What is Drug Intolerance?

Drug intolerance is a relatively common medical issue. Every medication, whether it’s an antihistamine, anti-depressant, or painkiller, has the potential to cause adverse reactions or side effects. When choosing the right prescription for a patient, doctors select drug quantities based on the average tolerance the general population will have for the specific drug being prescribed.

However, different people can respond to specific ingredients in medications in unique ways. Some people might even have a genetic intolerance to certain specific prescription drugs.

The standard dosage for a drug for most people may cause enhanced adverse reactions in certain patients.

An increased risk of adverse reactions, or side effects, often indicates the presence of a drug intolerance. The more intolerant a person is to a drug, the more issues they’ll encounter with the medication, even when taking lower doses than most patients.

Drug intolerances are a regular research subject within the realm of pharmacokinetics. They’re heavily influenced by genetic factors, which impact how the body can process, metabolise, and clear drugs from the human bloodstream.

What is Drug Intolerance? The Basics

A drug intolerance is essentially an increased sensitivity to the potential adverse effects of a medication. Some people are more sensitive to certain medications than others. In fact, hypersensitivity to drugs is more common than many people realize, affecting approximately 7% of the population.

When a person is intolerant to a drug, this indicates they’re unable to manage the side effects of a substance, either at therapeutic or sub-therapeutic doses. Alternatively, a person is considered tolerant of a drug when they can withstand its adverse effects. Crucially, people who experience side effects from a medication aren’t necessarily intolerant to the substance.

While many people experience side effects, those who are drug intolerant may need to stop taking a specific medication completely, or reduce the dosage significantly to avoid serious symptoms.

Interestingly, people can also be particularly tolerant of certain medications. When a person is hyper-tolerant of a drug, they may experience no negative side effects, but they may also need higher doses of the medication to experience the same beneficial effects of the drug as other individuals. Tolerance can develop over time, often after repeat exposure to the same medication.

What’s the Difference Between Drug Intolerance and a Drug Allergy?

Drug intolerance is not the same as a drug allergy. Allergic reactions to a drug are caused by immune system responses, wherein the body’s protective system goes into overdrive to react to a perceived threat. When a person is allergic to a drug, or a substance within a medication, the body’s immune system sees the ingredient as harmful, and triggers an inflammatory response.

Similar to most allergies, drug allergies can be mild or severe. In the less serious cases, an allergic reaction may lead to symptoms such as rashes or fever. However, severe drug allergies can cause life-threatening side effects, such as anaphylaxis, which can constrict the airways and cause kidney damage. While people with a drug intolerance may be able to continue using a medication at lower doses, people with an allergy need to avoid exposure to the medication at all costs.

Drug intolerances do not involve an immune reaction. Instead, they cause people to be more susceptible to negative or adverse effects commonly caused by the drug. For instance, a person with an intolerance to a pain medication which could cause gastrointestinal symptoms may be more likely to experience severe stomach pain and discomfort, even when consuming a small dose.

What are the Symptoms of Drug Intolerance?

Drug intolerance is the term used to refer to an inability to accommodate negative side effects caused by medications, and experiencing more negative side effects than what’s expected. As such, the symptoms of drug intolerance can vary depending on the medication provided. In most cases, intolerances usually lead to symptoms affecting the gastrointestinal tract, as many medications have side effects caused by changes in the gut microbiome.

Some people with a drug intolerance may be more susceptible to diarrhea, vomiting, and nausea when taking a certain medication. Depending on the common side effects of the drug, other symptoms can include headaches, dizziness, or general discomfort.

Typically, respiratory changes, flushing and rashes aren’t a symptom of intolerance, but could indicate the presence of a drug allergy. Additionally, it’s worth noting that the symptoms of a drug intolerance often manifest over time, after repeated exposure to the drug.

Some people can take medication for several days without experiencing any side effects before the symptoms of their intolerance appear. Alternatively, for people with a drug allergy, side effects would manifest immediately, within a few minutes of exposure.

What Causes Drug Intolerance?

While drug allergies are caused by issues with immune system response, drug intolerances are largely affected by the way the body metabolizes medications.

FDA-approved and pharmaceutical drugs are designed to deliver beneficial ingredients at a certain concentration level within the bloodstream.

Pharmacologists examine the Minimum Effective Concentration, or MEC of each drug when testing it for human consumption. This indicates the minimum level of a substance that needs to be present within the bloodstream to generate a specific effect. Alongside the MEC, pharmacologists also consider the Minimum Toxic Concentration, or MTC of a treatment.

The Minimum Toxic Concentration of a drug determines the lowest level at which the drug might begin to cause adverse reactions or side effects. The difference between both measurements is known as the therapeutic window. When prescribing a drug to a patient, a doctor must consider the potential benefits of the drug, and the possible side effects each patient might encounter.

Just as different types of drugs have unique therapeutic windows, different people can have different personal MECs and MTCs for each substance. A person with a very low MTC for a drug is considered to be intolerant to the substance, as they’re more likely to experience adverse reactions to the medication, even at lower doses.

Is Drug Intolerance Genetic?

There are various factors which can influence a person’s MTC and MEC levels. Some people with pre-existing medical issues, such as problems with kidney and liver function, may not be able to metabolize drugs at the same level as the general population. This is something doctors can often easily account for when prescribing a medication.

However, understanding a person’s unique tolerance to a drug can also be more difficult, as specific liver enzyme genes, metabolic genes, and other components can also influence a person’s drug tolerance.

In the 1970s,researchers discovered that drug metabolism can be affected by genetics. An inability to tolerate certain medications can be passed down through generations, similar to food intolerances, or an increased risk of specific allergies.

DNA testing and genetic study are providing medical professionals with greater insights into the specific types of genes and enzymes which can lead to drug intolerance. For instance, a person with a defect in the cytochrome P450 superfamily of metabolizing enzymes in their DNA may not be able to tolerate and metabolize steroidal drugs at the same rate as the average person.

When a person doesn’t have the right genetic components to create enzymes for drug metabolization, the drug can build up within the bloodstream to higher concentrations than pharmacologists typically accommodate for during testing trials. This means a person taking only 10mg of a certain drug could end up encountering side effects similar to those they would experience from taking 100mg.

You can find out which drugs you might be genetically intolerant to by reading the genetic drug interaction section of your CircleDNA test report.

Are Drug Intolerances Dangerous?

Drug intolerances can vary in severity. Just as a person with increased sensitivity to a certain food may be able to continue eating that food with mild side effects without it being life-threatening, those with higher drug intolerances may be able to persevere with some treatments. However, if a person does experience a drug intolerance, their response to a drug will often be closely monitored.

In some cases, variations in drug metabolism caused by differences in genetic components can be almost imperceptible. Some people may have an increased intolerance to drugs, but may not recognize the issue, or brush their symptoms off as common side effects. With drugs that have a high therapeutic margin for safety, drug intolerance issues are often overlooked.

However, variations in drug metabolism and drug tolerance can be particularly problematic for drugs which have a lower therapeutic margin for safety. For instance, if a person is intolerant to a blood thinning drug such as warfarin, they could suffer from dangerous excess bleeding.

People with an increased sensitivity to beta-blocker drugs could experience problematic changes in blood pressure. Certain drugs are considered to be particularly dangerous for those with drug sensitivities. The painkiller codeine, when taken by an individual with a rare genetic variation, can lead to respiratory collapse, and even death.

Because of this, medical professionals are investing heavily in research into molecular genetics, to assist with the prediction of drug sensitivities and intolerances. With DNA test kits such as the CircleDNA test, patients can even discover their own predisposition to drug intolerances.

How Common Are Drug Intolerances?

It’s difficult to know for certain how many people have a drug intolerance today. Some people might have a drug intolerance to a specific drug, but they’d never know if they’ve never been prescribed that drug and never taken it.

Furthermore, often, mild drug intolerances are overlooked, as most people expect to experience side effects when taking medications. A large range of drugs can be susceptible to changes in metabolic function caused by genetic markers, which may make people more prone to side effects.

Antidepressants, antibiotics, painkillers, and blood thinners can all be influenced by metabolic variations. However, some intolerances are considered more common than others.

Problems with analgesic medications and NSAIDs are quite common, and are thought to be caused by genetic variations in the ability to metabolize arachidonic acids. Specialists have also begun looking into the issue of multiple drug intolerance syndrome, in which individuals are intolerant to a wide range of medications from different therapeutic families.

While not all drug intolerances are extremely dangerous, they can be very problematic, and cause a range of side effects and symptoms. You can learn more about which intolerances you may be more susceptible to by checking the genetic drug interaction section of your CircleDNA test report.


  1. NCBI: Multiple Drug Intolerance Syndrome: An Underreported Distinct Clinical Entity
  2. NCBI: Polymorphic hydroxylation of Debrisoquine in man
  3. NCBI: Codeine, ultrarapid-metabolism genotype, and postoperative death
  4. NCBI: Analgesic intolerance: pathogenesis, diagnosis and treatment https://pubmed.ncbi.nlm.nih.gov/20088346/
    https://www.pillcheck.ca/2019/06/06/what-is-the-difference-between-a-drug-allergy-and-drug-intolerance/#:~:text=Drug intolerance and drug sensitivity,a few days or weeks.

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