Drug-Drug Interactions

Mechanisms of Drug Interactions

• Pharmacokinetic: altered drug concentrations.
• Pharmacodynamic: altered drug effect.
• Pharmaceutic: altered drug physicochemical properties.
• Advice is available from the Ward Pharmacists or Medicines Information ( 80900).

Pharmacokinetic (affecting drug concentrations)

• Interactions may relate to altered oral bioavailability (including first pass metabolism) or clearance.
• Enzyme inhibition (common) may increase substrate concentrations.
• Enzyme induction may decrease substrate concentrations.
• Transporters are subject to competition that may alter substrate concentrations (e.g., competition for renal excretion or for gut transporters). See Drug transporters for more information.
• Prodrugs may be particularly affected by interactions if production of the active metabolite is affected (e.g., codeine to the active metabolite morphine). See Prodrugs and Dosing for more information.

Pharmacodynamic (affecting drug action)

• These are often predictable from respective additive or opposing drug actions.
• May increase desired response (e.g., two antihypertensive drugs).
• May decrease desired response (e.g., beta-agonist with a beta-blocker).
• May increase adverse reactions (e.g., benzodiazepines with opioids).
• May decrease adverse reactions (e.g., antiemetics with opioids).

Pharmaceutic (affecting the drug itself)

• These are mainly important in relation to compatibilities (e.g., intravenous drug infusions and diluents, nasogastric feeds, and phenytoin).

  E.g., phosphate orally (avoid calcium, iron, magnesium and indigestion remedies (e.g., Acidex™) within two hours of oral phosphate dose as these preparations may form a complex with phosphate and prevent absorption).

• For intravenous infusion compatibility information, see Notes on Injectable Drugs (NOIDS).

Topic Code: 93247

must be prescribed or recommended by a consultant.