Active ingredients: Rifaximin
NORMIX 200 mg film-coated tablets NORMIX 2 g / 100 ml granules for oral suspension
Indications Why is Normix used? What is it for?
Normix is a Rifaximin-based drug, belonging to the category of antidiarrheal, anti-inflammatory and intestinal anti-infectives, antibiotics.
THERAPEUTIC INDICATIONS
- Acute and chronic intestinal infections sustained by gram-positive and gram-negative bacteria; diarrheal syndromes.
- Diarrhea due to an altered balance of the intestinal microbial flora (summer diarrhea, traveler's diarrhea, enterocolitis)
- Pre and post-operative prophylaxis of infectious complications in gastrointestinal tract surgery
- Adjuvant in the therapy of hyperammonemia
Contraindications When Normix should not be used
- Hypersensitivity to the active substance, rifamycins or to any of the excipients.
- Cases of intestinal obstruction, even partial, or severe ulcerative lesions of the intestine.
- Normix must not be used in patients with diarrhea complicated by fever or blood in the stool
Precautions for use What you need to know before taking Normix
Normix is not effective in treating intestinal infections caused by certain intestinal pathogens that normally cause diarrhea, fever, blood in the stool and high frequency of bowel movements. If symptoms worsen or persist for more than 48 hours, discontinue treatment and seek medical attention.
Due to the effects on the intestinal flora, the efficacy of oral contraceptives containing estrogen may decrease after administration of Normix. If you are taking oral contraceptives (particularly if the estrogen content is less than 50 mcg), you are advised to take additional precautions contraceptives.
Hepatic impairment: No dose adjustments are anticipated, however the drug should be used with caution in patients with severe hepatic impairment.
Interactions Which drugs or foods can modify the effect of Normix
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, even those obtained without a prescription.
In particular, tell your doctor or pharmacist if you are taking any of these drugs: warfarin, antiepileptics, antiarrhythmics, cyclosporine.
In case of taking activated charcoal, it is recommended to take Normix at least 2 hours after activated charcoal
Warnings It is important to know that:
Despite the negligible absorption of the drug (less than 1%), rifaximin, like all derivatives of rifamycin, can cause a reddish discoloration of the urine.
As with the use of most antibiotics, cases of Clostridium difficile associated diarrhea (CDAD) have been reported during rifaximin treatment, therefore the potential association of rifaximin treatment with CDAD or pseudomembranous colitis cannot be excluded.
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
Pregnancy
As a precaution, Normix should not be used during pregnancy.
Feeding time
It is unknown whether rifaximin and its metabolites are excreted in human milk. Since a risk to breast-fed infants cannot be excluded, a decision must be made whether to discontinue breast-feeding or to discontinue / abstain from rifaximin therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy. for the mother.
Driving and using machines
Dizziness and somnolence have been reported in clinical trials of the medicine, however the active substance Rifaximin has negligible influence on the ability to drive and use machines. If you feel dizzy or sleepy, you should not drive or use machines.
Important information about some of the ingredients
Normix granules for oral suspension contains sucrose If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
Patients with diabetes mellitus should take into account that the single dose of 10 ml oral suspension contains 2.88 g of sucrose.
Dosage and method of use How to use Normix: Dosage
Antidiarrheal treatment - Recommended dosage:
- Adults and children over 12 years: 1 tablet of 200 mg or 10 ml of oral suspension (equivalent to 200 mg of Rifaximin) every 6 hours;
Pre and post-operative treatment - Recommended dosage:
- Adults and children over 12 years: 2 tablets of 200 mg or 20 ml of oral suspension (equivalent to 400 mg of Rifaximin) every 12 hours;
Adjuvant treatment of hyperammonaemia - Recommended dosage:
- Adults and children over 12 years: 2 tablets of 200 mg or 20 ml of oral suspension (equivalent to 400 mg of Rifaximin) every 8 hours.
The medicine can be given with or without food.
In the opinion of the physician, the dosage can be varied in quantity and frequency.
Unless otherwise prescribed by a doctor, the treatment should not exceed 7 days.
Elderly patients
No dose adjustments are required because the safety and efficacy data of Normix revealed no differences between the elderly population and younger patients.
Hepatic impairment
No dose adjustments are required in patients with hepatic impairment, but caution should be exercised in patients with severe hepatic impairment (see "Precautions for use").
Renal impairment
Although no dose modifications are anticipated, caution should be exercised in patients with impaired renal function.
Children and adolescents
The safety and efficacy of rifaximin in children aged less than 12 years have not been established. No dose recommendations can be made in patients less than 12 years of age.
Method of administration
- Film-coated tablets: orally, with a glass of water
- Granules for oral suspension: orally. For instructions on preparing the suspension before administration, see the section below.
Preparation of the suspension
A measuring spoon is included in the package of granules for oral suspension (5 ml of suspension contain 100 mg of active ingredient).
5 ml = 100 mg of active ingredient
- Add water to the granules contained in the bottle up to the level mark and shake well. Then add water again to bring the suspension level back to the indicated mark.
- Shake the bottle vigorously before each administration.
- The suspension thus prepared is stable for 7 days at room temperature.
Overdose What to do if you have taken too much Normix
In case of accidental ingestion / intake of an overdose of Normix, notify your doctor immediately or go to the nearest hospital.
If you have any questions about the use of Normix, ask your doctor or pharmacist.
Side Effects What are the side effects of Normix
Like all medicines, Normix can have side effects, although not everybody gets them.
It is possible that many of the reactions listed, especially the gastrointestinal ones, coincide with the same symptoms as the diseases treated.
Common side effects (may affect up to 1 in 10 people)
- Headache, dizziness
- Abdominal pain, abdominal bloating and distension, flatulence (gas), constipation, diarrhea, urgency to evacuate stool, nausea, vomiting, painful and ineffective contractions to empty the bowel
- Fever
Uncommon side effects (may affect up to 1 in 100 people)
- Candida infections, inflammation or infections of the nose and throat, infections of the upper respiratory tract, herpes of the lips
- Abnormal blood test results (increased lymphocytes, increased monocytes, decreased neutrophils)
- Decreased appetite, reduced body fluids (dehydration)
- Abnormal dreams, mood depression, nervousness, insomnia, drowsiness,
- Headache localized on the forehead or on only one side of the head, tingling sensation, decreased tactile sensitivity
- Double vision
- Ear pain, dizziness
- Palpitations, hot flashes, increased blood pressure
- Difficulty in breathing, nasal congestion, dry throat, cough, nasal discharge, sore throat.
- Stomach pain, digestive difficulties, bowel motility disorders, dry lips, hard stools, blood in stools, mucus in stools, loss of taste sensation, collection of fluid in the abdomen (ascites)
- Increased liver enzyme (AST) values
- Localized skin reaction or spots, sun burns
- Muscle cramps, muscle weakness, muscle aches, neck pain, back pain
- Blood in urine, sugar in urine, protein in urine, increased frequency of urine emissions, increased volume of urine passed
- Close menstrual cycles
- Fatigue, feeling of weakness, cold sweats, profuse sweating, chest pain or discomfort, flu-like symptoms, swelling in the legs or arms, chills
The following undesirable effects have also been reported, the frequency of which cannot be estimated based on the available data
- Clostridium difficile infections
- Feeling faint, fainting, shaking
- Red skin (allergic dermatitis), skin with peeling skin (exfoliative dermatitis)
- Burning of the esophagus
- Presence of small purplish patches (purpura)
- Abnormal blood tests (decreased number of platelets, abnormal liver function tests, changes in blood clotting: international normalized ratio (INR) abnormal)
- Allergic reactions to the drug, in some very severe cases, up to shock
- Swelling of the face, lips, larynx
- Generalized itching, itchy genitals, local or generalized urticaria, erythema, red palms, widespread or measles-like skin reaction.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.
You can also report side effects directly via the Italian Medicines Agency - Website: http://www.agenziafarmaco.gov.it/it/responsabili.
By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Expiry: see the expiry date indicated on the package.
Do not use the medicine after the expiry date stated on the package. The expiry date refers to the last day of that month.
The suspension prepared by adding water to the granules for oral suspension is stable for 7 days at room temperature.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
Composition and Pharmaceutical Form
Film-coated tablets 200 mg
One tablet contains: Active ingredient: Rifaximin 200 mg Excipients: Sodium starch glycolate (type A), glycerol distearate, anhydrous colloidal silica, talc, microcrystalline cellulose, hypromellose, titanium dioxide E171, disodium edetate, propylene glycol, red iron oxide E172.
Granules for oral suspension 2 g / 100 ml 100 ml
of reconstituted suspension contain: Active ingredient: Rifaximin 2 g Excipients: Microcrystalline cellulose, croscarmellose sodium, pectin, kaolin, sodium saccharin, sodium benzoate, sucrose, black cherry flavor.
PHARMACEUTICAL FORM AND CONTENT
Film-coated tablets 200 mg: blister packs of 12 tablets.
Granules for oral suspension 2 g / 100 ml: bottle of 60 ml
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
NORMIX
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
A coated tablet with film contains:
Active ingredient: rifaximin 200 mg
100 ml of Suspension reconstituted contain:
Active ingredient: rifaximin 2 g
Excipients with known effects: the granules for oral suspension contain sucrose.
For the full list of excipients, see section 6.1
03.0 PHARMACEUTICAL FORM
Film-coated tablets.
Granules for oral suspension.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
• Acute and chronic intestinal infections caused by gram-positive and gram-negative bacteria; diarrheal syndromes.
• Diarrhea due to an altered balance of the intestinal microbial flora (summer diarrhea, traveler's diarrhea, enterocolitis).
• Pre and post-operative prophylaxis of infectious complications in gastrointestinal tract surgery.
• Adjuvant in the therapy of hyperammonemia.
04.2 Posology and method of administration
Antidiarrheal treatment
Recommended dosage:
Adults and children over 12 years old: 1 tablet of 200 mg or 10 ml of oral suspension (equivalent to 200 mg of Rifaximin) every 6 hours;
Pre and post-operative treatment
Recommended dosage:
Adults and children over 12 years old: 2 tablets of 200 mg or 20 ml of oral suspension (equivalent to 400 mg of Rifaximin) every 12 hours;
Adjuvant treatment of hyperammonemia
Recommended dosage:
Adults and children over 12 years old: 2 tablets of 200 mg or 20 ml of oral suspension (equivalent to 400 mg of Rifaximin) every 8 hours; in the opinion of the physician, the dosage can be varied in quantity and frequency.
Unless otherwise prescribed by a doctor, the treatment should not exceed 7 days.
Pediatric population
The safety and efficacy of Rifaximin in children aged less than 12 years have not been established.
Currently available data are described in section 5.1 but no recommendation on a posology can be made.
Method of administration of the granules for oral suspension
A measuring spoon is included in the package of granules for oral suspension (5 ml of suspension contain 100 mg of active ingredient).
Preparation of the suspension
Add water to the granules contained in the bottle up to the level mark and shake well. Then add water again to bring the suspension level back to the indicated mark.
Shake the bottle vigorously before each administration.
The suspension thus prepared is stable for 7 days at room temperature.
04.3 Contraindications
Hypersensitivity to the active substance, rifamycins or to any of the excipients listed in section 6.1.
Cases of intestinal obstruction, even partial, or severe ulcerative lesions of the intestine.
Rifaximin should not be used in patients with diarrhea complicated by fever or blood in the stool.
04.4 Special warnings and appropriate precautions for use
During prolonged treatments at high doses, or if there are lesions of the intestinal mucosa, it is possible that the product is absorbed in a small part (less than 1%) and causes, being eliminated in the urine, a pink-red color of the same: this it depends exclusively on the active ingredient, which has a red-orange color, like most of the antibiotics of the family to which it belongs (rifamycins).
In the event of the development of microorganisms that are not sensitive to the antibiotic, treatment must be interrupted and suitable therapy instituted.
Cases of Diarrhea associated with have been reported with the use of most antibiotics, including Rifaximin Clostridium difficile (CDAD). A possible association of Rifaximin treatment with CDAD or pseudomembranous colitis cannot be excluded.
Important information about some of the ingredients
NORMIX 2 g / 100 ml granules for oral suspension contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrase isomaltase insufficiency should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction
Absorption of Rifaximin from the gastrointestinal tract is less than 1% of the oral dose; the antibiotic therefore does not pose problems of drug interactions at a systemic level.
Clinical studies of pharmacokinetic interactions between Rifaximin and drugs metabolised by isoenzymes of the cytochrome P450 group have shown that Rifaximin does not alter the pharmacokinetic behavior of midazolam or an oral contraceptive containing ethinyl estradiol and norgestimate. Therefore, clinical interactions with drugs metabolised by these isoenzymes are not expected.
However, changes in intestinal flora during treatment with antibiotics may have an effect on the enterohepatic circulation of estrogens, with a possible decrease in plasma estrogen concentrations which may affect contraceptive efficacy. It is recommended to use additional contraceptives, particularly if the estrogen content is less than 50 mcg.
Patients should take Rifaximin at least 2 hours after administration of activated charcoal.
04.6 Pregnancy and lactation
Fertility
Animal studies do not indicate direct or indirect harmful effects with respect to fertility (see section 5.3).
Due to the effects on the intestinal flora, the efficacy of oral estrogenic contraceptives may decrease after administration of Rifaximin. However, such interactions have not been commonly reported. However, it is advisable to take additional contraceptive precautions, particularly if the estrogen content is less than 50 micrograms (see section 4.5).
Pregnancy
There are no data on the use of Rifaximin in pregnant women.
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).
As a precautionary measure, the use of Rifaximin during pregnancy is not recommended.
Feeding time
It is not known whether Rifaximin or its metabolites are excreted in human milk.
A risk to the baby during breastfeeding cannot be excluded.
A decision must be made whether to discontinue breast-feeding or to discontinue / abstain from Rifaximin therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
04.7 Effects on ability to drive and use machines
Dizziness and somnolence have been reported in placebo-controlled clinical trials, however Rifaximin has negligible influence on the ability to drive and use machines.
04.8 Undesirable effects
Adverse reactions, considered at least possibly related to Rifaximin, were classified by organ system and by frequency:
• very common (≥ 1/10)
• common (≥ 1/100
• uncommon (≥ 1/1.000, ≤ 1/100)
• rare (≥ 1 / 10,000, ≤ 1 / 1,000)
• very rare (≤ 1 / 10,000)
not known (frequency cannot be estimated from the available data).
Clinical trials
The effects of Rifaximin with placebo or other antibiotics have been compared in double-blind controlled clinical trials or clinical pharmacology studies, for which quantitative safety data are available.
Note: Many of the listed reactions (particularly gastrointestinal reactions) may be the same symptoms attributable to the underlying disease being treated and have been reported with a similar frequency in placebo-treated patients during clinical trials.
Infections and infestations
Uncommon: candidiasis, herpes simplex, nasopharyngitis, pharyngitis, upper respiratory tract infections.
Disorders of the blood and lymphatic system
Uncommon: lymphocytosis, monocytosis, neutropenia.
Metabolism and nutrition disorders
Uncommon: anorexia, dehydration.
Psychiatric disorders
Uncommon: insomnia, abnormal dreams, mood depression, nervousness.
Nervous system disorders
Common: dizziness, headache.
Uncommon: ageusia, migraine, hypoesthesia, paraesthesia, sinus headache, somnolence.
Eye disorders
Uncommon: diplopia.
Ear and labyrinth disorders
Uncommon: vertigo, ear pain.
Cardiac pathologies
Uncommon: palpitations.
Vascular pathologies
Uncommon: hot flashes.
Respiratory, thoracic and mediastinal disorders
Uncommon: dyspnoea, nasal congestion, dry throat, pharyngolaryngeal pain, cough, rhinorrhea.
Gastrointestinal disorders
Common: constipation, abdominal pain, abdominal distension, diarrhea, flatulence, nausea, rectal tenesmus, urgency to evacuate, vomiting.
Uncommon: ascites, dyspepsia, gastrointestinal motility disorders, upper abdominal pain, haematochezia, mucous stools, hard stools, dry lips.
Hepatobiliary disorders
Uncommon: increased aspartate aminotransferase.
Skin and subcutaneous tissue disorders
Uncommon: rash, macular rash, cold sweat.
Musculoskeletal and connective tissue disorders
Uncommon: back pain, muscle weakness, myalgia, muscle spasms, neck pain.
Renal and urinary disorders
Uncommon: glycosuria, pollakiuria, polyuria, proteinuria.
Diseases of the reproductive system and breast
Uncommon: polymenorrhea.
General disorders and administration site conditions
Common: pyrexia.
Uncommon: fatigue, asthenia, chills, pain, chest pain, chest discomfort, peripheral edema, flu-like symptoms, hyperhidrosis.
Diagnostic tests
Uncommon: blood pressure increased, blood in urine.
Injury, poisoning and procedural complications
Uncommon: sun burn.
Post-marketing experience
After the introduction of the product on the market, the following adverse reactions have been reported very rarely, the frequency of which cannot be estimated: oesophageal burning, edema of the face, edema of the larynx, presyncope, syncope, anaphylactic reactions (including anaphylactic shock) , hypersensitivity, agitation, angioneurotic edema, purpura, generalized pruritus, genital pruritus, erythema, palmar erythema, exfoliative dermatitis, allergic dermatitis, exanthema, erythematous rash, morbilliform rash, local or generalized urticaria, clostridial infections (C. difficult), thrombocytopenia, altered international normalized ratio (INR), altered liver function tests.
04.9 Overdose
There have been no reported cases of overdose with Rifaximin.
In clinical studies with patients with traveler's diarrhea, doses up to 1,800 mg / day were tolerated without any severe clinical symptoms. Even in patients / subjects with normal bacterial flora, Rifaximin at dosages up to 2,200 mg / day for 7 days did not cause any relevant clinical symptoms that could be related to the high dosage.
Therefore, in the event of an accidental overdose, symptomatic treatment and supportive measures are recommended if necessary.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
The NORMIX specialty contains Rifaximin [4-deoxy-4 "-methyl pyrido (1", 2 "-1,2) imidazo (5,4-c) Rifamycin SV] in the polymorphic alpha (α) form.
Pharmacotherapeutic group: antidiarrheals, intestinal anti-inflammatory and anti-infectives, antibiotics.
ATC code: A07AA11.
The in-depth investigations carried out on the antibacterial activity of Rifaximin have shown that this antibiotic, derivative of Rifamycin, possesses the same broad spectrum of activity against numerous aerobic and anaerobic gram-positive and gram-negative bacterial species. The characteristic of Rifaximin in the polymorphic alpha (α) form it is poorly absorbed in the gastrointestinal tract; it is therefore an agent with local activity that exerts an "effective antimicrobial action both against pathogenic species and in clinical situations in which it is useful to reduce the intestinal endogenous bacterial load .
Pediatric use
The efficacy, safety and posology of Rifaximin in children below 12 years of age have not been established.
A review of the scientific literature identified 9 efficacy studies in the pediatric population that included 371 children, 233 of whom were treated with Rifaximin. Most of the children enrolled were over 2 years old. The common feature of all studies was diarrhea of bacterial origin (ascertained before, during or after treatment).
The data (the studies "for itself"and a meta-analysis) show the existence of a positive trend demonstrating the efficacy of Rifaximin in a particular condition (acute diarrhea - mainly recurrent or relapsing - which is known or hypothesized to be caused by non-invasive bacteria sensitive to Rifaximin , like l "Escherichia Coli).
The most commonly used dosage in children aged 2-12 years in these limited studies with a few patients was in the range of 20-30 mg / kg / day in 2-4 administrations (see section 4.2).
05.2 Pharmacokinetic properties
Pharmacokinetic studies performed in rats, dogs and humans with Rifaximin have shown very poor absorption (less than 1%) of the product administered orally. In comparative pharmacokinetic studies it has been shown that Rifaximin in polymorphic forms other than the & aplha; it has considerably higher absorptions.
The pharmacokinetics of Rifaximin 400 mg, after single oral administration to fasted adult subjects, are characterized by mean values of C max not exceeding 5 ng / ml and AUC not exceeding 15 ng.h / ml. The accurate determination of these values is possible through the use of analytical methods that allow the determination of the plasma levels of Rifaximin with a sensitivity of 0.5 ng / ml. The urinary excretion in humans after oral administration of Rifaximin does not exceed 0.4% of the administered dose.
05.3 Preclinical safety data
The pharmaco-toxicological experiments carried out in various animal species (rat - rabbit - dog) with Rifaximin have not highlighted phenomena attributable to the toxicity of the product. In repeated toxicity tests in rats (6 months) and dogs (9 months), Rifaximin up to the maximum doses tested per os (rat: 300 mg / kg; dog: 1,000 mg / kg) did not modify the most important functional parameters. , confirming the excellent tolerability of the product.
Studies of reproduction, teratology and neonatal development excluded any modification and alteration of the "maternal-fetal" unit balance attributable to the treatment.
Rifaximin is not mutagenic.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Film-coated tablets: sodium starch glycolate, glycerol distearate, anhydrous colloidal silica, talc, microcrystalline cellulose, hypromellose, titanium dioxide E 171, disodium edetate, propylene glycol, red iron oxide E 172.
Granules for oral suspension: microcrystalline cellulose, croscarmellose sodium, pectin, kaolin, sodium saccharin, sodium benzoate, sucrose, black cherry flavor.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
Film-coated tablets and granules for oral suspension: 3 years.
The suspension prepared by adding water to the granules for oral suspension is stable for 7 days at room temperature.
06.4 Special precautions for storage
This medicine does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
Film-coated tablets: a blister consisting of PVC-PE-PVDC / Aluminum containing 12 film-coated tablets.
Granules for oral suspension: dark glass bottle, hermetically sealed with an aluminum cap, containing granules for oral suspension. A measuring cup is included in the package.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
ALFA WASSERMANN S.p.A.
Registered office: Via E. Fermi, n. 1 - Alanno (PE)
Administrative office: Via Ragazzi del "99, n. 5 - Bologna
08.0 MARKETING AUTHORIZATION NUMBER
NORMIX 200 mg film-coated tablets - 12 tablets - AIC n. 025300029
NORMIX 2 g / 100 ml granules for oral suspension - bottle of 60 ml - AIC n. 025300043
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
23/04/1985 - 01/06/2010
10.0 DATE OF REVISION OF THE TEXT
AIFA Determination of 07/09/2012
