ARYMO ER
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ARYMO ER (ARYMO ER).
ARYMO ER (morphine sulfate) is a full opioid agonist that binds to mu-opioid receptors in the central nervous system (CNS), inhibiting ascending pain pathways and altering pain perception. It also activates descending inhibitory pathways.
| Metabolism | Primarily metabolized via glucuronidation in the liver to morphine-3-glucuronide (M3G, inactive) and morphine-6-glucuronide (M6G, active). Minor pathways include N-demethylation to normorphine via CYP3A4, and conjugation. Excreted primarily in urine. |
| Excretion | Primarily renal (90%), with approximately 10% excreted unchanged in urine; the remainder as glucuronide conjugates (morphine-3-glucuronide, morphine-6-glucuronide) and minor metabolites. Biliary/fecal excretion accounts for <10%. |
| Half-life | Terminal elimination half-life is approximately 11–13 hours in healthy adults. This extended half-life compared to immediate-release morphine (2–4 hours) allows for once-daily dosing. In elderly or hepatic/renal impairment, half-life may be prolonged up to 22 hours. |
| Protein binding | Approximately 20–35% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | 1.0–4.7 L/kg. The large Vd indicates extensive tissue distribution, including sequestration in skeletal muscle, liver, and CNS, contributing to prolonged terminal half-life. |
| Bioavailability | Oral (extended-release): 20–40% due to extensive first-pass metabolism in the liver and gut wall. Food does not significantly alter bioavailability. |
| Onset of Action | Oral (extended-release): 1–2 hours after administration, due to the extended-release formulation requiring gradual dissolution and absorption. |
| Duration of Action | 12–24 hours with analgin (dipyrone); ARYMO ER is designed for 24-hour dosing interval. Clinical analgesic effect persists for the entire dosing interval in opioid-tolerant patients. |
15 mg to 30 mg orally every 12 hours; titrate to effect; maximum 60 mg per dose.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | GFR 30-60 mL/min: reduce dose by 25%; GFR 15-29 mL/min: reduce dose by 50%; GFR <15 mL/min: use alternative therapy. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 25%; Child-Pugh Class C: reduce dose by 50%. |
| Pediatric use | Not recommended for pediatric patients under 18 years of age. |
| Geriatric use | Initiate at lowest possible dose (15 mg every 12 hours) and titrate cautiously; monitor for CNS depression and constipation. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ARYMO ER (ARYMO ER).
| Breastfeeding | Codeine is excreted in breast milk. M/P ratio approximately 2.5. AAP recommends caution; risk of infant sedation and respiratory depression. Avoid use in breastfeeding women, especially those with CYP2D6 ultra-rapid metabolizer phenotype. |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: No adequate studies; potential risk based on animal data. Second/third trimester: Chronic use may cause neonatal opioid withdrawal syndrome (NOWS). Labor/delivery: May cause respiratory depression in neonate. |
■ FDA Black Box Warning
ARYMO ER exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Serious, life-threatening, or fatal respiratory depression may occur. Accidental ingestion of even one dose, especially by children, can cause fatal overdose. Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome. Concomitant use with benzodiazepines or CNS depressants may cause profound sedation, respiratory depression, coma, and death.
| Serious Effects |
["Significant respiratory depression","Acute or severe bronchial asthma in an unmonitored setting or without resuscitative equipment","Known or suspected gastrointestinal obstruction, including paralytic ileus","Hypersensitivity to morphine or any component of ARYMO ER"]
| Precautions | ["Life-threatening respiratory depression","Addiction, abuse, and misuse potential","Neonatal opioid withdrawal syndrome with prolonged use during pregnancy","CNS depressant effects (e.g., sedation, respiratory depression) when used with other CNS depressants","Risk of hypotension, especially in hypovolemic patients","Severe hypotension, including orthostatic hypotension","Gastrointestinal effects: constipation, ileus","Seizures in patients with seizure disorders","Adrenal insufficiency","Androgen deficiency with long-term use"] |
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| Fetal Monitoring |
| Maternal: Respiratory rate, sedation level, oxygen saturation, bowel function. Fetal: Heart rate monitoring during labor; assessment for NOWS post-delivery. |
| Fertility Effects | Opioids may impair fertility by affecting hypothalamic-pituitary-gonadal axis, leading to amenorrhea or anovulation. Reversible upon discontinuation. |
| Food/Dietary | Alcohol must be avoided as it can block the extended-release mechanism, leading to rapid release of oxymorphone and potential fatal overdose. Grapefruit juice may alter metabolism; caution advised. No other known significant food interactions. |
| Clinical Pearls | ARYMO ER is an extended-release formulation of oxymorphone, a mu-opioid receptor agonist. It is not interchangeable with immediate-release oxymorphone or other opioid ER products. Use with caution in patients with impaired respiratory function, hepatic or renal impairment, or history of substance abuse. Coadministration with CNS depressants may potentiate sedation and respiratory depression. Abrupt discontinuation can precipitate withdrawal. Due to the ER property, crushing or chewing can lead to dangerous dose dumping. |
| Patient Advice | Swallow capsules whole; do not crush, chew, or dissolve. Crushing can release the full dose at once, causing a fatal overdose. · Do not stop taking this medication abruptly; consult your doctor for a tapering schedule to avoid withdrawal symptoms. · Avoid alcohol and other CNS depressants (e.g., benzodiazepines, sedatives) as they can increase the risk of severe drowsiness, respiratory depression, and death. · Store in a secure place out of reach of children and others. Dispose of unused medication via a take-back program or flushing if no other option. · Contact your doctor if you experience difficulty breathing, severe drowsiness, or signs of allergic reaction (rash, hives, swelling). · ARYMO ER is for long-term daily use and not for as-needed (prn) pain. |