Xifaxan

Package leaflet: Information for the user

Warning! Keep this leaflet! Information on the immediate packaging in a foreign language.
Xifaxan (Normix 200 mg), 200 mg, film-coated tablets
Rifaximinum
Xifaxan and Normix 200 mg are different trade names for the same medicine.
Please read the leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet for future reference.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not give it to others. The medicine may harm another person, even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of the leaflet:

1. What Xifaxan is and what it is used for
2. Important information before taking Xifaxan
3. How to take Xifaxan
4. Possible side effects
5. How to store Xifaxan
6. Contents of the pack and other information

1. What Xifaxan is and what it is used for

Xifaxan is an oral antibacterial medicine. It contains rifaximin, an antibiotic belonging to a class of medicines called rifamycins. Unlike other rifamycins, it is only minimally absorbed from the intestine into the bloodstream (the α polymorphic form is absorbed at less than 1% of the administered dose), thus acting exclusively on microorganisms present in the intestine. Xifaxan is active against most bacteria responsible for intestinal infections.
Indications

For adults and children over 12 years of age:

• intestinal infections caused by bacteria sensitive to rifaximin, excluding diarrhoea associated with fever and/or blood in the stool, and also when the number of unformed stools is equal to or exceeds 8 per day;
• travellers' diarrhoea, excluding diarrhoea associated with fever and/or blood in the stool, and also when the number of unformed stools is equal to or exceeds 8 per day.

For adults only:

• hepatic encephalopathy;
• symptomatic, uncomplicated diverticular disease of the colon in adult patients following a high-residue diet.

2. Important information before using Xifaxan

When not to use Xifaxan:

• if the patient is allergic to rifaximin or other rifamycins, or to any of the other ingredients of this medicine (listed in section 6);
• if the patient has intestinal obstruction, even partial (a blockage in the intestine that prevents food from passing through), or severe ulcerative intestinal damage.

Warnings and precautions
Before starting treatment, discuss the following issues with your doctor:

• if the patient has diarrhoea accompanied by fever or blood in the stool, or frequent bowel movements (8 times or more per day) – such symptoms are usually caused by significant intestinal mucosal involvement by invasive intestinal pathogens (such as Campylobacter, Salmonella, and Shigella). Due to minimal absorption of Xifaxan in the gastrointestinal tract, it is not effective in these cases, and therefore this medicine should not be used;
• if the patient has impaired kidney function, as there are no studies available in this patient group;
• in patients with liver cirrhosis (a type of liver disease), a severe, potentially life-threatening skin reaction may occur, characterized by painful rash or formation of blisters on the skin, mouth, eyes, and genitals. If a severe skin reaction or any other hypersensitivity reaction occurs, the drug must be discontinued immediately and medical advice sought.

If diarrhoea worsens or persists for longer than 24–48 hours, discontinue Xifaxan. The doctor will consider alternative therapy.
Diarrhoea caused by Clostridium difficile infection (leading to a condition called pseudomembranous colitis) has been reported during treatment with nearly all antibacterial agents. The most common symptoms of this infection include frequent watery stools, sometimes with blood, severe cramps or abdominal pain, and fever. A potential association between rifaximin treatment and the occurrence of this infection cannot be excluded. Contact your doctor if symptoms of this disease occur.
Contact your doctor if reddish discoloration of urine occurs after taking Xifaxan. This is due to the active substance, which, like most antibiotics in the same class (rifamycins), has a red-orange color.

Children
Xifaxan should not be given to children under 12 years of age.

Xifaxan and other medicines
Inform your doctor about all medicines you are currently taking, including those available without a prescription.
In particular, inform your doctor if you are taking any of the following medicines: another antibiotic from the rifamycin group for systemic bacterial infection, warfarin, antiepileptic drugs, antiarrhythmic drugs, or cyclosporine.
If you are taking activated charcoal, Xifaxan should be taken at least 2 hours after activated charcoal.

In patients receiving warfarin who were also prescribed Xifaxan, both decreased and increased values of the International Normalized Ratio (INR) have been observed. If concomitant use of both medicines is necessary, INR should be carefully monitored at the start and after completion of Xifaxan treatment. Your doctor may need to adjust the dose of oral vitamin K antagonists (anticoagulants).

Pregnancy, breastfeeding, and fertility
If you are pregnant, think you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor before using this medicine.
As a precautionary measure, the use of rifaximin during pregnancy is not recommended.
If Xifaxan is used in breastfeeding women, the doctor will discuss with the patient whether to discontinue breastfeeding or to stop treatment with Xifaxan.

Animal studies have not shown any direct or indirect harmful effects on male or female fertility.

Driving and operating machinery
The effect of Xifaxan on the ability to drive vehicles or operate machinery is negligible.
However, caution is advised. If adverse effects such as dizziness, double vision, or drowsiness occur, the patient should not drive or operate machinery.

Xifaxan contains less than 1 mmol (23 mg) of sodium per 2 tablets, meaning the medicine is considered "sodium-free".

3. How to take Xifaxan

This medicine should always be taken exactly as directed by your doctor. If you are unsure, consult your doctor or pharmacist.

The recommended dosage of Xifaxan is as follows:

Bacterial intestinal infections caused by rifaximin-sensitive bacteria:
Patients over 12 years of age: 200 mg (1 tablet) every 8 hours up to 400 mg (2 tablets) every 8–12 hours.

Traveler's diarrhea:
Patients over 12 years of age: 200 mg (1 tablet) every 8 hours for 3 days. Do not use for longer than 3 days. Do not repeat the treatment if diarrhea symptoms return after a short period following recovery (see "Warnings and precautions").

Hepatic encephalopathy:
Adult patients: 400 mg (2 tablets) every 8 hours.
The treatment duration should not exceed 7 days.

Symptomatic uncomplicated diverticular disease of the colon:
Adult patients on a high-fiber diet: 400 mg (2 tablets of 200 mg) every 12 hours for 7 days. If necessary, your doctor may recommend repeating the treatment once per month over the next 11 months, for a maximum of 12 cycles of 7 days each. After complete resolution of symptoms, treatment should be discontinued.

A single course of treatment with rifaximin should not last longer than 7 days.
Each new course of treatment with rifaximin should be preceded by a 30-day treatment-free interval. If symptoms worsen or recur during this interval, the patient should contact their doctor immediately.

Patients with renal impairment: although dosage adjustment is not recommended, caution should be exercised in this patient group.

Patients with hepatic impairment: no dose adjustment is necessary in this patient group.

Elderly patients: no dosage adjustment is required, as safety and efficacy data for Xifaxan have shown no differences between elderly patients and younger individuals.

Children: the efficacy and safety of rifaximin have not been established in children under 12 years of age.

Method of administration
This medicine may be taken with or without food. Administer orally with a glass of water.

Taking more Xifaxan than prescribed
If you take more than the prescribed dose, contact your doctor or pharmacist immediately.
If possible, bring the Xifaxan medicine and its packaging with you to show the doctor or pharmacist.

Missing a dose of Xifaxan
If you miss a dose at the scheduled time, take it as soon as possible.
However, if it is almost time for your next dose, do not take the missed dose. Instead, take the next dose at the regular time. Do not take a double dose to make up for a missed tablet.

4. Possible adverse reactions

Like all medicines, Xifaxan may cause adverse reactions, although not everyone experiences them.

You should contact a doctor or the emergency department of the nearest hospital immediately if the patient experiences:

• fever or severe generalized allergic reaction usually affecting: the circulatory system, lungs, skin (pseudo-anaphylactic reaction), allergic reaction manifesting as skin swelling (dermatitis, exfoliative dermatitis, purpura, rash, rough skin, skin redness, itching, blisters) and (or) mucous membranes (angioedema), pre-syncopal state
• life-threatening reaction with influenza-like symptoms and painful skin rash affecting the skin, mouth, eyes, and genitals (Stevens-Johnson syndrome)*
• life-threatening reaction with influenza-like symptoms and blister formation on the skin, mouth, eyes, and genitals*.
  * These reactions have been observed in patients with liver cirrhosis. See also "Warnings and precautions" in section 2.

Frequent adverse reactions (occurring in 1 to 10 out of 100 patients): upper abdominal pain, constipation, sudden urge to defecate, diarrhoea, bloating with passage of gas, increased abdominal wall tension, nausea, painful straining at stool, vomiting, fever, headache, dizziness.

Uncommon adverse reactions (occurring in 1 to 10 out of 1,000 patients): upper abdominal pain, fluid in the abdominal cavity (ascites), dyspepsia, dry mouth, disturbances in gastrointestinal transit, presence of blood in stool, hard stools, stools containing mucus, taste disturbances, abnormal blood test results (increased white blood cells, i.e. lymphocytes, increased monocytes, decreased neutrophils), palpitations, dizziness, ear pain, double vision, asthenia, pain and discomfort, chills, cold sweats, excessive sweating, influenza-like illness, swelling of legs and (or) hands, increased aspartate aminotransferase activity, fungal infections (candidiasis), candidal vaginal infection, Herpes simplex, nasopharyngitis, pharyngitis, upper respiratory tract infections, decreased appetite, dehydration, back pain, muscle cramps, muscle weakness, muscle pain, neck pain, hypoesthesia (sensory disturbances), migraine, peripheral paraesthesia, sinus pain, somnolence, sleep disturbances, low mood, insomnia, restlessness, presence of blood in urine, glucose in urine, frequent urination, excessive urination, protein in urine, abnormally frequent menstruation, cough, dry throat, shortness of breath (dyspnoea), nasal congestion, sore throat and larynx, watery rhinorrhoea, skin rashes, skin lesions, urticaria (skin changes), photoallergic reactions, sudden facial flushing, increased blood pressure.

Frequency unknown (frequency cannot be estimated from available data): abnormal blood test results (decreased platelet count, abnormal liver function tests, abnormalities in international normalized ratio), infections with bacteria of the genus Clostridium (C. difficile), anaphylactic reactions, hypersensitivity, pre-syncopal state, angioedema (allergic reaction manifesting as swelling of the skin and (or) mucous membranes), dermatitis, exfoliative dermatitis, rash, skin redness, pruritus, petechiae, urticaria.

Reporting of adverse reactions

If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, phone: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl.

Reporting adverse reactions allows the collection of further information on the safety of the medicine.

5. How to store the medicine Xifaxan

Keep this medicine out of sight and reach of children.
No special storage instructions apply.
Do not use Xifaxan after the expiry date stated on the packaging. The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Following this advice helps protect the environment.

6. Contents of the pack and other information

What Xifaxan contains

• The active substance is rifaximin. One coated tablet contains 200 mg of rifaximin.
• The other ingredients are:
  Tablet core: sodium carboxymethyl starch (type A), glycerol distearate, colloidal anhydrous silicon dioxide, talc, microcrystalline cellulose.
  Coating: hypromellose, titanium dioxide (E 171), disodium edetate, propylene glycol, iron oxide red (E 172).

What Xifaxan looks like and contents of the pack
Xifaxan is a medicine in the form of pink, round, biconvex coated tablets.
Xifaxan tablets are packed in blisters made of PVC-PE-PVDC/Aluminum, placed in a cardboard box.
Pack containing 12 tablets: 1 blister packed in a cardboard box.
Pack containing 24 tablets: 2 blisters packed in a cardboard box.
For more detailed information, please contact the marketing authorisation holder or the parallel importer.
Marketing Authorisation Holder in Italy, the country of export:
Alfasigma S.p.A.
Via Ragazzi del ‘99, n. 5
40133 Bologna (BO), Italy
Manufacturer:
Alfasigma S.p.A.
Via Pontina Km 30,400
00071 Pomezia (RM), Italy
Alfasigma S.p.A.,
Via E. Fermi, n. 1
65020 Alanno (PE), Italy
Parallel Importer:
InPharm Sp. z o.o.
ul. Strumykowa 28/11
03-138 Warsaw, Poland
Repackaged in:
Pharma Innovations Sp. z o.o.
ul. Jagiellońska 76
03-301 Warsaw, Poland
InPharm Sp. z o.o. Services sp. k.
ul. Chełmżyńska 249
04-458 Warsaw, Poland
Marketing Authorisation Number in Italy, the country of export: 025300029
Parallel Import Marketing Authorisation Number: 65/19