Naldemedine for Treating Opioid‑Induced Constipation

NICE Technology Appraisal 651: Naldemedine for treating opioid‑induced constipation

The production of this Guidelines card has been commissioned by Sandoz Ltd. Rizmoic®▼(naldemedine): NICE TA651

1 Recommendations1 to be lower in patients with non-cancer pain. The clinical expert also highlighted 1.1 Naldemedine is recommended, within its that in clinical practice, many patients marketing authorisation, as an option for taking a PAMORA have mixed aetiology treating opioid-induced constipation in adults constipation and so need a combination who have had laxative treatment. treatment to target the different causes of constipation. For some patients the burden 2 Information about naldemedine1 of opioid-induced constipation on quality of life is greater than the pain that needs Marketing authorisation indication an opioid. This often means patients stop opioid treatment. The clinical expert said that 2.1 Naldemedine (Rizmoic, Shionogi) has a a key benefit of a PAMORA is that patients marketing authorisation in the UK for ‘the can have a normal stool, while those taking treatment of opioid-induced constipation conventional laxatives often experience a in adult patients who have previously been continual back and forth of being constipated treated with a laxative’. and then having diarrhoea. This is a huge burden for both patients and carers in terms 3 Committee discussion1 of continually managing bowel function. The committee concluded that people with opioid- 3.1 ...Naldemedine is an alternative oral PAMORA induced constipation would welcome a new taken as a single daily dose. The clinical treatment that improves their constipation expert explained that opioid-induced symptoms and quality of life. constipation is very common in people with non-cancer and cancer pain, and continues PAMORA=peripherally acting m-opioid receptor antagonist regardless of the type of opioid used. The expert estimated that over 80% of patients For access to summaries of national clinical with cancer pain will have opioid-induced guidelines, and to download this constipation, while the prevalence is likely Guidelines TA card, please visit Guidelines.co.uk Reference

1. NICE. Naldemedine for treating opioid-induced constipation. NICE Technology Appraisal Guidance 651. NICE, September 2020. www.nice.org.uk/guidance/TA651 When NICE recommends a treatment, the NHS must make sure it is available to those people it could help, normally within 3 months of the guidance being issued. The production and printing of this Guidelines summary card has been commissioned by Sandoz Ltd. Sandoz Ltd has reviewed the card for technical accuracy and regulatory compliance and supplied the prescribing information. This summary card only displays the concise guidance; readers are strongly advised to refer to the full guidance at www.nice.org.uk/guidance/TA651

NICE guidance is prepared for the National Health Service in England. All NICE guidance is subject to regular review and may be updated or withdrawn. NICE accepts no responsibility for the use of its content in this publication. MGP Ltd owns copyright of the Guidelines brand, logo, and the design and format of this summary card. The views and opinions expressed are not necessarily those of Sandoz Ltd, or of Guidelines, its publisher, advisers, or advertisers. UK/P/RZM/20-0016 © MGP Ltd 2020 Date of preparation: September 2020 taking Rizmoic. Severe hepatic impairment: Naldemedine has

Rizmoic▼(naldemedine) Prescribing Information not been studied in patients with severe hepatic impairment, not Please refer to the Summary of Product Characteristics (SPC) recommended in these patients. Concomitant use with strong before prescribing. CYP3A inhibitors and inducers: Concomitant use with strong Each film coated tablet contains 200 micrograms Presentation: CYP3A inhibitors leads to an increase in naldemedine exposure, naldemedine (as tosylate) for oral administration. may increase the risk of adverse reactions and should be Rizmoic is indicated for the treatment of opioid- Indication: avoided. Concomitant use of naldemedine with strong CYP3A induced constipation (OIC) in adult patients who have previously inducers leads to a decrease in naldemedine exposure and been treated with a laxative. may reduce the efficacy of naldemedine. Concomitant use with The recommended dose is Dosage and Method of Use: strong CYP3A inducers is not recommended, use in caution 200 micrograms (one tablet) daily. Rizmoic may be used with with moderate CYP3A inducers. or without laxative(s) and can be taken with or without food. It Naldemedine is primarily metabolised by CYP3A may be taken at any time of the day but it is recommended to Interactions: with some contribution from UGT1A3 and is a substrate of be taken at the same time every day. Alteration of the analgesic P-glycoprotein (P-gp). Interactions with CYP3A inhibitors: dosing regimen prior to initiating Rizmoic is not required. Concomitant use with strong CYP3A inhibitors should be Rizmoic must be discontinued if treatment with the opioid is avoided. If use is unavoidable, monitor for adverse reactions. discontinued. Special populations Elderly patients (> 65 years Concomitant use of moderate CYP3A inhibitors may increase of age): No dose adjustment required, initiate in caution in those the plasma concentration. If used, monitor for adverse ≥ 75 years. Renal impairment: No dose adjustment required. reactions. There is no risk of interaction with concomitant use Patients with severe renal impairment should be clinically of mild CYP3A inhibitors. Interaction with strong and moderate monitored during initiation. Hepatic impairment: No dose CYP3A inducers: Concomitant use of strong CYP3A inducers adjustment required in mild or moderate hepatic impairment, is not recommended. Concomitant use of naldemedine with not recommended in severe hepatic impairment. Opioid pain moderate inducers has not been established, and patients medicinal products: Limited experience in patients treated with should be monitored. Interaction with strong P-gp inhibitors: daily doses > 400 mg equivalent of morphine. No experience in Concomitant use may increase plasma concentrations of patients treated for constipation induced by partial opioid mu- naldemedine. If used with strong P-gp inhibitors, monitor for agonists (e.g. buprenorphine). Paediatric population (<18 years adverse reactions. of age): The safety and efficacy have not yet been established. Pregnancy: Should No data are available. Pregnancy, Breast-feeding and Fertility: not be used during pregnancy unless the clinical condition of the Hypersensitivity to the active substance Contraindications: woman requires treatment with naldemedine. Breast-feeding: or to any of the excipients; patients with known or suspected Should not be used during breast-feeding. Fertility: No human gastrointestinal obstruction or perforation or patients at data are available. Studies in rats found to have no clinically increased risk of recurrent obstruction, due to the potential for relevant adverse effects on fertility or reproductive performance. gastrointestinal perforation. No or Gastrointestinal perforation: Effects on Ability to Drive and Use Machines: Warnings and Precautions: negligible influence on the ability to drive and use machines. Cases of gastrointestinal perforation have been reported In patients with non-cancer pain: The in the post-marketing setting, including fatal cases, when Undesirable Effects: most commonly reported adverse reactions were abdominal naldemedine was used in patients who were at an increased pain, diarrhoea, nausea, and vomiting. The majority of these risk of gastrointestinal (GI) perforation. Naldemedine must not were of mild to moderate severity and resolved without be used in patients with known or suspected GI obstruction or discontinuation. One serious case of abdominal pain and in patients at increased risk of recurrent obstruction. Caution one serious case of nausea were reported. Common (≥ should be exercised in patients with any conditions which might 1/100 to < 1/10) adverse events: diarrhoea, abdominal pain, result in impaired integrity of the GI tract wall. The overall benefit nausea, vomiting. Adverse events less frequently reported: risk for each patient should be taken into account. Patients opioid withdrawal syndrome, hypersensitivity, gastrointestinal should be monitored for the development of severe, persistent perforation. In patients with cancer pain: The most commonly or worsening abdominal pain. If obstruction or perforation are reported adverse reactions were diarrhoea and abdominal pain. suspected, naldemedine must be discontinued. Gastrointestinal The majority of these were of mild to moderate severity and adverse reactions: Abdominal adverse reactions have been resolved with treatment. Two serious cases of diarrhoea were reported. Patients should be advised to report severe, persistent reported. Very common (≥ 1/10) adverse events: diarrhoea, or worsening symptoms to their physician. In cases of severe common (≥ 1/100 to < 1/10): abdominal pain, less commonly diarrhoea or abdominal pain, the patient should be monitored reported adverse events: opioid withdrawal syndrome and and treated for dehydration using rehydration and appropriate gastrointestinal perforation. Prescribers should consult the SPC treatment as needed. Opioid withdrawal syndrome: Caution in relation to other adverse reactions. should be exercised with regards to opioid withdrawal. Patients POM. £41.72 per should be advised to discontinue naldemedine and to contact Legal Category: Basic NHS List Price: pack of 28 tablets. their physician if opioid withdrawal occurs. Cases of possible Marketing Authorisation (MA) Number: EU/1/18/1291/002. Shionogi B.V., Kingsfordweg, opioid withdrawal syndrome have been reported. Patients MA Holder: 151 1043GR Amsterdam, The Netherlands. having disruptions to the blood-brain barrier may be at increased Local Sandoz UK Limited, Park View, Riverside risk of opioid withdrawal or reduced analgesia, and the overall Representative: Way, Watchmoor Park, Camberley, Surrey, GU15 3YL, UK. benefit-risk should be considered with close monitoring for January 2020. UK/MKT/RZM/19- symptoms of opioid withdrawal. Patients with cardiovascular Last Date of Revision: 0002(1). conditions: Naldemedine was not studied in the clinical trial programme in patients who had a recent history of myocardial Adverse events should be reported. Reporting forms infarction, stroke or transient ischaemic attack within 3 months and information can be found at www.mhra.gov.uk/ of screening. These patients should be clinically monitored when yellowcard. Adverse events should also be reported to Sandoz Ltd at: [email protected].