Natubiotin

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT NUTUBIOTIN (NATUBIOTIN)

Composition:

Active substance: biotin;

1 tablet contains 5 mg or 10 mg of biotin;

Excipients: microcrystalline cellulose; lactose monohydrate; povidone K30; crospovidone; magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical characteristics: round, white or almost white tablets.

Pharmatherapeutic group.

Simple vitamin preparations. ATC code A11H A05.

Pharmacological Properties

Pharmacodynamics

Biotin is a prosthetic group for various enzymes involved in numerous carboxylation and decarboxylation reactions. Thus, biotin plays an important role in gluconeogenesis, lipogenesis, fatty acid synthesis, propionate biotransformation, and leucine catabolism.

Natural occurrence and daily human requirement

Biotin, widely distributed in the diet, is mostly protein-bound and occurs as biocytin (in animal-derived foods), and is rapidly reabsorbed after hydrolysis in the small intestine. In plants, biotin is partially present in free form. Since biotin is synthesized by intestinal microflora, only the daily human requirement can be estimated. An intake of 50 to 200 mcg per day, provided by a normal balanced diet, is considered sufficient. Even the administration of relatively high single doses of biotin does not produce any pharmacological effects.

Symptoms of biotin deficiency

Biotin deficiency is very rare. However, consumption of large amounts of raw egg white may cause dermatitis, known as egg-white-induced lesion. Egg white contains the glycoprotein avidin, which forms a stable complex with biotin that is not cleaved in the gastrointestinal tract. Thus, biotin becomes unavailable to the body, potentially leading to biotin deficiency. Additionally, in biotin-responsive multiple carboxylase deficiency associated with a genetic defect, the requirement for biotin is increased. Deficiency manifests with skin and appendage reactions, and may lead to specific neuropsychiatric symptoms and gastrointestinal disturbances.

Pharmacokinetics

Absorption of free biotin begins in the upper part of the small intestine. Here, the biotin molecule passes through the intestinal wall unchanged. Absorption occurs mainly by diffusion. Recent studies also suggest active transport of the substance via a biotin-sodium carrier complex.

The extent of biotin binding to plasma proteins is approximately 80%.

The concentration of free or only weakly bound biotin in blood generally ranges from 200 to 1200 mcg/L. Biotin is excreted in urine (6 to 50 mcg per day) and feces. Biotin is excreted unchanged (about 50%) and half as biologically inactive metabolites. The optimal plasma concentration is not precisely known. The elimination half-life is dose-dependent and is approximately 26 hours after an oral dose of 100 mcg per kilogram of body weight. In patients with biotinidase deficiency, the half-life after administration of the same dose is reduced to 10–14 hours.

Clinical characteristics.

Indications.

Treatment and prevention of diseases caused by biotin deficiency: skin, nails, and hair disorders.

Treatment of genetically determined biotin-associated enzymopathies (multiple carboxylase deficiency).

Contraindications. Hypersensitivity to biotin or to any of the excipients.

Special precautions.

Egg white contains the protein avidin, which binds to biotin; therefore, simultaneous intake should be avoided.

Consumption of large amounts of raw eggs over 2–3 weeks may lead to biotin deficiency.

The product contains lactose; therefore, patients with rare hereditary forms of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome should not take this medicine.

Interaction with other medicinal products and other forms of interaction.

Concomitant use of biotin with anticonvulsant drugs may reduce biotin plasma concentration due to increased urinary excretion. Valproic acid reduces biotinidase activity, impairing mitochondrial function in the liver.

Pantothenic acid in high doses competes with biotin; therefore, concomitant administration should be avoided.

Special precautions for use.

Effect on clinical laboratory tests.

Biotin may interfere with laboratory test results due to biotin's interaction with streptavidin. Depending on the assay method, test results may be falsely high or falsely low as a result of taking a biotin-containing medicinal product. The risk of interference is higher in children and patients with impaired renal function and increases with higher doses.

When interpreting laboratory test results, the potential influence of biotin should be considered, especially if there is a lack of correlation with the clinical picture (e.g., thyroid function test results mimicking Graves' disease in asymptomatic patients taking biotin, or falsely negative troponin test results in patients with myocardial infarction who are taking biotin). When biotin interference is suspected, alternative tests that are not susceptible to biotin interference should be used.

When ordering laboratory tests for patients taking biotin, consultation with laboratory personnel is recommended.

Use during pregnancy or breastfeeding.

According to general accepted principles, Natubiotin should be used during pregnancy or breastfeeding only when the expected benefit to the woman outweighs the potential risk to the fetus/infant.

To date, there is no information regarding any adverse effects of the drug during pregnancy or breastfeeding. Biotin crosses the placenta and is excreted into breast milk. Breast milk usually contains 7–13 μg of biotin per liter.

Ability to influence the reaction rate when driving or operating machinery.
No influence.

Dosage and Administration.

The recommended dose for adults in the treatment of biotin deficiency (nail, hair, and skin disorders) is 1 tablet of 5 mg daily.

For the treatment of genetically determined biotin-associated enzymopathies (multiple carboxylase deficiency), 1–2 tablets are prescribed (daily dose – 10 mg of biotin).

Tablets should be taken before meals, without chewing, and with sufficient fluid.

The duration of treatment depends on the nature and course of the disease.

Children.

Due to limited experience with use, the drug is not administered to children under 12 years of age.

In children aged 12 years and older, the drug may be used as prescribed by a physician; however, dosage recommendations are unavailable due to limited data.

Overdose.
To date, there have been no reports of biotin overdose.

Side effects

From the immune system: very rare (˂ 1/10,000) – allergic reactions, including chest pain, dyspnea, urticaria, skin rashes.

If any adverse reactions occur, it is recommended to discontinue treatment and consult a physician.

Reporting of side effects

Reporting of adverse reactions after drug registration is of great importance. It enables continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy to physicians via the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua.

Shelf life. 5 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C, in a place inaccessible to children.

Packaging. 30 tablets per blister; 1 or 2 blisters per cardboard box.

Availability. Over-the-counter (without prescription).

Manufacturer. Dr. Gustav Klein GmbH & Co. KG.

Manufacturer's address and place of business.

Steinenfeld 3, 77736 Zell am Harmersbach, Germany.