DHC PLUS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DHC PLUS (DHC PLUS).

How it works

DHC PLUS is a combination of codeine (an opioid agonist) and homatropine (an anticholinergic). Codeine binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering perception of pain. Homatropine antagonizes muscarinic acetylcholine receptors, reducing GI motility and secretions, which may decrease opioid-induced nausea and vomiting.

What the body does with it

Metabolism	Codeine is metabolized by CYP2D6 to morphine (active), and by CYP3A4 to norcodeine. Homatropine is metabolized via ester hydrolysis and N-demethylation. Both are excreted renally.
Excretion	Renal: ~90% as glucuronide conjugates, with 10% as unchanged dihydrocodeine and 5-10% as nordihydrocodeine; biliary/fecal: <5%.
Half-life	3.5-5 hours for dihydrocodeine; prolonged in hepatic impairment (up to 8-10 hours) and may require dose adjustment.
Protein binding	20-30% bound to albumin.
Volume of Distribution	1.5 L/kg; reflects moderate tissue distribution due to lipophilicity.
Bioavailability	Oral: ~60-70% due to first-pass metabolism; subcutaneous: ~80-90%; rectal: ~70-80%.
Onset of Action	Oral: 30-60 minutes; subcutaneous: 15-30 minutes; rectal: 45-90 minutes.
Duration of Action	4-6 hours for oral and parenteral routes; sustained-release formulations extend to 12 hours.

Classification & Brands

Dosing & administration

1-2 tablets (dihydrocodeine 40 mg/paracetamol 500 mg per tablet) orally every 4-6 hours as needed, maximum 8 tablets per day.

Dosage form	CAPSULE
Renal impairment	GFR 30-50 mL/min: Administer every 6-8 hours; GFR 10-29 mL/min: Administer every 8-12 hours; GFR <10 mL/min: Avoid or use with extreme caution, reduce dose by 50% and monitor for toxicity.
Liver impairment	Child-Pugh Class A: No adjustment; Child-Pugh Class B: Reduce dose by 50% and extend interval to every 8 hours; Child-Pugh Class C: Avoid use due to risk of paracetamol hepatotoxicity and dihydrocodeine accumulation.
Pediatric use	Not recommended for children under 12 years of age. For adolescents (12-18 years): Same adult dosing based on weight, typically 1 tablet every 4-6 hours, maximum 4 tablets per day.
Geriatric use	Initiate with lowest effective dose, 1 tablet every 6-8 hours; maximum 4 tablets per day; monitor for CNS depression and constipation.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for DHC PLUS (DHC PLUS).

Breastfeeding	Dihydrocodeine and paracetamol are excreted in breast milk in low amounts. M/P ratio for dihydrocodeine is approximately 0.5-1.0. Use with caution; monitor infant for sedation and respiratory depression. Paracetamol is considered compatible with breastfeeding.
Teratogenic Risk	DHC PLUS (dihydrocodeine/paracetamol): First trimester risk of neural tube defects with paracetamol use is low but not zero; dihydrocodeine may cause respiratory depression in neonate if used near term. Chronic use in third trimester can lead to neonatal opioid withdrawal syndrome.

Warnings & precautions

■ FDA Black Box Warning

Warning: Risk of addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; interactions with alcohol and CNS depressants; risk of medication errors with codeine; risks from concomitant use with benzodiazepines or other CNS depressants; and risks of use in children under 12 years, and in adolescents with certain respiratory conditions.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to codeine, homatropine, or any component","Significant respiratory depression","Acute or severe bronchial asthma","Paralytic ileus","Children under 12 years (codeine)"]

Clinical Precautions

Precautions

["Risk of respiratory depression","CYP2D6 ultrarapid metabolizers: increased toxicity","Anticholinergic effects (e.g., urinary retention, constipation)","Use caution in elderly, renal/hepatic impairment","Avoid in patients with severe respiratory conditions"]

Clinical Tips & Counseling

Drug interactions

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DHC PLUS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DHC PLUS (DHC PLUS).

How it works

What the body does with it

Metabolism	Codeine is metabolized by CYP2D6 to morphine (active), and by CYP3A4 to norcodeine. Homatropine is metabolized via ester hydrolysis and N-demethylation. Both are excreted renally.
Excretion	Renal: ~90% as glucuronide conjugates, with 10% as unchanged dihydrocodeine and 5-10% as nordihydrocodeine; biliary/fecal: <5%.
Half-life	3.5-5 hours for dihydrocodeine; prolonged in hepatic impairment (up to 8-10 hours) and may require dose adjustment.
Protein binding	20-30% bound to albumin.
Volume of Distribution	1.5 L/kg; reflects moderate tissue distribution due to lipophilicity.
Bioavailability	Oral: ~60-70% due to first-pass metabolism; subcutaneous: ~80-90%; rectal: ~70-80%.
Onset of Action	Oral: 30-60 minutes; subcutaneous: 15-30 minutes; rectal: 45-90 minutes.
Duration of Action	4-6 hours for oral and parenteral routes; sustained-release formulations extend to 12 hours.

Classification & Brands

Dosing & administration

1-2 tablets (dihydrocodeine 40 mg/paracetamol 500 mg per tablet) orally every 4-6 hours as needed, maximum 8 tablets per day.

Dosage form	CAPSULE
Renal impairment	GFR 30-50 mL/min: Administer every 6-8 hours; GFR 10-29 mL/min: Administer every 8-12 hours; GFR <10 mL/min: Avoid or use with extreme caution, reduce dose by 50% and monitor for toxicity.
Liver impairment	Child-Pugh Class A: No adjustment; Child-Pugh Class B: Reduce dose by 50% and extend interval to every 8 hours; Child-Pugh Class C: Avoid use due to risk of paracetamol hepatotoxicity and dihydrocodeine accumulation.
Pediatric use	Not recommended for children under 12 years of age. For adolescents (12-18 years): Same adult dosing based on weight, typically 1 tablet every 4-6 hours, maximum 4 tablets per day.
Geriatric use	Initiate with lowest effective dose, 1 tablet every 6-8 hours; maximum 4 tablets per day; monitor for CNS depression and constipation.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for DHC PLUS (DHC PLUS).

Breastfeeding	Dihydrocodeine and paracetamol are excreted in breast milk in low amounts. M/P ratio for dihydrocodeine is approximately 0.5-1.0. Use with caution; monitor infant for sedation and respiratory depression. Paracetamol is considered compatible with breastfeeding.
Teratogenic Risk	DHC PLUS (dihydrocodeine/paracetamol): First trimester risk of neural tube defects with paracetamol use is low but not zero; dihydrocodeine may cause respiratory depression in neonate if used near term. Chronic use in third trimester can lead to neonatal opioid withdrawal syndrome.

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to codeine, homatropine, or any component","Significant respiratory depression","Acute or severe bronchial asthma","Paralytic ileus","Children under 12 years (codeine)"]