skip to main content
ukmla 2026

Drug Interactions

Clinically significant modifications of drug effect by another drug, food, or substance — classified as pharmacokinetic (affecting absorption, distribution, metabolism, excretion) or pharmacodynamic (additive, synergistic, or antagonistic effects)

Review date
reviewed 2026-04-05
Reading time
5 min read
Author
Dr Kola Tytler MBBS CertHE MBA MSt MRCGP
Clinical Pharmacologycommonchronic
On this page
Condition details
Clinical Pharmacology
common
5 min read
reviewed 2026-04-05
practice ukmla questions →

About This Page

This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.

Key points

  • Pharmacokinetic: one drug alters the absorption, distribution, metabolism, or excretion of another
  • Pharmacodynamic: two drugs act on the same physiological system producing additive, synergistic, or antagonistic effects
  • CYP450 INDUCERS (reduce drug levels): Rifampicin, Phenytoin, Carbamazepine, St John’s Wort, Phenobarbital — mnemonic: "CRAP GPS"
  • CYP450 INHIBITORS (increase drug levels): Ciprofloxacin, Erythromycin/clarithromycin, Fluconazole/ketoconazole, Grapefruit juice, Isoniazid, Sodium valproate, Cimetidine — mnemonic: "ODEVICES"
  • Warfarin is the most commonly examined drug for interactions — affected by dozens of drugs and foods

Overview

Drug interactions occur when the effect of one drug is modified by another drug, food, drink, or environmental chemical. Pharmacokinetic interactions alter the concentration of a drug reaching its site of action (e.g. enzyme inhibition increasing drug levels, enzyme induction decreasing them). Pharmacodynamic interactions alter the pharmacological effect without changing drug concentrations (e.g. additive CNS depression from opioids + benzodiazepines). Clinically significant interactions are most important with narrow therapeutic index drugs (warfarin, digoxin, lithium, phenytoin, theophylline, ciclosporin) where small changes in level have major clinical consequences.

Epidemiology

Drug interactions contribute to approximately 20–30% of all ADRs. Risk increases with polypharmacy — patients on 5+ drugs have a ~50% probability of a clinically important interaction; on 8+ drugs this rises to ~100%. Elderly patients, those with hepatic/renal impairment, and those on narrow therapeutic index drugs are at highest risk. CYP450-mediated interactions are the most common type of pharmacokinetic interaction and the most frequently tested in exams.

Clinical Features

Symptoms
Increased drug effect/toxicity (e.g. bleeding from warfarin + NSAID/macrolide)
Decreased drug effect/treatment failure (e.g. OCP failure with rifampicin, transplant rejection with carbamazepine reducing ciclosporin levels)
QT prolongation and arrhythmias (e.g. macrolide + antipsychotic, amiodarone + any QT-prolonging drug)
Serotonin syndrome (SSRIs + MAOIs/tramadol/linezolid): agitation, clonus, hyperthermia, autonomic instability
Hyperkalaemia (ACEi + spironolactone + potassium supplements)
Signs
Signs depend on the specific interaction and drugs involved

Investigations

First-line
BNF interaction checkerCheck ALL new prescriptions against existing medications — interactions are graded by severity
Drug levelsMonitor levels of narrow therapeutic index drugs when interacting drugs are started/stopped (warfarin INR, digoxin, lithium, phenytoin)
Second-line
ECGIf QT prolongation risk — measure QTc before and after starting interacting drugs
U&EsMonitor potassium when combining drugs that affect renal potassium handling

Management

BNF Drug Interactions guidance
1
Prevention
  • Always check the BNF appendix on interactions before prescribing
  • Be particularly cautious with narrow therapeutic index drugs
  • Use electronic prescribing systems with interaction alerts where available
  • Ask about OTC medications, herbal remedies (St John’s Wort), and grapefruit juice
2
Management of identified interaction
  • Avoid the combination if possible — choose an alternative drug without the interaction
  • If combination essential: adjust doses, increase monitoring frequency (drug levels, INR, ECG)
  • Counsel the patient about symptoms to watch for
  • Document the interaction and monitoring plan in the clinical record

Complications

  • Drug toxicity: From enzyme inhibition increasing levels of a narrow TI drug
  • Treatment failure: From enzyme induction reducing levels below therapeutic range
  • Life-threatening arrhythmias: From QT prolongation caused by drug combinations
  • Serotonin syndrome: Potentially fatal — from serotonergic drug combinations
UKMLA Exam Tips
  • 1ENZYME INDUCERS (reduce drug levels, increase clearance): Rifampicin, Phenytoin, Carbamazepine, Barbiturates, St John’s Wort, Chronic alcohol
  • 2ENZYME INHIBITORS (increase drug levels, cause toxicity): Erythromycin, Clarithromycin, Ciprofloxacin, Fluconazole, Ketoconazole, Isoniazid, Cimetidine, Grapefruit, Acute alcohol, Sodium valproate
  • 3Rifampicin is the MOST POTENT enzyme inducer — reduces efficacy of warfarin, OCP, ciclosporin, antiretrovirals
  • 4Warfarin + macrolide (erythromycin/clarithromycin) = increased INR = bleeding risk
  • 5SSRI + MAOI = serotonin syndrome. NEVER prescribe together. 2-week washout after stopping MAOI
  • 6Methotrexate + trimethoprim = myelosuppression (both are folate antagonists)
  • 7Grapefruit juice inhibits CYP3A4 in the gut wall — increases levels of statins, ciclosporin, calcium channel blockers

Put your reading into practice

Topic-specific question practice is not linked for this article yet.

Choose UKMLA questions from the existing bank. General exam practice covers your selected topics; it is not filtered to this article. Your usual question-bank access applies.

Choose UKMLA practice

After your session, return to this section to revisit the reading and choose your next review.

Verified Sources & References

BNF — Drug interactions
Your learning path

Save your place and choose what comes next

sign in to save your learning

Clinical Pharmacology · Article 3 of 16