Tradjenta
Tradjenta
Generic Name
Tradjenta
Mechanism
- Inhibits renal sodium‑glucose co‑transporter 2 (SGLT2) in the proximal tubule.
- Blocks re‑uptake of ~90 % of filtered glucose, leading to increased glucosuria.
- Reduces plasma glucose independent of insulin secretion or sensitivity.
- Lowers intraglomerular pressure, confers renal and cardiovascular protection.
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Pharmacokinetics
| Parameter | Typical Value (12 h oral dose) |
| Absorption | Oral bioavailability ~55 %; peak plasma concentration (T_max) 1–2 h. |
| Distribution | Volume of distribution ~15 L; ~60 % protein bound. |
| Metabolism | Primarily hepatic CYP3A4/3A5 (~30 %); minor pathways via UGT1A9. |
| Elimination | Renal excretion (≈70 % unchanged); half‑life ~12 h. |
| Special Populations | Dose reduction for CrCl 30–60 mL/min; renal function avoid. |
| Drug Interactions | Strong CYP3A4 inhibitors or inducers can alter exposure; caution with nephrotoxic agents. |
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Indications
- Adjunct to diet and exercise for glycemic control in adult patients with T2DM.
- Combination therapy: dapagliflozin + metformin, sulfonylurea, or insulin.
- Cardiovascular benefit: reduces major adverse cardiovascular events in patients with established atherosclerotic disease (per DECLARE‑TIMI 58).
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Contraindications
- Absolute contraindication: severe renal impairment (eGFR < 45 mL/min/1.73 m²) or end‑stage renal disease.
- Pregnancy: category B; avoid due to potential teratogenic risk.
- Breastfeeding: not recommended.
- Risks: genital mycotic infections, volume depletion, ketoacidosis (especially in insulin‑dependent or low‑carbohydrate diets).
- Monitoring: renal function, electrolytes, blood pressure; assess for signs of ketoacidosis.
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Dosing
- Initial dose: 5 mg once daily (PO) in the morning, with or without food.
- Maintenance: 10 mg once daily.
- Titration: Increase to 10 mg after at least 4 weeks if glycemic targets are unmet and renal function remains adequate.
- In patients with renal impairment:
- CrCl ≥ 45 mL/min – 5–10 mg qd.
- CrCl 30–44 mL/min – 5 mg qd only.
- Adjunctive therapy: Can be combined safely with metformin, sulfonylureas, α‑glucosidase inhibitors, insulin, GLP‑1 RAs, or DPP‑4 inhibitors.
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Adverse Effects
| Common (≥ 10 %) | Serious (≥ 1 %) |
| Genital/urinary tract infections | Diabetic ketoacidosis |
| Volume depletion (dry mouth, dizziness) | Hypotension |
| Hyperuricemia | Fournier’s gangrene |
| Urinary tract infections | Severe hypoglycemia (with sulfonylureas/insulin) |
| Headache | Acute kidney injury (rare) |
Management tips
• Educate patients on genital hygiene; treat infections promptly.
• Encourage adequate fluid intake; monitor blood pressure.
• Counsel on ketoacidosis symptoms (Nausea, vomiting, abdominal pain, lethargy).
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Monitoring
- Baseline: eGFR, serum electrolytes, HbA1c, blood pressure.
- Periodic (every 3–6 months):
- Renal function (eGFR, creatinine).
- Glycemic control (HbA1c, fasting glucose).
- Serum uric acid.
- Adjuvant labs if on insulin/sulfonylurea: monitor for hypoglycemia.
- Patient‑reported: signs of infection, dehydration, new pain.
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Clinical Pearls
1. Renal Threshold Concept – Dapagliflozin’s glucose‑lowering effect declines when eGFR 3 mmol/L.
6. Drug–Drug Interaction Check – Strong CYP3A4 inhibitors (e.g., ketoconazole) can raise plasma levels; dose adjustments may be needed.
Key Takeaway
*Tradjenta* offers effective, insulin‑independent glycemic control with added cardio‑renal protection, but requires vigilant renal monitoring and patient education on infection, volume status, and ketoacidosis.