pivmecillinam Hydrochloride (BANM, JAN) is also known as Pivmecillinam (Rec.INN)
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Glossary
| BANM | British Approved Name (Modified) |
| JAN | Japanese Accepted Name |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
Avistar may be available in the countries listed below.
Amlodipine besilate (a derivative of Amlodipine) is reported as an ingredient of Avistar in the following countries:
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Melicam may be available in the countries listed below.
Meloxicam is reported as an ingredient of Melicam in the following countries:
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0000352-21-6
C4-H9-N-O3
119
Vasodilator
Antiepileptic agent
4-Amino-3-hydroxybuyric acid
Butanoic acid, 4-amino-3-hydroxy-
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Glossary
| IS | Inofficial Synonym |
Trazep may be available in the countries listed below.
Diazepam is reported as an ingredient of Trazep in the following countries:
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Cibalgin may be available in the countries listed below.
Propyphenazone is reported as an ingredient of Cibalgin in the following countries:
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In the US, Mirena (levonorgestrel systemic) is a member of the following drug classes: contraceptives, progestins and is used to treat Abnormal Uterine Bleeding and Birth Control.
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UK matches:
Levonorgestrel is reported as an ingredient of Mirena in the following countries:
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Fluphenazine DBL may be available in the countries listed below.
Fluphenazine decanoate (a derivative of Fluphenazine) is reported as an ingredient of Fluphenazine DBL in the following countries:
Fluphenazine dihydrochloride (a derivative of Fluphenazine) is reported as an ingredient of Fluphenazine DBL in the following countries:
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Triaval may be available in the countries listed below.
Estradiol 17ß-valerate (a derivative of Estradiol) is reported as an ingredient of Triaval in the following countries:
Medroxyprogesterone is reported as an ingredient of Triaval in the following countries:
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Enalapril Naturgen may be available in the countries listed below.
Enalapril is reported as an ingredient of Enalapril Naturgen in the following countries:
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UTINOR 400 mg Tablets
(norfloxacin)
Utinor contains a medicine called norfloxacin. This is an antibiotic which works against a large number of bacteria.
Utinor is used for infections of the urinary system. It works by killing bacteria that can cause infections of your urinary system.
Do not take Utinor if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before taking Utinor.
Check with your doctor or pharmacist before taking your medicine if:
If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before taking Utinor.
Diarrhoea is a common problem caused by antibiotics, which usually ends when the antibiotic is discontinued. Sometimes after starting the treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two more months after having taken the last dose of the antibiotic. If this occurs, you should speak to your doctor as soon as possible.
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. This includes herbal medicines. This is because Utinor can affect the way some other medicines work. Also some other medicines can affect the way Utinor works.
Some medicines can reduce the amount of Utinor that gets into the body. Leave a gap of at least two hours after taking Utinor before taking any of these medicines:
If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before taking Utinor.
It is also particularly important to tell your doctor or pharmacist if you take:
If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before taking Utinor.
Take Utinor with a glass of water. Take Utinor at least one hour before or two hours after food or milk.
Keep out of the sun as much as possible while taking Utinor. This is because the medicine may cause an allergic reaction in some patients when they go in the sun.
Do not take Utinor if you are pregnant or think you might become pregnant. This is because it may affect the baby.
Do not breast-feed if you are taking Utinor. This is because small amounts may pass into the mother’s milk.
Ask your doctor for advice before taking any medicine, if you are pregnant or breast-feeding.
You may feel dizzy while taking Utinor. If this happens do not drive or use any tools or machines.
Always take Utinor exactly as your doctor told you. You should check with your doctor or pharmacist if you are not sure.
REMEMBER, this medicine is for you. Do not share it with anyone else. It may not suit them.
The dose depends on your illness and how bad it is. The usual dose is:
If the infection comes back, your treatment can be for up to 12 weeks.
If you take more Utinor than you should, talk to your doctor straight away.
Keep taking these tablets until the course is finished. Keep taking them, even if you start to feel better after a few days.
If you have any further questions on the use of this product, ask your doctor or pharmacist.
Like all medicines Utinor can cause side effects, although not everybody gets them. The following side effects may happen with this medicine:
Heart and circulation
Skin and hair
Nervous system
Eyes or ears
Infections
Stomach and gut
Blood
Joints and muscles
Urinary
Mental illness
If any of these side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
Keep your tablets out of the reach of children.
Your tablets should be kept below 25°C, in a dry place out of direct sunlight.
Do not put your tablets in another container, as they might get mixed up.
If you have any tablets left over when your doctor tells you to stop taking them, return them to the pharmacist.
Do not take them after the expiry date that is clearly marked on the pack.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.
Utinor tablets are off-white oval shaped tablets marked ‘MSD 705’.
Utinor Tablets are available in blister packs of 2, 6, 7 and 14 tablets, and bottles of 50.
Not all pack sizes may be marketed.
The marketing Authorisation Holder is
Utinor tablets are made by
This leaflet was last approved in March 2009
This leaflet gives you some of the most important patient information about Utinor. If you have any questions after you have read it, ask your doctor or pharmacist, who will give you further information.
denotes registered trademark of
© Merck Sharp & Dohme Limited 2009. All rights reserved.
(logo) MSD
PIL.NRX.08.UK.2828
Fenacop Retard may be available in the countries listed below.
Diclofenac sodium salt (a derivative of Diclofenac) is reported as an ingredient of Fenacop Retard in the following countries:
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Penicillin G Sodium Panpharma may be available in the countries listed below.
Benzylpenicillin is reported as an ingredient of Penicillin G Sodium Panpharma in the following countries:
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Pressolat may be available in the countries listed below.
Nifedipine is reported as an ingredient of Pressolat in the following countries:
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Atracurium-DeltaSelect may be available in the countries listed below.
Atracurium Besilate is reported as an ingredient of Atracurium-DeltaSelect in the following countries:
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Mitotax may be available in the countries listed below.
Paclitaxel is reported as an ingredient of Mitotax in the following countries:
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In the US, Permitil (fluphenazine systemic) is a member of the drug class phenothiazine antipsychotics and is used to treat Psychosis.
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Sildenafil citrate (a derivative of Sildenafil) is reported as an ingredient of Permitil in the following countries:
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In the US, Panadol Extend is a member of the drug class miscellaneous analgesics and is used to treat Fever, Muscle Pain, Pain and Sciatica.
Paracetamol is reported as an ingredient of Panadol Extend in the following countries:
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Epirubicin Lemery may be available in the countries listed below.
Epirubicin hydrochloride (a derivative of Epirubicin) is reported as an ingredient of Epirubicin Lemery in the following countries:
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Terracortril Ophth may be available in the countries listed below.
Hydrocortisone is reported as an ingredient of Terracortril Ophth in the following countries:
Oxytetracycline is reported as an ingredient of Terracortril Ophth in the following countries:
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Farsorbid may be available in the countries listed below.
Isosorbide Dinitrate is reported as an ingredient of Farsorbid in the following countries:
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Ciclosterona may be available in the countries listed below.
Progesterone is reported as an ingredient of Ciclosterona in the following countries:
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Hétacilline may be available in the countries listed below.
Hétacilline (DCF) is also known as Hetacillin (Prop.INN)
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Glossary
| DCF | Dénomination Commune Française |
| Prop.INN | Proposed International Nonproprietary Name (World Health Organization) |
Padrin may be available in the countries listed below.
Prifinium Bromide is reported as an ingredient of Padrin in the following countries:
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Risedronat Teva may be available in the countries listed below.
Risedronic Acid monosodium (a derivative of Risedronic Acid) is reported as an ingredient of Risedronat Teva in the following countries:
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Hysan may be available in the countries listed below.
Hyaluronic Acid sodium salt (a derivative of Hyaluronic Acid) is reported as an ingredient of Hysan in the following countries:
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Brucarcer may be available in the countries listed below.
Carbamazepine is reported as an ingredient of Brucarcer in the following countries:
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Relanium may be available in the countries listed below.
Diazepam is reported as an ingredient of Relanium in the following countries:
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Rivastigmine Sandoz 4.5 mg hard capsules
Each capsule contains rivastigmine hydrogen tartrate corresponding to rivastigmine 4.5 mg.
For a full list of excipients, see section 6.1.
Hard capsule
Off-white to slightly yellow powder in a capsule with red cap and red body, with white imprint “RIV 4.5 mg” on the body.
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.
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. Diagnosis should be made according to current guidelines. Therapy with rivastigmine should only be started if a caregiver is available who will regularly monitor intake of the medicinal product by the patient.
Rivastigmine should be administered twice a day, with morning and evening meals. The capsules should be swallowed whole.
Initial dose
1.5 mg twice a day.
Dose titration
The starting dose is 1.5 mg twice a day. If this dose is well tolerated after a minimum of two weeks of treatment, the dose may be increased to 3 mg twice a day. Subsequent increases to 4.5 mg and then 6 mg twice a day should also be based on good tolerability of the current dose and may be considered after a minimum of two weeks of treatment at that dose level.
If adverse reactions (e.g. nausea, vomiting, abdominal pain or loss of appetite), weight decrease or worsening of extrapyramidal symptoms (e.g. tremor) in patients with dementia associated with Parkinson's disease are observed during treatment, these may respond to omitting one or more doses. If adverse reactions persist, the daily dose should be temporarily reduced to the previous well-tolerated dose or the treatment may be discontinued.
Maintenance dose
The effective dose is 3 to 6 mg twice a day; to achieve maximum therapeutic benefit patients should be maintained on their highest well tolerated dose. The recommended maximum daily dose is 6 mg twice a day.
Maintenance treatment can be continued for as long as a therapeutic benefit for the patient exists. Therefore, the clinical benefit of rivastigmine should be reassessed on a regular basis, especially for patients treated at doses less than 3 mg twice a day. If after 3 months of maintenance dose treatment the patient's rate of decline in dementia symptoms is not altered favourably, the treatment should be discontinued. Discontinuation should also be considered when evidence of a therapeutic effect is no longer present.
Individual response to rivastigmine cannot be predicted. However, a greater treatment effect was seen in Parkinson's disease patients with moderate dementia. Similarly a larger effect was observed in Parkinson's disease patients with visual hallucinations (see section 5.1).
Treatment effect has not been studied in placebo-controlled trials beyond 6 months.
Re-initiation of therapy
If treatment is interrupted for more than several days, it should be re-initiated at 1.5 mg twice daily. Dose titration should then be carried out as described above.
Renal and hepatic impairment
Due to increased exposure in moderate renal and mild to moderate hepatic impairment, dosing recommendations to titrate according to individual tolerability should be closely followed (see section 5.2).
Patients with severe liver impairment have not been studied (see section 4.3).
Children
Rivastigmine is not recommended for use in children.
The use of this medicinal product is contraindicated in patients with
- hypersensitivity to the active substance, other carbamate derivatives or to any of the excipients used in the formulation,
- severe liver impairment, as it has not been studied in this population.
The incidence and severity of adverse reactions generally increase with higher doses. If treatment is interrupted for more than several days, it should be re-initiated at 1.5 mg twice daily to reduce the possibility of adverse reactions (e.g. vomiting).
Dose titration: Adverse reactions (e.g. hypertension and hallucinations in patients with Alzheimer's dementia and worsening of extrapyramidal symptoms, in particular tremor, in patients with dementia associated with Parkinson's disease) have been observed shortly after dose increase. They may respond to a dose reduction. In other cases, rivastigmine has been discontinued (see section 4.8).
Gastrointestinal disorders such as nausea and vomiting may occur particularly when initiating treatment and/or increasing the dose. These adverse reactions occur more commonly in women. Patients with Alzheimer's disease may lose weight. Cholinesterase inhibitors, including rivastigmine, have been associated with weight loss in these patients. During therapy patient's weight should be monitored.
In case of severe vomiting associated with rivastigmine treatment, appropriate dose adjustments as recommended in section 4.2 must be made. Some cases of severe vomiting were associated with oesophageal rupture (see section 4.8). Such events appeared to occur particularly after dose increments or high doses of rivastigmine.
Care must be taken when using rivastigmine in patients with sick sinus syndrome or conduction defects (sino-atrial block, atrio-ventricular block) (see section 4.8).
Rivastigmine may cause increased gastric acid secretions. Care should be exercised in treating patients with active gastric or duodenal ulcers or patients predisposed to these conditions.
Cholinesterase inhibitors should be prescribed with care to patients with a history of asthma or obstructive pulmonary disease.
Cholinomimetics may induce or exacerbate urinary obstruction and seizures. Caution is recommended in treating patients predisposed to such diseases.
The use of rivastigmine in patients with severe dementia of Alzheimer's disease or associated with Parkinson's disease, other types of dementia or other types of memory impairment (e.g. age-related cognitive decline) has not been investigated and therefore use in these patient populations is not recommended.
Like other cholinomimetics, rivastigmine may exacerbate or induce extrapyramidal symptoms. Worsening (including bradykinesia, dyskinesia, gait abnormality) and an increased incidence or severity of tremor have been observed in patients with dementia associated with Parkinson's disease (see section 4.8). These events led to the discontinuation of rivastigmine in some cases (e.g. discontinuations due to tremor 1.7% on rivastigmine vs 0% on placebo). Clinical monitoring is recommended for these adverse reactions.
As a cholinesterase inhibitor, rivastigmine may exaggerate the effects of succinylcholine-type muscle relaxants during anaesthesia. Caution is recommended when selecting anaesthetic agents. Possible dose adjustments or temporarily stopping treatment can be considered if needed.
In view of its pharmacodynamic effects, rivastigmine should not be given concomitantly with other cholinomimetic substances and might interfere with the activity of anticholinergic medicinal products.
No pharmacokinetic interaction was observed between rivastigmine and digoxin, warfarin, diazepam or fluoxetine in studies in healthy volunteers. The increase in prothrombin time induced by warfarin is not affected by administration of rivastigmine. No untoward effects on cardiac conduction were observed following concomitant administration of digoxin and rivastigmine.
According to its metabolism, metabolic interactions with other medicinal products appear unlikely, although rivastigmine may inhibit the butyrylcholinesterase mediated metabolism of other substances.
For rivastigmine no clinical data on exposed pregnancies are available. No effects on fertility or embryofoetal development were observed in rats and rabbits, except at doses related to maternal toxicity. In peri/postnatal studies in rats, an increased gestation time was observed. Rivastigmine should not be used during pregnancy unless clearly necessary.
In animals, rivastigmine is excreted into milk. It is not known if rivastigmine is excreted into human milk. Therefore, women on rivastigmine should not breast-feed.
Alzheimer's disease may cause gradual impairment of driving performance or compromise the ability to use machinery. Furthermore, rivastigmine can induce dizziness and somnolence, mainly when initiating treatment or increasing the dose. As a consequence, rivastigmine has minor or moderate influence on the ability to drive and use machines. Therefore, the ability of patients with dementia on rivastigmine to continue driving or operating complex machines should be routinely evaluated by the treating physician.
The most commonly reported adverse reactions are gastrointestinal, including nausea (38%) and vomiting (23%), especially during titration. Female patients in clinical studies were found to be more susceptible than male patients to gastrointestinal adverse reactions and weight loss.
The following adverse reactions, listed below in Table 1, have been accumulated in patients with Alzheimer's dementia treated with rivastigmine.
Adverse reactions in Table 1 are listed according to MedDRA system organ class and frequency category. Frequency categories are defined using the following convention: very common (
Table 1
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The following additional adverse reactions have been observed with rivastigmine transdermal patches: anxiety, delirium, pyrexia (common).
Table 2 shows the adverse reactions reported in patients with dementia associated with Parkinson's disease treated with rivastigmine.
Table 2
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Table 3 lists the number and percentage of patients from the specific 24-week clinical study conducted with rivastigmine in patients with dementia associated with Parkinson's disease with pre-defined adverse events that may reflect worsening of parkinsonian symptoms.
Table 3
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Symptoms
Most cases of accidental overdose have not been associated with any clinical signs or symptoms and almost all of the patients concerned continued rivastigmine treatment. Where symptoms have occurred, they have included nausea, vomiting and diarrhoea, hypertension or hallucinations. Due to the known vagotonic effect of cholinesterase inhibitors on heart rate, bradycardia and/or syncope may also occur. Ingestion of 46 mg occurred in one case; following conservative management the patient fully recovered within 24 hours.
Treatment
As rivastigmine has a plasma half-life of about 1 hour and a duration of acetylcholinesterase inhibition of about 9 hours, it is recommended that in cases of asymptomatic overdose no further dose of rivastigmine should be administered for the next 24 hours. In overdose accompanied by severe nausea and vomiting, the use of antiemetics should be considered. Symptomatic treatment for other adverse reactions should be given as necessary.
In massive overdose, atropine can be used. An initial dose of 0.03 mg/kg intravenous atropine sulphate is recommended, with subsequent doses based on clinical response. Use of scopolamine as an antidote is not recommended.
Pharmacotherapeutic group: anticholinesterases, ATC code: N06DA03
Rivastigmine is an acetyl- and butyrylcholinesterase inhibitor of the carbamate type, thought to facilitate cholinergic neurotransmission by slowing the degradation of acetylcholine released by functionally intact cholinergic neurones. Thus, rivastigmine may have an ameliorative effect on cholinergic-mediated cognitive deficits in dementia associated with Alzheimer's disease and Parkinson's disease.
Rivastigmine interacts with its target enzymes by forming a covalently bound complex that temporarily inactivates the enzymes. In healthy young men, an oral 3 mg dose decreases acetylcholinesterase (AChE) activity in CSF by approximately 40% within the first 1.5 hours after administration. Activity of the enzyme returns to baseline levels about 9 hours after the maximum inhibitory effect has been achieved. In patients with Alzheimer's disease, inhibition of AChE in CSF by rivastigmine was dose-dependent up to 6 mg given twice daily, the highest dose tested. Inhibition of butyrylcholinesterase activity in CSF of 14 Alzheimer patients treated by rivastigmine was similar to that of AChE.
Clinical studies in Alzheimer's dementia
The efficacy of rivastigmine has been established through the use of three independent, domain specific, assessment tools which were assessed at periodic intervals during 6 month treatment periods. These include the ADAS-Cog (a performance based measure of cognition), the CIBIC-Plus (a comprehensive global assessment of the patient by the physician incorporating caregiver input), and the PDS (a caregiver-rated assessment of the activities of daily living including personal hygiene, feeding, dressing, household chores such as shopping, retention of ability to orient oneself to surroundings as well as involvement in activities relating to finances, etc.).
The patients studied had an MMSE (Mini-Mental State Examination) score of 10–24.
The results for clinically relevant responders pooled from two flexible dose studies out of the three pivotal 26-week multicentre studies in patients with mild-to-moderately severe Alzheimer's Dementia, are provided in Table 4 below. Clinically relevant improvement in these studies was defined a priori as at least 4-point improvement on the ADAS-Cog, improvement on the CIBIC-Plus, or at least a 10% improvement on the PDS.
In addition, a post-hoc definition of response is provided in the same table. The secondary definition of response required a 4-point or greater improvement on the ADAS-Cog, no worsening on the CIBIC-Plus, and no worsening on the PDS. The mean actual daily dose for responders in the 6-12 mg group, corresponding to this definition, was 9.3 mg. It is important to note that the scales used in this indication vary and direct comparisons of results for different therapeutic agents are not valid.
Table 4
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*p<0.05, **p<0.01, ***p<0.001
Clinical studies in dementia associated with Parkinson's disease
The efficacy of rivastigmine in dementia associated with Parkinson's disease has been demonstrated in a 24-week multicentre, double-blind, placebo-controlled core study and its 24-week open-label extension phase. Patients involved in this study had an MMSE (Mini-Mental State Examination) score of 10–24. Efficacy has been established by the use of two independent scales which were assessed at regular intervals during a 6-month treatment period as shown in Table 5 below: the ADAS-Cog, a measure of cognition, and the global measure ADCS-CGIC (Alzheimer's Disease Cooperative Study-Clinician's Global Impression of Change).
Table 5
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1 Based on ANCOVA with treatment and country as factors and baseline ADAS-Cog as a covariate. A positive change indicates improvement.
2 Mean data shown for convenience, categorical analysis performed using van Elteren test
ITT: Intent-To-Treat; RDO: Retrieved Drop Outs; LOCF: Last Observation Carried Forward
Although a treatment effect was demonstrated in the overall study population, the data suggested that a larger treatment effect relative to placebo was seen in the subgroup of patients with moderate dementia associated with Parkinson's disease. Similarly a larger treatment effect was observed in those patients with visual hallucinations (see Table 6).
Table 6
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1 Based on ANCOVA with treatment and country as factors and baseline ADAS-Cog as a covariate. A positive change indicates improvement.
ITT: Intent-To-Treat; RDO: Retrieved Drop Outs
Absorption
Rivastigmine is rapidly and completely absorbed. Peak plasma concentrations are reached in approximately 1 hour. As a consequence of rivastigmine's interaction with its target enzyme, the increase in bioavailability is about 1.5-fold greater than that expected from the increase in dose. Absolute bioavailability after a 3 mg dose is about 36%±13%. Administration of rivastigmine with food delays absorption (tmax) by 90 min and lowers Cmax and increases AUC by approximately 30%.
Distribution
Protein binding of rivastigmine is approximately 40%. It readily crosses 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 in plasma approximately 1 hour), primarily via cholinesterase-mediated hydrolysis to the decarbamylated metabolite. In vitro, this metabolite shows minimal inhibition of acetylcholinesterase (<10%). Based on evidence from in vitro and animal studies the major cytochrome P450 isoenzymes are minimally involved in rivastigmine metabolism. Total plasma clearance of rivastigmine was approximately 130 l/h after a 0.2 mg intravenous dose and decreased to 70 l/h after a 2.7 mg intravenous dose.
Excretion
Unchanged rivastigmine is not found in the urine; renal excretion of the metabolites is the major route of elimination. Following administration of 14C-rivastigmine, renal elimination was rapid and essentially complete (>90%) within 24 hours. Less than 1% of the administered dose is excreted in the faeces. There is no accumulation of rivastigmine or the decarbamylated metabolite in patients with Alzheimer's disease.
Elderly subjects
While bioavailability of rivastigmine is greater in elderly than in young healthy volunteers, studies in Alzheimer patients aged between 50 and 92 years showed no change in bioavailability with age.
Subjects with hepatic impairment
The Cmax of rivastigmine was approximately 60% higher and the AUC of rivastigmine was more than twice as high in subjects with mild to moderate hepatic impairment than in healthy subjects.
Subjects with renal impairment
Cmax and AUC of rivastigmine were more than twice as high in subjects with moderate renal impairment compared with healthy subjects; however there were no changes in Cmax and AUC of rivastigmine in subjects with severe renal impairment.
Repeated-dose toxicity studies in rats, mice and dogs revealed only effects associated with an exaggerated pharmacological action. No target organ toxicity was observed. No safety margins to human exposure were achieved in the animal studies due to the sensitivity of the animal models used.
Rivastigmine was not mutagenic in a standard battery of in vitro and in vivo tests, except in a chromosomal aberration test in human peripheral lymphocytes at a dose 104 times the maximum clinical exposure. The in vivo micronucleus test was negative.
No evidence of carcinogenicity was found in studies in mice and rats at the maximum tolerated dose, although the exposure to rivastigmine and its metabolites was lower than the human exposure. When normalised to body surface area, the exposure to rivastigmine and its metabolites was approximately equivalent to the maximum recommended human dose of 12 mg/day; however, when compared to the maximum human dose, a multiple of approximately 6-fold was achieved in animals.
In animals, rivastigmine crosses the placenta and is excreted into milk. Oral studies in pregnant rats and rabbits gave no indication of teratogenic potential on the part of rivastigmine.
Gelatin
Magnesium stearate
Hypromellose
Microcrystalline cellulose
Silica, colloidal anhydrous
Yellow iron oxide (E172)
Red iron oxide (E172)
Titanium dioxide (E171)
Not applicable.
5 years
Do not store above 30°C.
