MILGAMMA 50mg/250mg x 50 film tabl
BRIEF DESCRIPTION OF THE PRODUCT
1. NAME OF THE MEDICINAL PRODUCT
Milgamma 50 mg/250 microgram film-coated tablets
milgamma 50 mg/250 micrograms coated tablets
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each film-coated tablet contains:
Benfotiamine (S-benzoylthiamine-O-monophosphate) ( Benfotiamine) 50 mg
Cyanocobalamin ( Cyanocobalamin ) 250 micrograms
Excipients with known action :
Each tablet contains 101,225 mg lactose monohydrate, 1,750 mg red brilliant (Quinoline yellow (E104), Azorubin (E122), Ponceau 4R (E124)), 144,100 mg sucrose and 2,800 mg glucose
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Coated tablet
Red, round, convex, film-coated tablets without facet.
4. CLINICAL DATA
4.1 Therapeutic indications
In the complex treatment of the following diseases:
Neurological diseases of various origins, neuropathies and polyneuropathies (diabetic, alcoholic, etc.), neuralgia, neuritis, herpes zoster, facial paresis (facial paresis), heart muscle damage due to vitamin B 1 deficiency; rheumatic complaints, muscle pains; with symptoms of severe stress and in a period of recovery (restoration of the body).
Milgamma coated tablets are used in adults
4.2 Dosage and method of administration
Dosage
Four times a day, 1 coated tablet without chewing. In milder cases, as a tonic and in a period of convalescence, 1-2 coated tablets are sufficient.
Pediatric population
The safety and efficacy of Milgamma film-coated tablets in children under 18 years of age have not been established.
Missing data.
Application method
The coated tablets should be taken after a meal with a little liquid, without chewing.
4.3 Contraindications
- Suspected hypersensitivity to the active substances or to any of the excipients listed in point 6.1.
- In ileus.
4.4 Special warnings and precautions for use
Due to the content of castor oil, nausea, vomiting, colic could occur, and in higher doses - a laxative effect.
Due to the content of lactose, sucrose and glucose, patients with rare hereditary problems of fructose intolerance, lactose intolerance, glucose-galactose malabsorption, sucrose-isomaltase deficiency, lactase deficiency or galactosemia should not take this medicinal product.
In patients with psoriasis, treatment with milgamma coated tablets should be started only after a careful assessment of the benefit and risk of therapy, since the use of vitamin B 12 can lead to worsening of skin efflorescences.
4.5 Interaction with other medicinal products and other forms of interaction
Thiamine is inactivated by 5-fluorouracil because 5-fluorouracil competitively inhibits the phosphorylation of thiamine to thiamine pyrophosphate.
Absorption of vitamin B12 is reduced by colchicine, aminoglycoside antibiotics (eg neomycin), p -aminosalicylic acid, antiepileptic drugs (eg phenytoin, phenobarbital and primidone), cholestyramine, extended-release potassium preparations, methyldopa, gastric acid inhibitors (eg omeprazole, cimetidine) and biguanides (oral antidiabetic agents).
Patients treated with chloramphenicol may show poor response to vitamin B12 therapy.
Concomitant administration of Vitamin C and Vitamin B12 may result in a decrease in the amount of Vitamin B12 available in serum and body stores.
4.6 Fertility, pregnancy and lactation
Pregnancy
During pregnancy and breastfeeding, the recommended daily dose is 1.4 - 1.6 mg for vitamin B1 and 4 micrograms for vitamin B12 . For vitamin B1 , this dose can be increased during pregnancy, only in case of diagnosed vitamin B1 deficiency, as the safety profile for doses higher than the recommended daily doses has not been established. Vitamin B12 has not shown harmful effects at higher doses.
Breastfeeding
Vitamin B1 and vitamin B12 pass into breast milk.
4.7 Effects on the ability to drive and use machines
Milgamma coated tablets do not affect the ability to drive and operate machinery.
- Adverse drug reactions
The following data on the frequency of their occurrence were used in the assessment of adverse drug reactions:
Very common (≥ 1/10)
Common (≥ 1/100 to ≤ 1/10)
Uncommon (≥ 1/1,000 to < 1/100)
Rare (≥ 1/10,000 to <1/1,000)
Very rare (<1/10,000),
Disorders of the immune system
Very rare: In isolated cases, hypersensitivity reactions (hives, skin rashes, asthma) may occur. The risk is higher in patients with hypersensitivity to acetylsalicylic acid.
Gastrointestinal disorders
Very rare: Single cases of gastrointestinal disturbances such as flatulence, diarrhea, constipation, nausea, abdominal pain have been reported. Their relationship to the product as well as the dose dependence still remain unclear.
Due to the content of castor oil, nausea, vomiting, colic could occur.
Disorders of the skin and subcutaneous tissue
Very rare: Acneiform and bullous rashes.
Reporting of suspected adverse reactions
Post-marketing reporting of suspected adverse reactions is important. This allows continued monitoring of the benefit/risk ratio of the medicinal product. Healthcare professionals are required to report any suspected adverse reaction by:
Bulgaria
Medicines Executive Agency
8 Damyan Gruev St
1303 Sofia
Phone: +35 928903417
website: www.bda.bg
4.9 Overdose
Cases of poisoning or overdose phenomena are not known so far.
a) Symptoms of intoxication
Not applicable, see above.
b) Treatment in case of intoxication:
Not applicable, see above
Antidotes:
Not applicable, see above
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Vitamin B 1 , in combination with vitamin B 6 and/or vitamin B 12 , ATC code: A11 DB 00
Neurotropic vitamins from the vitamin B-complex group have a beneficial effect in degenerative nerve diseases related to metabolism and diseases of the locomotor apparatus. B-complex vitamins are not only used to treat vitamin deficiency conditions. In high doses, group B vitamins possess pharmacological properties that explain the analgesic, anti-neuralgic and regenerative effects that can be achieved by treatment with milgamma coated tablets.
Benfotiamine belongs to the group of alithiamines and is a fat-soluble precursor of vitamin B1 .
It has the following advantages compared to water-soluble vitamin B1 :
- Benfotiamine is absorbed 3 to 5 times better than equivalent amounts
thiamine hydrochloride.
- The percentage of conversion to active cocarboxylase after taking benfotiamine is 2-5 times higher than after taking the same amounts of water-soluble vitamin B1.
- Benfotiamine is incomparably more resistant to degradation by the thiaminase enzyme.
- After oral administration of even large amounts of benfotiamine, no anaphylactic reactions were observed.
- While thiamine hydrochloride inhibits intestinal peristalsis, benfotiamine has a mild excitatory effect on smooth muscle.
- Benfotiamine is tasteless and odorless. When taking it, the familiar unpleasant body odor does not appear, as with the application of ordinary vitamin B 1 .
Vitamin B 12 (cyanocobalamin) is indispensable for cellular metabolism, for normal blood formation and the functioning of the nervous system. It catalyzes the biological synthesis of nucleic acids, and thus the construction of new cell nuclei. In addition, in high doses, vitamin B 12 exhibits analgesic, anti-allergic and blood circulation-stimulating effects.
5.2 Pharmacokinetic properties
After oral administration of benfotiamine, it is dephosphorylated to fat-soluble S-benzoylthiamine (SBT) by intestinal phosphatases. It is absorbed better, compared to water-soluble thiamine derivatives, and from the circulating blood passes into the cell interior, where enzymatic debenzoylation takes place to thiamine, which is then converted into the active coenzyme form (cocarboxylase, synonym - thiamine diphosphate) by thiamine kinases ). About 1 mg of thiamine is broken down daily in the body. Excess thiamine is excreted in the urine.
Cocarboxylase is a coenzyme of pyruvate dehydrogenase, which plays a key role in the oxidative breakdown of glucose. Since the energy supply in nerve cells is mainly through the oxidative catabolism of glucose, an adequate supply of thiamine is extremely important for nerve function. As the glucose level increases, so does the need for thiamine. Greater intracellular concentrations of thiamine and active coenzyme are achieved with benfotiamine than with oral administration of water-soluble thiamine derivatives.
The lack of sufficient amounts of cocarboxylase in the blood leads to the accumulation of intermediate breakdown products such as pyruvate, lactate and ketoglutarate in the blood and tissues, to which the muscles, myocardium and central nervous system react particularly sensitively. Benfotiamine reduces the accumulation of these toxic substances. In therapeutic use, benfotiamine shows an analgesic effect.
Released from food during the digestive process in the stomach, vitamin B12 binds to intrinsic factor (IF). This glycoprotein is formed by the parietal cells of the stomach. The vitamin B 12 -IF-complex is resistant to proteolytic enzymes and reaches the distal ileum, where it binds to specific receptors and thus resorption of the vitamin takes place. Vitamin B 12 is transferred from the mucosa to the capillary circulation, where it binds to its transport protein - transcobalamin. This complex is rapidly taken up by the liver, bone marrow and other proliferating cells.
Absorption is impaired in patients with a missing intrinsic factor, as well as in patients with malabsorption, or with diseases, respectively changes in the intestine, after gastrectomy, or with the formation of autoimmune antibodies. In the normal case, only 1.5-3.5 micrograms of vitamin B 12 are absorbed from food.
Vitamin B12 is excreted through the bile and is included in the enterohepatic circulation. Vitamin B12 crosses the placenta.
Bioavailability
A comparative study by Bitsch (1990) on 10 male subjects showed a significantly higher bioavailability of benfotiamine than water-soluble thiamine mononitrate. The absorption of benfotiamine is proportional to the dose, since the substance, based on its fat solubility (unlike thiamine), has absorption kinetics in which there is no saturation phase. On the other hand, after oral intake of water-soluble vitamin B1 , a maximum of only 10 mg can be absorbed. In addition, benfotiamine is retained longer in the tissues.
Benfotiamine clearly outperforms other fat-soluble thiamine derivatives. Bitsch (1992) in a comparative cross - over study showed that e.g. AUC-values (area under the concentration-time curve) in the plasma after administration of benfotiamine exceed four times the corresponding values for fursultiamine. The maximum thiamine concentration (c max ) in plasma after administration of benfotiamine showed a value more than two times higher compared to the values for fursultiamine.
Appropriate for determining vitamin B1 status are measurements of thiamine diphosphate-dependent enzyme activity in erythrocytes, such as that of transketolase (ETK) and the extent to which they can be activated (α-ETK activation coefficient). Concentrations for ETC in plasma are between 2 and 4 micrograms/100 ml.
Plasma concentrations of vitamin B 12 amount to 200-900 pg/ml in the normal case, and < 200 pg/ml in case of deficiency. Circulating vitamin B 12 corresponds to only 0.1% of the total amount of the vitamin.
The daily requirement of vitamin B 12 amounts to about 1 microgram. Non-circulating vitamin B 12 accumulates mainly in the liver. With a body pool of 3-5 mg, the amount contained in the liver represents 50-90% of the total.
Absorption of vitamin B12 is inhibited by colchicine, ethanol, and neomycin (parenteral application is shown here). Oral antidiabetic agents of the biguanide type, para-aminosalicylic acid, as well as chloramphenicol and vitamin C interfere with the absorption of vitamin B 12 .
The biological half-life of cyanocobalamin in plasma is 123 hours.
5.3 Preclinical safety data
The available literature and decades of therapeutic experience do not give any indication of the manifestation of mutagenic, carcinogenic or toxic properties for reproduction on the part of benfotiamine and vitamin B 12 .
6. PHARMACEUTICAL DATA
6.1 List of excipients
talc,
Lactose monohydrate,
Sucrose,
Cornstarch,
Gelatin,
Microcrystalline cellulose,
stearic acid,
dextrin,
Calcium carbonate,
shellac,
Glucose syrup,
Castor oil,
white wax,
carnauba wax,
Dyes:
Titanium Dioxide (171),
Red brilliant (Quinoline yellow (E104), Azorubin (E122), Ponceau 4R (E124).
6.2 Incompatibilities
In most cases, benfotiamine does not show the incompatibilities characteristic of thiamine. Only in combination with aminophylline, with vitamin C, and at high temperatures, as well as with high air humidity and in combination with vitamin B 2 , color changes of the substance occur.
Vitamin B 12 is incompatible with oxidizing and reducing substances and with salts of heavy metals. In thiamine-containing solutions, vitamin B 12 , like other B-complex factors, is rapidly destroyed by the breakdown products of thiamine (iron ions in low concentrations could prevent this). Riboflavin, especially when exposed to light, also has a destructive effect; nicotinamide accelerates photolysis, while antioxidants inhibit it.
6.3 Expiry Date
Five years.
6.4 Special storage conditions
To be stored below 25° C!
Store in the original package in order to protect from light.
- Type and contents of packaging
Coated tablets in white opaque PVC/PVDC/Al blisters.
Original packs of 20, 50 or 100 coated tablets.
Not all types of packaging can be put on sale.
6.6 Special precautions for disposal < and handling >
There are no special disposal requirements.
Any unused medicinal product or waste materials derived from it should be disposed of in accordance with local requirements.
7. HOLDER OF THE USE AUTHORIZATION
Wörwag Pharma GmbH & Co.KG
Calwer Staße 7
71034 Böblingen
Germany
Tel.: +49(0)7031/6204-0
Fax: +49(0)7031/6204-31
Email: info@woerwagpharma.com
8. USE AUTHORIZATION NUMBER(S).
20010371
9. DATE OF FIRST AUTHORIZATION/RENEWAL OF THE MARKETING AUTHORIZATION
Date of first authorisation: 26 April 1994
Date of last renewal: 05 December 2011
10. TEXT UPDATE DATE
10/2017
