MYDCOMBI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MYDCOMBI (MYDCOMBI).
MYDCOMBI contains midodrine and dapagliflozin. Midodrine is a prodrug that is converted to desglymidodrine, an alpha-1 adrenergic receptor agonist, causing vasoconstriction and increased blood pressure. Dapagliflozin inhibits sodium-glucose cotransporter 2 (SGLT2) in the renal proximal tubule, reducing glucose reabsorption and promoting glucosuria.
| Metabolism | Midodrine is rapidly metabolized by hepatic esterases to its active metabolite desglymidodrine, which is further metabolized via glucuronidation and oxidation. Dapagliflozin is primarily metabolized via glucuronidation by UGT1A9 to an inactive metabolite. |
| Excretion | Renal excretion accounts for approximately 70% of the dose, primarily as unchanged drug; biliary/fecal elimination accounts for the remaining 30%. |
| Half-life | Terminal elimination half-life is approximately 12-14 hours in healthy adults; may be prolonged in renal impairment. |
| Protein binding | Approximately 95% bound primarily to albumin. |
| Volume of Distribution | Vd is approximately 0.5 L/kg, indicating distribution primarily into extracellular fluid. |
| Bioavailability | Oral bioavailability is approximately 40% due to first-pass metabolism. |
| Onset of Action | Oral: 30-60 minutes; Intravenous: within 5 minutes. |
| Duration of Action | Duration of action is 8-12 hours after oral administration; clinical effect may persist longer in patients with hepatic impairment. |
Adults: 1 tablet (40 mg telmisartan/25 mg hydrochlorothiazide) orally once daily; maximum dose 1 tablet daily.
| Dosage form | SPRAY, METERED |
| Renal impairment | GFR ≥30 mL/min: No adjustment; GFR <30 mL/min or dialyzed: Contraindicated due to hydrochlorothiazide component. |
| Liver impairment | Child-Pugh A: No adjustment; Child-Pugh B: Contraindicated (telmisartan is highly metabolized); Child-Pugh C: Contraindicated. |
| Pediatric use | Not recommended for pediatric patients; safety and efficacy not established. |
| Geriatric use | Initiate at lower end of dosing range; monitor renal function and electrolytes; no specific dose adjustment required. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MYDCOMBI (MYDCOMBI).
| Breastfeeding | Both amiloride and hydrochlorothiazide are excreted in human milk in small amounts. M/P ratio not specifically reported for the combination. Hydrochlorothiazide may suppress lactation. Risk to nursing infant includes potential for electrolyte disturbances. Decision to breastfeed should consider importance of drug to mother and potential risks; alternative antihypertensives preferred during lactation. |
| Teratogenic Risk | MYDCOMBI contains amiloride and hydrochlorothiazide. Amiloride: No adequate studies in pregnant women; animal studies show no teratogenicity at clinically relevant doses. Hydrochlorothiazide: Crosses placenta; may cause fetal or neonatal jaundice, thrombocytopenia, and electrolyte disturbances. Risk in first trimester is low; second and third trimester exposure associated with adverse fetal effects including hyponatremia, hypokalemia, and possible association with congenital anomalies (limited data). Given the combination, avoid use during pregnancy, especially in second and third trimesters, unless no alternative. |
■ FDA Black Box Warning
Midodrine can cause marked supine hypertension (systolic >200 mmHg). Supine blood pressure should be monitored and patients should be advised to elevate the head of the bed and avoid supine positions.
| Serious Effects |
["Severe organic heart disease (e.g., unstable angina, recent MI, severe aortic stenosis)","Supine hypertension (systolic blood pressure >180 mmHg or diastolic >110 mmHg)","Urinary retention (midodrine)","Pheochromocytoma (midodrine)","Thyrotoxicosis (midodrine)","Severe renal impairment (eGFR <30 mL/min/1.73 m²) or dialysis (dapagliflozin)","Hypersensitivity to any component","Concomitant use with other alpha-adrenergic agonists may exacerbate hypertension"]
| Precautions | ["Supine hypertension and potential for severe hypertension if supine","Symptomatic hypotension may occur upon standing","Urinary retention (midodrine may cause bladder contraction with outlet obstruction)","Ketoacidosis in patients with diabetes, even with normal glucose levels","Volume depletion and hypotension (dapagliflozin)","Acute kidney injury and renal impairment (dapagliflozin)","Hypoglycemia when used with insulin or sulfonylureas (dapagliflozin)","Necrotizing fasciitis of the perineum (Fournier’s gangrene) with SGLT2 inhibitors","Increased risk of lower limb amputations (dapagliflozin)","Urosepsis and pyelonephritis (dapagliflozin)"] |
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| Fetal Monitoring | If used during pregnancy, monitor maternal blood pressure, serum electrolytes (especially potassium and sodium), renal function, and fluid balance. Monitor fetal growth and amniotic fluid volume via ultrasound. Newborns exposed in utero should be monitored for electrolyte disturbances, jaundice, and thrombocytopenia. |
| Fertility Effects | No human data on fertility effects. In animal studies, hydrochlorothiazide and amiloride did not impair fertility at clinically relevant doses. Theoretical impact from electrolyte disturbances may affect reproductive function. |