Health care Side effects of medicinal products

Side effects are harmful and unintended reactions to a medicinal product. They are often also referred to as adverse drugs reactions (ADRs). Side effects can be known or unforeseen. Known side effects are described in the package insert accompanying the medicinal product.

Differentiation is also made between non-serious and serious side effects. Serious side effects are side effects that

• are fatal or life-threatening
• require hospital admission or lengthen a stay in hospital
• lead to permanent or serious disability or incapacity
• cause birth defects

Medicinal products contain one or more active ingredients. These have various effects on the body. Medicinal products are used for their desired effects. However, they can also cause other, unwanted reactions known as side effects. 

Side effects do not always necessarily occur. There are various factors that determine whether a person will experience side effects. For example, side effects depend on the way in which the medicinal product works. Certain side effects also depend on the dosage at which the medicinal product is taken. 

Individual differences, such as age, sex, genetic predisposition or certain pre-existing conditions also play an important role. In addition, side effects may be caused by interactions with other medicinal products or foods. Taking medication incorrectly can also lead to side effects. 

Treatment with medicinal products must be carefully and individually adjusted to reduce the risk of side effects.

How the medicinal product works

Many active ingredients contained in medicinal products interfere with complex metabolic processes in the body. As well as having the desired effects, they may also impact other processes or organs. For example, cortisol is used to suppress the immune system thereby reducing allergic reactions or autoimmune reactions. This is its desired effect. At the same time, however, it makes people more susceptible to infections with pathogens. This is an unwanted or adverse effect. 

Dosage

Taking medication at too high a dosage or too frequently increases the risk of unwanted side effects. Side effects can also occur when medication is taken incorrectly, e.g., at the wrong time or in the wrong form.

Pre-existing conditions

Various pre-existing conditions influence the risk of side effects. For example, impaired liver or kidney function can slow the breakdown or excretion of a medicinal product. As a result, too much of the active ingredient remains in the body and side effects can occur as a result.

Genetic predisposition

Certain genetic factors determine the rate at which medication is broken down in the liver. Active ingredients are broken down more slowly in some people than in others. This can make side effects more likely.

Gender differences

Differences can also exist between the way men and women metabolize and break down a medicinal product. This can mean that different doses should be used depending on a person’s gender. Such gender-specific aspects are being increasingly taken into account in modern medicine.

Drug interactions

Interactions with other medication or foods can also lead to side effects. For example, if a person takes several drugs to reduce blood pressure at the same time and all of these influence blood pressure via a similar mechanism, side effects are more likely to occur. 

Some drugs or foods can also influence the function of certain liver enzymes. These CYP enzymes are involved in the metabolization of drugs. Grapefruit juice, for example, can inhibit the breakdown of cholesterol-lowering drugs (statins), causing muscle damage.

All known side effects and their currently known prevalence are listed in the package insert (package leaflet) and the specialist information for doctors. Prevalence information is divided into several categories, ranging from “very common” to “very rare”:

• very common: affects more than 1 in 10 people
• common: affects 1 to 10 in 100 people
• uncommon: affects 1 to 10 in 1,000 people
• rare: affects 1 to 10 in 10,000 people
• very rare: affects fewer than 1 in 10,000 people

Side effects can vary greatly from person to person. If minor, temporary side effects occur after taking medication, you can first wait and see what happens. You can also check the package insert for information about the effect.

In the event of more prolonged side effects or side effects that are getting worse, professional advice should be sought – even if the symptoms are only mild. For example, a doctor or pharmacist can be consulted. If symptoms are severe, the person should see a doctor immediately or contact the non-emergency medical assistance service. In an emergency, dial 112 for emergency services.

Reporting a side effect or suspected side effect helps make the use of medicinal products even safer.

Healthcare professionals have an obligation to report side effects. However, patients can also choose to report them. Information about how to do this can also be found in the package insert. You can, for example, notify your doctor or a pharmacy. You can also contact the pharmaceutical company that manufactured the product or the relevant higher federal authorities. Information about which authorities to report to can be found in the package insert.

The simplest way to report side effects to the relevant higher federal authority is to submit a report online at nebenwirkungen.bund.de. Alternatively, you can also send your report by e‑mail or post.

Important information

The following information is important when reporting a side effect:

• information about the person who experienced the side effect (for example age and gender)
• a description of the side effect
• details about how long it took for the side effect to occur after taking the medication
• the dosage that was taken and the name of the active ingredient, as well as the exact trade name under which the medicinal product is sold
• the batch details of the medicinal product (these can be found on the packaging)
• all other medicinal products taken or injected at the same time (including over-the-counter medicinal products, herbal medicinal products and contraceptives)
• all health problems of the person who experienced the side effect
• contact details, in case further information is required

For more information about the reporting system for side effects, see the website of the Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM).

Side effects that were already identified in clinical trials prior to a medicinal product being approved are subjected to a benefit-risk assessment during the approval process. However, rare and very rare side effects, side effects among certain groups (such as pregnant women) and possible interactions with other drugs may not yet be known at the time of approval. New information about the form and extent of known side effects may also come to light following approval.

Therefore, medicinal products are also continually monitored for new, previously unknown risks of use and side effects after they have been approved. In Germany, this continuous monitoring is the responsibility of the relevant higher authority – the Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM), the Paul Ehrlich Institute (PEI) in cooperation with the European Medicines Agency (EMA) or other EU approval authorities.

The reporting of side effects makes an important contribution towards making medicinal products safer. New findings are also incorporated into the ongoing benefit-risk assessment. This enables the authorities to respond quickly and reasonably with appropriate measures. 

Examples of potential measures include:

• an order requiring the manufacturer to perform further trials on the safety of the medicinal product
• additions or changes to the package insert and specialist information
• additional training material with recommendations for patients on what they should do in the event of a side effect – identifiable by the blue hand symbol
• restrictions on the use of a medicinal product

Red hand letters notify medical professionals

It can take time for the package insert and specialist information to be updated. However, doctors and pharmacists should be notified about important new findings as quickly as possible. In Germany, this is where “red hand letters” come in. These are sent to medical professionals by the approval holder in consultation with the relevant authorities and provide information about new usage risks as well as the measures that can be used to minimize them.

The benefit must outweigh the risk

As a general rule, the benefit of a medicinal product must outweigh the risks of its use. If the benefit is extremely great – for example because the medicinal product cures the patient of cancer – more severe side effects are justifiable. On the other hand, headache tablets or cough medicine should only have very mild side effects. The same applies to medicinal products used to prevent illnesses, for example vaccines.