Naldemedine

Contraindications

Known or suspected GI obstruction and patients at increased risk of recurrent obstruction, owing to the potential for GI perforation

History of hypersensitivity to naldemedine; bronchospasm and rash reported

Cautions

Gastrointestinal perforation

• GI perforation reported with use of another PAMORA in patients with conditions that may be associated with localized or diffuse reduction of structural integrity in the wall of the GI tract (eg, peptic ulcer disease, Ogilvie syndrome, diverticular disease, infiltrative GI tract malignancies, peritoneal metastases)
• Consider risk with use in patients with these conditions or other conditions that might result in impaired integrity of the GI tract wall (eg, Crohn disease)
• Monitor for severe, persistent, or worsening abdominal pain and discontinue naldemedine in patients who develop this symptom

Opioid withdrawal

• Clusters of symptoms consistent with opioid withdrawal include hyperhidrosis, chills, increased lacrimation, hot flush/flushing, pyrexia, sneezing, feeling cold, abdominal pain, diarrhea, nausea, and vomiting
• Patients with blood-brain barrier disruption may be at increased risk for opioid withdrawal or reduced analgesia
• Take into account the overall risk-benefit profile when prescribing naldemedine in such patients
• Monitor for symptoms of opioid withdrawal

Drug interaction overview

• Substrate of CYP3A4 (major), P-gp, and UGT1A3 (minor)
• Opioid antagonists: Avoid use with another opioid antagonist
• Strong CYP3A4 inducers: Avoid coadministration, owing to potential for decreased efficacy of naldemedine
• Moderate or strong CYP3A4 inhibitors: Monitor for potential naldemedine adverse effects, owing to increased plasma concentrations
• P-gp inhibitors: Monitor for potential naldemedine adverse effects, owing to increased plasma concentrations

This is not a complete list of Naldemedinedrug interactions. Ask your doctor or pharmacist for more information.

Take naldemedine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects.

naldemedine should come with a Medication Guide. Read and follow these instructions carefully. Ask your doctor if you have any questions.

Swallow the tablet whole. Do not crush, break, or chew it. You may take it with or without food.

Dosing

The dose of naldemedine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of naldemedine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For constipation caused by opioids:
    • Adults—0.2 milligrams (mg) once a day in the morning. Your doctor may adjust your dose as needed.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of naldemedine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Refer to adult dosing.

Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Naldemedine. Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Naldemedine. Avoid combination

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Naldemedine. Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Naldemedine. Monitor therapy

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Methylnaltrexone: May enhance the adverse/toxic effect of Opioid Antagonists. Specifically, the risk for opioid withdrawal may be increased. Avoid combination

Naloxegol: Opioid Antagonists may enhance the adverse/toxic effect of Naloxegol. Specifically, the risk for opioid withdrawal may be increased. Avoid combination

Opioid Antagonists: May enhance the adverse/toxic effect of Naldemedine. Specifically, the risk for opioid withdrawal may be increased. Avoid combination

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of Naldemedine. Monitor therapy

Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

St John's Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Animal studies have not shown adverse effects on embryofetal development. This drug does cross the placenta and may precipitate opioid withdrawal in a fetus due to the immature fetal blood-brain barrier. There are no controlled data in human pregnancy. US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

This drug should be used during pregnancy only if the benefit outweighs the potential risk to the fetus US FDA pregnancy category: Not assigned Risk Summary: There are no available data to inform a drug-associated risk of major birth defects and miscarriage. Comment: There is a potential for opioid withdrawal in a fetus when this drug is used in pregnant women.

• It is used to treat constipation caused by some pain drugs.

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.
• Loose stools (diarrhea).
• Upset stomach.

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-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

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.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time this medicine is refilled. If you have any questions about naldemedine, please talk with the doctor, pharmacist, or other health care provider.
• 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.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about naldemedine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using naldemedine.

Review Date: November 1, 2017

Naldemedine blocks certain effects of opioid medication. An opioid is sometimes called a narcotic.

Naldemedine reduces constipation caused by opioid pain medicine used to treat severe chronic pain. Naldemedine works by treating constipation without reducing the pain-relieving effects of the narcotic.

Naldemedine is used in people who have been taking opioid pain medicine for at least 4 weeks, to treat chronic pain that is not caused by cancer.

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

Naldemedine is usually taken once per day. Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Naldemedine may be habit-forming. Never share this medicine with another person, especially someone with a history of drug abuse or addiction. MISUSE OF NARCOTIC MEDICINE CAN CAUSE ADDICTION, OVERDOSE, OR DEATH, especially in a child or other person using the medicine without a prescription. Selling or giving away naldemedine is against the law.

You may take naldemedine with or without food.

Call your doctor if your symptoms do not improve, or if they get worse.

Store in the original container at room temperature, away from moisture and heat.

Keep track of your medicine. Naldemedine is a drug of abuse and you should be aware if anyone is using your medicine improperly or without a prescription.

After you stop using your pain medication, you should also stop taking naldemedine.