Hydrocodone and ibuprofen
Hydrocodone
Generic Name
Hydrocodone
Mechanism
- Hydrocodone
- Selective activation of µ‑opioid receptors in the central nervous system → ↓ pain perception, ↓ respiratory drive, ↑ sedation.
- Increases neuronal after‑hyperpolarization, impairs nociceptive signal transmission, and produces analgesia, euphoria, and respiratory depression.
- Ibuprofen
- Competitive inhibition of COX‑1 and COX‑2 → ↓ prostaglandin synthesis (PGE₂, PGI₂) → ↓ inflammation, pain, fever.
- Reduced prostaglandins diminish peripheral sensitization of nociceptors and limit central excitatory pathways.
Combination effect: Local NSAID‑mediated reduction of peripheral nociception allows lower opioid stimulation of CNS receptors for adequate pain control.
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Pharmacokinetics
| Parameter | Hydrocodone | Ibuprofen |
| Absorption | Rapid oral uptake (Tmax ≈ 1 h) | Rapid oral uptake (Tmax ≈ 0.5 h) |
| Distribution | Lipid‑soluble; crosses the blood‑brain barrier; moderate protein binding (≈ 80 %) | Lipid‑soluble; plasma protein bound (≈ 99 %) |
| Metabolism | Phase I via CYP2D6 → hydromorphone; Phase II via glucuronidation | CYP2C9 conjugation → glucuronide |
| Elimination Half‑Life | 3–4 h (± variability) | 3–4 h (shorter in renal impairment) |
| Route of Excretion | Renal (≈ 20 % unchanged) | Renal (≈ 50 % unchanged; remaining via hepatic metabolism) |
| Drug‑Drug Interactions | CYP2D6 inhibitors ↑ dose; opioids ↑ respiratory depression | COX inhibitors ↑ bleeding risk; NSAIDs + serotonin reuptake inhibitors ↑ GI bleeding; NSAID + diuretics ↑ renal dysfunction |
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Indications
- Post‑operative or acute moderate‑to‑severe pain where adjunctive anti‑inflammatory action is desirable.
- Trauma or musculoskeletal injury with associated inflammation and edema.
- Chronic pain requiring on‑demand dosing in outpatient settings (rarely indicated).
- Prescription for pain in adults; not recommended for patients under 12 years.
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Contraindications
| Category | Notes |
| Absolute Contraindications | Severe respiratory insufficiency (due to opiates), known hypersensitivity to hydrocodone or ibuprofen, concurrent use of other opioid analgesics or CNS depressants. |
| Relative Contraindications | History of gastrointestinal ulcers/patients on chronic steroids, renal or hepatic impairment, uncontrolled hypertension, pregnancy (especially 3rd trimester for NSAIDs), age >85 with frailty. |
| Warnings |
• Respiratory depression → dangerous in opioid‑naïve or low‑body‑weight patients. • GI bleeding risk amplified with NSAID‑use, especially cu‑to‑2° trauma patients. • Renal impairment → accumulation of both drugs. • Cardiovascular risk → NSAIDs can cause fluid retention, hypertension, ischemic events. • Risk of opioid dependence/abuse. • QTc+ prolongation with NSAID + serotonergic drugs. |
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Dosing
| Population | Hydrocodone (5 mg/400 mg ibuprofen) | Hydrocodone (10 mg/400 mg ibuprofen) |
| Adults | 1 tablet q4‑6 h as needed (max 4 tablets/24 h – 20 mg hydrocodone/800 mg ibuprofen). | 1 tablet q6‑8 h as needed (max 3 tablets/24 h – 30 mg hydrocodone/800 mg ibuprofen). |
| Pediatrics | Not approved for 600 mg/day. | |
| Renal or Hepatic Impairment | Decrease frequency; consider lower maintenance doses; monitor creatinine clearance. | Same caution; no dose adjustment for mild hepatic impairment. |
| Administration | Oral tablets swallowed whole with water; may be taken with food to reduce GI upset. | |
| Drug Interactions | Avoid concomitant oxycodone, methadone, benzodiazepines, or alcohol. | Avoid NSAID + steroid combos; consider alternative analgesic if high GI risk. |
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Adverse Effects
| System | Common | Serious |
| Central Nervous System | Drowsiness, constipation, mild nausea, dizziness | Respiratory depression, seizures, delirium, coma |
| Gastrointestinal | Nausea, dyspepsia, mild GI upset | GI bleeding, ulceration, perforation |
| Renal | Reduced urine output, mild edema | Acute kidney injury, rhabdomyolysis (rare) |
| Cardiovascular | Mild tachycardia, increased blood pressure | Hypertension crisis, myocardial infarction, stroke |
| Allergic | Pruritus, rash | Anaphylaxis, angioedema |
| Others | Liver enzyme elevations | Hepatotoxicity, myelosuppression (rare) |
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Monitoring
- Respiratory: rate (≥ 12 /min), depth, O₂ saturation.
- Pain and Sedation: visual analog scale, Richmond Agitation–Sedation Scale (RASS).
- GI: stool occult blood, signs of nausea or vomiting.
- Renal: serum creatinine, eGFR, urine output (especially in chronic users).
- Cardiac: blood pressure, heart rate.
- Hematologic: CBC (anemia, leukopenia) if prolonged use.
- Drug‑specific: observe for signs of opioid dependence or abuse (e.g., dose escalation, insomnia).
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Clinical Pearls
- Synergistic Dosing: The NSAID component permits a lower hydrocodone dose, mitigating opioid‑related adverse effects while adequately controlling pain.
- Avoid Extended‑Release NSAIDs: Use immediate‑release ibuprofen; extended‑release formulations can lead to prolonged GI exposure and enhanced bleeding risk.
- Tailor for Renal/Osteoporosis: In patients with chronic kidney disease or osteoarthritis, consider a switch to a safer COX‑2 selective agent or low‑dose acetaminophen.
- Scrutinize Alcohol Use: Chronic alcoholics are at higher risk of respiratory depression; screen thoroughly before prescription.
- Pregnancy & Lactation: NSAIDs are generally avoided beyond the first trimester; hydrocodone crosses the placenta – use OCP or sedation‑cum‑safe dog.
- Medication Review: Check for CYP2D6 inhibitors (fluoxetine, paroxetine) that may increase hydrocodone plasma levels.
- Patient Education: Instruct on “Do Not Replicate” – do not double up on over‑the‑counter NSAIDs or other opioids; emphasize scheduled dosing, not “take when needed.”
- Monitoring of GI Symptoms: For patients on NSAIDs >2 weeks, consider a proton‑pump inhibitor or H₂ blocker prophylaxis.
- Dosage Holidays: In long‑term use, the concept of *opioid holiday* may reduce tolerance; discuss timed-dose interruptions with patients.
- Documentation of Pain Relief: Maintain a simple pain diary or digital app to objectively track effectiveness and side‑effects.
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