Budesonide, sold under the brand name Pulmicort, among others, is a steroid medication. It is available as an inhaler, nebulization solution,

pill Pill or The Pill may refer to: Drugs * Pill (pharmacy), referring to anything small for a specific dose of medicine * "The Pill", a general nickname for the combined oral contraceptive pill Film and television * ''The Pill'' (film), a 2011 fil ...

nasal spray Nasal sprays are used to deliver medications Route of administration#Local, locally in the nasal cavities or systemic administration, systemically. They are used locally for conditions such as nasal congestion and allergic rhinitis. In some sit ...

, and rectal forms. The inhaled form is used in the long-term management of

asthma Asthma is a common long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wh ...

and

chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by chronic respiratory symptoms and airflow limitation. GOLD defines COPD as a heterogeneous lung condition characterized by chronic respiratory s ...

(COPD). The nasal spray is used for

allergic rhinitis Allergic rhinitis, of which the seasonal type is called hay fever, is a type of inflammation in the nose that occurs when the immune system overreacts to allergens in the air. It is classified as a type I hypersensitivity reaction. Signs a ...

and nasal polyps. Modified-release pills or capsules and rectal forms may be used for

inflammatory bowel disease Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, with Crohn's disease and ulcerative colitis (UC) being the principal types. Crohn's disease affects the small intestine and large intestine ...

including

Crohn's disease Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea, fever, abdominal distension, and weight loss. Complications outside of the ...

ulcerative colitis Ulcerative colitis (UC) is one of the two types of inflammatory bowel disease (IBD), with the other type being Crohn's disease. It is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary sympto ...

, and microscopic colitis. Common

side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s with the inhaled form include respiratory infections, cough, and headaches. Common side effects with the pills include feeling tired, vomiting, and

joint pain Arthralgia () literally means 'joint pain'. Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication Medication (also called medicament, medicine, pharmaceutic ...

s. Serious side effects include an increased risk of infection, loss of bone strength, and

cataracts A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision of the eye. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colours, blurry or double vision, halos around ligh ...

. Long-term use of the pill form may cause

adrenal insufficiency Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones. The adrenal glands—also referred to as the adrenal cortex—normally secrete glucocorticoids (primarily cortisol), mineraloco ...

. Stopping the pills suddenly following long-term use may therefore be dangerous. The inhaled form is generally safe in

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

. Budesonide chiefly acts as a

glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebra ...

. Budesonide was initially patented in 1973. Commercial use as an asthma medication began in 1981. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

. Some forms are 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 2022, it was the 177th most commonly prescribed medication in the United States, with more than 2million prescriptions.

Medical uses

Asthma

Budesonide is given by

metered-dose inhaler A metered-dose inhaler (MDI) is a device that delivers a specific amount of medication to the lungs in the form of a short burst of aerosolized medicine that is usually self-administered by the patient via inhalation. It is the most commonly used ...

or nebulizer for maintenance and prophylactic treatment of

, including patients who require oral

corticosteroids Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invol ...

and those who may benefit from a systemic dose reduction.

Inflammatory bowel disease

Formulations of delayed-release budesonide are an effective treatment for mild-to-moderately active

involving the

ileum The ileum () is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine may ...

and/or

ascending colon In the anatomy of humans and homologous primates, the ascending colon is the part of the colon located between the cecum and the transverse colon. Characteristics and structure The ascending colon is smaller in calibre than the cecum from wh ...

. A Cochrane review found evidence for up to three months (but not longer) of maintenance of remission in Crohn's disease, concluding that budesonide is not effective for maintenance of remission in CD. Budesonide assists in the induction of remission in people with active

. Budesonide is highly effective and recommended as the drug of choice in microscopic colitis, for induction and maintenance of remission, and for both the lymphocytic colitis and collagenous colitis forms.

Allergic rhinitis

Budesonide in the form of nasal sprays is a treatment for

Eosinophilic esophagitis

Topical budesonide has considerable effects in eosinophilic esophagitis. For this use, it is formulated as a tablet that disperses in the mouth, and sold under the brand name Jorveza.

Berger's disease

Budesonide (Tarpeyo (US); Kinpeygo (EU, UK)) is indicated to reduce proteinuria (increased protein levels in the urine) in adults with primary immunoglobulin A (IgA) nephropathy (Berger's disease) at risk of rapid disease progression.

Side effects

Nasal budesonide inhalers have been associated with a number of side effects. These include nose irritation or burning, bleeding or sores in the nose, lightheadedness, upset stomach, cough, hoarseness, dry mouth, rash, sore throat, bad taste in mouth, change in

mucus Mucus (, ) is a slippery aqueous secretion produced by, and covering, mucous membranes. It is typically produced from cells found in mucous glands, although it may also originate from mixed glands, which contain both Serous fluid, serous and muc ...

, and blurred vision. Other symptoms which should be reported immediately include difficulty in breathing, swelling of the face, white patches in the throat, mouth, or nose, irregular

menstrual period The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that makes pregnancy possible. The ovarian cycle controls the production and release of eg ...

s, severe acne, and on rare occasions, behavioral changes (mostly affecting children).

Overdose

Acute toxicity from an overdose of budesonide is significantly more rare than an overdosing of budesonide over a prolonged period of therapy, however both can cause systemic toxicity that manifests as hypercortisolism. Symptoms of an overdose include more specific symptoms such as darkening and thinning of the skin, changes in body fat around the face, neck, back, and waist, increased acne or facial hair, menstrual problems, impotence, or loss of interest in sex, as well as some less specific symptoms such as diarrhea, dizziness, loss of appetite, mental depression, nausea, skin rash, unusual tiredness or weakness, or vomiting.

Contraindications

Budesonide is

contraindicated In medicine, a contraindication is a condition (a situation or factor) that serves as a reason not to take a certain medical treatment due to the harm that it would cause the patient. Contraindication is the opposite of indication, which is a rea ...

in people with: * Known hypersensitivity to budesonide or any component of the formulation. * Status asthmaticus or other acute episodes of asthma which would require intensive, immediate measures. In Canada, there are additional contraindications labeled for Budesonide for people with: * Systemic or local bacterial, fungal and viral infections. * Active or quiescent pulmonary tuberculosis.

Interactions

Budesonide is mainly metabolized in the liver by the 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 ( ...

. Drugs that are CYP3A4 inhibitors such as

ketoconazole Ketoconazole, sold under the brand name Nizoral, among others, is an antiandrogen, antifungal drug, antifungal, and antiglucocorticoid medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin inf ...

clarithromycin Clarithromycin, sold under the brand name Biaxin among others, is an antibiotic used to treat various bacterial infections. This includes strep throat, pneumonia, skin infections, '' H. pylori'' infection, and Lyme disease, among others. Clari ...

ritonavir Ritonavir, sold under the brand name Norvir, is an antiretroviral medication used along with other medications to treat HIV/AIDS. This combination treatment is known as highly active antiretroviral therapy (HAART). Ritonavir is a protease inhi ...

, and nefazodone, among many others, may inhibit the metabolism of Budesonide, prolonging its elimination and leading to possible increased rates of corticosteroid adverse effects due to unwanted drug accumulation.

Grapefruit The grapefruit (''Citrus'' × ''paradisi'') is a subtropical citrus tree known for its relatively large, sour to semi-sweet, somewhat bitter fruit. The flesh of the fruit is segmented and varies in color from pale yellow to dark red. Grapefru ...

is also a potent inhibitor of CYP3A4, and therefore its consumption is not recommended while on budesonide treatment.

Pharmacology

Mechanism of action

Budesonide is an

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

of glucocorticoid receptors. Among its effects are: * Controls the rate of

protein synthesis Protein biosynthesis, or protein synthesis, is a core biological process, occurring inside cells, balancing the loss of cellular proteins (via degradation or export) through the production of new proteins. Proteins perform a number of critica ...

. * Depresses the migration of polymorphonuclear leukocytes and

fibroblasts A fibroblast is a type of biological cell typically with a spindle shape that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibrobla ...

. * Reverses capillary permeability and lysosomal stabilization at the cellular level to prevent or control inflammation. * Has a potent glucocorticoid activity and weak

mineralocorticoid Mineralocorticoids are a class of corticosteroids, which in turn are a class of steroid hormones. Mineralocorticoids are produced in the adrenal cortex and influence salt and water balances (electrolyte balance and fluid balance). The primary ...

activity.

Pharmacokinetics

Different pharmacokinetic proprieties can be seen in the absorption of budesonide depending on how it is formulated. When taken as an extended-release oral capsule, budesonide has an oral

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...

of 9–21% and reaches peak plasma concentrations (C_max) within 2–8 hours. A high fat meal when taken with the capsule can lengthen the time it takes to reach C_max by another 2.3 hours, but will not have any other affects on the pharmacokinetics properties of budesonide. When inhaled through an metered dose inhaler, 34% of budesonide is deposited in the lung with a

of 39% and reaches C_max within 10 minutes. When nebulized, budesonide has an

of 6% and reaches C_max within 1–3 hours. When formulated as a rectal foam, budesonide has an

of 3% to 27% and reaches C_max around 1.5 hours. The plasma protein binding of budesonide is around 85-90%, with an apparent volume of distribution of 2.2-3.9L/kg. Budesonide is 80-90% metabolized at first pass in the liver by the hepatocytic cytochrome P450 isoenzyme 3A4 (

) into two metabolites: 16 alpha-hydroxyprednisolone and 6 beta-hydroxybudesonide. Both of these metabolites have a negligible glucocorticoid activity of less than 1% compared to the parent compound budesonide. 60% of budesonide is excreted is through the urine as its metabolites, no unchanged budesonide is detectable in urine. The average

elimination half-life Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the blood plasma. ...

in plasma is between 2-3.6 hours.

Chemistry

Budesonide, also known as 11β,21-dihydroxy-16α,17α-(butylidenebis(oxy))pregna-1,4-diene-3,20-dione, is a synthetic pregnane

steroid A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes t ...

and non-

halogen The halogens () are a group in the periodic table consisting of six chemically related elements: fluorine (F), chlorine (Cl), bromine (Br), iodine (I), and the radioactive elements astatine (At) and tennessine (Ts), though some authors would ...

ated cyclic ketal

corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invo ...

. It is the C16α

hydroxyl In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...

, C16α,17α cyclic ketal with butyraldehyde

derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

prednisolone Prednisolone is a corticosteroid, a steroid hormone used to treat certain types of allergies, inflammation, inflammatory conditions, autoimmune disorders, and cancers, Electrolyte imbalance, electrolyte imbalances and skin conditions. Some of ...

(11β,17α,21-trihydroxypregna-1,4-diene-3,20-dione).

Stereoisomerism

Society and culture

Brand names

Budesonide is marketed under various brand and generic names internationally. Notable examples for each formulation include: Inhalation: Pulmicort, Pulmicort Flexhaler, Pulmicort Nebuamp, Pulmicort Turbuhaler, TARO-Budesonide, TEVA-Budesonide, Novolizer budesonid meda, Budenova. Systemic (oral pills): Tarpeyo, Uceris, Eohilia, Cortiment, Entocort Jorveza. Nasal: MYLAN-Budesonide AQ, Rhinocort Aqua, Formancis. Topical: Entocort, Uceris, Budenofalk.

Economics

In 2019, 44 US states filed a lawsuit claiming that leading drug companies including Teva, Pfizer, Novartis and Mylan conspired to inflate the prices of over a hundred generic drugs, including budesonide, as much as tenfold.

Legal status

Kinpeygo, a hybrid medicine of Entocort (which has been authorised in the EU since 2 April 1992) that contains the same active substance as Entocort but has a different formulation and a different indication, Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. was approved for medical use in the European Union in July 2022. The FDA granted the application breakthrough therapy designation.

Research

COVID-19

Budesonide was recommended in April 2021 by the UK's NHS to treat COVID-19 on a case-by-case basis for those aged 50 years of age and older. After a

University of Oxford The University of Oxford is a collegiate university, collegiate research university in Oxford, England. There is evidence of teaching as early as 1096, making it the oldest university in the English-speaking world and the List of oldest un ...

research team found in a trial with 1,700 patients that budesonide could benefit many people over 50 with

COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by the coronavirus SARS-CoV-2. In January 2020, the disease spread worldwide, resulting in the COVID-19 pandemic. The symptoms of COVID‑19 can vary but often include fever ...

symptoms, it was recommended from 12 April 2021, by the

National Health Service The National Health Service (NHS) is the term for the publicly funded health care, publicly funded healthcare systems of the United Kingdom: the National Health Service (England), NHS Scotland, NHS Wales, and Health and Social Care (Northern ...

in the UK for

general practitioner A general practitioner (GP) is a doctor who is a Consultant (medicine), consultant in general practice. GPs have distinct expertise and experience in providing whole person medical care, whilst managing the complexity, uncertainty and risk ass ...

s (GPs) to treat COVID-19 on a case-by-case basis. Results of a large-scale trial published in August 2021 suggest that inhaled budesonide improves the time of recovery and people's well-being during the recovery process. Inhalational budesonide was added to the recommended treatment for cases of COVID-19 in

India India, officially the Republic of India, is a country in South Asia. It is the List of countries and dependencies by area, seventh-largest country by area; the List of countries by population (United Nations), most populous country since ...

in April 2021. The NIH recommendation was withdrawn in December 2021 citing the need for more research.

References

External links

* * {{Portal bar , Medicine Aldols Antiasthmatic drugs Drugs developed by AstraZeneca Corticosteroid cyclic ketals Corticosteroids Cyclic acetals with aldehydes Diketones Diols Enones Glucocorticoids Orphan drugs Pregnanes World Health Organization essential medicines Wikipedia medicine articles ready to translate