Bilobil®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Bilobil® (Bilobil®)

Composition:

Active substances: 1 capsule contains dry extract of Ginkgo biloba leaves (Ginkgo biloba L., folium) (35-67:1) with the following content:

• 8.8–10.8 mg flavonoids as flavonoid glycosides;
• 1.12–1.36 mg ginkgolides A, B, C;
• 1.04–1.28 mg bilobalides – 40 mg;

Extraction solvent – acetone.

Excipients: lactose monohydrate, corn starch, talc, colloidal anhydrous silicon dioxide, magnesium stearate, glucose solution;

Capsule shell: gelatin, titanium dioxide (E 171), indigo carmine dye (E 132), azorubine dye (E 122), red iron oxide (E 172), black iron oxide (E 172).

Pharmaceutical form. Capsules.

Main physicochemical characteristics: violet-brown capsules. The capsules contain powder ranging from light to dark brown in color, with visible dark particles and possible small lumps.

Pharmacotherapeutic group. Drugs used in dementia.

ATC code N06D X02.

Pharmacological Properties

Pharmacodynamics

A plant-derived preparation that normalizes cellular metabolism, blood rheological properties, and microcirculation.

The drug improves cerebral circulation and enhances oxygen and glucose supply to the brain. It prevents erythrocyte aggregation and inhibits platelet-activating factor. It exerts a dose-dependent regulatory effect on the vascular system by stimulating the production of endothelium-derived relaxing factor (nitric oxide – NO), dilating small arteries, and increasing venous tone, thereby regulating vascular blood filling. It reduces vascular wall permeability (exhibiting anti-edematous effects both in the brain and peripherally). It demonstrates antithrombotic activity due to stabilization of platelet and erythrocyte membranes, influence on prostaglandin synthesis, and reduction of the effects of biologically active substances and platelet-activating factor. It prevents the formation of free radicals and lipid peroxidation of cell membranes. It normalizes the release, reuptake, and catabolism of neurotransmitters (noradrenaline, dopamine, acetylcholine) and their ability to bind to receptors. It has anti-hypoxic properties, improves metabolism in organs and tissues, promotes accumulation of macroergic compounds in cells, enhances oxygen and glucose utilization, and normalizes neurotransmitter processes in the central nervous system.

Pharmacokinetics

Active ingredient: standardized dry extract of Ginkgo biloba containing 24% flavonoid glycosides and 6% terpene lactones (ginkgolides A, B, and bilobalide C). After oral administration, the bioavailability of ginkgolides A, B, and bilobalide C ranges between 80–90%. Maximum plasma concentration is reached within 1–2 hours after administration. Elimination half-lives are approximately 4 hours (for bilobalide and ginkgolide A) and 10 hours (for ginkgolide B).

These substances are not metabolized in the body and are excreted almost entirely via urine, with a small portion eliminated in feces.

Clinical characteristics.

Indications.

Symptomatic treatment of cognitive disorders in elderly patients, excluding patients with confirmed dementia, Parkinson's disease, cognitive disorders of iatrogenic origin, or those arising as a result of depression or metabolic disturbances.

Contraindications.

Hypersensitivity to Ginkgo biloba extract or to any inactive component of the medicinal product. Pregnancy.

Interaction with other medicinal products and other forms of interaction.

Concomitant use of the medicinal product with anticoagulants (phenprocoumon, warfarin) or antiplatelet agents (clopidogrel, acetylsalicylic acid, and other nonsteroidal anti-inflammatory drugs) may affect the action of these agents.

In studies conducted with warfarin, no interaction between warfarin and ginkgo-containing medicinal products was observed; however, appropriate monitoring is recommended when initiating or discontinuing concomitant treatment with warfarin and ginkgo-based medicinal products, or when changing the medicinal product.

An interaction study with talinolol indicates a potential ability of ginkgo to inhibit P-glycoproteins in the small intestine, which may increase exposure to medicinal products sensitive to P-glycoproteins in the gastrointestinal tract, such as dabigatran etexilate. Ginkgo should be used with caution when taken concomitantly with dabigatran.

Interaction studies have shown that Cmax of nifedipine may increase by up to 100% under ginkgo administration in some patients, who experienced dizziness and increased flushing.

Concomitant use of ginkgo-containing medicinal products with efavirenz is not recommended due to the potential for reduced plasma concentrations of efavirenz resulting from induction of cytochrome CYP3A4 (see section "Special precautions for use").

Special precautions for use

Before starting treatment with this medicinal product, it should be ensured that the symptoms are not caused by another disease requiring specific treatment.

If symptoms worsen during use of the medicinal product, medical advice should be sought.

Patients with a tendency to bleeding (hemorrhagic tendency) who are receiving concomitant therapy with anticoagulants or antiplatelet medicinal products should consult a physician before using this medicinal product.

Medicinal products containing ginkgo may increase the risk of bleeding. As a precautionary measure, treatment with this medicinal product should be discontinued 3–4 days prior to any surgical intervention.

In patients with epilepsy, the occurrence of additional seizures during treatment with ginkgo-containing medicinal products cannot be excluded.

Concomitant use of ginkgo-containing medicinal products with efavirenz is not recommended (see section "Interaction with other medicinal products and other forms of interaction").

If hypersensitivity occurs, the patient should discontinue use of the product.

Excipients

Bilobil® contains lactose and glucose. This medicinal product is contraindicated in patients with rare hereditary forms of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.

Bilobil® capsules contain the azo dye azorubine (E 122), which may cause allergic reactions.

Use during pregnancy or breastfeeding:

Pregnancy

Ginkgo extract may reduce platelet aggregation. This may increase the risk of bleeding. Animal studies are insufficient to draw conclusions regarding reproductive toxicity.

The medicinal product is contraindicated during pregnancy.

Breastfeeding period

There are no data on whether ginkgo metabolites are excreted in human breast milk. Risk to newborns and infants cannot be excluded.

Due to the lack of sufficient data, use of this medicinal product during breastfeeding is not recommended.

Fertility

Specific studies on the effect of ginkgo on human fertility have not been conducted. However, certain effects have been observed in female mice.

Effect on ability to drive and use machines

Studies on the effect of this medicinal product on the ability to drive or operate machinery have not been conducted.

During treatment, caution should be exercised when driving or engaging in other potentially hazardous activities requiring increased attention and rapid psychomotor reaction times.

Dosage and Administration.

For adults, the recommended dosage is 1 capsule three times a day.

The capsules should be swallowed whole with half a glass of water during meals.

Initial signs of improvement are usually observed after one month. For a more sustained effect, it is recommended to take the capsules for at least 3 months. After 3 months, consult a physician regarding the need for continued treatment.

The treatment course is determined individually by a physician.

Children.

There is insufficient experience with the use of the drug in children; therefore, treatment in this patient group is not recommended.

Overdose.

To date, there have been no reported cases of intoxication caused by ingestion of a standardized amount of Ginkgo biloba extract. Intoxication may occur following ingestion of large quantities of ginkgo seeds or inadequately purified Ginkgo biloba extracts.

Side effects

Very common: ≥ 1/10.

Common: ≥ 1/100 to < 1/10.

Uncommon: ≥ 1/1000 to < 1/100.

Rare: ≥ 1/10000 to < 1/1000.

Very rare: < 1/10000.

Frequency not known: Cannot be estimated based on available data. Bleeding in individual organs has been reported (ocular bleeding, nasal bleeding, cerebral bleeding, and gastrointestinal bleeding).

If any adverse reactions not listed above occur, consult a physician.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after the medicinal product has been authorized is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions via the national reporting system.

Shelf life. 3 years.

Storage conditions.

Store at temperatures not above 25 °C in the original packaging to protect from moisture.

Keep out of reach and sight of children.

Packaging.

10 capsules in a blister; 2 or 6 blisters in a cardboard box.

Pharmaceutical classification. Over-the-counter (no prescription required).

Manufacturer.

KRKA, d.d., Novo mesto, Slovenia.

Manufacturer's address and location of operations.

Smarjeska cesta 6, 8501 Novo mesto, Slovenia.