Clinical beta

FMBM is currently in clinical beta. Content is for professional review/testing and must not replace local protocols, senior clinical judgment, or official prescribing references.

Drug Monograph

Hydrocodone

USE IF: Moderate-severe acute pain, step-down oral opioid, selected cough suppression

AVOID IF: Significant respiratory depression, severe hepatic failure with combo products, MAOI use

Hydrocodone

Semi-synthetic opioid (mu-opioid receptor agonist)

OpioidHCPParacetamol-comboCYP3A4CYP2D6

Indication

Moderate-severe acute pain, step-down oral opioid, selected cough suppression

At a glance

INDICATION -> Oral opioid for moderate-severe pain when non-opioids are inadequate

ADULT DOSE -> 5–10 mg hydrocodone PO q4–6h (IR combination)

MAX DOSE -> Maximum dose determined by paracetamol limit (<=4 g/day total from all sources)

CONTRA -> Significant respiratory depression, severe hepatic failure with combo products, MAOI use

ANTIDOTE -> Naloxone; add N-acetylcysteine if combination-product overdose

Quick facts

Onset

20–30 min (IR PO)

Duration

Peak 1–1.3 h (IR); duration 4–6 h (IR), 8–24 h (ER product-dependent). Half-life ~4 h (IR), ~7–9 h (ER).

Routes

PO only

Pregnancy

Short-term only if needed

Renal

Reduce dose in impairment

Hepatic

Reduce dose; extra caution with paracetamol combinations

Do not miss

Time to action: 20—30 min (IR PO)

Max dose

  • Maximum dose determined by paracetamol limit (<=4 g/day total from all sources).

Critical risks

  • Respiratory depression.
  • Paracetamol hepatotoxicity in combination products.
  • ER dose-dumping risk.

Antidote

  • Naloxone.
  • Add N-acetylcysteine when paracetamol threshold is met.

High-risk scenarios

  • CYP3A4 inhibitors.
  • Benzodiazepines.
  • Liver disease.
  • Elderly.
  • CKD.

Key interactions

  • Fluconazole/clarithromycin/ritonavir.
  • Paroxetine/fluoxetine.
  • Alcohol.

Indications

Primary

  • Moderate-severe acute pain
  • Dental pain
  • Post-op step-down pain

Secondary

  • Chronic severe pain requiring ER opioid
  • Severe dry cough

Other

  • Cancer pain step 2–3
  • Refractory chronic cough
  • Palliative dyspnea

Dosing

Standard: 5—10 mg hydrocodone PO q4—6h PRN

Max daily dose

  • Usually <=8 tablets/day in common IR combinations.
  • Limit is commonly paracetamol ceiling rather than hydrocodone ceiling.
  • Ensure total daily paracetamol from all sources stays within safe limits (typically <=4 g/day; lower in high-risk patients).

Adult - PO

  • IR combination: 2.5–10 mg hydrocodone q4–6h PRN.
  • ER single-entity: 10–20 mg q12–24h depending on product.
  • Antitussive: 5 mg q4–6h PRN.

Adult - IV

  • Not available.

Pediatric

  • Solution/tablet specialist dosing only.
  • Avoid ER in <18 years.

Renal adjustment

  • ESRD/CrCl <30: start at ~50% dose and extend interval.

Hepatic adjustment

  • Severe impairment: start at ~50% dose and avoid high paracetamol exposure.

Warnings

Clinical warnings

  • Respiratory depression (highest risk first 24–72 h).
  • Paracetamol hepatotoxicity in combination products.
  • ER dose-dumping if crushed/chewed.
  • Addiction, misuse, dependence.
  • CNS depression with benzodiazepines/alcohol.
  • Neonatal opioid withdrawal.
  • Analgesic failure with CYP2D6 inhibitors.
  • Opioid-induced constipation is universal.

Adverse effects

  • Common: sedation, nausea, constipation, dizziness.
  • Serious: respiratory depression, severe sedation, hepatotoxicity (combo products), misuse/dependence.

Contraindications / caution

Do not use

  • Significant respiratory depression.
  • Acute/severe bronchial asthma without monitoring.
  • Paralytic ileus.
  • MAOI use within 14 days.
  • Severe hepatic failure with combination products when safer alternatives exist.
  • Severe hepatic impairment (combination products — paracetamol toxicity risk).

Use caution / avoid high doses

  • Liver disease.
  • Renal impairment.
  • Elderly/frail patients.
  • COPD/OSA.
  • Concurrent CYP3A4 inhibitors.
  • Concurrent CYP2D6 inhibitors.

Drug interactions

  • CYP3A4 inhibitors -> increased hydrocodone exposure and toxicity.
  • CYP3A4 inducers -> reduced analgesia / withdrawal risk.
  • CYP2D6 inhibitors -> reduced hydromorphone formation and analgesic failure.
  • Benzodiazepines/CNS depressants -> coma, apnea, death risk.
  • Alcohol -> additive CNS depression; ER dose-dumping risk.
  • Warfarin -> paracetamol component may increase INR.

Special populations

Pediatrics

Specialist oral dosing only; avoid ER in <18 years.

Pregnancy

Short-term supervised use only; prolonged use risks NOWS.

Breastfeeding

Not preferred; monitor infant closely if unavoidable.

Elderly

Start low (2.5–5 mg IR) with slower titration.

Liver disease

Reduce dose and keep total paracetamol low; avoid combo products in severe disease.

Renal impairment

Reduce dose; monitor for prolonged sedation.

Administration

  • PO only; no IV hydrocodone formulation.
  • IR hydrocodone is commonly available only as combination product.
  • ER must be swallowed whole (do not crush/chew).
  • Always calculate total daily paracetamol from all sources.
  • Use a calibrated device for oral solutions.

Infusion / dilution

  • No IV formulation exists.

Monitoring

  • LFTs.
  • Renal function.
  • Paracetamol level if overdose is suspected.
  • Track cumulative paracetamol dose across all medications (mandatory with combination product use).
  • INR if on warfarin with high paracetamol exposure.
  • Respiratory rate.
  • Sedation score.
  • Pain response.
  • Bowel function.
  • Signs of hepatotoxicity.
  • Misuse/dependence behaviors.

Overdose / toxicity

IF SUSPECTED HYDROCODONE OVERDOSE: ABC first; assume dual toxicity if combination product involved.

Recognition

  • Opioid toxic dose is context-dependent.
  • Paracetamol toxicity threshold remains critical in combination products.
  • Miosis, respiratory depression, decreased consciousness.
  • Delayed RUQ pain/LFT rise if paracetamol overdose occurs.

Immediate actions

  • Naloxone for opioid toxicity.
  • Activated charcoal when early and airway protected.
  • N-acetylcysteine if paracetamol treatment threshold is met.
  • Initiate N-acetylcysteine early if paracetamol toxicity is suspected (do not delay for labs in high-risk scenarios).
  • Use Rumack-Matthew nomogram where applicable.

Antidote

  • Naloxone for opioid toxicity.
  • N-acetylcysteine when indicated for paracetamol co-ingestion.

Decontamination

  • Activated charcoal if early and airway protected.

Escalation

  • ER overdose: observe 12–24 h.
  • Naloxone infusion for re-narcotization.

Clinical pearls

Common mistakes, resistance logic, and bedside traps

Hidden ceiling

  • Clinical ceiling is usually paracetamol, not hydrocodone.

IR formulation

  • IR hydrocodone commonly lacks single-entity oral formulation.

Route reality

  • No IV hydrocodone formulation exists.

CYP3A4 risk

  • Fluconazole/clarithromycin can silently precipitate toxicity.

CYP2D6 failure

  • Paroxetine/fluoxetine can cause analgesic failure.

Overdose dual-path

  • Naloxone alone may be insufficient when paracetamol is co-ingested.

OTC duplication risk

  • Avoid duplication with OTC paracetamol-containing products (common overdose cause).

ER intent

  • ER is for stable around-the-clock pain, not PRN use.

Regional practicality

  • Hydrocodone is largely US-dominant; regional alternatives are often more practical.

Pharmacokinetics

  • Oral bioavailability ~70%.
  • Protein binding ~36%.
  • Hepatic metabolism via CYP3A4 and CYP2D6.
  • No parenteral formulation.
  • Renal excretion of parent drug and metabolites.
  • ER steady state reached in about 3 days.

Mechanism of action

  • Full mu-opioid receptor agonist.
  • Parent drug provides major opioid effect.
  • CYP2D6 converts part of dose to hydromorphone.
  • CYP3A4 converts major fraction to norhydrocodone.

Common brand names

Saudi Arabia

Vicodin · Norco · Zohydro ER · Hysingla ER

Global

Lortab · Lorcet · Hycodan · Tussionex ER

Common trade names are curated examples only — formulations and availability vary. Verify the exact product name with your local pharmacy and national regulator before prescribing or dispensing.

Country practice notes

  • Limited use in Gulf/Middle East; morphine, oxycodone, and fentanyl are more commonly used.
  • Hydrocodone products are tightly controlled where available.
  • Availability is institution-dependent and often restricted to specialist/import channels.
  • Regional prescribing must account for narcotic authorization requirements.
  • Gulf practice should strongly favor checking total paracetamol exposure in imported combination products.

Saudi Arabia — confirm with local formulary.