DHC PLUS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DHC PLUS (DHC PLUS).
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.
| 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. |
| Molecular Weight | 299.4 Da (for codeine); dihydrocodeine: 301.4 Da; combination product molecular weight considered per active ingredient. |
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. |
| 1st trimester | Avoid due to risk of fetal opioid dependence and neonatal abstinence syndrome; limited data but potential for teratogenicity with first-trimester exposure. |
| 2nd trimester | Use only if clearly needed; risk of premature labor, low birth weight, and neonatal opioid withdrawal. |
| 3rd trimester | Avoid; high risk of neonatal respiratory depression, withdrawal symptoms, and prolonged hospitalization. |
Clinical note
Comprehensive clinical and safety monograph for DHC PLUS (DHC PLUS).
| Placental transfer | Both codeine and dihydrocodeine cross the placenta; codeine has documented placental transfer about 0.5-1.3 of maternal concentration; dihydrocodeine expected to transfer similarly; evidence of fetal exposure and neonatal withdrawal risk. |
| Breastfeeding | Codeine is excreted into breast milk at low levels, but there is a risk of infant accumulation, especially in CYP2D6 ultra-rapid metabolizers, leading to potentially life-threatening respiratory depression. Dihydrocodeine is present; caution. Equivalent to L3 (Moderately Safe) with monitoring; use lowest effective dose shortest duration, avoid in ultra-rapid metabolizers, and monitor infant for sedation, poor feeding, or respiratory issues. |
■ 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.
| Serious Effects |
Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipmentKnown hypersensitivity to codeine, dihydrocodeine, or any componentSignificant respiratory depressionConcurrent use of monoamine oxidase inhibitors (MAOIs) or within 14 days of such therapy
| 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 |
| Food/Dietary | Avoid alcohol as it increases sedation and hepatotoxicity risk. High-fat meals may delay absorption but not significantly alter efficacy. |
Loading safety data…
| Lactation Rating | L3 |
| 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. |
| Fetal Monitoring | Monitor maternal liver function for paracetamol toxicity (especially with prolonged use). Fetal ultrasound for growth restriction if chronic opioid exposure. Neonatal monitoring for withdrawal symptoms after delivery if used chronically. |
| Fertility Effects | Both drugs may affect fertility: Paracetamol has been associated with reduced fecundity in some studies; dihydrocodeine may cause menstrual irregularities and decreased libido. Opioids may impair spermatogenesis in males. |
| Clinical Pearls | DHC PLUS contains dihydrocodeine and paracetamol. Avoid in CYP2D6 ultra-rapid metabolizers due to morphine toxicity risk. Use with caution in patients with respiratory compromise, as dihydrocodeine can cause respiratory depression. Monitor liver function with prolonged paracetamol use. |
| Patient Advice | Do not exceed recommended dose due to paracetamol hepatotoxicity risk. · Avoid alcohol while taking this medication. · May cause drowsiness or dizziness; avoid driving or operating machinery. · Take with food if gastrointestinal upset occurs. · Do not crush or chew extended-release formulations. |