Fioricet
Fioricet
Generic Name
Fioricet
Mechanism
Fioricet is a combination analgesic containing acetaminophen (160 mg) and oxycodone (10 mg).
• Acetaminophen: Inhibits central prostaglandin synthesis via COX‑4-like activity, reducing nociceptive pain without significant anti‑inflammatory effects.
• Oxycodone: Acts as a potent μ‑opioid receptor agonist, increasing the pain threshold and altering pain perception through G‑protein mediated inhibition of adenylate cyclase and potassium channel activation.
• The combination yields synergistic analgesia, allowing lower opioid doses while maintaining efficacy for moderate to severe musculoskeletal pain.
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Pharmacokinetics
| Parameter | Fioricet |
| Absorption | Rapid oral absorption; peak plasma concentrations in 30–60 min. |
| Bioavailability | 30–45 % for oxycodone; > 70 % for acetaminophen. |
| Metabolism | Oxycodone: (CYP2D6) → oxymorphone, (CYP3A4) → noroxycodone; Acetaminophen: glucuronidation & sulfation in the liver. |
| Elimination half‑life | Oxycodone 3–4 h; Acetaminophen 2–3 h. |
| Excretion | Renal clearance (20–30 % unchanged acetaminophen) and hepatic biliary excretion of metabolites. |
| Drug Interactions | Strong (CYP2D6) inhibitors (e.g., fluoxetine) reduce oxymorphone formation → ↓ efficacy; potent inhibitors of (CYP3A4) (ketoconazole) increase oxymorphone → ↑ toxicity. NSAIDs or aspirin can synergistically increase bleeding risk with oxycodone. |
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Indications
* Acute, moderate‑to‑severe pain from musculoskeletal or post‑operative causes.
* Short‑term management (≤ 7 days) when opioid therapy is clinically indicated and acetaminophen dose limits are respected.
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Contraindications
| Category | Precautions |
| Contraindications |
• Severe respiratory depression or obstructive pulmonary disease. • Acute liver failure or severe hepatic impairment. • Known allergy to components. |
| Warnings |
• Risk of sedation, respiratory depression, and opioid tolerance. • Hepatotoxicity with concomitant hepatotoxic drugs or chronic alcohol use. • QT prolongation risk when combined with drugs that prolong QT interval. |
| Precautions |
• Caution in elderly, renal impairment, or chronic opioid users. • Monitor for signs of dependence, especially with prolonged use. |
| Drug‑Drug Interactions | Avoid concomitant use with monoamine oxidase inhibitors, serotonergic agents (risk of serotonin syndrome), or other CNS depressants. |
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Dosing
| Situation | Standard Dose | Maximum Daily Dose | |
| Initial | 10 mg oxycodone / 160 mg acetaminophen every 6 h | 40 mg oxycodone / 640 mg acetaminophen (≤ 6 days) | |
| Titration | Increase by one dose every 12 h if pain uncontrolled, not exceeding 40 mg oxycodone/day. | 40 mg oxycodone/day is the upper dosing limit. | |
| Renal Dose Adjustment | 10 mg/160 mg q6 h for CrCl > 60 mL/min. | Lower dose or dosing interval extension for CrCl 65 yrs – start at lowest dose, titrate cautiously. • Pregnancy – category C; use only if benefits outweigh risks. | — |
| Discontinuation | Taper opioid dose over 48–72 h; gradually reduce acetaminophen to 160 mg q12 h if no pain >10 days. | — |
*Take care that total acetaminophen intake (including all sources) does not exceed 4 g/day.*
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Adverse Effects
- Common
- Somnolence, dizziness
- Nausea, vomiting, constipation
- Dry mouth, headache
- Serious
- Respiratory depression, especially in opioid-naïve or chronic opioid users
- Hepatotoxicity (especially with concomitant hepatotoxic drugs or chronic alcohol use)
- Acute allergic reactions (rash, anaphylaxis)
- QT prolongation (rare, with concurrent QT‑prolonging agents)
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Monitoring
| Parameter | Frequency |
| Clinical | Pain score, respiratory rate, sedation level – every 6 h initially. |
| Laboratory | Liver function tests (ALT, AST) baseline and every 3 days during >3 day therapy or in at-risk patients. |
| Renal | Serum creatinine daily during initial 72 h in CKD; thereafter every 5–7 days if dose adjusted. |
| Drug‑Use | Prescription monitoring programs; check for signs of diversion. |
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Clinical Pearls
1. Synergistic Advantage – The acetaminophen component allows the oxycodone dose to be *halved*, reducing opioid exposure while maintaining analgesic effectiveness.
2. Safe Liver Use – Keep total daily acetaminophen ≤ 4 g; consider therapeutic drug monitoring if polypharmacy or chronic liver disease is present.
3. Elderly Sensitivity – Start at 5 mg oxycodone / 160 mg acetaminophen q6 h; monitor for falls and respiratory compromise.
4. Avoid Alcohol – Strongly discourage simultaneous alcohol intake due to additive CNS depression and hepatotoxicity.
5. Dissolve or Swallow – Do not crush; the formulation is designed for whole tablet ingestion to ensure controlled release and bioequivalence.
6. Rescue Strategy – For breakthrough pain, use a short‑acting opioid (e.g., hydrocodone) and not an extra Fioricet dose to avoid exceeding acetaminophen limits.
7. Add‐On NSAID – If needed for inflammatory pain, pair with a safe NSAID (e.g., naproxen 220 mg BID) but monitor for GI bleeding and renal function.
These pearls help balance efficacy with safety and optimize patient outcomes when prescribing Fioricet.