

Drug-Food Interactions
The timing of medicine administration with regard to food is not important for most medicines.
Limit advice about food to those few medicines where the interaction is clinically relevant.
Pharmacokinetics
Food effects on drug oral bioavailability and clearance
Food may alter the oral bioavailability and clearance of drugs. (See Pharmacokinetic Table for individual medicines).
Absorption
- Extent of absorption is more important than rate of absorption.
- The extent of absorption is reduced by divalent/trivalent ions (e.g. calcium) that may chelate some drugs (e.g. fluoroquinolones, tetracyclines).
- The rate of absorption is reduced by fatty meals, and usually increased by liquid meals.
- Drug transporters are involved with absorption and some foods alter this (e.g. folate reduces methotrexate absorption).
- Where food impact on absorption or other aspect of medicine use is clinically relevant, specific directions are given in the Pharmacokinetic Table in the bioavailability column or under additional points.
- Example medicines to take without food (wo) include:
alendronate and
tacrolimus.Clinically relevant decrease in tacrolimus absorption when taken with food.
Clinically relevant decrease in alendronate absorption when taken with food.
- Example medicines to take with food (w) include:
doxycycline,
itraconazole, and
sprionolactone.Food significantly increases spironolactone bioavailability.
Food significantly increases itraconazole bioavailability.
Food does not significantly impact absorption of doxycycline – advice to take with food reduces the risk of oesophageal adverse effects.
First pass (pre-systemic) metabolism
- First pass metabolism comprises gut and hepatic metabolism, e.g. by CYP3A.
- Some drugs, especially those subject to high metabolic clearance (e.g. lipid-soluble beta-blockers such as metoprolol) undergo significant first pass metabolism, and therefore have low oral bioavailability.
- Grapefruit (furanocoumarins) may increase concentrations of susceptible drugs mostly by inhibiting first pass metabolism by gut CYP3A. The increase may be significant (e.g. simvastatin and concomitant grapefruit leads to over 5-fold concentrations).
Clearance
- High protein meals, barbequed foods, and cruciferous vegetables (e.g. broccoli, cabbage) can induce hepatic CYP1A2 and reduce concentrations of substrates for this enzyme (e.g. clozapine and theophylline - see CYP1A2).
Drug effects on food oral bioavailability and clearance
Drugs may alter the oral availability and clearance of foods. See pharmacokinetic table.
Absorption
- Orlistat, bile-acid sequestrants (e.g. colestyramine) – decrease absorption of fat-soluble vitamins (A, D, E, K).
Clearance
- Enzyme inducers (e.g. carbamazepine, phenytoin) – increase vitamin D metabolism, and thus clearance, causing reduced vitamin D concentrations resulting in osteomalacia.
Pharmacodynamics
Food can alter the effects of drugs
- Liquorice (glycyrrhizic acid) in large amounts (> 20 g/day for two or more weeks or less over months to years) is similar to aldosterone. It causes fluid retention and hypertension. This can antagonise the effects of antihypertensive medications.
- Foods high in vitamin K (e.g. liver, avocado, leafy green vegetables, egg yolk, lentils) can decrease INR and antagonise the anticoagulation effect of warfarin.
- Alcohol can cause sedation and respiratory depression. This can potentiate the effect of CNS depressant medications (e.g. antihistamines, benzodiazepines).
Drugs can alter the effects of food
- Non-selective Monoamine Oxidase Inhibitors (MAOIs) (e.g. tranylcypromine, phenelzine) have a ‘cheese reaction’ with tyramine-containing foods (e.g. aged cheese, meat or yeast extracts, processed meats, and fish). This may lead to a hypertensive crisis. This is less likely with selective MAOIs (e.g. moclobemide and selegiline).
Topic Code: 93256