Instructions for Beloretin soft capsules 10 mg No. 30
Composition
active ingredient: isotretinoin;
1 capsule contains 10 mg or 20 mg of isotretinoin;
excipients:
capsule contents: refined soybean oil, all-rac-ɑ-tocopherol (E 307), disodium edetate (dihydrate), butylhydroxyanisole (E 320), partially hydrogenated soybean oil, hydrogenated vegetable oil, yellow wax (E 901);
10 mg capsule shell: gelatin; glycerol (E 422); sorbitol solution, non-crystallizing (E 420); purified water; titanium dioxide (E 171); ponceau 4 R (E 124); iron oxide black (E 172);
20 mg capsule shell: gelatin; glycerol (E 422); sorbitol solution, non-crystallizing (E 420); purified water; titanium dioxide (E 171); ponceau 4 R (E 124); indigo carmine (E 132).
Dosage form
Soft capsules.
Main physicochemical properties:
10 mg capsules: oval soft gelatin capsules of light purple color, containing a yellow-orange opaque viscous liquid;
20 mg capsules: oval, burgundy-colored soft gelatin capsules containing a yellow-orange opaque viscous liquid.
Pharmacotherapeutic group
Means for systemic treatment of acne.
ATX code D10B A01.
Pharmacological properties
Pharmacodynamics.
Mechanism of action
Isotretinoin is a stereoisomer of all-trans retinoic acid (tretinoin). The exact mechanism of action of isotretinoin has not yet been fully elucidated, but it has been established that the improvement of the clinical picture of severe acne is associated with a decrease in the activity of the sebaceous glands and a histologically confirmed decrease in their size. In addition, the anti-inflammatory effect of isotretinoin on the skin has been proven.
Efficiency
Hyperkeratosis of the epithelial cells of the hair follicle and sebaceous gland leads to desquamation of corneocytes in the gland duct and to blockage of the latter with keratin and excess sebum. After which a comedone is formed and in some cases an inflammatory process joins. Beloretin inhibits the proliferation of sebocytes and acts on acne, restoring the normal process of cell differentiation. Sebum is the main substrate for the growth of Propinibacterium acnes, a decrease in sebum production inhibits bacterial colonization of the duct.
Pharmacokinetics.
Absorption
The absorption of isotretinoin from the gastrointestinal tract is variable and linearly dependent on the dose of the drug in the therapeutic dosage range. The absolute bioavailability of isotretinoin has not been determined, since there is no dosage form for intravenous administration, but extrapolation of the results of a study in dogs suggests a very low and variable systemic bioavailability. Taking isotretinoin with food increases its bioavailability by twofold compared to taking it on an empty stomach.
Distribution
Isotretinoin is almost completely bound to plasma proteins (99.9%), mainly albumin. The volume of distribution of isotretinoin in humans is unknown, as there is no intravenous formulation. Epidermal concentrations of isotretinoin are only half those in serum. Plasma concentrations of isotretinoin are approximately 1.7 times higher than whole blood concentrations due to poor penetration of isotretinoin into erythrocytes.
Metabolism
After oral administration, three major metabolites are observed in plasma: 4-oxo-isotretinoin, tretinoin (all-trans retinoic acid), and 4-oxo-retinoin. These metabolites have demonstrated biological activity in several in vitro tests. 4-oxo-isotretinoin has been shown in several clinical studies to provide a significant proportion of the therapeutic activity of isotretinoin (sebum suppression, independent of plasma levels of isotretinoin and tretinoin). The major metabolite is 4-oxo-isotretinoin, with steady-state plasma concentrations 2.5-fold higher than those of the parent drug. Other metabolites, including glucuronide conjugates, are minor.
Since isotretinoin and tretinoin (all-trans-retinoic acid) are reversibly converted to each other, the metabolism of tretinoin is linked to that of isotretinoin. It has been found that 20–30% of the isotretinoin dose is metabolized by isomerization.
Enterohepatic circulation may play a significant role in the pharmacokinetics of isotretinoin in humans.
In vitro metabolism studies have shown that several CYP enzymes are involved in the conversion of isotretinoin to 4-oxo-isotretinoin and tretinoin. No one isoform appears to play a dominant role. Beloretin and its metabolites have no significant effect on the activity of CYP enzymes.
Breeding
After oral administration of radiolabeled isotretinoin, approximately equal amounts are recovered in urine and feces. The terminal elimination half-life of unchanged drug after oral administration in acne patients is on average
19 hours. The terminal half-life of 4-oxo-isotretinoin is longer and averages 29 hours.
Isotretinoin belongs to the natural (physiological) retinoids. Endogenous retinoid concentrations are restored approximately 2 weeks after discontinuation of Beloretin.
Since isotretinoin is contraindicated in patients with impaired liver function, data on the pharmacokinetics of the drug in this group of patients are limited.
Renal failure does not significantly reduce the plasma clearance of isotretinoin and 4-oxo-isotretinoin.
Indication
Severe forms of acne (including nodular and conglobatic acne, acne with a tendency to permanent scarring) that are not amenable to standard treatment methods (systemic antibacterial therapy, topical treatment).
Contraindication
Pregnancy or breastfeeding, failure to comply with all conditions of the "Pregnancy Prevention Program" by women of reproductive age, hypersensitivity to isotretinoin or any components of the drug, liver failure, severe hyperlipidemia, hypervitaminosis A, concomitant therapy with tetracyclines.
Due to the fact that Beloretin contains refined soybean oil, partially hydrogenated soybean oil and hydrogenated soybean oil, the drug is contraindicated for use in patients with peanut or soy allergies.
Interaction with other medicinal products and other types of interactions
Due to the possible exacerbation of symptoms of hypervitaminosis A, the simultaneous administration of Beloretin and vitamin A should be avoided.
Cases of benign intracranial hypertension (pseudotumor cerebri) have been reported with concomitant use of isotretinoin with tetracyclines. Therefore, concomitant use with tetracyclines is contraindicated (see sections "Contraindications", "Special warnings and precautions for use").
Combined use with topical keratolytic or exfoliative drugs for the treatment of acne should be avoided due to possible increased local irritation (see section "Special instructions").
Application features
Teratogenic effects
The drug Beloretin is a strong teratogen for humans and induces a high incidence of severe and life-threatening congenital malformations.
The drug Beloretin is clearly contraindicated:
pregnant women,
women of reproductive age who do not meet all the conditions of the "Pregnancy Prevention Program".
"Pregnancy Prevention Program"
This drug is TERATOGENIC.
Beloretin is contraindicated in women of reproductive age unless all of the following conditions are met:
a woman has been diagnosed with a severe form of acne (nodular and conglobatic acne, acne with a tendency to permanent scarring), which is not amenable to standard treatment methods (systemic antibacterial therapy, topical treatment) (see the "Indications" section);
The potential for pregnancy should be assessed in all women;
the woman understands the teratogenic risk of the drug;
the woman understands the need for a mandatory visit to the doctor every month;
the woman understands and agrees to the need to use effective contraception continuously for 1 month before starting treatment, during the entire treatment period and for one month after the end of treatment. At least one highly effective method of contraception (i.e. one that is not dependent on the user) or two complementary methods of contraception that are dependent on the user should be used simultaneously;
When choosing a contraceptive method, individual circumstances should be assessed in each specific case. The patient should be involved in the discussion of the choice of contraceptive method to ensure her commitment and agreement to follow the rules for using the chosen methods;
Even with amenorrhea, a woman should use reliable methods of contraception;
the woman is informed about the risk of pregnancy during treatment with Beloretin and understands the need for immediate consultation in case of suspicion of pregnancy or in case of pregnancy;
the woman understands the need and agrees to regularly perform a pregnancy test before treatment, ideally monthly during treatment and 1 month after completion of treatment;
the woman confirms that she is aware of the dangers of using isotretinoin and the need to take precautions;
These conditions also apply to sexually inactive women, unless the doctor is confident that there is no risk of pregnancy.
The doctor must be sure that:
the patient is able to understand and comply with all of the above conditions for preventing pregnancy, and also has an appropriate level of understanding;
the patient confirms that she is familiar with the above conditions;
the patient is aware of the need to consistently and correctly use one highly effective method of contraception (i.e. a user-independent method) or two complementary user-dependent methods of contraception at the same time for at least 1 month before starting treatment, as well as to continue using effective contraception during the entire treatment period and for at least 1 month after stopping treatment;
A negative pregnancy test result was obtained before starting the drug, during treatment, and 1 month after the end of therapy. The dates and results of the pregnancy test should be documented.
If pregnancy occurs after treatment has ended, there is a risk of severe and serious birth defects in the fetus. This risk persists until the drug is completely eliminated from the body, which lasts for 1 month after treatment has ended.
Pregnancy prevention.
Patients should be informed about contraceptive methods. If they are not using contraceptive methods, the physician should provide the necessary recommendations. If the attending physician is unable to provide such information, the patient should be referred to a physician with an appropriate specialty.
As a minimum, women of reproductive age should use at least one highly effective method of contraception (i.e., one that is not dependent on the user) or two complementary methods of contraception that are dependent on the user at the same time. Contraceptive methods should be used for at least 1 month before starting treatment, as well as during the entire treatment period and for at least 1 month after stopping treatment with Beloretin, even in patients with amenorrhea.
When choosing a contraceptive method in each specific case, individual conditions should be assessed, and the patient should be invited to discuss the choice of contraceptive method, in order to ensure her adherence and agreement to follow the rules for using the selected methods.
Pregnancy test.
In accordance with current practice, it is recommended to perform a pregnancy test under medical supervision, with a minimum sensitivity of 25 mIU/ml, as indicated below.
Before starting treatment
At least 1 month after the patient has started using contraception, and shortly (preferably a few days) before the first dose of the drug, the patient should undergo a pregnancy test under medical supervision to ensure that the patient is not pregnant at the time of initiation of isotretinoin treatment.
During treatment
The patient should see her doctor on a regular basis, ideally monthly. The need for monthly supervised pregnancy testing is determined according to local practice, taking into account the patient's sexual activity, recent menstrual history (abnormal menstruation, amenorrhea, or amenorrhea), and contraceptive method. If indicated, a pregnancy test should be performed on the day of the scheduled visit or 3 days prior to the visit.
Completion of treatment
One month after the end of treatment, a final pregnancy test is performed.
For women of reproductive age, the duration of Beloretin prescription should ideally be limited to 30 days to ensure regular follow-up, including pregnancy tests and monitoring. It is recommended that the pregnancy test, prescription, and receipt of Beloretin be performed within the same day. Beloretin should only be dispensed by the pharmacy within a maximum of 7 days of the prescription.
This monthly follow-up will allow for regular pregnancy testing and monitoring, as well as to ensure that the patient is not pregnant before receiving the next course of medication.
Male patients.
Available data indicate that in women, exposure to the drug from the semen and seminal fluid of men using Beloretin is insufficient to cause teratogenic effects.
Male patients should be reminded that they should not give the drug to other individuals, especially women.
Additional warnings
Microdoses of progesterone preparations may be an inadequate method of contraception during treatment with Beloretin.
Patients should never give this medicine to other people and should return any unused capsules to their doctor after treatment is finished.
Patients should not donate blood during treatment and for 1 month after its discontinuation, as there is a risk of transfusion transmission to the fetus of a pregnant woman.
Educational materials
To help doctors, pharmacists, and patients avoid the risk of Beloretin exposure to the fetus, the manufacturing company provides educational materials aimed at preventing the teratogenic effects of the drug, recommendations on the use of contraception before starting therapy, and the need for pregnancy testing.
Full information about teratogenic risk and pregnancy prevention measures, contained in the “Pregnancy Prevention Program”, should be provided to all patients, both male and female.
Mental disorders
Depression, aggravated depression, anxiety, aggressive tendencies, mood swings, psychotic symptoms and very rarely suicidal thoughts, suicide attempts and suicide have been reported in patients treated with Beloretin (see section 4.8). Caution should be exercised in patients with a history of depression and patients should be monitored for the development of depression during treatment and, if necessary, referred to appropriate specialists. However, withdrawal of Beloretin may not resolve the symptoms of psychiatric disorders, in which case the patient should be monitored closely by a specialist.
Awareness from family or friends can be helpful in identifying mental disorders.
Skin and subcutaneous tissue disorders
Excessive exposure to sunlight or UV rays should be avoided. If sun protection is necessary, use a sunscreen with an SPF of at least 15.
Deep chemical dermabrasion and laser treatment should not be performed during treatment with Beloretin and for 5–6 months after treatment, as there is a high risk of hypertrophic scars in atypical areas and, less commonly, hyper- and hypopigmentation in the treatment areas. Waxing should not be performed during treatment with Beloretin and for 6 months after treatment due to the risk of epidermal detachment.
The simultaneous use of Beloretin with topical keratolytic or exfoliative agents for the treatment of acne should be avoided due to possible increased local irritation (see section "Interaction with other medicinal products and other types of interactions").
Patients receiving Beloretin are recommended to use moisturizing ointments or body creams, lip balm to reduce dryness of the skin and lips at the beginning of treatment.
In the post-marketing period, cases of severe skin reactions (erythema multiforme exudative, Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported. Since these cases can be difficult to distinguish from other possible skin reactions (see section "Adverse reactions"), patients should be warned about the symptoms of these diseases and carefully monitored for severe skin reactions. If severe skin reactions are suspected, isotretinoin treatment should be discontinued.
Allergic reactions
Anaphylactic reactions have been reported rarely, in some cases after topical retinoids. Allergic skin reactions have been reported infrequently. Serious cases of allergic vasculitis of the extremities, often with purpura (bruising and red spots), and non-cutaneous manifestations, have been reported. Serious allergic reactions require discontinuation of therapy and careful monitoring of the patient.
Vision disorders
Dry eyes, corneal clouding, night vision impairment, and keratitis usually resolve after drug discontinuation. Cases of dry eyes that persisted after discontinuation of therapy have been reported. In case of dryness of the ocular mucosa, moisturizing eye ointment or artificial tears may be used. In case of intolerance to contact lenses, glasses should be worn during treatment.
Some patients may experience a decrease in twilight vision, sometimes occurring suddenly (see section "Ability to affect the speed of reactions when driving vehicles or other mechanisms"). If there are complaints about vision, such patients should be referred to an ophthalmologist and the issue of drug withdrawal should be considered.
Musculoskeletal and connective tissue disorders
Muscle and joint pain and increased serum creatine phosphokinase, particularly during strenuous exercise, have been reported in patients receiving isotretinoin (see section 4.8). In some cases, this may progress to rhabdomyolysis, which is a potentially life-threatening condition.
Several years after the use of Beloretin for the treatment of dyskeratosis at very high doses, bone changes developed, including premature closure of the epiphyseal growth plates, hyperostosis, and calcification of ligaments and tendons. The doses, duration of treatment, and total cumulative dose in these patients generally exceeded those recommended for the treatment of acne.
Cases of sacroiliitis have been reported in patients receiving isotretinoin. To differentiate sacroiliitis from other causes of back pain, patients with clinical manifestations of sacroiliitis may require additional examination, including imaging methods such as MRI. In cases reported in the post-marketing period, sacroiliitis regressed after discontinuation of Belotretin and appropriate treatment.
Benign intracranial hypertension
Cases of benign intracranial hypertension have been described, some of which were caused by concomitant use with tetracyclines (see sections "Contraindications", "Interaction with other medicinal products and other types of interactions"). Symptoms of benign intracranial hypertension include headache, nausea and vomiting, visual disturbances and swelling of the optic nerve head. Patients who develop benign intracranial hypertension should immediately discontinue the drug.
Hepatobiliary disorders
It is recommended to monitor liver enzymes before treatment, 1 month after its initiation, and then every 3 months, unless there is a clinical indication for more frequent monitoring. Transient and reversible increases in liver transaminase levels have been observed, in most cases within normal limits, which returned to baseline values during treatment. If transaminase levels exceed the normal range, the dose of the drug should be reduced or discontinued.
Kidney failure
Renal impairment or renal failure does not affect the pharmacokinetics of isotretinoin. Therefore, isotretinoin can be administered to patients with renal failure. However, it is recommended to start with a low dose and titrate it to the maximum tolerated dose (see section "Method of administration and dosage").
Fasting serum lipid levels should be measured (prior to treatment, 1 month after initiation, then every 3 months unless clinically indicated for more frequent monitoring). Elevated serum lipids usually resolve after dose reduction or discontinuation and with diet. Isotretinoin has been associated with increases in triglycerides. Isotretinoin should be discontinued in the event of uncontrolled hyperlipidemia or symptoms of pancreatitis. Elevated triglycerides above 800 mg/dL or 9 mmol/L may be associated with the development of acute pancreatitis, which may be fatal.
Gastrointestinal disorders
Inflammatory bowel disease (including regional ileitis) may develop during treatment with isotretinoin. Patients with severe (hemorrhagic) diarrhea should immediately discontinue the drug.
High-risk groups
Patients with diabetes mellitus, obesity, alcoholism, or lipid disorders may require more frequent monitoring of serum glucose and/or lipids during treatment with isotretinoin. Increased fasting blood sugar levels and new cases of diabetes mellitus have been reported during treatment with isotretinoin.
Excipients
This medicine contains 2-3.05 mg of sorbitol (E 420) in each 10 mg capsule.
This medicine contains 3.2-4.86 mg of sorbitol (E 420) in each 20 mg capsule.
The additive effect of concomitantly used medicinal products containing sorbitol (or fructose) and the consumption of sorbitol (or lactose) with food should be taken into account.
The sorbitol content of oral medicinal products may affect the bioavailability of other oral medicinal products when used concomitantly.
Use during pregnancy or breastfeeding
Pregnancy
Pregnancy is an absolute contraindication to the use of Beloretin (see section "Contraindications"). Women of childbearing potential should use effective contraception during treatment and for 1 month after treatment. If, despite precautions, pregnancy occurs while the woman is taking Beloretin or within a month after the end of therapy, there is a very high risk of severe and serious fetal malformations.
Fetal malformations associated with isotretinoin include central nervous system abnormalities (hydrocephalus, cerebellar malformations/abnormalities, microcephaly), facial malformations, cleft palate, external ear abnormalities (absence of external ear, small or absent external auditory canal), eye malformations (microphthalmia), cardiac and vascular anomalies (conotruncal heart defects such as tetralogy of Fallot, transposition of the great vessels, septal defects), thymic and parathyroid gland abnormalities. In addition, the risk of spontaneous abortions is increased.
If pregnancy occurs in a woman receiving isotretinoin treatment, therapy should be discontinued and a physician specializing and experienced in teratology should be consulted for evaluation and advice.
Breast-feeding.
Due to the high lipophilicity of isotretinoin, there is a high probability that it will pass into breast milk. Due to possible side effects in the child associated with the action of the drug through breast milk, the use of Beloretin is contraindicated in women during breastfeeding (see section "Contraindications").
Fertility
Isotretinoin in therapeutic doses does not affect the number, motility, or morphology of sperm and does not compromise the formation and development of the embryo in men taking isotretinoin.
Ability to influence reaction speed when driving vehicles or other mechanisms
The drug Beloretin can potentially affect the ability to drive vehicles and other mechanisms.
During treatment and rarely after it, some patients have experienced a decrease in twilight vision (see sections "Adverse reactions", "Special instructions for use"). Since in some individuals these phenomena occurred suddenly, patients should be informed of the possibility of this problem and warned about the need to be careful when driving vehicles and working with other mechanisms.
Very rarely, drowsiness, dizziness, and visual disturbances have been reported. Patients should be advised not to drive, operate machinery, or engage in activities that could put themselves or others at risk if they experience these symptoms.
Method of administration and doses
Standard dosage regimen.
Isotretinoin treatment should only be prescribed and administered by a physician who is experienced in the use of systemic retinoids for the treatment of severe acne and is fully aware of the risks of retinoid therapy and the requirements for monitoring patient conditions.
Take capsules with meals 1–2 times a day.
Long-term remission and relapse rate are more related to the total dose administered than to the duration of treatment or daily dose. It has been shown that no additional benefit should be expected from a course dose above 120–150 mg/kg. The duration of therapy depends on the daily dose. A course of treatment of 16–24 weeks is usually sufficient to achieve remission.
In most patients, acne completely disappears after a single course of treatment. In case of severe relapse, a second course of treatment with Beloretin should be carried out in the same daily and course dose as the first. Since the condition may improve within 8 weeks after the end of treatment, a second course should be prescribed no earlier than the end of this period.
Dosage in special cases.
Patients with renal impairment: In patients with severe renal impairment, treatment should be initiated at a lower dose (e.g. 10 mg/day) and then increased to 1 mg/kg/day or the maximum tolerated dose (see section 4.4).
Patients with intolerance. Patients who develop severe intolerance to the recommended dose may be continued at a lower dose. In this case, the duration of therapy will be longer and the risk of relapse is higher. In order to achieve the maximum possible efficacy, the highest tolerated dose should be used.
Children.
Beloretin should not be used to treat acne in the prepubertal period, the drug is not recommended for children under 12 years of age due to the lack of data on efficacy and safety.
Overdose
Isotretinoin is a derivative of vitamin A. Although the acute toxicity of isotretinoin is low, signs of hypervitaminosis A may occur in the event of accidental overdose. Symptoms of acute vitamin A toxicity include severe headache, nausea or vomiting, drowsiness, irritability, and itching. Symptoms of accidental or intentional overdose of isotretinoin are likely to be similar. These symptoms are reversible and resolve without the need for treatment.
Side effects
Some side effects of isotretinoin are dose-related. Adverse reactions are usually reversible after dose adjustment or discontinuation of the drug, but some may persist after discontinuation of treatment. The most commonly reported symptoms with isotretinoin are dryness of the skin, mucous membranes, including the lips (cheilitis), nose (epistaxis), and eyes (conjunctivitis).
The following categories are used to describe the frequency of adverse reactions: very common (≥ 1/10), common (≥ 1/100, < 1/10), rare (≥ 1/10,000, < 1/1,000), very rare (< 1/10,000) and frequency unknown (cannot be estimated from the available data). Within each frequency grouping and system organ class, adverse reactions are presented in order of decreasing seriousness.
Infections: very rarely common – gram-positive bacterial infections of the skin and mucous membranes.
From the blood and lymphatic system: very common - anemia, increased ESR, thrombocytopenia, thrombocytosis; common - neutropenia; very rare - lymphadenopathy.
On the part of the immune system: rarely - allergic skin reactions, anaphylactic reactions, hypersensitivity reactions.
Metabolic disorders: very rarely common – diabetes mellitus, hyperuricemia.
Psychiatric disorders: rare – depression, increased depression, tendency to aggression, anxiety, mood changes; very rare – conduct disorder, psychotic disorders, suicidal thoughts, suicide attempts, suicide.
Nervous system disorders: common - headache; very rare - benign intracranial hypertension, convulsions, drowsiness, dizziness.
On the part of the organs of vision: very common - blepharitis, conjunctivitis, dry eyes, eye irritation; very rare - blurred vision, cataract, color vision impairment, contact lens intolerance, corneal opacity, decreased twilight vision, keratitis, optic nerve head swelling (as a manifestation of benign intracranial hypertension), photophobia, visual impairment.
From the side of the organs of hearing and labyrinth: very rarely - hearing impairment.
Vascular disorders: very rare - vasculitis (e.g. Wegener's granulomatosis, allergic vasculitis).
Respiratory, thoracic and mediastinal disorders: common - epistaxis, dry nose, nasopharyngitis; very rare - bronchospasm (especially in patients with asthma), dysphonia.
Gastrointestinal: very rarely - colitis, ileitis, dry throat, gastrointestinal bleeding, hemorrhagic diarrhea, inflammatory bowel disease, nausea, pancreatitis. Cases of severe diarrhea have also been reported (see section "Special warnings and precautions for use").
Skin and subcutaneous tissue disorders: very common - cheilitis, dermatitis, dry skin, localized peeling, itching, erythematous rash, skin trauma (risk of damage from friction); rare - alopecia; very rare - acne fulminant forms, acne exacerbation (acne hyperemia), erythema (face), exanthema, hair disorders, hirsutism, onychodystrophy, paronychia, photosensitivity, pyogenic granuloma, skin hyperpigmentation, increased sweating; frequency unknown - erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Bone, muscle and connective tissue disorders: very common - arthralgia, myalgia, back pain (especially in children and adolescents); very rare - arthritis, calcinosis (calcification of ligaments and tendons), premature closure of epiphyseal growth plates, exostosis, hyperostosis, decreased bone density, tendonitis; frequency unknown - rhabdomyolysis, sacroiliitis.
On the part of the kidneys and urinary system: very rarely - glomerulonephritis; frequency unknown - urethritis.
Reproductive system and breast disorders: frequency unknown - sexual dysfunction, including erectile dysfunction and decreased libido, gynecomastia, vulvovaginal dryness.
General disorders: very rarely common – granulation tissue (increased formation), fatigue.
Laboratory parameters: very common - hypertriglyceridemia, decreased high-density lipoprotein levels; common - hypercholesterolemia, hyperglycemia, hematuria, proteinuria; very rare - increased CPK in the blood.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after registration of a medicinal product is important. This allows monitoring of the benefit/risk ratio of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the link: https://aisf.dec.gov.ua.
Expiration date
36 months.
Storage conditions
Store in the original packaging to protect from light at a temperature not exceeding 30 0C.
Keep out of reach of children.
Packaging
15 capsules in a blister, 2 or 4 blisters in a cardboard pack.
Vacation category
According to the recipe.
Producer
Belupo, pharmaceuticals and cosmetics, Inc.
Location of the manufacturer and address of its place of business.
Danica Street 5, 48000 Koprivnica, Croatia/Ulica Danica 5, 48000 Koprivnica, Croatia.
