Budesonide: Mechanism of Action, Clinical Studies, Warnings and Precautions, Adverse Effects, Dosage, Pregnancy and Lactation

It is a corticosteroid to treat different conditions, including asthma.

On April 29, 2016, the United States Food and Drug Administration extended the approval of controlled-release ileal budesonide to include the treatment of mild to moderate active Crohn’s disease in the ileum and / or ascending colon in children of 8 years old and older.

Corticosteroids have long been recommended to induce remission in children with active Crohn’s disease. Controlled ileal release budesonide, first approved by the FDA in 2001, produces less systemic exposure to corticosteroids than prednisolone and may reduce the incidence of adverse effects.

The use of budesonide in children produces less reduction in the rate of growth than prednisone.

In the European Crohn’s and Colitis Organization and the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ECCO / ESPGHAN), the consensus guidelines on the management of Crohn’s disease, 96% of panel experts agreed on that budesonide can be used as an alternative to systemic corticosteroids for children with colonic ileal or ascending disease.

Mechanism of action

Budesonide, (RS) -11β, 16α, 17, 2-tetrahydroxy pregna-1,4-diene, 3,20-cyclic dione 16,17-acetal butyraldehyde, is a high potency non-halogenated glucocorticoid with weak mineralocorticoid effects. Budesonide has an intrinsic potency approximately 200 times greater than that of cortisol and 15 times greater than prednisolone.

Pharmacokinetics and pharmacodynamics

It provides a high degree of topical glucocorticoid activity in the distal ileum compared to its systemic effects. This local effect is the result of its low bioavailability (approximately 10%) caused by an important first-pass metabolism through CYP3A4 enzymes in the intestinal mucosa and liver.

In the pharmacokinetic studies prior to commercialization, the average maximum plasma concentration and the area under the concentration time curve (AUC) after a dose of 9 mg administered once a day were 5.3 ± 1.8 nmol / L and 37.0 ± 14.6 nmol • h / L in healthy adults, and 4.0 ± 2.1 nmol / L and 35.0 ± 19.8 nmol • h / L in adults with active Crohn’s disease.

The time to peak concentrations varied from 30 to 600 minutes. Administration with a high-fat meal delayed the maximum concentration time but did not alter the AUC, suggesting that the medication can be taken with or without food. The average volume of distribution varied from 2.2 to 3.9 L / kg, with 85-90% bound to plasma proteins.

Budesonide has an elimination half-life of 2 to 3.6 hours. The primary metabolites, 6β-hydroxy budesonide and 16α-hydroxy prednisolone, have no significant corticosteroid activity and are excreted in the urine.

The pharmacokinetic and pharmacodynamic profiles of budesonide were compared in six adults and eight children aged between 9 and 14 years.

After a week of 9 mg of budesonide administered once a day, the median maximum plasma concentration in children was 6.0 ± 3.5 nmol / h, with an average AUC of 41.3 ± 12.2 nmol • h / L, approximately 17% greater than that observed in adult subjects. The average bioavailability of budesonide in children was 9.2%.

The mean volume of distribution was 2.2 ± 0.4 L / kg, with a normalized clearance by weight of 20.5 ml / min / kg, compared to 15.9 ml / min / kg in adults. The half-life was 1.9 ± 0.2 hours.

There was a greater decrease in plasma cortisol AUC in children compared to adults (64% ± 18% compared to 50% ± 27%), but the difference was not statistically significant. The authors summarized that the pharmacokinetics of budesonide is similar in children and adults; however, there was a trend towards a higher degree of suppression of cortisol in pediatric patients.

Clinical studies

Induction of referral

In 2001, Kundhal and colleagues at the Hospital for Sick Children in Toronto published the first retrospective study of controlled release ileal budesonide in children with mild to moderate Crohn’s disease. [6] Thirty-two children aged 8 to 18 years with a Pediatric Crohn’s Disease Activity Index (PCDAI) were enrolled between 12.5 and 40 points.

Twenty-three patients had localized disease in the ileum and nine had ileal and colonic involvement. All patients received 9 mg of budesonide once a day.

The five newly diagnosed patients received budesonide alone, while patients with relapsing disease received budesonide in addition to their other maintenance medications (5-aminosalicylic acid, sulfasalazine, metronidazole, ciprofloxacin, or azathioprine).

At the first follow-up visit (a mean of 8.7 ± 6 weeks after the start of therapy), 59% of patients had a positive response to treatment as determined by the physician’s overall assessment and PCDAI scores . Eight patients (25%) were classified with a complete response, and eleven patients (34%) had a partial response.

In the 22 patients with complete documentation, the mean PCDAI decreased from 33 ± 14 to 22 ± 16 (p = 0.001). The PCDAI fell to <15, indicating remission, in six patients. After the acute phase of treatment, six patients continued to receive 6 mg of budesonide daily as maintenance therapy. Only one of the six experienced an exacerbation during the treatment.

The other five children experienced good control of their symptoms and gained weight during follow-up. The six patients on maintenance therapy had a slower growth rate, with a linear growth rate <4 cm / year, more than two standard deviations lower than the mean for prepubertal children.

The average growth rate during the 6-month treatment period was similar to that before treatment at 2.3 ± 1.0 cm / year, compared with 3.0 ± 1.8 cm / year before starting budesonide (p = 0.31). It is not clear at this time, this indicates an impairment of drug-induced growth or the presence of active disease despite normal PCDAI scores.

In 2003, Escher and colleagues from the European Collaborative Research Group on Budesonide in Pediatric Inflammatory Bowel Disease published the results of their prospective randomized, double-blind, active multicenter comparative trial. Forty-six children from 6 to 16 years of age with active Crohn’s disease were enrolled.

All children had disease affecting the ileum and / or ascending colon and a standard Crohn’s disease activity index (CDAI) ≥ 200, indicating significant disease.

Patients received budesonide controlled ileal release 9 mg once daily for 8 weeks followed by 6 mg daily for 4 weeks or prednisolone 1 mg / kg daily for 4 weeks followed by a gradual reduction for 8 weeks. The primary end point for the study was the percentage of patients in remission, defined as a CDAI of ≤ 150, at 8 weeks.

The remission rates were similar between the groups at 8 weeks: 55% of the children who received budesonide and 71% of the prednisone group (p = 0.25). These findings were similar to both the Kundhal study and the remission rates reported in trials in adults. Approximately half of the patients in both groups achieved remission in 2 weeks.

Both treatment groups reached the maximum clinical effect at week 8. Mean CDAI scores remained highest in the budesonide group throughout the study, with an average of 149 at 8 weeks compared with 97 in the group. of prednisolone (p = 0.047). Adverse effects were common in both groups, with abdominal pain and headache being the most frequent.

Other adverse effects of glucocorticoids, such as acne and the lunar face, occurred in fewer children who received budesonide (5% and 23%, respectively, compared to 27% and 58% in the prednisolone group, p = 0.01 and 0.033).

The mean erythrocyte sedimentation rate (ESR) decreased to a greater extent in the prednisolone group than in the budesonide group (13 mm / h compared with 5 mm / h, p <0.05), suggesting a lower systemic exposure to corticosteroids with budesonide over time.

The average morning cortisol level was significantly higher in the budesonide group, 200 nmol / L (6.3 mcg / dL), compared with 98 nmol / L (2.6 mcg / dL) in the prednisolone group (p = 0.0028), which confirms less adrenal suppression.

Additional information on the effectiveness and safety of budesonide has been obtained with the study of an alternative dosage formulation available in Canada and Europe.

This product, sold as Budeson® or Budenofalk®, is designed to dissolve at pH> 5.5, making it available for the lower ileum. In 2003, Levine and his colleagues, who wrote for the Israeli-Israel Pediatric Budesonide Study Group, evaluated this product in 33 children and adolescents (average age 14.3 years).

Patients were randomized to receive budesonide pH-dependent release of 9 mg or 40 mg of prednisone per day for 12 weeks. The remission rates were similar, 47% in the budesonide group and 50% in the prednisone group. The reduction in PCDAI scores at week 12 was also similar (9.3 ± 14.8 for budesonide and 13.4 ± 10.6 for prednisone).

However, there were significant differences in the percentage of patients who experienced adverse effects (32% in the budesonide group and 71% in the prednisone group, p <0.05).

As in the study of controlled release ileal budesonide, there were lower rates of cosmetic adverse effects (lunar face, acne and hirsutism) with budesonide pH-dependent release compared to prednisone (p <0.01).

Significant adverse effects were uncommon; A patient who received prednisone developed a herpetic infection of the skin and one patient in each group was diagnosed with depression. Although it was not a statistically significant difference, muscle pain or proximal muscle weakness occurred more frequently in the prednisone group (36%) than in the budesonide group (8%).

These researchers conducted a follow-up study in 2009 that compared two budesonide regimens of pH-dependent release. Seventy children were randomly assigned to a standard regimen of 9 mg once a day for 7 weeks followed by 6 mg daily for 3 weeks (group 1) or induction with 12 mg once a day for a month followed by the standard regimen used in the group 1 (group 2).

The primary outcomes were the remission rate and change in PCDAI in week 7. Clinical response was reported in 51.4% of patients in group 1 versus 74.3% in group 2. Rates of remission at the end of treatment were 42.9% and 65.7% in the two groups, respectively (p = 0.054).

The authors concluded that an induction dose of budesonide can produce higher remission rates without an increase in adverse effects induced by steroids.

Although the results of these two studies can not be extrapolated to controlled release ileal budesonide, they confirm the ability of budesonide to produce control and remission rates similar to those produced by systemic corticosteroids in children with Crohn’s disease.

A summary of the clinical experience with budesonide was published by the Collaborative Pediatric Intestinal Disease Research Group in 2012. The group maintains a registry of patients from 21 pediatric gastroenterology centers in North America.

Of the 932 patients <16 years of age with Crohn’s disease in the registry, 119 (13%) received a total of 148 cycles of budesonide. Both pH-dependent release and controlled ileal release preparations were included. The average age of the patients was 12.5 ± 2.1 years.

Thirty-five percent of the patients had ileum and / or ascending colon disease, while 65% had a more widespread disease. The most commonly prescribed dose was 9 mg once a day (105 patients), followed by 6 mg (10 patients), 3 mg (9 patients) and 12 mg (one patient).

Budesonide was typically prescribed as adjuvant therapy with 5-aminosalicylates or immunomodulators in patients with active disease, or as a means of weaning from systemic corticosteroids. Of the 56 newly diagnosed patients, only five took budesonide as monotherapy.

In the 63 children with established disease, only one patient received budesonide alone. The authors concluded that the use of budesonide is increasing, mainly as initial treatment in newly diagnosed children or as complementary therapy for patients to minimize exposure to systemic corticosteroids, 5-aminosalicylates, azathioprine or methotrexate.

Maintenance Therapy

Although approved for maintenance of clinical remission for up to 3 months in adults, budesonide has not been approved for maintenance therapy in children.

Prescribing information for the drug states that an open-label maintenance therapy study with controlled ileal release for children 5 to 17 years of age did not meet the requirements to establish safety and efficacy.

As demonstrated in the Kundhal study of controlled ileal release budesonide, as well as in Levine’s study of budesonide pH-dependent release, long-term administration in children and adolescents with Crohn’s disease has the potential to produce reductions clinically significant in the linear growth rate.

Warnings and precautions

Hypersensitivity reactions, including anaphylaxis, are rare but cases of budesonide have been reported. As a result, it is contraindicated in patients with previous evidence of hypersensitivity to any form of budesonide or any of the other ingredients in the product.

As with all corticosteroids, the use of budesonide may increase the risk of infection. Chronic administration of corticosteroids has been associated with an increase in cortisol levels and suppression of the adrenal axis.

In patients receiving budesonide who undergo surgery or significant stress, supplementation with a systemic corticosteroid is recommended.

Patients transitioning from a corticosteroid with increased systemic absorption, such as prednisone, to budesonide should be closely monitored for signs of steroid withdrawal. It is recommended to gradually reduce the systemic dose of corticosteroids.

Adverse effects

Adverse effects reported most frequently with budesonide controlled ileal release in adults include headache (21%), respiratory infection (11%), nausea (11%), back pain (7%), dizziness (7%), dyspepsia (6%), abdominal pain (6%), flatulence (6%), vomiting (6%), fatigue (5%) and pain (5%).

The most frequent adverse effects in the 22 patients with budesonide in the Escher study were headache (18%), abdominal pain (14%), fatigue (14%), vomiting (14%) and myalgias, pharyngitis or nausea (9%). ) Similar results were observed in the 2004 Levine study.

The budesonide data from the Collaborative Pediatric Intestinal Disease Research Group did not include reports of fractures, opportunistic or serious infections or other serious adverse effects.

Use with other medications

Budesonide is a CYP3A4 substrate and should not be used with CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, erythromycin, cyclosporine, and grapefruit juice. Concomitant use with ketoconazole may increase serum concentrations of budesonide eight times. A similar degree of CYP3A4 is produced by the derivatives of furocoumarin in grapefruit juice.

As a result, it should not be taken at any time during treatment to avoid high concentrations of budesonide as a result of inhibition of CYP3A4 in the intestine. In contrast, administration with potent inducers of CYP3A4, such as phenobarbital, phenytoin, or rifampin, may result in subtherapeutic concentrations.

The clinical significance of reduced concentrations of serum budesonide is not known

Dosage and uses for Adults

Dosage forms and effects

  • Capsule, enteric-coated and extended-release (Entocort CE) 3 mg
  • Tablet, enteric-coated and extended-release (Uceris) 9 mg

Ulcerative colitis

Induction of remission of active mild to moderate ulcerative colitis

Uceris: 9 mg PO qAM for up to 8 weeks

Crohn’s disease

Treatment of mild to moderate active Crohn’s disease with ileum or ascending colon; maintenance of clinical remission of mild to moderate Crohn’s disease for up to 3 months

Entocort EC: 9 mg PO qAM for up to 8 weeks; for recurrent episodes of active disease, 8-week courses can be repeated

Once the symptoms are controlled, it can be reduced to 6 mg PO qAM for maintenance

Maintenance of Crohn’s disease
  • Entocort EC: 6 mg PO qAM for up to 3 months
  • If the control of the symptoms is maintained after 3 months, you can try to decrease (complete cessation) (recommended)
Immunoglobulin A nephropathy

Decreased progression of immunoglobulin A nephropathy; delay the onset of kidney failure in patients affected by this disease

Use for children

Budesonide [Uceris] is used for the treatment of ulcerative colitis in pediatric patients from 0 to 16 years

Adverse effects

> 10%

  • Headache (21%)
  • Acne (<5-15%)
  • Nausea (11%)
  • Respiratory infection (11%)

1-10%

  • Back pain (7%)
  • Dizziness (7%)
  • Abdominal pain (6%)
  • Dyspepsia (6%)
  • Vomiting (6%)
  • Fatigue (5%)

Frequency not defined

  • Adrenal suppression
  • Amnesia
  • Anaphylactic reactions
  • Benign intracranial hypertension
  • Diarrhea
  • Edema facial
  • Fever
  • Flu syndrome
  • Gastrointestinal irritation
  • Hypokalemia
  • Increased appetite
  • Insomnia
  • Migraine
  • Nervousness
  • Pharyngitis
  • Eruption
  • Xerostomia
  • Weight gain

Post-marketing reports

  • Rectal bleeding
  • Peripheral edema
  • Muscle cramps / spasms
  • Humor changes
  • Elevation of blood presure

Warnings

Contraindications

Documented hypersensitivity

Precautions

High fat food delays absorption can increase the risk of serious or fatal infection in people exposed to viral diseases such as chicken pox or measles.

Use with caution in patients with diabetes mellitus, hypertension, hypothyroidism, electrolyte abnormalities, sodium and water retention, infections, immunizations, ocular herpes simplex, myasthenia gravis, peptic ulcer disease, psychosis or renal failure

Thromboembolic disorders and myopathy may occur

Delayed healing of the wound is possible

Patients receiving corticosteroids should avoid people infected with varicella or measles if they are not vaccinated

Latent tuberculosis can be reactivated (patients with positive tuberculin skin test should be monitored)

Any suggestion (not fully substantiated) of slightly increased risk of cleft palate if corticosteroids are used in pregnancy

Prolonged use of corticosteroids can cause elevated intraocular pressure, glaucoma or cataracts and has been associated with the development of Karposi’s sarcoma.

Myopathy has been reported

Secreted in human milk; there are no controlled trial data on possible serious adverse reactions in infants; use with caution

When glucocorticosteroids are used chronically, systemic effects such as hypercorticism and suprarenal suppression may occur; glucocorticosteroids can reduce the response of the hypothalamic-pituitary-adrenal (HPA) axis to stress; In situations where patients are subject to surgery or other stress situations, supplementation with systemic glucocorticosteroid is recommended

Care is needed in the transfer of glucocorticosteroid therapy with higher systemic effects to glucocorticosteroids with lower systemic effects; Symptoms attributed to the withdrawal of steroid therapy, including those of acute adrenal suppression or benign intracranial hypertension, may develop.

Monitoring of corticosuprarenal function may be necessary in these patients and the dose of glucocorticosteroid therapy with high systemic effects should be reduced with caution.

Glucocorticosteroids should be used with caution, in any case, in patients with active or quiescent tuberculosis infection, viral or parasitic infections not treated, fungal, bacterial, systemic

The replacement of systemic glucocorticosteroids with budesonide tablets can unmask allergies (eg, rhinitis and eczema), which were previously controlled by the systemic drug.

Reduced liver function affects the elimination of glucocorticosteroids; A greater systemic availability of oral budesonide has been demonstrated in patients with liver cirrhosis

Pregnancy and lactation

The pregnancy

Limited published studies report in pregnant women; however, the data are insufficient to inform a risk associated with drugs for major congenital defects and spontaneous abortion.

There are clinical considerations; in studies of animal reproduction with rats and pregnant rabbits, the administration of budesonide subcutaneously during organogenesis at doses of approximately 0.5 times or 0.05 times, respectively, the maximum recommended human dose, resulted in an increase in fetal loss , decrease of the weight of the offspring and skeletal anomalies.

Maternal toxicity was observed in both rats and rabbits at these dose levels; Based on animal data, advise pregnant women about the potential risk to a fetus

Some published epidemiological studies show an association of adverse pregnancy outcomes in women with Crohn’s disease, including premature and low birth weight infants, during periods of increased disease activity (including increased stool frequency and abdominal pain).

Pregnant women with Crohn’s disease should be counseled about the importance of controlling the disease

Hypoadrenalism can occur in babies born to mothers who receive corticosteroids during pregnancy; Babies should be observed carefully for signs of hypoadrenalism, such as poor nutrition, irritability, weakness and vomiting, and should be treated accordingly

Lactation

Breastfeeding studies conducted with oral budesonide, and there is no information available on the effects of the drug on the infant or on the effects of the drug on milk production; A published study reports that budesonide is present in human milk after maternal inhalation of budesonide.

The benefits of the development and health of breastfeeding should be considered together with the mother’s clinical need for therapy and any possible adverse effects on the infant or the underlying maternal condition

Pregnancy categories

A: Generally acceptable Controlled studies in pregnant women show no evidence of fetal risk.

B: It may be acceptable. Either the animal studies show no risk, but studies in humans are not available or studies in animals showed minor risks and human studies were conducted and showed no risk.

C: Use caution if the benefits outweigh the risks. Studies in animals show risk studies and in humans not available or studies were not conducted in animals or humans.

D: Use it in emergencies that put LIFE IN DANGER when there is no safer medication available. Positive evidence of human fetal risk.

X: do not use in pregnancy The risks involved outweigh the potential benefits. There are safer alternatives.

Pharmacology

Mechanism of action

Anti-inflammatory corticosteroid; potent glucocorticoid activity but weak mineralocorticoid activity; controls the rate of protein synthesis; reduces inflammation by suppressing the migration of polymorphonuclear leukocytes (MLP) and reducing capillary permeability.

Stabilizes cell and lysosomal membranes, increases surfactant synthesis, increases serum vitamin A concentration, and inhibits prostaglandin and proinflammatory cytokines; suppresses the proliferation of lymphocytes through direct cytolysis, inhibits mitosis and breaks down granulocyte aggregates

Absorption

Bioavailability: capsule, 9-21%

Peak plasma time: capsule, 5-10 h

Distribution

Bound protein: 85-90%

Vd: 2.2-3.9 L / kg

Metabolism

Extensive first-pass metabolism by CYP3A4 in the liver

Metabolitos: 6-Beta-hydroxybudesonide, 16-alpha-hydroxyprednisolone (inactive)

Elimination

Average life: 2-3.6 h

Excretion: Urine (60%), stool (minimum)

Patient education

Budesonida nasal

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all the possible information about this product. This information does not guarantee that this product is safe, effective or appropriate for you.

This information is not individual medical advice and does not replace the advice of your health professional. Always check with your health care professional for complete information about this product and your specific health needs.

APPLICATIONS:

Budesonide is used to prevent and treat the symptoms of seasonal allergies and throughout the year (such as stuffy / runny nose, itchy eyes / nose / throat, sneezing). Budesonide belongs to a class of medications known as corticosteroids. It works by reducing swelling (inflammation) in the nasal passages.

OTHER USES:

This section contains uses of this medication that are not on the approved professional label for the medication, but may be prescribed by your healthcare professional. Use this medication to treat a condition listed in this section only if prescribed by your healthcare professional.

In Canada, this medication can also be used to treat growths in the nose (nasal polyps) or to prevent it from coming back after extraction by surgery.

How to use:

If you are taking an over-the-counter product for self-treatment, read and follow all instructions in the product package before using this medication. If you have any questions, ask your pharmacist.

If your doctor has prescribed this medication, read the Patient Information Leaflet before you start using budesonide and each time you refill it. If you have any questions, ask your doctor or pharmacist.

This medication is for use in the nose, usually 1 or 2 aerosols in each nostril once or twice a day or as directed by your doctor. Avoid spraying this medication in your eyes. Gently blow your nose before using this drug. Shake the container gently before each use.

Follow the instructions to properly prime the spray pump if you are using it for the first time or if you have not used it for 2 or more days. Follow the instructions to clean / prime the spray pump if you have not used it for 14 or more days.

To use the spray, first remove the plastic cap. Close a nostril by pressing it with your finger. Tilt the head slightly forward and, keeping the bottle upright, carefully insert the nasal applicator into the other nostril. Press the pump firmly to administer the prescribed amount of aerosols while breathing gently through the nose, keeping the mouth closed.

Do not spray directly on the middle wall of the nose (nasal septum). After spraying, remove the tip of the applicator and tilt the head back for a few seconds. This will allow the medication to spread through the back of the nose. Repeat in the other nostril. Clean the tip of the applicator and replace the plastic cap. Avoid blowing your nose for 15 minutes after using this medication.

The dosage is based on your age, medical condition and response to treatment. Younger children may need a smaller dose and the help of an adult to use this medication properly. Use this medication regularly to get the most benefit from it.

To help you remember, use it at the same time every day. Do not increase your dose or use this medication more often or for longer than indicated. Your condition will not improve faster, and your risk of side effects will increase.

This medicine does not work immediately. Some people will feel that this medication works within 1 to 2 days, but it may take up to 2 weeks before the full benefit of this medication becomes effective.

Ask your doctor or pharmacist if you should also use other medications (such as nasal drops / sprays, allergy medications taken by mouth) with this medicine until it has full effect. Talk to your doctor if your child needs to use this medication more than 2 months a year.

Keep a record of the amount of aerosols used in the bottle. Discard the bottle after using the amount of aerosols specified in the manufacturer’s package. Do not pour the remaining medication into another container. Follow the package instructions to unlock the spray nozzle if necessary and to clean the spray bottle.

If your condition does not improve after 2 weeks or if it gets worse, stop using this medicine and consult your doctor or pharmacist. If you think you may have a serious medical problem, get medical help immediately.

Side effects:

It may cause dryness or irritation of the nose / throat, coughing, sneezing, nosebleeds or unpleasant taste / odor. If any of these side effects persist or worsen, inform your doctor or pharmacist promptly.

If your doctor has told you to use this medication, remember that he or she has determined that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have serious side effects, which include: loss of taste or smell, pain / sores in the nose.

Rarely, corticosteroids given in the nose may be absorbed into the bloodstream. This can cause side effects of too much corticosteroid. These side effects are more likely in children and people who use this medication for a long time and in high doses.

Tell your doctor immediately if you experience any of the following side effects: unusual / extreme tiredness, weight loss, headache, swelling of the ankles / feet, increased thirst / urination, vision problems.

Corticosteroids can weaken the body’s ability to fight infections. This can increase the chance of getting a serious (rarely fatal) infection or worsening any infection. This effect can also rarely occur with inhaled corticosteroids through the nose (such as budesonide).

The risk can increase if high doses are used, especially when used for a long time. Tell your doctor immediately if you have any signs of infection (such as earache, persistent sore throat, fever, chills, white patches inside the nose or in the back of the throat).

A very serious allergic reaction to this medication is rare. However, seek medical attention immediately if you notice any symptoms of a severe allergic reaction, which includes: rash, itching / swelling (especially of the face / tongue / throat), severe dizziness, wheezing / shortness of breath.

This is not a complete list of possible side effects. If you notice other effects not mentioned above, contact your doctor or pharmacist.

Precautions:

Before using budesonide nasal, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies This product may contain inactive ingredients, which may cause allergic reactions or other problems. Consult your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially about: eye problems (such as glaucoma, cataracts), infections (including tuberculosis), recent nose problems (such as injuries, ulcers, surgery).

Avoid contact with people who have infections that can spread to other people (such as chicken pox, measles, flu). Consult your doctor if you have been exposed to an infection or for more information.

Rarely, the use of corticosteroid medications for a long time can make it harder for your body to respond to physical stress. Therefore, before having surgery or emergency treatment, or if you get a serious illness / injury, tell your doctor or dentist that you are using this medicine or that you have used it in recent months.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, over-the-counter medications, and herbal products).

Although it is unlikely, this medication can slow a child’s growth if it is used for a long time. The effect on final adult height is unknown. Consult your doctor regularly so that your child’s height can be checked.

Tell your doctor if you are pregnant before using budesonide nasal. Rarely, babies born to mothers who have been using corticosteroids (including budesonide) for a prolonged period may have low levels of corticosteroid hormone.

Tell your doctor immediately if you notice symptoms such as persistent nausea / vomiting, severe diarrhea or weakness in your newborn. Discuss the risks and benefits with your doctor.

It is not known if nasal budesonide passes into breast milk. However, similar drugs pass into breast milk. Budesonide nasal can also pass into breast milk in very small amounts that are unlikely to harm the infant. Consult your doctor before breast-feeding.

Iinteractions with medicines:

Interactions with other medications can change how your medications work or increase the risk of serious side effects. This document does not contain all possible drug interactions.

Keep a list of all the products you use (including over-the-counter and non-prescription medicines and herbal products) and share it with your doctor and pharmacist. Do not start, stop or change the dosage of any medication without your doctor’s approval.

Check all prescription labels carefully with similar medications (other corticosteroids such as prednisone) may increase your risk of side effects if taken with this medication. Ask your doctor or pharmacist if you have any questions about your medications.

Overdose:

If someone has an overdose and has severe symptoms, such as fainting or difficulty breathing, call emergency. Otherwise, call a poison control center immediately.

Notes:

Keep all regular medical and laboratory appointments.

If you use this medication for a long time, lab and / or medical tests (such as nose exams, height measurement in children) can be done to monitor your progress and detect side effects.

Avoid substances (such as pollen, pet dander, dust mites, mold and smoke) that can worsen allergy symptoms.

Missed dose:

If you use this product on a regular schedule and forget a dose, use it as soon as you remember. If you are near the time of the next dose, skip the missed dose. Use your next dose at the usual time. Do not double the dose to catch up.

Storage:
Store at room temperature with the protective cap in a place away from light and moisture. Keep the container upright. Keep all medications out of the reach of children and pets.

Do not throw medicines into the toilet or pour them into the drain unless instructed to do so. Discard this product correctly when it has expired or is no longer necessary. Consult your pharmacist or local waste disposal company.

Budesonide in inhaler

Applications:

Budesonide is used to control and prevent symptoms (wheezing and difficulty breathing) caused by asthma. This medicine belongs to a class of medications known as corticosteroids. It works directly in the lungs to facilitate breathing by reducing irritation and swelling of the airways.

This medication must be used regularly to be effective. It does not work immediately and should not be used to relieve sudden attacks of asthma. If an asthma attack occurs, use your fast-relief inhaler as prescribed.

Other uses:

This section contains uses of this medication that are not on the approved professional label for the medication, but may be prescribed by your healthcare professional. Use this medication to treat a condition listed in this section only if prescribed by your healthcare professional.

This medicine can also be used to treat lung diseases such as bronchitis and emphysema.

How to use:

Read the Patient Information Leaflet provided by your pharmacist before you start using budesonide and each time you get a refill. Read the instructions provided by the manufacturer on the correct use of this device (including a dose counter, if one is available). If you have any questions, ask your doctor or pharmacist.

Follow the instructions to prime the inhaler if you are using it for the first time. It is not necessary to prime the device again. If you are using the Canadian product: it is not necessary to prime the inhaler before use.

Do not shake this product, and do not use a spacer with it. Keep the device upright while using. If the inhaler device falls or is shaken, or if you accidentally inhale into the device after you have loaded the dose, you will lose the dose. Load another dose Do not use the inhaler if it has been damaged or if the mouthpiece has come loose.

Inhale this medication orally, usually once or twice a day, or as directed by your doctor. Inhale deeply and forcefully while using the device. Turn your mouth away from the device to exhale before inhaling. Do not exhale back to the device.

If your prescribed dose is 2 inhalations, wait at least one minute between them. If you are using other inhalers at the same time, wait at least 1 minute between the use of each medication and use this medication (the corticosteroid) last.

To prevent dry mouth, hoarseness, and oral fungal infections from developing, gargle and rinse your mouth with water after each use. Do not swallow the rinse water.

Keep a record of each dose of medication you use. Discard the device after you have delivered the marked dose number or when the red mark reaches the end of the dose indicator window.

The dosage is based on your medical condition and response to treatment. Use this medication regularly to get the most benefit from it. To help you remember, use it at the same time every day. Do not increase your dose or use this medication more often or for longer than prescribed. Your condition will not improve faster, and your risk of side effects will increase.

Know which of your inhalers you should use every day (controller medications) and which ones to use if your breathing suddenly gets worse (quick-relief medications).

Ask your doctor ahead of time what to do if you have new or worsening coughing or breathing difficulties, wheezing, sputum increase, worsening peak flow meter readings, waking up at night with trouble breathing, if you use your inhaler quick relief more often (more than 2 days a week), or if your quick-relief inhaler does not seem to be working well.

Know when you can treat yourself sudden respiratory problems and when you should get medical help immediately.

If you regularly use a different corticosteroid (such as prednisone), you should not stop using it unless your doctor tells you to. You may have withdrawal symptoms if the medication stops suddenly. Some conditions (such as asthma, allergies) can get worse when the medication is suddenly stopped.

To prevent withdrawal symptoms (such as weakness, weight loss, nausea, muscle pain, headache, tiredness, dizziness), your doctor may tell you to slowly lower the dose of your previous medicine after using budesonide.

Consult your doctor or pharmacist for more information and report any abstinence reactions immediately.

You may notice a benefit within 24 hours after you start taking this medication. It may take 1 to 2 weeks before the full benefit of this medication goes into effect. Tell your doctor if your symptoms do not improve or if they get worse.

The Canadian inhaler is not the same as the American inhaler. Do not substitute the 2 products without talking to your doctor. Your dose may need to be changed.

Side effects:

It can cause dryness / irritation in the throat, hoarseness, changes in the voice, nausea, bad taste in the mouth, nasal discharge / congestion or nosebleeds. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Infrequently, this medication can cause a sudden and severe worsening of respiratory problems / asthma immediately after use. If you have a sudden worsening of breathing, use your quick-relief inhaler and seek immediate medical attention.

Because this medication works by weakening the immune system, it can decrease your ability to fight infections. This can increase the chance of getting a serious (rarely fatal) infection or worsening any infection.

Tell your doctor right away if you have any signs of infection (such as earache, sore throat, fever, chills). The use of this medication for prolonged or repeated periods may cause oral thrush (fungal infection). Contact your doctor if you notice white spots on your mouth or tongue.

Tell your doctor immediately if you have any of these rare but serious side effects: unusual tiredness, vision problems, bruising / bleeding, swelling, unusual hair growth, mental / mood changes (such as depression, mood swings, agitation) , muscle weakness / pain, thinning of the skin, slow healing of the wound, increased thirst / urination.

A very serious allergic reaction to this medication is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction: rash, itching / swelling (especially of the face / tongue / throat), severe dizziness, trouble breathing.

PRECAUTIONS:

Before using budesonide, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies This product may contain inactive ingredients (such as lactose, milk proteins found in some brands), which can cause allergic reactions or other problems. Consult your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially: eye disease (such as cataracts, glaucoma), high blood pressure, liver disease, thyroid problems, diabetes, stomach / intestinal problems (such as diverticulitis, ulcer ). , bone loss (osteoporosis), current / past infections (such as tuberculosis, positive tuberculosis test, herpes, fungi), bleeding problems, mental / mood conditions (such as psychosis, anxiety, depression).

If you have switched from an oral corticosteroid (such as prednisone tablets) to this inhaler in the past 12 months, or if you have been using this product in higher than usual doses for an extended period, it may be more difficult. so that your body responds to physical stress.

Therefore, before having surgery or emergency treatment, or if you have a serious illness / injury, tell your doctor or dentist that you are using this medication or that you have used an oral corticosteroid in the last 12 months.

Tell your doctor immediately if you develop unusual / extreme tiredness or weight loss. Carry a warning card or medical identification bracelet that says you use (or have used) corticosteroid medications.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, over-the-counter medications, and herbal products).

This medicine may mask signs of infection. It can increase the chance of getting infections or worsen current infections. Therefore, wash your hands thoroughly to avoid spreading the infection.

Avoid contact with people who have infections that can spread to other people (such as chicken pox, measles, flu). Consult your doctor if you have been exposed to an infection or for more information.

Budesonide can cause vaccines to not work as well. Therefore, do not get vaccinated / vaccinated while using this medication without your doctor’s consent. Avoid contact with people who have recently received live vaccines (such as the flu vaccine inhaled through the nose).

This medication can slow a child’s growth if used for a long time, but poorly controlled asthma can also slow growth. The effect on final adult height is unknown. Consult your doctor regularly so that your child’s height can be checked.

Tell your doctor if you are pregnant before using this medicine. Babies born to mothers who have used corticosteroids for a long time can develop hormonal problems. Tell your doctor immediately if you notice symptoms such as persistent nausea / vomiting, severe diarrhea or weakness in your newborn.

This medicine passes into breast milk. Consult your doctor before breast-feeding.

Interaction with other medications:

Interactions with other medications can change how your medications work or increase the risk of serious side effects. This document does not contain all possible drug interactions.

Keep a list of all the products you use (including over-the-counter and non-prescription medicines and herbal products) and share it with your doctor and pharmacist. Do not start, stop or change the dosage of any medication without your doctor’s approval.

Some products that may interact with this medicine include: aldesleukin, mifepristone.

This product may interfere with certain laboratory tests (such as skin tests). Make sure that the laboratory staff and all your doctors know you are using this medicine.

Overdose:

If someone has an overdose and has severe symptoms, such as fainting or difficulty breathing, call emergency. Otherwise, call a poison control center immediately.

Notes:

Do not share this medicine with others.

Learn how to use a peak flow meter, use it daily and promptly report a worsening of asthma (such as readings in the yellow / red range or increased use of quick relief inhalers).

Laboratory and / or medical tests (such as cortisol levels, bone density tests, eye exams, height / weight measurements) should be performed to detect side effects. Check with your doctor for more details.

Avoid allergens (such as pollen, pet dander), irritants, smoking / secondhand smoke and other factors that make asthma worse. Most people with asthma or ongoing lung disease should receive a flu shot annually. Discuss with your doctor

In adults, this medication may increase the risk of bone loss (osteoporosis) if it is used for a long time. Talk to your doctor about your risk and the treatments available for osteoporosis. Lifestyle changes that reduce the risk of bone loss include exercising with weights, getting enough calcium and vitamin D, quitting smoking and limiting alcohol consumption.

To help prevent osteoporosis later in life, encourage children to exercise and eat a healthy diet (including calcium).

Missed dose:

If you miss a dose, use it as soon as you remember. If you are near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

Storage:

Store the product at room temperature between 68-77 degrees F (20-25 degrees C) with the lid firmly, away from light / moisture. Do not store in the bathroom. Keep all medications out of the reach of children and pets.

Store the Canadian product at room temperature between 59 and 86 degrees F (15 to 30 degrees C) with the cover firmly, away from light / moisture.

Do not throw medicines into the toilet or pour them into the drain unless instructed to do so. Discard this product correctly when it has expired or is no longer necessary. Consult your pharmacist or local waste disposal company for more information on how to dispose of your product safely.

Bunesonida rectal

Applications:

This medication is used to treat the symptoms of a certain intestinal disease (ulcerative colitis). It works by reducing swelling (inflammation). Budesonide belongs to a class of medications known as corticosteroids.

Budesonide does not cure ulcerative colitis, but it can help relieve symptoms such as abdominal pain, diarrhea, and bloody stools. Using this medication in the form of foam allows you to work directly on the intestine and rectum.

How to use:

Read the Patient Information Leaflet, if your pharmacist has it, before you start using budesonide and each time you get a refill. Follow the illustrated instructions for the proper use of this medication. If you have any questions, ask your doctor or pharmacist.

Use this medicine as a foam in the rectum as directed by your doctor, usually in the morning and at night for the first 2 weeks, then once a day at night for the next 4 weeks. It is best to use this medicine just before going to bed at night.

This medicine is flammable. Avoid smoking when applying this medication and immediately afterwards. Do not use it or store it near heat or open flames.

It is best to use this medicine after a bowel movement. You can apply this medication while you are standing, lying or sitting. Do not insert any part of the boat into the anus. Use the attached applicator to apply this medication. Follow the instructions to attach the applicator to the container.

Heat the container in your hands and shake the container well for 10 to 15 seconds before using it. Hold the container upside down and gently insert the applicator tip into the anus. Press the pump and keep it in that position for 2 seconds to apply the foam.

Then, release your finger from the pump and continue to hold the applicator in place for 10 to 15 seconds. Then, remove the applicator and throw it away. Wash hands after use. Keep the medicine in your rectum as long as possible, for example during the night.

If you take corticosteroids orally on a regular basis (such as prednisone), you should not stop taking them unless your doctor tells you to. Some conditions (such as asthma, allergies) can get worse when the medication is suddenly stopped.

You may also have withdrawal symptoms if the medication stops suddenly. To prevent withdrawal symptoms (such as weakness, weight loss, nausea, muscle pain, headache, tiredness, dizziness), your doctor may tell you to slowly lower the dose of your previous medicine when you are using budesonide.

Consult your doctor or pharmacist for more information and report any abstinence reactions immediately. See also the Precautions section.

Use this medication regularly to get the most benefit from it. To help you remember, use it at the same time every day. Do not increase your dose or use this medication more often or for longer than prescribed. Your condition will not improve faster, and your risk of side effects will increase.

Do not stop using this medicine without consulting your doctor. Some conditions can get worse when this medicine is stopped suddenly. Your dose may need to be decreased gradually.

Tell your doctor if your condition persists or worsens.

Side effects:

There may be nausea. If this effect persists or worsens, inform your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

In rare cases, this medication may be absorbed into the bloodstream. This can cause side effects of too much corticosteroid. These side effects are more likely in children and people who use this medication for a long time.

Tell your doctor immediately if you experience any of the following side effects: unusual / extreme tiredness, weight loss, headache, swelling of the ankles / feet, increased thirst / urination, vision problems.

This medicine may decrease your ability to fight infections. This can increase the chance of getting a serious (rarely fatal) infection or worsening any infection. Tell your doctor immediately if you have any signs of infection (such as fever, chills, persistent sore throat, cough).

A very serious allergic reaction to this medication is rare. However, seek medical attention immediately if you notice any symptoms of a serious allergic reaction, which includes: rash, itching / swelling (especially on the face / tongue / throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not mentioned above, contact your doctor or pharmacist.

PRECAUTIONS:

Before using budesonide, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies This product may contain inactive ingredients, which may cause allergic reactions or other problems. Consult your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist about your medical history, especially about: liver disease, high blood pressure, personal or family history of diabetes, bone loss (osteoporosis), stomach / intestinal ulcer, certain intestinal disease (diverticulitis), mental / mood disorders (such as depression, psychosis), personal or family history of high pressure in the eye (glaucoma), cataracts, current / past infections (such as tuberculosis, ocular herpes simplex, fungi), thyroid problems.

Rarely, the use of corticosteroid medications for a long time can make it harder for your body to respond to physical stress. Therefore, before having surgery or emergency treatment, or if you get a serious illness / injury, tell your doctor or dentist that you are using this medicine or that you have used it in recent months.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, over-the-counter medications, and herbal products).

Budesonide may mask signs of infection. It can increase the chance of getting infections or worsen current infections. Therefore, wash your hands thoroughly to avoid spreading the infection.

Avoid contact with people who have infections that can spread to other people (such as chicken pox, measles, flu). Consult your doctor if you have been exposed to an infection or for more information.

Budesonide can cause vaccines to not work as well. Therefore, you do not have immunizations / vaccines without the consent of your doctor. Avoid contact with people who have recently received live vaccines (such as the flu vaccine inhaled through the nose).

Although it is unlikely, this medication can slow a child’s growth if it is used for a long time. The effect on final adult height is unknown. Consult your doctor regularly so that your child’s height can be checked.

During pregnancy, this medication should be used only when clearly necessary. Discuss the risks and benefits with your doctor. Babies born to mothers who have used corticosteroids for a long time can develop hormonal problems.

Tell your doctor immediately if you notice symptoms such as persistent nausea / vomiting, severe diarrhea or weakness in your newborn.

This medicine passes into breast milk. Consult your doctor before breast-feeding.

Interaction with other medications:

Interactions with other medications can change how your medications work or increase the risk of serious side effects. This document does not contain all possible drug interactions.

Keep a list of all the products you use (including over-the-counter and non-prescription medicines and herbal products) and share it with your doctor and pharmacist. Do not start, stop or change the dosage of any medication without your doctor’s approval.

Some products that may interact with this medicine include: aldesleukin, mifepristone.

Overdose:

This medicine can be harmful if swallowed. If someone has an overdose and has severe symptoms, such as fainting or difficulty breathing, call emergency. Otherwise, call a poison control center immediately.

Notes:

Do not share this medicine with others.

Lifestyle changes that can help reduce the risk of bone loss (osteoporosis) during long-term corticosteroid treatment include exercise with weights, getting enough calcium and vitamin D, quitting smoking and limiting consumption of alcohol. Ask your doctor about changes in lifestyle that may benefit you.

Missed dose:

If you miss a dose, use it as soon as you remember. If you are near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

Storage:

This medicine is flammable. Store at room temperature away from heat and open flames. Keep all medications out of the reach of children and pets.

Do not throw medicines into the toilet or pour them into the drain unless instructed to do so. Discard this product correctly when it has expired or is no longer necessary. Consult your pharmacist or local waste disposal company.