Clinical Trials 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 clinical practice. The adverse event information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.
The data described below reflect exposure to ENTEREG in 1,650 patients in 9 placebo-controlled studies worldwide. The population was 19 to 97 years old, 68% were female, and 83% were Caucasian; 61% were undergoing bowel resection surgery. The first dose of ENTEREG was administered 30 minutes to 5 hours before the scheduled start of surgery and then twice daily until hospital discharge (or for a maximum of 7 days of postoperative treatment).
Table 1 presents treatment-emergent adverse reactions reported in ≥ 3% patients treated with ENTEREG and for which the rate for ENTEREG was ≥ 1% than placebo. Treatment-emergent adverse reactions are those events occurring after the first dose of study medication treatment and within 7 days of the last dose of study medication or those events present at baseline that increased in severity after the start of study medication treatment.
Table 1. Treatment-Emergent Adverse Reactions That Were Reported
in ≥ 3% of Either Bowel Resection Patients Treated With ENTEREG or All
Surgical Patients Treated With ENTEREG and for Which the Rate for ENTEREG Was
≥ 1% Than Placebo
|System Organ Class||Bowel Resection Patients||All Surgical Patients|
(n = 986)
(n = 999)
(n = 1,365)
(n = 1,650)
|Blood and lymphatic system disorders|
|Metabolism and nutrition disorders|
|Musculoskeletal and connective tissue disorders|
|Renal and urinary disorders|
Read the Entereg Capsules (alvimopan capsules) Side Effects Center for a complete guide to possible side effects
Potential for Drugs to Affect Alvimopan Pharmacokinetics
Based on in vitro data, alvimopan is not a substrate of CYP enzymes. Therefore, concomitant administration of ENTEREG with inducers or inhibitors of CYP enzymes is unlikely to alter the metabolism of alvimopan. No clinical studies have been performed to assess the effect of concomitant administration of inducers or inhibitors of cytochrome P450 enzymes on alvimopan pharmacokinetics.
In vitro studies suggest that alvimopan and its 'metabolite' are substrates for p-glycoprotein. A population PK analysis did not reveal any evidence that alvimopan or 'metabolite' pharmacokinetics were influenced by concomitant medications that are mild-to-moderate p-glycoprotein inhibitors. No clinical studies of concomitant administration of alvimopan and strong inhibitors of p-glycoprotein (e.g., verapamil, cyclosporine, amiodarone, itraconazole, quinine, spirinolactone, quinidine, diltiazem, bepridil) have been conducted.
A population PK analysis suggests that the pharmacokinetics of alvimopan were not affected by concomitant administration of acid blockers or antibiotics. However, plasma concentrations of the 'metabolite' were lower in patients receiving acid blockers or preoperative oral antibiotics (49% and 81%, respectively). Because the 'metabolite' is not required for efficacy, no dosage adjustments are necessary in these patients.
Potential for Alvimopan to Affect the Pharmacokinetics of Other Drugs
Alvimopan and its 'metabolite' are not inhibitors of CYP 1A2, 2C9, 2C19, 3A4, 2D6, and 2E1 in vitro at concentrations far in excess of those observed clinically. Alvimopan and its 'metabolite' are not inducers of CYP 1A2, 2B6, 2C9, 2C19 and 3A4. In vitro studies also suggest that alvimopan and its 'metabolite' are not inhibitors of p-glycoprotein. These in vitro findings suggest that ENTEREG is unlikely to alter the pharmacokinetics of coadministered drugs through inhibition or induction of CYP enzymes or inhibition of p-glycoprotein.
Coadministration of alvimopan does not appear to alter the pharmacokinetics of morphine and its metabolite, morphine-6-glucuronide, to a clinically significant degree when morphine is administered intravenously. Dosage adjustment for intravenously administered morphine is not necessary when it is coadministered with alvimopan.
Drug Abuse And Dependence
ENTEREG has no known potential for abuse or dependence.
Read the Entereg Capsules Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 12/3/2009
Additional Entereg Capsules Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.