NORMIX

Trade name of the medicinal product

NORMIX

Composition

200 mg film-coated tablets

One film-coated tablet contains:

Active ingredient: Rifaximin 200 mg.

Excipients: sodium starch glycolate, glycerol distearate, colloidal anhydrous 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 reconstituted suspension contains:

Active ingredient: Rifaximin 2 g.

Excipients: microcrystalline cellulose, croscarmellose sodium, pectin, kaolin, sodium saccharin, sodium benzoate (E211), sucrose, cherry flavouring.

Pharmaceutical forms and packagings

• 200 mg film-coated tablets. Blister containing 12 film-coated tablets.
• 2 g/100 ml granules for oral suspension. Bottle containing 60 ml.

Pharmacotherapeutic class

Anti-diarrhoea, anti-inflammatory and intestinal anti-infective, antibiotics.

Name and address of the manufacturer

Alfasigma S.p.A. - Alanno (Pescara) - Italy

Therapeutic indications

• Acute and chronic intestinal infections sustained by gram-positive and gram-negative bacteria; diarrhoeic syndrome.
• Diarrhoea caused by an altered equilibrium of the intestinal microbial flora (summer diarrhoea, traveller's diarrhoea, enterocholitis).
• Pre- and post-operative prophylaxis of infective complications in surgery of the gastroenteric region.
• Coadjuvant in the treatment of hyperammonemia.

Contra-indications

• Hypersensitivity to the active substance, rifamycin-derivatives or any of the excipients.
• Cases of intestinal obstruction, even partial, or severe ulcerous lesions of the intestine.
• Normix should not be administered in patients with diarrhoea complicated by fever or blood in the stool.

Precautions for use

Normix is not effective in the treatment of intestinal infections due to intestinal pathogens, which typically cause diarrhoea, fever, blood in the stools and high stool frequency.

Discontinue the treatment if symptoms get worse or persist for more than 48 hours and consult your doctor.

Hepatic impairment: although no dosage change is expected, caution should be used in patients with severe hepatic impairment.

Fertility, pregnancy and breast-feeding

Pregnancy

Normix is not recommended during pregnancy.

Breast-feeding

It is unknown whether rifaximin and its metabolites are excreted in human milk. A risk for the newborns/infants cannot be excluded. A decision must be taken whether to discontinue breast-feeding or to discontinue/abstain from Normix therapy taking into account the benefits of breast-feeding for the child and the benefit of therapy for the mother.

Fertility

Animal studies do not indicate direct or indirect harmful effects with respect to male and female fertility.

Interaction with other medicaments and other form of interaction

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicine. In particular, inform your doctor or pharmacist if you are taking any of these drugs: warfarin, antiepileptics, antiarrhythmics, cyclosporine and oral contraceptives.

Both decreases and increases in international normalized ratio have been reported in patients maintained on warfarin and prescribed rifaximin. If co-administration is necessary, the international normalized ratio should be carefully monitored with the addition or withdrawal of rifaximin. Adjustments in the dose of oral anticoagulants may be necessary.

In case of charcoal administration, it is advisable to take NORMIX at least 2 hours after charcoal.

Special warnings

Talk to your doctor or pharmacist before taking NORMIX.

If you have ever developed a severe skin rash or skin peeling, blistering and/or mouth sores after taking rifaximin.

Clostridioides-difficile-associated diarrhoea (CDAD) has been reported with the use of nearly all antibacterial agents, including rifaximin. The potential association of rifaximin treatment with CDAD or pseudomembranous colitis cannot be ruled out.

Caution should be used when concomitant use of rifaximin and a P-glycoprotein inhibitor such as cyclosporine is needed.

Both decreases and increases in international normalized ratio (in some cases with bleeding events) have been reported in patients maintained on warfarin and prescribed rifaximin. If co-administration is necessary, the international normalized ratio should be carefully monitored with the addition or withdrawal of treatment with rifaximin. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation.

Despite the negligible absorption of the drug (less than 1%), like all rifamycin derivatives, rifaximin may cause a reddish discoloration of the urine.

Keep out of the sight and reach of children.

NORMIX granules for oral suspension contains sucrose, sodium benzoate, and sodium

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

This medicinal product contains 2.88 g of sucrose (sugar) per 10 ml of reconstituted suspension. This should be taken into consideration in patients with diabetes mellitus.

This medicinal product contains 6 mg of sodium benzoate per 10 ml dose of reconstituted suspension, equivalent to 60 mg per 100 ml.

This medicine contains less than 1 mmol (23 mg) of sodium per dose (10 ml of reconstituted suspension), meaning it is essentially “sodium-free”.

NORMIX film-coated tablets contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning it is essentially “sodium-free”.

Driving and using machines

Dizziness and somnolence have been reported in clinical studies on this medicine; however, the active substance rifaximin has negligible influence on the ability to drive and use machines. Do not drive vehicles and do not use machines if you react to the use of Normix by dizziness or somnolence.

Posology and method of administration

Anti-diarrhoeic treatment - Recommended dose

• Adults and children over 12 years of age: one 200 mg tablet every 6 hours.
• Children from 6 to 12 years of age: half to one 200 mg tablet every 6 hours.
• Children from 2 to 6 years of age: one 5 ml dose of oral suspension (equal to 100 mg) every 6 hours.

Pre- and post-operative treatment - Recommended dose

• Adults and children over 12 years of age: two 200 mg tablets every 12 hours.
• Children from 6 to 12 years of age: one to two 200 mg tablets every 12 hours.
• Children from 2 to 6 years of age: one to two 5 ml doses (equal to 100-200 mg) every 12 hours.

Coadjuvant treatment of hyperammonemia - Recommended dose

• Adults and children over 12 years of age: two 200 mg tablets every 8 hours.
• Children from 6 to 12 years of age: one to one and a half 200 mg tablets every 8 hours.
• Children from 2 to 6 years of age: one to two 5 ml doses (equal to 100-200 mg) every 8 hours.

Doses may be modified in quantity and frequency, depending on the doctor's advice.

Unless otherwise prescribed, treatment should not exceed 7 days.

Elderly

No dosage adjustment is necessary as the safety and efficacy data of NORMIX showed no differences between the elderly and the younger patients.

Hepatic impairment

No dosage adjustment is necessary for patients with severe hepatic impairment.

Renal impairment

Although dosage change is not anticipated, caution should be used in patients with impaired renal function.

Method of administration

• Film-coated tablets: orally with a glass of water. This medicine can be administered with or without food.
• Granules for oral suspension: orally. For instructions on preparation of the suspension before administration, see below.

Content of the pack

The granules for oral suspension include a dosing spoon (5 ml of suspension contains 100 mg of active ingredient).

5 ml = 100 mg of active substance

Reconstitution of the suspension

1. Add water to the granules contained in the bottle up to the line, and shake it well.
2. Add water again until the suspension level reaches the line indicated.

Suspension, when reconstituted as above, is stable for 7 days at room temperature.

Shake it well before use.

Overdosage

In case of accidental ingestion/administration of an excessive dose of NORMIX, contact immediately your doctor or go to the nearest hospital.

In clinical trials with patients suffering from traveller's diarrhoea, doses of up to 1800 mg/day have been tolerated without any severe clinical sign. Even in patients/subjects with normal bacterial flora, rifaximin in dosages of up to 2400 mg/day for 7 days did not result in any relevant clinical symptoms related to the high dosage.

If you have doubts on the use of NORMIX, consult your doctor or pharmacist.

Side effects

Like all medicines, NORMIX can cause side effects, although not everybody gets them.

Stop using rifaximin and seek medical attention immediately if you notice any of the following symptoms:

Reddish non-elevated, target-like or circular patches on the trunk, often with central blisters, skin peeling, ulcers of mouth, throat, nose, genitals and eyes. These serious skin rashes can be preceded by fever and flu-like symptoms.

It is possible that many of the listed reactions, in particular those gastrointestinal, coincide with the same symptoms of the treated diseases.

Common side effects (may affect up to 1 in 10 people)

• Headache, dizziness.
• Abdominal pain, abdominal distension, flatulence (gas), constipation, diarrhoea, urgency to evacuate stool, nausea, vomiting, painful contractions and inability to empty the bowel at defecation.
• Fever.

Uncommon side effects (may affect up to 1 in 100 people)

• Candida infections, inflammation or infection of the nose and throat, infections of upper respiratory tract, cold sores (herpes lips).
• Abnormal blood test results (increase of lymphocytes, monocytes increased, neutrophils decreased).
• Decreased appetite, reduction of body fluids (dehydration).
• Abnormal dreams, mood depression, nervousness, insomnia, drowsiness.
• Headache localized on the forehead or on one side of the head, physical sensation of tingling or tickling “pins and needles”, reduced sense of touch/sensation.
• Double vision.
• Ear pain, sensation of the room going round (vertigo).
• Heart racing (palpitation), flushing, increased blood pressure.
• Shortness of breath, cough, blocked nose, runny nose, sore throat, dry throat.
• Stomach pain, digestive problems, intestinal-movement disorders, dry lips, hard stools, blood in stool, mucus in stool, taste disorders, collection of fluid in the abdomen (ascites).
• Elevations of liver enzymes (AST).
• Localized skin reaction, blotchy skin, sunburn.
• Muscle cramps, muscle weakness, muscle pain, neck pain, back pain.
• Blood in urine, sugar in urine, proteins in urine, frequent urination, excessive urination.
• Frequent menstrual cycles.
• Fatigue, weakness, cold sweat, increased perspiration, chest pain or discomfort, flu-like symptoms, legs or arms swelling, chills.

Side effects with frequency not known

The following side effects have also been reported; however, their frequency cannot be estimated from the available data:

• Clostridium difficile infections.
• Feeling faint.
• Flushed skin (allergic dermatitis), peeling skin (exfoliative dermatitis).
• Presence of small violet patches on skin (purpura).
• Alteration of blood tests (decreased number of platelets, abnormal liver function tests, alterations in blood clotting: results of international normalized ratio (INR) abnormal).
• Allergic reactions to the drug, in some cases very severe, which may lead to shock.
• Swelling of the face, lips, larynx.
• Generalized itching, genital itching, local or generalized hives, rash, redness of the palms, skin reaction diffuse or similar to measles.

The compliance with the instructions contained in the leaflet reduces the risk of side effects.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.

Should any more severe or different side effects occur, please inform your doctor.

Revision of information leaflet: July 2024