Valsartan/hydrochlorothiazide

Last updated

Valsartan/hydrochlorothiazide
Valsartan.svg
Hydrochlorothiazide.svg
Combination of
Valsartan Angiotensin II receptor antagonist
Hydrochlorothiazide Thiazide diuretic
Clinical data
Trade names Co-vasotec, Diovan HCT, Co-Diovan, others
AHFS/Drugs.com Professional Drug Facts
MedlinePlus a611032
License data
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
KEGG
CompTox Dashboard (EPA)
   (verify)

Valsartan/hydrochlorothiazide, sold under the brand name Diovan HCT among others, is a medication used to treat high blood pressure when valsartan is not sufficient. [6] It is a combination of valsartan, an angiotensin receptor blocker with hydrochlorothiazide, a diuretic. [7] It is taken by mouth. [7]

Contents

Common side effects include dizziness and headaches. [7] Serious side effects may include allergic reactions, electrolyte abnormalities, and glaucoma. [2] Use in pregnancy is not recommended. [2]

The combination was approved for medical use in the United States in 1998. [7] It is available as a generic medication. [6] In 2020, it was the 235th most commonly prescribed medication in the United States, with more than 1 million prescriptions. [8] [9]

Structure–activity relationship

Valsartan has the structure that most ARBs have with the extended biphenyl group and tetrazole which mimics the carboxylate group as a bioisostere but is not held to the same metabolic inactivation. One special note about the molecule in terms of how it differs with other angiotensin receptor blockers, is that the molecule at the 2-prime position has a tetrazole, which has an acidic hydrogen attached to it.

Medical uses

High blood pressure

Valsartan and hydrochlorothiazide are both medications indicated as initial therapy for high blood pressure. When high blood pressure is not effectively controlled on a single medication they can be used in a combination. [10]

Contraindications

The use of valsartan in pregnancy is avoided due to the potential risk of fetal toxicity. [11] The U.S. Food and Drug Administration has a black box warning for valsartan/hydrochlorothiazide use during pregnancy. [2] The use of hydrochlorothiazide is avoided in those with anuria or severe kidney disease. [12]

Adverse effects

Side effects that are most often seen with this medication include dizziness, hypotension, headache. [2] A clinical trial done on over 7000 participants showed higher rates of nasopharyngitis in those taking valsartan/hydrochlorothiazide (2.4% versus 1.9% in placebo). [2] [12] A dose-related side effect seen is hypotension, occurring in 0.7% of participants on the highest dose of the medication. [2] [12] Risk of hypotension and hyperkalemia increases when valsartan/hydrochlorothiazide is used with ACE inhibitors or aliskiren. [2] [13] Less common side effects that occur less than 1% of the time include angina pectoris, rash, syncope, abdominal pain, and vertigo. [2] [12]

Overdose

Cases of overdose are quite rare. In the event of an overdose people may experience severe hypotension, electrolyte imbalances or abnormal heart rhythms. People are advised to contact emergency services or a poison control centre and are treated based on symptoms. [2] [14]

Interactions

There are a few types of medications that interact with valsartan. Combined use with nonsteroidal anti-inflammatory drugs (NSAID) such as naproxen or ibuprofen can result in kidney injury in people who are elderly, dehydrated, or have reduced kidney function. [2] One study conducted Lapi F., et al. found that there was no increased risk of kidney injury when only using either a diuretic or angiotensin receptor blocker with an NSAID but did find an increased risk when all three medications were used together. [15] Valsartan usage with angiotensin receptor blocker, ACE inhibitors, or aliskiren results in additive side effects. [12]

Pharmacology

Valsartan is an angiotensin II receptor blocker this class of drug competes with angiotensin II for the angiotensin type I (AT1) receptors located throughout the body. [2] Angiotensin II is a key component of the renin-angiotensin-aldosterone system which is responsible for vasoconstriction of blood vessels and promotes release of vasopressin from the posterior pituitary gland of the hypothalamus which helps promote water retention. [16] Aldosterone is also released by the adrenal gland in response to angiotensin II which helps to reabsorb sodium which leads to water reabsorption that results in a rise in blood pressure. [16] Blocking angiotensin II from binding to AT1 receptors will in turn prevent it from raising blood pressure which is why angiotensin II receptor blockers are useful medications in the treatment of blood pressure. [2] [16] Hydrochlorothiazide inhibits the NaCl co-transporters in the distal convoluted tubule of the nephrons located in the kidneys which are responsible for the excretion of sodium and chloride in exchange for reabsorption of calcium. [2] [16] Inhibition of the NaCl co-transporters result in water excretion which is believed to be the mechanism of action in diuresis and lowering blood pressure. [17]

Pharmacokinetics

Valsartan has an oral bioavailability of approximately 25% and reaches peak blood concentrations around 2–4 hours after ingestion. [2] [13] The estimated elimination half-life is determined to be approximately 6 hours, volume distribution of 17 litres, and a protein binding of 95% is seen. [12] [13] [18] The elderly may see increases in half life of the drug by up to 35% but dosing adjustment will not typically be warranted, however the drug should be used with caution in severe liver or kidney impairment. [13] Majority of the drug is eliminated through the feces (83%) while only a small portion is eliminated in the urine (13%). [18] Most of the drug excreted is unchanged, only small portion of the drug is metabolized to its inactive form 4-hydroxyvaleryl valsartan, the enzyme suspected to be responsible for this is the liver enzyme CYP2C9. [18] Hydrochlorothiazide has an oral bioavailability of 70% and reaches peak concentration around 1.5–2 hours following ingestion. The half-life is quite variable for this drug and can range from 5–15 hours. This drug is not metabolized and is mostly excreted unchanged in the urine (60-70%). [13] [19] Protein binding ranges between 40 and 70% and volume of distribution varies from 4-8L/kg. [12] [13]

Related Research Articles

<span class="mw-page-title-main">Hydrochlorothiazide</span> Diuretic medication

Hydrochlorothiazide, sold under the brand name Hydrodiuril among others, is a diuretic medication used to treat hypertension and swelling due to fluid build-up. Other uses include treating diabetes insipidus and renal tubular acidosis and to decrease the risk of kidney stones in those with a high calcium level in the urine. Hydrochlorothiazide is taken by mouth and may be combined with other blood pressure medications as a single pill to increase effectiveness. Hydrochlorothiazide is a thiazide medication which inhibits reabsorption of sodium and chloride ions from the distal convoluted tubules of the kidneys, causing a natriuresis. This initially increases urine volume and lowers blood volume. It is believed to reduce peripheral vascular resistance.

Antihypertensives are a class of drugs that are used to treat hypertension. Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke, heart failure, kidney failure and myocardial infarction. Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34% and of ischaemic heart disease by 21%, and can reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease. There are many classes of antihypertensives, which lower blood pressure by different means. Among the most important and most widely used medications are thiazide diuretics, calcium channel blockers, ACE inhibitors, angiotensin II receptor antagonists (ARBs), and beta blockers.

<span class="mw-page-title-main">Amlodipine</span> Dihydropyridine calcium channel blocker used to treat cardiovascular diseases

Amlodipine, sold under the brand name Norvasc among others, is a calcium channel blocker medication used to treat high blood pressure, coronary artery disease (CAD) and variant angina. It is taken orally.

<span class="mw-page-title-main">Angiotensin II receptor blocker</span> Group of pharmaceuticals that modulate the renin–angiotensin system

Angiotensin II receptor blockers (ARBs), formally angiotensin II receptor type 1 (AT1) antagonists, also known as angiotensin receptor blockers, angiotensin II receptor antagonists, or AT1 receptor antagonists, are a group of pharmaceuticals that bind to and inhibit the angiotensin II receptor type 1 (AT1) and thereby block the arteriolar contraction and sodium retention effects of renin–angiotensin system.

<span class="mw-page-title-main">Irbesartan</span> Chemical compound

Irbesartan, sold under the brand name Avapro among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It is a reasonable initial treatment for high blood pressure. It is taken by mouth. Versions are available as the combination irbesartan/hydrochlorothiazide.

<span class="mw-page-title-main">Quinapril</span> ACE inhibitor used in the treatment of hypertension and congestive heart failure

Quinapril, sold under the brand name Accupril by the Pfizer corporation. It a medication used to treat high blood pressure (hypertension), heart failure, and diabetic kidney disease. It is a first line treatment for high blood pressure. It is taken by mouth.

<span class="mw-page-title-main">Telmisartan</span> Angiotensin II receptor antagonist

Telmisartan, sold under the brand name Micardis among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It is a reasonable initial treatment for high blood pressure. It is taken by mouth. Versions are available as the combination telmisartan/hydrochlorothiazide, telmisartan/cilnidipine and telmisartan/amlodipine.

<span class="mw-page-title-main">Benazepril</span> Medication used to treat high blood pressure and heart failure

Benazepril, sold under the brand name Lotensin among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It is a reasonable initial treatment for high blood pressure. It is taken by mouth. Versions are available as the combinations benazepril/hydrochlorothiazide and benazepril/amlodipine.

<span class="mw-page-title-main">Losartan</span> Blood pressure medication

Losartan, sold under the brand name Cozaar among others, is a medication used to treat high blood pressure (hypertension). It is in the angiotensin receptor blocker (ARB) family of medication, and is considered protective of the kidneys. Besides hypertension, it is also used in diabetic kidney disease, heart failure, and left ventricular enlargement. It comes as a tablet that is taken by mouth. It may be used alone or in addition to other blood pressure medication. Up to six weeks may be required for the full effects to occur.

<span class="mw-page-title-main">Valsartan</span> Angiotensin II receptor antagonist

Valsartan, sold under the brand name Diovan among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It belongs to a class of medications referred to as angiotensin II receptor blockers (ARBs). It is a reasonable initial treatment for high blood pressure. It is taken by mouth. Versions are available as the combination valsartan/hydrochlorothiazide, valsartan/amlodipine, valsartan/amlodipine/hydrochlorothiazide, or valsartan/sacubitril.

<span class="mw-page-title-main">Olmesartan</span> Angiotensin II receptor antagonist

Olmesartan, sold under the brand name Benicar among others, is a medication used to treat high blood pressure (hypertension). It is taken by mouth. Versions are available as the combination olmesartan/hydrochlorothiazide and olmesartan/amlodipine.

<span class="mw-page-title-main">Aliskiren</span> Medication

Aliskiren is the first in a class of drugs called direct renin inhibitors. It is used for essential (primary) hypertension. While used for high blood pressure, other better studied medications are typically recommended due to concerns of higher side effects and less evidence of benefit.

<span class="mw-page-title-main">Amlodipine/valsartan</span> Antihypertensive medication

Amlodipine/valsartan, sold under the brand name Exforge among others, is a blood pressure lowering combination drug. It contains amlodipine, as the besilate, a dihydropyridine-type calcium channel blocker, and valsartan, an angiotensin II receptor antagonist. This combination is usually well tolerated and effective for the reduction of blood pressure.

<span class="mw-page-title-main">Azilsartan</span> Chemical compound

Azilsartan, sold under the brand name Edarbi among others, is used for the treatment of hypertension. It is used as the prodrug azilsartan medoxomil, is an angiotensin II receptor antagonist, and was developed by Takeda.

Telmisartan/hydrochlorothiazide, sold under the brand name Micardis HCT among others, is a fixed-dose combination medication used to treat high blood pressure. It is a combination of telmisartan an angiotensin II receptor antagonist with hydrochlorothiazide a diuretic. It may be used if telmisartan by itself is not sufficient. It is taken by mouth.

Losartan/hydrochlorothiazide, sold under the brand name Hyzaar among others, is a fixed-dose combination medication used to treat high blood pressure when losartan is not sufficient. It consists of losartan and hydrochlorothiazide. It is taken by mouth.

<span class="mw-page-title-main">Sacubitril/valsartan</span> Combination medication

Sacubitril/valsartan, sold under the brand name Entresto, is a fixed-dose combination medication for use in heart failure. It consists of the neprilysin inhibitor sacubitril and the angiotensin receptor blocker valsartan. The combination is sometimes described as an "angiotensin receptor-neprilysin inhibitor" (ARNi). In 2016, the American College of Cardiology/American Heart Association Task Force recommended it as a replacement for an ACE inhibitor or an angiotensin receptor blocker in people with heart failure with reduced ejection fraction.

An ACE inhibitor and thiazide combination is a drug combination used to treat hypertension. They are given by mouth. ACE inhibitors reduce the activity of angiotensin-converting enzyme (ACE) which produces angiotensin II, a hormone that constricts blood vessels. Thiazides are a class of diuretics that inhibit the thiazide receptor, thereby increasing urine production and reducing excess water and salt in the body. Several organizations recommend combination therapy for hypertension in cases of failure of a single drug to achieve target blood pressure, or even as a first line treatment for some patients.

Olmesartan/hydrochlorothiazide, sold under the brand name Benicar HCT among others, is a fixed-dose combination medication used to treat high blood pressure. It is a combination of olmesartan medoxomil, an angiotensin II receptor blocker and hydrochlorothiazide, a diuretic. It may be used if olmesartan is not sufficient to manage blood pressure. It is taken by mouth.

Aliskiren/hydrochlorothiazide, sold under the brand name Tekturna HCT among others, is a fixed-dose combination medication for the treatment of hypertension. It contains aliskiren, a renin inhibitor, and hydrochlorothiazide, a diuretic. It is taken by mouth.

References

  1. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA . Retrieved 22 October 2023.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 "Diovan HCT- valsartan and hydrochlorothiazide tablet, film coated". DailyMed. Retrieved 20 January 2021.
  3. ↑ "Active substance: valsartan, hydrochlorothiazide / valsartan" (PDF). List of nationally authorised medicinal products. European Medicines Agency. 14 January 2021.
  4. ↑ "Dafiro HCT EPAR". European Medicines Agency (EMA). Retrieved 21 April 2021.
  5. ↑ "Exforge HCT EPAR". European Medicines Agency (EMA). Retrieved 21 April 2021.
  6. 1 2 British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 179. ISBN   9780857113382.
  7. 1 2 3 4 "Hydrochlorothiazide and valsartan Uses, Side Effects & Warnings". Drugs.com. Retrieved 10 March 2019.
  8. ↑ "The Top 300 of 2020". ClinCalc. Retrieved 7 October 2022.
  9. ↑ "Hydrochlorothiazide; Valsartan - Drug Usage Statistics". ClinCalc. Retrieved 7 October 2022.
  10. ↑ "VIII. Choice of therapy for adults with hypertension without compelling indications for specific agents". Hypertension Canada. Retrieved 21 April 2021.
  11. ↑ Briggs G, Freeman R, Towers C, Forinash A (2017). Drugs in Pregnancy and Lactation. Philadelphia: Wolters Kluwer. ISBN   9781496349620.
  12. 1 2 3 4 5 6 7 "Drug Product Database Online Query". Health Canada. 25 April 2012. Retrieved 22 April 2021.
  13. 1 2 3 4 5 6 Kondrack R, Mohiuddin S (September 2009). "Valsartan/hydrochlorothiazide: pharmacology and clinical efficacy". Expert Opinion on Drug Metabolism & Toxicology. 5 (9): 1125–34. doi:10.1517/17425250903136730. PMID   19689218. S2CID   207490609.
  14. ↑ "Valsartan/Hydrochlorothiazide - Oral". HealthLink BC. Retrieved 23 April 2021.
  15. ↑ Lapi F, Azoulay L, Yin H, Nessim SJ, Suissa S (January 2013). "Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury: nested case-control study". BMJ. 346: e8525. doi:10.1136/bmj.e8525. PMC   3541472 . PMID   23299844.
  16. 1 2 3 4 Silverthorn DU (2015). Human Physiology An Integrated Approach 7th Edition. San Francisco, CA: Pearson Education. pp. 595, 630–633. ISBN   978-0321981226.
  17. ↑ Herman L, Bashir K (2021). "Hydrochlorothiazide". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID   28613517 . Retrieved 23 April 2021.
  18. 1 2 3 "Valsartan". PubChem. U.S. National Library of Medicine. Retrieved 23 April 2021.
  19. ↑ "Hydrochlorothiazide". PubChem. U.S. National Library of Medicine. Retrieved 23 April 2021.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.