Drug reference

Codeine

Opioid analgesic (weak) / antitussive / prodrug · Analgesic

Also known as Codeine phosphate, Codeine sulfate, Methylmorphine

START

15-30 mg PO q4-6h PRN; assess pain severity; check CYP2D6 status if available; warn about constipation and drowsiness; avoid in children <12 and breastfeeding UMs

TYPICAL MAX

360 mg/day

STOP IF

Respiratory rate <10/min, severe constipation, signs of dependence, inadequate pain control (step up to stronger opioid)

WATCH

Pain scores, respiratory rate (especially when initiating or increasing dose), bowel function, sedation level, signs of misuse/dependence

CDSCO approvedATC R05DA04 (antitussive); N02AA59 (analgesic)

Dose laddermg/d

Renal dose adjustmenteGFR mL/min/1.73m²

KDIGO 2024 + manufacturer label

Pharmacokineticsplasma · t hours

ONSET: 45min · 30-45 min (analgesia)
PEAK: 1.3h · 1-1.5 hours
t½: 3h · Codeine: 2.5-3.5h; Morphine: 2-4h
DURATION: 5h · 4-6 hours

EXCRETION

Renal (metabolites)

route + CYP

INTERACTIONS

12 major

incl. contraindicated

PREGNANCY

Avoid in third trimester; risk of neonatal withdrawal; use only if clearly needed in first/second trimester

FDA category + note

Top interactionssee all 12 →

MaoisContraindicatedDatabaseKimi deep-research + Cla
ChlorpromazineSevereTextbook-citedKDT 7e · p950
DiazepamSevereTextbook-citedKDT 7e · p950
ImipramineSevereTextbook-citedKDT 7e · p950

Available in India

6 branded formulations and 195 fixed-dose combinations. Look up specific brands in the Drugs workspace.

Mechanism

Prodrug metabolized by CYP2D6 to morphine (active metabolite, ~10% conversion). Binds to mu-opioid receptors in CNS, producing analgesia, euphoria, sedation, and respiratory depression. Also acts on medullary cough center as an antitussive. Codeine itself has weak opioid activity.

Indications

Mild to moderate pain (when paracetamol/NSAIDs insufficient)Cough suppression (short-term)Diarrhea (off-label, limited use)

Dosing

Adult: Analgesia: 15-60 mg PO q4-6h PRN (max 360 mg/day). Cough: 10-20 mg PO q4-6h PRN (max 120 mg/day)
Pediatric: Contraindicated under 12 years for analgesia/cough; 12-18 years: use only if other analgesics contraindicated or insufficient
Renal adjustment: eGFR <30: avoid or use lowest dose; morphine accumulates
Hepatic adjustment: Reduce dose; avoid in severe hepatic impairment
Geriatric: Start 15 mg; increased sensitivity to respiratory depression and sedation
Max dose: 360 mg/day (analgesia); 120 mg/day (cough)

Pharmacokinetics

Onset

Analgesia: 30-45 minutes; Cough: 15-30 minutes

Peak effect

1-1.5 hours (Tmax)

Duration

4-6 hours

Half-life

Codeine: 2.5-3.5 hours; Morphine (metabolite): 2-4 hours

Bioavailability

~50% (oral)

Protein binding

7-25%

Metabolism

Hepatic CYP2D6 (to morphine, 10%), CYP3A4 (to norcodeine), glucuronidation (codeine-6-glucuronide, 70-80%)

Excretion

Renal (primarily as metabolites)

Contraindications

Hypersensitivity to codeine
Respiratory depression
Acute or severe bronchial asthma
Paralytic ileus
GI obstruction
Ultra-rapid CYP2D6 metabolizers (increased morphine conversion, especially in children)
Children under 12 years (contraindicated for analgesia/cough)
Breastfeeding mothers (especially CYP2D6 UMs - infant morphine toxicity)
Post-operative pain in children following tonsillectomy/adenoidectomy (contraindicated)

Side effects

Common

ConstipationNauseaDrowsinessDizzinessDry mouthSweatingItchingUrinary retention

Serious

Respiratory depression (dose-related, potentially fatal)
Dependence and addiction
Severe constipation / ileus
Hypotension
Bradycardia
Seizures (overdose)
Anaphylaxis

Pregnancy & lactation

Pregnancy

Avoid in third trimester; risk of neonatal withdrawal; use only if clearly needed in first/second trimester

Lactation

Excreted in breast milk; CYP2D6 UMs can produce toxic morphine levels in infant; avoid if possible, especially in UMs

Drug interactions

Maois

Contraindicated

Database

Risk of serotonin syndrome and severe adverse reactions

Avoid combination

Source: Kimi deep-research + Cla

Chlorpromazine

Severe

Textbook-cited

Enhanced sedation and respiratory depression.

Avoid concurrent use

Source: KDT 7e · p950

Diazepam

Severe

Textbook-cited

Excessive sedation, respiratory depression, motor impairment.

Avoid concurrent use

Source: KDT 7e · p950

Imipramine

Severe

Textbook-cited

Enhanced sedation and respiratory depression

Avoid concurrent use

Source: KDT 7e · p950

Acetaminophen

Severe

Textbook

Acetaminophen-related hepatotoxicity, a significant cause for liver failure.

Many practitioners have moved away from opioid-acetaminophen combination analgesics to avoid the risk of excessive acetaminophen exposure.

Source: Harrison 22e · p98-99

Barbiturates

Severe

Textbook

Exaggerated CNS depression.

Source: KDT 7e · p401

Benzodiazepines

Severe

Textbook

Marked depression of respiration, cardiac contractility, and blood pressure.

Carefully monitor respiratory and cardiovascular functions when co-administering benzodiazepines with opioids due to increased risk of severe depression of vital signs.

Source: KDT 7e · p383

Chlordiazepoxide Hydrochloride

Severe

Textbook

Increased rates of accidental overdose and death.

Caution is advised, especially for patients with a history of drug abuse.

Source: G&G 14e

Clomethiazole

Severe

Textbook

Increased rates of accidental overdose and death.

Caution is advised, especially for patients with a history of drug abuse.