Before, With or After Food?

Introduction

The administration of oral medication with or without food is an important consideration for some drugs.

In other words, only some medicine should be taken with or without food for certain reasons. For the most of them, it is not a matter of concern.
Taking medication with an empty stomach is often defined as taking the medications half an hour (up to 1 hour) before food or two hours after food.

A drug should be taken with food because

Food reduces gastrointestinal side effects, such as allopurinol, NSAIDs
To reduce the risk of hypoglycemic episodes, such as sulfonylureas
To increase the extent of absorption of a drug, such as itraconazole, griseofulvin

A drug should be taken without food because

Food may delay or reduce the absorption of a drug and hence reducing effectiveness, such as flucloxacillin, rifampicin
To reduce side effects by reducing absorption of a drug, such as efavirenz

NOTE: There are cases where we know a drug is best taken at empty stomach for better efficacy, but taking it with food may be recommended to reduce gastrointestinal distress (e.g. frusemide). Another interesting systematic review will be on effects of food on pharmacokinetics of immediate release oral formulations of aspirin, dipyrone, paracetamol and NSAIDs. More examples will be discussed in Before, With or After Food: Case Studies.

With a clear understanding on the reasoning behind, it is easier for us to convince patients to follow the advice given.

Since it is actually easier to be take medicines consistently after foods (for better compliance), we tend to specify the need to take with empty stomach for a few medications where necessary and advise patients to take after food for the rest of medications.

Once I received a call from a patient, he was asking if it is okay to take syrup amoxicillin with empty food because the pharmacist at Emergency Department told him to take them after food but he forgot to do so.

So, what are your thoughts on this case?

Reference

Oral administration advice can be sought in a couple of ways, such as

Product leaflet
Lexicomp: under category of “Administration: Oral”
Micromedex Drug Reference: under category of “Administration”
British National Formulary 70 and later: under category of “Directions for administration”
MIMS pre- and post-prandial advice: available in MIMS gateway under “MIMS clinical table”

Below, I have provided a short list of medications that should be taken before or after food or consistently. Certainly, the list is not exhaustive.

List of Medications that Should be Taken Before Food

Abiraterone
Swallow tablets whole. Do not take abiraterone with food as this may increase the risk of serious side effects. Take it at least 2 hours after food and then wait at least 1 hour before eating again.
Ademetionine
Take 1 hour before or 2 hours after meals for better absorption of ademetionine and complete therapeutic effect.
Afatinib
Absorption decreased with high-fat meals. Take at least 1 hour before or 3 hours after meals.
Alendronate
Each oral tablet should be taken in the morning with at least 6 oz (180ml) of plain water (not coffee, juice, mineral water or milk) at least 30 minutes before consuming any food, supplements or medications. The patient should remain upright (sitting or standing) for at least 30 minutes.
Amisulpiride
Preferably taken before meals.
Ampicillin
Take 1 hour before or 2 hours after meals. Ampicillin can be given by mouth but less than half the dose is absorbed, and absorption is further decreased by the presence of food in the gut.
Benserazide + Levodopa (standard capsule, HBS capsule, dispersible tablet)
Best taken at least 30 min before or 1 hour after meals, whenever possible. GI discomfort which occurs mainly in the early stages of treatment may be controlled by taking with food or liquid or by increasing the dose slowly.
Bilastine
Administer 1 hour before or 2 hours after intake of food. Food decreases bioavailability by 33%.
Cabozantinib
Take on an empty stomach. Do not eat any food in the 2 hours before and 1 hour after taking the tablet.
Captopril
Administer 1 hour before meals.
Carbidopa + Levodopa
May be taken with meals if GI discomfort occurs.
Chlorambucil
Absorption is decreased when administered with food. Administer preferably on an empty stomach.
Cilostazol
Take on an empty stomach (half an hour before or 2 hours after meal) as food can increase the likelihood of side effects.
Cloxacillin
Administer with water 1 hour before or 2 hours after meals.
Deferasirox Dispersible Capsule
Administer at same time each day on an empty stomach, at least 30 minutes before food. Completely disperse tablets in water, orange juice, or apple juice (use 105 mL for total doses <1 g; 210 mL for doses ≥1 g); stir to form a fine suspension and drink entire contents. Rinse remaining residue with more fluid; drink. Avoid dispersion of tablets in milk (due to slowed dissolution) or carbonated drinks (due to foaming).
Dexketoprofen
Take 30 minutes before meals, especially for quick relief of acute pain.
Didanosine Capsule
Administer on an empty stomach at least 30 minutes before or 2 hours after eating. Food decreases AUC and Cmax.
Domperidone
In GI motility disorders, administer 15 to 30 minutes prior to meals and at bedtime if needed.
Efavirenz
Administer on an empty stomach. Dosing at bedtime is recommended to limit central nervous effects. Tablets must not be broken.
Entecavir
Take entecavir on an empty stomach as it is absorbed better this way.
Erlotinib
Bioavailability is increased with food. Take on an empty stomach at least 1 hour before or 2 hours after the ingestion of food.
Etoposide
Swallow capsules whole, on an empty stomach.
Ferrous fumarate
Ferrous salts are absorbed best if taken on an empty stomach 1 hour before, or 2 hours after, food. If it upsets your stomach it can be taken with or shortly after food. Avoid taking with tea or coffee.
Gemfibrozil
This medicine is absorbed best if you take it half an hour before food. However, if it upsets your stomach, take it with meals.
Hydrotalcite
Should be taken on an empty stomach: Take between meals and at bedtime.
Ibandronic acid
Tablets should be swallowed whole with plenty of water while sitting or standing; to be taken on an empty stomach at least 30 minutes (for most ibandronic acid tablets, 50 mg) or 1 hour (for Bonviva® tablets, 150 mg) before first food or drink (other than water) of the day, or another oral medicine; patient should stand or sit upright for at least 1 hour after taking tablet.
Imidapril
Administer about 15 minutes before meals. High fat meals significantly reduce absorption of imidapril.
Isoniazid
It is absorbed best if you take it on an empty stomach (1 hour before or 2 hours after a meal).
Itopride
Administer before meals.
Itraconazole oral liquid
Take on an empty stomach, at least 1 hour before food.
Ixazomib
Take at least 1 hour before or at least 2 hours after eating. High-fat meals decreased AUC by 28% and Cmax by 69%.
Lapatinib
Administer once daily on an empty stomach, 1 hour before or 1 hour after a meal at the same time each day. Systemic exposure of lapatinib is increased when administered with food (AUC three- to fourfold higher).
Lemborexant
Time to sleep onset may be delayed if taken with or soon after a meal.
Lercanidipine
This medicine is absorbed best if you take it at least 15 minutes before a meal.
Levothyroxine
Administer consistently in the morning on an empty stomach, at least 30 to 60 minutes before food. Alternatively, may consistently administer at night 3 to 4 hours after the last meal. Do not administer within 4 hours of calcium- or iron-containing products.
Mebeverine
Administer tablets ~20 minutes before meal. Tablets should not be chewed due to unpleasant taste.
Melphalan
Take tablets on an empty stomach, at least half an hour before, or 2 hours after, food.
Mercaptopurine
This medicine is absorbed best if taken on an empty stomach 1 hour before, or 2 hours after, food. However, it may be taken with food if needed.
Methotrexate
Methotrexate peak serum levels may be decreased if taken with food. Milk-rich foods may decrease methotrexate absorption. Management: Administer without regard to food.
Metoclopramide
Administer 30 minutes prior to meals and at bed time.
Nilotinib
Do not take nilotinib with food as this may increase the risk of serious side effects. Take it at least 2 hours after food and then wait at least 1 hour before eating again.
Pazopanib
Systemic absorption of pazopanib is increased when administered with food (AUC two-fold higher with a high fat[~50% fat] or low fat [~5%] meal.) Take on an empty stomach 1 hour before or 2 hours after a meal.
Penicillamine
This medicine is absorbed best if you take it on an empty stomach 1 hour before, or 2 hours after, a meal.
Perindopril
Administer prior to a meal. Perindopril active metabolite concentrations may be lowered if taken with food.
Phenoxymethylpenicillin
Administer around-the-clock to promote less variation in peak and trough serum levels. Take on an empty stomach 1 hour before or 2 hours after meals, to enhance absorption.
Propranolol
Propranolol serum levels may be increased if taken with food. Protein-rich foods may increase bioavailability; a change in diet from high carbohydrate/low protein to low carbohydrate/high protein may result in increased oral clearance. Management: Tablets (immediate release) should be taken on an empty stomach. Capsules (extended release) may be taken with or without food, but be consistent with regard to food.
Proton pump inhibitors (e.g. omeprazole, esomeprazole, pantoprazole, lansoprazole)
All PPIs are most effective if taken about 30 minutes before a meal because they inhibit only actively secreting proton pumps, and meals are the main stimulus of proton pump activity.
Repaglinide
When given with food, the AUC for repaglinide is decreased. Taking medications without eating may cause hypoglycaemia. Management: Administer within 30 minutes prior to a meal. If a meal is skipped, skip dose for that meal.
Rifampicin
Rifampicin is absorbed best if you take it at least half an hour before food.
Riluzole
A high-fat meal decreases absorption of riluzole (decreasing AUC by 20% and peak blood levels by 45%). Management: Administer at the same time each day, at least 1 hour before or 2 hours after a meal.
Risedronate
Take in the morning with a full glass of plain water at least 30 minutes before food or drink. Remain upright during this time and until after you eat. Do not take antacids, calcium, iron or mineral supplements within 2 hours of risedronate as they may interfere with its absorption.
Semaglutide
Take at least 30 minutes before the first food/drink/medication of the day with plain water only. Swallow whole, do not chew/crush/cut tablet.
Strontium
This medication is best taken at bedtime, at least 2 hours after eating, because food and drink (especially calcium-containing products such as milk) can reduce its absorption. Mix the granules in water and drink immediately.
Sucralfate
Administration of sucralfate and enteral feeds should be separated by 1 hour and for administration by mouth, sucralfate should be given 1 hour before meals.
Sulodexide
Administer without food.
Tetracycline
This medicine is absorbed best if you take it 1 hour before, or 2 hours after, a meal. Take with a large glass of water, and remain upright (do not lie down) for an hour after taking a tetracycline. This is to stop tablets or capsules sticking on the way to your stomach, and causing painful damage to the lining of your throat.
Thalidomide
Take at least 1 hour after food and preferably at night to avoid feeling sleepy during the day.
Tianeptine
Take immediately before meals. Tablets should not be broken, opened or chewed.
Trospium
Administer with water on an empty stomach at least 1 hour prior to meals. Administration with a fatty meal reduces the absoprtion and bioavailability of trospium.
Voriconazole
Take voriconazole either 1 hour before or 1 hour after food.
Zolpidem
Do not administer with or immediately after a meal (may delay onset).

List of Medications that Should be Taken Before Food or With a Light Meal

Deferasirox film coated tablet
Administer on an empty stomach or with a light meal (contains <7% fat content and ~250 calories)
Felodipine
Swallow tablet whole; tablet should not be divided, crushed or chewed. May be administered without food or with a small meal that is low in fat and carbohydrates. Compared to a fasted state, felodipine peak plasma concentrations are increased up to twofold when taken after a meal high in fat or carbohydrates.
Quetiapine controlled release tablet
ER tablet: Administer without food or with a light meal (≤300 calories), preferably in the evening. Swallow tablet whole; do not break, crush or chew.
Regorafenib
Swallow tablets whole with water after a low-fat meal (containing <600 calories and <30% fat).
Sorafenib
Bioavailability is decreased 29% with a high-fat meal containing 900 calories, 50% from fat (bioavailability is similar to fasting state when administered with a moderate-fat meal). Management: Administer without food, at least 1 hour or 2 hours after a meal.

List of Medications that Should be Taken With Food

Acarbose
Tablets should be chewed with first mouthful of food or swallowed whole with a little liquid immediately before food. The mechanism action of acarbose is actually to delay the digestion and absorption of starch and glucose.
Acetazolamide
Take tablets with meals to reduce the risk of stomach upset. However, it may cause an alteration in taste, especially carbonated beverage.
Acitretin
This medicine is absorbed best if taken with food (preferably with the main meal of the day). ~72% absorbed when given with food.
Alectinib
Administer with food. A high-fat, high calorie meal increased the combined exposure of alectinib plus its active metabolite M4 by 3.1-fold.
Alfuzosin
Take immediately after a meal for best absorption. Absorption is decreased 50% under fasting conditions.
Allopurinol
Take this medicine with or shortly after food to reduce the possibility of stomach upset.
All-Trans Retinoic Acid
This medicine is absorbed best if taken with food.
Alpelisib
Administer with food at approximately the same time each day.
Amantadine
Take with food to reduce stomach upset.
Amiloride
Administer with food or meals to avoid GI upset.
Amoxicillin and clavulanic acid
Administer with food to increase absorption and decrease stomach upset.
Artemether and Lumefantrine
Administer with a full meal for best absorption.
Atazanavir
Administer with food to enhance absorption.
Atovaquone and proguanil
This medicine is absorbed best if taken with food.
Baclofen
Take tablets with food to minimize stomach upset.
Bedaquiline
Administer with food. Administration with a standard meal (~22 g fat; 558 calories) increases bioavailability by approximately two-fold.
Bezafibrate
Take with or just after a meal.
Bosutinib
Administer with food. Swallow tablet whole; do not cut, crush or break.
Bromocriptine
Administer with food to decrease GI distress.
Cabergoline
Administer with meals to lessen the chance of nausea or stomach upset.
Capecitabine
Administer within 30 minutes after a meal. Food reduced the rate and extent of absorption of capecitabine.
Carbamazepine
Take with food to prevent stomach upset and carbamazepine serum levels may be increased if take with food and/or grapefruit juice.
Carvedilol
Administer with food to minimize the risk of orthostatic hypotension. Food decreases rate but not extent of absorption.
Cefuroxime
Bioavailability: Tablet: fasting, 37%; Following food, 52%. Cefuroxime axetil suspension is less bioavailable than the tablet (91% of the AUC for tablets).
Ceritinib
Administer with food. NOTE: Ceritinib was previously recommended to be administered at a higher dose on empty stomach, but should now be administered at 450 mg once daily with food. Similar drug exposure and less GI toxicity compared with dosing at 750 mg once dialy in a fasted state.
Chlortalidone
Administer as a single dose in the morning with food.
Cimetidine
Administer with meals.
Cinacalcet
Administer with food or shortly after a meal. Food increases bioavailability.
Clofazimine
Absorption: Variable and incomplete (45 to 62%); may be increased when administered with food.
Clomipramine
Administer with meals to decrease gastrointestinal side effects.
Corticosteroid (e.g. Dexamethasone, Hydrocortisone, Prednisolone)
Administer with meals to help prevent GI upset.
Cyproterone actetate
Take this medicine after a meal.
Dapsone
Administer with meals if GI upset occurs.
Darunavir
Administer with food. Absorption and bioavailability are increased when administered with food.
Diacerein
Take with or immediately after meals.
Dutasteride and tamsulosin
Take this medicine about 30 minutes after the same meal (e.g. breakfast) each day. Do not take it on an empty stomach as this may increase the risk of side effects, e.g. dizziness on standing.
Eperisone
Administer after meals.
Etravirine
Absoprtion increased 50% with food. Administer after meals.
Exemestane
Administer after a meal. AUC and Cmax were increased by 59% and 39%, respectively, when exemestane was administered with a high-fat breakfast.
Galantamine
Take with food.
Griseofulvin
Administer with a fatty meal to increase absorption.
Hydroxychloroquine
Take with food or a glass of milk to reduce stomach upset.
Imatinib
Administer with a meal and a large glass of water.
Isotretinoin
Administer with a meal. Absorption is enhanced with a high-fat meal.
Ivabradine
Administer with food. Bioavailability: ~40%; AUC increased 20% to 40% with food.
Lithium
Administer with meals to decrease GI upset
Lopinavir and ritonavir
Moderate- to high-fat meals increase the Cmax and AUC of lopinavir/ritonavir oral solution; no significant changes observed with oral tablets. Management: Take oral solution with food; take tablet with or without food.
Lovastatin
Administer with the evening meal.
Lubiprostone
Administer with food and water. Swallow whole; do not break or chew.
Lurasidone
Take this medicine with food to increase its absorption.
Mefloquine
Administer with food and with at least 240 ml of water.
Metformin
Administer with a meal to reduce GI upset.
Methoxsalen
To reduce nausea, capsules should be administered with food or milk.
Metoprolol
Food increases absorption. Metoprolol serum levels may be increased if taken with food. Management: Take immediate release tartrate tablets with food; extended release succinate can be taken with or without food.
Midostaurin
This medicine is absorbed best if taken with food; this also helps reduce nausea and vomiting.
Moclobemide
Moclobemide is best taken with, or soon after, food.
Neratinib
Administer orally with food at approximately the same time each day. Swallow tablets whole; do not crush, chew or split tablets.
Nintedanib
Administer with food. Swallow capsules whole with liquid; do not open, chew or crush (bitter taste). Food increases exposure ~20% and delays absorption.
Nitrofurantoin
Administer with meals to improve absorption and decrease adverse effects.
NSAIDs (e.g. diclofenac, ibuprofen, indomethacin, ketoprofen, mefenamic acid, naproxen, piroxicam)
Administer with food to reduce GI upset, but food may reduce effectiveness.
Orlistat
Administer during or up to 1 hour after each meal contain containing fat; separate dose by at least 2 hours form multivitamin containing fat-soluble vitamins. Omit dose if a meal is missed or contains no fat.
Palbociclib
Swallow capsule whole; do not chew, crush or open them. Take with food at the same time each day.
Pancreatin
Administer with meals or snacks and swallow whole with a generous amount of liquid.
Pentoxyfylline
Take with food to reduce stomach upset.
Phosphate binding agent (e.g. Lanthanum, Sevelamer)
Take with meals. If you miss a meal, then skip your dose.
Pinaverium bromide
Do not crush, chew, or suck tablet. Should be taken with a glass of water with meals or snacks. The tablet should not be swallowed when in the lying position or just before bedtime.
Piribedil
Should be taken with food; take at the end of a main meal.
Posaconazole suspension
Suspension must be administered with or within 20 minutes of a full meal. Increased bioavailability when administered with a meal.
Potassium Chloride
Oral dosage forms should be taken with meals and a full glass of water or other liquid to minimize the risk of GI irritation.
Primaquine
Take with food to avoid stomach upset and pain.
Probenecid
Administer with food to minimize GI effects.
Propafenone
Administration of food with single-dose propafenone increased propafenone serum concentrations and bioavailability; however, with multidose administration, propafenone bioavailability was not significantly different between fed and fasted state. Management: Administer without regard to meals.
Pyridostigmine bromide
Should be taken with food.
Rilpivirine
Take rilpivirine with a main meal for best absorption.
Rivaroxaban
To take rivaroxaban 15 mg or 20 mg tablets with food.
Rivastigmine
Administer with meals. Food delays absorption by 90 minutes, lowers Cmax by 30% and increases AUC by 30%.
Rufinamide
Administer with food. Tablets may be swallowed whole, split in half, or crushed. Food increases the absorption of rufinamide.
Silodosin
AUC decrease by 4% to 49% and Cmax decreased by ~18% to 43% with moderate calorie/fat meal. Management: Take once daily with a meal.
Sodium valproate
Take with food to reduce stomach upset.
Sulfasalazine
Take tablets with food to reduce stomach upset.
Sulfonylureas (e.g. glibenclamide, gliclazide, glimerpiride, glipizide, tolbutamide)
Take with food to minimise risk of hypoglycaemia.
Tenofovir Alafenamide
Administer with food.
Ticlopidine
Ticlopidine bioavailability may be increased (20%) if taken with food. High-fat meals increase absorption, antacids decrease absorption. Take with food to reduce stomach upset.
Trimetazidine
Administer with food.
Valganciclovir
Coadministration with a high-fat meal increased AUC by 30%. Management: valganciclovir should be taken with meals.
Venetoclax
Administer with a meal and water at approximately the same time each day. Swallow whole; do not crush, chew, or break prior to administration.
Venlafaxine
Administer with food to minimize stomach upsets.
Vericiguat
Administer with food. Bioavailability is increased when taken with food.(5)
Ziprasidone
Administer capsule with food (≥500 calories). Swallow capsule whole; do not open, crush, or chew capsules.

List of Medications that Should be Taken Consistenly With or Without Food

Aliskiren
Administer at the same time daily with or without a meal, but consistent administration with regards to meals is recommended; high-fat meal reduces absorption.
Amiodarone
Administer consistently with regard to meals. Take in divided doses with meals if GI upset occurs or if taking large daily dose (≥1000 mg). If GI intolerance occurs with single-dose therapy, use twice daily dosing.
Cyclosporine
Administer this medication consistently with relation to time of day and meals.
Danazol
Administer consistently with regards to food; either always administer with food or administer on an empty stomach. Food delays time to peak levels. A high-fat meal increases plasma concentration and extent of availability.
Digoxin
Administer consistently with relationship to meals; avoid concurrent administration (i.e. administer digoxin 1 hour before or 2 hours after) with meals high in fiber or pectin and with drugs that decrease oral absorption of digoxin.
Everolimus
May be taken with or without food; to reduce variability, take consistently with regard to food.
Labetalol
Administer without regard to food; however, the absolute bioavailability of labetalol is increased when administered with food. Administer in a consistent manner with regards to meals.
Paliperidone
Do not cut, crush or chew tablets; swallow them whole. Take them the same way each day (always with food or always on an empty stomach).
Propranolol
Propranolol serum levels may be increased if taken with food. Protein-rich foods may increase bioavailability; a change in diet from high carbohydrate/low protein to low carbohydrate/high protein may result in increased oral clearance. Management: Tablets (immediate release) should be taken on an empty stomach. Capsules (extended release) may be taken with or without food, but be consistent with regard to food.
Sirolimus
Ingestion with high-fat meals decrease peak concentrations but increases AUC by 23% to 35%. Management: Take consistently (either with or without food) to minimize variability.
Spironolactone
Administer with or without food; however, administer consistently with respect to food. Food increases the bioavailability of unmetabolized spironolactone by ~90% to 95%.
Tacrolimus
Administer with or without food; be consistent with timing and composition of meals if GI intolerance occurs and administration with food becomes necessary.
Temozolomide
Administer consistenly with respect to food (either consistently fasting or nonfasting). Administer on an empty and/or at bedtime to reduce nausea and vomiting.
Theophylline
Extended release: Administer consistently with or without food (to maintain a consistent drug level); do not chew or crush tablets; may split tablet if scored. An intact matrix tablet may pass in stool.

Relevant Links

Timing of medication (morning, afternoon or night) is discussed at a separate post.

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