Usage
This combination drug is prescribed for the treatment of hypertension (high blood pressure) in patients whose blood pressure is not adequately controlled by two-drug combinations of the individual components or by other antihypertensive agents from two of the three drug classes it contains. It is not indicated for initial therapy of hypertension.
It falls under the following pharmacological classifications:
- Angiotensin II Receptor Blocker (ARB): Olmesartan medoxomil blocks the action of angiotensin II, a hormone that constricts blood vessels.
- Calcium Channel Blocker (CCB): Amlodipine relaxes and widens blood vessels by blocking calcium channels.
- Thiazide Diuretic: Hydrochlorothiazide helps the kidneys eliminate excess salt and water, thereby reducing blood volume and lowering blood pressure.
The combined mechanism of action results in synergistic blood pressure reduction through different pathways.
Alternate Names
This triple combination drug is often referred to by the brand name Tribenzor. It is also available as generic olmesartan medoxomil/amlodipine/hydrochlorothiazide. There aren’t widely used international or regional variations of this combined name, although individual components may have different names in certain regions.
How It Works
Pharmacodynamics:
- Olmesartan: Blocks angiotensin II receptors, leading to vasodilation and reduced aldosterone secretion, which lowers blood volume.
- Amlodipine: Inhibits calcium influx into vascular smooth muscle cells, causing vasodilation.
- Hydrochlorothiazide: Inhibits sodium reabsorption in the distal convoluted tubule of the kidney, increasing sodium and water excretion, thus reducing blood volume.
Pharmacokinetics:
- Olmesartan: Administered as a prodrug (olmesartan medoxomil), rapidly converted to olmesartan during absorption. High bioavailability, metabolized by ester hydrolysis, primarily excreted in feces and urine. Peak plasma concentration is reached within 1 to 2 hours.
- Amlodipine: Well absorbed orally, high bioavailability, extensively metabolized in the liver by CYP3A4 enzymes. Has a long half-life (approximately 30-50 hours), allowing for once-daily dosing. Excreted mainly in urine and feces. Peak plasma concentration is reached within 6 to 12 hours.
- Hydrochlorothiazide: Orally administered, incompletely absorbed, not metabolized significantly, primarily excreted unchanged in urine. Peak plasma concentration is reached within 1 to 2.5 hours.
Mode of Action/Receptor Binding/Enzyme Inhibition:
- Olmesartan: Selectively binds to the AT1 subtype of angiotensin II receptors.
- Amlodipine: Inhibits L-type calcium channels in vascular smooth muscle.
- Hydrochlorothiazide: Inhibits sodium-chloride symporter in the distal convoluted tubule.
Elimination Pathways:
- Olmesartan: Primarily biliary and renal excretion.
- Amlodipine: Hepatic metabolism (CYP3A4) followed by renal and fecal excretion.
- Hydrochlorothiazide: Renal excretion.
Dosage
Standard Dosage
Adults:
Initial dose: Typically starts with 20 mg olmesartan medoxomil / 5 mg amlodipine / 12.5 mg hydrochlorothiazide once daily.
Dosage may be increased in 2-week intervals as needed, titrating each component individually up to a maximum of 40 mg olmesartan medoxomil / 10 mg amlodipine / 25 mg hydrochlorothiazide once daily.
Children:
Not recommended for use in patients below 18 years due to a lack of data on safety and efficacy.
Special Cases:
- Elderly Patients: Use with caution, particularly in patients over 75 years old. Dose adjustments may be necessary.
- Patients with Renal Impairment: Avoid use in patients with severe renal impairment (creatinine clearance < 30 mL/min). No adjustment is generally required for mild to moderate impairment.
- Patients with Hepatic Dysfunction: Use with caution in patients with mild to moderate hepatic impairment. Avoid use in patients with severe hepatic impairment.
- Patients with Comorbid Conditions: Careful monitoring is required in patients with diabetes, heart failure, or electrolyte imbalances.
Clinical Use Cases
This drug is specifically designed for chronic hypertension management. It is not indicated for acute situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dosage adjustments may be necessary based on individual patient response, renal function, hepatic function, and concomitant medications.
Side Effects
Common Side Effects
Dizziness, peripheral edema, headache, fatigue, nasopharyngitis, muscle spasms, nausea, upper respiratory tract infection, diarrhea, urinary tract infection, joint swelling.
Rare but Serious Side Effects
Hypotension (especially in volume-depleted individuals), syncope, angioedema, increased angina or myocardial infarction (especially upon initiating or increasing dose), hyperkalemia, acute renal failure, worsening of renal function, hyponatremia, hypokalemia, hypomagnesemia, exacerbation or activation of systemic lupus erythematosus, acute angle-closure glaucoma, sprue-like enteropathy.
Long-Term Effects
Potential long-term effects include electrolyte imbalances, renal impairment, and cardiovascular events if blood pressure is not adequately controlled.
Adverse Drug Reactions (ADR)
Clinically significant ADRs requiring immediate intervention include severe hypotension, angioedema, acute renal failure, and electrolyte imbalances.
Contraindications
Hypersensitivity to any component, anuria, severe hepatic impairment, cholestasis, biliary obstructive disorders, second and third trimesters of pregnancy, concomitant use with aliskiren in patients with diabetes mellitus or renal impairment.
Drug Interactions
Many drug interactions can occur. Some significant ones include:
- Aliskiren: Contraindicated in patients with diabetes or renal impairment.
- Lithium: Increased lithium levels and toxicity.
- NSAIDs: Reduced antihypertensive effect, increased risk of renal impairment.
- CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir): Increased amlodipine levels.
- Cyclosporine, Tacrolimus: Increased cyclosporine and tacrolimus levels.
- Diuretics: Additive effects.
- Antidiabetic drugs: May require dosage adjustment.
Interactions may also occur with alcohol, potassium supplements, and other antihypertensive medications. Consult a comprehensive drug interaction resource for a complete list.
Pregnancy and Breastfeeding
- Pregnancy: Contraindicated during the second and third trimesters. Not recommended during the first trimester. Can cause fetal harm.
- Breastfeeding: Not recommended. Excreted in breast milk.
Drug Profile Summary
- Mechanism of Action: ARB/CCB/Thiazide diuretic combination, synergistically reducing blood pressure via different pathways.
- Side Effects: Dizziness, edema, headache, fatigue, electrolyte imbalances, hypotension, and others.
- Contraindications: Hypersensitivity, anuria, severe hepatic impairment, pregnancy (2nd/3rd trimester), concomitant use with aliskiren in patients with diabetes or renal impairment.
- Drug Interactions: Numerous drug interactions, notably with aliskiren, lithium, NSAIDs, CYP3A4 inhibitors.
- Pregnancy & Breastfeeding: Contraindicated in 2nd/3rd trimester pregnancy, not recommended during breastfeeding.
- Dosage: Titrate to a maximum of 40 mg olmesartan medoxomil/10 mg amlodipine/25 mg hydrochlorothiazide once daily.
- Monitoring Parameters: Blood pressure, renal function, electrolytes (potassium, sodium, magnesium).
Popular Combinations
Although this medication is itself a combination, other antihypertensive agents may be added if blood pressure control is inadequate. The choice of additional medication will depend on the patient’s specific circumstances and other comorbidities.
Precautions
- General Precautions: Assess renal and hepatic function, electrolyte levels, and volume status before initiating therapy. Monitor blood pressure and electrolytes regularly.
- Specific Populations: Use with caution in elderly patients and those with renal or hepatic impairment. Contraindicated in pregnancy (2nd/3rd trimester). Not recommended during breastfeeding.
- Lifestyle Considerations: Encourage lifestyle modifications such as sodium restriction, weight loss, and regular exercise.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Amlodipine + Hydrochlorothiazide + Olmesartan Medoxomil?
A: Initial dose is usually 20 mg olmesartan medoxomil/5 mg amlodipine/12.5 mg hydrochlorothiazide once daily. The maximum recommended dose is 40 mg/10 mg/25 mg once daily. Dosage should be titrated based on individual patient response and tolerability.
Q2: Can this combination be used as initial therapy for hypertension?
A: No, this medication is intended for patients whose blood pressure is not adequately controlled on two-drug combinations of its components or other antihypertensive agents. It is not for initial therapy.
Q3: What are the most serious side effects to watch out for?
A: Severe hypotension, angioedema, acute renal failure, and electrolyte imbalances require immediate attention.
Q4: What are the key drug interactions to consider?
A: Interactions with aliskiren, lithium, NSAIDs, and CYP3A4 inhibitors are particularly important. Refer to a comprehensive drug interaction resource before prescribing.
Q5: Can this drug be used during pregnancy or breastfeeding?
A: It’s contraindicated during the second and third trimesters of pregnancy and is not recommended during breastfeeding. Not recommended during the first trimester.
Q6: Are there any special considerations for elderly patients?
A: Yes, elderly patients, especially those over 75, may be more sensitive to the drug’s effects and require closer monitoring and possible dose adjustments.
Q7: How should the dosage be adjusted for patients with renal impairment?
A: Avoid use in patients with severe renal impairment (CrCl < 30 ml/min). No adjustment is typically needed for mild to moderate impairment.
Q8: What are the key monitoring parameters for this combination?
A: Closely monitor blood pressure, renal function, and electrolyte levels, especially potassium, sodium, and magnesium.
Q9: What should be done if a patient develops angioedema?
A: Discontinue the medication immediately and provide appropriate medical support. Angioedema can be life-threatening.
