Usage
- This combination drug is prescribed for the treatment of essential hypertension (high blood pressure) in adults. It is particularly beneficial for patients whose blood pressure is not adequately controlled by dual-drug therapy. It may also be used in the management of chronic kidney disease (CKD) associated with hypertension.
- Pharmacological Classification: Antihypertensive (comprising an angiotensin II receptor blocker (ARB), a calcium channel blocker (CCB), and a thiazide-like diuretic).
- Mechanism of Action: This triple-combination therapy targets multiple pathways involved in blood pressure regulation. Olmesartan blocks angiotensin II receptors, leading to vasodilation. Cilnidipine inhibits calcium influx into vascular smooth muscle cells, further promoting vasodilation. Chlorthalidone increases the excretion of sodium and water, reducing blood volume.
Alternate Names
While there isn’t an official international nonproprietary name for this specific combination, it’s often described by its constituent drugs. Some regional variations may exist.
- Brand Names: Several brand names are available including Olmevac Trio, Olmistrum Trio, Olkem Trio, Nulong Trio, Olnyd Trio, Olsong Trio, Olvan Trio, Olmin Trio, Trinexovas.
How It Works
- Pharmacodynamics: Olmesartan medoxomil, a prodrug, is rapidly hydrolyzed to olmesartan during absorption. Olmesartan selectively blocks the binding of angiotensin II to the type 1 angiotensin II receptor (AT1) subtype, reducing blood pressure by inhibiting vasoconstriction and aldosterone secretion. Cilnidipine, a dihydropyridine calcium channel blocker, inhibits calcium ion influx across cell membranes, promoting vasodilation. Chlorthalidone inhibits sodium reabsorption in the distal convoluted tubule, leading to increased excretion of sodium and water, thus decreasing blood volume and lowering blood pressure.
- Pharmacokinetics: Olmesartan medoxomil is orally administered. Cilnidipine is well-absorbed orally, reaching peak plasma concentrations in approximately 1 to 4 hours. Chlorthalidone is also well-absorbed orally, reaching peak plasma concentrations in approximately 3-6 hours. The elimination half-lives of these agents are approximately 13 hours for olmesartan, 6-12 hours for cilnidipine and 30-60 hours for chlorthalidone.
- Mode of Action (Cellular/Molecular): Olmesartan acts by blocking the AT1 receptor. Cilnidipine blocks L-type and N-type calcium channels. Chlorthalidone inhibits the sodium-chloride symporter in the distal convoluted tubule of the kidney.
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Olmesartan binds to and blocks the AT1 receptor. Cilnidipine blocks calcium channels. Chlorthalidone inhibits the sodium-chloride symporter.
- Elimination Pathways: Olmesartan is primarily eliminated through biliary excretion with some renal elimination; Cilnidipine is primarily eliminated via hepatic metabolism; Chlorthalidone is mainly excreted unchanged in the urine.
Dosage
Standard Dosage
Adults:
- The standard dose is one tablet containing Olmesartan 40mg, Cilnidipine 10mg, and Chlorthalidone 12.5mg taken orally once daily, preferably in the morning with or without food.
Children:
- The safety and effectiveness of this combination have not been established in the pediatric population. It is not recommended for use in children below 12 years of age.
Special Cases:
- Elderly Patients: Start with a lower dose and monitor closely for hypotension (low blood pressure). More frequent blood pressure monitoring is recommended.
- Patients with Renal Impairment: For mild to moderate impairment, the maximum recommended olmesartan dose is 20mg. In patients with moderate renal impairment, monitoring serum potassium and creatinine levels is advised. This combination is contraindicated in severe renal impairment (creatinine clearance < 30 mL/min).
- Patients with Hepatic Dysfunction: Use with caution in patients with mild to moderate hepatic dysfunction. Dose adjustment may be required. The combination is contraindicated in severe hepatic impairment.
- Patients with Comorbid Conditions: Caution is advised in patients with heart failure, diabetes, gout, hyperlipidemia, and electrolyte imbalances. Monitor serum electrolytes, uric acid, and blood glucose as needed.
Clinical Use Cases
This combination is primarily indicated for chronic hypertension management and is not typically used in acute clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dose modifications should be based on individual patient response and tolerability, with consideration for renal/hepatic function and comorbid conditions.
Side Effects
Common Side Effects:
- Dizziness
- Lightheadedness
- Headache
- Fatigue
- Increased urination
- Peripheral edema (swelling of legs and feet)
Rare but Serious Side Effects:
- Hypotension
- Electrolyte disturbances (e.g., hypokalemia)
- Renal impairment
- Allergic reactions
- Angioedema
Long-Term Effects:
Chronic complications from prolonged use are generally related to uncontrolled hypertension or the underlying comorbidities.
Adverse Drug Reactions (ADR):
Clinically significant ADRs include severe hypotension, syncope, acute renal failure, angioedema, and electrolyte disturbances.
Contraindications
- Hypersensitivity to any component of the drug.
- Anuria (inability to urinate).
- Concomitant use of aliskiren in patients with diabetes.
- Severe renal or hepatic impairment.
- Pregnancy and breastfeeding.
Drug Interactions
- Other antihypertensives: May potentiate hypotensive effects.
- Potassium-sparing diuretics: May increase risk of hyperkalemia.
- NSAIDs: May reduce the antihypertensive effect.
- Lithium: May increase lithium levels.
- Alcohol: May enhance hypotensive effects.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: D (contraindicated). This drug can cause fetal harm.
- Fetal risks include renal and cardiovascular developmental abnormalities.
- This combination is contraindicated during breastfeeding due to the potential for adverse effects in the neonate.
Drug Profile Summary
- Mechanism of Action: Combined vasodilatory and diuretic effects leading to blood pressure reduction.
- Side Effects: Dizziness, lightheadedness, headache, fatigue, increased urination, peripheral edema.
- Contraindications: Hypersensitivity, anuria, concomitant use of aliskiren in patients with diabetes, severe renal/hepatic impairment, pregnancy, and breastfeeding.
- Drug Interactions: Other antihypertensives, potassium-sparing diuretics, NSAIDs, lithium, alcohol.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: One tablet (Olmesartan 40mg/Cilnidipine 10mg/Chlorthalidone 12.5mg) once daily.
- Monitoring Parameters: Blood pressure, renal function (serum creatinine, potassium), electrolytes.
Popular Combinations
This triple combination itself is a popular strategy for managing resistant hypertension. The combination leverages the different mechanisms of action to enhance blood pressure control.
Precautions
- General Precautions: Monitor blood pressure, renal function, and electrolytes. Assess for allergies and other comorbidities.
- Specific Populations: Avoid in pregnancy and breastfeeding. Use with caution in elderly patients and those with renal/hepatic impairment.
- Lifestyle Considerations: Encourage lifestyle modifications like diet, exercise, and smoking cessation.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Chlorthalidone + Cilnidipine + Olmesartan Medoxomil?
A: The standard adult dosage is one tablet containing Olmesartan 40mg, Cilnidipine 10mg, and Chlorthalidone 12.5mg taken orally once daily. Dosage should be adjusted based on individual patient characteristics and response.
Q2: What are the common side effects?
A: Common side effects include dizziness, headache, increased urination, fatigue, and peripheral edema.
Q3: Can this combination be used during pregnancy or breastfeeding?
A: No, this combination is contraindicated during pregnancy and breastfeeding due to potential harm to the fetus/infant.
Q4: How does this combination drug lower blood pressure?
A: It combines three different mechanisms: blocking angiotensin II receptors (Olmesartan), inhibiting calcium channels (Cilnidipine), and increasing sodium and water excretion (Chlorthalidone).
Q5: Are there any drug interactions I should be aware of?
A: Yes, this combination can interact with other antihypertensives, potassium-sparing diuretics, NSAIDs, lithium, and alcohol. Concomitant use should be carefully evaluated.
Q6: What should I do if a patient misses a dose?
A: If a dose is missed, advise the patient to take it as soon as they remember, unless it is close to the time for their next dose. Do not double the dose.
Q7: Can this combination be used in patients with renal impairment?
A: It can be used with caution in mild to moderate renal impairment, with dose adjustments for Olmesartan. It is contraindicated in severe renal impairment.
Q8: What are the monitoring parameters for patients on this medication?
A: Monitor blood pressure, renal function (creatinine, potassium), and electrolytes regularly. Monitor uric acid and glucose levels in patients with gout or diabetes, respectively.
Q9: Is this combination safe for use in the elderly?
A: It can be used in the elderly, but start with a lower dose and closely monitor blood pressure due to increased sensitivity to hypotensive effects.
