Naloxegol

What is naloxegol?

Naloxegol is  a prescription medicine that is used to treat constipation caused by some pain drugs.

Description

MOVANTIK (naloxegol), an opioid antagonist, contains naloxegol oxalate as the active ingredient. (Naloxegol is a PEGylated derivative of naloxone.)

The chemical name for naloxegol oxalate is: (5α,6α)-17-allyl-6-(2,5,8,11,14,17,20-heptaoxadocosan-22-yloxy)-4,5-epoxymorphinan-3,14-diol oxalate. The structural formula is:

The empirical formula for naloxegol oxalate is C34H53NO11.C2H2O4 and the molecular weight is 742.

Naloxegol oxalate is a white to off-white powder, with high aqueous solubility across the physiologic pH range.

MOVANTIK (naloxegol) tablets for oral use contain 14.2 mg and 28.5 mg of naloxegol oxalate, respectively, equivalent to 12.5 mg and 25 mg of naloxegol.

Excipients in tablet core are: mannitol, cellulose microcrystalline, croscarmellose sodium, magnesium stearate, and propyl gallate.

Excipients in tablet coat are: hypromellose, titanium dioxide, polyethylene glycol, iron oxide red, and iron oxide black.

Mechanism of Action

Naloxegol is an antagonist of opioid binding at the mu-opioid receptor. When administered at the recommended dose levels, naloxegol functions as a peripherally-acting mu-opioid receptor antagonist in tissues, such as the gastrointestinal tract, thereby decreasing the constipating effects of opioids.

Naloxegol is a PEGylated derivative of naloxone and is a substrate for the P-glycoprotein transporter (P-gp). Also, the presence of the PEG moiety in naloxegol reduces its passive permeability as compared with naloxone. Due to the reduced permeability and increased efflux of naloxegol across the blood-brain barrier, related to P-gp substrate properties, the CNS penetration of naloxegol is expected to be negligible at the recommended dose levels limiting the potential for interference with centrally mediated opioid analgesia.

Before taking naloxegol, tell your doctor:

• If you are allergic to naloxegol; any part of this medicine; or any other drugs, foods, or substances. Tell your doctor about the allergy and what signs you had.
• If you have liver disease.
• If you have ever had bowel block.
• If you take any drugs (prescription or OTC, natural products, vitamins) that must not be taken with naloxegol, like certain drugs that are used for HIV, infections, or seizures. There are many drugs that must not be taken with naloxegol.
• If you are taking St. John’s wort. Do not take St. John’s wort with naloxegol. This medicine may not work as well.
• If you are using another drug like this one. If you are not sure, ask your doctor or pharmacist.
• If you are breast-feeding. Do not breast-feed while you take naloxegol.

This is not a list of all drugs or health problems that interact with naloxegol.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take naloxegol with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some things I need to know or do while I take naloxegol?

• Tell all of your health care providers that you take naloxegol. This includes your doctors, nurses, pharmacists, and dentists.
• Talk with your doctor before using a laxative with naloxegol.
• Avoid grapefruit and grapefruit juice.
• This medicine is only for use in patients who take pain drugs. Tell your doctor if you stop taking your pain drug.
• Signs of opioid withdrawal have happened with naloxegol. Call your doctor right away if you have more sweating, chills, diarrhea or stomach pain that is not normal, anxiety, feeling irritable, or yawning.
• If you are taking methadone for pain, talk with your doctor. Stomach problems like diarrhea and stomach pain may happen more often in people taking methadone with naloxegol than in people taking other pain drugs.
• This medicine may not work as well for people who have been taking pain drugs for less than 4 weeks.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using naloxegol while you are pregnant.
• If naloxegol is used during pregnancy, it may cause withdrawal in the unborn baby. A doctor will need to check on the unborn baby after naloxegol is used.

How is naloxegol best taken?

Use naloxegol as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take on an empty stomach. Take at least 1 hour before or 2 hours after the first meal of the day.
• If you are not able to swallow naloxegol whole, it can be crushed and mixed in 4 ounces (120 mL) of water. Drink right away after mixing. Refill the glass with 120 mL of water, stir, and drink.
• Those who have feeding tubes may use naloxegol. Use as you have been told. Flush the feeding tube after naloxegol is given.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

What are the side effects of naloxegol that I need to call my doctor about immediately?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Very bad stomach pain and diarrhea have happened with naloxegol. Most of the time, these problems have happened within a few days after starting naloxegol. Sometimes, these problems have led to the need to go to the hospital. Call your doctor right away if you have very bad diarrhea or very bad stomach pain.
• Tears in the stomach or bowel wall have happened in certain people taking drugs like this one. Call your doctor right away if you have swelling or pain in your stomach that is very bad, gets worse, or does not go away. Call your doctor right away if you throw up blood or have throw up that looks like coffee grounds; upset stomach or throwing up that does not go away; or black, tarry, or bloody stools.

What are some other side effects of naloxegol?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Stomach pain or diarrhea.
• Gas.
• Headache.
• Upset stomach or throwing up.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-332-1088. You may also report side effects at https://www.fda.gov/medwatch.

If overdose is suspected:

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.

How do I store and/or throw out naloxegol?

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.