valsartan/hydrochlorothiazide

Action and Spectrum

Mechanism of action

valsartan/hydrochlorothiazide is a combination medication used to treat high blood pressure. valsartan is an angiotensin II receptor blocker (ARB) that works by blocking the action of angiotensin II, a hormone that causes blood vessels to narrow and constrict, resulting in increased blood pressure. hydrochlorothiazide is a diuretic that helps the body eliminate excess fluid and salt, which can also help lower blood pressure.

The combination of valsartan and hydrochlorothiazide can have a synergistic effect, meaning that their combined action is more effective than each drug alone. valsartan/hydrochlorothiazide is indicated for the treatment of hypertension in adults

Spectrum

The spectrum of activity of valsartan/hydrochlorothiazide is limited to hypertension. It is not indicated for the treatment of any other medical condition. It is important to note that this medication may not be suitable for everyone and may interact with other medications or medical conditions

Drug Interaction

Adverse Reaction

Frequency defined:

1-10%

Valsartan

Dizziness (2-8%)

Fatigue (3%)

Hyperkalemia (4-10%)

Hypotension (1-7%)

Frequency defined:

Hydrochlorothiazide

Anemia

Confusion

Epigastric distress

Exfoliative dermatitis

Hyperuricemia

Orthostatic hypotension

Stevens-Johnson syndrome

Anaphylaxis

Anorexia

Dizziness

Erythema multiforme

Headache

Hypokalemia

Photosensitivity

Post-marketing reports

Elevated liver failure

Impaired renal function

Alopecia

Angioedema

Vasculitis

Rhabdomyolysis

Non-melanoma skin cancer

Renal failure

Hyperkalemia

Black Box Warning

Black box warning

Drugs that immediately affect the renin-angiotensin system can harm or even kill a growing baby. If pregnancy is found, stop taking the medication as soon as possible

Contraindication / Caution

Contraindications

• Hypersensitivity to valsartan, hydrochlorothiazide, or any of the components of the medication
• Anuria (a condition where the body cannot produce urine)
• Severe hepatic impairment or obstructive biliary disorders
• Severe renal impairment (creatinine clearance less than 30 mL/min)
• Pregnancy and breastfeeding

Caution

It should also be used with caution in patients with certain medical conditions, such as diabetes, gout, and hyperlipidemia, and in patients taking other medications that may interact with it, such as lithium, potassium supplements, and nonsteroidal anti-inflammatory drugs (NSAIDs)

Pregnancy / Lactation

Pregnancy consideration: Drugs that interfere with the renin-angiotensin system can harm or even kill a growing baby. As soon as a pregnancy is discovered, stop immediately

Lactation: Excretion of the drug in human breast milk is unknown

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 available 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

• valsartan: Blocks binding of angiotensin II to type 1 angiotensin II receptors; blocks vasoconstrictor and aldosterone-secreting effects of angiotensin II
• hydrochlorothiazide: Thiazide diuretic that inhibits sodium reabsorption in distal renal tubules; results in increased excretion of sodium ions and water, as well as potassium and hydrogen ions

Pharmacodynamics

• valsartan is an angiotensin II receptor blocker (ARB) that selectively blocks the binding of angiotensin II to the type 1 angiotensin II receptor. Angiotensin II is a potent vasoconstrictor and stimulates the release of aldosterone, promoting sodium and water retention. By blocking the action of angiotensin II, valsartan reduces the vasoconstriction and the release of aldosterone, leading to vasodilation and decreased blood pressure
• hydrochlorothiazide is a diuretic that works by inhibiting the reabsorption of sodium and chloride in the distal convoluted tubules of the kidney. This promotes the excretion of sodium, chloride, and water, leading to a reduction in blood volume and a decrease in blood pressure.
• It is important to note that the pharmacodynamics of valsartan/hydrochlorothiazide can vary depending on the individual patient and other factors such as age, weight, and other medical conditions

Pharmacokinetics

Absorption

valsartan and hydrochlorothiazide have different absorption characteristics. Here is a breakdown of their absorption properties:

valsartan:

Bioavailability: approximately 25%

Onset: around 2 hours

Peak plasma time: 2-4 hours

Peak response: 4-6 hours

Duration: approximately 24 hours

hydrochlorothiazide:

The onset of diuresis: approximately 2 hours

The onset of anti-hypertensive effect: 3-4 days

Peak plasma time: 1-2.5 hours

The peak effect of diuresis: 4-6 hours

Distribution

valsartan:

Protein binding: approximately 94-95%

The volume of distribution: 17 L

hydrochlorothiazide:

Protein binding: approximately 68%

The volume of distribution: 3.6-7.8 L/kg

Metabolism

valsartan:

valsartan is minimally metabolized in the liver, with less than 10% of the dose converted to an inactive metabolite called valeryl-4-hydroxyvalsartan

hydrochlorothiazide:

hydrochlorothiazide is minimally metabolized in the liver, with less than 10% of the dose undergoing biotransformation

Elimination/Excretion

valsartan:

Renal clearance: 0.62 L/hr

Total body clearance: 2.2 L/hr

approximately 83% of the dose is eliminated unchanged in the feces, and approximately 13% is eliminated unchanged in the urine

hydrochlorothiazide:

most of the dose (approximately 70-80%) is eliminated unchanged in the urine

Adminstartion

Administration

valsartan/hydrochlorothiazide is usually administered orally in the form of tablets. Taking valsartan/hydrochlorothiazide with food is generally recommended to improve its absorption and reduce the risk of an upset stomach

Patient Information Leaflet

Patient information leaflet

Generic Name: valsartan/hydrochlorothiazide

Why do we use valsartan/hydrochlorothiazide?

• Treatment of hypertension in patients who require multiple medications for blood pressure control
• Reducing the risk of cardiovascular events in patients with hypertension and left ventricular hypertrophy (enlarged heart)
• Treatment of heart failure in patients who cannot tolerate an angiotensin-converting enzyme (ACE) inhibitor or require additional therapy beyond an ACE inhibitor
• Management of fluid retention (edema) associated with certain medical conditions, such as nephrotic syndrome or hepatic cirrhosis