Normicron 200 Mg Film-Coated Tablets
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
T Normicron 200 mg film-coated tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
One film-coated tablet contains:
Rifaximin 200 mg
Excipients:
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Film-coated tablet
Pink circular biconvex film-coated tablets, with “AW” printed on both sides.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Normicron is indicated for the treatment of traveller’s diarrhoea that is not associated with any of:
Fever
Bloody diarrhoea
Eight or more unformed stools in the previous 24 h Occult blood or leucocytes in the stool.
Normicron may shorten the duration of diarrhoea when this is associated with noninvasive strains of E.coli (see sections 4.4 and 5.1).
4.2 Posology and method of administration
Posology 200 mg every 8 hours for three days (total 9 doses).
Rifaximin must not be used for more than 3 days even if symptoms continue and a second course of treatment must not be taken (see section 4.4).
Rifaximin can be administered with or without food.
Paediatric population
The safety and efficacy of Normicron 200 mg film-coated tablets in children (aged less than 18 years) have not been established.
A dosage adjustment for patients with hepatic or renal insufficiency is not necessary.
Method of administration Orally with a glass of water.
4.3 Contraindications
Hypersensitivity to the active substance, to any rifamycin (e.g. rifampicin or rifabutin) or to any of the excipients.
4.4 Special warnings and precautions for use
Clinical data have shown that rifaximin is not effective in the treatment of traveller’s diarrhoea caused by invasive enteric pathogens such as Campylobacter, Salmonella and Shighella, which typically produce dysenterylike diarrhoea characterised by fever, blood in the stool and high stool frequency.
If symptoms worsen treatment with rifaximin should be interrupted.
If symptoms have not resolved after 3 days of treatment, or recur shortly afterwards, a second course of rifaximin should not be administered.
Clostridium difficile associated diarrhoea (CDAD) has been reported with use of nearly all antibacterial agents, including rifaximin. The potential association of rifaximin treatment with CDAD and pseudomembranous colitis (PMC) cannot be ruled out.
Caution should be exercised when concomitant use of rifaximin and a P-glycoprotein inhibitor such as ciclosporin is needed (see section 4.5).
Paediatric population
Normicron 200 mg film-coated tablets are not recommended for use in children (<18 years old).
4.5 Interaction with other medicinal products and other forms of interaction
There is no experience regarding administration of rifaximin to subjects who are taking another rifamycin antibacterial agent to treat a systemic bacterial infection. Due to the lack of data and the potential for severe disruption of gut flora with unknown consequences rifaximin should not be administered concomitantly with other rifamycins.
Due to the negligible gastrointestinal absorption of orally administered rifaximin (less than 1%), the systemic drug interaction potential is low. In vitro data show that rifaximin is a weak inducer of the CYP3A4 isoenzyme of the P450 cytochrome.
Drug-drug interaction studies investigating the clinical interaction between rifaximin and drugs metabolised by the human cytochrome P450 isoenzymes demonstrated that rifaximin did not significantly affect the pharmacokinetics of midazolam or an oral contraceptive containing ethinyl estradiol and norgestimate.
Therefore, clinical interactions with drugs metabolised by these isoenzymes are not expected.
The potential for drug-drug interactions to occur at the level of gut transporter systems has been evaluated.
In healthy subjects, co-administration of a single dose of ciclosporin (600 mg), a potent P-glycoprotein inhibitor, with a single dose of rifaximin (550mg) resulted in 83-fold and 124-fold increases in rifaximin mean Cmax and AUCot. The clinical significance of this increase in systemic exposure is unknown.
No drug interaction studies investigating the concomitant intake of rifaximin and other drugs that might be used during an episode of traveller’s diarrhoea (e.g. loperamide, charcoal) are available. Patients should take rifaximin at least 2 hours after the administration of charcoal.
4.6 Pregnancy and lactation
For Rifaximin no clinical data on exposed pregnancies are available.
Animal studies have shown reproductive toxicity (see 5.3).
Rifaximin is not recommended during pregnancy and in women of childbearing potential not using contraception (see Section 5.3).
It is not known whether rifaximin is excreted in human milk. A decision should be taken whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
4.7 Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been performed.
In clinical controlled trials dizziness has been reported but rifaximin has negligible influence on the ability to drive and use machines.
4.8 Undesirable effects
In clinical studies in subjects who received Rifaximin for treatment of traveller’s diarrhoea Adverse Reactions considered as being at least possibly related to Rifaximin have been categorised by organ system and frequency.
|
MedDRA System Organ Class (ver. 12.1) |
Common (>1/100 to <1/10) |
Uncommon (> 1/1.000 to < 1/100) |
|
Infections and infestations |
Candidiasis, Herpes simplex, Nasopharyngitis, Pharyngitis, Upper respiratory tract infection | |
|
Blood and lymphatic system disorder |
Lymphocytosis, Monocytosis, Neutropenia | |
|
Metabolism and nutrition disorders |
Decreased appetite, Dehydration | |
|
Psychiatric Disorders |
Abnormal dreams, Depressed mood, Insomnia, Nervousness | |
|
Nervous system disorders |
Dizziness, Headache |
Hypoesthesia, Migraine, Paraesthesia, Sinus headache, Somnolence |
|
Eye disorders |
Diplopia | |
|
Ear and labyrinth disorders |
Ear pain, Vertigo | |
|
Cardiac disorders |
Palpitations | |
|
Vascular disorders |
Blood pressure increased Hot flush |
|
MedDRA System Organ Class (ver. 12.1) |
Common (>1/100 to <1/10) |
Uncommon (> 1/1.000 to < 1/100) |
|
Respiratory, thoracic, and mediastinal disorders |
Cough, Dry throat, Dyspnoea, Nasal congestion, Oropharyngeal pain, Rhinorrhea |
|
MedDRA System Organ Class (ver. 12.1) |
Common (>1/100 to <1/10) |
Uncommon (> 1/1.000 to < 1/100) |
|
Gastrointestinal disorders |
Abdominal pain, Constipation, Defecation urgency, Diarrhoea, Flatulence, bloating and distension, Nausea and vomiting symptoms, Rectal tenesmus |
Abdominal pain upper, Dry lips, Dyspepsia, Gastrointestinal motility disorder, Faeces hard, Haematochezia, Mucous stools, Taste disorders |
|
Hepatobiliary disorders |
Aspartate aminotransferase increased | |
|
Skin and subcutaneous tissue disorders |
Rashes, eruptions and exanthemas NEC Sunburn | |
|
Musculoskeletal and connective tissue disorders |
Back pain, Muscle spasms, Muscular weakness, Myalgia Neck pain | |
|
Renal and urinary disorders |
Blood in urine present Glycosuria, Pollakiuria, Polyuria Proteinuria | |
|
Reproductive system and breast disorders |
Polymenorrhoea | |
|
General disorders and administration site conditions |
Pyrexia |
Asthenic conditions, Chills, Cold sweat, Hyperhidrosis, Influenza like illness, Oedema peripheral, Pain and discomfort NEC |
Post-marketing experience
During post-approval use of Rifaximin further undesirable effects have been reported.
The frequency of these reactions is not known (cannot be estimated from the available data).
|
MedDRA System Organ Class (ver. |
Frequency not known |
|
12.1) |
|
MedDRA System Organ Class (ver. 12.1) |
Frequency not known |
|
Infections and infestations |
Clostridial infections |
|
Blood and lymphatic system disorder |
Thrombocytopenia |
|
Immune system disorders |
Anaphylactic responses, Angioedemas, Hypersensitivity |
|
Vascular disorders |
Presyncope |
|
Hepatobiliary disorders |
Liver function tests abnormalities |
|
Skin and subcutaneous tissue disorders |
Dermatitis Eczema Erythemas Pruritus NEC Urticarias |
|
Investigations |
International normalised ratio abnormalities |
4.9 Overdose
No case of overdose has been reported.
In clinical trials with patients suffering from traveller’s diarrhoea doses of up to 1800 mg/day have been tolerated without any severe clinical signs.
In case of overdose gastric emptying and administration of appropriate supportive treatment are recommended.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: intestinal anti-infective agents, antibiotics. ATC code: A07AA11
Mode of action
Rifaximin is an antibacterial agent of the rifamycin class that binds irreversibly to the beta sub-unit of the bacterial enzyme DNA-dependent RNA polymerase and consequently inhibits bacterial RNA synthesis.
Mechanism of resistance
The main mechanism of acquiring resistance to rifaximin appears to involve: a mutation in the rpoB gene encoding the bacterial RNA polymerase.
Susceptibility
Rifaximin is a non-absorbed antibacterial agent.In vitro susceptibility testing cannot be used to reliably establish susceptibility or resistance of bacteria to Rifaximin. There are currently insufficient data available to support the setting of a clinical breakpoint for susceptibility testing.
5.2 Pharmacokinetic properties Absorption
Pharmacokinetic studies in rats, dogs and humans demonstrated that after oral administration Rifaximin in the polymorph a form is virtually not absorbed (less than 1%). Following the administration of therapeutic doses of Rifaximin in healthy volunteers and patients with damaged intestinal mucosa (Inflammatory Bowel Disease), plasma levels are negligible (less than 10 ng/ml). Systemic absorption of Rifaximin is increased but not by a clinically relevant extent by administration within 30 minutes of a high-fat breakfast.
Elimination
The urinary recovery of Rifaximin does not exceed 0.4% of the administered dose.
Special Populations
No clinical data are available on the use of Rifaximin in patients with impaired renal function.
In patients with hepatic encephalopathy mean peak plasma concentrations of 13.5 ng/mL Rifaximin were detected after administration of 800 mg Rifaximin three times daily for 7 days. Less than 0.1% of the administered dose was recovered after 7 days. Because of the limited systemic absorption of Rifaximin, no specific dosing adjustments are recommended for patients with hepatic insufficiency.
5.3 Preclinical safety data
Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity and genotoxicity Morphological alterations have been observed in the foetuses of Rifaximin orally administered rats and rabbits.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Tablet core:
Sodium starch glycolate type A glycerol distearate colloidal anhydrous silica talc
microcrystalline cellulose
Tablet coating: hypromellose, titanium dioxide disodium edetate propylene glycol red iron oxide E172.
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
Original packing: 3 years.
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
PVC/PE/PVDC-Aluminium blister packs containing 9 tablets.
6.6 Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
Alfa Wassermann S.p.A.
Via E. Fermi, 1 65020 Alanno (Pescara),
ITALY
MARKETING AUTHORISATION NUMBER(S)
PL 13687/0001
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DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
02/12/2010
DATE OF REVISION OF THE TEXT
27/03/2015