Retinol acetate

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT RETINOL ACETATE (RETINOL ACETATE)

Composition:

Active substance: retinol (vit A);

1 ml of solution contains retinol (in the form of retinol acetate) – 34.4 mg (100,000 IU of vitamin A) – 18-20 drops;

1 drop contains approximately 5,000 IU of vitamin A;

Excipient: soybean oil.

Pharmaceutical form. Topical and oral oil solution.

Main physicochemical properties: clear oily liquid ranging from light yellow to dark yellow, without rancid taste; a specific odor may be present.

Pharmacotherapeutic group.

Simple vitamin A preparations. Retinol (vitamin A). ATC code A11C A01.

Pharmacological properties.

Pharmacodynamics.

Vitamin A (retinol) belongs to the group of fat-soluble vitamins.

Retinol acetate preparation is an analogue of natural vitamin A and is necessary for restoring normal retinol concentration in the body. Vitamin A plays an important role in the synthesis of proteins, lipids, and mucopolysaccharides, and regulates mineral balance.

The most specific function of vitamin A is supporting visual processes (photoreception). Retinol participates in the synthesis of visual purple—rhodopsin—located in the rods of the retina.

Vitamin A modulates the differentiation processes of epithelial cells, participates in the development of secretory glands, keratinization processes, and regeneration of mucous membranes and skin.

Vitamin A is essential for normal functioning of endocrine glands and body growth, as it acts as a synergist of somatomedins.

Vitamin A affects the division of immunocompetent cells and the synthesis of factors of specific (immunoglobulin) and non-specific (interferon, lysozyme) defense against infectious and other diseases, and stimulates myelopoiesis.

Retinol increases glycogen levels in the liver, stimulates the production of trypsin and lipase in the gastrointestinal tract, inhibits photochemical free-radical reactions and cysteine oxidation, activates the incorporation of sulfates into components of connective tissue, cartilage, and bones, satisfies the demand for sulfocerebrosides and myelin, ensuring conduction and transmission of nerve impulses.

Vitamin A deficiency leads to impaired twilight vision (night blindness) and atrophy of the conjunctival, corneal, and lacrimal gland epithelium. Degenerative-dystrophic processes occur in the respiratory tract (mucous membranes of the nasopharynx, paranasal sinuses, trachea, bronchi), in the urogenital system (epithelium of renal pelvis, ureters, urinary bladder, urethra, vagina, ovaries, fallopian tubes and endometrium, seminal vesicles and ducts, prostate gland), and in the digestive system (mucous membrane of the gastrointestinal tract, salivary glands, pancreas). Vitamin A deficiency causes impaired skin trophism (hyperkeratosis), poor hair and nail growth and quality, and dysfunction of sebaceous and sweat glands. Additionally, weight loss, delayed bone growth, reduced synthesis of glucocorticoids and steroid hormones, and decreased resistance to infectious and other diseases are observed. There is also an increased tendency toward chole- and nephrolithiasis.

Deficiency or excess of vitamin A in a woman's body may cause fetal developmental abnormalities.

Retinol exerts an antitumor effect, which does not extend to non-epithelial tumors.

Pharmacokinetics.

Retinol biotransformation occurs in the liver, after which it is excreted by the kidneys as inactive metabolites. Retinol can be partially excreted with bile and participate in enterohepatic circulation. Elimination of retinol is slow—34% of the administered dose is eliminated from the body within 3 weeks.

Orally administered retinol acetate is well absorbed in the upper segments of the small intestine. It is then transported via chylomicrons from the intestinal wall into the lymphatic system and reaches the bloodstream through the thoracic duct. Transport of vitamin A esters in the blood is mediated by β-lipoproteins. Maximum serum levels of vitamin A esters are observed 3 hours after administration. The main storage site of vitamin A is the liver parenchyma, where it accumulates in stable ester forms. In addition, high concentrations of vitamin A are found in the retinal pigment epithelium. This depot is essential for the continuous supply of vitamin A to the outer segments of rods and cones.

Clinical characteristics.

Indications.

Vitamin A deficiency and hypovitaminosis A, eye diseases (pigmentary retinitis, xerophthalmia, night blindness, superficial keratitis, corneal lesions, conjunctivitis, pyoderma and eczematous eyelid lesions), as part of combination therapy for:

• rickets;
• acute respiratory diseases occurring against the background of exudative diathesis;
• acute and chronic bronchopulmonary diseases;
• hypotrophy;
• collagenoses;
• skin pathological conditions (frostbite, burns, wounds, ichthyosis, follicular keratosis, senile keratosis, cutaneous tuberculosis, certain forms of eczema, psoriasis);
• inflammatory and ulcerative-erosive intestinal lesions;
• liver cirrhosis.

Contraindications.

Hypersensitivity to the components of the drug, acute and chronic nephritis, cardiac failure in decompensation stage, cholelithiasis, chronic pancreatitis, hypervitaminosis A, retinoid overdose, hyperlipidemia, obesity, chronic alcoholism.

Interaction with other medicinal products and other types of interactions.

Estrogens increase the risk of developing hypervitaminosis A.

Retinyl acetate reduces the anti-inflammatory effect of glucocorticoids.

Retinyl acetate should not be taken simultaneously with nitrates and cholestyramine, as they impair absorption of the drug.

Retinyl acetate should not be used concurrently with other vitamin A derivatives due to the risk of overdose and development of hypervitaminosis A.

Combination with vitamin E promotes preservation of retinyl acetate in its active form, enhances intestinal absorption, and contributes to anabolic effects.

Simultaneous use of mineral (vaseline) oil may impair vitamin absorption in the intestine.

Concurrent use of vitamin A and anticoagulants increases the tendency to bleeding.

Special precautions for use.

The drug should be taken under medical supervision. During prolonged use of retinol acetate, biochemical parameters and blood coagulation time should be monitored.

When treating impaired twilight vision (night blindness), retinol acetate should be administered together with riboflavin and nicotinic acid.

Use with caution in severe hepatic and biliary system disorders, and in diseases associated with impaired blood coagulation.

The drug is not recommended during prolonged therapy with tetracyclines.

Retinol should be taken 1 hour before or 4–6 hours after cholestyramine administration.

The drug has the property of accumulating and remaining in the body for a prolonged period. Women who have taken high doses of retinol should plan pregnancy no earlier than 6–12 months after discontinuation. This is due to the risk of fetal developmental abnormalities caused by high vitamin A levels in the body during this period.

The presence of dietary fats is essential for normal vitamin A absorption.

Excessive alcohol consumption and smoking impair drug absorption from the gastrointestinal tract.

The medicinal product contains soybean oil. This medicinal product should not be used in patients with peanut or soy allergy.

Use during pregnancy or breastfeeding.

Due to the high dose of vitamin A in this medicinal product, it is contraindicated for oral use during pregnancy or breastfeeding.

Ability to affect reaction rate when driving or operating machinery.

There is no data available regarding the effect of the drug on the ability to drive or operate complex machinery.

Administration and Dosage.

Administer retinol acetate orally 10–15 minutes after eating, and externally.

1 drop contains approximately 5000 IU of vitamin A.
1 ml of the preparation contains 100,000 IU (18–20 drops) of vitamin A.

When determining dosage, note that the maximum single dose of vitamin A for adults is 50,000 IU. The maximum daily dose of vitamin A for adults is 100,000 IU. Therapeutic doses of vitamin A for mild to moderate avitaminosis are up to 33,000 IU per day in adults. For this purpose, it is preferable to use the drug in the form of dragees or capsules (1 dragee of 10 mg or 1 capsule per day). In skin diseases, as well as in pigmentary retinitis, xerophthalmia, and hemeralopia, the daily dose of vitamin A is 50,000–100,000 IU (riboflavin (vitamin B2) should be administered simultaneously at a daily dose of 0.02 g). For skin surface lesions (ulcers, burns, frostbite), after hygienic cleaning, affected areas should be treated with the solution and covered with a gauze dressing (5–6 times daily, reducing the number of applications to one as epithelialization progresses). The drug should also be administered internally at the same time. For prevention of concrement formation, prophylactic doses should be established based on the daily requirement of the human body for vitamin A. Treatment duration ranges from 10 days to 1 month.

Children.

Do not administer this preparation orally to children at this dosage.

Overdose.

Symptoms: dizziness; confusion, diarrhea, severe dehydration, irritability; generalized exanthema followed by extensive desquamation starting from the face; gingival bleeding, dryness and ulceration of the oral mucosa, lip desquamation, sharply painful palpation of long tubular bones due to subperiosteal hemorrhages.

Acute and chronic hypervitaminosis A is accompanied by severe headache, fever, drowsiness, vomiting, visual disturbances (diplopia), dry skin, joint and muscle pain, appearance of pigmented spots, enlargement of the liver and spleen, jaundice, changes in blood picture, weakness, and loss of appetite. In severe cases, seizures, cardiac weakness, and hydrocephalus may develop.

Treatment: symptomatic; as an antagonist, administer thyroxine; the use of ascorbic acid and vitamin E is also rational.

Side effects.

Prolonged administration of high doses of vitamin A may cause the development of vitamin A hypervitaminosis.

From the nervous system and sensory organs: increased fatigue, drowsiness, lethargy, irritability, headache, sleep loss, convulsions, discomfort, intracranial hypertension, visual disturbances.

From the gastrointestinal tract: loss of appetite, weight loss, nausea, very rarely – vomiting. Possible exacerbation of liver diseases, increased activity of transaminases and alkaline phosphatase.

From the urinary system: polyuria, nocturia, polyuria.

From the hematopoietic system: hemolytic anemia.

From the musculoskeletal system: changes on bone X-rays, gait disturbance, bone pain in the lower limbs.

Allergic reactions: lip skin fissures, yellow-orange spots on the soles, palms, and in the nasolabial triangle area; subcutaneous edema; in individual cases, on the first day of use, itchy maculopapular eruptions may occur, requiring discontinuation of the drug; pruritus; erythema and rash; dry skin; dry mouth; increased temperature; facial hyperemia followed by desquamation.

Other: hair loss, menstrual cycle disturbances, abdominal pain, aphthae, photosensitivity, hypercalcemia.

Side effects resolve spontaneously with dose reduction or temporary discontinuation of the medication.

In skin diseases, administration of high doses of the drug after 7–10 days of treatment may be accompanied by exacerbation of local inflammatory reaction, which does not require additional treatment and subsequently decreases. This effect is associated with the myelo- and immunostimulating action of the drug.

Shelf life. 2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging. 10 ml in bottles, placed in a carton.

Availability category. Over-the-counter.

Manufacturer.

JSC "VITAMINS".

Manufacturer's location and address of business activity.

Ukraine, 20300, Cherkasy region, Uman, Usypenska St., 31.

Marketing Authorization Holder.

JSC "VITAMINS".

Location of the Marketing Authorization Holder and/or its representative.

Ukraine, 20300, Cherkasy region, Uman, Usypenska St., 31.