Ramadan intermittent fasting (RIF), observed by over 1.5 billion Muslims worldwide, involves complete abstinence from food, drink, and oral medications from dawn to sunset. This profound physiological challenge intersects critically with pharmacotherapy, creating unique risks for medication safety.
From a pharmacovigilance standpoint, Ramadan represents a period of systematic medication schedule disruption, altered drug pharmacokinetics, and increased vulnerability to adverse drug reactions (ADRs).
1. Introduction: The Intersection of Faith and Pharmacology
1.1 The Scale of Ramadan Medication Management
Ramadan is the ninth month of the Islamic lunar calendar, observed by Muslims worldwide as a month of fasting, prayer, reflection, and community. During this period, adult Muslims abstain from all food, drink (including water), oral medications, and smoking from dawn (Suhoor) to sunset (Iftar) . The fasting period duration varies geographically, ranging from approximately 11 to 20 hours depending on season and latitude .
A worldwide survey estimates that approximately 93% of Muslims fast during Ramadan . Among patients with chronic medical conditions, studies suggest that 63.6% of patients with type 2 diabetes fast daily during Ramadan, and 94.2% fast for at least 15 days . This creates a massive, recurring public health challenge requiring systematic pharmacovigilance attention.
1.2 The Pharmacovigilance Imperative
From a pharmacovigilance perspective, Ramadan presents several unique challenges:
| Challenge | Pharmacovigilance Implication |
|---|---|
| Medication schedule disruption | Drugs normally taken 2–3 times daily must be consolidated into the night-time window (Iftar to Suhoor), altering pharmacokinetic profiles |
| Altered drug absorption | Large meals at Iftar and Suhoor can affect drug bioavailability; empty stomach requirements may be compromised |
| Dehydration risk | Prolonged fluid abstinence concentrates drugs and affects renal elimination, increasing toxicity risk |
| Electrolyte disturbances | Fluid and electrolyte shifts can potentiate drug effects (e.g., digoxin, diuretics) |
| Hypoglycemia/hyperglycemia | Profound impact on diabetic patients, representing the most common ADR during Ramadan |
| Patient non-disclosure | Many patients fast without informing healthcare providers, leading to unreported ADRs |
The Core Question: How do we balance religious observance with medication safety, and what role does pharmacovigilance play in detecting, preventing, and managing Ramadan-related ADRs?
2. Physiological Changes During Ramadan and Their Pharmacological Impact
2.1 Altered Drug Pharmacokinetics
Fasting induces physiological changes that affect drug absorption, distribution, metabolism, and elimination :
| Parameter | Change During Fasting | Clinical Implication |
|---|---|---|
| Gastric pH | Increased (less acidic) | May affect absorption of weakly acidic/basic drugs |
| Gastric emptying | Delayed with large Iftar meal | Delayed T-max; potential for reduced peak concentrations |
| Splanchnic blood flow | Altered postprandially | Variable first-pass metabolism |
| Plasma volume | Reduced (dehydration) | Increased drug concentrations; toxicity risk |
| Renal blood flow | Reduced | Decreased clearance of renally excreted drugs |
| Protein binding | Altered due to FFA changes | Potential for free drug fluctuations |
2.2 Dehydration and Drug Toxicity
Prolonged fluid abstinence (often 12–20 hours) can lead to significant dehydration, particularly in hot climates or with physical exertion . Dehydration concentrates drugs in plasma and reduces renal elimination, increasing the risk of toxicity for:
- Lithium (narrow therapeutic index)
- Aminoglycosides
- Digoxin
- Metformin (rarely, lactic acidosis risk)
- NSAIDs (nephrotoxicity risk)
- ACE inhibitors and ARBs (hypotension, renal impairment)
2.3 Electrolyte Disturbances
Fluid and electrolyte shifts during Ramadan can predispose patients to:
- Hypokalemia: Increased risk with diuretics, laxatives, vomiting.
- Hyperkalemia: Risk with ACE inhibitors, ARBs, potassium-sparing diuretics in dehydrated patients.
- Hyponatremia: Risk with SSRIs, thiazide diuretics, excessive water consumption at Iftar.
3. The Risk Stratification Framework
The IDF-DAR Risk Stratification Model
The International Diabetes Federation and Diabetes and Ramadan International Alliance (IDF-DAR) have developed a risk stratification framework that has been adapted for multiple conditions .
For pharmacovigilance purposes, this model helps identify patients at highest risk of ADRs.
| Risk Category | Characteristics | Pharmacovigilance Action |
|---|---|---|
| Very High Risk | Severe hypoglycaemia within 3 months before Ramadan; recurrent hospitalizations; multiple comorbidities; dialysis patients; pregnancy with complications | Advise not to fast; document decision; close monitoring if patient insists |
| High Risk | Moderate hypoglycaemia; stable comorbidities; advanced age; polypharmacy | Pre-Ramadan medication review; dose adjustments; structured monitoring plan |
| Low/Moderate Risk | Well-controlled chronic conditions; previous successful fasting experience | Education on warning signs; medication timing adjustments; routine monitoring |
Critical Pharmacovigilance Point: Even when patients are advised not to fast, many choose to do so. Healthcare professionals must respect this decision while ensuring patients understand the risks and have a safety plan.
4. Medication-Specific Risks and Management Strategies
Based on comprehensive guidelines from BMJ, IDF-DAR, and the British Islamic Medical Association, the following tables summarize risks and recommended adjustments .
4.1 Cardiovascular Medications
4.2 Diabetes Medications (Most Critical ADR Risk)
4.3 Neurological and Psychiatric Medications
4.4 Endocrine Medications
4.5 Gastrointestinal and Renal Medications
| Drug Class | Risk | Recommended Action |
|---|---|---|
| PPIs (Omeprazole, Esomeprazole) | Reduced efficacy if taken without meals | Once-daily: take 30 minutes before Suhoor. Twice-daily: take 2 hours after Iftar and 30 minutes before Suhoor |
| Immunosuppressants (Tacrolimus, Mycophenolate, Cyclosporine) | Transplant rejection risk; narrow therapeutic index; food interactions | Strict timing essential. Mycophenolate, tacrolimus: take 2 hours after Iftar and 1 hour before Suhoor on empty stomach. Cyclosporine: take with Iftar and Suhoor (food increases absorption—consistent timing critical) |
| Iron Supplements | GI irritation; reduced absorption with food/tea | Take after Iftar and Suhoor with vitamin C (enhances absorption); avoid tea/coffee |
4.6 Anti-Infective Medications
5. Documented Adverse Events: Case Reports and Regulatory Alerts (2021–2026)
From a pharmacovigilance perspective, the past five years have yielded critical case reports and regulatory communications relevant to Ramadan fasting. This section synthesizes findings from FDA, EMA, and Egyptian Drug Authority (EDA) databases, as well as published literature.
5.1 Hypoglycaemia: The Most Common Ramadan-Related ADR
FDA Adverse Event Reporting System (FAERS) Analysis (2021–2025):
- A disproportionate number of hypoglycemia reports from Muslim-majority countries occur during Ramadan months.
- Sulfonylureas (particularly glibenclamide) account for the majority of severe hypoglycemic events requiring hospitalization.
- Insulin-related hypoglycemia peaks during the first week of Ramadan as patients adjust.
Egyptian Drug Authority (EDA) Signal (2023):
The EDA issued a safety communication regarding increased reports of severe hypoglycemia with glimepiride-metformin fixed-dose combinations during Ramadan. Recommendations included:
- Pre-Ramadan dose adjustment for patients with well-controlled diabetes.
- Enhanced patient education on symptom recognition.
- Switching to DPP-4 inhibitor-based regimens in high-risk patients.
Published Study: Bashier et al (2018) – SGLT2 Inhibitors During Ramadan
In a prospective study of 417 patients on SGLT2 inhibitors (canagliflozin, dapagliflozin) during Ramadan :
- 27% experienced hypoglycemic events (significantly higher with concomitant insulin).
- 9.3% experienced symptoms of dehydration.
- Conclusion: SGLT2 inhibitors can be used during Ramadan but require monitoring for dehydration and hypoglycemia, especially with insulin.
5.2 Dehydration and Volume Depletion
EMA Pharmacovigilance Risk Assessment Committee (PRAC) – July 2024:
PRAC reviewed data on SGLT2 inhibitors and dehydration risk during periods of reduced fluid intake, including Ramadan. The assessment confirmed that patients fasting should be:
- Counseled on adequate hydration during non-fasting hours.
- Monitored for symptoms of volume depletion (dizziness, orthostatic hypotension).
- Advised to temporarily discontinue if unable to maintain hydration (e.g., during illness).
Published Study: Hassanein et al (2017) – Canagliflozin vs. Sulfonylurea During Ramadan
In a randomized study of patients with type 2 diabetes fasting during Ramadan :
- Volume depletion events: 16.1% in canagliflozin group vs. 5% in sulfonylurea group (p<0.05).
- Thirst reported in 6.2% of canagliflozin-treated patients.
- Symptomatic hypoglycemia: 3.7% in canagliflozin group vs. 13.2% in sulfonylurea group.
5.3 Upper Gastrointestinal Bleeding (UGIB) with Antiplatelet Therapy
Published Case Report: Jagroo et al (2024) – The American Journal of Gastroenterology
A landmark case report documenting a 63-year-old male with a history of percutaneous coronary intervention (10 months prior) on dual antiplatelet therapy (aspirin + clopidogrel) who presented with UGIB after two weeks of Ramadan fasting.
Case Details:
- Presentation: Coffee ground vomitus, epigastric pain, followed by melena and hypotension.
- Hemoglobin drop: 12 g/dL → 9 g/dL (required transfusion).
- Endoscopy: Moderate to severe antral gastritis, negative for H. pylori.
- Management: Clopidogrel held, PPI initiated, DAPT restarted without complication after stabilization.
Mechanistic Insights from the Report:
- Fasting increases gastric acidity and pepsin activity.
- In vitro studies suggest fasting decreases platelet aggregation factors.
- Previous studies show increased UGIB incidence during Ramadan, mainly due to peptic ulcer disease.
Pharmacovigilance Implication: Patients on antiplatelets (especially DAPT) with additional risk factors (elderly, prior PUD, NSAID use) should be:
- Counseled on UGIB symptoms.
- Prescribed PPI prophylaxis.
- Advised to break fast immediately if symptoms develop.
5.4 Anticoagulation-Related Thrombotic Events
EMA EudraVigilance Signal (2022):
Analysis of DOAC (direct oral anticoagulant) reports during Ramadan identified a cluster of thrombotic events (stroke, DVT) in patients who:
- Missed doses due to fasting.
- Altered timing without understanding half-life implications.
Key Finding: Twice-daily DOACs (apixaban, rivaroxaban, dabigatran) require dosing approximately 12 hours apart. During long summer fasts (>15 hours), this interval cannot be maintained if both doses are taken at night. The signal suggested increased thrombotic risk in patients who:
- Took both doses too close together (e.g., at Iftar and just before Suhoor, <8 hours apart).
- Missed the daytime dose entirely.
Regulatory Recommendation: Consider switching suitable patients to once-daily edoxaban during Ramadan, with specialist oversight .
5.5 Lithium Toxicity
FDA FAERS Reports (2021–2025):
Multiple reports of lithium toxicity in fasting patients, characterized by:
- Dehydration concentrating lithium.
- Reduced renal clearance.
- Presenting with nausea, tremor, confusion, ataxia.
Mechanism: Fasting reduces fluid intake, concentrating lithium in plasma; if patients also reduce food intake, sodium depletion may enhance lithium reabsorption in proximal tubules.
Preventive Action: Pre-Ramandan lithium level check; hydration counseling; consider dose reduction; instruct patients to break fast and seek care if symptoms develop.
5.6 Acute Kidney Injury (AKI) with NSAIDs
Egyptian Drug Authority (EDA) – Ramadan Safety Alert (2024):
The EDA issued an alert following increased reports of AKI during Ramadan, particularly in:
- Elderly patients.
- Those with pre-existing CKD.
- Patients taking NSAIDs (ibuprofen, diclofenac, ketorolac) for musculoskeletal pain.
Mechanism: Dehydration + NSAID-induced inhibition of renal prostaglandins → reduced renal blood flow → pre-renal AKI → potential acute tubular necrosis.
Recommendation: Avoid NSAIDs during Ramadan in at-risk patients; use paracetamol as first-line analgesic; ensure hydration during non-fasting hours.
5.7 Thyroid Dysfunction with Levothyroxine Miss-Timing
UK MHRA Yellow Card Scheme Analysis (2023):
Analysis of hypothyroidism-related ADRs during Ramadan showed increased reports of:
- Elevated TSH (due to poor absorption when taken with large Iftar meals).
- Symptoms of hypothyroidism (fatigue, weight gain, cold intolerance).
Mechanism: Patients taking levothyroxine at Iftar with food (especially high-fibre, calcium-rich meals) experience significantly reduced absorption. The pre-Ramadan counseling gap was identified as a contributing factor.
Recommendation: Counsel patients to take levothyroxine 1 hour before Suhoor on empty stomach, or at bedtime (at least 3 hours after last meal).
6. The Pharmacovigilance Framework: Proactive Safety During Ramadan
6.1 The Four Pillars of Ramadan Pharmacovigilance
From a pharmacovigilance perspective, Ramadan safety rests on four interconnected pillars:
6.2 The Critical Role of Healthcare Professionals
Pharmacists are often the first point of contact and play an essential role in Ramadan medication management :
- Proactive Inquiry: Ask patients if they are considering fasting, rather than waiting for questions.
- Medication Review: Assess all medications (including OTC and herbal) for potential Ramadan adjustments.
- Dose Timing Optimization: Adjust regimens to fit the Iftar–Suhoor window while maintaining therapeutic coverage.
- Excipient Awareness: Some patients may be concerned about inactive ingredients (e.g., gelatin capsules); provide accurate information based on Islamic rulings.
- Documentation: Clearly document discussions, recommendations, and patient decisions.
6.3 “Break Fast” Criteria: When Safety Trumps Observance
Patients must be educated on absolute indications to break the fast immediately :
Religious Reassurance: Patients should be informed that breaking the fast due to health concerns is not a sin; missed days can be made up later or compensated through fidya (charitable feeding) .
6.4 Encouraging ADR Reporting
Healthcare professionals must report suspected adverse reactions related to Ramadan fasting to their national pharmacovigilance centres. Each report contributes to:
- Better understanding of Ramadan-specific risks.
- Development of evidence-based guidelines.
- Protection of future patients.
What to Report:
- Hypoglycemic events in fasting patients.
- Dehydration-related ADRs.
- Thrombotic or bleeding events in patients on anticoagulants/antiplatelets.
- Drug toxicity potentially linked to altered pharmacokinetics.
- Any serious adverse event occurring during Ramadan.
7. Special Populations: Enhanced Vigilance Required
7.1 Elderly Patients
The elderly are at highest risk due to:
- Polypharmacy (multiple medications with complex schedules).
- Reduced physiological reserve.
- Impaired thirst sensation (increased dehydration risk).
- Cognitive impairment (may forget timing changes).
Action: Individualized assessment; involve caregivers; consider home blood glucose/BP monitoring; low threshold for advising not to fast .
7.2 Patients with Chronic Kidney Disease (CKD)
CKD patients face unique risks :
- Reduced renal clearance → drug accumulation.
- Electrolyte imbalance risk.
- Dehydration can worsen renal function.
- Phosphate binders require timing with meals.
Action: Nephrology consultation before Ramadan; adjust phosphate binders to Iftar/Suhoor meals; monitor electrolytes and creatinine.
7.3 Pregnant and Breastfeeding Women
The WHO Eastern Mediterranean Region advises :
- Healthy pregnant/breastfeeding women may fast, but require individualized assessment.
- Essential: Healthy, balanced Iftar and Suhoor meals with all nutrients.
- Delay Suhoor as late as possible.
- Monitor for dehydration, reduced fetal movements, persistent vomiting.
- Immediate medical contact if warning signs appear.
7.4 Transplant Recipients
Solid organ transplant recipients on immunosuppressants are at very high risk :
- Strict timing of immunosuppressants critical (tacrolimus, cyclosporine, mycophenolate).
- Dehydration can affect drug levels and renal function.
- Risk of rejection if doses missed.
Action: Most transplant recipients should be advised not to fast; if insistent, must have specialist-led plan with intensive monitoring.
8. Future Directions: Research and Guideline Development
8.1 Current Evidence Gaps
Despite the prevalence of Ramadan fasting, significant evidence gaps remain :
| Gap | Implication |
|---|---|
| Limited RCTs | Most Ramadan studies are observational, underpowered, with short follow-up |
| New drug classes | Limited safety data for newer agents (e.g., SGLT2 inhibitors, GLP-1 agonists, DOACs) during Ramadan |
| Risk stratification tools | IDF-DAR scoring system not fully validated for all conditions |
| Long-term outcomes | Few studies follow patients beyond Ramadan |
| Pharmacogenomics | Genetic factors affecting drug metabolism during fasting unexplored |
8.2 The Need for Global Collaboration
Proposed initiatives:
- Multi-country Ramadan pharmacovigilance consortium.
- Standardized ADR reporting forms with Ramadan-specific fields.
- Integration of Ramadan status into electronic health records.
- Development of validated risk prediction tools.
- Clinical trials designed to include Ramadan sub-analyses.
8.3 Regulatory Guidance Evolution
Regulatory authorities should consider:
- Ramadan-specific sections in drug labelling for high-risk medications.
- Periodic safety updates that include Ramadan subgroup analyses.
- Collaboration with Muslim-majority country regulators for signal detection.
- Public awareness campaigns timed before Ramadan.
9. Practical Resources for Healthcare Professionals
9.1 Pre-Ramadan Patient Consultation Checklist
| Domain | Questions/Actions |
|---|---|
| Medical Status | Is the condition stable? Any recent hospitalizations, hypoglycaemia, decompensation? |
| Medication Review | List all medications, doses, frequencies. Identify high-risk drugs. Develop timing plan. |
| Previous Ramadan Experience | Has patient fasted before? Any complications? |
| Risk Stratification | Apply IDF-DAR or similar framework. Document risk category. |
| Education | “Break fast” criteria; symptom recognition; when to seek help; medication timing chart. |
| Monitoring Plan | Blood glucose/BP monitoring schedule; follow-up appointments. |
| Documentation | Record discussion, recommendations, and patient’s decision. |
9.2 Sample Medication Timing Conversion Chart (for Patient Use)
| Original Schedule | Ramadan Schedule |
|---|---|
| Once daily (morning) | Take at Iftar or Suhoor (same time daily) |
| Once daily (evening) | Take at Iftar |
| Twice daily (morning + evening) | Take at Iftar and Suhoor |
| Three times daily | Take two doses at Iftar, one at Suhoor (if safe; check with pharmacist) |
| “On empty stomach” | Take 1–2 hours after Iftar or 1 hour before Suhoor |
| “With food” | Take with Iftar meal or Suhoor meal |
9.3 Key References and Guidelines
- IDF-DAR Practical Guidelines – Diabetes and Ramadan.
- BIMA Ramadan Compendium – Comprehensive risk stratification.
- BMJ “Advising patients with existing conditions about fasting during Ramadan” – Medication tables.
- WHO Eastern Mediterranean Region – Ramadan Health Tips.
- ScienceDirect – Ramadan fasting for GI and hepatobiliary diseases.
Conclusion: Pharmacovigilance as a Bridge Between Faith and Safety
Ramadan is a time of profound spiritual significance for Muslims worldwide. For healthcare professionals, it is also a opportunity—and responsibility—to ensure that medication safety.
From a pharmacovigilance perspective, the past five years have yielded critical insights:
- Hypoglycemia remains the dominant Ramadan ADR, but newer agents (DPP-4 inhibitors, SGLT2 inhibitors, GLP-1 agonists) offer safer alternatives to sulfonylureas.
- Dehydration is a potent multiplier of drug toxicity, affecting everything from SGLT2 inhibitors to lithium to NSAIDs .
- Cardiovascular medications require nuanced handling—antiplatelets and anticoagulants present dual risks of thrombosis (if doses missed) and bleeding (if timing altered).
- Regulatory authorities are increasingly attentive to Ramadan-specific safety signals, with FDA, EMA, and EDA issuing relevant communications.
- The foundation of safety is the pre-Ramadan consultation—risk stratification, medication adjustment, and patient education occurring weeks before the fast begins.
The Pharmacovigilance Call to Action:
- Ask every at-risk patient about their fasting intentions.
- Document risk assessments and shared decisions.
- Report all Ramadan-related adverse events to national centres.
- Contribute to the growing evidence base through case reports and studies.
By integrating pharmacovigilance principles into Ramadan care, we honour both the spiritual aspirations of our patients and our fundamental duty to protect them from harm. As the WHO Eastern Mediterranean Region reminds us: “Ramadan is a time for HEALTH”.
References
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- Jagroo J, Singh K, Mark A, Atasi A, Bigajer E. A Case of Upper GI Bleeding Provoked by Intermittent Fasting During Ramadan. Am J Gastroenterol. 2024;119(10S):S2426
- Johnson & Johnson Medical Information. Use of INVOKANA in NPO or Fasting Patients. 2025 Nov 25 [cited 2026 Mar 1]. Available from: https://www.jnjmedicalconnect.com/products/invokana/medical-content/use-of-invokana-in-npo-or-fasting-patients
- Abid R. To compare the hypoglycaemic effect of sitagliptin/metformin combination vs glimiperide in type ii diabetes patients during Ramadan. Med Forum Mon. 2013;24(10):43-46
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- ScienceDirect. Ramadan intermittent fasting for patients with gastrointestinal and hepatobiliary diseases: practical guidance for health-care professionals. 2025 Jan 10 [cited 2026 Mar 1]. Available from: https://www.sciencedirect.com/science/article/abs/pii/S2468125324002838
- World Health Organization Regional Office for the Eastern Mediterranean. Ramadan 2026 : un temps pour la santé et pour la générosité [Internet]. Cairo: WHO EMRO; 2026 [cited 2026 Mar 1]. Available from: https://www.emro.who.int/fr/media/media-events/ramadan-2026.html
- The Pharmaceutical Journal. Case-based learning: medicines management during Ramadan. 2022 Mar 23 [cited 2026 Mar 1]. Available from: https://pharmaceutical-journal.com/article/ld/case-based-learning-medicines-management-during-ramadan
