MS CONTIN
Clinical safety rating
cautionComprehensive clinical and safety monograph for MS CONTIN (MS CONTIN).
Mu-opioid receptor agonist; binds to mu-opioid receptors in the CNS, modulating pain perception and emotional response to pain.
| Metabolism | Hepatic via CYP3A4 and to a lesser extent CYP2D6; major metabolites include morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). |
| Excretion | Renal: ~90% (mostly as morphine-3-glucuronide and morphine-6-glucuronide, with ~10% as unchanged morphine); Fecal: <10% |
| Half-life | Terminal elimination half-life: 11-13 hours (range 8-24 hours). In elderly or hepatic impairment, half-life may be prolonged; acute dosing half-life ~2-4 hours. |
| Protein binding | 30-35% bound to albumin. |
| Volume of Distribution | 1.0-4.7 L/kg (mean ~3.5 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Oral: 20-40% (first-pass metabolism); Rectal: ~50%; IV: 100%. |
| Onset of Action | Immediate-release: 30-60 minutes; Controlled-release (MS Contin): 1-2 hours (peak effect at 3-4 hours). |
| Duration of Action | Immediate-release: 3-6 hours; Controlled-release (MS Contin): 8-12 hours (up to 24 hours in some patients, but typical dosing is every 12 hours). |
| Molecular Weight | 758.83 |
Oral: 15-30 mg every 8-12 hours; adjust based on pain severity and prior opioid use. Extended-release tablets must be swallowed whole; do not crush or chew. For opioid-naïve patients, start at 15 mg every 12 hours.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | eGFR 30-59 mL/min: Administer 75% of usual dose every 12 hours. eGFR 15-29 mL/min: Administer 50% of usual dose every 12 hours. eGFR <15 mL/min: Administer 50% of usual dose every 12 hours, consider alternative. For dialysis patients: not recommended (accumulation of toxic metabolites). |
| Liver impairment | Child-Pugh Class A: No adjustment needed. Child-Pugh Class B: Reduce dose by 25% and increase dosing interval to every 12 hours. Child-Pugh Class C: Reduce dose by 50% and consider alternative therapy. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. For opioid-tolerant adolescents (≥13 years) transitioning from immediate-release to extended-release: use conversion guidelines, starting at the calculated equianalgesic dose, rounding down, with close monitoring. |
| Geriatric use | Start at lowest possible dose (e.g., 15 mg every 12 hours). Titrate cautiously due to increased sensitivity, decreased renal/hepatic function, and risk of falls, respiratory depression, and delirium. Monitor for accumulation. Consider avoidance or alternative in frail elderly. |
| 1st trimester | Avoid due to risk of neural tube defects and congenital malformations with first-trimester exposure. |
| 2nd trimester | Use only if clearly needed; prolonged use may lead to fetal opioid dependence. |
| 3rd trimester | Avoid; may cause neonatal opioid withdrawal syndrome (NOWS) and respiratory depression at delivery. |
Clinical note
Comprehensive clinical and safety monograph for MS CONTIN (MS CONTIN).
| Placental transfer | Morphine crosses the placenta readily; detectable in fetal plasma and amniotic fluid. |
| Breastfeeding | Morphine is excreted into breast milk in low amounts. Use with caution; monitor infant for drowsiness, difficulty feeding, and respiratory depression. Avoid if maternal dose >30 mg/day or multiple daily doses. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Limited data, but opioid use associated with neural tube defects (OR 1.5-2.0) and gastroschisis. Second/third trimester: Chronic use may cause fetal dependence, intrauterine growth restriction, premature labor. At delivery: Risk of neonatal opioid withdrawal syndrome (NOWS) in 60-80% of exposed neonates. |
| Fetal Monitoring | Maternal: Assess pain control, sedation level, respiratory rate, bowel function, and signs of abuse/dependence. Fetal: Nonstress test (NST) and biophysical profile (BPP) for growth restriction or distress. Monitor for preterm labor. Neonatal: Observe for symptoms of NOWS for at least 48-72 hours after delivery. |
| Fertility Effects | Chronic opioid use may disrupt hypothalamic-pituitary-gonadal axis, leading to hypogonadism with irregular menses, anovulation, and reduced fertility in both sexes. Effects are reversible upon discontinuation. |
■ FDA Black Box Warning
Addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants.
| Common Effects | Flushing sense of warmth in the face ears neck and trunk Abdominal pain Diarrhea Nausea Vomiting Indigestion Stomach inflammation Increased liver enzymes Rash |
| Serious Effects |
Hypersensitivity to morphine or any componentAcute or severe bronchial asthmaRespiratory depression in the absence of resuscitative equipmentParalytic ileusConcurrent MAO inhibitors or within 14 days
| Precautions | Respiratory depression; additive CNS effects with other depressants; hypotension; gastrointestinal obstruction; seizure threshold; serotonin syndrome; adrenal insufficiency; severe renal/hepatic impairment; elderly/debilitated; pregnancy (prolonged use); avoid abrupt discontinuation. |
| Food/Dietary | Avoid alcohol and foods containing alcohol (e.g., some sauces, desserts). High-fat meals may slow absorption; take consistently with or without food to maintain steady effect. No specific food restrictions beyond alcohol. |
| Clinical Pearls | MS Contin (morphine sulfate extended-release) is an opioid agonist indicated for around-the-clock management of moderate to severe pain requiring opioid treatment. Key pearls: 1) Do not crush, chew, or dissolve tablets; this can cause rapid release and fatal overdose. 2) Use with caution in patients with respiratory compromise, alcohol or benzodiazepine use, or obstructive sleep apnea. 3) Monitor for signs of constipation; prescribe bowel regimen prophylactically. 4) Tolerance and dependence develop; avoid abrupt discontinuation. 5) Use lowest effective dose for shortest duration. 6) Respiratory depression risk peaks after initial dosing and titration. |
| Patient Advice | Take exactly as prescribed; do not change dose or frequency without consulting your doctor. · Swallow tablets whole; do not crush, chew, or dissolve them. · Avoid alcohol and other sedatives (e.g., benzodiazepines) as they can increase risk of severe drowsiness, respiratory depression, and death. · If you miss a dose, skip it and take next dose at regular time; do not double dose. · Common side effects include constipation, nausea, drowsiness, and dizziness. Report severe constipation or difficulty breathing. · Do not stop suddenly without doctor guidance; withdrawal symptoms may occur. · Keep out of reach of children and others; store in a secure place. · Do not share medication with others; it can cause fatal overdose. · Use caution when driving or operating machinery until you know how the medication affects you. · Notify doctor if you are pregnant, breastfeeding, or planning to become pregnant. |
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