Paracetamol Action, History, Uses, Side Effects, Dosage & Top Brands

Introduction

Paracetamol, or acetaminophen, is an analgesic (pain reliever) and antipyretic (fever reducer) drug commonly used to relieve mild-to-moderate pain and fever. It is recommended as a first-line therapy for pain conditions by the World Health Organization (WHO). It is commonly taken worldwide and is available in various forms, including syrup, regular tablets, effervescent tablets, injections, and suppositories.

History of Paracetamol

The medicinal use of paracetamol has a rich history, dating back to the late 19th century. Initially synthesized in 1877 by Harmon Northrop Morse, it wasn’t until the mid-20th century that paracetamol gained recognition as a safe and effective analgesic. Today, it remains a staple in many home medicine cabinets across the globe.

FDA Approval and Regulation

Paracetamol was initially approved by the U.S. Food and Drug Administration (FDA) in 1951. The FDA has taken action to improve the safety of consumers when using acetaminophen, providing information on its use during pregnancy, in children, and the risk of rare skin diseases.

How Paracetamol Works

According to its FDA labeling, while the exact way paracetamol works isn’t fully known, it’s often grouped with NSAIDs because it can inhibit the COX pathways. This action is believed to happen centrally in the brain, which helps reduce pain. One theory suggests that acetaminophen blocks two forms of the COX enzyme, COX-1, and COX-2, involved in making prostaglandins that cause pain. Unlike aspirin, which directly blocks COX, acetaminophen seems to indirectly affect it.

Some studies even propose that it blocks a unique COX variant, called COX-3. Acetaminophen’s ability to lower fever might be due to its direct effect on heat-regulating centers in the brain. While its full mechanism isn’t clear yet, ongoing research could provide more insights in the future.

Uses of Paracetamol

Worldwide, doctors frequently recommend Paracetamol for pain relief and fever reduction due to its broad efficacy and safety profile. Here are some common uses:

Pain Relief

Paracetamol is widely used to alleviate mild to moderate pain, including headaches, toothaches, muscle aches, menstrual cramps, and backaches.

Fever Reduction

It’s commonly used to reduce fever associated with various conditions, such as colds, flu, and other infections.

Pain and Fever in Children

Paracetamol is often recommended for children to relieve pain and reduce fever caused by common childhood illnesses.

Post-Surgical Pain Management

It is sometimes prescribed to manage pain after surgical procedures when other pain relievers are not suitable.

Arthritis Pain

For individuals with arthritis, paracetamol helps to relieve joint pain and stiffness, although it’s not typically as effective as nonsteroidal anti-inflammatory drugs (NSAIDs) for this purpose.

Combination Medications

Paracetamol is also included in many combination medications for colds, flu, and other ailments, often alongside other active ingredients like decongestants or antihistamines.

Chronic Pain Management

While not as potent as some other pain relievers, paracetamol may be used as part of a regimen for managing chronic pain conditions, often in conjunction with other medications or therapies.

Modified-release paracetamol

Modified-release paracetamol, also known as sustained-release, slow-release, extended-release, or Osteo paracetamol, is a formulation of paracetamol that is designed to release the medication into the body more slowly compared to immediate-release paracetamol. It is formulated with a higher dose of paracetamol per tablet (typically 665 mg) compared to immediate-release paracetamol (usually 500 mg per tablet).

The modified-release formulation allows for a more convenient dosing regimen, typically taken every 8 hours, compared to immediate-release paracetamol, which is usually taken every 4–6 hours. This sustained-release feature aims to provide longer-lasting pain relief.

Dosage and Administration

Paracetamol dosage varies depending on age, weight, and overall health condition. For adults and children over 12 years old, the general dose is 500mg-1g every 4 to 6 hours, not exceeding 4g in 24 hours. It’s crucial to adhere to the recommended dosage to avoid potential health risks.

Use in pregnancy and nursing

Paracetamol (also known as acetaminophen) is generally considered safe to use during pregnancy and breastfeeding. It’s often recommended as the first choice for pain relief or fever reduction in pregnant women because it has been extensively studied and is believed to pose minimal risk to the developing fetus.

During breastfeeding, only a small amount of paracetamol passes into breast milk. The dose that the baby receives is typically much lower than what would be given directly to the baby for pain relief or fever reduction. As a result, it’s considered safe for breastfeeding mothers to take paracetamol when needed for pain or fever management.

 Side Effects and Risks

Although paracetamol is generally safe when taken as directed, excessive use sometimes leads to serious health problems, including :

1. Allergic reactions, which include:
   • Skin rashes
   • Itching or hives
   • Swelling of the throat, tongue, or face
   • Shortness of breath or wheezing
   • Skin rash or peeling
   • Mouth ulcers
2. Breathing problems, especially if experienced previously with other painkillers such as ibuprofen and aspirin,
3. Unexplained bruising or bleeding, or becoming unusually tired, indicating potential issues with blood clotting or platelet function.
4. Liver problems are characterized by symptoms such as:
   • Nausea
   • Sudden weight loss
   • Loss of appetite
   • Yellowing of the eyes and skin (jaundice)
   • Abdominal pain

Interactions with drugs

Before taking paracetamol, it’s important to inform your doctor or pharmacist about all the medicines you currently take, including prescription and over-the-counter medications, vitamins, and herbal supplements. Here are some specific medications to mention:

1. Blood-thinning medications (anticoagulants): If you’re taking anticoagulants like warfarin and require daily pain relief, inform your doctor. Occasional doses of paracetamol are taken with anticoagulants, but regular use should be monitored closely.
2. Medications for nausea relief: Inform your doctor if you’re taking medications like metoclopramide or domperidone for nausea.
3. Cholesterol-lowering medications (cholestyramine): Let your doctor know if you’re taking cholestyramine for high cholesterol.
4. Medications for epilepsy (lamotrigine): Inform your doctor if you’re taking lamotrigine for epilepsy.
5. Medications for tuberculosis (isoniazid): Tell your doctor if you’re taking isoniazid for tuberculosis.
6. Medications for fever or mild pain (aspirin, salicylamide): Inform your doctor if you’re taking aspirin or salicylamide for fever or mild pain.
7. Barbiturate and tricyclic antidepressants (e.g., amitriptyline): Let your doctor know if you’re taking medications like amitriptyline for depression.
8. Medication for gout (probenecid): Inform your doctor if you’re taking probenecid for gout.
9. Medication for bacterial infections (chloramphenicol): Tell your doctor if you’re taking chloramphenicol for bacterial infections.
10. Medication for HIV/AIDS (zidovudine): Inform your doctor if you’re taking zidovudine for HIV/AIDS.
11. Flucloxacillin (antibiotic): Be cautious if taking flucloxacillin with paracetamol, especially if you have severe renal impairment, sepsis, malnutrition, chronic alcoholism, or if using maximum daily doses of paracetamol. This combination may lead to high anion gap metabolic acidosis, requiring urgent treatment.

Warnings and precautions

Paracetamol is a commonly used over-the-counter medication, and while it is generally safe when used as directed, it’s essential to be aware of warnings and precautions associated with its use. Here are some key points:

1. Dosage: Follow the recommended dosage instructions carefully. Taking more than the recommended dose leads to liver damage.
2. Liver health: Paracetamol is metabolized in the liver. Individuals with liver problems or chronic liver disease should consult a healthcare professional before taking paracetamol.
3. Alcohol: Avoid consuming alcohol while taking paracetamol, as it can increase the risk of liver damage.
4. Medication interactions: it interacts with other medications, including certain antibiotics and blood thinners. Always consult a healthcare professional before taking paracetamol with other medications.
5. Allergies: If you have a known allergy to paracetamol or any of its ingredients, avoid using it and seek alternative pain relief options.
6. Long-term use: Prolonged or excessive use of paracetamol can lead to liver damage or other adverse effects. If you need to use it for an extended period, discuss it with a healthcare professional.
7. Underlying health conditions: Individuals with certain health conditions, such as kidney problems or G6PD deficiency, should use paracetamol with caution and under medical supervision.
8. Overdose: An accidental overdose of paracetamol can cause severe liver damage and even be fatal. If you suspect an overdose, seek immediate medical attention, even if there are no symptoms.
9. Children: Use pediatric formulations and dosages appropriate for the child’s age and weight. Never give adult-strength paracetamol to children without consulting a healthcare professional.

Paracetamol: Brand Names and Global Presence

Paracetamol, known as acetaminophen, is commonly found in more than 600 over-the-counter (OTC) medications and is widely available under various brand names across the globe. Some of the most notable brands include Tylenol, Calpol, and Panadol, each catering to specific markets and consumer needs.

(1) Panadol: Global Reach and Gentle Relief

Panadol, marketed by GlaxoSmithKline, enjoys a presence in over 85 countries worldwide. Originally introduced as a prescription medication in clinics in 1953, Panadol gained popularity for being gentle on the stomach, especially compared to other analgesic agents containing aspirin. Its availability expanded over the years, making it accessible over the counter in various countries.

Historical Evolution of Panadol

Panadol came into commercial use in 1955 after being used in clinics from 1953. Phillips, Scott & Turner started its commercial business, and later it was acquired by Frederick Stearns & Co, which was a part of Sterling Drug Inc. They marketed it as being easy on the stomach because other painkillers back then had aspirin, which could upset the stomach.

In 1955, Panadol was introduced to hospitals in the UK, initially only available with a prescription but now sold over the counter. In 1983, it was introduced to the United States market.

Sterling Winthrop, which owned Panadol, was bought by Eastman Kodak in 1988. Then, in 1994, Eastman Kodak sold the over-the-counter drug business to SmithKline Beecham, except for North American rights to Panadol.

Two weeks later, SmithKline Beecham sold the over-the-counter medication business in the US, Canada, and Puerto Rico to Bayer for US$1 billion, but they retained the rights to Panadol in North America. Panadol has been recognized as one of the most frequently counterfeited medicines worldwide.

(2) Calpol: Trusted Children’s Medication

Calpol, which is particularly popular in the UK and other regions, offers paracetamol-based medications specifically tailored for children. Its flagship product, Calpol Infant Suspension, is widely used to treat fever and pain. Despite being a common cause of accidental child poisoning due to its pleasant taste, Calpol remains a trusted brand in the pediatric healthcare sector.

History of Calpol

Calpol was started in 1959 by a company called Calmic Ltd in England. They named it after the words ‘Cheshire and Lancashire Medical Industries Corporation’. Later, Wellcome, which is now part of GlaxoSmithKline, bought Calmic in 1966. Calpol became popular in the UK during the 1980s.

Then Pfizer Consumer Healthcare took over, and in 2006, Johnson & Johnson acquired Pfizer. Now Calpol is under Johnson & Johnson’s McNeil Consumer Healthcare. In 2020, it was the most popular children’s pain-relief medicine in the UK, making £60.1 million in sales.

(3) Tylenol: Reducing Pain and Fever

Tylenol stands out as a prominent brand recognized for its efficacy in reducing pain and fever. Owned by McNeil Consumer Healthcare, a subsidiary of Kenvue, Tylenol is available in multiple countries, including Brazil, Canada, China, and the United States. 

Other brands

1. Provas is manufactured by SAMI Pharmaceuticals.
2. Nuberol forte is manufactured by SEARLE Pharmaceuticals.
3. Panadol drops are manufactured by G.S.K. Pharmaceuticals.
4. Febrol is manufactured by Barrett Pharma.

Additional Information

• Paracetamol is included as an ingredient in many over-the-counter cold and flu medications, combination pain relievers, and prescription medications.
• The prices of Paracetamol Active Pharmaceutical Ingredients (API) have experienced a downward trend in recent months, reflecting dynamics within the global pharmaceutical supply chain.