Drug Interactions: Pharmacology and Patient Safety

Interactions

· Checking for drug interactions and why this is important . It's important to always check for drug interactions because drug interactions can cause harm to patients. . Some common examples of interactions are included in this lesson but they are NOT exhaustive, always check, a key resource for this is Stockley's! . Don't forget to consider drug-food/drink interactions and herbal/alternative medicine interactions or recreational drug interactions.

Drug-Herbal Medicine Interactions

· Drug-herbal medicine interactions . St. John's Wort . Always check with patients if they are taking any herbal remedies and then check whether these herbal medicines interact with anything else they are taking (one of the resources for this is Stockley's/Stockley's Herbal Medicine Interactions). . One example is St John's Wort which is a herbal medicine used for the treatment of depression and interacts with lots of medicines.

Drug-Disease Interactions

· Drug-disease interactions · Cautions and contraindications . Sometimes the term drug-disease interactions is used. This is essentially cautions and contraindications: . Cautions: when a drug can be used in a patient with another specific medical condition but this has to be done with caution for example with additional monitoring. (One example NOT exhaustive: tricyclic antidepressants must be used with caution in patients with a history of ischaemic heart disease). . Contraindications: When a drug must not be used in patients with another specific medical condition. (One example NOT exhaustive: tricyclic antidepressants must not be used in the acute phase after a heart attack).

Drug-Food/Drink Interactions

· Drug-food/drink interactions · Drug and food interactions . The next section of this lesson is about drug-food/drink interactions. . You can check the following resources to see whether a drug interacts with food or drink:

• Stockley's Drug Interactions also includes food-drug interactions

. Also the Cautionary and Advisory labels that appear on dispensing labels and in the BNF MAY include warning about interactions with food but NOT ALWAYS

• Summary of product characteristics (SPC) on the following website: https://www.medicines.org.uk/emc#gref

Monoamine Oxidase Inhibitors (MAOIs) and Food/Drink

. Monoamine Oxidase Inhibitors (MAOIs) interact with food and drink . Cheese, wine and aged foods interact with MAOIs . MAOIs (Monoamine Oxidase Inhibitors) are a type of antidepressant (specialist use only). Examples include: Phenelzine, moclobemide, tranylcypromine, isocarboxazid. Linezolid is an antibiotic which is also classed as an MAOI. . MAOIs interact with tyramine-containing foods, MAOI suppresses metabolism of catecholamines and tyramine. Tyramine is indirectly sympathomimetic and liberates stored catecholamines including norepinephrine, causing potentially fatal hypertensive crisis, arrhythmias, hyperthermia, cerebral haemorrhage, severe headache. . This is sometimes known as the "Cheese Reaction"! . Patients on MAOIs must avoid foods and drinks which are aged, stale, fermented, overly ripe, or pickled as these contain a high tyramine content. Examples include (NOT exhaustive):

• Drinks: undistilled alcoholic beverages, wine, beer, lager, excessive amounts of tea and coffee.

. Foods: chocolate and yeast-containing foods, mature cheeses, yeast extracts, fermented soya bean products such as soy sauce, aged meat, aged fish, aged poultry, offal, game, yogurt, sour cream, cured meats, caviar, sauerkraut, miso soup, Oxo, Bovril, Marmite, brewer's yeast, broad beans and excessive amounts of chocolate. . Interaction persists for up to 2 weeks after treatment with MAOIs is stopped.

• Patients must also avoid alcohol where possible.
• Patients must be counselled on this.

Grapefruit and Medicine Interactions

· Grapefruit or grapefruit juice interacts with many medicines · Grapefruit can interact with lots of medicines · Grapefruit juice interacts with lots of different drugs (over 700 drugs according to Stockleys). . Many drugs are metabolised by the isoenzyme CYP3A4, grapefruit juice can block the action of CYP3A4 leading to higher levels of the drug in the bloodstream. . A common interaction is with statins (used to lower cholesterol), particularly simvastatin and lovastatin, amiodarone (for cardiac arrythmmias), clopidogrel (used post stroke and for cardiovascular disease), azithromycin (an antibiotic) but this is not exhaustive, there are lots more interactions between other drugs and grapefruit juice.

Coumarins and Food/Drink

. Coumarins (warfarin, phenindone and acenocoumarol) and food and drink . Warfarin and anticoagulant book should be provided to all patients taking warfarin or other anticoagulants . Coumarins such as warfarin, phenindione and acenocoumarol are used to thin the blood to prevent blood clots including stroke and venous thromboembolism. · Activity: Look in the BNF or Stockleys to make sure you know how food and drink can affect warfarin therapy, including:

• Foods and drinks high in vitamin K e.g. salad and green vegetables reducing efficacy of warfarin (reducing INR)
• Fermented soya products
• Cranberry
• Alcohol

Bisphosphonates and Food/Drink

· Bisphosphonates and food and drink · Bones showing signs of osteoporosis . Make sure you know the following: . Bisphosphonates such as alendronic acid, risedronate and sodium clodronate are used to prevent bone fractures. . Bisphosphonates can form complexes with a number of polyvalent metallic ions in food (e.g. Al3+, Ca2+, Fe, Mg2+), which can impair absorption of bisphosphonates. . Bisphosphonates should be taken after an overnight fast and patients should wait at least 30 minutes after taking bisphosphonates before taking any other drug or food, and bisphosphonates should be taken with plain water only. This is because of the interaction with food. . Bisphosphonate tablets should be swallowed whole and oral solution should be swallowed as a single dose. Doses should be taken with plenty of water while sitting or standing, on an empty stomach at least 30 minutes before breakfast (or another oral medicine); patient should stand or sit upright for at least 30 minutes after administration. The reason bisphosphonates need to be taken with plenty of water whilst the patient is upright is to reduce the risk of ulcers and bleeding.

Dairy Products and Medicines

· Dairy products and medicines · Dairy products interact with some medicines . Sometimes consuming dairy products can reduce the absorption of medicines:

• Tetracyclines (a type of antibiotic e.g. doxycycline, tetracycline, demeclocycline) should be taken one hour before or two hours after meals, and not taken with milk because it binds calcium and iron, forming insoluble chelates reducing its bioavailability
• Quinolones (a type of antibiotic e.g. ciprofloxacin and levofloxacin): Milk and yoghurt reduce the concentrations of ciprofloxacin by up to about 50%. Patients should be advised not to take dairy products within 1 to 2 hours of ciprofloxacin
• Bisphosphonates: The absorption of bisphosphonates is reduced by milk and calcium-rich foods.

. This is NOT exhaustive .... Some medicines DO HOWEVER need to be taken with food to reduce the risk of adverse drug reactions . Some medicines do need to be taken with food however to reduce the risk of adverse drug reactions (side-effects). Make sure you know the following examples:

• NSAIDS (including ibuprofen, aspirin, naproxen, diclofenac and others) need to be taken with food to protect the stomach as NSAIDs can cause stomach ulcers (peptic ulcers) and Gl bleeding.
• Corticosteroids need to be taken with food to protect the stomach as corticosteroids can cause stomach ulcers (peptic ulcers) and Gl bleeding.
• Sulfonylureas (e.g. gliclazide, glimepiride and glibenclamide: used for type 2 diabetes) need to be taken with food to reduce the risk of hypoglycaemia. Metformin is also used for type 2 diabetes and is often taken with sulfonylureas but metformin does not cause hypoglycaemia.

. This is NOT exhaustive ...

Drug and Alcohol Interactions

· Drug and alcohol interactions · Image of alcoholic drinks . Here are some examples of clinically-significant drug-alcohol interactions (NOT exhaustive):

• Patients on MAOIs (a type of antidepressant) should not drink tyramine-rich drinks such as beers, lagers, wines and undistilled alcoholic drinks. In addition, the hypotensive effects of the MAOIs can sometimes be exaggerated in a few patients by alcohol.

. Metronidazole and tinidazole (a type of antibiotic) and alcohol: "disulfiram reaction". Warn all patients of the potential effects (flushing and tachycardia). Note that a reaction can occur up to 72 hours after stopping metronidazole. · Alcohol and methotrexate or leflunomide (drugs used for autoimmune diseases, methotrexate is also used in cancer and other treatment) increased risk of methotrexate/leflunomide-induced hepatic cirrhosis and fibrosis. . Alcohol can increase the sedative effects of other sedative drugs.

Drug-Tobacco Interactions

· Drug-tobacco interactions · No Smoking Sign · Smoking can interact with some medicines. Examples include reduced drug concentrations caused by smoking:

• Theophylline and aminophylline (used for asthma and COPD): cleared more quickly in those who use tobacco or who are heavily exposed to passive smoking. Higher aminophylline and theophylline doses might be needed in heavy smokers. It might be prudent to monitor theophylline concentrations. On stopping smoking, gradual dose reductions might be necessary.
• Clozapine (an antipsychotic): Tobacco smoking reduces clozapine concentrations. Clozapine doses need to be increased in patients who smoke. Patients who stop smoking will therefore also probably need a dose reduction within 2 to 4 weeks.
• Other drugs interact with smoking: Combined hormonal contraceptives: Smoking increases the risk of cardiovascular disease in women given oral combined hormonal contraceptives.

. This is NOT exhaustive ...

Adverse Drug Reactions

. Where can I find out what adverse drug reactions or side-effects a drug can cause? . 2 examples of places to look to find out what adverse drug reactions or side-effects a drug has are:

• Undesirable effects section of the SPC on the following website: https://www.medicines.org.uk/emc#gref
• BNF side-effects section in each drug monograph.

. Activity: Think of a drug and have a look at the SPC and the BNF to find out what side-effects it has.