Cernevit dry substance vial 10 pieces buy online

composition

Active ingredients

Retinol (vitamin A), colecalciferol (vitamin D 3 ), α-tocopherol (vitamin E), ascorbic acid (vitamin C), thiamine (vitamin B 1 ), riboflavin (vitamin B 2 ), pyridoxine (vitamin B 6 ), cyanocobalamin ( Vitamin B 12 ), folic acid (vitamin B 9 ), pantothenic acid (vitamin B 5 ), biotin (vitamin B 8 ), nicotinamide (vitamin PP)

Excipients

Glycine, glycocholic acid, phospholipids from soybeans, sodium hydroxide or hydrochloric acid

Galenic form and amount of active ingredient per unit

Powder, parenteral.

1 injection bottle with 750 mg dry substance contains:

Indications/applications

• Impaired or difficult oral food intake: esophageal and gastrointestinal stenosis, comatose states, persistent vomiting.

• Contraindicated oral feeding: abdominal fistulas, severe cases of Crohn's disease and ulcerative colitis, certain pre- and post-operative conditions.

• Refused oral food intake: for example anorexia nervosa.

• Inadequate oral food intake: unbalanced diet, tumor cachexia, severe burns, short bowel syndrome.

• Cernevit can also be administered as an additional source of vitamins when food intake is partially restricted.

Dosage/Application

Usual dosage

Adults and children over 11 years: 1 injection bottle per day intravenously or intramuscularly.

Cernevit should be infused slowly (over at least 1-2 hours) intravenously (see “ Warnings and Precautions ” section).

Special dosage instructions

Patients with liver dysfunction

Patients with impaired liver function may require individual vitamin supplementation.
Particular attention should be paid to the prevention of vitamin A toxicity, as the presence of liver disease is associated with increased susceptibility to vitamin A toxicity, especially in combination with chronic excessive alcohol consumption (see also Hypervitaminosis A and effects on the liver in the chapter “ Warnings/Precautions ”).

Patients with renal impairment

Patients with impaired renal function may require vitamin supplementation individually, depending on the degree of impairment of renal function and overall condition. In patients with severe renal impairment, the focus is on maintaining adequate vitamin D levels and preventing vitamin A toxicity, which can develop in such patients with even low-dose vitamin A supplementation or even without supplementation.

Pyridoxine (vitamin B 6 ) hypervitaminosis and toxicity (peripheral neuropathy, involuntary movements) have been reported in patients on chronic hemodialysis administered intravenous multivitamins containing 4 mg of pyridoxine three times per week .

For conditions that require increased nutrient intake (severe burns, etc.), Cernevit can also be administered in two to three times higher dosage (continuous drip).

The patient's clinical status and vitamin levels should be monitored to ensure adequate vitamin levels.

It should be taken into account that some vitamins, especially A, B 2 , and B 6, are sensitive to UV light (for example, direct or indirect sunlight). In addition, the loss of vitamins A, B 1 , C and E can increase with higher oxygen concentrations in the solution. These factors should be taken into account if adequate vitamin levels are not achieved.

In general, dosage adjustments should be considered for elderly patients (reducing the dose and/or longer dosing intervals) due to the higher incidence of reduced liver, kidney or cardiac function and concomitant diseases or drug treatment.

The safety and effectiveness of Cernevit have not been established in children under 11 years of age.

Contraindications

•Do not administer at the same time as other medicines containing vitamin A or D.

•In order to avoid hypercalcemic complications, Cernevit should not be used in patients with severe allergic diathesis or in patients with hyperparathyroidism.

•Hypersensitivity to any of the ingredients or soy proteins/products.

•Cernevit must not be administered to infants under 1 year of age as there is no experience in these patients to date.

•Hypervitaminosis of a vitamin contained in Cernevit.

Warnings and Precautions

Severe systemic hypersensitivity reactions have been reported with Cernevit, other multivitamin preparations and individual vitamins (including B1 , B2 , B12 and folic acid). Fatal reactions have been reported with Cernevit and other parenteral vitamin preparations (see Adverse Reactions section ).

In some cases, the manifestations of a hypersensitivity reaction during intravenous administration of multivitamins can be attributed to the infusion rate.

The infusion or injection must be stopped immediately if signs or symptoms of a hypersensitivity reaction occur. The technical and personnel requirements for correct shock treatment must be present.

The amount of vitamins present in Cernevit does not exactly meet the needs of children under 11 years of age in quantitative terms. Cernevit is therefore less suitable for this group of people.

Cernevit contains lecithin from soybeans and should be used with caution in patients with peanut allergy due to a possible cross-reaction.

If there is an existing vitamin K deficiency (increased tendency to bleed), vitamin K must be administered separately as Cernevit does not contain vitamin K.

Vitamin toxicity

Clinical status and blood vitamin concentrations should be monitored to avoid overdoses and toxic effects, especially with vitamins A, D and E, and especially in patients receiving additional vitamins from other sources or other substances that increase the risk of vitamin C Increase vitamin toxicity.

Monitoring is particularly important in patients receiving long-term therapy.

Hypervitaminosis A

The risk of hypervitaminosis A and vitamin A toxicity (e.g. skin and bone changes, double vision, cirrhosis) are increased with, for example:

- protein malnutrition,

- Renal insufficiency (even in the absence of vitamin A supplementation),

- liver dysfunction,

- small body size (e.g. pediatric patients) and

- chronic therapy.

Patients with saturated vitamin A stores in the liver may experience manifestations of vitamin A toxicity in acute liver disease.

Refeeding syndrome in patients receiving parenteral nutrition

Refeeding severely malnourished patients can result in refeeding syndrome, which is characterized by intracellular shifts in potassium, phosphorus, and magnesium as the patient becomes anabolic. Thiamine deficiency and fluid retention may also develop. Careful monitoring and slowly increasing nutrient intake while avoiding overeating can prevent these complications.

Precipitates in patients receiving parenteral
nutrition Pulmonary vascular precipitates have been reported in patients receiving parenteral nutrition. In some cases the outcome was fatal. Excessive addition of calcium and phosphate increases the risk of calcium phosphate precipitate formation. Precipitates were also observed in the absence of phosphate salts in the solution. Precipitate formation on the distal side of the in-line filter and precipitates suspected of having formed in the bloodstream have also been reported.

In addition to checking the solution, the infusion set and catheter should also be checked periodically for precipitates.
If signs of respiratory distress occur, the infusion should be stopped and medical evaluation initiated.

Effects on the liver

Monitoring of liver function parameters is recommended in patients receiving Cernevit. Particularly close monitoring is recommended in patients with hepatic jaundice or evidence of cholestasis.
Cases of liver enzyme elevations have been reported in patients administered Cernevit, including isolated elevations of alanine aminotransferase (ALT) in patients with inflammatory bowel disease (see Adverse Reactions section ).

In addition, an increase in bile acid levels (total and individual bile acids, including glycocholic acid) has been reported in patients treated with Cernevit.

Due to the content of glycocholic acid, careful monitoring of liver functions is required during repeated or long-term administration in patients with hepatic jaundice or in patients in whom laboratory parameters suggest cholestasis.

General monitoring

Patients receiving long-term parenteral multivitamins as the sole source of vitamins should have their clinical status and vitamin levels monitored. In particular, it is important to ensure adequate administration of the following vitamins:

•Vitamin A in patients with pressure ulcers, wounds, burns, short bowel syndrome, or cystic fibrosis.

•Vitamin B 1 in dialysis patients.

•Vitamin B 2 in cancer patients.

•Vitamin B 6 in patients with renal impairment.

•Individual vitamins, the need for which may be increased due to interactions with other drugs (see « Interactions» ).

Deficiency of one or more vitamins must be corrected through specific supplementation.

Cernevit does not contain vitamin K, which must be taken separately if necessary.

Patients with vitamin B 12 deficiency

Evaluation of vitamin B 12 status is recommended before starting Cernevit supplementation in patients at risk of vitamin B 12 deficiency and/or when Cernevit supplementation is planned for several weeks.

After a few days of administration, the amount of cyanocobalamin (vitamin B 12 ) and folic acid in Cernevit may be sufficient to cause an increase in red blood cell counts, reticulocytes and hemoglobin levels in some patients with vitamin B 12 deficiency-associated megaloblastic anemia. This can mask a pre-existing vitamin B12 deficiency . Effective treatment of vitamin B 12 deficiency requires higher doses of cyanocobalamin than those present in Cernevit.

Folic acid supplementation in patients with vitamin B 12 deficiency who are not receiving vitamin B 12 does not prevent the development or progression of neurological manifestations of vitamin B 12 -associated deficiency. It is even thought to accelerate neurological deterioration.

When interpreting the vitamin B 12 values, it should be noted that a recent intake of vitamin B 12 can lead to a normal vitamin B 12 level despite a deficiency in the tissue.

Sodium content

Cernevit contains 24 mg sodium (1 mmol) per vial. This should be taken into account in patients on a sodium-controlled diet.

Effects on clinical laboratory tests

Biotin can have effects on laboratory tests that are based on an interaction between biotin and streptavidin and that, depending on the test method, can lead to either falsely low or falsely elevated test results. The risk of effects is increased in children and patients with renal insufficiency and increases with higher doses. When interpreting the results of laboratory tests, a possible effect of biotin must be taken into account, especially when a discrepancy with the clinical picture is observed (e.g. results of thyroid tests that appear to suggest Graves' disease in asymptomatic patients taking biotin or false negative troponin test results in heart attack patients taking biotin). If there is suspicion of an influence by biotin, alternative tests that are not susceptible to the effects of biotin should be used, if available. Laboratory personnel should be consulted when requesting laboratory testing in patients taking biotin.

Interactions

The following interactions between specific vitamins in Cernevit and other substances should be noted:

•Substances that can cause pseudotumor cerebri (including certain tetracyclines): Increased risk of pseudotumor cerebri with additional administration of vitamin A.

•Alcohol (chronic excessive): Increases the risk of vitamin A hepatotoxicity.

•Anticonvulsants (phenytoin, fosphenytoin, phenobarbital, primidone): Folic acid supplementation may decrease serum concentrations of anticonvulsants and increase the risk of seizures.

•Platelet coagulation inhibitors (e.g. aspirin): Vitamin E can contribute to the inhibition of platelet function.

•Aspirin (high-dose therapy): May lower folic acid levels by increasing urine excretion.

•Certain anticonvulsants (e.g., phenytoin, carbamazepine, phenobarbital, valproate): Can lead to folic acid, pyridoxine, and vitamin D deficiencies.

•Certain antiretroviral agents: Decreased vitamin D levels have been associated with, for example, efavirenz and zidovudine. Decreased formation of the active vitamin D metabolite has been associated with protease inhibitors.

•Chloramphenicol: May inhibit the hematologic response to vitamin B 12 therapy.

•Deferoxamine: Increased risk of iron-induced heart failure due to increased mobilization of iron by increased physiologic vitamin C supplementation. For special precautionary measures, the product information for deferoxamine should be consulted.

•Ethionamides: May cause pyridoxine deficiency.

•Fluoropyrimidines (5-fluorouracil, capecitabine, tegafur): increase in cytotoxicity when combined with folic acid.

•Folate antagonists, e.g., methotrexate, sulfasalazine, pyrimethamine, triamterene, trimethoprim, and high doses of tea catechins: Block the conversion of folic acid to its active metabolites and reduce the effectiveness of the supplement.

•Folate antimetabolites (methotrexate, raltitrexed): Folic acid supplementation may reduce the effects of antimetabolites.

•Pyridoxine antagonists including cycloserine, hydralazine, isoniazid, penicillamine, phenelzine: May cause pyridoxine deficiency.

• Retinoids, including bexarotene: increase the risk of toxicity when taken at the same time as vitamin A (see section “ Warnings and precautions : hypervitaminosis A”).

• Theophylline: May cause pyridoxine deficiency.

• Tipranavir oral solution: Contains 116 IU/ml vitamin E, which is above the recommended daily dose.

• Vitamin K antagonists (e.g. phenprocoumon): Increased anticoagulant effect due to vitamin E.

•L-Dopa: Cernevit contains pyridoxine, which is why the effect of L-Dopa may be reduced.

Substances that bind to alpha1-acid glycoprotein (AAG):

These include propranolol, prazosin, and a variety of other substances. In an in vitro study using human serum, glycocholic acid concentrations approximately 4 times higher than the glycochol serum concentration following a bolus injection with Cernevit in adults increased the unbound fraction of such drugs by 50 to 80%.

It is not known whether this effect is clinically relevant when the amount of glycocholic acid contained in a standard dose of Cernevit (as a component of the mixed micelles) is administered by slow intravenous injection, intramuscular injection or as an infusion over a prolonged period of time.
Patients receiving Cernevit and those drugs that bind to alpha-1 acid glycoprotein should be closely monitored for increases in the response of these drugs.

Interactions with other vitamin supplements

Some medicines may interact with certain vitamins at significantly higher doses than those contained in Cernevit. This should be considered in patients receiving vitamins from multiple sources and, if applicable, patients should be monitored for such interactions and treated accordingly.

Pregnancy/breastfeeding

Vitamins can be taken in an amount that corresponds to daily requirements. There are no controlled studies available in animals or pregnant women at daily doses such as those administered with Cernevit. Although no adverse consequences are known to date, the drug should not be administered during pregnancy or breastfeeding unless clearly necessary.

Cernevit contains vitamin A. It must be taken into account that with a balanced diet the daily requirement for vitamin A (contained, for example, in liver, products containing liver, milk, dairy products, margarine, eggs, cooking oil) is met or even exceeded.

There are data showing that taking higher doses of vitamin A (above 10,000 IU/day) during pregnancy may increase the risk of teratogenic damage.

For pregnant women in the first trimester and for women who can become pregnant, a daily dose of 10,000 IU of vitamin A should not be exceeded. This fact must be taken into account when taking Cernevit and large amounts of foods containing vitamin A at the same time.

Effects on the ability to drive and operate machines

No data is known.

unwanted effects

Adverse effects from clinical studies:

The adverse reactions listed below are from three clinical studies of local and systemic tolerance of Cernevit in adult patients (N=267) requiring parenteral vitamin supplementation. In all three studies, Cernevit was administered intramuscularly over 5 days, as a slow intravenous injection over 5 days, and as an intravenous infusion over 10 days.

The frequency was divided into the following categories: very common (≥1/10), common (≥1/100, <1/10), uncommon (>1/1,000, <1/100), rare (≥1/10 000, <1/1 000) and very rare (<1/10 000).

Diseases of the gastrointestinal tract

Uncommon: vomiting, nausea

General disorders and administration site conditions

Common: Pain at the injection/infusion site

The following additional adverse reactions have been reported from several other clinical studies (various study designs and durations) with Cernevit as a component of parenteral nutrition:

Metabolism and nutritional disorders

Very common (with daily administration for 3 months): Retinol-binding protein increased, vitamin A increased (without clinical symptoms)

Affections of the liver and gallbladder

Very common: bile acids increased, isolated alanine aminotransferase increased

Common: transaminases increased, blood alkaline phosphatase increased, glutamate dehydrogenase increased

Adverse effects from post-marketing experience

The frequency of undesirable effects that were spontaneously reported after marketing cannot be estimated.

Immune system diseases

Systemic hypersensitivity reactions with manifestations such as shortness of breath, chest discomfort, tightness of the throat, urticaria, rash, erythema, epigastric discomfort and, in a few individual cases, cardiac arrest with fatal outcome.

Diseases of the nervous system

Taste disorder (metal taste in the mouth)

Heart disease

Tachycardia

Respiratory, thoracic and mediastinal diseases

Tachypnea

Gastrointestinal disorders
Diarrhea

Diseases of the skin and subcutaneous tissue

Pruritus

Affections of the liver and gallbladder

Gamma-glutamyltransferase increased

General disorders and administration site conditions

Fever, generalized pain, reactions at the infusion site such as burning, rash

Overdose

Acute or chronic overdose of vitamins (particularly A, B 6 , D and E) can lead to symptomatic hypervitaminosis.

Signs of Cernevit overdose are usually due to excessive intake of vitamin A.

Symptoms of acute overdose of vitamin A (over 150,000 IU): Gastrointestinal disorders, headache, increased intracranial pressure, papilledema, psychiatric disorders, drowsiness, convulsions, delayed generalized desquamation / desquamation.

The risk of overdose is particularly high when vitamins are administered to a patient from multiple sources and the supplementation of a vitamin is not consistent with the patient's individual needs, and in patients with an increased susceptibility to hypervitaminosis (see section "Warnings and precautions " ) .

Symptoms of long-term administration of vitamin A with high doses in patients without vitamin A deficiency:

Increased intracranial pressure, cortical hyperostosis (cortical excessive bone formation) of the long bones and premature epiphyseal closure. Diagnosis is generally based on the appearance of tender or painful subcutaneous swellings on the acral areas of the extremities. Radiographs show periosteal thickening of the diaphyses of the ulna, fibula, clavicles, and ribs.

Symptoms of vitamin D hypervitaminosis: Ergocalciferol (vitamin D 2 ) and colecalciferol (vitamin D 3 ) increase calcium and phosphate absorption from the intestinal lumen and mobilize calcium from the bone.

Vitamin D is more antirachitic and its reduction product DHT (dihydrotachysterol) is more effective in mobilizing calcium from the bones. All of these substances have only a relatively narrow therapeutic range. The toxic threshold in adults is >0.5 mg/d for vitamin D and >0.25 mg/d for DHT. Single acute doses are generally not toxic.

Treatment of vitamin overdose usually consists of discontinuation of vitamin administration and other measures as clinically indicated. (See also “ Interactions ” section).

Properties/Effects

ATC code: B05XC

Cernevit contains all the vitamins essential for metabolism that adults and children over 11 years of age need. The composition and amounts of each vitamin comply with the recommendations of the American Medical Association, the Food and Drug Administration, and the Food and Nutrition Board for parenteral nutrition.

Thanks to the physiological solubilizer and the resulting good tolerability, Cernevit can be administered directly intravenously or intramuscularly.

Cernevit supplements parenteral nutrient solutions and ensures the regulated intermediate metabolism of the parenterally supplied energy and building materials. Cernevit is well tolerated with common infusion solutions.

Pharmacokinetics

There is no information.

Preclinical data

No toxic effects on humans are expected at physiological concentrations.

acute toxicity

For Cernevit solution, an LD 50 of 21 ml/kg was determined in mice after intravenous administration.

Chronic toxicity

In a study on chronic toxicity in dogs over 30 days, an approximately 3-fold therapeutic dose was tolerated without symptoms. After an approximately 10-fold therapeutic dose, the first toxic signs appeared (lipomatosis of the bone marrow, slight increase in SGPT) and after an approximately 40-fold therapeutic dose, additionally increased cholesterol and phospholipid levels as well as a slight increase in alkaline phosphatase appeared.

Local tolerance

The local tolerance after intravenous administration to rabbits can be assessed as good. However, after intradermal and intramuscular injection, tissue damage occurred in the animal.

Mutagenic and tumorigenic potential

There are no studies on the mutagenic or carcinogenic potential of Cernevit.

Under the conditions of clinical use, mutagenic and tumorigenic effects of retinol are not to be expected. The available literature does not provide any information about mutagenic or carcinogenic properties of vitamin B 12 . No mutagenic effects of folic acid are to be expected at physiological doses.

There are no long-term studies on the tumorigenic potential.

Reproductive toxicity

There are no embryotoxicity studies with Cernevit. However, the carrier system - the so-called mixed micelles (glycocholic acid + lecithin) - was examined.

Embryotoxicity studies in rats and rabbits have shown no evidence of teratogenic potential.

In rabbits, an approximately 10-fold therapeutic dose caused abortions. The use of approximately 10 to 20 times the therapeutic dose in the peri-/postnatal period resulted in increased offspring mortality in rats.

There is no experience in humans with use during pregnancy and breastfeeding.

In animal experiments, both vitamin A deficiency and vitamin A overdose have teratogenic effects.

In animal studies on reproductive toxicity, malformations (skeletal defects, microcephaly, cardiac malformations) were caused by overdose of colecalciferol during pregnancy in rats, mice and rabbits.

The available literature does not provide any information about the reproductively toxic properties of vitamin B 12 . There are no animal studies to clarify the reproductive toxicological properties of folic acid (see also “ Warnings and precautionary measures” ).

Other information

Incompatibilities

Cernevit may only be mixed with the preparations listed under Instructions for Handling.

Influencing diagnostic methods

Depending on the reagents used, the presence of ascorbic acid in blood and urine may cause falsely high or low glucose readings in some urine and blood glucose testing systems, including test strips and glucose meters. The technical information for each laboratory test should be consulted to determine potential interactions with vitamins.

durability

The medicine may only be used until the date marked “EXP” on the container.

Special storage instructions

Do not store above 25 °C and do not freeze. Store away from light.

Keep medicines out of the reach of children.

As an undiluted reconstituted solution, it has a shelf life of 24 hours at 5 °C or 8 hours at a maximum of 25 °C. As a diluted reconstituted solution, the shelf life is 8 hours at a maximum of 25 °C. The infusion solution must be protected from light.

For microbiological reasons, the ready-to-use preparation should be used immediately after dilution/reconstitution. Any remaining quantities must be discarded.

Instructions for handling

Aseptic conditions must be ensured during reconstitution and also during admixture with a parenteral nutrition solution.

Cernevit as an addition to infusion solutions is prepared as follows: 5 ml of water for injections are transferred into the Cernevit injection bottle using a syringe. Cernevit can also be dissolved with 5 ml of glucose solution 5%, sodium chloride solution 0.9% or Ringer's solution. The lyophilisate dissolves when gently swirled. The ready-to-use solution is yellow-orange to orange in color.

Cernevit can be added to infusion solutions such as sodium chloride 0.9%, glucose solution 5% or Ringer's solution.

The ready-to-use solution can be mixed with common nutritional solutions such as Numeta Neo/Ped and Olimel/PeriOlimel.
From a microbiological point of view, if not used immediately, storage times and conditions prior to use are the responsibility of the user and should normally not be longer than 24 hours at 2 to 8 °C, unless reconstitution has taken place under controlled conditions validated aseptic conditions took place.

For intramuscular injection, the lyophilisate of the injection bottle is dissolved with 2.5 ml of water for injections in the same manner as described above.

Before transferring from the vial, Cernevit must be completely dissolved.

Parenteral medications should be inspected visually. If visible changes such as discoloration, cloudiness or precipitation occur when mixed with infusion solutions, the mixture should be discarded.

If Cernevit is added as an admixture to a parenteral nutrient solution, the final solution must be mixed completely. Any unused reconstituted Cernevit solution should be discarded and not used for subsequent admixture.

The use of a final filter is recommended during administration of all parenteral nutrition solutions

In principle, Cernevit should not be administered at the same time as other medications unless their compatibility with Cernevit has been explicitly proven.

Approval number

47,953 (Swissmedic)

Authorization holder

Baxter AG, 8152 Opfikon