naldemedine

REMS

Treatment of opioid-induced constipation in patients with chronic noncancer pain, including those with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation.

Action ⬆ ⬇

Acts peripherally as a mu-opioid receptor antagonist, blocking opioid effects on the GI tract.

Therapeutic effects:

Blocks constipating effects of opioids on the GI tract without loss of analgesia.

Pharmacokinetics ⬆ ⬇

Absorption: Rapidly absorbed; absorption delayed by high-fat meal by 2 hr.

Distribution: Moderate tissue distribution, does not cross the blood-brain barrier.

Protein Binding: 93–94%.

Metabolism/Excretion: Primarily metabolized by liver via the CYP3A isoenzyme to an active metabolite (nor-naldemedine); 57% excreted in urine (16–18% as unchanged drug), 35% excreted in feces.

Half-Life: 11 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	0.75 hr	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Known/suspected mechanical GI obstruction;
↑risk of recurrent GI obstruction;
Severe hepatic impairment;
Lactation: Lactation.

Use Cautiously in:

Known/suspected lesions of GI tract (↑ risk for GI perforation);
Receiving opioids for <4 wk (may be less responsive to naldemedine);
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

GI: abdominal pain, diarrhea, gastroenteritis, GI PERFORATION, nausea, vomiting

Misc: opioid withdrawal

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A inducers, including carbamazepine, phenytoin, or rifampin, may ↓ levels and effectiveness; avoid concurrent use.
Other opioid antagonists may cause additive effects and ↑ risk of opioid withdrawal.
Moderate CYP3A inhibitors and strong CYP3A inhibitors, including aprepitant, atazanavir, clarithromycin, diltiazem, erythromycin, fluconazole, itraconazole, ketoconazole, or ritonavir, may ↑ levels and risk of toxicity.
P-glycoprotein inhibitors, including amiodarone, captopril, cyclosporine, quinidine, or verapamil, may ↑ levels and risk of toxicity.

Drug-Natural Products:

St. John's wort may ↓ levels and its effectiveness; avoid concurrent use.

Route/Dosage ⬆ ⬇

PO (Adults ): 0.2 mg once daily.

Availability ⬆ ⬇

Assessment ⬆ ⬇

Assess bowel sounds and frequency, quantity, and consistency of stools periodically during therapy.
Monitor pain intensity during therapy. Naldemedine does not affect pain or effects of opioid analgesics on pain control. Discontinue naldemedine if opioid analgesic is discontinued. Patients receiving opioids for <4 wk may be less responsive to naldemedine.
Monitor for signs and symptoms of GI perforation (severe, persistent, or worsening abdominal pain) periodically during therapy. Discontinue naldemedine if symptoms occur.

Implementation ⬆ ⬇

PO: Administer once daily without regard to food.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take naldemedine as directed. Advise patient to read Medication Guide prior to starting therapy and with each refill in case of changes.
Advise patient to notify health care professional immediately if stomach pain that does not go away occurs.
Advise patient to notify health care professional if signs and symptoms of opioid withdrawal (sweating, chills, diarrhea, stomach pain, anxiety, irritability, yawning) occur. Patients taking methadone for pain are at increased risk for stomach pain and diarrhea.
Instruct patient to stop taking naldemedine if they stop taking opioid medications.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during and for 3 days after last dose of therapy.

Evaluation/Desired Outcomes ⬆ ⬇

Relief of opioid induced constipation, especially if opioid therapy has been for 4 wk or more.

US Brand Names ⬆ ⬇

Code ⬆

NDC Code

59011- Purdue Pharma LP
- 59011-523- Symproic
  - 59011-523-07- 1 BLISTER PACK in 1 CAPSULE (59011-523-07) > 7 TABLET in 1 BLISTER PACK

59011- Purdue Pharma LP
- 59011-523- Symproic
  - 59011-523-30- 30 TABLET in 1 BOTTLE (59011-523-30)

59011- Purdue Pharma LP
- 59011-523- Symproic
  - 59011-523-90- 90 TABLET in 1 BOTTLE (59011-523-90)

59385- BioDelivery Sciences International Inc
- 59385-041- SYMPROIC
  - 59385-041-30- 30 TABLET in 1 BOTTLE, PLASTIC (59385-041-30)

59630- Shionogi Inc.
- 59630-222- SYMPROIC
  - 59630-222-07- 1 BLISTER PACK in 1 CARTON (59630-222-07) > 7 TABLET in 1 BLISTER PACK

59630- Shionogi Inc.
- 59630-222- SYMPROIC
  - 59630-222-30- 30 TABLET in 1 BOTTLE (59630-222-30)

59630- Shionogi Inc.
- 59630-222- SYMPROIC
  - 59630-222-90- 90 TABLET in 1 BOTTLE (59630-222-90)

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇