A drug interaction occurs when the effect of one medicine is altered by another substance, potentially changing how well a medicine works or increasing or decreasing the likelihood of unwanted effects. The interacting substance may be another medicine, an over-the-counter product, a herbal remedy, a vitamin or supplement, food or drink. The MHRA describes medicine interactions broadly as situations in which another substance affects the way a medicine works and distinguishes categories such as drug-drug and drug-food interactions. An interaction can therefore involve substances that a person might not ordinarily think of as drugs.
Pharmacological interactions can occur through several mechanisms. Pharmacodynamic interactions happen when substances affect the same physiological system or pathway, so their effects may add together, oppose one another or otherwise modify the body's response. For example, two medicines that both increase sedation can produce more pronounced drowsiness when combined. Pharmacokinetic interactions occur when one substance changes the absorption, distribution, metabolism or elimination of another medicine, thereby altering its concentration at the site of action. Enzyme inhibition can increase exposure to a medicine, while enzyme induction can reduce exposure by accelerating metabolism. Transport proteins, renal elimination and gastrointestinal absorption can also be involved.
Drug interactions are not automatically harmful. Some combinations are deliberately used because one medicine modifies another in a predictable and therapeutically useful way. Combination therapy is common in medicine, and clinicians sometimes prescribe several medicines precisely because their effects complement each other. The term interaction simply describes a change in effect or exposure caused by another substance; whether the interaction is clinically beneficial, irrelevant, manageable or dangerous depends on the particular medicines, doses, timing, patient characteristics and therapeutic objectives. This is why an interaction warning should not automatically be interpreted as meaning that two medicines can never be taken together.
Drug-drug interactions can involve prescription medicines, OTC medicines and multiple products purchased independently. A familiar practical problem occurs when a person takes an OTC preparation without realising that it contains an ingredient already present in a prescribed medicine. NHS guidance, for example, warns that paracetamol is contained in some cold and flu products, creating a risk of unintentionally taking duplicate paracetamol-containing medicines. Ibuprofen also has interactions with medicines such as anticoagulants, steroids and some antidepressants, while warfarin has interactions with several medicines and certain foods and supplements.
Food and drink can affect medicines through mechanisms such as altered absorption, metabolism or physiological effects. Grapefruit is a well-known example for certain medicines because constituents of grapefruit can affect enzymes involved in drug metabolism, although the relevance is medicine-specific rather than universal. Alcohol can increase sedation or other adverse effects with some medicines, while dietary vitamin K can affect anticoagulation with warfarin. Herbal products are also pharmacologically active and can interact with conventional medicines; St John's wort, for example, is listed by the NHS as an interaction concern with several medicines. Therefore, "natural" does not mean interaction-free.
The likelihood and severity of an interaction depend on factors such as dose, duration, age, kidney and liver function, genetics, other illnesses and the number of medicines being taken. Polypharmacy, meaning the use of multiple medicines, increases the number of possible combinations and can make medication review more important. Some interactions alter drug concentrations only slightly and have little practical significance, while others can produce major changes in blood pressure, heart rhythm, bleeding risk, sedation, seizure control or other physiological processes. Timing can sometimes reduce an interaction, but the correct timing is medicine-specific and should not be improvised without appropriate advice.
Preventing clinically important interactions involves maintaining an accurate list of all medicines, including prescription drugs, OTC products, herbal remedies, vitamins and supplements, and sharing that list with doctors, pharmacists and other relevant healthcare professionals. Patient information leaflets contain product-specific interaction information, while pharmacists can check combinations and identify potential problems. The NHS specifically advises people taking medicines such as apixaban, rivaroxaban and metoclopramide to tell their doctor or pharmacist about other medicines, herbal remedies, vitamins and supplements.
An interaction is distinct from a side effect and from an adverse drug reaction, although the concepts can overlap. A side effect is an unwanted or additional effect attributable to a medicine, whereas an interaction describes the modification of a medicine's effect or exposure by another substance. An interaction may cause a side effect, increase the severity of an adverse reaction or reduce therapeutic effectiveness.
The absence of a known interaction does not guarantee that an individual will experience no adverse effects, because medicines can cause reactions independently of interactions. Suspected clinically important reactions or safety concerns can be reported through the UK's MHRA Yellow Card system, which monitors suspected medicine safety problems.
