MS CONTIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MS CONTIN (MS CONTIN).

How it works

Mu-opioid receptor agonist; binds to mu-opioid receptors in the CNS, modulating pain perception and emotional response to pain.

What the body does with it

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).

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for MS CONTIN (MS CONTIN).

Breastfeeding	MS Contin (morphine) is excreted in breast milk with an M/P ratio of approximately 2.6. Relative infant dose is about 2-4% of maternal weight-adjusted dose. Avoid use in breastfeeding due to risk of infant sedation and respiratory depression; if necessary, monitor infant for drowsiness, difficulty feeding, and adequate weight gain.
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.

Warnings & precautions

■ 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.

Side Effect Profile

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

Absolute Contraindications

Significant respiratory depression; acute or severe bronchial asthma; known or suspected GI obstruction; hypersensitivity to morphine or any component; concurrent use of MAOIs or within 14 days.

Clinical Precautions

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.

Clinical Tips & Counseling

Drug interactions

Loading safety data…

MS CONTIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MS CONTIN (MS CONTIN).

How it works

Mu-opioid receptor agonist; binds to mu-opioid receptors in the CNS, modulating pain perception and emotional response to pain.

What the body does with it

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).

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for MS CONTIN (MS CONTIN).

Breastfeeding	MS Contin (morphine) is excreted in breast milk with an M/P ratio of approximately 2.6. Relative infant dose is about 2-4% of maternal weight-adjusted dose. Avoid use in breastfeeding due to risk of infant sedation and respiratory depression; if necessary, monitor infant for drowsiness, difficulty feeding, and adequate weight gain.
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.

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

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

Absolute Contraindications

Significant respiratory depression; acute or severe bronchial asthma; known or suspected GI obstruction; hypersensitivity to morphine or any component; concurrent use of MAOIs or within 14 days.