ALVIMOPAN Drug Interactions: What You Need to Know

INTERACTIONS

7.1 Effects of Alvimopan on Intravenous Morphine 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.

7.2 Effects of Concomitant Acid Blockers or Antibiotics A population pharmacokinetic analysis suggests that the pharmacokinetics of alvimopan were not affected by concomitant administration of acid blockers (proton pump inhibitors (PPIs), histamine-2 (H 2 ) receptor antagonists) or antibiotics. No dosage adjustments are necessary in patients taking acid blockers or antibiotics with alvimopan.

Alvimopan capsules are contraindicated in patients who have taken therapeutic doses of opioids for more than 7 consecutive days immediately prior to taking alvimopan capsules [see Warnings and Precautions ( 5.3 )] . Patients who have taken therapeutic doses of opioids for more than 7 consecutive days prior to taking alvimopan capsules. ( 4 )

AND PRECAUTIONS

• Myocardial Infarction : A higher number of myocardial infarctions was reported in patients treated with alvimopan 0.5 mg twice daily compared with placebo in a 12-month study in patients treated with opioids for chronic non-cancer pain, although a causal relationship with long-term use has not been established. ( 5.1 )
• Gastrointestinal Adverse Reactions in Opioid Tolerant Patients : Patients recently exposed to opioids may be more sensitive to the effects of alvimopan and experience gastrointestinal adverse reactions (e.g., abdominal pain, nausea and vomiting, and diarrhea). ( 5.3 )
• Patients with Severe Hepatic Impairment : Increased risk of serious adverse reactions due to higher plasma concentrations; use is not recommended. ( 5.4 , 8.6 )
• Patients with End-Stage Renal Disease : No studies have been conducted; use is not recommended. ( 5.5 , 8.7 )
• Patients with Complete Gastrointestinal Obstruction : No studies have been conducted in patients with complete gastrointestinal obstruction or in patients who have surgery for correction of complete bowel obstruction; use is not recommended. ( 5.6 )
• Patients with Pancreatic and Gastric Anastomoses : No studies have been conducted; use is not recommended. ( 5.7 )

5.1 Potential Risk of Myocardial Infarction with Long-Term Use There were more reports of myocardial infarctions in patients treated with alvimopan 0.5 mg twice daily compared with placebo-treated patients in a 12-month study of patients treated with opioids for chronic non-cancer pain (alvimopan 0.5 mg, n = 538; placebo, n = 267). In this study, the majority of myocardial infarctions occurred between 1 and 4 months after initiation of treatment. This imbalance has not been observed in other studies of alvimopan in patients treated with opioids for chronic pain, nor in patients treated within the surgical setting, including patients undergoing surgeries that included bowel resection who received alvimopan 12 mg twice daily for up to 7 days (the indicated dose and patient population; alvimopan 12 mg, n = 1,142; placebo, n = 1,120). A causal relationship with alvimopan with long-term use has not been established. Alvimopan capsules are available only through a program under a REMS that restricts use to enrolled hospitals <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.2 )]</span> .

5.2 Alvimopan REMS Program Alvimopan capsules are available only through a program called the Alvimopan REMS Program that restricts use to enrolled hospitals because of the potential risk of myocardial infarction with long-term use of alvimopan capsules <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.1 )]</span> . Notable requirements of the Alvimopan REMS Program include the following: Alvimopan capsules are available only for short-term (15 doses) use in hospitalized patients. Only hospitals that have enrolled in and met all of the requirements for the Alvimopan REMS Program may use alvimopan capsules. To enroll in the Alvimopan REMS Program, an authorized hospital representative must acknowledge that:

• hospital staff who prescribe, dispense, or administer alvimopan capsules have been provided the educational materials on the need to limit use of alvimopan capsules to short-term, inpatient use;
• patients will not receive more than 15 doses of alvimopan capsules; and
• alvimopan capsules will not be dispensed to patients after they have been discharged from the hospital. Further information is available at www.alvimopanREMS.com or 1-800-278-0340.

5.3 Gastrointestinal-Related Adverse Reactions in Opioid-Tolerant Patients Patients recently exposed to opioids are expected to be more sensitive to the effects of mu-opioid receptor antagonists, such as alvimopan. Since alvimopan acts peripherally, clinical signs and symptoms of increased sensitivity would be related to the gastrointestinal tract (e.g., abdominal pain, nausea and vomiting, diarrhea). Patients receiving more than 3 doses of an opioid within the week prior to surgery were not studied in the postoperative ileus clinical trials. Therefore, if alvimopan is administered to these patients, they should be monitored for gastrointestinal adverse reactions. Alvimopan is contraindicated in patients who have taken therapeutic doses of opioids for more than 7 consecutive days immediately prior to taking alvimopan <span class="opacity-50 text-xs">[see Contraindications ( 4 )]</span> .

5.4 Risk of Serious Adverse Reactions in Patients with Severe Hepatic Impairment Patients with severe hepatic impairment may be at higher risk of serious adverse reactions (including dose-related serious adverse reactions) because up to 10-fold higher plasma concentrations of alvimopan have been observed in such patients compared with patients with normal hepatic function. Therefore, the use of alvimopan is not recommended in this population <span class="opacity-50 text-xs">[see Use in Specific Populations ( 8.6 )]</span> .

5.5 End-Stage Renal Disease No studies have been conducted in patients with end-stage renal disease. Alvimopan is not recommended for use in these patients <span class="opacity-50 text-xs">[see Use in Specific Populations ( 8.7 )]</span> .

5.6 Risk of Serious Adverse Reactions in Patients with Complete Gastrointestinal Obstruction No studies have been conducted in patients with complete gastrointestinal obstruction or in patients who have surgery for correction of complete bowel obstruction. Alvimopan is not recommended for use in these patients.

5.7 Risk of Serious Adverse Reactions in Pancreatic and Gastric Anastomoses Alvimopan has not been studied in patients having pancreatic or gastric anastomosis. Therefore, alvimopan is not recommended for use in these patients.