ATACAND HCT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ATACAND HCT (ATACAND HCT).
ATACAND HCT is a combination of candesartan, an angiotensin II receptor blocker (ARB), and hydrochlorothiazide, a thiazide diuretic. Candesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively antagonizing the AT1 receptor, leading to vasodilation and reduced blood pressure. Hydrochlorothiazide inhibits the sodium-chloride symporter in the distal convoluted tubule of the nephron, increasing sodium, chloride, and water excretion, thereby reducing plasma volume and blood pressure.
| Metabolism | Candesartan is primarily metabolized by hepatic O-deethylation via CYP2C9 to an inactive metabolite. Hydrochlorothiazide is not significantly metabolized and is excreted unchanged by the kidneys. |
| Excretion | Candesartan: ~33% renal, ~67% biliary/fecal. Hydrochlorothiazide: >95% renal. |
| Half-life | Candesartan: ~9 hours (terminal). Hydrochlorothiazide: 6-15 hours (terminal, mean ~10 hours). |
| Protein binding | Candesartan: >99% (primarily albumin). Hydrochlorothiazide: 40-70% (primarily albumin). |
| Volume of Distribution | Candesartan: 0.13 L/kg (extensive tissue distribution). Hydrochlorothiazide: 0.83-2.5 L/kg (distributes into plasma and red blood cells). |
| Bioavailability | Candesartan: ~15% (absolute, prodrug conversion). Hydrochlorothiazide: ~70% (oral). |
| Onset of Action | Candesartan: 2-4 hours; Hydrochlorothiazide: 2 hours (oral). |
| Duration of Action | Candesartan: ~24 hours; Hydrochlorothiazide: 6-12 hours (but may persist up to 24 hours for some effects). |
| Molecular Weight | Candesartan cilexetil: 610.66 Da; Hydrochlorothiazide: 297.74 Da; combination product: not applicable. |
One tablet orally once daily. Initial dose: 16 mg candesartan/12.5 mg hydrochlorothiazide. Titrate to maximum 32 mg candesartan/25 mg hydrochlorothiazide once daily.
| Dosage form | TABLET |
| Renal impairment | Contraindicated if GFR <30 mL/min/1.73 m2. No adjustment for GFR 30-50 mL/min/1.73 m2. Use with caution and monitor renal function. |
| Liver impairment | Mild to moderate hepatic impairment (Child-Pugh A or B): No dose adjustment. Severe impairment (Child-Pugh C): Not recommended due to hydrochlorothiazide accumulation risk. |
| Pediatric use | Safety and efficacy not established in pediatric patients (<18 years). |
| Geriatric use | No initial dose adjustment required. Use caution due to increased sensitivity to hypotension and electrolyte disturbances; monitor renal function and electrolytes. |
| 1st trimester | Category D: Associated with increased risk of fetal renal dysfunction, oligohydramnios, skull ossification defects, and hypotension. Use only if no alternative. |
| 2nd trimester | Category D: Fetal renal impairment, oligohydramnios, anuria, and neonatal hypotension. Avoid use; discontinue if pregnancy detected. |
| 3rd trimester | Category D: High risk of fetal and neonatal morbidity, including persistent ductus arteriosus, pulmonary hypertension, and death. Contraindicated. |
Clinical note
Comprehensive clinical and safety monograph for ATACAND HCT (ATACAND HCT).
| Placental transfer | Candesartan crosses the placenta (fetal levels ~50% of maternal) and can cause fetal nephrotoxicity and oligohydramnios. Hydrochlorothiazide crosses the placenta and can cause fetal electrolyte disturbances. |
| Breastfeeding | Candesartan is excreted in human milk in low amounts; hydrochlorothiazide is also excreted. Due to potential for hypotension and renal effects in the infant, avoid use during breastfeeding, especially in neonates or with high doses. |
■ FDA Black Box Warning
None.
| Serious Effects |
AnuriaHypersensitivity to candesartan, hydrochlorothiazide, or sulfonamide-derived drugsPregnancy (second and third trimesters)Severe renal impairment (CrCl <30 mL/min)Hepatic coma or pre-comaRefractory hypokalemia or hypercalcemia
| Precautions | Fetal toxicity: Use in pregnancy can cause oligohydramnios, fetal renal dysfunction, and skull ossification defects. Discontinue as soon as possible when pregnancy is detected., Hypotension: Symptomatic hypotension may occur in volume-depleted patients. Correct volume depletion before initiation., Impaired renal function: Monitor renal function due to risk of acute renal failure, especially in patients with renal artery stenosis., Electrolyte imbalances: Hydrochlorothiazide can cause hypokalemia, hyponatremia, hypomagnesemia, and hypercalcemia; candesartan can cause hyperkalemia., Metabolic effects: Thiazides may increase serum cholesterol, triglycerides, and uric acid levels; may cause hyperglycemia., Acute angle-closure glaucoma: Hydrochlorothiazide can cause acute transient myopia and acute angle-closure glaucoma., Systemic lupus erythematosus: Thiazides have been reported to cause exacerbation or activation of SLE., Non-melanoma skin cancer: Thiazide diuretics may increase risk; monitor for skin lesions. |
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| Lactation Rating | L4 - Possibly Hazardous |
| Teratogenic Risk | Pregnancy Category D. First trimester: potential fetotoxicity; second and third trimesters: ACE inhibitor exposure causes oligohydramnios, fetal renal dysfunction, skull ossification defects, and neonatal renal failure. Angiotensin receptor blocker (ARB) component: similar adverse effects. Thiazide diuretic: risk of fetal/neonatal jaundice, thrombocytopenia, and electrolyte disturbances. Use contraindicated in pregnancy. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function (serum creatinine, BUN), and serum electrolytes (especially potassium, sodium). Fetal monitoring: ultrasound for amniotic fluid volume (oligohydramnios), fetal growth, and renal function. Neonatal monitoring: assess for hypotension, oliguria, hyperkalemia, and hyperbilirubinemia. |
| Fertility Effects | ACE inhibitors and ARBs have been associated with decreased fertility in animal studies; limited human data. Hydrochlorothiazide may not directly affect fertility. Overall, potential for reversible impairment of fertility in males and females. |
| Food/Dietary | Avoid salt substitutes containing potassium chloride unless approved by your doctor. Limit high-potassium foods (e.g., bananas, oranges, tomatoes) if hyperkalemia risk is present. Take hydrochlorothiazide with food or milk to reduce gastrointestinal upset. Grapefruit juice has no significant interaction with this combination. |
| Clinical Pearls | ATACAND HCT is a fixed-dose combination of candesartan (an angiotensin II receptor blocker) and hydrochlorothiazide (a thiazide diuretic). Monitor renal function and electrolytes, especially potassium and sodium, within 2 weeks of initiation and periodically thereafter. Avoid use in pregnancy; discontinue as soon as pregnancy is detected. May cause symptomatic hypotension, particularly in volume-depleted patients; correct volume depletion before starting. Can exacerbate gout due to thiazide-induced hyperuricemia. Not recommended for use with aliskiren in patients with diabetes or renal impairment (GFR <60 mL/min). |
| Patient Advice | Do not take if you are pregnant, plan to become pregnant, or are breastfeeding. · Take exactly as prescribed; do not skip doses or double up. · Drink adequate fluids to prevent dehydration unless instructed otherwise by your doctor. · Avoid alcohol and NSAIDs (e.g., ibuprofen) as they may increase side effects. · Report symptoms like lightheadedness, excessive thirst, muscle cramps, or irregular heartbeat. · Monitor blood pressure regularly at home and keep a log. · This medication may increase sensitivity to sunlight; use sunscreen and protective clothing. |