Xifaxan

Package leaflet: Information for the user

Xifaxan, 100 mg/5 ml, granules for oral suspension
Rifaximinum
Please read this leaflet carefully before taking this medicine, as it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm them even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet contents:

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 the class of drugs known as rifamycins. However, 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), so it acts locally on microorganisms present in the intestine. Xifaxan is active against most bacteria responsible for intestinal infections.

Indications for use

In adults and children over 12 years of age:

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

In adults:

• Irritable bowel syndrome with diarrhoea (IBS-D).
• Hepatic encephalopathy.
• Symptomatic, uncomplicated diverticular disease of the colon in adult patients on 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 with your doctor or pharmacist:

• If the patient has ever experienced severe skin rash, skin peeling, blisters, or sores in the mouth and/or oral mucosal ulcers after taking rifaximin.
• if the patient has diarrhoea accompanied by fever or blood in the stool, or frequent bowel movements (8 times or more per day) – see below
• if the patient has impaired kidney function, as there are no studies available in this patient group

Special caution is required when using rifaximin. Severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported during treatment with rifaximin. Most of these cases were reported in patients with liver disease (such as cirrhosis or hepatitis). If any severe skin reaction described in section 4 occurs, rifaximin should be discontinued immediately and the patient should contact their doctor.

If diarrhoea symptoms worsen or persist for longer than 24–48 hours, Xifaxan should be discontinued and the doctor will consider alternative therapy.

Xifaxan should not be used in patients with diarrhoea associated with fever or blood in the stool, or with high stool frequency (8 or more per day). These symptoms are usually indicative of significant intestinal mucosal involvement by invasive enteric pathogens such as Campylobacter, Salmonella, and Shigella. Due to its minimal gastrointestinal absorption, Xifaxan has not been effective in such cases.

Diarrhoea caused by Clostridium difficile infection (leading to a condition known as pseudomembranous colitis) has been reported 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 ruled out. 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 colour.

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, antiarrhythmics, or cyclosporine.

If taking activated charcoal, Xifaxan should be taken at least 2 hours after the charcoal.

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

Pregnancy, breastfeeding, and fertility
If you are pregnant, suspect you may be pregnant, are planning to become pregnant, or are 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 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 influence of Xifaxan on the ability to drive 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 sucrose, sodium benzoate, and sodium
If the patient has previously been diagnosed with intolerance to certain sugars, they should contact their doctor before taking this medicine.

Each 20 ml of suspension contains approximately 5.8 g of sucrose. This should be taken into account in patients with diabetes.

Xifaxan contains 12 mg of sodium benzoate in each 20 ml of suspension.

Xifaxan contains less than 1 mmol (23 mg) of sodium per 20 ml of suspension, meaning the medicine is considered "sodium-free".

3. How to use Xifaxan

This medicine should always be used exactly as directed by your doctor. If in doubt, consult your doctor or pharmacist.
The recommended dose of Xifaxan is as follows:
Intestinal infections caused by bacteria sensitive to rifaximin:
Patients over 12 years of age: 200 mg (10 ml of suspension) every 8 hours up to 400 mg (20 ml of suspension) every 8–12 hours
Traveler's diarrhea:
Patients over 12 years of age: 200 mg (10 ml of suspension) every 8 hours for 3 days
Do not use for longer than 3 days.
Do not reinitiate treatment if diarrhea symptoms recur after a short period following recovery (see "Warnings and precautions").
Irritable bowel syndrome with diarrhea:
Adults: 550 mg (27.5 ml of suspension, i.e. measure 15 ml then 12.5 ml) every 8 hours for 14 days.
The method of measuring 27.5 ml of suspension is shown below.

Hepatic encephalopathy:
Adults: 400 mg (20 ml of suspension) every 8 hours.
The treatment period should not exceed 7 days.
Symptomatic uncomplicated diverticular disease of the colon:
Adults on a high-fiber diet: 400 mg (20 ml of suspension) every 12 hours for 7 days.
If necessary, your doctor may recommend repeating the treatment once a month for the next 11 months, i.e. up to 12 cycles of 7 days each.
Once symptoms have completely resolved, the medication should be discontinued.
A single course of treatment with rifaximin should not exceed 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 these patients.
Elderly patients: no dose adjustment is required, as safety and efficacy data have not shown any differences between elderly and younger patients.
Children: the efficacy and safety of rifaximin in children under 12 years of age have not yet been established.
Method of administration
The medicine may be taken with or without food. The suspension should be shaken vigorously before each administration. A graduated measuring device is provided with the bottle containing the granules.
Administer orally, followed by a glass of water.
Instructions for preparing the medicine for use
The granules for oral suspension are contained in a tightly closed bottle. Open the bottle, add drinking-quality water up to the mark and shake vigorously. Then add more water up to the mark.
The concentration of rifaximin in the resulting suspension is 100 mg/5 ml.
Taking more Xifaxan than recommended
If you take more medicine than recommended, contact your doctor or pharmacist immediately.
If possible, bring the Xifaxan medicine and its packaging with you to show to your doctor or pharmacist.
If you forget to take 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. Take the next dose at the regular time. Do not take a double dose to make up for a missed dose of suspension.

4. Possible adverse reactions

Like all medicines, Xifaxan may cause adverse reactions, although not everyone experiences them.
Rifaximin must be discontinued immediately and the patient should contact a doctor or the emergency department of the nearest hospital if any of the following symptoms occur:

• Reddish, flat, target-like or circular skin lesions on the trunk, often with a centrally located blister, skin peeling, and mucosal erosions affecting the mouth, throat, nose, genitals, and eyes. These severe skin reactions may be preceded by fever and flu-like symptoms:
• fever or severe systemic allergic reaction affecting: the circulatory system, lungs, skin (anaphylactoid reaction), allergic reaction manifesting as skin swelling (dermatitis, exfoliative dermatitis, purpura, rash, rough skin, redness of the skin, itching, blisters) and (or) mucous membranes (angioedema), pre-syncopal state.

See also "Warnings and precautions" in section 2.
Common adverse reactions (affecting 1 to 10 patients out of 100): upper abdominal pain, constipation, sudden need for bowel movement, diarrhea, bloating with passage of gas, increased abdominal tension, nausea, painful straining at stool, vomiting, fever, headache, dizziness.
Uncommon (affecting 1 to 10 patients out of 1,000): upper abdominal pain, fluid in the abdominal cavity (ascites), dyspepsia, dry mouth, disturbances in gastrointestinal motility, presence of blood in stool, hard stools, stools containing mucus, taste disturbances, abnormal blood test results (increased white blood cell count, i.e. lymphocytes, increased monocyte count, decreased neutrophil granulocyte count), palpitations, dizziness, ear pain, double vision, weakness, pain and discomfort, chills, cold sweats, excessive sweating, influenza-like illness, swelling of legs and (or) hands, increased aspartate aminotransferase activity, oral candidiasis (thrush), candidal vaginal infection, Herpes simplex, pharyngitis, sore throat, upper respiratory tract infections, decreased appetite, dehydration, back pain, muscle cramps, muscle weakness, muscle pain, neck pain, hypoesthesia (sensory disturbances), migraine, paresthesia in limbs, sinus pain, somnolence, sleep disorders, low mood, insomnia, nervousness, presence of blood in urine, glucose in urine, frequent urination, excessive urination, protein in urine, abnormally frequent menstruation, cough, dry throat, shortness of breath (dyspnea), nasal congestion, sore throat and larynx, watery rhinorrhea, rash, skin eruptions, exanthema (skin lesions), photoallergic reactions, sudden facial flushing, increased blood pressure.
Frequency not known (frequency cannot be estimated from available data): abnormal blood test results (decreased platelet count, abnormal liver function tests, abnormalities in international normalized ratio), Clostridium bacterial infections (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, redness of the skin, itching, 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 Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, phone: +48 22 4921301, fax: +48 22 4921309, website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store the medicine Xifaxan

Keep the medicine out of the sight and reach of children.
No special precautions for storage are required.
Do not use the medicine Xifaxan, granules for oral suspension, after the expiry date stated on the bottle and cardboard box, following: Expiry date. The expiry date refers to the last day of the stated month.
Warning!
The reconstituted suspension, prepared and ready for patient use as described above, remains stable for 7 days at a temperature not exceeding 25°C.

6. Contents of the pack and other information

What Xifaxan contains

• The active substance is rifaximin.
• The granules for oral suspension contain 100 mg of rifaximin per 5 ml of prepared suspension.
• Other ingredients are: microcrystalline cellulose, sodium carboxymethylcellulose, pectin, kaolin, sodium saccharin, sodium benzoate, sucrose, black cherry flavour.

What Xifaxan looks like and contents of the pack
Xifaxan is a medicine in the form of granules for oral suspension. The medicine pack consists of a
cardboard box containing a tightly closed, yellowish-brown 60 ml glass bottle with an enamelled
aluminium screw cap. A graduated measuring spoon is attached to the bottle.
Marketing Authorisation Holder
Alfasigma S.p.A.
Via Ragazzi del ’99, n. 5
40133 Bologna (BO), Italy
Manufacturer
Alfasigma S.p.A.
Via Enrico Fermi 1
65020 Alanno (PE)
Italy
For further information, please contact the Marketing Authorisation Holder.
Alfasigma Polska Sp. z o.o.
Al. Jerozolimskie 96
00-807 Warsaw
Tel. +48 22 824 03 64
e-mail: [email protected]
{Logo of the Marketing Authorisation Holder Alfasigma}