Movantik

Administration Instructions

• Discontinue all maintenance laxative therapy prior to initiation of MOVANTIK. Laxative(s) can be used as needed if there is a suboptimal response to MOVANTIK after three days.
• Alteration in analgesic dosing regimen prior to initiating MOVANTIK is not required.
• Patients receiving opioids for less than 4 weeks may be less responsive to MOVANTIK [see Clinical Studies (14)] .
• Take MOVANTIK on an empty stomach at least 1 hour prior to the first meal of the day or 2 hours after the meal.
• For patients who are unable to swallow the MOVANTIK tablet whole, the tablet can be crushed to a powder, mixed with 4 ounces (120 mL) of water, and drunk immediately. The glass should be refilled with 4 ounces (120 mL) of water, stirred and the contents drunk.
• MOVANTIK can also be administered via a nasogastric (NG) tube, as follows:
  • Flush the NG tube with 1 ounce (30 mL) of water using a 60 mL syringe.
  • Crush the tablet to a powder in a container and mix with approximately 2 ounces (60 mL) of water.
  • Draw up the mixture using the 60 mL syringe and administer the syringe contents through the NG tube.
  • Add approximately 2 ounces (60 mL) of water to the same container used to prepare the dose of MOVANTIK.
  • Draw up the water using the same 60 mL syringe and use all the water to flush the NG tube and any remaining medicine from the NG tube into the stomach.
• Avoid consumption of grapefruit or grapefruit juice during treatment with MOVANTIK.
• Discontinue MOVANTIK if treatment with the opioid pain medication is also discontinued.

Adult Dosage

The recommended MOVANTIK dosage is 25 mg once daily in the morning. If patients are not able to tolerate MOVANTIK, reduce the dosage to 12.5 mg once daily [see Clinical Pharmacology (12.2)] .

Dosage in Adult Patients with Renal Impairment

The starting dosage for patients with creatinine clearance (CLcr) <60 mL/min (i.e., patients with moderate, severe, or end-stage renal impairment) is 12.5 mg once daily. If this dosage is well tolerated but OIC symptoms continue, the dosage may be increased to 25 mg once daily taking into consideration the potential for markedly increased exposures in some patients with renal impairment and the increased risk of adverse reactions with higher exposures [see Use in Specific Populations (8.6)and Clinical Pharmacology (12.3)] .

Dosage Recommendations due to Drug Interactions

Avoid concomitant use of MOVANTIK with moderate CYP3A4 inhibitor drugs (e.g., diltiazem, erythromycin, verapamil). If concurrent use is unavoidable, reduce the MOVANTIK dosage to 12.5 mg once daily and monitor for adverse reactions [see Drug Interactions (7.1)and Clinical Pharmacology (12.3)] .

Pregnancy

Risk Summary

Limited available data with MOVANTIK use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes. MOVANTIK may precipitate opioid withdrawal in the pregnant women and the fetus (see Clinical Considerations) .

In animal development studies, no effects on embryo-fetal development were observed following administration of naloxegol in pregnant rats during the period of organogenesis at doses up to 1452 times the human AUC (area under the plasma concentration-time curve) at the maximum recommended human dose. No effects on embryo-fetal development were observed following administration of naloxegol in pregnant rabbits during the period of organogenesis at doses up to 409 times the human AUC at the maximum recommended human dose.

The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically-recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations

Maternal and Fetal/Neonatal adverse reactions

The use of MOVANTIK may be associated with opioid withdrawal in the pregnant woman and the fetus.

Data

Animal Data

Oral administration of up to 750 mg/kg/day naloxegol in rats (1452 times the human AUC at the maximum recommended human dose) and 450 mg/kg/day naloxegol in rabbits (409 times the human AUC at the maximum recommended human dose) during the period of organogenesis produced no adverse effects on embryo-fetal development. Oral administration of up to 500 mg/kg/day in rats (195 times the maximum recommended human dose based on body surface area) during the period of organogenesis through lactation produced no adverse effects on parturition or the offspring.

Lactation

There are no data on the presence of naloxegol in human milk, the effects in nursing infants, or the effects on milk production. Naloxegol is present in rat milk (see Data). Because of the potential for adverse reactions, including opioid withdrawal in breastfed infants, advise women that breastfeeding is not recommended during treatment with MOVANTIK.

Data

Following oral administration of naloxegol in lactating rats, concentrations of naloxegol in milk were approximately 3- to 4-fold higher than concentrations of naloxegol in maternal plasma. Naloxegol was detected in plasma from pups.

Pediatric Use

The safety and effectiveness of MOVANTIK have not been established in pediatric patients.

Geriatric Use

Of the total number of subjects in clinical studies of MOVANTIK, 11% were 65 and over, while 2% were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

MOVANTIK exposure was higher in elderly healthy Japanese subjects compared to young subjects [see Clinical Pharmacology (12.3)] . No dosage adjustment is needed in elderly patients.

Renal Impairment

Some subjects with creatinine clearance (CLcr) values <60 mL/minute (i.e., moderate, severe, or end-stage renal disease) were shown to exhibit markedly higher systemic exposure of naloxegol compared to subjects with normal renal function. The reason for these high exposures is not understood. However, as the risk of adverse reactions increases with systemic exposure, a lower starting dosage of 12.5 mg once daily is recommended. No dosage adjustment is needed in patients with mild renal impairment [see Dosage and Administration (2.3)and Clinical Pharmacology (12.3)] .

Hepatic Impairment

The effect of severe hepatic impairment (Child-Pugh Class C) on the pharmacokinetics of naloxegol has not been evaluated. Avoid use of MOVANTIK in patients with severe hepatic impairment, as the dosage in these patients has not been determined. No dosage adjustment is required for patients with mild or moderate hepatic impairment [see Clinical Pharmacology (12.3)] .

Opioid Withdrawal

Clusters of symptoms consistent with opioid withdrawal, including hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning have occurred in patients treated with MOVANTIK [see Adverse Reactions (6.1)] . In addition, patients receiving methadone as therapy for their pain condition were observed in clinical trials to have a higher frequency of gastrointestinal adverse reactions that may have been related to opioid withdrawal than patients receiving other opioids [see Adverse Reactions (6.1)] . Patients having disruptions to the blood-brain barrier may be at increased risk for opioid withdrawal or reduced analgesia. Take into account the overall risk-benefit profile when using MOVANTIK in such patients. Monitor for symptoms of opioid withdrawal in such patients.

Severe Abdominal Pain and/or Diarrhea

Reports of severe abdominal pain and/or diarrhea have been reported, some of which resulted in hospitalization. Most of the cases of severe abdominal pain were reported in patients taking the 25 mg dosage. Symptoms generally occurred within a few days of initiation of MOVANTIK. Monitor patients for the development of abdominal pain and/or diarrhea with MOVANTIK and discontinue therapy if severe symptoms occur. Consider restarting MOVANTIK at 12.5 mg once daily, if appropriate.

Gastrointestinal Perforation

Cases of gastrointestinal (GI) perforation have been reported with use of peripherally acting opioid antagonists, including MOVANTIK. Postmarketing cases of GI perforation, including fatal cases, were reported when MOVANTIK was used in patients at risk of GI perforation (e.g., infiltrative gastrointestinal tract malignancy, recent gastrointestinal tract surgery, diverticular disease including diverticulitis, ischemic colitis, or concomitantly treated with bevacizumab). MOVANTIK is contraindicated in patients with known or suspected gastrointestinal obstruction or in patients at risk of recurrent obstruction [see Contraindications (4)] . Take into account the overall risk-benefit profile when using MOVANTIK in patients with these conditions or other conditions which might result in impaired integrity of the gastrointestinal tract wall (e.g., Crohn’s disease). Monitor for the development of severe, persistent or worsening abdominal pain; discontinue MOVANTIK in patients who develop this symptom.