EDUCATING PATIENTS on when to take their medication can be the difference between success and failure in treatment. Many studies have investigated correlations between the circadian rhythm, the production of endogenous substances, and the timing of medication doses. This article discusses safe practices in the timely administration of select common drugs and drug classes for optimal patient outcomes.

The following information is intended for use in adult patients unless otherwise indicated. Consult with a pharmacist or review product inserts for more information on the safety of these medications for those who are pregnant or breastfeeding. For additional information on precautions, drug interactions, and adverse reactions for each of the following medications and drug classes, review the prescribing information and a current, comprehensive drug reference or speak with a pharmacist.

In the morning

Diuretics. By altering the body's electrolyte composition, especially sodium, diuretics influence the amount of urine production. Teach patients to take these medications in the morning or early afternoon to avoid nocturia and subsequent sleep interruptions.1 Ask them about their sleep quality and adjust the timing of diuretics accordingly.

Attention-deficit hyperactivity disorder (ADHD) stimulants. These drugs should be taken early in the day to manage ADHD. Patients with ADHD have poor prefrontal cortex functioning, which regulates attention, behavior, and emotion.2 Stimulants enhance neurotransmission in the brain to correct neural deficits. Because they increase brain activity, they may also cause patients to feel "hyper." Counsel patients about administering these medications in the morning or at their earliest convenience to avoid insomnia.2

Levothyroxine. Administration early in the day on an empty stomach can improve drug absorption. Levothyroxine may be poorly absorbed if administered with calcium, iron, certain foods, and other drugs. Fasting can greatly improve absorption and bioavailability. Patients should take levothyroxine on an empty stomach immediately after rising in the morning, 30 to 60 minutes before breakfast.1 If patients experience difficulties with early morning administration, such as forgetfulness or dietary needs, studies recommend taking levothyroxine 2 to 4 hours after the last meal of the day as an alternative dosing strategy.1

Bisphosphonates. Because food may prevent absorption, bisphosphonates should be taken before breakfast. These drugs inhibit bone resorption and increase bone mineral density, mainly in postmenopausal women with osteoporosis. Educate patients to take this medication in the morning, 30 to 60 minutes before breakfast.1 Following administration, they should remain upright until after breakfast to avoid esophageal or gastric irritation.

At night

Histamine2-receptor antagonists (H2RAs). These drugs inhibit acid secretion by blocking H2 receptors on the gastric parietal cells.3 H2RAs can be administered to coincide with the natural circadian production of endogenous histamine.1 The nighttime production of histamines stimulates acid release and causes patients with gastroesophageal reflux disease and similar disorders to experience increased disturbances. Instruct these patients to take medications such as ranitidine at night for fewer sleep interruptions. Simple education can also help patients manage their symptoms. For example, explain that they should avoid eating or drinking before bed and avoid caffeine for 4 to 6 hours beforehand.1,4

Statins. Cholesterol production is based on circadian rhythms, and most cholesterol is produced at night. Medications in this class with a shorter duration of action should be administered at bedtime to be effective. These include lovastatin, simvastatin, and fluvastatin. Other statin drugs with a longer duration of action, such as rosuvastatin and atorvastatin, can be taken at any time of the day.1

Sedatives. Certain sedatives, including lorazepam or alprazolam, are prescribed to manage behavioral health disorders such as anxiety or panic attacks. Patients may take them throughout the day, so advise them on the possibility of drowsiness and mental delays and tell them to avoid activities requiring mental alertness, such as driving, until they learn how the medication affects them.

Patients can expect drowsiness from various drug classes including benzodiazepines, opioids, first-generation antihistamines, muscle relaxants, and melatonin receptor agonists. Warn patients to expect drowsiness and recommend that they take these medications closer to bedtime if possible.5

With meals

Sulfonylureas. These medications should be taken with food to avoid the risk of severe hypoglycemia. Sulfonylureas activate beta cells in the pancreas to increase the release of endogenous insulin, decreasing blood glucose levels. Patients with diabetes should take sulfonylureas with food as prescribed to prevent hypoglycemia. Severe hypoglycemia may lead to diabetic coma.6

Insulin. Similarly, both rapid- and short-acting insulin should be administered at mealtimes to minimize the risk of hypoglycemia and severe complications. Endogenous insulin decreases circulating blood glucose by stimulating uptake and metabolic pathways in the liver, skeletal muscle, and fat tissue. When injected, exogenous insulin does the same.

Educate patients with diabetes about the signs and symptoms of hypoglycemia, including dizziness, lightheadedness, tremors, diaphoresis, and headache. Patients must understand the importance of testing their blood glucose levels if they experience these signs and symptoms to recognize when they have fallen below the 70 mg/dL threshold.6 Hypoglycemic symptoms are subjective to each patient's average blood glucose levels, however, so patients may experience these symptoms at higher levels.7

On an empty stomach

Proton pump inhibitors (PPIs). Drugs such as omeprazole work best on an empty stomach. These medications bind to proton pumps in the stomach to decrease acid production throughout the day. Given the irreversible nature of this drug class, the body must synthesize and replace the proton pumps to continue acid production, which may take 24 to 36 hours.8 As such, patients are often instructed to take them 30 to 60 minutes before breakfast, but PPIs can be taken 30 to 60 minutes before any meal on an empty stomach.1

Certain antimicrobials. Some antimicrobials should be taken on an empty stomach. For example, tetracyclines can interact with the calcium in dairy products and should not be administered with food. Similarly, ampicillin and rifampin each have a decreased absorption rate when taken with any meal; voriconazole has a decreased absorption rate when taken with high-fat meals.1 Check the specific pharmacokinetics of the antibiotic before counseling patients on how it should be administered.

At specific times

Antiparkinsonian drugs. These may represent the most crucial time-sensitive medications. Scheduled dosing for this drug class is patient-specific and often fine-tuned by a neurologist. Omitted or delayed administration of medications such as carbidopa-levodopa could lead to severe Parkinson symptoms. Teach patients to adhere to their individualized schedules.1,9

Antidepressants. Dosing instructions for antidepressants vary depending on the specific drug. Selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors can cause either activating or sedating adverse reactions. Administer activating drugs in the morning and sedating drugs in the evening to avoid insomnia or daytime drowsiness, respectively. Some adverse reactions can be used as an advantage. For example, amitriptyline has sedative effects and may help patients sleep. Ask patients their indication for taking these medications and educate them accordingly.10

Take time for safety

The timing of drug administration is crucial to the safety and success of different therapies. Consider the whole patient when administering medications. By looking at a drug's indications, pharmacodynamics, and pharmacokinetics, healthcare professionals help minimize the risk of adverse reactions and maximize the benefits of drug therapies for their patients.

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