CODRIX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for CODRIX (CODRIX).

How it works

Codrix is a combination of codeine (a mu-opioid receptor agonist) and paracetamol (cyclooxygenase inhibitor, primarily in the CNS). Codeine is metabolized to morphine via CYP2D6, which mediates opioid effects. Paracetamol inhibits prostaglandin synthesis, providing analgesic and antipyretic effects.

What the body does with it

Metabolism	Codeine: primarily via CYP3A4 and CYP2D6 to morphine and norcodeine. Paracetamol: mainly via glucuronidation (UGT1A1, UGT1A6, UGT1A9) and sulfation; minor CYP2E1 oxidation to NAPQI.
Excretion	Primarily renal (60% unchanged) and biliary/fecal (30%); 10% metabolized.
Half-life	Terminal half-life 12-15 hours; steady-state reached in 2-3 days.
Protein binding	85-95% to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	1.5-2.0 L/kg, indicating extensive tissue distribution.
Bioavailability	Oral: 70-80%; IM: 90%.
Onset of Action	Oral: 30-60 min; IV: immediate; IM: 15-30 min.
Duration of Action	6-8 hours for oral; 4-6 hours for IM; IV duration dose-dependent.

Classification & Brands

Dosing & administration

2 mg orally once daily.

Dosage form	TABLET
Renal impairment	eGFR >=60 mL/min: no adjustment; eGFR 30-59 mL/min: reduce dose to 1 mg orally once daily; eGFR <30 mL/min: not recommended.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose to 1 mg orally once daily; Child-Pugh C: contraindicated.
Pediatric use	Safety and efficacy not established; use not recommended in pediatric patients.
Geriatric use	Initiate at 1 mg orally once daily; titrate cautiously due to increased sensitivity and renal function decline.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for CODRIX (CODRIX).

Breastfeeding	CODRIX is excreted in human breast milk with an M/P ratio of 0.85. Due to the potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during therapy and for at least 1 week after the last dose.
Teratogenic Risk	CODRIX is contraindicated in pregnancy. First trimester exposure is associated with a high risk of major congenital malformations, including neural tube defects, craniofacial abnormalities, and cardiovascular defects. Second and third trimester exposure may cause fetal growth restriction, oligohydramnios, and neonatal renal impairment.

Warnings & precautions

■ FDA Black Box Warning

Risk of medication errors due to confusion between codeine and other opioids; respiratory depression in children with CYP2D6 ultra-rapid metabolizers; addiction, abuse, and misuse; neonatal opioid withdrawal syndrome with prolonged use during pregnancy.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to codeine or paracetamol; significant respiratory depression; acute or severe bronchial asthma; suspected surgical abdomen; paralytic ileus; concomitant use with MAOIs or within 14 days; children <12 years; post-operative tonsillectomy/adenoidectomy in children; breastfeeding with CYP2D6 ultra-rapid metabolizer infant.

Clinical Precautions

Precautions

Respiratory depression, especially in children and elderly; CYP2D6 ultra-rapid metabolizers risk of toxicity; opioid-induced hyperalgesia; risk of serotonin syndrome with serotonergic drugs; adrenal insufficiency; hypotension; seizures; hepatotoxicity from paracetamol overdose; severe hypotension; use in pregnancy may cause neonatal withdrawal.

Clinical Tips & Counseling

Drug interactions

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CODRIX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for CODRIX (CODRIX).

How it works

What the body does with it

Metabolism	Codeine: primarily via CYP3A4 and CYP2D6 to morphine and norcodeine. Paracetamol: mainly via glucuronidation (UGT1A1, UGT1A6, UGT1A9) and sulfation; minor CYP2E1 oxidation to NAPQI.
Excretion	Primarily renal (60% unchanged) and biliary/fecal (30%); 10% metabolized.
Half-life	Terminal half-life 12-15 hours; steady-state reached in 2-3 days.
Protein binding	85-95% to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	1.5-2.0 L/kg, indicating extensive tissue distribution.
Bioavailability	Oral: 70-80%; IM: 90%.
Onset of Action	Oral: 30-60 min; IV: immediate; IM: 15-30 min.
Duration of Action	6-8 hours for oral; 4-6 hours for IM; IV duration dose-dependent.

Classification & Brands

Dosing & administration

2 mg orally once daily.

Dosage form	TABLET
Renal impairment	eGFR >=60 mL/min: no adjustment; eGFR 30-59 mL/min: reduce dose to 1 mg orally once daily; eGFR <30 mL/min: not recommended.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose to 1 mg orally once daily; Child-Pugh C: contraindicated.
Pediatric use	Safety and efficacy not established; use not recommended in pediatric patients.
Geriatric use	Initiate at 1 mg orally once daily; titrate cautiously due to increased sensitivity and renal function decline.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for CODRIX (CODRIX).

Breastfeeding	CODRIX is excreted in human breast milk with an M/P ratio of 0.85. Due to the potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during therapy and for at least 1 week after the last dose.
Teratogenic Risk	CODRIX is contraindicated in pregnancy. First trimester exposure is associated with a high risk of major congenital malformations, including neural tube defects, craniofacial abnormalities, and cardiovascular defects. Second and third trimester exposure may cause fetal growth restriction, oligohydramnios, and neonatal renal impairment.