Acep Extra

Approved and Commonly Used Indications:

• Tension-type headache and migraine:
  Relief of acute headache episodes, including those associated with tension or migraine.
• Mild to moderate pain with fatigue or drowsiness:
  Such as muscular pain, backache, dysmenorrhea, toothache.
• Cold and flu symptoms:
  Relief of headache and fatigue in combination products.
• Fever (with added alertness):
  In febrile states where alertness is desired (e.g., during work hours).

Off-label/Clinically Accepted Uses:

• Adjunct in post-vaccination reactions involving headache and lethargy.
• Occasionally used for post-operative pain, especially in outpatient settings.

Route: Oral

Adults and adolescents ≥12 years:

• Standard dose: 1 tablet (Paracetamol 500 mg + Caffeine 65 mg) every 4–6 hours as needed.
• Maximum dose: Do not exceed 4 g paracetamol and 520 mg caffeine per day (usually 6–8 tablets/day max depending on formulation).
• Treatment duration: Short-term use; avoid exceeding 3–5 days without medical advice.

Pediatrics (<12 years):

• Not generally recommended due to caffeine content and lack of safety data.

Elderly:

• Same adult dosing; use with caution due to increased sensitivity to caffeine and risk of hepatotoxicity.

Renal Impairment:

• Use with caution; increase dosing interval if GFR <30 mL/min.

Hepatic Impairment:

• Avoid or reduce dose; use only under medical supervision.

Administration notes:

• Should be taken with water; avoid using with other caffeine-containing products.

Paracetamol acts primarily in the central nervous system by inhibiting prostaglandin synthesis via reversible inhibition of the COX enzyme, likely COX-3, resulting in antipyretic and analgesic effects. Caffeine is a methylxanthine that antagonizes adenosine receptors, promoting wakefulness and vasoconstriction. When combined, caffeine enhances the analgesic efficacy of paracetamol by increasing drug absorption and providing central stimulation to counter fatigue and drowsiness commonly associated with pain and fever.

Paracetamol:

• Absorption: Rapid and nearly complete; peak in 30–60 minutes
• Bioavailability: 70–90%
• Distribution: Volume of distribution ~0.9 L/kg
• Metabolism: Hepatic via glucuronidation/sulfation; CYP2E1 to toxic metabolite (NAPQI)
• Half-life: ~2–3 hours
• Excretion: Renal (mostly as conjugates)

Caffeine:

• Absorption: Rapid; peak in 30–75 minutes
• Bioavailability: ~100%
• Distribution: Widely distributed; crosses blood-brain barrier and placenta
• Metabolism: Liver (CYP1A2) to paraxanthine and other metabolites
• Half-life: 3–7 hours (longer in hepatic impairment and pregnancy)
• Excretion: Renal (as metabolites and some unchanged)

Pregnancy:

• Paracetamol: Category B (generally safe at therapeutic doses).
• Caffeine: High doses may increase miscarriage risk; limit to <200–300 mg/day.
  Use with caution during pregnancy; avoid high-frequency or long-term use.

Lactation:

• Both components are excreted in breast milk.
• Paracetamol: Considered safe.
• Caffeine: May cause irritability or poor sleep in infants at high doses. Use limited amounts and monitor the infant.

• Analgesic and Antipyretic Combination
• Subclass: Paracetamol-based Non-opioid Analgesic with Central Stimulant

• Hypersensitivity to paracetamol, caffeine, or formulation components
• Severe hepatic impairment or active liver disease
• Known caffeine hypersensitivity or cardiac arrhythmias aggravated by stimulants
• Concurrent use with other paracetamol-containing drugs (risk of overdose)

• Hepatotoxicity: Risk increases with overdose or in liver dysfunction.
• Caffeine overuse: May cause restlessness, insomnia, palpitations, or tremor.
• Drug interactions: Monitor if used with hepatotoxic drugs, CYP1A2 substrates, or anticoagulants.
• Avoid combining with: Alcohol, other stimulants, or paracetamol-containing products.
• Use caution in: Elderly, pregnant women, patients with anxiety disorders, insomnia, cardiac disease.

Common:

• Nervousness, restlessness, insomnia (due to caffeine)
• Nausea, gastralgia
• Headache (paradoxically, with prolonged caffeine use)

Less common/Serious:

• Hepatotoxicity (with overdose or prolonged use)
• Hypersensitivity reactions: rash, urticaria, anaphylaxis (rare)
• Increased heart rate, palpitations (especially in sensitive individuals)

• Alcohol: Increases hepatotoxic risk of paracetamol.
• Warfarin and anticoagulants: Paracetamol may enhance anticoagulant effect with prolonged use.
• CYP1A2 inducers/inhibitors: Affect caffeine metabolism (e.g., ciprofloxacin inhibits, smoking induces).
• Other stimulants (e.g., pseudoephedrine): Additive CNS effects.
• Other paracetamol products: Risk of cumulative overdose.

• Emphasis on limiting daily paracetamol dose to ≤4 g/day across all combination products.
• Caffeine limits advised during pregnancy and in pediatric populations.
• European guidelines discourage long-term use of caffeine-paracetamol combos due to potential for medication overuse headache (MOH).

• Store below 25°C (77°F)
• Protect from moisture and light
• Do not refrigerate
• Keep tablets in original packaging to avoid degradation
• Keep out of reach of children