Lesinurad (brand name Zurampic) is a urate transporter inhibitor for treating high blood uric acid levels associated with

gout Gout ( ) is a form of inflammatory arthritis characterized by recurrent attacks of pain in a red, tender, hot, and Joint effusion, swollen joint, caused by the deposition of needle-like crystals of uric acid known as monosodium urate crysta ...

. It is recommended only as an

adjuvant In pharmacology, an adjuvant is a drug or other substance, or a combination of substances, that is used to increase the efficacy or potency of certain drugs. Specifically, the term can refer to: * Adjuvant therapy in cancer management * Anal ...

with either

allopurinol Allopurinol is a medication used to decrease hyperuricemia, high blood uric acid levels. It is specifically used to prevent gout, prevent specific types of kidney stones and for the high uric acid levels that can occur with chemotherapy. It i ...

febuxostat Febuxostat, sold under the brand name ''Uloric'' among others, is a medication used long-term to treat gout due to hyperuricemia, high uric acid levels. It is generally recommended only for people who cannot take allopurinol. It is taken by mo ...

when these medications are not sufficient. It received FDA approval on 22 December 2015. The

European Commission The European Commission (EC) is the primary Executive (government), executive arm of the European Union (EU). It operates as a cabinet government, with a number of European Commissioner, members of the Commission (directorial system, informall ...

granted a marketing authorisation valid throughout the

European Union The European Union (EU) is a supranational union, supranational political union, political and economic union of Member state of the European Union, member states that are Geography of the European Union, located primarily in Europe. The u ...

on 18 February 2016. In February 2019, lesinurad was discontinued in the United States by its manufacturer for business reasons, and was subsequently withdrawn in Europe in July 2020.

Medical uses

Lesinurad is used in combination with a

xanthine oxidase inhibitor A xanthine oxidase inhibitor is any substance that inhibits the activity of xanthine oxidase, an enzyme involved in purine metabolism. In humans, inhibition of xanthine oxidase reduces the production of uric acid, and several medications that inh ...

, such as

, for treating hyperuricemia (high levels of

uric acid Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the Chemical formula, formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the meta ...

in the

blood serum Serum () is the fluid and solvent component of blood which does not play a role in clotting. It may be defined as blood plasma without the clotting factors, or as blood with all cells and clotting factors removed. Serum contains all proteins ex ...

) associated with gout. It is approved only for patients who have not achieved target uric acid levels with a xanthine oxidase inhibitor alone.

Contraindications

The drug is contraindicated in people with

tumour lysis syndrome Tumor lysis syndrome (TLS) is a group of metabolic abnormalities that can occur as a complication from the treatment of cancer, where large amounts of tumor cells are killed off ( lysed) from the treatment, releasing their contents into the blood ...

Lesch–Nyhan syndrome Lesch–Nyhan syndrome (LNS) is a rare inherited disorder caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). This deficiency occurs due to mutations in the '' HPRT1'' gene located on the X chromosome. ...

(juvenile gout), as well as severe impairment of kidney function, including

kidney transplant Kidney transplant or renal transplant is the organ transplant of a kidney into a patient with end-stage kidney disease (ESRD). Kidney transplant is typically classified as deceased-donor (formerly known as cadaveric) or living-donor transplantat ...

and

hemodialysis Hemodialysis, American and British English spelling differences#ae and oe, also spelled haemodialysis, or simply ''"'dialysis'"'', is a process of filtering the blood of a person whose kidneys are not working normally. This type of Kidney dialys ...

patients.: Zurampic. Accessed 19 July 2017.

Adverse drug reactions

In clinical trials,

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 impor ...

(an important marker for kidney function) was elevated in 4.3 to 7.8% of patients depending on the dose, as compared to 2.3% under

placebo A placebo ( ) can be roughly defined as a sham medical treatment. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. Placebos are used in randomized clinical trials ...

. Manifest kidney problems were less frequent under the standard dose than under placebo:

Kidney failure Kidney failure, also known as renal failure or end-stage renal disease (ESRD), 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 fa ...

occurred in 2.1% of placebo patients, in 1.2% of patients with the therapeutic standard dose, and in 3.5% of patients with the double dose. For

kidney stone Kidney stone disease (known as nephrolithiasis, renal calculus disease, or urolithiasis) is a crystallopathy and occurs when there are too many minerals in the urine and not enough liquid or hydration. This imbalance causes tiny pieces of cr ...

s, the frequencies were 1.7%, 0.6% and 2.5%, respectively. Other common side effects were influenza (5.1% vs. 2.7% under placebo), headache (5.3% vs. 4.1%), and

gastroesophageal reflux disease Gastroesophageal reflux disease (GERD) or gastro-oesophageal reflux disease (GORD) is a chronic upper gastrointestinal disease in which stomach content persistently and regularly flows up into the esophagus, resulting in symptoms and/or ...

(2.7% vs. 0.8%).

Hypersensitivity Hypersensitivity (also called hypersensitivity reaction or intolerance) is an abnormal physiological condition in which there is an undesirable and adverse immune response to an antigen. It is an abnormality in the immune system that causes Imm ...

reactions were rare (<0.1%).

Interactions

The substance is a mild inducer of the liver enzyme

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...

. Some drugs that are metabolized by this enzyme have been shown to be slightly less effective when combined with lesinurad, examples including

simvastatin Simvastatin, sold under the brand name Zocor among others, is a statin, a type of lipid-lowering medication. It is used along with exercise, diet, and weight loss to decrease hyperlipidemia, elevated lipid levels. It is also used to decrease t ...

and

warfarin Warfarin, sold under the brand name Coumadin among others. It is used as an anticoagulant, anticoagulant medication. It is commonly used to prevent deep vein thrombosis and pulmonary embolism, and to protect against stroke in people who ha ...

. It might also be a mild inducer of

CYP2B6 Cytochrome P450 2B6 is an enzyme that in humans is encoded by the ''CYP2B6'' gene. CYP2B6 is a member of the cytochrome P450 group of enzymes. Along with CYP2A6, it is involved with metabolizing nicotine, along with many other substances. Func ...

. On the other hand, lesinurad concentrations in the blood are decreased by drugs that induce

CYP2C9 Cytochrome P450 family 2 subfamily C member 9 (abbreviated CYP2C9) is an enzyme protein. The enzyme is involved in the metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, t ...

and increased by substances that inhibit this enzyme (such as

fluconazole Fluconazole is an antifungal medication used for a number of fungal infections. These include candidiasis, blastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and tinea versicolor. It is also used to pr ...

), as well as in people who have genetically determined low CYP2C9 activity. The same may be true of

microsomal epoxide hydrolase In enzymology, a microsomal epoxide hydrolase (mEH) () is an enzyme that catalysis, catalyzes the hydrolysis reaction between an epoxide and water to form a diol. This enzyme plays a role in the uptake of bile salts within the large intestine. ...

inhibitors (such as

valproic acid Valproate (valproic acid, VPA, sodium valproate, and valproate semisodium forms) are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches. They are useful for the prevention of seizures in those with ...

). High dose

aspirin Aspirin () is the genericized trademark for acetylsalicylic acid (ASA), a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and inflammation, and as an antithrombotic. Specific inflammatory conditions that aspirin is ...

and related drugs reduce the effectiveness of other anti-gout medications. It is not known conclusively whether this also applies to lesinurad, but

low dose aspirin Aspirin () is the genericized trademark for acetylsalicylic acid (ASA), a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and inflammation, and as an antithrombotic. Specific inflammatory conditions that aspirin is us ...

does not negatively affect its activity.

Pharmacology

Mechanism of action

Lesinurad inhibits

URAT1 Solute carrier family 22 (organic anion/cation transporter), member 12, also known as SLC22A12 and URAT1, is a protein which in humans is encoded by the ''SLC22A12'' gene. Function The protein encoded by this gene is a uric acid, urate transpor ...

, a protein that is responsible for

reabsorption In renal physiology, reabsorption, more specifically tubular reabsorption, is the process by which the nephron removes water and solutes from the tubular fluid (pre-urine) and returns them to the circulating blood. It is called ''reabsorption' ...

of uric acid in the kidneys. This leads to increased uric acid excretion with the urine, and consequently lower blood levels. It also inhibits the protein

OAT4 Organic anion transporter 4 (OAT4) can refer to either of these carrier proteins: * Solute carrier family 22 member 9 (SLC22A9) * Solute carrier family 22 member 11 (SLC22A11) {{Short pages monitor