Paracetamol

Paracetamol (acetaminophen) is a pain and fever medication. It relieves pain and reduces fever but, unlike NSAIDs, has no notable anti-inflammatory effect.

The great advantage of paracetamol is its good gastric tolerability. Occasional use has no significant effect on the tendency to bleed. However, repeated use for longer than one week enhances the effect of anticoagulants. During pregnancy, it can be used if clinically necessary.

At low doses, paracetamol is available without a prescription. Higher single doses and combination products (e.g., Talvosilen forte® with codeine) are prescription-only.

The exact mechanism of action of paracetamol has still not been fully clarified:

Suspected mechanisms:

• Inhibition of prostaglandin synthesis in the central nervous system (CNS)
• Influence on the serotonin system
• Activation of descending pain-inhibiting pathways
• Possible involvement of the endocannabinoid system

Effect profile:

• Analgesic: Pain-relieving (mild to moderate pain)
• Antipyretic: Fever-reducing
• Not antiphlogistic: No relevant anti-inflammatory effect

Pharmacokinetics:

• Onset of action: 30–60 minutes
• Duration of action: 4–6 hours
• Metabolized in the liver

Paracetamol is suitable for:

• Mild to moderately severe pain
• Headaches
• Toothache
• Fever
• Cold symptoms
• Pain during pregnancy, if clinically necessary
• Patients with stomach disorders (no GI toxicity)
• Patients on anticoagulants, for occasional use (long-term use only under medical supervision)

Not suitable:

• In severe hepatic impairment
• In alcohol dependence (increased liver toxicity)
• For severe inflammatory pain (no anti-inflammatory effect)

Tablets:

• 500 mg, 1000 mg

Suppositories:

• 500 mg, 1000 mg

Usual dosage (adults):

• 500–1000 mg every 4–6 hours
• Maximum daily dose: 4000 mg (4 g)

In liver disease or underweight:

• Maximum daily dose: 2000 mg (2 g)

Important: The maximum daily dose must not be exceeded – there is a risk of liver damage!

How to take:

• Take tablets with water
• Regardless of meals
• Minimum interval between single doses: 4–6 hours

Important notes:

• Never exceed the maximum daily dose of 4 g
• Watch out for hidden sources of paracetamol (cold remedies, combination products)
• No alcohol while taking it
• Lower dose in case of liver problems

Overdose – emergency! Even taking the total daily dose all at once can lead to severe liver damage. From approx. 6 g as a single dose (adults), liver cells are destroyed. Call an emergency physician immediately! Antidote: N-acetylcysteine (must be given early).

Paracetamol must not be taken in case of:

• Severe hepatic impairment
• Hypersensitivity to paracetamol

Caution in case of:

• Mild to moderate hepatic impairment
• Chronic alcohol consumption
• Renal impairment
• Underweight / malnutrition (lower glutathione reserves)
• Gilbert's syndrome

Pregnancy: If clinically necessary, paracetamol can be used during pregnancy. It should then be used at the lowest effective dose, for the shortest possible time, as infrequently as possible and not in combination with other medicines.

Breastfeeding: Can be taken at therapeutic doses. Small amounts pass into breast milk. No undesirable effects during breastfeeding are known to date.

When used as directed: Paracetamol is very well tolerated at therapeutic doses.

Rare:

• Allergic skin reactions
• Changes in blood count
• Bronchospasm (in predisposed individuals)

In case of overdose (> 4 g/day):

• Severe liver damage (liver failure possible!)
• Nausea, vomiting
• Symptoms often appear only after 24–48 hours
• Immediate emergency treatment required

Important: Toxicity in overdose is the greatest risk of paracetamol. The therapeutic range is narrow.

Relevant interactions:

• Warfarin/Marcumar – with regular use, the INR may increase
• Carbamazepine, phenytoin, rifampicin – accelerated breakdown of paracetamol, increased toxicity
• Alcohol – increased risk of liver damage
• Metoclopramide – accelerated absorption of paracetamol

Advantage: Unlike NSAIDs, no relevant interactions with blood pressure medications, no increased risk of GI bleeding, no effect on platelet function.