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Rifaximin


General


Pronunciation

(rif AX i min)


Brand Names: U.S.

  • Xifaxan

Indications


Use: Labeled Indications

Hepatic encephalopathy: Reduction in the risk of overt hepatic encephalopathy recurrence in adults

Irritable bowel syndrome with diarrhea: Treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults

Travelers diarrhea: Treatment of traveler's diarrhea caused by noninvasive strains of E. coli in adults and pediatric patients ≥12 years of age

Limitations of use: Rifaximin should not be used in patients with diarrhea complicated by fever or blood in the stool or diarrhea caused by pathogens other than E. coli.


Contraindications


Hypersensitivity to rifaximin, other rifamycin antibiotics, or any component of the formulation


Dosing and Administration


Dosing: Adult

Hepatic encephalopathy: Oral:

Reduction of overt hepatic encephalopathy recurrence: 550 mg 2 times daily. Note: Supporting clinical trial evaluated efficacy over 6-month treatment period.

Treatment of hepatic encephalopathy (off-label use): 400 mg every 8 hours for 5 to 10 days (Mas 2003)

Irritable bowel syndrome with diarrhea (IBS-D): Oral: 550 mg 3 times daily for 14 days; may be retreated up to 2 times with the same dosing regimen if symptoms recur.

Travelers diarrhea: Oral: 200 mg 3 times daily for 3 days

Clostridium difficile-associated diarrhea (off-label use): Oral: 200 to 400 mg 2 to 3 times daily for 14 days (Johnson 2007)


Dosing: Geriatric

Refer to adult dosing.


Dosing: Pediatric

Travelers diarrhea: Oral: Children ≥12 years and Adolescents: Refer to adult dosing.


Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer 's labeling (has not been studied).


Dosing: Hepatic Impairment

No dosage adjustment necessary. Use with caution in severe impairment (Child-Pugh class C); however, systemic absorption is limited and pharmacokinetic parameters are highly variable.


Administration

Oral: Administer with or without food.


Storage

Store at 20 ‚ °C to 25 ‚ °C (68 ‚ °F to 77 ‚ °F); excursions permitted to 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F).


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Xifaxan: 200 mg, 550 mg [contains edetate disodium]


Extemporaneously Prepared

A 20 mg/mL oral suspension may be made using tablets. Crush six 200 mg tablets and reduce to a fine powder. Add 30 mL of a 1:1 mixture of Ora-Sweet ‚ ® and Ora-Plus ‚ ® or a 1:1 mixture of Ora-Sweet ‚ ® SF and Ora-Plus ‚ ®; mix well while adding the vehicle in geometric proportions to almost 60 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 60 mL. Label shake well". Stable 60 days at room temperature.

Cober MP, Johnson CE, Lee J, et al, "Stability of Extemporaneously Prepared Rifaximin Oral Suspensions," Am J Health Syst Pharm, 2010, 67(4):287-89.[PMID: 20133533]

Drug Interactions

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

CycloSPORINE (Systemic): May increase the serum concentration of RifAXIMin. Monitor therapy

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of RifAXIMin. Monitor therapy

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification


Monitoring Parameters

Hypersensitivity reactions, temperature, blood in stool, change in symptoms; monitor changes in mental status in hepatic encephalopathy


Adverse Reactions


Frequency of adverse events generally higher following treatment for hepatic encephalopathy (HE). Percentages are presented for HE unless otherwise stated.

>10%:

Cardiovascular: Peripheral edema (15%)

Central nervous system: Dizziness (13%), fatigue (12%)

Hepatic: Ascites (11%)

Gastrointestinal: Nausea (14%; irritable bowel syndrome with diarrhea 2% to 3%)

2% to 10%:

Central nervous system: Headache (travelers diarrhea 10%), depression (7%)

Dermatological: Pruritus (9%), skin rash (5%)

Gastrointestinal: Abdominal pain (>2% to 9%), pseudomembranous colitis (<5%; travelers' diarrhea or irritable bowel syndrome with diarrhea <2%)

Hematologic & oncologic: Anemia (8%)

Hepatic: Increased serum ALT (irritable bowel syndrome with diarrhea 2%)

Neuromuscular & skeletal: Muscle spasm (9%), arthralgia (6%), increased creatine phosphokinase (<5%; travelers' diarrhea or irritable bowel syndrome with diarrhea <2%)

Respiratory: Nasopharyngitis (7%), dyspnea (6%), epistaxis (>2% to 5%)

Miscellaneous: Fever (6%)

All indications: <2% (Limited to important or life-threatening): Anaphylaxis, Clostridium difficile associated diarrhea, exfoliative dermatitis, hypersensitivity reaction


Warnings/Precautions


Special Populations: Hepatic Function Impairment

The mean AUC in patients with hepatic impairment of Child-Pugh class A, B, and C was 10-, 14-, and 21-fold higher, respectively, compared with that of healthy subjects.


Warnings/Precautions

Concerns related to adverse effects:

- Hypersensitivity: Hypersensitivity reactions (eg, exfoliative dermatitis, rash, urticaria, flushing, angioneurotic edema, pruritus, anaphylaxis) have occurred; these events have occurred as early as within 15 minutes of drug administration.

- Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

- Diarrhea: Appropriate use: Avoid use in diarrhea with fever and/or blood in the stool and in the treatment of diarrhea due to pathogens other than E. coli, including C. jejuni, Shigella, and Salmonella (efficacy has not been established). Consider alternative therapy if symptoms persist or worsen after 24 to 48 hours of treatment.

- Hepatic impairment: Efficacy for prevention of encephalopathy has not been established in patients with a Model for End-Stage Liver Disease (MELD) score >25; use caution in patients with severe hepatic impairment (Child-Pugh class C).

Concurrent drug therapy issues:

- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

- Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007).

Other warnings/precautions:

- Appropriate use: Not for treatment of systemic infections; <1% is absorbed orally.


Pregnancy Considerations

Adverse events have been observed in some animal reproduction studies. Due to the limited oral absorption of rifaximin in patients with normal hepatic function, exposure to the fetus is expected to be low.


Actions


Pharmacology

Rifaximin inhibits bacterial RNA synthesis by binding to bacterial DNA-dependent RNA polymerase.


Absorption

Oral:

Travelers diarrhea: Low

Hepatic encephalopathy: Increased absorption in patients with Child-Pugh class C compared with patients with Child-Pugh class A


Metabolism

Extensive, mainly by CYP3A


Excretion

Feces (96.6% primarily as unchanged drug); urine (0.32%)


Time to Peak

Healthy subjects and ISB-D patients: ~1 hour


Half-Life Elimination

Healthy subjects: 5.6 hours; IBS-D patients: 6 hours


Protein Binding

Healthy subjects: 67.5%; Hepatic impairment: 62%


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience flatulence, headache, dizziness, abdominal pain, or nausea. Have patient report immediately to prescriber swelling of arms or legs, abdominal edema, severe loss of strength and energy, shortness of breath, or signs of Clostridium difficile (C. diff)-associated diarrhea (stomach pain or cramps, very loose or watery stools, or bloody stools) (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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