KLOTRIX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KLOTRIX (KLOTRIX).
KLOTRIX is a combination of an angiotensin II receptor blocker (ARB) and a thiazide diuretic. The ARB component blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively antagonizing the AT1 receptor, leading to vasodilation and reduced blood pressure. The thiazide diuretic increases sodium and water excretion by inhibiting the sodium-chloride cotransporter in the distal convoluted tubule of the kidney.
| Metabolism | The ARB component is primarily metabolized by CYP2C9 and to a lesser extent by CYP3A4. The thiazide diuretic is not extensively metabolized and is excreted unchanged in the urine. |
| Excretion | Renal 70% as unchanged drug, fecal 30% via biliary secretion |
| Half-life | Terminal half-life 12 hours; prolonged to 24–30 hours in moderate renal impairment (CrCl <50 mL/min) |
| Protein binding | 98% bound to serum albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 0.25 L/kg (reflects extensive tissue binding with low free fraction) |
| Bioavailability | Oral: 90% (minimal first-pass metabolism) |
| Onset of Action | Oral: 30–45 minutes; intravenous: 5–10 minutes |
| Duration of Action | Oral: 8–12 hours (dose-dependent); intravenous: 6–8 hours |
Adults: 500-1000 mg orally every 6 hours; maximum 4000 mg/day.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | GFR >50 mL/min: no adjustment; GFR 10-50 mL/min: 250-500 mg every 6 hours; GFR <10 mL/min: 250-500 mg every 12 hours. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 50% dose reduction; Child-Pugh C: 75% dose reduction. |
| Pediatric use | Children >12 years: same as adult; Children 6-12 years: 250 mg orally every 6 hours; <6 years: 5-10 mg/kg every 6 hours. |
| Geriatric use | Consider lower initial dose (250-500 mg every 6 hours); monitor renal function; avoid in CrCl <30 mL/min unless necessary. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for KLOTRIX (KLOTRIX).
| Breastfeeding | Excreted in breast milk; M/P ratio 0.8. Use caution, especially in neonates with G6PD deficiency. |
| Teratogenic Risk | First trimester: Limited data; theoretical risk of neural tube defects if folate antagonist. Second/third trimester: Potential for decreased fetal growth and oligohydramnios with prolonged use. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function, and fetal growth ultrasound. Assess amniotic fluid volume if used >48 hours. |
■ FDA Black Box Warning
Fetal Toxicity: Drugs acting directly on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected.
| Serious Effects |
["Pregnancy","Anuria (thiazide component)","History of hypersensitivity to sulfonamide-derived drugs (thiazide component) or ARBs","Severe renal impairment (CrCl < 30 mL/min)","Concomitant use with aliskiren in patients with diabetes or renal impairment (eGFR < 60 mL/min/1.73 m²)","Hereditary fructose intolerance (if product contains sorbitol)"]
| Precautions | ["Hypotension in volume- or salt-depleted patients","Renal impairment: Monitor renal function periodically","Hyperkalemia: Avoid with potassium-sparing diuretics or potassium supplements","Electrolyte imbalances: Hypokalemia, hyponatremia, hypomagnesemia","Acute angle-closure glaucoma or exacerbation of myopia (thiazide component)","Exacerbation or activation of systemic lupus erythematosus","Metabolic acidosis"] |
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| Fertility Effects | Reversible impairment of spermatogenesis in males; no significant effect on female fertility. |