Movantik by AstraZeneca Pharmaceuticals LP

Pharmacy Times, February 2015 Autoimmune Disorders, Volume 81, Issue 2

The FDA has approved Astra-Zeneca's Movantik (naloxegol) tablets for the treatment of opioid-induced constipation (OIC) in adults with chronic noncancer pain.

The FDA has approved Astra-Zeneca’s Movantik (naloxegol) tablets for the treatment of opioid-induced constipation (OIC) in adults with chronic noncancer pain.1 Due to its structural similarity to noroxymorphone, Movantik was initially approved as a Schedule II controlled substance; however, its labeling stated that it carried no risk of abuse or dependency. The Drug Enforcement Administration descheduled Movantik in February 2015, and AstraZeneca requested that the FDA remove the controlled substance designation.1,2 Movantik could be available by June 2015.2

Pharmacology and Pharmacokinetics

Opioids bind to mu-receptors in the central nervous system (CNS), resulting in pain relief; however, they also bind to mu-receptors in the gastrointestinal (GI) tract, resulting in constipation. Movantik is an oral peripherally acting mu-opioid receptor antagonist (PAMORA) that exerts its effect by preventing binding with mu-receptors in the GI tract, with negligible CNS interference.1,2

After oral administration, Movantik achieves peak concentration in less than 2 hours. A high-fat meal increases the rate and extent of absorption; therefore, Movantik should be taken on an empty stomach. Its metabolism is primarily through the CYP3A enzyme system.1

Dosage and Administration

Movantik should be given at a dosage of 25 mg orally once daily; if not tolerated, the dosage may be decreased to 12.5 mg once daily. Patients with a creatinine clearance level less than 60 mL/min should begin at a dosage of 12.5 mg once daily; if this is tolerated, it may be increased to 25 mg once daily.

Maintenance laxative therapy should be discontinued prior to initiation of treatment with Movantik, but may be resumed if patients experience OIC symptoms after taking Movantik for 3 days. Changes in opioid therapy are not required before starting Movantik. Movantik has been shown to be efficacious in patients who have been using opioids for at least 4 weeks. It should be taken on an empty stomach at least 1 hour before the first meal of the day or 2 hours after the meal. The tablets should be swallowed whole and never chewed or crushed. Grapefruit and grapefruit juice should be avoided during treatment with Movantik. Movantik should be discontinued if opioid therapy is discontinued.1

Clinical Trials

Movantik was evaluated in 2 replicate, randomized, doubleblind placebo-controlled trials in patients with OIC and non—cancerrelated pain. For 12 weeks, 1352 patients received Movantik 12.5 mg, Movantik 25 mg, or placebo. A statistically significant increase in the number of bowel movements per week occurred in the 12.5- and 25-mg groups in study 1 and in the 25-mg group in study 2.1,3

Contraindications, Warnings, and Precautions

Movantik is contraindicated in patients (1) with known or suspected GI obstruction, (2) who are at increased risk for recurrent GI obstruction, (3) who are using strong CYP3A4 inhibitors, such as clarithromycin and ketoconazole, or (4) with a known serious or severe hypersensitivity reaction to Movantik or any of its excipients.

The overall risks and benefits of Movantik should be considered in patients with known or suspected lesions of the GI tract. These patients should be monitored for severe, persistent, or worsening abdominal pain, and Movantik should be discontinued if these symptoms develop. The overall risks and benefits should also be considered in patients with disruptions to the blood—brain barrier; these patients should be monitored for symptoms of opioid withdrawal.

Concomitant use with moderate CYP3A4 inhibitors, such as diltiazem, erythromycin, and verapamil, should be avoided, as the combination may increase Movantik concentrations. If the combination is unavoidable, the dosage of Movantik should be decreased to 12.5 mg once daily. Concomitant use with strong CYP3A4 inducers, such as rifampin, should be avoided, as the combination may decrease Movantik concentrations. Movantik should not be used in combination with other opioid antagonists.

Movantik is a Pregnancy Category C medication. It should not be used during breast-feeding or in patients with severe hepatic impairment.

In clinical trials, the most common adverse reactions (≥3%) were abdominal pain, diarrhea, nausea, flatulence, vomiting, and headache.1

Dr. Holmberg earned her PharmD from the University of Connecticut and completed an ambulatory care residency at the Phoenix VA Healthcare System. Her practice has also included pediatrics and inpatient mental health. She resides in Phoenix, Arizona.

References

1. Movantik [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2014. www.azpicentral.com/movantik/movantik.pdf#page=1. Accessed November 2014.

2. FDA approves Movantik (naloxegol) tablets C-II for the treatment of opioid-induced constipation in adult patients with chronic non-cancer pain. AstraZeneca website. www.astrazeneca-us.com/media/press-releases/Article/20140916-fda-approves-movantik-naloxegol-tablets-cii. Accessed November 2014.

3. FDA approves Movantik for opioid-induced constipation. FDA website. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm414620.htm. Accessed November 2014.