Xifaxan

Xifaxan

rifaximin

Manufacturer:

Alfa Wassermann

Distributor:

Chong Lap
Full Prescribing Info
Contents
Rifaximin.
Description
Each tablet also contain the following excipients: Tablet Core: Sodium starch glycolate type A, glycerol distearate, anhydrous colloidal silica, talc, microcrystalline cellulose. Tablet Coating: Hypromellose, titanium dioxide, disodium edetate, propylene glycol, red iron oxide E172.
Action
Pharmacotherapeutic Group: Intestinal anti-infective agents, antibiotics. ATC Code: A07AA11.
Pharmacology: Pharmacodynamics: Mode of Action: Rifaximin is an antibacterial agent of the rifamycin class that binds irreversibly to the β 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 break point for susceptibility testing.
Pharmacokinetics: Absorption: Pharmacokinetic studies in rats, dogs and humans demonstrated that after oral administration, rifaximin in the polymorph α form is virtually not absorbed (<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 (<10 ng/mL). Systemic absorption of rifaximin is increased but not by a clinically relevant extent by administration within 30 min 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 3 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.
Toxicology: 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.
Indications/Uses
Treatment of traveller’s diarrhoea that is not associated with fever, bloody diarrhoea, 8 or more unformed stools in the previous 24 hrs, occult blood or leucocytes in the stool. It may shorten the duration of diarrhoea when this is associated with non-invasive strains of E.coli.
Dosage/Direction for Use
Dosage: Adults: Recomended Dose: 200 mg every 8 hrs for 3 days (total 9 doses).
Rifaximin must not be used >3 days even if symptoms continue and a 2nd course of treatment  must not be taken (see Precautions).
Dosage adjustment for patients with hepatic or renal insufficiency is not necessary.
Administration: Xifaxan can be administered with or without food.
Orally with a glass of water.
Overdosage
No case of overdose has been reported.
In clinical trials with patients suffering from traveller’s diarrhoea, doses of up to 1,800 mg/day have been tolerated without any severe clinical signs.
In case of overdose, gastric emptying and administration of appropriate supportive treatment are recommended.
Contraindications
Hypersensitivity to rifaximin and any rifamycin derivatives (eg, rifampicin or rifabutin) or to any of the excipients of Xifaxan.
Special Precautions
Clinical data have shown that rifaximin is not effective in the treatment of traveller’s diarrhoea caused by invasive enteric pathogens eg, Campylobacter, Salmonella and Shighella, which typically produce dysentery-like 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.
Effects on the Ability to Drive or Operate Machinery: 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.
Use in children: Xifaxan is not recommended for use in children <18 years.
Use in pregnancy and lactation: No clinical data on exposed pregnancies are available. Animal studies have shown reproductive toxicity. (see Preclinical Safety Data under Toxicology under Actions.)
Rifaximin is not recommended during pregnancy and in women of child-bearing potential not using contraception. (see Preclinical Safety Data under Toxicology under Actions.)
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.
Use In Pregnancy & Lactation
No clinical data on exposed pregnancies are available. Animal studies have shown reproductive toxicity. (see Preclinical Safety Data under Toxicology under Actions.)
Rifaximin is not recommended during pregnancy and in women of child-bearing potential not using contraception. (see Preclinical Safety Data under Toxicology under Actions.)
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.
Adverse Reactions
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: Common: (≥1/100 to <1/10), Uncommon: (≥ 1/1,000 to < 1/100).
Infections and Infestations: Uncommon: Candidiasis, herpes simplex, nasopharyngitis, pharyngitis, upper respiratory tract infection.
Blood and Lymphatic System Disorder: Uncommon: Lymphocytosis, monocytosis, neutropenia.
Metabolism and Nutrition Disorders: Uncommon: Decreased appetite, dehydration.
Psychiatric Disorders: Abnormal dreams, depressed mood, insomnia, nervousness.
Nervous System Disorders: Common: Dizziness, headache. Uncommon: Hypoesthesia, migraine, paraesthesia, sinus headache, somnolence.
Eye Disorders: Uncommon: Diplopia.
Ear and Labyrinth Disorders: Uncommon: Ear pain, vertigo.
Cardiac Disorders: Uncommon: Palpitations.
Vascular Disorders: Uncommon: Increased blood pressure, hot flush.
Respiratory, Thoracic, and Mediastinal Disorders: Uncommon: Cough, dry throat, dyspnoea, nasal congestion, oropharyngeal pain, rhinorrhea.
Gastrointestinal Disorders: Common: Abdominal pain, constipation, defecation urgency, diarrhoea, flatulence, bloating and distension, nausea and vomiting symptoms, rectal tenesmus. Uncommon: Upper abdominal pain, dry lips, dyspepsia, gastrointestinal motility disorder, hard faeces, haematochezia, mucous stools, taste disorders.
Hepatobiliary Disorders: Uncommon: Increased aspartate aminotransferase.
Skin and Subcutaneous Tissue Disorders: Uncommon: Rashes, eruptions and exanthemas, NEC, sunburn.
Musculoskeletal and Connective Tissue Disorders: Uncommon: Back pain, muscle spasms, muscular weakness, myalgia, neck pain.
Renal and Urinary Disorders: Uncommon: Blood in urine, glycosuria, pollakiuria, polyuria, proteinuria.
Reproductive System and Breast Disorders: Uncommon: Polymenorrhoea.
General Disorders and Administration Site Conditions: Common: Pyrexia. Uncommon: Asthenic conditions, chills, cold sweat, hyperhidrosis, influenza-like illness, peripheral oedema, 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).
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.
Drug Interactions
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 (<1%), the systemic drug interaction potential is low.
In vitro data show that rifaximin is a weak inducer of the CYP3A4 isoenzyme of the P-450 cytochrome. Drug-drug interaction studies investigating the clinical interaction between rifaximin and drugs metabolised by the human cytochrome P-450 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 not been evaluated and cannot be ruled out. No drug interaction studies investigating the concomitant intake of rifaximin and other drugs that might be used during an episode of traveller’s diarrhoea (eg, loperamide, charcoal) are available. Patients should take rifaximin at least 2 hrs after the administration of charcoal.
Storage
Shelf-Life: 3 years.
MIMS Class
ATC Classification
A07AA11 - rifaximin ; Belongs to the class of antibiotics. Used in the treatment of intestinal infections.
Presentation/Packing
FC tab 200 mg (pink, circular, biconvex) x 12's.
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