KADIAN
Clinical safety rating
cautionComprehensive 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 |
| Molecular Weight | 337.8 |
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 | Limited human data; animal studies show increased risk of neural tube defects and cardiac malformations at high doses. Use only if potential benefit justifies risk. |
| 2nd trimester | Associated with risks of growth restriction and preterm birth with chronic use. Use with caution; avoid prolonged use. |
| 3rd trimester | Prolonged use may cause neonatal opioid withdrawal syndrome (NOWS) and respiratory depression. Avoid in late pregnancy, especially near term. |
Clinical note
Comprehensive clinical and safety monograph for KADIAN (KADIAN).
| Placental transfer | Morphine readily crosses the placenta with maternal-to-fetal ratios of 0.6-1.0 in cord blood. |
| Breastfeeding | Morphine (active metabolite of KADIAN) is excreted into breast milk in low concentrations. Monitor infant for signs of sedation, respiratory depression, and poor feeding. Use with caution; consider benefits of breastfeeding vs. risk of infant exposure. |
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
■ 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 |
Hypersensitivity to morphine or any component of the formulationSignificant respiratory depressionAcute or severe bronchial asthmaKnown or suspected paralytic ileusConcurrent use of MAO inhibitors or within 14 days of such therapy
| 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 |
| Food/Dietary | Avoid alcohol and any products containing alcohol (e.g., alcoholic beverages, certain mouthwashes, over-the-counter liquid medications) as alcohol can increase the release rate of morphine from the extended-release formulation, risking overdose. Grapefruit juice may theoretically alter morphine metabolism; caution advised. High-fat meals may delay absorption but do not significantly affect overall exposure; take consistently with regard to meals. |
| Clinical Pearls | KADIAN is an extended-release morphine formulation requiring q12h dosing; capsules can be opened and sprinkled on applesauce but should not be crushed or chewed. Given the high opioid content, use with caution in opioid-naïve patients; start with lowest available strength. Monitor for respiratory depression, especially during titration. KADIAN levels may be affected by hepatic impairment; reduce dose in moderate to severe hepatic disease. Do not use for as-needed analgesia. |
| Patient Advice | Take KADIAN exactly every 12 hours; do not take more frequently. · Swallow capsules whole; if you have trouble, open the capsule and sprinkle the beads onto a small amount of applesauce and swallow immediately without chewing. · Do not crush, chew, or dissolve the capsule contents as that can cause a fatal overdose. · Avoid alcohol and any medicines containing alcohol while taking KADIAN. · Store securely out of reach of children and others; dispose of unused pills via a take-back program. · Do not stop taking abruptly; consult your doctor for a tapering schedule. · Contact your healthcare provider if you experience severe drowsiness, confusion, or difficulty breathing. |
Loading safety data…