What is the optimal timing for taking medications and supplements, and how do they interact with each other?

From the Guidelines

The best approach to taking medications and supplements is to prioritize consistency and take them at the same time each day to maintain steady blood levels, as there is no clear evidence that the timing of medication administration has a significant impact on major cardiovascular outcomes. For most medications, consistency is key, and taking them at the same time each day helps improve adherence, as noted in the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1.

Key Considerations for Medication Timing

• Morning is often ideal for stimulating medications, such as thyroid medications, ADHD medications, and some antidepressants.
• Evening may be better for sedating medications, like certain antihistamines and sleep aids.
• Some medications should be taken with food to reduce stomach irritation, including NSAIDs like ibuprofen and many antibiotics.
• Others work best on an empty stomach, such as thyroid medications and bisphosphonates for osteoporosis.

Drug Interactions

Regarding drug interactions, it is crucial to consult your healthcare provider or pharmacist before combining medications, as some combinations can be dangerous. Common concerning interactions include:

• Blood thinners with NSAIDs, which can increase the bleeding risk.
• Certain antibiotics with dairy products, which can reduce absorption.
• Some antidepressants with pain medications or alcohol, which can have potentially dangerous central nervous system effects. The 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults also emphasizes the importance of simplifying medication regimens to improve adherence 1.

Special Considerations

For specific medications like orlistat, used for obesity management, taking 1 capsule during or within 1 hour after meals is recommended, and patients should be aware of the risk of deficiencies of fat-soluble vitamins and the potential need for supplementation, as outlined in the 2022 AGA clinical practice guideline on pharmacological interventions for adults with obesity 1.

General Recommendations

Always read medication labels carefully and create a consistent schedule that works with your daily routine. The timing recommendations are based on how medications are metabolized and absorbed by your body, with some being fat-soluble and needing food for proper absorption, while others may compete for absorption pathways if taken together. Prioritizing consistency and being mindful of potential drug interactions can significantly impact morbidity, mortality, and quality of life.

From the FDA Drug Label

Effect of Omeprazole on Other Drugs Omeprazole is a time-dependent inhibitor of CYP2C19 and can increase the systemic exposure of co-administered drugs that are CYP2C19 substrates. In addition, administration of omeprazole increases intragastric pH and can alter the systemic exposure of certain drugs that exhibit pH-dependent solubility Antiretrovirals For some antiretroviral drugs, such as rilpivirine, atazanavir and nelfinavir, decreased serum concentrations have been reported when given together with omeprazole RILPIVIRINE Following multiple doses of rilpivirine (150 mg, daily) and omeprazole (20 mg, daily), AUC was decreased by 40%, C maxby 40%, and C minby 33% for rilpivirine NELFINAVIR Following multiple doses of nelfinavir (1250 mg, twice daily) and omeprazole (40 mg daily), AUC was decreased by 36% and 92%, C maxby 37% and 89% and C minby 39% and 75% respectively for nelfinavir and M8. ATAZANAVIR Following multiple doses of atazanavir (400 mg, daily) and omeprazole (40 mg, daily, 2 hours before atazanavir), AUC was decreased by 94%, C maxby 96%, and C minby 95% SAQUINAVIR Following multiple dosing of saquinavir/ritonavir (1000/100 mg) twice daily for 15 days with omeprazole 40 mg daily co-administered days 11 to 15. AUC was increased by 82%, C maxby 75%, and C minby 106%. Clopidogrel In a crossover clinical study, 72 healthy subjects were administered clopidogrel (300 mg loading dose followed by 75 mg per day) alone and with omeprazole (80 mg at the same time as clopidogrel) for 5 days. The exposure to the active metabolite of clopidogrel was decreased by 46% (Day 1) and 42% (Day 5) when clopidogrel and omeprazole were administered together Mycophenolate Mofetil Administration of omeprazole 20 mg twice daily for 4 days and a single 1000 mg dose of MMF approximately one hour after the last dose of omeprazole to 12 healthy subjects in a cross-over study resulted in a 52% reduction in the C maxand 23% reduction in the AUC of MPA Cilostazol Omeprazole acts as an inhibitor of CYP2C19. Omeprazole, given in doses of 40 mg daily for one week to 20 healthy subjects in cross-over study, increased C maxand AUC of cilostazol by 18% and 26% respectively. Diazepam Concomitant administration of omeprazole 20 mg once daily and diazepam 0. 1 mg/kg given intravenously resulted in 27% decrease in clearance and 36% increase in diazepam half-life Digoxin Concomitant administration of omeprazole 20 mg once daily and digoxin in healthy subjects increased the bioavailability of digoxin by 10% (30% in two subjects) Effect of Other Drugs on Omeprazole Voriconazole Concomitant administration of omeprazole and voriconazole (a combined inhibitor of CYP2C19 and CYP3A4) resulted in more than doubling of the omeprazole exposure

The best time for medicines and supplements is not explicitly stated in the provided drug labels. However, it is mentioned that omeprazole delayed-release capsules should be taken before meals 2.

Regarding drug interactions, omeprazole can interact with various drugs, including:

• Antiretrovirals: decreased serum concentrations of rilpivirine, atazanavir, and nelfinavir when given together with omeprazole 2
• Clopidogrel: decreased exposure to the active metabolite of clopidogrel when administered with omeprazole 2
• Mycophenolate Mofetil: reduced C max and AUC of MPA when administered with omeprazole 2
• Cilostazol: increased C max and AUC of cilostazol when administered with omeprazole 2
• Diazepam: decreased clearance and increased half-life of diazepam when administered with omeprazole 2
• Digoxin: increased bioavailability of digoxin when administered with omeprazole 2
• Voriconazole: increased exposure of omeprazole when administered with voriconazole 2

From the Research

Medication Regimen Complexity

• Medication regimens can be complex and error-prone, especially for patients taking multiple medications, which may impact medication adherence and safety 3
• The complexity of medication regimens can be measured using various scales, including the Medication Regimen Complexity Index (MRCI), which takes into account factors such as dosing frequency, units per dose, and non-oral routes 3, 4
• Patient-level medication regimen complexity can vary significantly across different populations with chronic diseases, such as geriatric depression, HIV, diabetes mellitus, and hypertension 4

Drug Interactions

• Drug-drug interactions (DDIs) can occur when one drug affects the absorption, distribution, metabolism, or excretion of another drug, or when two drugs have additive effects, such as increasing the risk of seizures or prolonging the QT interval 5, 6
• DDIs can cause significant morbidity and mortality, and are associated with a substantial burden on the healthcare system 5
• The risk of DDIs increases exponentially with the number of medications consumed, making polypharmacy a significant concern, especially in elderly patients 7
• Common DDIs include interactions between antihypertensive agents, such as clopidogrel and esomeprazole, and between medications that increase the risk of central nervous system depression or serotonin syndrome 5, 7, 6

Managing Medication Regimens and Drug Interactions

• Clinicians can prevent clinically significant DDIs and optimize drug safety by using drug interaction software, collaborating with pharmacists, and considering patient-specific factors, such as dexterity and cognition 5, 7
• Simplifying medication regimens, reducing multiple dosing frequencies, and using standardized tools to assess medication regimen complexity can help improve patient adherence and safety 3, 4
• Regular monitoring of potential drug interactions and making appropriate dosage or therapy adjustments can help minimize the risk of morbidity or mortality associated with DDIs 5, 6