TIMOLIDE 10-25
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TIMOLIDE 10-25 (TIMOLIDE 10-25).
Timolol is a non-selective beta-adrenergic receptor antagonist that blocks beta-1 and beta-2 receptors, reducing heart rate, myocardial contractility, and blood pressure. Hydrochlorothiazide is a thiazide diuretic that inhibits the sodium-chloride symporter in the distal convoluted tubule, increasing excretion of sodium and water, reducing plasma volume and blood pressure.
| Metabolism | Timolol is extensively metabolized in the liver primarily by CYP2D6; hydrochlorothiazide is not metabolized and is excreted unchanged in urine. |
| Excretion | Timolol is primarily eliminated by renal excretion of unchanged drug and metabolites. Approximately 20% of a dose is excreted unchanged in urine, with the remainder as metabolites (mostly inactive). Fecal elimination accounts for less than 5%. |
| Half-life | The terminal elimination half-life of timolol is approximately 4 hours in patients with normal renal function, but may be prolonged to 12-20 hours in patients with renal impairment or hepatic dysfunction. The half-life of hydrochlorothiazide is 6-15 hours. |
| Protein binding | Timolol is approximately 10-60% bound to plasma proteins (primarily albumin). Hydrochlorothiazide is about 40-70% bound to plasma proteins. |
| Volume of Distribution | Timolol: Vd approximately 1.3-3.6 L/kg, indicating extensive tissue distribution. Hydrochlorothiazide: Vd approximately 0.8-1.2 L/kg. |
| Bioavailability | Oral bioavailability of timolol is approximately 50-75% due to first-pass metabolism. Hydrochlorothiazide bioavailability is about 65-70%. Ophthalmic timolol undergoes systemic absorption, with measurable plasma levels. |
| Onset of Action | Oral: antihypertensive effect begins within 1-2 hours; diuretic effect of hydrochlorothiazide begins within 2 hours. Ophthalmic: reduction of intraocular pressure occurs within 30 minutes. |
| Duration of Action | Oral: antihypertensive effect lasts 12-24 hours, supporting once-daily dosing. Ophthalmic: IOP reduction persists for 12-24 hours. Hydrochlorothiazide's diuretic effect lasts 6-12 hours. |
One tablet (timolol 10 mg / hydrochlorothiazide 25 mg) orally once daily. May be increased to two tablets once daily if needed.
| Dosage form | TABLET |
| Renal impairment | GFR 30-50 mL/min: maximum dose of timolol 10 mg/hydrochlorothiazide 25 mg once daily. GFR <30 mL/min: contraindicated (hydrochlorothiazide ineffective, risk of thiazide accumulation). |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose; start with lowest dose (timolol 10 mg/hydrochlorothiazide 25 mg) and titrate cautiously. Child-Pugh C: contraindicated (risk of hepatic encephalopathy and beta-blocker toxicity). |
| Pediatric use | Not recommended; safety and efficacy not established in pediatric patients. |
| Geriatric use | Start with lowest dose (timolol 10 mg/hydrochlorothiazide 25 mg once daily); monitor renal function, electrolytes, and heart rate. Avoid in patients with significant bradycardia or heart block. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TIMOLIDE 10-25 (TIMOLIDE 10-25).
| Breastfeeding | Timolol is excreted into breast milk (M/P ratio approximately 1.4). Hydrochlorothiazide is also present in low amounts. Due to potential for infant bradycardia, hypoglycemia, and electrolyte disturbances, use during breastfeeding is generally not recommended. If essential, monitor infant for signs of beta-blockade and thiazide effects. |
| Teratogenic Risk | First trimester: Risk category D. Timolol (beta-blocker) and hydrochlorothiazide (diuretic) are associated with potential fetal bradycardia, hypoglycemia, and growth restriction. Thiazides may cause fetal electrolyte imbalances and jaundice. Second and third trimesters: Continued risk of fetal bradycardia, reduced placental perfusion, and neonatal complications (hypoglycemia, bradycardia, respiratory depression). Thiazides may cause oligohydramnios and neonatal thrombocytopenia. |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | Burning eyes Stinging in the eyes |
| Serious Effects |
["Bronchial asthma","Sinus bradycardia","Heart block greater than first degree","Cardiogenic shock","Overt cardiac failure","Anuria","Hypersensitivity to timolol or hydrochlorothiazide"]
| Precautions | ["Exacerbation of angina or myocardial ischemia upon abrupt withdrawal","Bronchospasm in patients with asthma or COPD","Masking of hypoglycemia in diabetic patients","Electrolyte imbalances, hypokalemia, hypercalcemia, hyperuricemia due to hydrochlorothiazide","Fetal harm if used during pregnancy"] |
Loading safety data…
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and electrolytes. Fetal growth scans and amniotic fluid index assessment recommended. Neonatal monitoring for bradycardia, hypoglycemia, and respiratory depression post-delivery. |
| Fertility Effects | Beta-blockers may impair male fertility by reducing sperm motility. Thiazides have been associated with erectile dysfunction but no direct evidence of fertility impairment in females. |