Comprehensive Guide to Dapagliflozin: Uses, Dosage, Side Effects, and More
What is Dapagliflozin?
Overview of Dapagliflozin
Generic Name: Dapagliflozin
Brand Name: Farxiga, generics
Drug Group: SGLT2 inhibitor (antidiabetic)
Commonly Used For
- Manage type 2 diabetes mellitus (T2DM).
- Treat heart failure with reduced ejection fraction (HFrEF).
- Reduce cardiovascular risk.
Key Characteristics
Form: Oral tablets (5 mg, 10 mg) (detailed in Dosage section).
Mechanism: Inhibits SGLT2 in the kidneys, increasing glucose excretion.
Approval: FDA-approved (2014 for Farxiga) and EMA-approved for T2DM and heart failure.
Indications and Uses of Dapagliflozin
Dapagliflozin is indicated for metabolic and cardiovascular conditions, leveraging its glucose-lowering and protective effects:
Type 2 Diabetes Mellitus (T2DM): Improves glycemic control in adults, reducing HbA1c when used alone or with metformin, insulin, or other agents, supported by long-term trials.
Heart Failure with Reduced Ejection Fraction (HFrEF): Treats HFrEF (NYHA Class II-IV) in patients with or without T2DM, reducing hospitalizations and mortality, per cardiology guidelines.
Chronic Kidney Disease (CKD): Manages CKD in T2DM patients to slow progression and reduce albuminuria, with evidence from nephrology studies.
Cardiovascular Risk Reduction: Reduces risk of cardiovascular death or hospitalization in T2DM patients with established cardiovascular disease, enhancing outcomes.
Weight Management: Used off-label to promote modest weight loss in obese T2DM patients, supporting lifestyle interventions, with endocrinology data.
Polycystic Ovary Syndrome (PCOS): Investigated off-label to improve insulin sensitivity and menstrual regularity in PCOS, with promising results from gynecologic research.
Non-Alcoholic Fatty Liver Disease (NAFLD): Explored off-label to reduce liver fat in T2DM patients with NAFLD, with emerging hepatology evidence.
Diabetic Ketoacidosis Prevention: Employed off-label in high-risk T2DM patients to mitigate ketoacidosis risk when combined with insulin, under specialist care.
Post-Transplant Diabetes Mellitus: Used off-label to manage hyperglycemia in post-transplant patients, adjusting for immunosuppression, supported by transplant medicine studies.
Dosage of Dapagliflozin
Dosage for Adults
Type 2 Diabetes Mellitus:
- Initial: 5 mg once daily in the morning, with or without food.
- Maintenance: Increase to 10 mg once daily if tolerated, maximum 10 mg/day.
Heart Failure with Reduced Ejection Fraction (HFrEF):
- 10 mg once daily, with or without food, regardless of T2DM status.
Chronic Kidney Disease (CKD):
- 10 mg once daily, with eGFR ≥25 mL/min/1.73 m², under nephrologist supervision.
Dosage for Children
Type 2 Diabetes Mellitus (10+ years):
- 5 mg once daily, titrated to 10 mg if needed, under pediatric endocrinologist supervision.
Not recommended under 10 years.
Dosage for Pregnant Women
Pregnancy Category C: Avoid unless benefits outweigh risks (e.g., severe T2DM). Consult an obstetrician, with fetal monitoring.
Dosage Adjustments
Renal Impairment: Avoid if eGFR <25 mL/min/1.73 m²; discontinue if eGFR falls below 45 mL/min/1.73 m² during therapy.
Hepatic Impairment: No adjustment needed; monitor in severe cases (Child-Pugh C).
Elderly: Start with 5 mg once daily; increase to 10 mg if tolerated.
Concomitant Medications: Adjust if combined with diuretics, increasing dehydration risk.
Additional Considerations
- Take this active ingredient in the morning with water, with or without food.
- Monitor hydration status, especially in hot weather.
How to Use Dapagliflozin
Administration:
- Swallow tablets whole with a glass of water, with or without food; avoid excessive alcohol.
- Take at the same time daily, preferably in the morning.
Timing: Use once daily, maintaining consistency.
Monitoring: Watch for increased thirst, fatigue, or signs of ketoacidosis (e.g., nausea).
Additional Tips:
- Store at 20–25°C (68–77°F), protecting from moisture and heat.
- Keep out of reach of children due to toxicity risk.
- Report severe abdominal pain, confusion, or signs of infection immediately.
Contraindications for Dapagliflozin
Hypersensitivity: Patients with a known allergy to Dapagliflozin or SGLT2 inhibitors.
Severe Renal Impairment: Contraindicated if eGFR <25 mL/min/1.73 m².
End-Stage Renal Disease (ESRD): Avoid due to lack of efficacy.
Diabetic Ketoacidosis: Contraindicated due to exacerbation risk.
Warnings & Precautions for Dapagliflozin
General Warnings
Ketoacidosis: Risk even with normal glucose levels; monitor for symptoms.
Dehydration: Risk of hypotension and acute kidney injury; ensure hydration.
Urinary Tract Infections (UTIs): Increased risk; treat promptly.
Genital Mycotic Infections: Common in uncircumcised males and females; monitor hygiene.
Hypoglycemia: Risk when combined with insulin or sulfonylureas; adjust dose.
Additional Warnings
Bone Fractures: Increased risk with long-term use; assess bone density.
Lower Limb Amputation: Rare risk; monitor foot health.
Liver Injury: Rare elevation of liver enzymes; monitor in chronic use.
Hypotension: Risk in volume-depleted patients; start with lower dose.
Hypersensitivity Reactions: Rare anaphylaxis; discontinue if swelling occurs.
Use in Specific Populations
Pregnancy: Category C; avoid unless critical; use alternatives if possible.
Breastfeeding: Excreted in breast milk; monitor infant for effects.
Elderly: Higher risk of dehydration; start with lower doses.
Children: Limited to 10+ years; supervise closely.
Renal/Hepatic Impairment: Adjust dose; avoid in severe cases.
Additional Precautions
- Inform your doctor about kidney disease, infections, or medication history before starting this medication.
- Avoid abrupt cessation; taper if combined with other agents.
Overdose and Management of Dapagliflozin
Overdose Symptoms
- Increased urination, dehydration, or dizziness.
- Severe cases: Ketoacidosis, hypotension, or renal failure.
- Nausea, vomiting, or fatigue as early signs.
- Seizures with extremely high doses.
Immediate Actions
Contact the Medical Team: Seek immediate medical help.
Supportive Care: Administer IV fluids, monitor vital signs, and correct electrolytes.
Specific Treatment: Manage ketoacidosis with insulin if present; no specific antidote.
Monitor: Check kidney function, glucose levels, and mental status for 24–48 hours.
Additional Notes
- Overdose risk is low; store securely.
- Report persistent symptoms (e.g., severe weakness, fruity breath) promptly.
Side Effects of Dapagliflozin
Common Side Effects
- Genital Infections (5–10%, manageable with hygiene)
- Urinary Tract Infections (5–8%, treat with antibiotics)
- Thirst (3–7%, reduced with hydration)
- Nausea (2–6%, relieved with food)
- Fatigue (1–5%, decreases with tolerance)
These effects may subside with dose adjustment.
Serious Side Effects
Seek immediate medical attention for:
- Metabolic: Ketoacidosis, hyperkalemia, or hypoglycemia.
- Renal: Acute kidney injury or renal failure.
- Infectious: Severe UTIs or pyelonephritis.
- Cardiovascular: Hypotension or volume depletion.
- Allergic: Rash, angioedema, or anaphylaxis.
Additional Notes
- Regular monitoring for kidney function, glucose, and infection risk is advised.
- Report any unusual symptoms (e.g., severe abdominal pain, confusion) immediately to a healthcare provider.
Drug Interactions with Dapagliflozin
This active ingredient may interact with:
- Insulin/Sulfonylureas: Increases hypoglycemia risk; adjust dose.
- Diuretics: Enhances dehydration risk; monitor closely.
- Antihypertensives: Potentiates hypotension; adjust dose.
- UGT Inducers: Reduces levels (e.g., rifampin); monitor efficacy.
- Lithium: Alters renal clearance; monitor levels.
Action: Provide your healthcare provider with a complete list of medications.
Patient Education or Lifestyle
Medication Adherence: Take this SGLT2 inhibitor as prescribed to manage T2DM, following the exact schedule.
Monitoring: Report genital infections, thirst, or fatigue immediately.
Lifestyle: Maintain hydration; avoid prolonged sun exposure.
Diet: Take with or without food; monitor carbohydrate intake.
Emergency Awareness: Know signs of ketoacidosis or kidney issues; seek care if present.
Follow-Up: Schedule regular check-ups every 3–6 months to monitor kidney and glucose levels.
Pharmacokinetics of Dapagliflozin
Absorption: Well-absorbed orally (peak at 1–2 hours); unaffected by food.
Distribution: Volume of distribution ~118 L; 91% protein-bound.
Metabolism: Hepatic via UGT1A9 to inactive metabolites.
Excretion: Primarily renal (75%) as unchanged drug; half-life 12.9 hours.
Half-Life: 12.9 hours, with sustained glucose-lowering effect.
Pharmacodynamics of Dapagliflozin
This drug exerts its effects by:
Inhibiting SGLT2 in the proximal tubule, increasing urinary glucose excretion.
Lowering blood glucose and improving insulin sensitivity in T2DM.
Reducing cardiovascular and renal risk in heart failure and CKD.
Exhibiting dose-dependent risks of dehydration and infections.
Storage of Dapagliflozin
- Temperature: Store at 20–25°C (68–77°F); protect from moisture.
- Protection: Keep in original container, away from light.
- Safety: Store out of reach of children due to toxicity risk.
- Disposal: Dispose of unused tablets per local regulations or consult a pharmacist.
Frequently Asked Questions (FAQs)
Q: What does Dapagliflozin treat?
A: This medication treats type 2 diabetes and heart failure.
Q: Can this active ingredient cause infections?
A: Yes, genital infections may occur; maintain hygiene.
Q: Is Dapagliflozin safe for children?
A: Yes, for 10+ years with a doctor’s guidance.
Q: How is this drug taken?
A: Orally as tablets, once daily, as directed.
Q: How long is Dapagliflozin treatment?
A: Long-term for T2DM or heart failure.
Q: Can I use Dapagliflozin if pregnant?
A: No, avoid unless critical; consult a doctor.
Regulatory Information
This medication is approved by:
U.S. Food and Drug Administration (FDA): Approved in 2014 (Farxiga) for T2DM, later expanded to HFrEF and CKD.
European Medicines Agency (EMA): Approved for T2DM, HFrEF, and CKD.
Other Agencies: Approved globally for diabetes and heart failure; consult local guidelines.
References
- U.S. Food and Drug Administration (FDA). (2023). Farxiga (Dapagliflozin) Prescribing Information.
- Official FDA documentation detailing the drug’s approved uses, dosage, and safety.
- European Medicines Agency (EMA). (2023). Dapagliflozin Summary of Product Characteristics.
- EMA’s comprehensive information on the medication’s indications and precautions in Europe.
- National Institutes of Health (NIH). (2023). Dapagliflozin: MedlinePlus Drug Information.
- NIH resource providing detailed information on the drug’s uses, side effects, and precautions.
- World Health Organization (WHO). (2023). WHO Guidelines on Diabetes Management: Dapagliflozin.
- WHO’s recommendations for Dapagliflozin in diabetes care.
- New England Journal of Medicine. (2022). Dapagliflozin in Heart Failure.
- Peer-reviewed article on Dapagliflozin efficacy (note: access may require a subscription).
