Prospect: information for the user

Natrovit powder for concentrate for solution for infusion EFG

Retinol (vitamin A), colecalciferol (vitamin D3), α-tocoferol (vitamin E), ascorbic acid (vitamin C), thiamine (vitamin B1), riboflavin (vitamin B2), pyridoxine (vitamin B6), cyanocobalamin (vitamin B12), folic acid, pantothenic acid, biotin, nicotinamide (vitamin B3)

For use in adults and children over 11 years old.

Read this prospect carefully before starting to use this medication, as it contains important information for you.

- Keep this prospect, as you may need to read it again.

- If you have any doubts, consult your doctor, pharmacist or nurse.

- This medication has been prescribed only to you, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.

- If you experience adverse effects, consult your doctor, pharmacist or nurse, even if they do not appear in this prospect.See section 4.

The name of the medication is «Natrovit powder for concentrate for solution for infusion EFG». From now on in this prospect, it will be referred to as «Natrovit».

6. Contents of the package and additional information

Natrovitis a multivitamin preparation used as an appropriate supply of vitamins to cover the daily needs of adults and children over 11 years old, whenever oral administration is contraindicated or not possible and vitamin replacement is required as part of parenteral nutrition.

Contraindications are diseases or circumstances in which certain medications should not be used, or can only be used after a thorough evaluation by a doctor, because the relationship between the expected benefit and possible risks is generally not favorable. In order for the doctor to thoroughly check if there are contraindications, you must inform him of all the diseases you have suffered from previously, of the present diseases, of other treatments you are receiving and of your particular circumstances and habits. In addition, it is possible that contraindications may not occur or may not become apparent until after the start of treatment with this medication. In these cases, you must also inform your doctor.

Do not useNatrovit:

• if you are allergic to the active principles or to any of the other components of this medication, particularly to thiamine (Vitamin B1) or to soy and peanut proteins (included in section 6).
• if you have hypervitaminosis of any of the vitamins contained inNatrovit
• in children under 11years

Warnings and precautions

Consult your doctor, pharmacist or nurse before starting to useNatrovitif:

• you have kidney disease,
• you have liver disease,
• you have cancer,
• you have short bowel syndrome,
• you have cystic fibrosis,
• you are taking vitamins from other sources (e.g., supplements),
• you have a deficiency of vitamin B12,
• you have diabetes, asNatrovitmay affect blood glucose measurements.

Allergic reactions

Severe allergic reactions have been reported to vitamins B1, B2, B12, folic acid and soy lecithin.

Cross-allergic reactions between soy and peanut proteins have been observed.

Your doctor will keep you under observation during the infusion to ensure that you are receiving the appropriate amount of vitamins. Inform your doctor immediately if you notice signs of allergy, such as sweating, fever, chills, headache, skin rash, urticaria or redness, or if you experience breathing difficulties.The infusion will be stopped immediately and emergency measures will be taken.

Due to the content of glycolic acid, close monitoring of liver function is required with repeated or long-term administration ofNatrovitto patients with jaundice or significant biochemical signs of cholestasis.

Interference in laboratory tests

NATROVIT contains 69μgof biotin perpackage. If you are to undergo laboratory tests, you must inform your doctor or the laboratory staff that you are receiving or have recently received NATROVIT, as biotin may affect the results of these tests.Depending on the test, the results may show false elevations or false reductions due to biotin. Your doctor may instruct you to stop receiving NATROVIT before undergoing laboratory tests. You should also be aware that other products you may be taking, such as multivitamin preparations or supplements for hair, skin and nails, may also contain biotin and affect the results of laboratory tests. Inform your doctor or the laboratory staff if you are taking these types of products.

Use ofNatrovit with other medications

Inform your doctor if you are taking, have taken recently or may need to take any other medication.

You must exercise special caution if you are using any of the following types of medications:

• phenobarbital, phenytoin, primidone, carbamazepine, valproate (for epilepsy),
• aspirin (for pain and inflammation),
• chloramphenicol, trimethoprim, tetracyclines (for bacterial infections),
• deferoxamine (for iron poisoning or excess iron in the body),
• efavirenz, zidovudine, tipranavir (HIV treatments),
• ethionamide, cycloserine, isoniazid (for tuberculosis),
• fluoropyrimidines, raltitrexed, bexarotene (cancer treatments),
• methotrexate, sulfasalazine, penicillamine (for rheumatoid arthritis),
• pyrimethamine (for malaria),
• levodopa (used for Parkinson's disease),
• triamterene, hydralazine (for heart diseases),
• phenelzine (for depression),
• theophylline (for respiratory diseases and asthma),
• warfarin (anticoagulant).

Pregnancy, lactation and fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication.

Pregnancy

There are no data or these are limited regarding the use ofNatrovitin pregnant women. Your doctor will administer this infusion only if necessary. Prevent overdoses during pregnancy due to the risk of congenital malformations.

Lactation

The ingredients/metabolites ofNatrovitare excreted in breast milk, but at therapeutic doses ofNatrovitno effects are expected in newborns/infants. NATROVIT may be used during lactation.

Fertility

There are insufficient data on the use of NATROVIT with regard to fertility in male or female patients.

Natrovit containssodium

This medication contains 25 mg of sodium (main component of table salt/for cooking) in each vial. This is equivalent to 1.25% of the maximum daily sodium intake recommended for an adult.

Notable for patients following a sodium-controlled diet.

Natrovitis a preparation administered by healthcare professionals. You will normally receiveNatrovitin the form of an intravenous infusion.

Dosage and administration form

Dosage

Unless otherwise prescribed, the following dosage recommendations apply:

Adults and children over 11 years old: 1 vial per day.

Administration form

For intravenous infusion.

Natrovitis intended exclusively for use as an additive to infusion solutions.

The contents of the vial are dissolved by adding 5 ml of a suitable solution (injection-grade water) and gently agitating.

Infusion in a sodium chloride or glucose isotonic solution, for example.

Natrovitcan be added to certain parenteral nutrition solutions containing carbohydrates, lipids, amino acids, and electrolytes. However, compatibility and stability with the corresponding solution must be ensured first.

Reconstitution and addition to the infusion solution should take place immediately before administration.

If you have any questions about using this medication, consult your doctor or pharmacist.

If you have any other questions about using this medication, ask your doctor or pharmacist.

If you receive moreNatrovitthan you should

No cases of overdose are expected within the indicated dosage range.

The signs of overdose include, among others, nausea and vomiting, headache, confusion, and skin peeling.

If you notice any of these signs of overdose, contact your doctor.

Like all medications, this medication may produce adverse effects, although not all people may experience them.

The following adverse effect is frequent (may affect between 1 and 10 of every 100 patients):

• Pain at the infusion site

The following adverse effects are infrequent (may affect between 1 and 10 of every 1,000 patients):

• Nausea and vomiting

The following adverse effects have been reported, although their frequency is unknown:

• Allergic reactions with difficulty breathing, chest pain, sensation of throat constriction, skin rash, sensation of heat, hot flashes, abdominal pain, and cardiac problems.
• Increased levels of vitamin A and vitamin A-binding protein in the blood
• Alteration of taste (metallic taste)
• Fast heart rate
• Fast breathing
• Diarrhea
• Increased liver enzymes and bile acids
• Pruritus (itching)
• Fever, general malaise, reactions at the infusion site such as burning and sensation of heat

Soy lecithin may cause very rarely allergic reactions.

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or nurse,even if it is a possible adverse effect that does not appear in this leaflet.You can also report them directly through theSpanish System for Pharmacovigilance of Medicinal Products for Human Use,www.notificaRAM.es.

By reporting adverse effects, you can contribute to providing more information about the safety of this medication.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the vial and on the packaging after CAD. The expiration date is the last day of the month indicated.

After reconstitution, any unused solution must be discarded immediately.

Do not store at a temperature above 25°C.

Store the vials in the outer packaging to protect them from light.

The addition to the perfusion solution must take place immediately before administration.

Stability in physical and chemical use of Natrovit powder for perfusion solution EFG has been demonstrated for 24 hours after reconstitution with 5 ml of injectable water, 5 ml of 0.9% sodium chloride, and 5 ml of 5% dextrose, and storage at 25 ± 2°C and under refrigeration conditions. From a microbiological point of view, the medication must be used immediately. Otherwise, the previous storage times and conditions before use are the responsibility of the user and, generally, should not exceed 24 hours at a temperature between 2 °C and 8 °C, unless reconstitution/dilution, etc. has been carried out in controlled and validated aseptic conditions.

Natrovit should not be used if the solution is not transparent or the vial is not intact.

Since this product will be administered by healthcare professionals, they will be responsible for the correct storage of the product both before and during use, as well as its proper disposal.

Composition of Natrovit

- The active principles are:

- The other components are:

Glycine, glycolic acid, soy lecithin, sodium hydroxide (pH adjuster), and hydrochloric acid (pH adjuster).

Patients with low-sodium diets should be aware that this medication contains 25 mg (approximately 1.09 mmol) of sodium per vial.

Appearance of the product and contents of the package

Natrovit is a powder for concentrate for solution for infusion; it is presented in a brown glass vial, sealed with a rubber stopper and an aluminum cap.

Each package contains the vial with the lyophilized powder.

Natrovit is supplied in packages containing 1, 10, or 20 vials of lyophilized powder.

Only certain package sizes may be marketed.

Holder of marketing authorization and responsible for manufacturing

Holder of marketing authorization

Noridem Enterprises Ltd.

Evagorou & Makariou

Mitsi Building 3, Office 115

1065 Nicosia, Cyprus

Responsible for manufacturing

DEMO S.A. PHARMACEUTICAL INDUSTRY

21st Km National Road Athens-Lamia.

14568 Greece

Tel: +30 210 8161802, Fax: +30 2108161587.

This medication is authorized in the member states of the European Economic Area with the following names:

Germany: NATROVIT Powder for a Concentrate for the Preparation of an Infusion Solution

Spain: NATROVIT powder for concentrate for solution for perfusion EFG

Last review date of this leaflet: 09/2024

This information is intended solely for healthcare professionals:

A vial containing 750 mg of powder for concentrate for solution for infusion contains:

Excipients: glycine, glycolic acid, soy lecithin (phosphatidylcholine), sodium hydroxide (for pH adjustment), and hydrochloric acid (for pH adjustment)

Description: Powder concentrate, lyophilized, sterile, orange-red in color. After reconstitution, the resulting solution is clear and orange-red in color.

Dosage and administration

Dosage

Adults and children over 11 years: 1 vial/day.

Administration

For intravenous infusion.

Natrovit is intended exclusively for use as an additive to infusion solutions.

The contents of the single-dose vial are dissolved by adding 5 mL of an appropriate diluent (water for injection, sodium chloride 0.9%, or dextrose 5%) and mixing gently.

The infusion is administered slowly (for at least 1 to 2 hours) with, for example, sodium chloride or glucose.

Natrovit may be added to certain infusion solutions for parenteral nutrition that contain carbohydrates, lipids, amino acids, and electrolytes, in order to meet nutritional needs and prevent deficiency symptoms and complications. However, prior to administration, it must be ensured that the solution is compatible and stable.

The reconstitution and addition to the infusion solution should be carried out immediately before administration.

It should be taken into account that the total intake of vitamins from all sources, e.g., from food, other vitamin preparations, or medications containing vitamins as excipients, should be considered.

In order to maintain adequate concentrations, the patient's clinical status and vitamin levels should be monitored.

It should be noted that some vitamins, especially vitamins A, B2, and B6, are sensitive to ultraviolet light (direct or indirect sunlight). In addition, the concentration of vitamins A, B1, C, and E may decrease as the oxygen concentration in the solution increases. These factors should be taken into account if the desired vitamin concentration is not achieved.

Contraindications

Hypersensitivity to the active principles, especially suspected hypersensitivity to thiamine.

Patients who have presented signs of thiamine intolerance should not receive Natrovit.

Hypersensitivity to any other vitamin or to derivatives/proteins from soy contained in Natrovit (the phospholipids are an excipient obtained from soybeans), or proteins or products from peanuts, or any of the excipients listed in section 6.1.

Hyper-vitaminosis of any of the vitamins contained in Natrovit.

Warnings and special precautions for use

Warnings

Systemic hypersensitivity reactions

• Severe systemic hypersensitivity reactions have been reported in association with multivitamin preparations and individual vitamins (such as vitamins B1, B2, B12, and folic acid). Fatal reactions have been reported in association with multivitamin preparations and other parenteral vitamin preparations.

• Allergic cross-reactions between soy proteins and peanuts have been observed.

• In some cases, the manifestation of a hypersensitivity reaction during the administration of intravenous multiple vitamins may be related to the infusion rate. Therefore, Natrovit should be infused slowly.

• If signs or symptoms of a hypersensitivity reaction are detected, the infusion or injection should be discontinued immediately.

Toxicity by vitamins

• To avoid overdose and toxicity, the patient's clinical status and vitamin levels in the blood should be monitored, especially for vitamins A, D, and E. This measure is particularly important for patients who are receiving vitamins from other sources or who are taking substances that increase the risk of vitamin toxicity.

• Monitoring is particularly important in long-term replacement therapy.

Hyper-vitaminosis, vitamin A

• There is a higher risk of hyper-vitaminosis and vitamin A toxicity (cutaneous and osseous alterations, diplopia, cirrhosis), for example, in the following patients:

• Patients with protein malnutrition

• Patients with renal insufficiency (even without vitamin A replacement)

• Patients with liver insufficiency

• Short-stature patients (e.g., children)

• Patients receiving long-term treatment

• In patients with hepatic storage capacity for vitamin A depletion, acute hepatic damage may lead to the manifestation of vitamin A toxicity.

Syndrome of refeeding in patients with parenteral nutrition

In patients with extreme malnutrition, the introduction of nutrients may trigger a refeeding syndrome. This syndrome is characterized by the entry of potassium, phosphorus, and magnesium into the intracellular space, while the patient enters anabolism. In addition, thiamine deficiency and fluid retention may occur. These complications can be prevented by close monitoring and gradual increase in nutrient intake, avoiding overfeeding. In cases of nutritional deficiency, appropriate replacement treatment may be indicated.

Precipitates in patients with parenteral nutrition

In patients with parenteral nutrition, precipitates have been observed in the pulmonary vasculature. In some of these cases, the outcome was fatal. The excessive addition of calcium and phosphate increases the risk of calcium phosphate precipitate formation. Precipitates have also been observed with solutions without phosphate salts. In addition, precipitates have been found distal to the integrated filter and suspected cases of precipitate formation in the bloodstream have been reported.

The infusion solution, infusion set, and catheter should be inspected at regular intervals to detect the possible presence of precipitates.

If signs of respiratory difficulty are detected, the infusion should be discontinued and a medical examination should be performed.

Precautions

Hepatic effects

• It is recommended to monitor liver function tests during the use of Natrovit. Close monitoring is particularly recommended in patients with jaundice or significant biochemical signs of cholestasis.

In some cases, an isolated increase in alanine aminotransferase (ALT) has been reported in patients with inflammatory bowel disease during the use of multivitamins.

In addition, an increase in bile acid concentration has been reported with multivitamins (total and individual, such as glycolic acid).

• It is known that in some cases, hepatobiliary disorders may occur with parenteral nutrition (even with additional vitamin replacement). These disorders are cholestasis, steatosis, fibrosis, and cirrhosis, possibly with subsequent hepatic insufficiency, as well as cholecystitis and cholelithiasis. These diseases are likely to have a multifactorial underlying cause that may vary from patient to patient. In cases of analytical results or other signs of liver disease, appropriate measures should be taken to have a hepatologist perform a diagnostic study as soon as possible, in order to identify possible causal or contributing factors and initiate prophylaxis and treatment.

Use in patients with liver insufficiency

Patients with liver insufficiency may require personalized vitamin replacement.

Special attention should be paid to the prevention of vitamin A toxicity, as liver disease is associated with increased sensitivity to this, especially in the presence of excessive and prolonged alcohol consumption (see sections "Hyper-vitaminosis, vitamin A" and "Hepatic effects").

Due to the content of glycolic acid, close monitoring of liver function is required with repeated or long-term administration of Natrovit to patients with jaundice or significant biochemical signs of cholestasis.

Use in patients with renal insufficiency

Patients with renal insufficiency may require personalized vitamin replacement, depending on the degree of renal dysfunction and any concomitant diseases. In patients with severe renal insufficiency, special attention should be paid to ensuring adequate vitamin D concentrations and preventing vitamin A toxicity. These patients may experience vitamin A toxicity even with low doses or without replacement treatment.

In patients undergoing long-term hemodialysis who received an intravenous multivitamin solution three times a week with 4 mg of pyridoxine (vitamin B6), vitamin B6 toxicity and toxic effects have been reported.

General monitoring

In patients receiving vitamins for an extended period exclusively through parenteral multivitamin solutions, close monitoring of the patient's clinical status and vitamin levels, as well as verification of adequate replacement of the following, is necessary:

• Vitamin A in patients with scars, wounds, burns, short bowel syndrome, or cystic fibrosis

• Vitamin B1 in patients undergoing dialysis

• Vitamin B2 in patients with cancer

• Vitamin B6 in patients with renal insufficiency

• Vitamins required on an individual basis, whose needs may increase due to pharmacological interactions

The deficiency of one or more vitamins should be corrected through specific replacement.

If Natrovit is used for more than 3 weeks, hemograms and liver enzyme tests should be performed.

Natrovit does not contain vitamin K. If necessary, it should be administered separately.

Use in patients with vitamin B12 deficiency

If the patient is at risk of developing vitamin B12 deficiency and/or if several weeks of replacement with Natrovit are planned, the patient's vitamin B12 levels should be determined before starting Natrovit administration.

In the presence of megaloblastic anemia associated with vitamin B12 deficiency, an increase in red blood cell count, reticulocyte count, and hemoglobin concentration may occur in some cases, even after a few days of use, due to the amount of cyanocobalamin (vitamin B12) and folic acid supplied through Natrovit. These may mask an existing vitamin B12 deficiency. The dose of cyanocobalamin contained in Natrovit is not sufficient to effectively treat vitamin B12 deficiency.

In cases of vitamin B12 deficiency, folic acid replacement alone (without concomitant vitamin B12 intake) is not sufficient to prevent the occurrence or progression of neurological symptoms associated with this deficiency. It has been suggested that functional neurological deterioration may even be accelerated.

When interpreting vitamin B12 results, it should be remembered that values after vitamin B12 intake may be within the normal range, yet a tissue deficiency may still exist.

Interference in laboratory tests

The biotin may interfere with clinical laboratory tests based on an interaction between biotin and streptavidin, which may result in falsely reduced or elevated test results, depending on the type of test. The risk of interference is higher in children and patients with renal insufficiency and increases with higher doses. When interpreting laboratory test results, the possible interference of biotin should be taken into account, particularly if clinical presentation is inconsistent with test results (e.g., thyroid function tests that resemble Graves' disease in asymptomatic patients treated with biotin or falsely negative troponin results in patients with myocardial infarction treated with biotin). In cases where interference is suspected, alternative tests should be used if available, which are not susceptible to biotin interference. The laboratory staff should be consulted when ordering laboratory tests for patients receiving biotin.

In accordance with the test reagents used, the presence of ascorbic acid in the blood or urine may result in falsely high or low glucose values in some systems for glucose determination and glucoseuria (reactive strips, glucose meters, etc.). In order to determine the possible interference of vitamins, the test analytical information should be consulted.

Pediatric use

Natrovit is indicated in pediatric patients over 11 years of age (see also hyper-vitaminosis A in the Product Information section).

Use in elderly patients

In general, the possibility of adjusting the dosage regimen for elderly patients (reduction of dose and/or prolongation of administration intervals) should be evaluated, given the higher frequency of hepatic, renal, and cardiac insufficiency, as well as concomitant diseases and medications in this population.

Sodium content

This medication contains 25 mg of sodium per vial, equivalent to 1.09% of the maximum daily sodium intake of 2 g recommended by the WHO for an adult.

Do not dissolve directly in electrolyte and oligoelement concentrates.

Use only transparent solutions in intact containers.

Interactions with other medications and other forms of interaction

In the case of interactions between specific vitamins contained in Natrovit and other substances, appropriate measures should be taken.

Possible interactions:

• Medications that may cause pseudotumor cerebri (e.g., some tetracyclines): increased risk of pseudotumor cerebri with concomitant administration of vitamin A

• Alcohol (excessive and prolonged consumption): increased risk of vitamin A hepatotoxicity

• Anticonvulsants (phenytoin, fosphenytoin, phenobarbital, primidone): possible reduction of anticonvulsant concentrations and increased risk of seizures with concomitant administration of folic acid

• Antiplatelet agents (e.g., aspirin): vitamin E may potentiate platelet dysfunction

• Aspirin (high-dose treatment): may reduce folic acid concentrations by increasing urinary excretion

• Certain anticonvulsants (e.g., phenytoin, carbamazepine, phenobarbital, valproate): may cause folic acid, pyridoxine, and vitamin D deficiency

• Certain antiretroviral medications: efavirenz and zidovudine, for example, are associated with decreased vitamin D concentrations. Inhibitors of protease are associated with reduced formation of the active vitamin D metabolite

• Chloramphenicol: may inhibit hematologic response to vitamin B12 treatment

• Deferoxamine: increased risk of iron-induced cardiac insufficiency due to increased mobilization of iron caused by supraphysiological replacement of vitamin C. Appropriate preventive measures are listed in the product information for deferoxamine

• Ethionamide: may cause pyridoxine deficiency

• Fluoropyrimidines (5-fluorouracil, capecitabine, tegafur): increased cytotoxicity with concomitant administration of folic acid

• Antagonists of folic acid (e.g., methotrexate), sulfasalazine, pyrimethamine, triamterene, trimethoprim, and high doses of catechins in tea: block the conversion of folic acid to its active metabolites and reduce the efficacy of replacement therapy

• Antimetabolites of folic acid (methotrexate, raltitrexed): folic acid replacement may attenuate the effects of antimetabolites

• Antagonists of pyridoxine, such as cycloserine, hydralazine, isoniazid, penicillamine, and phenelzine: may cause pyridoxine deficiency

• Retinoids, such as bexarotene: increase the risk of toxicity with concomitant administration of vitamin A (see section Hyper-vitaminosis, vitamin A)

• Theophylline: may cause pyridoxine deficiency

• Oral solution of tipranavir: contains 116 IU/mL of vitamin E and therefore exceeds the recommended daily dose

• Anticoagulants (e.g., abciximab, clopidogrel, heparin, warfarin): increased risk of bleeding due to the anticoagulant effect associated with high doses of vitamin A

• Carbamazepine: high doses of nicotinamide may inhibit its metabolism

• Antineoplastic agents that produce reactive oxygen species: possible inhibition of antineoplastic activity due to antioxidant effects of high doses of vitamin E

• Insulin, antidiabetic agents: high doses of nicotinamide may reduce insulin sensitivity

• Iron: vitamin E replacement at high doses may reduce the hematologic response to iron therapy in patients with anemia

• Oral contraceptives (combined hormone products): high doses of vitamin C may cause metrorrhagia and ineffectiveness of the contraceptive

• Phenobarbital: high doses of pyridoxine may reduce its metabolism and decrease its effect

• Phenytoin, fosphenytoin: high doses of pyridoxine may reduce its concentration

• Primidone: high doses of nicotinamide may reduce the metabolism of phenobarbital and increase primidone concentrations

Overdose

No expected cases of overdose within the indicated dose range.

The acute or chronic overdose of vitamins (especially vitamins A, B6, D, and E) may cause symptomatic hyper-vitaminosis.

The risk of overdose is particularly high if vitamins are supplied from multiple sources and the total replacement of a particular vitamin does not meet the individual patient's needs or if the patient is particularly prone to hyper-vitaminosis (see section Hyper-vitaminosis, vitamin A).

a) Symptoms of intoxication

Symptoms of vitamin A hyper-vitaminosis:

Acute increase in cerebrospinal fluid pressure with headache, vomiting, dizziness, and loss of consciousness. In infants, fontanelle bulging.

Symptoms of multiple-dose overdose:

Symptoms of chronic overdose:

Symptoms of increased intracranial pressure, desquamation, and dryness of the skin, alopecia, osteodinia, and arthralgia, and radiological signs of transformation zones.

Symptoms of vitamin D hyper-vitaminosis:

The ergocalciferol (vitamin D2) and colecalciferol (vitamin D3) increase calcium and phosphate absorption from the intestinal lumen and mobilize calcium from bones, so vitamin D has a more antirachitic effect, while the product of its reduction, DHT (dihydrotaquisterol), is more effective in mobilizing calcium from bones. All these substances have a relatively narrow therapeutic index. The toxic threshold in adults is >0.5 mg/day for vitamin D and >0.25 mg/day for DHT. However, single doses generally have no toxic effect.

In cases of overdose, in addition to increased serum and urinary phosphate, a hypercalcemic syndrome may occur, which in turn causes calcium deposits in tissues and especially in kidneys (nephrolithiasis, nephrocalcinosis) and blood vessels (hypertension). The clinical picture of hypercalcemia is not characteristic: weakness, fatigue, exhaustion, headache, nausea, vomiting, and diarrhea, as well as polyuria, polydipsia, nocturia, and proteinuria in patients with decreased renal concentrating ability. Especially in cases where a psychosymptom with confusion is predominant, it is easy to overlook the symptoms of intoxication (e.g., diabetes mellitus, malignant neoplasia, psychosis). From a diagnostic point of view, it is characterized by increased calcium, phosphate, and non-protein nitrogen in plasma or serum, as well as possible osteoporosis and calcifications in tissues or kidneys, which are identifiable by radiology.

N.B.: repeated serum calcium monitoring and bone histology are required.

b) Treatment of intoxication

Immediate discontinuation of the product.

1. Vitamin A overdose

Relief of pressure and continuous monitoring of cardiac, hepatic, and renal function, hemograms, and ophthalmoscopy.

1. Hypercalcemia

In patients with adequate renal function, infusion of isotonic sodium chloride solution (3-6 L in 24 hours) plus furosemide, along with continuous monitoring of calcium and ECG, has a reliable hypocalcemic effect. However, in cases of oligoanuria, hemodialysis is indicated. Administration of glucocorticoids and calcitonin may be attempted. Warning: fatal outcomes often occur even after normalization of calcium levels.

Pharmacological data

Shelf life

Up to 2 years without opening.

Stability in physical and chemical use of Natrovit powder for solution for infusion has been demonstrated for 24 hours after reconstitution with 5 mL of water for injection, 5 mL of sodium chloride 0.9%, or 5 mL of dextrose 5%, and storage at 25 ± 2°C and under refrigeration conditions. From a microbiological point of view, the medication should be used immediately. Otherwise, the storage times and conditions prior to use are the responsibility of the user and, in general, should not exceed 24 hours at a temperature of 2°C to 8°C, unless the reconstitution/dilution, etc. has been carried out in controlled and validated aseptic conditions.

Special storage precautions

Do not store at temperatures above 25°C.

Store the vial in the outer packaging to protect it from light.

For storage conditions after reconstitution of the medication, see the "Shelf life" section.

Discard any unused solution.

Nature and contents of the package

Brown glass vial type I (Ph. Eur.) with a rubber stopper, containing sterile orange-red powder concentrate.

Box of 1, 10, or 20 vials of lyophilized powder.

Only certain package sizes may be marketed.

Incompatibilities

Compatibility with infusion solutions: no incompatibilities have been reported to date. The use of mixed infusion is decided by the responsible physician. Visible indicators of incompatibility are, for example, flocculation, cloudiness, and discoloration.

Special precautions for disposal and other manipulations

Do not use unless the solution is transparent and the container is intact.

Using a syringe, inject 5 mL of water for injection, glucose solution 5%, or sodium chloride solution 0.9% into the vial.

Mix gently to dissolve the powder.

The resulting solution is clear and orange-red in color.

Dispose of unused medication and all materials that have come into contact with it in accordance with local regulations.