Paracetamol

Acetaminophen, dymadon, lemsip, panadol, panamax, tylenol, triaminic, Disprol, Hedex, Medinol, and Panadol

Analgesicpain relieving, antipyreticfever breaking

Paracetamol is a pharmaceutical drug, which is used to treat a number of conditions including –

• mild pain,
• fever,
• strong pain (when combined with codeine),
• colds and ‘flu (when combined with antihistamines and decongestants) ¹, ².

You can buy most types of paracetamol from supermarkets or pharmacies. Some types are only available on prescription ³.

Paracetamol is available as –

• tablets, capsules or caplets,
• chewable tablet,
• geltab or gelcap,
• extended-release tablet
• liquid – usually for children,
• soluble tablets (tablets that dissolve in water to make a drink),
• suppositories (capsules inserted into the back passage),
• an injection given into a vein – normally only used in hospital ³.

In some products, such as cold and flu remedies or certain combination painkillers, paracetamol is combined with other ingredients.

It may be sold under the name paracetamol, or under various brand names (which may also contain other ingredients) ³.

Paracetamol is contained in countless pain formulations, cold products, sinus preparations, and more (e.g., Sinutab, Midol, Ultracet, Dristan). The wide availability of paracetamol, sold over-the-counter and in prescription products, make it one of the most common drugs associated with intentional or accidental poisoning. If you take multiple products that contain paracetamol and exceed the maximum allowable daily dose, serious side-effects and potentially fatal consequences may occur ⁴.

The Medicines and Healthcare products Regulatory Agency (MHRA) licensed dose of paracetamol is the same for all routes of administration in adults over 50 kg (i.e. 1 g up to four times a day), with a minimum of 4 hours between each administration.

However, in view of the pharmacokinetic data of paracetamol, a case has been made for a single loading dose of 2 g, followed by 4–6 hourly 1 g doses, and this has found its way into clinical practice over recent years ⁵.

Recommendations suggest that you may take paracetamol for up to 3 days when treating a fever, and for up to 10 days when treating pain. If symptoms persist beyond that time-frame, consult with a doctor to see if you should continue with paracetamol or change your treatment plan ⁴.

In your bodies, paracetamol finds its way into circulation via the gastrointestinal tract. Paracetamol is virtually 100% bioavailable making it both effective and potentially dangerous. It takes about 30 minutes for the analgesicpain relieving and antipyreticfever breaking properties of paracetamol to kick in, and, under normal circumstances, our bodies clear about half a dose of paracetamol 2.5 hours after ingestion.

When taken for pain in adults, paracetamol is dosed between 600 mg and 1000 mg every 4 to 6 hours. Nobody should take more than 4 grams a day. Tylenol caplets contain 500 mg of paracetamol so you should never take more than 2 caplets every 6 hours or 8 caplets per day. Of note, if you have a painful condition that requires you to take anywhere near 8 caplets of Tylenol a day, you should definitely seek medical attention.

When taken in therapeutic amounts, most paracetamol is safely broken down by the liver through the metabolic processes of sulfation and glucuronidation. Furthermore, a smaller amount of ingested paracetamol (less than 5%) is directly excreted via the kidneys. Finally, with therapeutic dosages, a very small percentage is oxidized by the cytochrome P-450 system reactive metabolite N-acetyl-p-benzoquinoneimine (NAPQI). NAPQ1 is quickly detoxified by hepatic glutathione to a nontoxic paracetamol-mercapturate compound which is also eliminated by the kidneys.

In cases of paracetamol poisoning, the liver enzyme cytochrome P-450 is quickly overwhelmed and stores of glutathione run out. Consequently, the reactive metabolite, NAPQ1, damages and kills liver cells thus leading to liver failure ⁸.

In 2008, the American Association of Poison Control Centers reported 71,328 exposures to paracetamol in combination and 80,845 exposures to paracetamol alone. Fifty-three people died of paracetamol poisoning secondary to combined preparations, and 69 people died on account of paracetamol alone. These statistics underline an important clinical truth about Tylenol poisoning: Sure some people end up overdosing on paracetamol because it appears ‘benign’, but nearly equal numbers of people end up poisoning themselves because they fail to realise that paracetamol was even in the medications that they were taking ⁸.

Make sure you take paracetamol as directed on the label or leaflet, or as instructed by a health professional.

How much you can take depends on your age, your weight, the type of paracetamol you’re taking and how strong it is ³. For example –

• Adults can usually take one or two 500mg tablets every 4–6 hours, but shouldn’t take more than 4g (eight 500mg tablets) in the space of 24 hours.
• Children under 16 need to take a lower dose, depending on their age or weight – check the packet or leaflet, or ask a pharmacist or doctor for advice. For very young children, paracetamol liquid is given using a measuring spoon or an oral syringe ³.

If you drink three or more alcoholic beverages every day or have had alcoholic liver disease, ask your doctor if you should take paracetamol. The combination of alcohol and paracetamol can be seriously damaging to the liver, with possible fatal outcomes ⁴.

Don’t take more than the recommended amount of paracetamol, even if you are still having pain. Be mindful of how much alcohol you drink when taking paracetamol, as more than 3 to 4 drinks per day can increase your risk of fatal liver damage. If you take other over-the-counter products, such as those for colds or flu, check first to see if they contain paracetamol. If you experience symptoms such as appetite loss or nausea and vomiting after taking paracetamol, call your doctor. These can be early warning signs of liver failure ¹¹.

Paracetamol is one of the most widely used of all drugs, with a wealth of experience clearly establishing it as the standard antipyreticfever breaking and analgesicpain relieving for mild to moderate pain states. First used clinically by von Mering in 1893, paracetamol did not appear commercially until 1950 in the United States and 1956 in Australia. During the 1960’s and 1970’s, increasing concern was raised about the toxicityThis is when too much of something is taken over a short period of time More of nonprescription analgesics, but in normal use paracetamol exhibited a consistent safety profile. Its exemplary safety record was marred by the discovery in 1966 that a major overdose could be complicated by severe and sometimes fatal liver damage. Fortunately, early treatment with N-acetylcysteine prevents liver toxicityThis is when too much of something is taken over a short period of time More. A turning point in the choice of paediatric analgesicpain relieving came in the 1980s when aspirin was linked to Reye’s syndrome. As a consequence, paracetamol became the mainstay analgesicpain relieving and antipyreticfever breaking for children with a subsequent reduction in the incidence of Reye’s syndrome ¹².

Paracetamol was first synthesised in 1878 by Morse, and introduced for medical usage in 1883. However, due to misinterpretation of its safety profile, it enjoyed only limited use until the 1950’s, when the chemically similar, and up until then preferred analgesicpain relieving, phenacetin was withdrawn because of renal toxicityThis is when too much of something is taken over a short period of time More. Paracetamol is now probably the most commonly used drug worldwide, available over the counter, used in almost all ages, and forming Step 1 of the WHO analgesicpain relieving ladder ⁵.