Instructions for Budenofalk rectal foam 2 mg/dose bottle with dispenser No. 1
Composition
active ingredient: budesonide;
each dose (1 spray) contains 2 mg of budesonide;
Excipients: cetyl alcohol, cetostearyl alcohol, polysorbate 60, purified water, disodium edetate, macrogol stearyl ether, propylene glycol, citric acid monohydrate, propane/n-butane/isobutane.
Dosage form
Rectal foam.
Main physical and chemical properties: White or off-white dense foam of oily consistency.
Pharmacotherapeutic group
Anti-inflammatory drugs used in intestinal diseases. Topical corticosteroids. ATX code A07E A06.
Pharmacological properties
Pharmacodynamics.
The exact mechanism of action of budesonide in the treatment of ulcerative colitis/proctosigmoiditis is not fully understood. Data from pharmacological studies and controlled clinical trials clearly indicate that the mode of action of budesonide is mainly based on local action in the intestine. Budesonide is a glucocorticosteroid with high anti-inflammatory activity. At a dose of 2 mg administered rectally, budesonide has virtually no suppression of the hypothalamic-pituitary-adrenal axis.
Budenofalk rectal foam, studied at a daily dose of up to 4 mg budesonide, has virtually no effect on blood cortisol levels.
Pharmacokinetics.
Absorption
After oral administration, the systemic availability of budesonide is about 10%. After rectal administration, the area under the concentration-time curve is approximately 1.5 times higher than in previous oral controls, given an identical oral dose of budesonide. Peak levels are reached on average 2–3 hours after administration of Budenofalk rectal foam 2 mg.
Distribution
Budesonide has a large volume of distribution (about 3 L/kg). Plasma protein binding is 85-90%.
Biotransformation
Budesonide undergoes extensive biotransformation in the liver (approximately 90%) to metabolites of low glucocorticosteroid activity. The glucocorticosteroid activity of the main metabolites, 6ß-hydroxybudesonide and 16α-hydroxyprednisolone, is less than 1% of that of budesonide.
Breeding
The mean elimination half-life is about 3–4 hours. The mean clearance is approximately 10–15 L/min for budesonide as determined by HPLC.
Dissemination
A scintigraphic study with technetium-labeled Budenofalk rectal foam, 2 mg/dose, in patients with ulcerative colitis showed that the foam spread throughout the sigmoid colon.
Specific patient populations (liver disease)
Depending on the type and severity of liver disease, the metabolism of budesonide may be reduced.
Indication
For the treatment of active ulcerative colitis limited to the rectum and sigmoid colon.
Contraindication
Budenofalk, rectal foam, 2 mg/dose, should not be used in patients with:
hypersensitivity to budesonide or to other ingredients included in the medicinal product;
cirrhosis of the liver.
Interaction with other medicinal products and other types of interactions
Pharmacodynamic interactions
Cardiac glycosides
The effect of glycosides may be enhanced by potassium deficiency.
Saluretics
Potassium excretion may increase.
Pharmacokinetic interactions
Cytochrome P450 3A (CYP3A)
CYP3A inhibitors
Concomitant use with CYP3A inhibitors, including cobicistat-containing products, is expected to increase the risk of systemic adverse reactions. This combination should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid adverse reactions. Patients should be monitored for systemic corticosteroid adverse reactions when these drugs are coadministered.
When co-administered with ketoconazole 200 mg once daily orally, the plasma concentration of budesonide (single dose of 3 mg) increased approximately 6-fold. When ketoconazole was administered 12 hours after budesonide, the concentration increased approximately 3-fold. Since there are insufficient data to make dose recommendations, this combination should be avoided.
Other potent CYP3A4 inhibitors such as ritonavir, itraconazole, clarithromycin and grapefruit juice may also cause a marked increase in budesonide plasma concentrations. Therefore, their concomitant administration with budesonide should be avoided.
CYP3A inducers such as carbamazepine and rifampicin may reduce both the systemic and local effects of budesonide on the intestinal mucosa. Dose adjustment of budesonide may be required.
CYP3A substrates such as ethinylestradiol inhibit the metabolism of budesonide. If the affinity of the competing CYP3A substrate is higher, this may lead to an increase in the blood concentration of budesonide. If budesonide binds to CYP3A more strongly, this may increase the blood concentration of the competing substrate. Dose adjustment of budesonide or the competing substrate may be necessary.
Since adrenal function may be suppressed by budesonide, the adrenocortical hormone stimulation test for the diagnosis of pituitary insufficiency may show false results (low values).
Application features
Treatment with Budenofalk rectal foam provides lower systemic steroid levels than oral therapy with systemically acting glucocorticoids. Switching from another glucocorticoid therapy may result in a recurrence of symptoms associated with changes in systemic steroid levels. Medical supervision is necessary in patients with any of the following diseases: tuberculosis, hypertension, diabetes mellitus, osteoporosis, peptic ulcers, glaucoma, cataracts, a family history of diabetes and glaucoma, or any other condition in which the use of glucocorticoids may cause adverse reactions.
Systemic effects of glucocorticoids may occur, especially at high doses and over long periods of time. These effects may include Cushing's syndrome, adrenal suppression, growth retardation, decreased bone mineral density, cataracts, glaucoma and a wide range of mental/behavioural effects (see section 4.8).
Infections
Suppression of the inflammatory response and immune function increases susceptibility to infections and their severity. The risk of worsening bacterial, fungal, amoebic, and viral infections during treatment with glucocorticoids should be considered. Clinical manifestations can often be atypical, and serious infections such as sepsis and tuberculosis may be masked and progress to an advanced stage before they are recognized.
Smallpox
Varicella requires special attention because it can be serious or fatal in immunocompromised patients. Patients without a history of varicella should be advised to avoid close contact with patients with chickenpox or shingles (herpes zoster), and if they do develop it, they should be monitored closely. Passive immunization with varicella and shingles immunoglobulin is recommended for unimmunized patients who are receiving systemic glucocorticoids or have received them within the previous 3 months. Immunization should be given within 10 days of contact with a patient with varicella. If the diagnosis of varicella is confirmed, prompt treatment and specialist attention are warranted. Glucocorticoids should not be discontinued; the dose may need to be increased.
Measles
Immunocompromised patients who have been in contact with a measles patient should receive normal immunoglobulin immediately.
Vaccines
People taking glucocorticoids for a long time should not receive live vaccines. Antibody production to other (inactivated) vaccines may be reduced.
Patients with liver dysfunction
Based on experience in patients with advanced primary biliary cirrhosis (PBC) with cirrhosis, increased systemic exposure to budesonide is expected in all patients with severe hepatic impairment. However, in patients with liver disease without cirrhosis, budesonide at daily oral doses of 9 mg was safe and well tolerated. There is no evidence that dose adjustment is necessary in patients with non-cirrhotic liver disease or with mild hepatic impairment.
Vision impairment
Visual disturbances are possible with systemic and topical corticosteroids. If a patient presents with symptoms such as blurred vision or other visual disturbances, they should be referred to an ophthalmologist for evaluation of possible causes, which may include cataracts, glaucoma, or rare conditions such as central serous chorioretinopathy (CSR), which have been reported with systemic and topical corticosteroids.
Others
Budenofalk rectal foam may cause suppression of the hypothalamic-pituitary-adrenal (HPA) axis and a reduced stress response. If the patient is undergoing surgery or other stress, additional treatment with systemic glucocorticoids is recommended.
Concomitant therapy with ketoconazole or other CYP3A inhibitors should be avoided, as inhibition of the oxidative biotransformation of budesonide may lead to increased plasma levels of budesonide.
It should also be noted that systemic side effects similar to those of glucocorticoids may occur at doses exceeding those recommended.
This medicinal product contains cetyl alcohol and polyethylene glycol, which may cause local skin reactions (e.g. contact dermatitis).
Use during pregnancy or breastfeeding
Use during pregnancy should be avoided unless there are compelling reasons for treatment with Budenofalk. There are limited data on the course of pregnancy after oral administration of budesonide in humans. Although data on the use of inhaled budesonide in a large number of pregnant women do not indicate an adverse effect, it is to be expected that the maximum plasma concentration of budesonide will be higher with Budenofalk rectal foam than with inhaled budesonide. Budesonide, like other glucocorticoids, has been shown to cause foetal malformations in pregnant animals. The relevance of this finding to humans has not been established.
Breast-feeding
Budesonide is excreted in breast milk (there are data on its excretion after inhalation). However, after administration of Budenofalk rectal foam at therapeutic doses, only minor effects on the child during breastfeeding are expected. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from budesonide therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Fertility
There are no data on the effect of budesonide on human fertility. In animal studies, treatment with budesonide did not affect fertility.
The ability to influence the reaction speed when driving or working with other mechanisms
No studies have been conducted on the effects on the ability to drive and use machines.
Method of administration and doses
Used for adults:
one spray containing 2 mg of budesonide per day.
Method of administration
For rectal use.
Shake well before use.
Budenofalk rectal foam can be used in the morning or evening.
Budenofalk rectal foam should be used at room temperature. First, the applicator is attached to the can and then shaken vigorously for about 15 seconds. The applicator is inserted into the rectum as deeply as possible. It should be noted that the dose can only be sufficiently accurate when the pump cap is at the bottom in the most vertical position possible. To administer a dose of Budenofalk rectal foam, press the pump cap all the way down and release it very slowly. After activating the applicator, it should be held in this position for 10-15 seconds before removing it from the rectum. The used applicator is not suitable for reuse, so it must be placed in a special plastic bag for applicator disposal, which is included in the cardboard box.
The best result is achieved if the intestines are cleansed before using Budenofalk rectal foam.
Duration of use
The duration of use is determined by the doctor. Exacerbations usually subside after 6-8 weeks. Budenofalk rectal foam should not be used for longer than the specified period.
Children
Budenofalk foam should not be used in children (under 18 years of age) due to insufficient experience in this age group of patients.
Overdose
To date, there are no known cases of budesonide overdose.
Side effects
The frequency of adverse events is assessed using the following conditional criteria:
very common (≥ 1/10)
common (≥ 1/100 to < 1/10)
uncommon (≥ 1/1000 to < 1/100)
rare (≥ 1/10,000 to < 1/1,000)
very rare (< 1/10,000),
unknown (cannot be estimated from available data).
| Organ system class | Frequency according to MedDRA | Adverse reactions |
|---|
| Metabolic and nutritional disorders | Often | Cushing's syndrome: crescent face, obesity, decreased glucose tolerance, diabetes mellitus, high blood pressure, sodium retention due to edema formation, increased potassium excretion, inactivity and/or atrophy of the adrenal cortex, red striae, steroid acne, impaired secretion of sex hormones (e.g. amenorrhea, hirsutism, impotence) |
| Very rare | Growth retardation in children |
| Vision impairment | Rarely | Glaucoma, cataracts, blurred vision (see also section "Special warnings and precautions for use") |
| Gastrointestinal disorders | Often | Dyspepsia |
| Infrequently | Stomach or duodenal ulcer |
| Rarely | Pancreatitis |
| Very rare | Constipation |
| Immune system disorders | Often | Increased risk of infections |
| Musculoskeletal disorders | Often | Muscle and joint pain, muscle weakness and twitching, osteoporosis |
| Rarely | Osteonecrosis |
| Nervous system disorders | Often | Headache |
| Very rare | Pseudotumor cerebri with optic disc edema in adolescents |
| Mental disorders | Often | Depression, irritability, euphoria |
| Infrequently | Psychomotor hyperactivity, anxiety |
| Rarely | Aggression |
| Skin and subcutaneous tissue disorders | Often | Allergic exanthema, petechiae, delayed wound healing, contact dermatitis |
| Rarely | Ecchymosis |
| Vascular disorders | Increased risk of thrombosis, vasculitis (withdrawal syndrome after long-term therapy) |
| General disorders and administration site conditions | Often | Burning sensation in the rectum and pain |
| Very rare | Fatigue, malaise |
In clinical studies, the following adverse reactions were additionally reported with the use of Budenofalk rectal foam (frequency - uncommon): increased appetite, increased erythrocyte sedimentation rate, leukocytosis, nausea, abdominal pain, flatulence, abdominal paresthesia, anal fissure, aphthous stomatitis, frequent urge to defecate, rectal bleeding, increased transaminase levels (GOT, GPT), increased cholestasis indicators (GGT, AP), increased amylase levels, changes in cortisol indicators, urinary tract infections, dizziness, impaired sense of smell, insomnia, increased sweating, asthenia, weight gain.
Most of the side effects described in this leaflet can also be expected with other glucocorticoids.
Side effects typical of systemically acting glucocorticosteroids may occur. The side effects listed below depend on the dosage, duration of use, concomitant or previous administration of other glucocorticosteroids and individual sensitivity.
Some of these adverse events occurred after long-term oral use of budesonide.
Due to the local effect, the risk of side effects when using Budenofalk rectal foam is much lower than when using systemically acting glucocorticoids.
Worsening or recurrence of extraintestinal manifestations (especially in the skin and joints) may occur when a patient is switched from a systemically acting glucocorticoid to topical budesonide.
Expiration date
2 years.
Do not use after the expiry date stated on the packaging. The contents of the can should be used within 4 weeks from the moment of first spraying.
Storage conditions
Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Do not refrigerate or freeze!
Packaging
Hermetically sealed dispenser bottle complete with 14 foam applicators in a plastic tray and 14 plastic bags for hygienic disposal of the applicators in a cardboard box. Each bottle contains at least 14 doses of 1.2 g rectal foam.
Vacation category
According to the recipe.
Producer
Dr. Falk Pharma GmbH/Dr. Falk Pharma GmbH.
Location of the manufacturer and address of its place of business
Leinenweberstrasse 5, 79108 Freiburg, Germany / Leinenweberstrasse 5, 79108 Freiburg, Germany
