Alvimopan for Postoperative Ileus: An Insight

Overview:

After colon surgery, a drug termed Alvimopan is used to hasten the recovery of colon function. It functions by preventing some of the side effects of opioid drugs, which are frequently taken to control pain following surgery and have the potential to induce constipation. Alvimopan is used under the guidance of medical specialists. It is usually recommended for brief periods in a hospital setting. To cure postoperative ileus the United States Food and Drug Administration (FDA) authorized Alvimopan on 20th May 2008.

Drug Group:

Alvimopan is a medication that is part of the class of mu-opioid receptor antagonists with peripheral action. By inhibiting the effects of opioid drugs on the intestines, it is mainly used to speed up the recovery process after surgery related to the gastrointestinal system. Alvimopan reduces the negative effects of central opioid antagonists by specifically targeting peripheral opioid receptors. This medication is intended specifically to treat postoperative ileus (transient interruption of regular bowel function), which is a transient disturbance of the colon following abdominal surgery.

Dosages:

1. For Oral Dosage Form (Capsules):

For restoring normal bowel function after bowel surgery:

Adults: 12 milligrams (mg) 30 to five hours before surgery, followed by 12 mg twice a day starting from the next day following surgery and continuing for a maximum of 7 days or until discharged.

Children: Use and dose must be determined by the doctor.

For Patients:

What Is Postoperative Ileus?

Following surgery, postoperative ileus is a transient interruption of regular bowel function. Usually, it causes the synchronized contractions that drive food down the digestive tract to momentarily stop. This illness results in delayed gas and feces passage, bloating, and discomfort in the abdomen. Although it normally goes away on its own, if it gets severe, complications may arise. Postoperative ileus can be caused by inflammation, the handling of the intestines during surgery, and the effects of anesthesia. Medical intervention may be necessary in severe situations to relieve symptoms and avoid consequences.

What Is the Management of Postoperative Ileus?

• Early Ambulation: To promote bowel function, encourage the patient to move as rapidly as feasible following surgery.

• Fluid Management: Make sure the body is properly hydrated without overtaxing it.

• Pain Control: Effectively manage pain to encourage movement and avoid constipation brought on by opioids.

• Opioid Avoidance: Reduce the use of opioids or, if at all possible, employ methods that spare them.

• Dietary Advancement: Start from clear liquids to a regular diet immediately as it is suitable.

• Nasogastric Tube: The use of nasogastric tubes should be sparing; avoid regular implantation.

• Pharmacological Options: In some situations, take into account prokinetic medicines such as Neostigmine or Metoclopramide.

• Monitoring: Tracking the development of flatus, bowel movements, and bowel noises regularly.

• Patient Education: Patient education should include teaching patients the value of staying hydrated, walking as promptly as possible, and taking their prescriptions as directed.

How Does Alvimopan Work?

Peripherally acting mu-opioid receptor antagonists (PAMORAs) like Alvimopan are used to mitigate the negative effects of opioid medicines, especially those that affect the gastrointestinal tract. It functions by specifically preventing opioids' pain-relieving effects in the stomach without impairing their ability to relieve pain in other areas of the body. This lessens constipation induced by opiate use, a typical and uncomfortable side effect.

How Should the Drug Be Taken?

Alvimopan is available as a capsule for oral use. Usually, it is administered once just before a bowel operation. It is normally used twice a day for up to seven days following surgery or until discharge from the hospital. When the moment arrives for each patient to receive the dose, the healthcare professional will provide the medication.

What Are the Benefits of Using Alvimopan for Postoperative Ileus?

• Speeds up the digestive system's healing following colon surgery.

• It shortens the time it takes to have bowel motions.

• Reduces the possibility of problems associated with postoperative ileus.

• Reduces the need for extended hospital stays following surgery.

• Increases patient contentment and comfort.

What Must the Patient Inform the Doctor Before Taking Alvimopan?

Patients should discuss all medical history with their doctor before starting Alvimopan, particularly if the individuals have allergies, gastrointestinal problems, or have recently undergone surgery. Given that some pharmaceuticals may interact with Alvimopan, it is imperative to report any medications, supplements, and herbal products being taken. Tell the doctor if there is a history of liver or kidney issues as well. For a treatment plan that is both safe and effective, always heed the advice of the physician and disclose the relevant facts.

What Are the Side Effects of Using Alvimopan?

• Abdominal pain.

• Nausea.

• Vomiting.

• Headache.

• Diarrhea.

• Flatulence (expulsion of gas through anal passage).

• Hypokalemia (low potassium level in blood).

For Doctors:

Description:

Alvimopan is a mu-opioid antagonist that functions peripherally. It accelerates the gastrointestinal healing process and helps prevent postoperative ileus after minor or big bowel resection.

• The substance known as Alvimopan has a molecular weight of 460.6 and an empirical formula of C25H32N2O4•2H2O.
• It is white to light beige.
• It is soluble in 0.1 mg/mL (milligrams per milliliter) in aqueous 0.1 N sodium hydroxide, one to five mg/mL in buffered solutions at pH 1.2, and less than 0.1 mg/mL in water or buffered solutions between pH 3.0 and 9.0. Because of its zwitterionic nature at physiological pH, Alvimopan has limited solubility. Polyethylene glycol, an inactive component, suspends 12 mg of anhydrous Alvimopan in Alvimopan Capsules for oral consumption.

Therapeutic Uses of Alvimopan:

• Postoperative Ileus: Following bowel resection surgery, Alvimopan is used to hasten the recovery of bowel function.

• Gastrointestinal Recovery: It facilitates a quicker recovery of gastrointestinal motility by shortening the time of postoperative ileus.

• Opioid-Induced Constipation: In patients who need long-term opioid medication for pain management, Alvimopan is recommended for short-term use in managing opioid-induced constipation.

Dosage Forms and Strengths:

Alvimopan is typically available in oral capsule form. Common strengths include 12 mg (milligrams) and 36 mg.

Dosage and Administration:

Adults should take 12 mg of Alvimopan 30 minutes to five hours before surgery, then 12 mg twice a day starting the day following surgery and continuing for a maximum of 7 days or until discharge. Only hospitals may use it.

There is no known risk of dependence or abuse with Alvimopan.

Overdose:

When using Alvimopan overdose, there is no specific antidote. Patients need to be treated with the right kind of supportive care. In clinical tests, normal, healthy volunteers received single doses of up to 120 mg and repeated doses of up to 48 mg for seven days, all of which were well tolerated.

Indications:

• Postoperative Ileus: After partial large or small bowel resection surgery with primary anastomosis, Alvimopan is recommended to hasten the healing of the upper and lower gastrointestinal tracts.

• Use in Hospitals Only: This product is not meant for use by outpatients; rather, it is usually utilized in hospital settings.

• Short-Term Use: A maximum of 15 doses of Alvimopan should be administered.

Contraindications:

• Hypersensitivity reported to Alvimopan or any of its ingredients.

• Individuals who have taken opioids at therapeutic levels for more than seven days in a row before surgery.

• Concomitant use of opioids at therapeutic doses on the day of surgery or after,

• Extreme liver impairment.

• Concurrent use of potent CYP3A4 inhibitors (such as Clarithromycin and Ketoconazole).

• Short QT syndrome in oneself or one's family history.

• Continuous use of medications that lengthen the QT interval.

• Severely impaired kidney function (creatinine clearance < 15 mL/min).

Precautions and Warnings:

• Risk of Heart-Related Events: Patients with a history of cardiovascular disease are particularly at higher risk for heart-related events when using Alvimopan.

• Use for a Brief Time: It is meant to be used for no more than 15 dosages. Extended usage might have detrimental effects.

• Not for Chronic Usage: Alvimopan is not recommended for long-term usage with opioids and should not be taken in place of laxatives while using non-restrictive opioids.

• Patients with Severe Hepatic Impairment: Because Alvimopan may alter the liver's metabolism, patients with severe hepatic impairment should avoid using this medication.

• Keep an Eye Out for Anastomotic Leakage or Gastrointestinal Perforation: Patients at risk for anastomotic leakage or gastrointestinal perforation should use Alvimopan with caution as it may conceal symptoms of these diseases.

• Possibility of Drug Absorption: There may be drug interactions with Alvimopan, so let the healthcare professional know about all of the medications being taken by the patient.

• Not to Be Used on Youngsters: It is unknown if treating patients less than 18 years old is safe or effective.

• Patients should be made aware that they are required to reveal any long-term or intermittent opioid pain treatment, as well as any opioid usage during the week before starting Alvimopan. They should be aware that having recently used opioids may increase their risk of experiencing negative side effects with Alvimopan, especially those that are confined to the gastrointestinal system (such as nausea and stomach pain).

What Are the Adverse Reactions of Alvimopan?

• Tachycardia (Fast heartbeat of more than 100 beats per minute).

• Hypertension.

• Nausea.

• Vomiting.

• Diarrhea.

• Abdominal pain.

• Headache.

What Are the Pharmacological Aspects of Alvimopan?

Mechanism of Action:

Alvimopan competes with other drugs to bind to the gastrointestinal tract's mu-opioid receptors. The study of the movement and distribution of Alvimopan in the body accounts for its selectivity for peripheral receptors, while methylnaltrexone binding is dependent on its electric charge. With an inhibition constant (Ki) of 0.2 ng/mL, Alvimopan binds to peripheral mu-receptors exclusively, demonstrating the potency of the compound in blocking receptor activity.

Pharmacodynamics:

Alvimopan (3 mg three times a day) appeared to lessen the slowing in gastrointestinal motility brought on by Morphine (30 mg twice a day) in healthy volunteers. An additional study component examining the effect on cardiac conduction revealed that Alvimopan did not significantly lengthen the QTc interval, a measure of heart rhythm, even at larger doses (up to 24 mg twice a day for seven days). Nevertheless, this investigation did not examine the impact of Alvimopan on QTc at even greater dosages.

Pharmacokinetics:

The pharmacokinetics of Alvimopan entail quick absorption, with peak plasma concentrations occurring in 30 to 60 minutes. The medication has a half-life of roughly ten hours and is metabolized primarily by cytochrome P450 enzymes in the liver. The primary excretion site for Alvimopan and its metabolites is the feces. Patients with hepatic impairment may require dose modifications.

Drug Interactions:

• Acetaminophen.

• Tocilizumab.

• Loxapine.

• Adempas (Riociguat).

• Insulin inhalation, rapid acting.

• Alosetron.

• Alprazolam.

• Amantadine.

• Amiodarone.

• Amoxicillin.

• Amytal sodium (Amobarbital).

• Cefazolin.

• Testosterone.

• Darbepoetin alfa.

• Donepezil.

• Aripiprazole.

• Aspirin.

• Atorvastatin.

• Clonidine.

• Apixaban.

• Tamsulosin.

• Furosemide.

• Gabapentin.

• Lidocaine.

• Metoprolol.

• Losartan.

• Enoxaparin.

• Vancomycin.

• Ondansetron.

• Piperacillin / Tazobactam.

Use in Specific Populations:

• Pregnancy: Pregnancy category B agents include Alvimopan. Even at oral dosages of up to 200 mg per day, there has been no proof of fetal damage seen in animal investigations. In human pregnancy, no controlled data exist.

• Breastfeeding: Little information is available regarding the usage of Alvimopan during breastfeeding. It is imperative that the individuals speak with a healthcare provider before using it during nursing to assess the advantages and disadvantages.

• Geriatrics: For older people, there is no need to modify the dosage. The usage of Alvimopan in the elderly is not well studied, although due to possible age-related changes in sensitivity and metabolism, care is usually taken when giving medication to older patients.

• Pediatrics: Appropriate research on the correlation between age and Alvimopan's effects in the pediatric population has not been done. The efficacy and safety have not been proven.

• Hepatic Impairment: Patients with mild-to-moderate hepatic impairment do not require dosage adjustments. It is not advised for patients with significant liver impairment to use Alvimopan.

• Renal Impairment: Patients with mild-to-severe renal impairment do not require dosage adjustments, but they should be watched for side effects. It is not advised for people with end-stage renal disease to use Alvimopan.

Clinical Studies:

The study examined the use of Alvimopan in speeding up recovery after benign abdominal urinary tract reconstruction, a treatment not previously explored. Between 12/2014 and 7/2019, 70 patients underwent urinary reconstruction; 46 were eligible for Alvimopan. From 5/2018-7/2019, 11 received Alvimopan, compared to 22 who did not. The Alvimopan group showed shorter hospital stays (median five vs. eight days), quicker first bowel movement (median four vs. six days), and some need for a nasogastric tube. Complications and readmissions were similar in both groups.