Med Administration: Timing is Everything

Full update June 2018

You may have heard the saying “timing is everything.” This is certainly true in the pharmacy world for timing the administration of medications. It’s advisable to take most meds at about the same time(s) each day, but some meds must be given at more specific times. Taking such meds at the wrong time can cause them to be less effective or more likely to cause unwanted side effects.

Taking medications regularly can be tough for some patients, let alone taking medications at specific times. But this is important, and with a little help, patients may be able to improve their ability to stick with specific schedules. Pharmacy technicians can use the information in this technician tutorial to help patients take their medications at the right times.

Med Adminstration

Felicity Adams is a 62-year-old female who brings in a new prescription for alendronate 70 mg tablets with directions to take one tablet every week. This is a new prescription for her, and she has a couple of additional meds she takes regularly including lisinopril and simvastatin.

Which meds should be TAKEN WITH FOOD OR MEALS?

Medications should be taken with food or meals usually for one of two reasons: food helps to prevent some side effects of the med, or food in the stomach is required for the best/quickest absorption of the drug into the bloodstream.

Meds that may be taken with food to prevent side effects (stomach upset, nausea, etc) include: amoxicillin/clavulanate (Augmentin [U.S.], Clavulin [Canada]); corticosteroids such as prednisone; NSAIDs such as ibuprofen or naproxen; and opioids such as codeine or oxycodone. It’s also best for patients who take niacin to take it with food to help avoid stomach upset as well as flushing.

Meds that may be taken with food to improve absorption include: some antibiotics such as amoxicillin/clavulanate, cefuroxime axetil oral suspension (Ceftin), etc; the antidepressant vilazodone (Viibryd); the antipsychotic ziprasidone (Geodon [U.S.], Zeldox [Canada]); HIV meds such as etravirine (Intelence) and ritonavir (Norvir); and the cholesterol med lovastatin.

Interestingly, the blood thinner rivaroxaban (Xarelto) must be taken with food at higher doses only. It comes in 10, 15, and 20 mg tablets, but only the 15 and 20 mg doses must be taken with food. This is because absorption is impacted more by food as the dose gets larger.

Several hepatitis C medications must be taken with food to maximize absorption. These include paritaprevir/ritonavir/ombitasvir/dasabuvir (Viekira Pak [U.S.], Viekira XR [U.S.], Holkira Pak [Canada]), paritaprevir/ritonavir/ombitasvir (Technivie), glecaprevir/pibrentasvir (Mavyret [U.S.], Maviret [Canada]), and sofosbuvir/velpatasvir/voxilaprevir (Vosevi).

Which meds should be TAKEN ON AN EMPTY STOMACH?

Medications that should be taken on an empty stomach are usually those that have reduced absorption through the stomach lining and into the blood when there’s food in the stomach. Generally, if a medication must be given on an empty stomach, it’s best to take it at least one hour before or two hours after a meal.

Meds that should be taken on an empty stomach include: some antibiotics such as ampicillin, azithromycin extended-release (Zmax [U.S.]), dicloxacillin (U.S.), penicillin VK, rifampin (Rifadin), tetracycline; the antifungal voriconazole (Vfend); the calcium channel blocker nisoldipine (Sular [U.S.]); and HIV meds such as didanosine (Videx), efavirenz (Sustiva), and indinavir (Crixivan).

Note that some meds are affected by dairy products specifically. This is because minerals such as calcium, which are found in dairy products, can actually bind to the med and reduce its effectiveness. Examples of meds that should not be taken at the same time as dairy products (e.g., milk, cheese) include ciprofloxacin and tetracycline.

Proton pump inhibitors, such as omeprazole (Prilosec OTC [U.S.], Olex [Canada]), esomeprazole (Nexium), lansoprazole (Prevacid), etc, should usually be taken 30 to 60 minutes before meals (before breakfast if dosed once daily and before breakfast and dinner if dosed twice daily). This is so they can work their best to reduce acid levels in the stomach.

Which meds should be TAKEN FIRST THING IN THE MORNING?

Many patients commonly take most of their meds in the morning, such as blood pressure meds, diabetes meds, etc, because it may be more convenient for them. However, there are a variety of reasons other than convenience to take meds first thing in the morning.

Taking diuretics (water pills), such as furosemide or hydrochlorothiazide, in the morning is often a good idea, to avoid unwanted trips to the bathroom overnight.

Meds that might cause a patient to feel hyper, such as ADHD meds including methylphenidate (Concerta, etc) or amphetamine salts (Adderall XR, etc), should be taken early in the day, and not in the evening, to prevent unwanted insomnia (difficulty sleeping).

Levothyroxine (Synthroid, etc) is best taken first thing in the morning, 30 to 60 minutes before eating and four hours before taking supplements such as calcium or iron. This is because its absorption through the stomach into the blood is lowered when there is food or other medications in the stomach. However, the important thing to remember with levothyroxine is consistency. If a patient has been taking it in the morning with food or at bedtime after dinner and is stable, he/she should continue to take it that way. Give patients our patient education handout, Answers to Your Questions About Levothyroxine, to provide information on timing of administration.

Most osteoporosis meds (bisphosphonates), such as alendronate (Fosamax, etc), risedronate (Actonel), and ibandronate (Boniva [U.S.]), should also be given first thing in the morning, 30 minutes (or 60 minutes for ibandronate) before eating. This is because the absorption of these meds is greatly decreased in the presence of food.

The new formulation of the old drug, bromocriptine (Cycloset [U.S.]), that’s used for diabetes must be given within two hours after waking in the morning. This is because its effects depend on the patient’s circadian rhythms, or cycles of the body that depend on the time of day.

You process Ms. Adams’ prescription for alendronate, careful to include the exact directions in the sig on the prescription label. Your computer system prints out a “take on an empty stomach” auxiliary label.

Which meds should be TAKEN AT BEDTIME?

As for taking meds first thing in the morning, there are a variety of reasons certain meds should be taken at night. The most obvious are those meds taken to help people sleep, such as eszopiclone (Lunesta [U.S.]), temazepam (Restoril), zolpidem (Ambien [U.S.], Sublinox [Canada], etc), and others.

Meds that can cause unwanted drowsiness during the day such as clonazepam (Klonopin [U.S.], Rivotril [Canada]) for anxiety, seizures, etc; clonidine (Catapres, etc) for blood pressure or ADHD; and tricyclic antidepressants like amitriptyline (Elavil), imipramine (Tofranil, etc), etc, can be taken at bedtime as well. Meds that can cause dizziness, such as doxazosin (Cardura) or terazosin (Hytrin), might also be best given at bedtime.

Other meds that may be helpful if taken at bedtime include H2-blockers such as cimetidine (Tagamet) or ranitidine (Zantac). These can work overnight, so that heartburn symptoms don’t interrupt sleep.

Some allergy medications, such as diphenhydramine (Benadryl) or levocetirizine (Xyzal [U.S.]), may be recommended to be taken at bedtime due to the potential for drowsiness.

Rectal or vaginal creams and suppositories, such as clotrimazole, metronidazole, estrogen (Premarin Vaginal Cream), etc, might be more convenient and less messy for patients when they are used at bedtime.

Which meds should be TAKEN AT SPECIFIC TIMES?

The reasons that some medications must be taken at specific times of day vary. One reason might be to space doses out to give the body a break from the med. Another reason might be to ensure there are continuous levels of the drug in the body. For some conditions, the drug is only needed to work at a specific time of day. Here are some examples.

The progestin-only oral contraceptive pill, norethindrone 0.35 mg (Jencycla, etc), must be taken at the same time every day. If norethindrone is taken more than three hours late, the risk of pregnancy increases and another form of contraception will be needed for at least two days.

Isosorbide mononitrate immediate-release (U.S.) should be taken in two doses daily, spaced seven hours apart. This gives the body a nitrate-free interval, to prevent tolerance to the therapeutic effects of the drug. For the same reason, nitroglycerin ointment and transdermal patches should only be left on for 12 to 14 hours a day.

The enacarbil salt of gabapentin (Horizant [U.S.]) should be taken at about 5 PM each day so that it’s working when symptoms of restless legs syndrome start at bedtime.

Patients with Parkinson’s disease can have longer hospitals stays when doses of their meds (e.g., levodopa-carbidopa [Sinemet, etc]) are delayed. These patients often require their meds to be given at very specific times, possibly at short intervals such as every one or two hours, to control symptoms.

There are also meds that should be spaced apart from other meds by a specific amount of time. This is because the absorption of one med may be decreased by another med. For example, certain antibiotics, such as fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin, etc) or tetracyclines (doxycycline, minocycline, tetracycline, etc), should not be taken at the same time as other meds that can bind to them and reduce absorption: magnesium-, aluminum-, or calcium-containing antacids; sucralfate (contains aluminum); or multivitamins or supplements containing iron, calcium, or zinc. Patients will be advised to take these antibiotics anywhere from two to four hours before or two to eight hours after taking the med that can bind to it. The absorption of iron can also be decreased by magnesium-, aluminum-, or calcium-containing antacids and supplements, so iron should be taken two hours before or four hours after these antacids or supplements.

What can I do to help patients remember when to take their medications?

Always include any specific timing instructions given by the prescriber on the prescription label. In addition, you can use auxiliary labels to reinforce the information for the patient. For example, place a label to “take on an empty stomach” on all scripts for bisphosphonates.

Be careful about abbreviations in sigs, such as “pc” (after meals), “ac” (before meals), AM, PM, “qhs” (at bedtime), etc. Some of these can be confusing, so clarify with the pharmacist if necessary. For example, “hs” can mean either half-strength or at bedtime. In addition, abbreviations such as q6pm can be misinterpreted as “every 6 hours” or “every 6 hours after meals” instead of “every day at 6 PM.”

Encourage patients to use tools to help them remember to take their medications. This could include calendar alerts, pillboxes, alarms, or medication reminder devices. There are also a number of medication adherence apps which can help patients manage and keep track of when to take their meds. We have more tips for helping patients stay adherent to their medications in our toolbox, Medication Adherence Strategies, and our technician tutorial, Med Adherence 101.

Since alendronate is a new prescription for Ms. Adams, the pharmacist spends time going over the medication with her. He explains to her that it’s important to take the alendronate with a full glass of water right when she wakes up in the morning, at least 30 minutes before eating, drinking, or taking any other medications. He tells her the reason, which is that other meds and food in the stomach can reduce the amount of alendronate absorbed through the stomach and into the bloodstream. He also advises her to not lie down for 30 minutes after taking alendronate because it can cause irritation in her throat if the medication sits there for too long. Ms. Adams seems concerned, because she normally has coffee and toast first thing in the morning. But she agrees that she can hold off on the coffee and toast for at least 30 minutes after she takes her med.

What are some special considerations for timing of medication administration in the hospital setting?

In the hospital setting, getting meds to the patient for administration at specific times of the day involves many people. From the pharmacy staff member who prepares a dose, to the pharmacy staff member who delivers the dose, to the nurse who must administer each and every dose, it can get pretty complicated. Plus, it’s important to remember that nurses might have multiple doses to administer to multiple patients at any given time.

Make sure that meds are available for nurses to administer on time. This might involve making sure that med carts or the IV batch are delivered on time, that a specific med is delivered to a patient care unit on time, or making sure that the automated dispensing cabinet is refilled promptly whenever necessary. Having meds available for on-time administration can prevent medication errors and help avoid the hassle of nurses needing to re-time meds or change their schedules due to late doses.

In addition to the reasons that outpatients need to take certain meds at specific times of day, it might be necessary for an inpatient to get a med at an exact time so a blood level of the drug can be measured. Pharmacists check the results of these lab tests to make sure that the right dose of a med is being given. It is key for blood levels to be drawn at specific times, such as right before or after a dose is given. If a dose is given too late or too early, the blood level might be relatively meaningless and another level will have to be drawn with the next dose. Examples of drugs whose blood levels are often monitored in inpatients include amikacin, cyclosporine, digoxin, gentamicin, phenytoin, tobramycin, and vancomycin.

Keep in mind that when meds are ordered STAT, getting them to the patient is critical. We go into more detail about this in our technician tutorial, Inpatient Emergencies 101. But sometimes meds aren’t ordered STAT and are still needed right away, so it is important to have an awareness of these situations just in case. One thing that can clue you in that a med is needed right away is if it’s a loading dose. Loading doses can be either IV or oral. They are used to quickly boost blood levels of a med when patients require urgent treatment. Usually, loading doses are larger than normal maintenance doses. An example is for IV vancomycin, where a loading dose may be 25 mg/kg/dose and the maintenance dose may be 15 or 20 mg/kg/dose. Another example is phenytoin, where the loading dose is often 1,000 mg or more, given IV or orally. Loading doses can be given all at one time or divided into a few smaller doses given at shorter than usual intervals. For instance, a 1,000 mcg digoxin loading dose may be given as 500 mcg once, then 250 mcg every 6 hours for two doses. Other meds that may be ordered with loading doses include acetylcysteine (for acetaminophen overdoses), alteplase, amiodarone, caspofungin, clopidogrel, gentamicin, levetiracetam, rivaroxaban (higher doses are used to start therapy for some conditions), and voriconazole. In fact, your pharmacy might have a list of meds that require loading doses. (If this is the case, it’s usually to help improve safety with these meds, since loading doses can be involved in some potentially serious errors.) Review the list so you can be prepared to ensure patients get these meds as soon as possible when they are ordered.

Lastly, there can be timing issues with transitions of care. For example, if you take med histories, be sure to document the date and time of the patient’s last dose for each of their meds whenever possible. This can help prevent them from getting doses too close together, or too far apart.

Project Leader in preparation of this technician tutorial (340680): Flora Harp, PharmD/Assistant Editor; last modified January 2021.

Cite this document as follows: Technician Tutorial, Med Administration: Timing is Everything. Pharmacist’s Letter/Pharmacy Technician’s Letter. June 2018.

“Cheat Sheet” of Some Common Drugs that Must be Given at Specific Times

Timing

Drug or Drug Class

Reason

With food or meals

Corticosteroids (prednisone, etc)

To reduce stomach irritation

Lovastatin

To improve absorption

Niacin

To reduce flushing & stomach upset

NSAIDs (ibuprofen, naproxen, etc)

To reduce stomach irritation

Opioids (codeine, oxycodone, etc)

To reduce stomach upset

Some antibiotics (amoxicillin/clavulanate, cefuroxime axetil oral suspension [Ceftin])

To improve absorption

Some blood thinners (rivaroxaban [Xarelto] 15 and 20 mg)

To improve absorption

Some hepatitis C meds (Holkira Pak, Mavyret, Maviret,
Technivie
, Viekira Pak, Viekira XR, Vosevi)

To improve absorption

Some psychiatric meds (vilazodone [Viibryd], ziprasidone [Geodon, Zeldox], etc)

To improve absorption

On an empty stomach

Proton pump inhibitors (esomeprazole [Nexium], lansoprazole [Prevacid], etc)
(30 to 60 minutes before meals)

To improve effectiveness

Some anti-infectives (ampicillin, azithromycin extended-release [Zmax], dicloxacillin, penicillin VK, rifampin, tetracycline, voriconazole [Vfend], etc)

To improve absorption

Some HIV meds (didanosine [Videx], efavirenz [Sustiva], indinavir [Crixivan], etc)

To improve absorption

In the morning

Bromocriptine (Cycloset, specifically)

To improve effectiveness

Diuretics (furosemide, hydrochlorothiazide, etc)

To avoid urination at night

Levothyroxine (Synthroid, etc)
(take immediately after rising, on an empty stomach)

To improve absorption

Osteoporosis meds (alendronate [Fosamax], etc)
(take immediately after rising, on an empty stomach)

To improve absorption

Stimulants (methylphenidate [Concerta, etc], etc)

To prevent insomnia

At bedtime

Drugs that cause dizziness or drowsiness (amitriptyline, clonidine [Catapres], clonazepam [Klonopin], doxazosin [Cardura], terazosin [Hytrin], diphenhydramine [Benadryl], etc)

To prevent
dizziness or drowsiness
during waking hours

H2-blockers (cimetidine [Tagamet],

ranitidine [Zantac], etc)

To improve effectiveness for nighttime heartburn symptoms

Sleep aids (eszopiclone [Lunesta], zolpidem, etc)

So they can work when needed

At specific times

Gabapentin (Horizant, specifically) (take at 5 PM)

To be effective when needed

Norethindrone (Micronor, Jencycla) (take at exact time each day)

To ensure efficacy

Some antibiotics (fluoroquinolones [ciprofloxacin, levofloxacin, etc]; tetracyclines [doxycycline, minocycline, etc])
(space by specific timeframe from antacids and multivitamins/minerals w/ aluminum, calcium, iron, or zinc)

To prevent reduced absorption

Some nitrates (isosorbide mononitrate immediate-release, nitroglycerin ointment and patches)
(space doses so that a nitrate-free period occurs daily)

To prevent tolerance

More examples and details can be found in our chart, Medication Administration Timing.

[June 2018; 340680]

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