Rizmoic®
About Rizmoic®
Rizmoic®▼contains naldemedine and is indicated for the treatment of opioid-induced constipation (OIC) in adult patients who have previously been treated with a laxative.1
Benefits Of Rizmoic®:
- A peripherally acting μ-opioid receptor antagonist (PAMORA) that directly targets the GI mechanism that causes OIC1
- Clinically proven to improve spontaneous bowel movement and QoL in OIC and in both cancer and non-cancer pain2.3
- Recommended by NICE for opioid-induced constipation in adults who have had laxative treatment4
GI, gastrointestinal; OIC, opioid induced constipation; PAMORA, peripherally acting mu-opioid receptor antagonist; QoL, quality of life; BBB, blood brain barrier
▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. Please navigate to the footer for how to report adverse reactions.
References:
- Rizmoic® Summary of Product Characteristics. Available at: https://www.medicines.org.uk/emc/product/10816. Last accessed: November 2024
- Katakami N, et al. Randomized Phase III and Extension Studies of Naldemedine in Patients with Opioid-Induced Constipation and Cancer. J Clin Oncol. 2017;35(34):3859–3866
- Hale M, et al. Naldemedine versus placebo for opioid-induced constipation (COMPOSE-1 and COMPOSE-2): two multicentre, phase 3, double-blind, randomised, parallel-group trials. J Lancet Gastroenterol Hepatol. 2017;2(8):555–564
- NICE TA651. Naldemedine for treating opioid-induced constipation. Available at: https://www.nice.org.uk/guidance/ta651. Last accessed: November 2024
Mode of Action & Efficacy
Rizmoic®▼ Targeted Action1,2
- An opioid antagonist that binds to the μ opioid receptors
- Blocks the opioid from binding to the μ opioid receptors in the gastrointestinal tract
Rizmoic® Does NOT Cross the Blood Brain Barrier (BBB)1
- Rizmoic® is a naltrexone derivative with an additional side chain; this increases its molecular mass and the polar surface area, reducing its ability to cross the BBB
- CNS penetration of Rizmoic® is expected to be negligible at the recommended dose
Rizmoic® Molecular Structure
Naldemedine is designed to optimise relief from opioid induced constipation without compromising pain relief.1
Key considerations for Rizmoic® from recognised clinical trials and bodies:3-9
BBB, blood-brain barrier; CNS, central nervous system; GI, gastrointestinal; OIC, opioid induced constipation.
▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. Please navigate to the footer for how to report adverse reactions.
References:
- Rizmoic® 200mcg Summary of Product Characteristics. Available at: https://www.medicines.org.uk/emc/product/10816. Last accessed: November 2024
- Streicher JM and Bilsky EJ. Peripherally Acting μ-Opioid Receptor Antagonists for the Treatment of Opioid-Related Side Effects: Mechanism of Action and Clinical Implications. J Pharm Pract. 2018;31(6):658-669
- Hale M et al. Naldemedine versus placebo for opioid-induced constipation (COMPOSE-1 and COMPOSE-2): two multicentre, phase 3, double-blind, randomised, parallel-group trials. Lancet Gastroenterol Hepatol 2017;2:555–564
- Webster LR et al. Long-term use of naldemedine in the treatment of opioid-induced constipation in patients with chronic noncancer pain: a randomized, double-blind, placebo-controlled phase 3 study. Pain 2018; 159:987–94
- Katakami N, et al. Randomized Phase III and Extension Studies of Naldemedine in Patients with Opioid-Induced Constipation and Cancer. J Clin Oncol. 2017;35(34):3859–3866
- Katakami N, et al. Randomized phase III and extension studies: efficacy and impacts on quality of life of naldemedine in subjects with opioid-induced constipation and cancer. Ann Oncol 2018;29:1461–1467
- European Medicines Agency (EMA). Naldemedine – Summary of Product Characteristics. EMA, 2018. Available at: EMA Product Information. Last accessed: November 2024
- NICE. Naldemedine for Treating Opioid-Induced Constipation. NICE Technology Appraisal Guidance [TA651], 2020. Available at: https://www.nice.org.uk/guidance/ta651/. Last Accessed: November 2024
- Farmer AD, Drewes AM, et al. Pathophysiology and management of opioid-induced constipation: European expert consensus statement. United European Gastroenterol J. 2019 Feb;7(1):7-20
Treatment, Dosing & Administration
Key Information About Rizmoic®▼1-2
▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. Please navigate to the footer for how to report adverse reactions.
References:
- Rizmoic® 200mcg Summary of Product Characteristics. Available at: https://www.medicines.org.uk/emc/product/10816. Last accessed: November 2024
- Rizmoic® 200 microgram tablets (Viatris UK Healthcare Ltd). Available at: https://dmd-browser.nhsbsa.nhs.uk/amp/view/153655. Last accessed: November 2024
Prescribing Information
PRESCRIBING INFORMATION
Rizmoic▼ micrograms film-coated tablets
(Each tablet contains 200 micrograms naldemedine (as tosylate))
Please refer to Summary of Product Characteristics (SmPC) before prescribing
Indication: Rizmoic is indicated for the treatment of opioid-induced constipation (OIC) in adult patients who have previously been treated with a laxative.
Presentation: Film-coated tablet (tablet). Round, approximately 6.5 mm diameter, yellow tablet debossed with '222' and Shionogi logo on one side and '0.2' on the other side.
Dosage and administration: Oral use. The recommended dose of naldemedine is 200 micrograms (one tablet) daily, with or without food. Rizmoic may be used with or without laxative(s). It may be taken at any time of the day but it is recommended to be taken at the same time every day. Alteration of the analgesic dosing regimen prior to initiating Rizmoic is not required. Rizmoic must be discontinued if treatment with the opioid pain medicinal product is discontinued.
Contraindications: Hypersensitivity to the active substance or to any of the excipients. Patients with known or suspected gastrointestinal obstruction or perforation or patients at increased risk of recurrent obstruction, due to the potential for gastrointestinal (GI) perforation.
Warning and precautions: Rizmoic must not be used in patients with known or suspected GI obstruction or in patients at increased risk of recurrent obstruction, due to the potential for GI perforation (see section 4.3 of the SmPC for further information). Caution with regards to the use of naldemedine should be exercised in patients with any conditions which might result in impaired integrity of the gastrointestinal tract wall (e.g. peptic ulcer disease, Ogilvie’s syndrome, malignancy of the GI tract, Crohn’s disease). Patients should be monitored for the development of severe, persistent or worsening abdominal pain. If obstruction or perforation are suspected, Rizmoic must be discontinued. Abdominal adverse reactions (e.g. abdominal pain, vomiting and diarrhoea) have been reported with Rizmoic. Opioid withdrawal syndrome is a cluster of three or more of the following signs or symptoms: dysphoric mood, nausea or vomiting, muscle aches, lacrimation or rhinorrhea, pupillary dilation or piloerection or sweating, diarrhoea, yawning, fever or insomnia. Patients should be advised to discontinue Rizmoic and to contact their physician if opioid withdrawal occurs. Patients having disruptions to the blood-brain barrier (e.g., primary brain malignancies, central nervous system (CNS) metastases or other inflammatory conditions, active multiple sclerosis and advanced Alzheimer’s disease) may be at increased risk of opioid withdrawal or reduced analgesia. Patents with a recent history of myocardial infarction, stroke or transient ischaemic attack should be clinically monitored when taking Rizmoic. Rizmoic has not been studied in patients with severe hepatic impairment. The use of naldemedine is not recommended in these patients. Concomitant use with strong CYP3A inhibitors should be avoided. Please refer to SmPC for further information.
Interaction with other medicinal products: Naldemedine is primarily metabolised by CYP3A with some contribution from UGT1A3 and is a substrate of P glycoprotein (P gp). Concomitant use of strong CYP3A inhibitors such as grapefruit juice, itraconazole, ketoconazole, ritonavir, indinavir, saquinavir, telithromycin and clarithromycin should be avoided. If use with strong CYP3A inhibitors is unavoidable, monitor for adverse reactions. Rifampicin, a strong CYP3A inducer, significantly decreased exposure to naldemedine by 83% . Concomitant use of strong CYP3A inducers such as St. John’s wort (Hypericum perforatum), rifampicin, carbamazepine, phenobarbital and phenytoin is not recommended. Concomitant use of moderate CYP3A inhibitors such as fluconazole, may increase the plasma concentration of naldemedine. If used with moderate CYP3A inhibitors, monitor for adverse reactions. There is no risk of interaction with concomitant use of mild CYP3A inhibitors.
Pregnancy and lactation: There are no data from the use of naldemedine in pregnant women. Naldemedine should not be used during pregnancy unless the clinical condition of the woman requires treatment with naldemedine. Naldemedine should not be used during breast-feeding.
Effects on ability to drive and use machines: Naldemedine has no or negligible influence on the ability to drive and use machines.
Undesirable effects:
- Chronic non-cancer pain and opioid induced constipation: Common: diarrhoea, abdominal pain, nausea, vomiting Uncommon: Opioid withdrawal syndrome
- Cancer and opioid induced constipation: Very Common: diarrhoea Common: Abdominal pain Uncommon: Opioid withdrawal syndrome. For details on uncommon, rare, very rare and unknown undesirable effects, please refer to the SmPC.
Legal Category: POM Marketing Authorisation Number: PLGB 50999/0003 MAH: Shionogi B.V. Herengracht 464, 1017 CA Amsterdam, Netherlands NHS Price: Pack size 30: £44.70 Date of Revision of Prescribing Information: September 2024
UK-RIZM-2024-00016
The SmPC for this product, including adverse reactions, precautions, contra-indications, and method of use can be found at: http://www.mhra.gov.uk/Safetyinformation/Medicinesinformation/SPCandPILs/index.htm and from Viatris Medical Information, Building 4, Trident Place, Hatfield Business Park, Mosquito Way, Hatfield, Hertfordshire, AL10 9UL, phone no. 01707 853000, Email: info.uk@viatris.com.
▼This medicine is subject to additional monitoring. This will allow quick identification of new safety information. It allows continued monitoring of the benefit/risk balance of the medicinal product. Please continue to report suspected adverse reactions with any medicine or vaccine to the MHRA through the Yellow Card Scheme. It is easiest and quickest to report adverse drug reactions online via the Yellow Card website: https://yellowcard.mhra.gov.uk/ or search for MHRA Yellow Card in the Google Play or Apple App Store. Alternatively, prepaid Yellow Cards for reporting are available by writing to FREEPOST YELLOW CARD (no other address details necessary), by emailing yellowcard@mhra.gov.uk, at the back of the British National Formulary (BNF), by telephoning the Commission on Human Medicines (CHM) free phone line: 0800-731-6789, or by downloading and printing a form from the Yellow Card section of the MHRA website. You can also report adverse reactions direct to pv.uk@viatris.com.
Safety & Tolerability
Contraindications1
Rizmoic®▼ is contraindicated in the following patient groups:
Hypersensitivity to the active substance or to any of the excipients.
Patients with known or suspected gastrointestinal obstruction or perforation or patients at increased risk of recurrent obstruction, due to the potential for gastrointestinal perforation.
Side Effects1
The adverse reactions with Rizmoic® 200mg tablets in patients with:
- chronic non-cancer pain and opioid induced constipation (OIC)
- cancer and OIC
These were reported in clinical studies are presented in the tables according to the MedDRA system organ classification.
The frequency categories are defined using the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000) and not known (frequency cannot be estimated from the available data).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Adverse events presented by System Organ Class and frequency in patients with chronic non-cancer pain and opioid-induced constipation
aOne serious report of hypersensitivity reaction was observed in clinical studies with naldemedine. The patient recovered following discontinuation from the study
bMedDRA Preferred Terms: abdominal pain, abdominal pain upper, abdominal pain lower and abdominal discomfort
Adverse reactions presented by System Organ Class and frequency in patients with cancer and opioid-induced constipation
bMedDRA Preferred Terms: abdominal pain, abdominal pain upper, abdominal pain lower and abdominal discomfort
For a full list of adverse reactions, precautions, contraindications, and method of use please consult the SmPC.1
Special Warnings and Precautions1
Gastrointestinal perforation: Rizmoic® must not be used in patients with known or suspected GI obstruction or in patients at increased risk of recurrent obstruction, due to the potential for GI perforation.
Gastrointestinal adverse reactions: Patients should be advised to report severe, persistent or worsening symptoms to their physician. In case of severe diarrhoea or abdominal pain, the patient should be monitored and treated for dehydration using rehydration and appropriate treatment as needed.
Opioid withdrawal syndrome: This typically develops within minutes to several days following administration of an opioid antagonist. Caution should be exercised with regards to opioid withdrawal. Patients should be advised to discontinue Rizmoic® and to contact their physician if opioid withdrawal occurs.
Patients with cardiovascular conditions: Patients with a recent history of myocardial infarction, stroke or transient ischaemic attack should be clinically monitored when taking Rizmoic®.
Severe hepatic impairment: Rizmoic® is not recommended in these patients.
Concomitant use with strong CYP3A inhibitors and inducers: Concomitant use of Rizmoic® with strong CYP3A inducers is not recommended. Concomitant use of Rizmoic® with moderate CYP3A inducers should be used with caution.
Sodium: Rizmoic® contains less than 1 mmol sodium (23mg) per tablet, essentially “sodium-free”
The long-term safety profile of Rizmoic® can help reassure you and your patients when considering its extended use in the management of OIC.2
▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. Please navigate to the footer for how to report adverse reactions.
References:
- Rizmoic® 200mcg Summary of Product Characteristics. Available at: https://www.medicines.org.uk/emc/product/10816. Last accessed: December 2024
- Webster L R et al. Long-term use of naldemedine in the treatment of opioid-induced constipation in patients with chronic noncancer pain: a randomized, double-blind, placebo-controlled phase 3 study. Pain. 2018;159(5):987–994.
Clinical Information
Naldemedine was evaluated in the COMPOSE programme of Phase 3 trials:1-5
- Taken together the COMPOSE studies provide the largest evidence base available for any PAMORA (Peripherally Acting μ-Opioid Receptor Antagonist)
- The studies involve more than 2500 patients from all over Europe and in Japan, South Africa and the USA
- Separate studies were conducted in patients with OIC secondary to non-cancer and cancer-related pain
- Long-term data (52 weeks) have been gathered to support the long-term safety of naldemedine
Rizmoic®▼improves spontaneous bowel movements and QoL in patients with non-cancer pain.1,3-4
Rizmoic® significantly improved spontaneous bowel movement (SBM) vs. placebo over 12 weeks achieving at least 3 SBM per week, in two studies of non-cancer patients with OIC1*
*Treatment response was defined as at least 3 SBMs per week and a change of ≥1 SBMs per week vs. baseline in at least 9/12 trial weeks and 3 out of the last 4 weeks1
- Rizmoic® achieved a timely onset of relief from OIC, with a median time to first SBM of 4.7 hours from baseline vs 26.6 hours for placebo (secondary endpoint, p<0.0001)3
- In 12-week and 52-week studies, patients on Rizmoic® reported significant improvements in OIC symptoms and quality of life2-3
▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. Please navigate to the footer for how to report adverse reactions.
References:
- Hale M, et al. Naldemedine versus placebo for opioid-induced constipation (COMPOSE-1 and COMPOSE-2): two multicentre, phase 3, double-blind, randomised, parallel-group trials. J Lancet Gastroenterol Hepatol. 2017;2(8):555–564
- Webster L R et al. Long-term use of naldemedine in the treatment of opioid-induced constipation in patients with chronic noncancer pain: a randomized, double-blind, placebo-controlled phase 3 study. Pain. 2018;159(5):987–994
- Katakami N, et al. Randomized phase III and extension studies: efficacy and impacts on quality of life of naldemedine in subjects with opioid-induced constipation and cancer. Ann Oncol 2018;29:1461–1467
- Katakami N, et al. Randomized Phase III and Extension Studies of Naldemedine in Patients with Opioid-Induced Constipation and Cancer. J Clin Oncol. 2017;35:3859–66
- Saito Y, et al. Naldemedine in Japanese patients with opioid-induced constipation and chronic noncancer pain: open-label Phase III studies. J Pain Res. 2019;12:127–38
