Alvimopan

Alvimopan is used to help the bowel recover more quickly after bowel surgery, so that you can eat solid foods and have regular bowel movements. Alvimopan is in a class of medications called peripherally acting mu-opioid receptor antagonists. It works by protecting the bowel from the constipation effects of opioid (narcotic) medications that are used to treat pain after surgery.

Take alvimopan exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The Alvimopan dose your doctor recommends will be based on the following (use any or all that apply):

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your weight
• your height
• your age
• your gender

Alvimopan is available in the following doses:

• Alvimopan 12 Mg Oral Capsule

Alvimopan is available in the following forms:

• Oral Capsule

Alvimopan reduces certain side effects of narcotic medicines that are often used to prevent pain caused by surgery. Narcotic medicine can cause stomach pain, bloating, nausea, vomiting, and constipation. These side effects can delay recovery in patients undergoing gastrointestinal surgery.

Alvimopan helps prevent these side effects without reducing the pain-relieving effects of the narcotic.

Alvimopan is used to help restore normal digestive functioning after surgery to remove a portion of your intestine.

Alvimopan is available only under a special program for short-term use (no more than 15 doses). You must be registered in the program and understand the risks and benefits of taking this medicine.

Alvimopan may also be used for purposes not listed in this medication guide.

You should not use alvimopan if you have severe liver or kidney disease, or if you have used a narcotic medicine for more than 7 days in a row just before your surgery.

Alvimopan is available only under a special program for short-term use.

Some people had heart attacks while taking alvimopan long-term during clinical studies. It is not clear whether alvimopan is the actual cause of heart attack. This medicine should not be used for longer than 7 days after your surgery.

Absorption

Bioavailability

Absolute bioavailability averages 6% (range 1–19%).1 7 11

Food

High-fat meal decreases rate and extent of absorption.1

Distribution

Extent

Does not readily cross blood-brain barrier.1 6 7 14 15 16

Distributed into milk in rats; not known whether distributed into human milk.1

Plasma Protein Binding

Alvimopan: 80%.1 Metabolite: 94%.1 Bound to albumin.1

Elimination

Metabolism

Metabolized by intestinal flora to active metabolite;1 metabolite not required for pharmacologic activity.8 16

No substantial hepatic metabolism.1

Elimination Route

Excreted principally via biliary secretion (65%) and in the urine (35%).1 16

Half-life

10–17 hours.1

Special Populations

Exposure to alvimopan is 1.5-fold to twofold higher in patients with mild or moderate hepatic impairment (Child-Pugh class A or B); accumulation possible after multiple doses.1 Exposure may be increased approximately tenfold in patients with severe hepatic impairment (Child-Pugh class C).1

Exposure to metabolite is twofold to fivefold higher in patients with moderate or severe renal impairment.1 Alvimopan half-life is prolonged in patients with severe renal impairment.1 Accumulation of alvimopan and metabolite is possible after multiple doses in patients with severe renal impairment.1 Not studied in patients with end-stage renal disease.1

Exposure to alvimopan is twofold higher in patients with quiescent Crohn’s disease relative to healthy individuals or those with active Crohn’s disease; metabolite concentrations are lower in patients with Crohn’s disease.1

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Acid or sour stomach
• belching
• bloated
• convulsions
• decreased urine
• difficulty having a bowel movement (stool)
• dry mouth
• excess air or gas in stomach or intestines
• full feeling
• heartburn
• increased thirst
• indigestion
• irregular heartbeat
• loss of appetite
• mood changes
• muscle pain or cramps
• nausea or vomiting
• numbness or tingling in hands, feet, or lips
• pale skin
• passing gas
• shortness of breath
• stomach discomfort, upset, or pain
• troubled breathing with exertion
• unusual bleeding or bruising
• unusual tiredness or weakness

• Decrease in frequency of urination
• decrease in urine volume
• difficulty in passing urine (dribbling)
• painful urination

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Back pain

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

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

Capsule, Oral:

Entereg: 12 mg

The half-life was comparable in patients with mild or moderate renal function impairment. There may be drug accumulation in patients with severe renal function impairment receiving multiple doses.

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

• 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?)

• Have patient report immediately to prescriber angina, tachycardia, severe dizziness, passing out, severe headache, severe nausea, vomiting, abdominal pain, or abdominal cramps (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.

1-10%

Constipation (10%)

Hypokalemia (9.5%)

Flatulence (8.7%)

Dyspepsia (7%)

Anemia (5.4%)

Back pain (3.4%)

Mechanism of Action

Peripheral mu-opioid receptor antagonist; limited ability to cross blood brain barrier so doesn't abolish opioid-induced analgesia nor cause withdrawal symptoms but decreases opioid-induced constipation

Pharmacokinetics

Peak Plasma Time: 2 hr

Bioavailability: 6%

Vd: 20-40 L

Protein Bound: drug 80%; metabolite 94%

Total Clearance: 402 mL/min

Half-Life, Terminal: 10-17 hr

Metabolism: Not by liver, gut microflora hydrolyzes to a metabolite

Excretion: Feces (via biliary excretion) & urine (35%)