Valsartan, sold under the brand name Diovan among others, is a
medication
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...
used to treat
high blood pressure
Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
,
heart failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...
, and
diabetic kidney disease
Diabetic nephropathy, also known as diabetic kidney disease, is the chronic loss of kidney function occurring in those with diabetes mellitus. Diabetic nephropathy is the leading causes of chronic kidney disease (CKD) and end-stage renal disease ...
.
[ It belongs to a class of medications referred to as ]angiotensin II receptor blocker
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 tha ...
s (ARBs). It is a reasonable initial treatment for high blood pressure.[ It is taken ]by mouth
Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...
.[ Versions are available as the combination ]valsartan/hydrochlorothiazide
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. It is a combination of valsartan, an angiotensin receptor blocker with hydroch ...
, valsartan/amlodipine
Amlodipine/valsartan, sold under the brand name Exforge among others, is a blood pressure lowering combination drug. It contains amlodipine, a dihydropyridine-type calcium channel blocker, and valsartan, an angiotensin receptor blocker. This c ...
, valsartan/amlodipine/hydrochlorothiazide
Amlodipine/valsartan, sold under the brand name Exforge among others, is a blood pressure lowering combination drug. It contains amlodipine, a dihydropyridine-type calcium channel blocker, and valsartan, an angiotensin receptor blocker. This c ...
, or valsartan/sacubitril
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 so ...
.
Common side effects include feeling tired, dizziness, high blood potassium
Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0mmol/L (3.5 and 5.0mEq/L) with levels above 5.5mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occasi ...
, diarrhea, and joint pain.[ Other serious side effects may include ]kidney problems
Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
, low blood pressure
Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...
, and angioedema
Angioedema is an area of swelling ( edema) of the lower layer of skin and tissue just under the skin or mucous membranes. The swelling may occur in the face, tongue, larynx, abdomen, or arms and legs. Often it is associated with hives, which ...
.[ Use in ]pregnancy
Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occurs by sexual intercourse, but ca ...
may harm the baby and use when breastfeeding
Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...
is not recommended. It is an angiotensin II receptor antagonist
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 tha ...
and works by blocking the effects of angiotensin II
Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adre ...
.
Valsartan was patented in 1990, and came into medical use in 1996. It is available as a generic medication
A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...
. In 2020, it was the 123rd most commonly prescribed medication in the United States, with more than 5million prescriptions.
Medical uses
Valsartan is used to treat high blood pressure
Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
, heart failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...
, and to reduce death for people with left ventricular dysfunction
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, an ...
after having a heart attack
A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may tr ...
.
High blood pressure
Valsartan (and other ARBs) are an appropriate initial treatment option for most people with high blood pressure and no other coexisting conditions, as are ACE inhibitor
Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of hypertension, high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease i ...
s, thiazide diuretics
Thiazide () refers to both a class of sulfur-containing organic molecules and a class of diuretics based on the chemical structure of benzothiadiazine. The thiazide drug class was discovered and developed at Merck and Co. in the 1950s. The first ...
and calcium channel blocker
Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as ...
s. If patients have coexisting diabetes or kidney disease, ARBs or ACE inhibitors may be considered over other classes of blood pressure medicines.
Heart failure
Valsartan has reduced rates of mortality and heart failure hospitalisations when used alone or in combination with beta-blockers
Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms, and to protect the heart from a second heart attack after a first heart attack (secondary prevention). They are al ...
in the treatment of heart failure. Importantly, the combination of valsartan and ACE inhibitor
Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of hypertension, high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease i ...
s has not shown morbidity or mortality benefits but rather increases mortality risk when added to combination beta-blocker and ACE-inhibitor therapy, and increases the risk of adverse events like hyperkalaemia
Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0mmol/L (3.5 and 5.0mEq/L) with levels above 5.5mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occasi ...
, hypotension
Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dias ...
and renal failure
Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
. As shown in the PARADIGM-HF study, valsartan combined with sacubitril for the treatment of heart failure, significantly reduced all cause and cardiovascular mortality and hospitalisations due to heart failure.
Diabetic kidney disease
In people with type 2 diabetes, antihypertensive therapy with valsartan decreases the rate of progression of albuminuria (albumin in urine), promotes regression to normoalbuminuria and may reduce the rate of progression to end-stage kidney disease.
Contraindications
The packaging for valsartan includes a warning stating the drug should not be used with the renin inhibitor
Renin inhibitors are pharmaceutical drugs inhibiting the activity of renin that is responsible for hydrolyzing angiotensinogen to angiotensin I, which in turn reduces the formation of angiotensin II that facilitates blood pressure.
Renin inhibit ...
aliskiren
Aliskiren (brand names Tekturna and Rasilez) 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 reco ...
in people with diabetes. It also states the safety of the drug in severe renal impairment has not been established.
Valsartan includes a black box warning
In the United States, a boxed warning (sometimes "black box warning", colloquially) is a type of warning that appears on the package insert for certain prescription drugs, so called because
the U.S. Food and Drug Administration specifies that it i ...
for fetal toxicity. Discontinuation of these agents is recommended immediately after detection of pregnancy
Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occurs by sexual intercourse, but ca ...
and an alternative medication should be started. Breastfeeding is not recommended.
Side effects
Rates of side effects depends on the reason the medication is used.
Heart failure
Rates of adverse effects are based on a comparison versus placebo
A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures.
In general ...
in people with heart failure. Most common side effects include dizziness
Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to disequilibrium or a non-specific feeling, such as giddiness or foolishness.
Dizziness is a common medical c ...
(17% vs 9% ), low blood pressure
Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...
(7% vs 2%), and diarrhea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
(5% vs 4%). Less common side effects include joint pain
Arthralgia (from Greek ''arthro-'', joint + ''-algos'', pain) literally means ''joint pain''. Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication.
According to MeSH, ...
, fatigue, and back pain (all 3% vs 2%).
Hypertension
Clinical trials for valsartan treatment for hypertension versus placebo demonstrate side effects like viral infection (3% vs 2%), fatigue (2% vs 1%) and abdominal pain (2% vs 1%). Minor side effects that occurred at >1% but were similar to rates from the placebo group include:
* headache
* dizziness
* upper respiratory infection
An upper respiratory tract infection (URTI) is an illness caused by an acute infection, which involves the upper respiratory tract, including the human nose, nose, Paranasal sinus, sinuses, pharynx, larynx or trachea. This commonly includes nasal ...
* cough
* diarrhea
* rhinitis
Rhinitis, also known as coryza, is irritation and inflammation of the mucous membrane inside the nose. Common symptoms are a stuffy nose, runny nose, sneezing, and post-nasal drip.
The inflammation is caused by viruses, bacteria, irritants o ...
/sinusitis
Sinusitis, also known as rhinosinusitis, is inflammation of the nasal mucosa, mucous membranes that line the paranasal sinuses, sinuses resulting in symptoms that may include thick Mucus#Respiratory system, nasal mucus, a nasal congestion, plugg ...
* nausea
* pharyngitis
Pharyngitis is inflammation of the back of the throat, known as the pharynx. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, difficulty swallowing, swollen lymph nodes, and a hoarse voice ...
* edema
Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's Tissue (biology), tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels t ...
* arthralgia
Kidney failure
People treated with ARBs including valsartan or diuretics
A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics in ...
are susceptible to conditions of developing low renal blood flow such as abnormal narrowing of blood vessel in kidney, hypertension
Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
, renal artery stenosis
Renal artery stenosis (RAS) is the narrowing of one or both of the renal arteries, most often caused by atherosclerosis or fibromuscular dysplasia. This narrowing of the renal artery can impede blood flow to the target kidney, resulting in renova ...
, heart failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...
, chronic kidney disease
Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vo ...
, severe congestive heart failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...
, or volume depletion
Hypovolemia, also known as volume depletion or volume contraction, is a state of abnormally low extracellular fluid in the body. This may be due to either a loss of both salt and water or a decrease in blood volume. Hypovolemia refers to the los ...
whose renal function is in part dependent on the activity of the renin-angiotensin system like efferent arteriolar vasoconstriction done by angiotensin II are at high risk of deterioration of renal function comprising acute kidney failure
Acute kidney injury (AKI), previously called acute renal failure (ARF), is a sudden decrease in kidney function that develops within 7 days, as shown by an increase in serum creatinine or a decrease in urine output, or both.
Causes of AKI are cla ...
, oliguria
Oliguria or hypouresis is the low output of urine specifically more than 80 ml/day but less than 400ml/day.Boon et al, Davidson's Principles & Practice of Medicine (20th Ed), p475 The decreased output of urine may be a sign of dehydration, kidney ...
, worsening azotemia
Azotemia (''azot'', "nitrogen" + '' -emia'', "blood condition") is a medical condition characterized by abnormally high levels of nitrogen-containing compounds (such as urea, creatinine, various body waste compounds, and other nitrogen-rich compou ...
or heightened serum creatinine
Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass).
Biological relevance
Serum creatinine (a blood measurement) is an import ...
. When blood flow to the kidneys is reduced, the kidney activates a series of response that triggers angiotensin release to constrict blood vessels and facilitate blood flow in the kidney. So long as the nephron function degradation is being progressive or reaches clinically significant level, withhold or discontinue valsartan is warranted.
Interactions
The U.S. prescribing information lists the following drug interactions for valsartan:
* Other inhibitors of the renin-angiotensin system may increase the risks of low blood pressure, kidney problems, and hyperkalemia.
* Potassium-sparing diuretics, potassium
Potassium is the chemical element with the symbol K (from Neo-Latin ''kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmosphe ...
supplements, salt
Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quantitie ...
substitutes containing potassium may increase the risk of hyperkalemia
Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0mmol/L (3.5 and 5.0mEq/L) with levels above 5.5mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occasi ...
.
* NSAID
Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...
s may increase the risk of kidney problems and may interfere with blood pressure-lowering effects.
* Valsartan may increase the concentration of lithium
Lithium (from el, λίθος, lithos, lit=stone) is a chemical element with the symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard conditions, it is the least dense metal and the least dense solid el ...
.
* Valsartan and other angiotensin-related blood pressure medications may interact with the antibiotics
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention o ...
co-trimoxazole
Trimethoprim/sulfamethoxazole, sold under the brand name Bactrim among others, is a fixed-dose combination antibiotic medication used to treat a variety of bacterial infections. It consists of one part trimethoprim to five parts sulfamethoxazo ...
or ciprofloxacin
Ciprofloxacin is a fluoroquinolone antibiotic used to treat a number of bacterial infections. This includes bone and joint infections, intra abdominal infections, certain types of infectious diarrhea, respiratory tract infections, skin infec ...
to increase risk of sudden death due to cardiac arrest
Cardiac arrest is when the heart suddenly and unexpectedly stops beating. It is a medical emergency that, without immediate medical intervention, will result in sudden cardiac death within minutes. Cardiopulmonary resuscitation (CPR) and possib ...
.
Food interaction
With the tablet, food decreases the valsartan tablet taker's exposure to valsartan by about 40% and peak plasma concentration (Cmax) by about 50%, evidenced by AUC change.
Pharmacology
Mechanism of action
Valsartan blocks the actions of angiotensin II
Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adre ...
, which include constricting blood vessels and activating aldosterone
Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays a c ...
, to reduce blood pressure. The drug binds to angiotensin type I receptors (AT1), working as an antagonist. This mechanism of action is different than that of the ACE inhibitor drugs, which block the conversion of angiotensin I to angiotensin II. As valsartan acts at the receptor, it can provide more complete angiotensin II antagonism since angiotensin II is generated by other enzymes as well as ACE. Also, valsartan does not affect the metabolism of bradykinin like ACE inhibitors do.
Pharmacodynamics
Pharmacokinetics
AUC and Cmax values of valsartan are observed to be approximately linearly dose-dependent over therapeutic dosing range. Owing to its relatively short elimination half life attribution, valsartan concentration in plasma doesn't accumulate in response to repeated dosing.
Society and culture
Economics
In 2010, valsartan (trade name Diovan) achieved annual sales of $2.052billion in the United States and $6.053billion worldwide. The patents for valsartan and valsartan/hydrochlorothiazide expired in September 2012.
Combinations
Valsartan is combined with amlodipine
Amlodipine, sold under the brand name Norvasc among others, is a calcium channel blocker medication used to treat high blood pressure and coronary artery disease. It is taken by mouth.
Common side effects include swelling, feeling tired, ab ...
or hydrochlorothiazide
Hydrochlorothiazide is a diuretic medication often used to treat high blood pressure 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 tho ...
(HCTZ) (or both) into single-pill formulations for treating hypertension with multiple drugs.[ Valsartan is also available as the combination ]valsartan/sacubitril
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 so ...
. It is used to treat heart failure with reduced ejection fraction.
Recalls
On 6 July 2018, the European Medicines Agency
The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...
(EMA) recalled certain batches of valsartan and valsartan/hydrochlorothiazide film-coated tablets distributed in 22 countries in Europe, plus Canada. Zhejiang Huahai Pharmaceutical Co. (ZHP) in Linhai, China manufactured the bulk ingredient contaminated by N-nitrosodimethylamine (NDMA), a carcinogen
A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive substan ...
. The active pharmaceutical ingredient
An active ingredient is any ingredient that provides biological activity, biologically active or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure or any function of the body of h ...
was subsequently imported by a number of generic drugmakers, including Novartis
Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and
Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loc ...
, and marketed in Europe and Asia under their subsidiary Sandoz
Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and
Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loc ...
labeling, and in the UK by Dexcel Pharma Ltd and Accord Healthcare.
In Canada
Canada is a country in North America. Its ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, covering over , making it the world's second-largest country by tot ...
, the recall involves five companies and a class action suit has been initiated by a private law firm. Authorities believe the degree of contamination is negligible, and advise those taking the drug to consult a doctor and not to cease taking the medication abruptly. On 12 July 2018, The National Agency of Drug and Food Control (NA-DFC or Badan POM Indonesia) announced voluntary recalls for two products containing valsartan produced by Actavis Indonesia and Dipa Pharmalab Intersains. On 13 July 2018, the U.S. Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) announced voluntary recalls of certain supplies of valsartan and valsartan/hydrochlorothiazide
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. It is a combination of valsartan, an angiotensin receptor blocker with hydroch ...
in the U.S. distributed by Solco Healthcare LLC, Major Pharmaceuticals, and Teva Pharmaceutical Industries
Teva Pharmaceutical Industries Ltd. (also known as Teva Pharmaceuticals) is an Israeli multinational pharmaceutical company with headquarters in Tel Aviv, Israel. It specializes primarily in generic drugs, but other business interests include ...
. Hong Kong's Department of Health initiated a similar recall. On 2 August 2018, the FDA published two lengthy, updated lists, classifying hundreds of specific U.S. products containing valsartan into those included versus excluded from the recall. A week later, the FDA cited two more drugmakers, Zhejiang Tianyu Pharmaceuticals of China and Hetero Labs Limited of India, as additional sources of the contaminated valsartan ingredient
An ingredient is a substance that forms part of a mixture (in a general sense). For example, in cooking, recipes specify which ingredients are used to prepare a specific dish. Many commercial product (business), products contain secret ingredie ...
.
In September 2018, the FDA announced that retesting of all valsartan supplies had found a second carcinogenic impurity, N-nitrosodiethylamine
''N''-Nitrosodiethylamine (NDEA) is an organic compound with the formula Et2NNO (Et = C2H5). A member of the nitrosamines, it is a light-sensitive, volatile, clear yellow oil that is soluble in water, lipids, and other organic solvents. It has ...
(NDEA), in the recalled products made by ZHP in China and marketed in the U.S. under the Torrent Pharmaceuticals
Torrent Pharmaceuticals Ltd is an Indian multinational pharmaceutical company, owned by Torrent Group and headquartered in Ahmedabad. It was promoted by U. N. Mehta, initially as Trinity Laboratories Ltd, and was later renamed Torrent Pharma ...
(India) brand.
According to a 2018 Reuters
Reuters ( ) is a news agency owned by Thomson Reuters Corporation. It employs around 2,500 journalists and 600 photojournalists in about 200 locations worldwide. Reuters is one of the largest news agencies in the world.
The agency was estab ...
analysis of national medicines agencies' records, more than 50 companies around the world have recalled valsartan mono-preparations or combination products manufactured from the tainted valsartan ingredient. The contamination has likely been present since 2012 when the manufacturing process was changed and approved by EDQM and FDA authorities. Based on inspections in late 2018, both agencies have suspended the Chinese and Indian manufacturers' certificates of suitability for the supply of valsartan in the EU and the U.S.
In 2019, many more preparations of valsartan and its combinations were recalled due to the presence of the contaminant NDMA.
In August 2020, the European Medicines Agency
The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...
(EMA) provided guidance to marketing authorization holders on how to avoid the presence of nitrosamine impurities in human medicines and asked them to review all chemical and biological human medicines for the possible presence of nitrosamines and to test the products at risk.[ Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.]
Shortages
Since July 2018, numerous recalls of losartan
Losartan, sold under the brand name Cozaar among others, is a medication used to treat high blood pressure (hypertension). It is in the angiotensin II receptor antagonist, angiotensin receptor blocker (ARB) family of medication, and is consider ...
, valsartan and irbesartan
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. Versio ...
drug products have caused marked shortages of these life saving medications in North America and Europe, particularly for valsartan. In March 2019, the FDA approved an additional generic version of Diovan™ to address the issue. According to the agency, the shortage of valsartan was resolved on 3 April 2020, but the availability of the generic form remained unstable into July 2020. Pharmacies in Europe were notified that the supply of the drug, particularly for higher dosage forms, would remain unstable well into December 2020.
Research
In people with impaired glucose tolerance, valsartan may decrease the incidence of developing diabetes mellitus type 2
Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, ...
. However, the absolute risk reduction is small (less than 1 percent per year) and diet, exercise or other drugs, may be more protective. In the same study, no reduction in the rate of cardiovascular events (including death) was shown.
In one study of people without diabetes, valsartan reduced the risk of developing diabetes mellitus over amlodipine
Amlodipine, sold under the brand name Norvasc among others, is a calcium channel blocker medication used to treat high blood pressure and coronary artery disease. It is taken by mouth.
Common side effects include swelling, feeling tired, ab ...
, mainly for those with hypertension.
A prospective study demonstrated a reduction in the incidence and progression of Alzheimer's disease and dementia.
References
External links
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