KADIAN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KADIAN (KADIAN).
Mu-opioid receptor agonist; modulates pain perception and emotional response to pain.
| Metabolism | Primarily via CYP3A4; also undergoes N-demethylation to normorphine. |
| Excretion | Renal: primarily as morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G); ~90% of total elimination is renal, with 10% biliary/fecal |
| Half-life | Terminal elimination half-life of morphine: 2–4 hours; KADIAN extended-release formulation: effective half-life ~12 hours due to prolonged absorption, dosing q12h or q24h |
| Protein binding | ~30–35% bound, primarily to albumin |
| Volume of Distribution | 1.0–4.0 L/kg; wide distribution reflects extensive tissue uptake |
| Bioavailability | Oral: ~20–40% due to extensive first-pass metabolism |
| Onset of Action | Oral: analgesic effect begins within 1–2 hours post-dose |
| Duration of Action | Extended-release formulation: analgesic duration 12–24 hours depending on dose and individual response; intended for around-the-clock dosing |
20-100 mg orally every 12 hours; titration based on pain severity and prior opioid exposure.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | GFR 30-60 mL/min: start with 75% of usual dose; GFR <30 mL/min: start with 50% of usual dose and increase cautiously. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: start with 50-75% of usual dose; Child-Pugh Class C: avoid or use with extreme caution. |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established. |
| Geriatric use | Start at lower end of dosing range (e.g., 10-20 mg every 12 hours); monitor for respiratory depression and constipation; consider extended dosing intervals. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for KADIAN (KADIAN).
| Breastfeeding | Morphine is excreted into breast milk. The M/P ratio is approximately 2.5:1 for morphine. Breastfeeding is generally considered compatible with caution; monitor infant for respiratory depression, sedation, and withdrawal symptoms. American Academy of Pediatrics considers morphine compatible with breastfeeding, but advise using lowest effective dose for shortest duration. |
| Teratogenic Risk | KADIAN (morphine sulfate extended-release) is classified as Pregnancy Category C. First trimester: risks are uncertain but opioid use has been associated with neural tube defects in some studies; however, data for morphine specifically are limited. Second and third trimesters: chronic use may lead to fetal dependence and withdrawal (neonatal abstinence syndrome). Near term: increased risk of respiratory depression in the neonate. Morphine crosses the placenta. |
■ FDA Black Box Warning
WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P450 3A4 INTERACTION; RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS.
| Serious Effects |
["Significant respiratory depression","Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment","Known or suspected gastrointestinal obstruction, including paralytic ileus","Hypersensitivity to morphine sulfate or any component of the product"]
| Precautions | ["Addiction, abuse, and misuse","Life-threatening respiratory depression","Accidental ingestion","Neonatal opioid withdrawal syndrome","Cytochrome P450 3A4 interaction","Risks from concomitant use with benzodiazepines or other CNS depressants","Adrenal insufficiency","Severe hypotension","Gastrointestinal effects","Seizures","Avoid in patients with known or suspected gastrointestinal obstruction, including paralytic ileus"] |
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| Fetal Monitoring | Maternal: monitor for respiratory depression, sedation, constipation, and signs of opioid withdrawal. Fetal: assess fetal growth and well-being with ultrasound in cases of chronic use; monitor for signs of neonatal abstinence syndrome (NAS) after delivery. Consider non-stress tests or biophysical profiles as indicated. |
| Fertility Effects | Opioids may affect fertility by altering hypothalamic-pituitary-gonadal axis, leading to reduced libido, erectile dysfunction, and anovulation in females. Chronic use can lead to hypogonadism. Limited data on morphine specifically. |