How to treat a fever when having a cold - should you choose ibuprofen or paracetamol?

Ibuprofen or paracetamol? Despite their similar effectiveness, patients often face the dilemma of which antipyretic drug to choose. There are many factors to consider when making this decision, including the patient's general condition, their comorbidities, and potential side effects caused by the chosen drug.

Fever as the body's defense reaction 

Fever is one of the human body's defense mechanisms and an important warning signal informing about a developing disease or its exacerbation. It is tied to the increased production of the so-called pyrogenic cytokines which activate specific enzymes - cyclooxygenases (COX) - in the hypothalamus. This leads to increased production of prostaglandins (including PGE2), which affect the thermoregulation center, resulting in an increase in body temperature. A slight increase (in the range of 37.1–38.0°C) is called a low-grade fever. A low-grade fever can positively influence the course of an infection. However, when the fever causes discomfort and a general feeling of being unwell, or when it exceeds 38.5°C, it is recommended to begin pharmacological treatment. The main goal of treating fever is not so much to lower it as to improve the patient's well-being. In order to achieve this goal, you can use various preparations containing, among others, paracetamol or non-steroidal anti-inflammatory drugs (e.g. ibuprofen). These drugs are characterized by an analgesic effect (painkillers), and thus allow you to additionally eliminate any unpleasant ailments accompanying a viral infection, such as headaches or muscle pain.

It is worth noting that body temperature exceeding 40°C can be life-threatening. Long-term high fever can have serious consequences. 

Body-temperature of over 40°C may lead to disturbances in the body's water and electrolyte balance or serious dehydration. It is especially dangerous for people with chronic diseases as puts an overwhelming strain on the body, which can lead to organ failure. 

How do antipyretic drugs work? 

The most popular drugs used to reduce fever and alleviate its accompanying symptoms are NSAIDs (e.g. ibuprofen) and paracetamol. These substances are also used as painkillers and are mostly available over the counter. Their use is recommended for mild and moderate pain of various origins, e.g. headaches, toothaches, muscle pains, bone pains, joint pains, or painful menstruation. In addition, NSAIDs have anti-inflammatory effects and can be used in the symptomatic treatment of rheumatoid arthritis or osteoarthritis. 

Ibuprofen has been widely used in medicine for almost 60 years. It has a well-documented antipyretic effect, confirmed by numerous clinical trials. Ibuprofen's mechanism of action is based on the inhibition of an enzyme called cyclooxygenase (COX), responsible for the synthesis of prostaglandins (including PGE2). This allows the drug to limit their influence on the thermoregulation center, and thus to effectively combat the symptoms of fever. It is worth emphasizing that prostaglandins also affect the pain threshold and the occurrence of typical symptoms of the inflammatory process. Therefore, ibuprofen, by limiting their synthesis, also exhibits analgesic and anti-inflammatory properties, and thus effectively reduces the symptoms often associated with fever. On the market, ibuprofen is sold in various chemical forms, including in the form of an acid, a sodium salt, a lysinate, or an arginate, which is also an important factor affecting the drug's absorption rate. Chemical modifications of ibuprofen’s molecule allow us to shorten the time needed to achieve the drug's maximum concentration in the bloodstream needed for it to exhibit its desired therapeutic effect.

Paracetamol is another common preparation with analgesic and antipyretic properties.  

Unlike ibuprofen, it has virtually no anti-inflammatory properties. Despite the fact that it has been widely used for over 60 years, its mechanism of action is still not fully understood. It probably causes the inhibition of cyclooxygenase located in the brain and spinal cord (COX-3). At the same time, paracetamol does not have a peripheral effect. It is suggested that paracetamol also influences the transmission of pain stimuli, related to the modulation of the serotonergic system or the activation of cannabinoid receptors. 

Paracetamol and ibuprofen dosage when treating fever

Both ibuprofen and paracetamol are analgesics and antipyretics. These preparations effectively relieve fever and improve the patient's comfort and well-being. They are used both on their own and as a part of numerous combined preparations. These products also contain substances that reduce swelling and congestion of the nasal mucosa, relieve sneezing, nasal discharge, and lacrimation. Paracetamol and ibuprofen are commonly found in many preparations used to relieve symptoms of the flu and the common cold. Therefore, more than one of these products should not be used simultaneously. Doing so can cause a high risk of overdosing and have serious consequences. 

Paracetamol and ibuprofen used in therapeutic doses are both safe and well-tolerated. Their dosage depends to a large extent on the indication, age, and condition of a particular patient.  

A standard single dose of orally administered ibuprofen in adults is 200-400 mg but make sure to wait at least 4 hours between doses. Long-term use of large amounts of ibuprofen may, among others, increase the risk of gastrointestinal irritation, ulceration, and bleeding.  

Therefore, the lowest effective dose of ibuprofen should be taken for the shortest possible amount of time. 

W przypadku paracetamolu standardowa dawka jednorazowa dla osób dorosłych wynosi 500-1000 mg. Działanie przeciwbólowe utrzymuje się przez 4–6 godzin, a działanie przeciwgorączkowe przez 6–8 godzin. Niezwykle istotne jest, aby nie przekraczać zalecanego dawkowania, ponieważ przedawkowanie paracetamolu może prowadzić do uszkodzenia wątroby, a w konsekwencji nawet do  śmierci. Substancja ta jest szczególnie niebezpieczna m.in. dla osób odwodnionych lub regularnie spożywających alkohol, ponieważ w tej grupie pacjentów istnieje zwiększone ryzyko wystąpienia działania toksycznego. 

It is also worth emphasizing that sometimes when treating a fever both substances are used simultaneously. This is not recommended, but some sources suggest taking ibuprofen and paracetamol alternately, especially if the discomfort recurs despite the use of one of the drugs. This practice has been justified in clinical trials - it has been found that the alternating use of paracetamol and ibuprofen in children leads to increased and longer antipyretic effect. 

Antipyretic efficacy of paracetamol and ibuprofen 

It is well known that both ibuprofen and paracetamol are effective in reducing fever in the course of infections of various etiologies. A wide selection of preparations in various pharmaceutical forms and doses is currently available on the market. According to the recommendations for the management of community-acquired respiratory infections, the use of one of the substances described above is highly recommended for antipyretic treatment. In exceptional situations, when one of the drugs proves to be ineffective, combination therapy is also allowed. However, if other severe symptoms of inflammation (pain, swelling, congestion, exudation) are observed, the use of ibuprofen is decidedly preferable.  

Data from clinical trials and analyses aimed at comparing the antipyretic efficacy of both drugs is widely available. Ibuprofen has been shown to lower fever more rapidly than paracetamol. In addition, its antipyretic effect is stronger and lasts longer. What is more, ibuprofen is as safe as paracetamol, as has been shown in a meta-analysis of over 36 studies covering a population of nearly 30,000 patients. However, it is worth emphasizing that when choosing an antipyretic drug, the patient's condition, possible accompanying diseases and potential side effects that may significantly affect the safety of the therapy should be taken into account.  

Antipyretic treatment during a SARS-CoV-2 infection 

In recent months, the use of ibuprofen in the treatment of fever caused by an infection with the SARS-CoV-2 virus, which causes the disease known as COVID-19, has raised much controversy. The discussion started with the hypothesis that the increased mortality of COVID-19 patients may be related to the increased expression of angiotensin-converting enzyme 2 (ACE2). This protein can potentially be used by the SARS-CoV-2 virus to enter the host cell where it replicates. Therefore, the authors suggested that the use of drugs modulating ACE2 expression (including drugs commonly used in the treatment of hypertension or ibuprofen) may exacerbate the course of the infection. In response to this news, official positions were taken by the World Health Organization (WHO) and the European Medicines Agency (EMA). 

The EMA statement concluded that there is currently no scientific evidence linking ibuprofen use with a worsened course of the COVID-19 disease. The EMA has also stressed that it monitors the situation on an ongoing basis and assures that it carefully analyzes each new piece of information. It was emphasized that patients and healthcare professionals should consider all available treatment options, including paracetamol and NSAIDs (including ibuprofen), when beginning the treatment of fever or pain caused by COVID-19. It has been suggested to use these drugs at the lowest effective dose for the shortest possible time. It is worth noting, however, that ibuprofen is sometimes used for prolonged periods of time, e.g. for the symptomatic treatment of rheumatoid arthritis and osteoarthritis. According to the EMA, on the basis of the currently available research, there is no reason for patients taking ibuprofen to forego treatment. Similar information was also shared in the statement of the President of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products in Poland.  

In a statement issued by the WHO on March 19, 2020, it is also not recommended to discontinue the use of ibuprofen, since there are currently no reports of negative effects resulting from its use, apart from the well-studied side effects that limit its use in some groups of patients. 

The information stated above has been confirmed by the scientific community. One of the most recent publications on the use of ibuprofen in the treatment of the symptoms of COVID-19 found that there is no data directly addressing the risk of NSAID use in COVID-19 treatment. Paracetamol has been chosen as the drug of choice, however, treatment should not be discontinued when patients have been using NSAIDs for a prolonged period of time.