Before, With or After Food: Case Studies

Introduction

Following reading of Before, With or After Food, let's now examine some drugs in particular.



Gliclazide - Before or After Food

All sulfonylureas are absorbed by the intestine, but each one with its specific absorption time and bioavailability.

  • Hyperglycaemia can reduce the absorption of sulfonylureas as it impairs intestinal motility, thereby reducing the absorption of all orally administered drugs.
  • For this reason, sulfonylureas should be taken 10-30 minutes before meals to optimize their absorption.

However, sulfonylureas possess high risk of hypoglycaemia, hence many references recommend taking sulfonylureas with food, including Australian Medicines Handbook, British National Formulary, Lexicomp and MIMS Malaysia.

  • Patients who take sulfonylureas with empty stomach should be aware of the symptoms of hypoglycaemia and how to manage it. The symptoms of hypoglycaemia include cold sweat, palpitations, hunger, fatigue and dizziness.



Rivaroxaban - With Food

A 2013 study found that the bioavailability of rivaroxaban is affected by food for 15 mg and 20 mg doses.
  • Independent of food and formulation, pharmacokinetic parameters of doses up to 10 mg rivaroxaban were dose proportional and had high oral bioavailability (≥ 80%).
  • Under fasting conditions, pharmacokinetic parameters of 15 mg and 20 mg rivaroxaban increased with dose but were less than dose proportional. However, when taken with food, high bioavailability (≥ 80%) of these doses was achieved independent of formulation.

In July 2019, MHRA has received a small number of reports suggesting lack of efficacy (thromboembolic events) in patients taking 15 mg or 20 mg rivaroxaban on an empty stomach.

  • Healthcare professionals are advised to remind patients to take 15 mg or 20 mg rivaroxaban tablets with food.
  • Doses of 2.5 mg and 10 mg may be administered without regard to meals.



Lenalidomide - With or Without Food

Depending on references, you may come across conflicting recommendations for lenalidomide oral administration.

  • Australian Medicines Handbook 2021 suggests patients to take lenalidomide at least an hour before or 2 hours after food.
  • Meanwhile, Lexicomp highlights that it may be administered with or without food.
In terms of pharmacokinetics, oral absorption of lenalidomide was rapid and the maximum plasma concentration was observed approximately 1 h post-dose.
  • Co-administration with a high-fat meal reduced the area under the concentration-time curve and Cmax by approximately 20 and 50 %, respectively, and delayed time to Cmax by 1.63 h.

However, phase III trials were dosed without regard to food. Although food reduced bioavailability, this was not considered clinically relevant.

  • The terminal elimination half-life was 3-4 h at doses up to 50 mg and was not affected by food.
  • The AUC and Cmax were proportional to lenalidomide single doses (5-400 mg), and total and renal clearance were dose-independent.



Levodopa and Benserazide - Preferably Empty Stomach

When I was filling medication at outpatient pharmacy, I received a phone call from my colleague, asking if patient should administer Madopar before or after food.

Below are my recommendations:

  • The drug is best taken at least 30 minutes before or 1 hour after meals, wherever possible.
  • However, if the patient is experiencing GI discomfort (which occurs mainly in the early stages of treatment), he or she may administer with or immediately after meals (BUT avoiding high protein diets).

Based on the information in Lexicomp, food reduces the extent of levodopa absorption by 15% and peak plasma concentration by 30%.

  • High protein diets have the potential to impair levodopa absorption; levodopa competes with certain amino acids for transport across gut wall or across the blood-brain barrier.



Alendronate and Levothyroxine

Here is what we normally counsel patient on these therapies individually:
  • Alendronate: Each oral tablet should be taken in the morning with a glass of water (NOT coffee, juice, mineral water or milk), at least 30 minutes before consuming any food, supplements of medications. The patient should remain upright (sitting or standing) for at least 30 minutes.
  • Levothyroxine: Administer consistently in the morning on an empty stomach, at least 30 to 60 minutes before food. Do not administer within 4 hours of calcium- or iron-containing products.

If a patient is on both alendronate and levothyroxine, there is a potential for drug interaction.

  • In other words, taking these medications at the same time could affect the absorption of both drugs.

To be on the safe side, I would recommend either

  • Taking alendronate first, followed by levothyroxine at least 30 minutes later. This is because alendronate is only taken once a week, so you would only need to wake up 30 minutes earlier once a week.
  • Taking alendronate and levothyroxine at different times of the day. For example, you could take alendronate in the morning on an empty stomach and levothyroxine at night 3 to 4 hours after the last meal.

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