US FDA Approves MOVANTIK™ (naloxegol) Tablets C-II
On September 16, the US Food and Drug Administration approved MOVANTIK™ (naloxegol) tablets C-II as the first once-daily oral peripherally acting mu-opioid receptor antagonist (PAMORA) for the treatment of opioid-induced constipation (OIC) in adults with chronic non-cancer pain.
Generic Name: naloxegol (nal OX ee gol)
Brand Names: Movantik
MOVANTIK Rx
Pharmacological Class:
Peripherally-acting mu-opioid receptor antagonist (PAMORA).

Active Ingredient(s):
Naloxegol 12.5mg, 25mg; tablets.

Company
AstraZeneca Pharmaceuticals
Indication(s):
Opioid-induced constipation in adults with chronic non-cancer pain.

Pharmacology:
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.

Clinical Trials:
The safety and efficacy of Movantik was eva luated in two replicate, randomized, double-blind, placebo-controlled trials (Study 1 and Study 2) in patients with opioid-induced constipation (OIC) and non-cancer related pain. Patients in Study 1 (n=652) and Study 2 (n=700) were randomized to receive Movantik 12.5mg, Movantik 25mg, or placebo once daily for 12 weeks. The primary endpoint was response defined as: ≥3 spontaneous bowel movements per week and a change from baseline of ≥1 spontaneous bowel movement per week for at least 9 out of the 12 study weeks and 3 out of the last 4 weeks.

In Study 1, there was a statistically significant difference for the Movantik 12.5mg and 25mg treatment groups vs. placebo for the primary endpoint. In the Movantik 12.5mg group, 41% showed response (difference 11.4%; [95% CI: 2.4, 20.4]; P=0.015), and 44% showed response (difference 15%; [95% CI: 5.9, 24.0]; P=0.001) in the Movantik 25mg group, as compared to 29% in the placebo group. In Study 2, there was a statistically significant difference for the Movantik 25mg treatment group vs. placebo, but not for the Movantik 12.5mg treatment group. In the Movantik 12.5mg group, 35% of patients had a response (difference 5.6%; [95% CI: −2.9, 14.1]; P=0.202), and 40% had a response in the Movantik 25mg treatment group (difference 10.3%; [95% CI: 1.7, 18.9]; P=0.021), as compared to 29% in the placebo group.

For more clinical trial data, see full labeling.

Legal Classification:
Rx
Adults:
Discontinue all laxative therapy prior to initiation; may use as needed if suboptimal response after 3 days. Discontinue if opioid pain therapy is also discontinued. Swallow whole. Take on an empty stomach. 25mg once daily in the AM; may reduce to 12.5mg once daily if unable to tolerate. Moderate, severe, or end-stage renal impairment (CrCl <60mL/min): 12.5mg once daily; may increase to 25 mg once daily if well tolerated and symptoms continue. Concomitant moderate CYP3A4 inhibitors: if unavoidable, reduce naloxegol to 12.5mg once daily; monitor.

Children:
Not established.

Contraindication(s):
Known or suspected GI obstruction. Patients at increased risk of recurrent obstruction. Concomitant strong CYP3A4 inhibitors (eg, clarithromycin, itraconazole, ketoconazole).

Warnings/Precautions:
Risk of GI perforation in those with conditions associated with reduction in structural integrity of the GI tract wall (eg, peptic ulcer disease, Ogilvie’s syndrome, diverticular disease, infiltrative GI tract malignancies, or peritoneal metastases). Monitor for severe, persistent or worsening abdominal pain; discontinue if occurs. Monitor for symptoms of opioid withdrawal (esp. patients receiving methadone or having disruptions to the blood brain barrier). Severe hepatic impairment (Child-Pugh Class C); avoid. Pregnancy (Category C). Nursing mothers: not recommended.

Interaction(s)
See Contraindications. Avoid concomitant moderate CYP3A4 inhibitors (eg, diltiazem, erythromycin, verapamil): if unavoidable, reduce dose (see Adults). Avoid concomitant other opioid antagonists, grapefruit, or grapefruit juice. Concomitant strong CYP3A4 inducers (eg, rifampin, carbamazepine, St. John’s Wort): not recommended.

Adverse Reaction(s)
Abdominal pain, diarrhea, nausea, flatulence, vomiting, headache, hyperhidrosis.

How Supplied:
Tabs—30, 90

LAST UPDATED:
4/28/2015