Paracetamol with Caffeine for Fever? – Mechanism Explained

Have Fever and Pain? And you want to get rid of it within minutes?? You are looking at Paracetamol with Caffeine tablets! Or maybe coffee plus PCM? In this post, we will give you clinical experimental information performed on how efficacious this miraculous combination can be.

Getting Started

“Increased intensity of action of drugs that are activated by metabolism. Acute paracetamol toxicity is due to one of its metabolites-toxicity occurs at lower doses in patients receiving enzyme inducers.”- K.D Tripathi Pharmacology (book for MBBS doctors).

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Mechanism of Combination therapy

Paracetamol metabolism is increased 2-4 folds by microsomal enzyme induction through cytochrome p450.

Effects of Combination

Increased Anti-pyretic and Analgesic effect (Mainly nociceptive). Inappropriate or higher dosages may cause paracetamol toxicity.

What doses can I take?

There are two routes for that. Either you take combined Paracetamol and Caffeine tablets, or you can try a more traditional way of taking it with coffee.

Paracetamol with Caffeine Tablets

These are available in 500/65 forms (meaning 500mg of PCM with 65mg of Caffeine).

Traditional Way

This is as follows:

  • 500mg of paracetamol+100mg of caffeine
  • 100mg= roughly one mug of coffee

The caffeine content of commonly consumed items compared with paracetamol with caffeine tablets

Beverage/item Container/size Typical caffeine content
— Instant
— Percolated
250 mL cup 60–80 mg
60–120 mg
Tea 250 mL cup 10–50 mg
Coca Cola 375 mL can 48.75 mg
Energy drink 250 mL can 80 mg
Chocolate bar 100 g bar 20 mg
Paracetamol with caffeine 1 dose (= 2 tablets) 130 mg

Adverse effects

Most problems involve Paracetamol toxicity, though it is rare (occurs with genetics or overdose). For this, one will have to take huge amounts of paracetamol to induce overdose effects causing liver failure, and death.

Here is how Paracetamol Overdose is managed:

Treatment of Overuse

It includes headaches as the most prominent sign of withdrawal. The right amount of paracetamol with caffeine is usually not harmful.

However, if you take tablets beyond the critical threshold (150mg/kg), you will require immediate hospitalization and management.

Contraindicated in Pregnant and Breast

  • Feeding women and pregnant women should not consume more than 200 mg of caffeine per day, as this may increase the risk of spontaneous miscarriage.
  • Consuming >300 mg per day may also increase the risk of preterm delivery and fetal growth retardation.
  • Caffeine is readily transferred to breast milk and young infants poorly metabolize caffeine. Infants who are breastfed by mothers consuming >300 mg of caffeine per day may become jittery and restless and may experience sleep difficulties.


K.D Tripathi: Page 27-28

The Original Trial

So does caffeine added to painkillers make them work better?

In light of a new Cochrane review, the simple answer seems to be yes. The reviewers looked for studies comparing the pain-relieving effect of common painkillers with and without added caffeine.

As well as searching key databases the authors contacted drug companies known to have carried out trials on Paracetamol with Caffeine that has not been published.

Randomised Control Trials
How Randomised Control Trials work

19 randomized controlled trials (RCTs) of 7238 people were included, assessing several acute pain conditions including headache, post-dental pain, postoperative pain following childbirth, and period pain.

Most studies used paracetamol (500 mg to 1500 mg) or ibuprofen (100 mg to 400 mg), with two using aspirin (650 mg and 800 mg), one aspirin (500 mg) plus paracetamol (400 mg), one diclofenac (100 mg), and one tolfenamic acid (200 mg).

Caffeine was added at doses of 50 mg to 260 mg, with most studies using between 100 mg and 200 mg. In most studies participants were not allowed to have any caffeine in food, drink, or other medicines for a specified time within the trial.


There was a small but statistically significant benefit with caffeine used at doses of 100 mg or more for all pain conditions and painkillers. About 5% to 10% more people achieve a good level of pain relief with the addition of paracetamol with caffeine.

There was only one serious health event in one person treated with caffeine plus painkiller and this was not considered related to the study medication.

Most of the studies were old, with only three (in headache) published since 2000, but they were generally of good methodological quality.

There are 20 more studies with over 9000 participants for which data for analysis were not obtainable. However, even if all the missing data showed no effect of caffeine, the additional effect of caffeine would still be statistically significant.

The authors concluded that the existing evidence is probably sufficient to support the use of caffeine with analgesics. This was in addition of ≥ 100 mg caffeine to a standard dose of commonly used analgesics. These analgesics provide a small but important increase in the proportion of people who experience a good level of pain relief.

100mg of caffeine is roughly equivalent to the caffeine in a mug of coffee. So if you’ve got a headache and have standard painkillers in the cupboard, you may do well to wash them down with a coffee. Otherwise, Paracetamol with Caffeine tablets is good to go.


Swallow down the PCM with coffee and feel the effects much faster than taking paracetamol with water.

This was all about the Paracetamol with Caffeine Combination for Fever.

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