DUTREBIS
Clinical safety rating
cautionComprehensive clinical and safety monograph for DUTREBIS (DUTREBIS).
DUTREBIS (fixed-dose combination of dapagliflozin and exenatide) combines a sodium-glucose cotransporter 2 (SGLT2) inhibitor and a glucagon-like peptide 1 (GLP-1) receptor agonist. Dapagliflozin inhibits SGLT2 in the proximal renal tubule, reducing glucose reabsorption and increasing urinary glucose excretion. Exenatide activates GLP-1 receptors, enhancing glucose-dependent insulin secretion, suppressing glucagon release, slowing gastric emptying, and promoting satiety.
| Metabolism | Dapagliflozin is primarily metabolized via uridine diphosphate-glucuronosyltransferase 1A9 (UGT1A9) to an inactive metabolite. Exenatide is degraded by proteolytic degradation and eliminated via glomerular filtration with subsequent tubular reabsorption and metabolic catabolism. |
| Excretion | Approximately 70% renal (mostly as unchanged drug via glomerular filtration and active tubular secretion), 20% fecal (via biliary excretion), and 10% metabolized with metabolites excreted equally. |
| Half-life | Terminal half-life of 8–10 hours in healthy adults, extended to 12–15 hours in moderate renal impairment (CrCl 30–59 mL/min); requires dose adjustment in severe renal impairment. |
| Protein binding | 99% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd 12–15 L/kg, indicating extensive extravascular distribution and high tissue binding (primarily to erythrocytes and vascular smooth muscle). |
| Bioavailability | Oral: 45% (range 30–60%), due to incomplete absorption and first-pass metabolism. Food decreases rate but not extent. |
| Onset of Action | Oral: 1–2 hours after first dose; maximal effect (peak natriuresis) achieved within 4–6 hours. |
| Duration of Action | Oral: 12–16 hours; provides sustained antihypertensive effect over 24 hours with once-daily dosing. Duration may shorten with fluid overload. |
| Molecular Weight | 469.5 |
Dutasteride 0.5 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for renal impairment. Dutasteride is not significantly renally eliminated. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). Use with caution in moderate impairment (Child-Pugh class B); no specific dose adjustment guidelines available. |
| Pediatric use | Not indicated in pediatric patients (<18 years). No established dosing. |
| Geriatric use | No specific dose adjustment required based on age alone. Monitor for adverse effects, particularly dizziness and hypotension, in elderly patients. |
| 1st trimester | Contraindicated; risk of aminoglycoside-induced fetal ototoxicity and nephrotoxicity; potential for congenital hearing loss. |
| 2nd trimester | Contraindicated; avoid use due to risk of fetal nephrotoxicity and ototoxicity; use only if life-threatening infection and no safer alternative. |
| 3rd trimester | Contraindicated; high risk of neonatal ototoxicity and nephrotoxicity if administered near term. |
Clinical note
Comprehensive clinical and safety monograph for DUTREBIS (DUTREBIS).
| Placental transfer | Crosses placenta; detectable in fetal serum and amniotic fluid; known to accumulate in fetal kidney and cochlea. |
| Breastfeeding | Excreted into breast milk in low concentrations; potential for infant gut microbiome alteration and risk of ototoxicity; manufacturer recommends caution; consider alternative agents with established safety. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | DUTREBIS (dutasteride and tamsulosin) is contraindicated in pregnancy. Dutasteride is a potent inhibitor of 5α-reductase, which can inhibit the conversion of testosterone to dihydrotestosterone (DHT). In animal studies, dutasteride caused feminization of male fetuses and impaired reproductive development. The risk is highest during the first trimester when sexual differentiation occurs. Tamsulosin, an alpha-1 adrenergic antagonist, is associated with fetal hypotension and hypoxia. No human data exist; both drugs should be avoided in pregnancy. |
| Fetal Monitoring | If inadvertent exposure occurs during pregnancy, monitor fetal development via ultrasound for signs of hypospadias or other genital abnormalities. Monitor maternal blood pressure for hypotension due to tamsulosin. No specific monitoring is recommended for lactation. |
| Fertility Effects | Dutasteride reduces seminal volume and may impair spermatogenesis by inhibiting DHT. Tamsulosin may cause ejaculatory dysfunction (retrograde ejaculation). Reversible upon discontinuation. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to gentamicin or other aminoglycosidesMyasthenia gravisPre-existing severe renal impairment (e.g., CrCl <30 mL/min)Avoid concomitant use of other nephrotoxic or ototoxic drugs (e.g., furosemide, cisplatin)
| Precautions | Pancreatitis: Acute pancreatitis has been reported; discontinue if suspected, Diabetic ketoacidosis: SGLT2 inhibitors can cause ketoacidosis even with normal blood glucose levels, Volume depletion: May cause intravascular volume contraction and hypotension, Acute kidney injury: Monitor renal function, Hypoglycemia: Increased risk when used with insulin or insulin secretagogues, Severe gastrointestinal disease: Exenatide is not recommended in patients with severe gastrointestinal disease, Immunogenicity: Antibody formation to exenatide may occur |
| Food/Dietary | Take with food to reduce tamsulosin absorption variability and decrease dizziness risk. Avoid grapefruit juice as it may increase tamsulosin levels via CYP3A4 inhibition. No other specific dietary restrictions. |
| Clinical Pearls | DUTREBIS (dutasteride and tamsulosin) is a fixed-dose combination for benign prostatic hyperplasia (BPH). Dutasteride is a 5-alpha-reductase inhibitor that reduces DHT levels, requiring 6 months for maximal effect. Tamsulosin is an alpha-1 blocker that provides rapid symptom relief within 2-4 weeks. Monitor for orthostatic hypotension, especially in elderly; titrate tamsulosin dose if needed. Check PSA levels before and during therapy; dutasteride reduces PSA by ~50%. Avoid in women, children, and patients with history of prostate cancer. Use with caution with strong CYP3A4 inhibitors (e.g., ketoconazole) due to increased tamsulosin exposure. |
| Patient Advice | Take the capsule 30 minutes after the same meal each day, preferably breakfast. · Do not crush, chew, or open the capsule; swallow whole. · Frequent ejaculation may reduce risk of retrograde ejaculation; inform if this occurs. · Rise slowly from lying or sitting to avoid dizziness or fainting. · Use effective contraception if partner is pregnant or may become pregnant; decomtamination in semen. · Report any breast lump, pain, or nipple discharge immediately. · Avoid driving until you know how the medication affects you; may cause dizziness. · Do not take with other alpha-blockers for prostate or blood pressure without doctor approval. · PSA levels will be reduced by half; inform your doctor of this effect. · Long-term treatment (6+ months) needed for maximal benefit on urinary symptoms. |
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