"The U.S. Food and Drug Administration today approved Dotarem (gadoterate meglumine) for use in magnetic resonance imaging (MRI) of the brain, spine and associated tissues of patients ages 2 years and older.
Dotarem is a gadolinium-based"...
Clinical Studies Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety of XIFAXAN 200 mg taken three times a day was evaluated in patients with travelers' diarrhea consisting of 320 patients in two placebo-controlled clinical trials with 95% of patients receiving three or four days of treatment with XIFAXAN. The population studied had a mean age of 31.3 (18-79) years of which approximately 3% were ≥ 65 years old, 53% were male and 84% were White, 11% were Hispanic.
Discontinuations due to adverse reactions occurred in 0.4% of patients. The adverse reactions leading to discontinuation were taste loss, dysentery, weight decrease, anorexia, nausea and nasal passage irritation.
The adverse reaction that occurred at a frequency ≥ 2% in XIFAXAN-treated patients (n=320) at a higher rate than placebo (n=228) in the two placebo-controlled trials of TD was:
- headache (10% XIFAXAN, 9% placebo)
The data described below reflect exposure to XIFAXAN in 348 patients, including 265 exposed for 6 months and 202 exposed for more than a year (mean exposure was 364 days).
The safety of XIFAXAN 550 mg taken two times a day for reducing the risk of overt hepatic encephalopathy recurrence in adult patients was evaluated in a 6-month placebo-controlled clinical trial (n=140) and in a long term follow-up study (n=280). The population studied had a mean age of 56 (range: 21 to 82) years; approximately 20% of the patients were ≥ 65 years old, 61% were male, 86% were White, and 4% were Black. Ninety-one percent of patients in the trial were taking lactulose concomitantly. The most common adverse reactions that occurred at an incidence ≥ 5% and at a higher incidence in XIFAXAN-treated subjects than in the placebo group in the 6-month trial are provided in Table 1.
Table 1: Most Common Adverse
Reactions* in HE Trial
|MedDRA Preferred Term||Number (%) of Patients|
|XIFAXAN Tablets 550 mg TWICE DAILY
|Peripheral edema||21 (15%)||13 (8%)|
|Nausea||20 (14%)||21 (13%)|
|Dizziness||18 (13%)||13 (8%)|
|Fatigue||17 (12%)||18 (11%)|
|Ascites||16 (11%)||15 (9%)|
|Muscle spasms||13 (9%)||11 (7%)|
|Pruritus||13 (9%)||10 (6%)|
|Abdominal pain||12 (9%)||13 (8%)|
|Anemia||11 (8%)||6 (4%)|
|Depression||10 (7%)||8 (5%)|
|Nasopharyngitis||10 (7%)||10 (6%)|
|Abdominal pain upper||9 (6%)||8 (5%)|
|Arthralgia||9 (6%)||4 (3%)|
|Dyspnea||9 (6%)||7 (4%)|
|Pyrexia||9 (6%)||5 (3%)|
|Rash||7 (5%)||6 (4%)|
|* reported in ≥ 5% of Patients Receiving XIFAXAN and at a higher incidence than placebo|
Irritable Bowel Syndrome with Diarrhea
The safety of XIFAXAN for the treatment of IBS-D was evaluated in 3 placebo-controlled studies in which 952 patients were randomized to XIFAXAN 550 mg three times a day for 14 days. Across the 3 studies, 96% of patients received at least 14 days of treatment with XIFAXAN. In Trials 1 and 2, 624 patients received only one 14-day treatment. Trial 3 evaluated the safety of XIFAXAN in 328 patients who received 1 open-label treatment and 2 double-blind repeat treatments of 14 days each over a period of up to 46 weeks. The combined population studied had a mean age of 47 (range: 18 to 88) years of whom approximately 11% of the patients were ≥ 65 years old, 72% were female, 88% were White, 9% were Black and 12% were Hispanic.
The adverse reaction that occurred at a frequency ≥ 2% in XIFAXAN-treated patients at a higher rate than placebo in Trials 1 and 2 for IBS-D was:
- nausea (3% XIFAXAN, 2% placebo)
The adverse reactions that occurred at a frequency ≥ 2% in XIFAXAN-treated patients (n=328) at a higher rate than placebo (n=308) in Trial 3 for IBS-D during the double-blind treatment phase were:
- ALT increased (XIFAXAN 2%, placebo 1%)
- nausea (XIFAXAN 2%, placebo 1%)
Less Common Adverse Reactions
The following adverse reactions, presented by body system, were reported in less than 2% of patients in clinical trials of TD and IBS-D and in less than 5% of patients in clinical trials of HE:
Investigations: Increased blood creatine phosphokinase
Musculoskeletal and connective tissue disorders: myalgia
The following adverse reactions have been identified during post-approval use of XIFAXAN. Because these reactions are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These reactions have been chosen for inclusion due to either their seriousness, frequency of reporting or causal connection to XIFAXAN.
Infections and Infestations
Hypersensitivity reactions, including exfoliative dermatitis, rash, angioneurotic edema (swelling of face and tongue and difficulty swallowing), urticaria, flushing, pruritus and anaphylaxis have been reported. These events occurred as early as within 15 minutes of drug administration.
Read the Xifaxan (rifaximin) Side Effects Center for a complete guide to possible side effects
Effects Of XIFAXAN On Other Drugs
Substrates of Cytochrome P450 enzymes
Rifaximin is not expected to inhibit cytochrome P450 isoenzymes 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1 and CYP3A4 in clinical use based on in vitro studies [see CLINICAL PHARMACOLOGY].
An in vitro study has suggested that rifaximin induces CYP3A4 [see CLINICAL PHARMACOLOGY]. However, in patients with normal liver function, XIFAXAN at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
Effects Of Other Drugs On XIFAXAN
In vitro studies suggested that rifaximin is a substrate of P-glycoprotein, OATP1A2, OATP1B1 and OATP1B3. Concomitant cyclosporine, an inhibitor of P-glycoprotein and OATPs, significantly increased the systemic exposure to rifaximin.
Co-administration of cyclosporine, with XIFAXAN resulted in 83-fold and 124-fold increases in rifaximin mean Cmax and AUC∞ in healthy subjects. The clinical significance of this increase in systemic exposure is unknown [see WARNINGS AND PRECAUTIONS, CLINICAL PHARMACOLOGY].
Read the Xifaxan Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 6/10/2015
This monograph has been modified to include the generic and brand name in many instances.
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