olmesartan, amlodipine and hydrochlorothiazide

Action and Spectrum

Actions and spectrum: 

olmesartan: 

Action: olmesartan is an ARB blocker. It acts by blocking the action of angiotensin II leading to increased blood pressure. By blocking angiotensin II receptors, olmesartan helps to relax and widen blood vessels, reducing blood pressure. 

Spectrum: olmesartan is primarily used for the treatment of hypertension. It is not used to treat acute hypertensive crises. 

amlodipine: 

Action: amlodipine is a calcium channel blocker (CCB). It works by blocking the influx of calcium into the smooth muscle cells of blood vessels, leading to relaxation and dilation of the blood vessels. This results in lowered blood pressure and improved blood flow. 

Spectrum: amlodipine is used to treat hypertension and angina caused by coronary artery disease. It is used as a monotherapy or combination therapy with other antihypertensive agents. 

hydrochlorothiazide: 

Action: hydrochlorothiazide is a thiazide diuretic. It works by increasing the excretion of sodium and water through the kidneys. This reduces fluid volume and decreases blood pressure. 

Spectrum: hydrochlorothiazide is primarily used for the management of hypertension and edema (fluid retention) associated with various conditions such as congestive heart failure, kidney disease, and liver cirrhosis.  

The combination of olmesartan, amlodipine, and hydrochlorothiazide provides a synergistic effect by targeting different mechanisms involved in blood pressure regulation. This combination therapy is often prescribed when single-agent treatment is not sufficient to control blood pressure effectively. 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% 

Peripheral edema (7.7%) 

Headache (6.4%) 

Muscle spasms (3.1%) 

Diarrhea (2.6%) 

Syncope (1%) 

Nasopharyngitis (4%) 

Dizziness (5.8-8.9%) 

Fatigue (4%) 

Nausea (3%) 

Joint swelling (2.1%) 

UTI (2%) 

URTI (3%)  

Postmarketing Reports 

increased blood creatinine, hepatic enzyme elevations, Acute renal failure, extrapyramidal disorder and jaundice. 

hydrochlorothiazide 

skin non-melanoma cancer 

Black Box Warning

Black Box Warning: 

There are no black box warnings associated with olmesartan, amlodipine, and hydrochlorothiazide 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Known hypersensitivity to olmesartan or any component of the formulation. 
• H/O of angioedema related to previous use of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB). 
• Severe hypotension (low blood pressure). 
• Obstruction of the left ventricle outflow tract. 
• Anuria (absence of urine production). 
• Severe renal impairment. 
• Severe hepatic impairment. 

Caution: 

• Hypotension: The combination of these medications can cause a decrease in blood pressure, potentially leading to symptoms such as dizziness, lightheadedness, and fainting.  
• Electrolyte Imbalance: Hydrochlorothiazide, a diuretic, can cause electrolyte imbalances, particularly low levels of potassium (hypokalemia) and sodium (hyponatremia). Close monitoring of electrolyte levels is important, especially in patients with conditions predisposing them to electrolyte abnormalities. 
• Renal Impairment: The use of these medications may affect renal function, particularly in patients with pre-existing renal impairment or those with renal artery stenosis. Dose adjustments or close monitoring may be necessary in such cases. 
• Hepatic Impairment: The combination may require caution in patients with severe hepatic impairment, as the metabolism and elimination of the medications may be affected. Dose adjustments or alternative treatment options may be necessary. 
• Pregnancy and Lactation: The combination of olmesartan, amlodipine, and hydrochlorothiazide should be used under caution in pregnant or lactating women. Each component has its own considerations regarding use during pregnancy and breastfeeding. 

Comorbidities: 

• Kidney Disease: Patients with kidney disease, may require close monitoring when using this combination. Dose adjustments or alternative treatment options may be necessary to ensure the medications are used safely. 
• Liver Disease: Patients with liver disease, including severe liver impairment or cirrhosis, may require caution when using this combination. The metabolism and elimination of the medications may be affected, and dose adjustments or alternative treatment options may be necessary. 
• Heart Failure: Patients with heart failure may require careful monitoring when using this combination. The medications can affect blood pressure and fluid balance, and adjustments to the treatment regimen may be necessary to optimize management. 
• Diabetes: Patients with diabetes may require careful monitoring of blood glucose levels when using this combination. hydrochlorothiazide can affect blood sugar levels, and adjustments in diabetes management may be needed. 
• Chronic Obstructive Pulmonary Disease or Asthma: Patients with asthma or COPD may require caution when using this combination. amlodipine can cause bronchospasm in some individuals, and monitoring respiratory symptoms is important. 
• Gout: Patients with gout may require careful monitoring when using this combination. hydrochlorothiazide can increase uric acid levels in some individuals, potentially triggering gout attacks. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: D 

Lactation: Excreted into human milk: Yes (amlodipine, hydrochlorothiazide); Unknown (olmesartan)  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

olmesartan selectively blocks the binding of angiotensin II to AT1 receptors, thereby inhibiting its vasoconstrictor and aldosterone-secreting effects. This results in vasodilation (widening of blood vessels) and reduction of blood pressure. 

amlodipine inhibits the influx of calcium ions into vascular smooth muscle cells by blocking L-type calcium channels. By doing so, it causes vasodilation, reduces peripheral resistance, and decreases blood pressure. 

hydrochlorothiazide increases the excretion of sodium and chloride ions from the DCT of the kidneys. This leads to increased urine output and reduced fluid volume in the body, resulting in decreased blood volume and blood pressure. 

The combination of these three medications provides a comprehensive approach to managing hypertension. olmesartan blocks the angiotensin II action, a potent vasoconstrictor, while amlodipine relaxes blood vessels by blocking calcium channels. hydrochlorothiazide enhances diuresis and helps to reduce fluid volume. Together, these medications act synergistically to lower blood pressure, reduce the workload on the heart, and improve overall cardiovascular function.  

Pharmacodynamics: 

olmesartan is an angiotensin II receptor blocker (ARB) that selectively inhibits the binding of angiotensin II to its receptors. By blocking angiotensin II, olmesartan causes vasodilation and reduces peripheral resistance, resulting in lowered blood pressure. It also inhibits the aldosterone-secreting effects of angiotensin II, leading to decreased sodium and water retention. 

amlodipine is a calcium channel blocker (CCB) that blocks L-type calcium channels in vascular smooth muscle cells. By doing so, it prevents the influx of calcium ions into these cells, leading to relaxation and dilation of the blood vessels. This results in decreased peripheral resistance, improved blood flow, and lowered blood pressure. 

hydrochlorothiazide is a thiazide diuretic that acts primarily in the distal convoluted tubules of the kidneys. It inhibits reabsorption of sodium and chloride ions, leading to increased excretion of these ions in the urine. This promotes diuresis (increased urine production), reduces fluid volume in the body, and subsequently lowers blood pressure.  

Pharmacokinetics: 

Absorption 

• olmesartan: Well-absorbed from the gastrointestinal tract, with peak plasma concentrations achieved within 1 to 2 hours after oral administration. 
• amlodipine: Well-absorbed from the gastrointestinal tract, with peak plasma concentrations reached within 6 to 12 hours after oral administration. 
• hydrochlorothiazide: Well-absorbed from the gastrointestinal tract, with peak plasma concentrations attained within 2 hours after oral administration. 

Distribution 

• olmesartan: Extensively bound to plasma proteins (99%). It has a large volume of distribution, indicating distribution into the extravascular tissues. 
• amlodipine: Approximately 93% bound to plasma proteins. It has a large volume of distribution, indicating extensive distribution into the tissues. 
• hydrochlorothiazide: Binds moderately to plasma proteins (40% to 68%). It distributes throughout the extracellular fluid, including the kidney and other tissues. 

Metabolism 

• olmesartan: Primarily metabolized by the liver via the cytochrome P450 enzyme system. The major metabolite, olmesartan medoxomil, is pharmacologically inactive. 
• amlodipine: Metabolized in the liver via cytochrome P450 3A4 (CYP3A4) enzyme. The metabolites are inactive and mainly excreted in the urine. 
• hydrochlorothiazide: Undergoes minimal metabolism and is eliminated unchanged by the kidneys. 

Elimination and excretion 

• olmesartan: Primarily eliminated via feces (35%) and urine (50%), with a mean elimination half-life of approximately 13 hours. 
• amlodipine: Eliminated via urine and feces, with an elimination half-life of 30 to 50 hours. 
• hydrochlorothiazide: Primarily excreted in the urine, with an elimination half-life ranging from 6 to 15 hours. 

Adminstartion

Administration: 

The administration of the combination of olmesartan, amlodipine, and hydrochlorothiazide is typically done orally, in the form of tablets or fixed-dose combination products. 

• Dosage: The specific dosage of the combination product will depend on the prescribed formulation and the individual patient’s needs.  
• Timing: The combination is usually taken once daily, preferably at the same time, to maintain consistent blood levels of the medications.  
• Food Intake: The combination can be taken with or without food, depending on the specific instructions provided with the medication. However, taking it with food may help reduce the potential for gastrointestinal side effects. 
• Swallowing: The tablets should be swallowed whole with glass of water and not be crushed, chewed, or split unless specifically instructed by the healthcare professional. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: olmesartan, amlodipine and hydrochlorothiazide 

Pronounced: (ol-meh-sar-tan-am-lo-di-peen-hy-droh-klor-oh-thy-uh-zahyd)  

Why do we use olmesartan, amlodipine and hydrochlorothiazide? 

The combination of olmesartan, amlodipine, and hydrochlorothiazide is primarily used in the treatment of hypertension (high blood pressure). The three medications work together to help control blood pressure levels. Here are the main uses: 

• Hypertension: The combination is prescribed for patients with essential hypertension. By targeting different mechanisms involved in blood pressure regulation, the combination helps to lower blood pressure effectively and maintain it within the desired range. 
• Blood Pressure Control: The combination may be used when monotherapy (single medication) has not adequately controlled blood pressure. The synergistic action of olmesartan, amlodipine, and hydrochlorothiazide provides multiple approaches to blood pressure reduction, increasing the chances of achieving optimal control.