Cernevit, Powder for Solution for Injection or Infusion

Ireland - English - HPRA (Health Products Regulatory Authority)

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Active ingredient:
Retinol palmitate; Colecalciferol; Dl-alfa tocoferol; Ascorbic acid; Pyridoxine hydrochloride; Cyanocobalamin; Folic acid; Dexpanthenol; Biotin; Nicotinamide; Cocarboxylase tetrahydrate; Riboflavin sodium phosphate
Available from:
Baxter Healthcare Limited
ATC code:
A11BA
INN (International Name):
Retinol palmitate; Colecalciferol; Dl-alfa tocoferol; Ascorbic acid; Pyridoxine hydrochloride; Cyanocobalamin; Folic acid; Dexpanthenol; Biotin; Nicotinamide; Cocarboxylase tetrahydrate; Riboflavin sodium phosphate
Dosage:
N/A
Pharmaceutical form:
Powder for solution for injection/infusion
Prescription type:
Product subject to prescription which may not be renewed (A)
Therapeutic area:
Multivitamins, plain
Authorization status:
Marketed
Authorization number:
PA0167/097/001
Authorization date:
1993-01-04

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PACKAGE LEAFLET:

INFORMATION FOR THE PATIENT

CERNEVIT Powder for Solution

for Injection or Infusion

Read all of this leaflet carefully before this medicine is given to you because it

contains important information for you.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor, pharmacist or nurse.

This medicine has been prescribed for you only. Do not pass it on to others. It may

harm them, even if their signs of illness are the same as yours.

If you get any side effects talk to your doctor, pharmacist or nurse. This includes

any possible side effects not listed in this leaflet. See section 4.

In this leaflet:

1. What CERNEVIT is and what it is used for

2. What you need to know before CERNEVIT is given

3. How CERNEVIT is given

4. Possible side effects

5. How to store CERNEVIT

6. Contents of the pack and other information

Throughout this leaflet CERNEVIT Powder for Solution for Injection or Infusion will

be called CERNEVIT.

1 What CERNEVIT is and what it is used for

CERNEVIT is a sterile powder for solution for injections or infusion. It contains 12

vitamins (see section 6).

CERNEVIT is used to give your daily requirement of vitamins straight into your blood.

It is used when you cannot take enough food by your mouth. It is usually given with

other things such as nutrition solutions and minerals.

2 What you need to know before CERNEVIT is given

You will not be given CERNEVIT if:

you are allergic (hypersensitive) to the active substance or any of the ingredients of

this medicine, especially vitamin B1 or soya protein or peanut protein

(see Section 6, Contents of the pack and other information),

you have too much of one of the vitamins in CERNEVIT stored in your body

(called ‘hypervitaminosis’).

Do not have CERNEVIT if any of the above applies to you. If you are not sure talk to

your doctor, nurse or pharmacist.

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Warnings and precautions

Talk to your doctor, pharmacist or nurse before you are given CERNEVIT if:

you are having vitamins, especially vitamin A (retinol) from other sources

you have liver problems. Your doctor will do blood tests to check how well your

liver is working. They will monitor the levels of certain ‘enzymes’ in your liver.

you have kidney problems or are on dialysis. In this case your doctor will carefully

monitor your fat-soluble vitamin levels. The fat-soluble vitamins are A, D, E and K

you have a low body weight for your age, or do not receive enough nutrition from

your diet

you have inflammatory bowel disease (enterocolitis) or short bowel syndrome

you are suffering from cystic fibrosis

you are suffering from pressure ulcers (bed sores), wounds, burns

you are suffering from pan excess of parathyroid hormone or from a cancer with

associated elevated calcium levels in blood . Your doctor may monitor the levels of

calcium and vitamin D.

you have a peanut allergy. CERNEVIT contains soy-derived lecithin and should be

used with caution in patients with peanut allergies due to potential cross-reactivity.

Your doctor will adapt the dose regimen based on you age and condition.

If you are not sure if any of the above applies to you, talk to your doctor, nurse or

pharmacist before being given CERNEVIT.

Your doctor will make sure that:

you are given additional vitamin K if you need it. CERNEVIT does not contain

vitamin K

your body has all that it needs for good health. If necessary, you may also be given

minerals, amino acids (the building blocks of protein), fatty acids (the building

blocks of fats), electrolytes (salts) and sugar solutions (such as glucose).

Other medicines and CERNEVIT

Before taking Cernevit, please tell you doctor, nurse or pharmacist if you are taking

or have recently taken any other medicines, or getting administered new or different

treatments in the course of parenteral nutrition. This includes medicines obtained

without a prescription, including herbal medicines.

This is because some of the ingredients in CERNEVIT can affect the way some

medicines work.

In particular tell your doctor, nurse or pharmacist if you are taking any of the following:

Medicines to

Treat Infections (Antibiotics)

Thin the blood

Prevent or treat seizures or convulsions

Treat HIV infection

Remove too much iron or copper from the body

Treat tuberculosis

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Treat cancers

Treat high blood pressure

Treat rheumatoid arthritis

Treat depression

Treat acne or psoriasis

Treat asthma or difficulty in breathing

Treat Parkinson’s disease

Before taking CERNEVIT, also tell you doctor, nurse or pharmacist if you are already on

vitamins and are taking medications for any of the following conditions:

Irregular heart beat

Hardening of blood vessels

Have an artificial heart valve or blood vessel.

Epilepsy, bipolar disorder, facial pain

Cancer

Diabetes mellitus

Anemia

Contraception

Your doctor may monitor the levels of these medicines in your blood and may have to

adjust their dose when you start or stop taking CERNEVIT.

Tests while you are having CERNEVIT

If you are due to have a blood test, tell your doctor you are having CERNEVIT. The folic

acid in CERNEVIT may stop the detection of a problem called vitamin B12 deficiency-

associated megaloblastic anaemia. This is when you have a drop in red blood cells

because your body cannot properly absorb vitamin B12 from your gut.

Important information about some of the ingredients of CERNEVIT

This medicinal product contains 1.04 mmol (or 24 mg) sodium per dose. To be taken

into account by patients on a controlled sodium diet.

Fertility, Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you might be pregnant or are planning to

have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

You may receive CERNEVIT during pregnancy if required, providing the indication

and dosages are observed to avoid vitamin overdose.

Breast-feeding

The use of CERNEVIT is not recommended if you are breast-feeding. If you

breast-feed whilst taking CERNEVIT there is a danger that your baby

could get an overdose of vitamin A.

Fertility

No data are available on the effect of CERNEVIT on male or female fertility.

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Use in Patients with liver disease

If you suffer from liver disease or from excessive alcohol consumption, tell your doctor.

He/she will decide if you can have CERNEVIT or adjust the dose you will receive as

necessary.

Use in Patients with kidney disease

If you suffer from kidney disease, tell your doctor. He/she will decide if you can have

CERNEVIT or adjust the dose you will receive as necessary.

Paediatric Use

Cernevit can be used in paediatric patients over 11 years of age.

Geriatric Use

The dose will be adapted to your condition and needs.

3 How CERNEVIT is given

CERNEVIT will be given to you by a doctor or nurse.

How CERNEVIT is given

The CERNEVIT powder will first be dissolved with a liquid such as ‘sterile water for

injection’. This will be mixed with a larger volume of fluid before it is given to you.

It will be given into a vein as a drip (slow intravenous infusion) over at least ten

minutes.

CERNEVIT can also be added to other nutrition solutions. This mixed nutrition

solution will be given to you as a drip into your vein.

The recommended dose

Your doctor will decide how much CERNEVIT you should be given. The amount you

will be given depends upon your age, weight and the reason you are being given the

medicine.

Adults and children over 11 years: the recommended dose is one vial (small glass

bottle) of CERNEVIT each day.

Children under 11 years: not recommended.

If you are given too much

Your doctor or nurse will give you CERNEVIT so it is unlikely that you will be given too

much. If you are worried that you have had too much, tell your doctor or nurse.

Signs of overdose of CERNEVIT are mostly the signs of overdose of vitamin A:

Signs of sudden overdose of vitamin A include:

gastrointestinal disorders (nausea, vomiting),

nervous system disorders (headache, swelling of the optic nerve, convulsions)

due to an increased pressure in your head,

psychiatric disorders (irritability),

skin disorders (delayed peeling of the skin).

Signs of long-term overdose of vitamin A include:

headache due to an increased pressure in your head,

bone disorders (tender or painful swellings at the ends of your limbs).

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If you notice any of these signs of overdose, tell your doctor or nurse. They may stop

your CERNEVIT infusion.

4 Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets

them. The following side effects may happen with this medicine.

The following side effect is common and could affect 1 to 10 users in 100:

Pain at the site of injection

The following side effects are uncommon and could affect 1 to 10 users in 1,000:

Feeling sick (nausea),

being sick (vomiting)

The following side effects have been reported at an unknown frequency:

Allergic reactions, with respiratory difficulties, chest pain, tightening of the throat,

urticaria, rash, skin redness, abdominal discomfort, as well as cardiac arrest

Severe allergic reaction (anaphylactic reaction)

Increased levels of vitamin A and vitamin A carrier protein in blood

Taste alteration (metallic taste)

Accelerated heart rate

Accelerated breathing rate

Diarrhoea

Increase in level of liver enzymes and bile acid

Pruritus (itching)

Fever, generalized soreness, reactions at the site of infusion such as burning

sensation, rash.

If you show any symptom of an allergic reaction such as respiratory difficulties, chest

pain, tightening of the throat, urticaria, rash, skin redness, abdominal discomfort,

inform a doctor or nurse immediately. They will stop the infusion and conduct the

necessary emergency measures.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any

possible side effects not listed in this leaflet. You can also report side effects directly via

HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2.

Tel: +353 1 6764971; Fax: +353 1 6762517,

Website: www.hpra.ie; E-mail: medsafety@hpra.ie

5 How to store CERNEVIT

Because CERNEVIT is usually given in hospital it will be stored safely and correctly by

the hospital staff. If you do need the storage conditions they are given below.

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

This medicine will not be used after the expiry date that is stated on the label after

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‘EXP’. The expiry date refers to the last day of that month.

Do not store above 25°C.

Store in the outer carton in order to protect from light.

CERNEVIT should not be used if the solution is not clear, the seal is broken or if the

vial is damaged in any way.

Once CERNEVIT has been mixed with water it should not be kept for more than

24 hours.

Partly used vials should not be used again. Any leftover CERNEVIT should be thrown

away safely by a healthcare professional.

All equipment used will be disposed of safely by a healthcare professional after use.

6 Contents of the pack and other information

What CERNEVIT contains

The active substances are retinol palmitate (vitamin A) 3500 IU, colecalciferol

(vitamin D3) 220 IU, DL-

-tocopherol (vitamin E) 10.20 mg, ascorbic acid (vitamin C)

125 mg, cocarboxylase tetrahydrate (vitamin B1) 5.80 mg, riboflavin dihydrated

sodium phosphate (vitamin B2) 5.67 mg, pyridoxine hydrochloride (vitamin B6)

5.50 mg, cyanocobalamin (vitamin B12) 6 microgram, folic acid 414 microgram,

dexpanthenol 16.15 mg, D-Biotin 69 microgram, nicotinamide (vitamin PP) 46 mg

per vial.

IU = International Units

mg = milligrams

The other ingredients are glycine, glycocholic acid and soybean phosphatides. It

may also contain small amounts of sodium hydroxide or hydrochloric acid for pH

adjustment.

What CERNEVIT looks like and the contents of the pack

CERNEVIT is a powder for solution for injection or infusion. It is an orange-yellow cake

of powder supplied in brown glass vials. It is packaged in cartons containing 1, 10 or

20 vials. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturers

The Marketing Authorisation holder is:

Baxter Healthcare Ltd., Caxton Way, Thetford, Norfolk, IP24 3SE, United Kingdom

Send all enquiries to this address.

CERNEVIT is made at:

Baxter S.A., Bd. R. Branquart 80, B-7860 Lessines, Belgium

This leaflet was last revised in May 2018.

For information about CERNEVIT or to request this leaflet in formats such as audio

or large print please contact the

Marketing Authorisation Holder: Tel: +44 1635 206345.

Baxter and Cernevit are trademarks of Baxter International Inc.

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TECHNICAL INFORMATION LEAFLET

CERNEVIT, Powder for Solution

for Injection or Infusion

Pharmacist – please remove this section from leaflet

Presentation

Powder for solution for injection or Infusion in brown glass vials.

Each vial of powder contains:

Retinol palmitate

3500 IU

Colecalciferol

220 IU

-tocopherol

10.20 mg

Ascorbic acid

125 mg

Cocarboxylase tetrahydrate

5.80 mg

Riboflavin dihydrated

sodium phosphate

5.67 mg

Pyridoxine hydrochloride

5.50 mg

Cyanocobalamin

0.006 mg

Folic acid

0.414 mg

Dexpanthenol

16.15 mg

D-Biotin

0.069 mg

Nicotinamide

46 mg

Equivalent to:

Vitamin A (Retinol)

3500 IU

Vitamin D3

220 IU

Vitamin E (

tocopherol)

11.20 IU

Vitamin C

125 mg

Vitamin B1 (thiamine)

3.51 mg

Vitamin B2 (riboflavin)

4.14 mg

Vitamin B6 (pyridoxine)

4.53 mg

Vitamin B12

0.006 mg

Folic Acid

0.414 mg

Pantothenic acid

17.25 mg

Biotin

0.069 mg

Vitamin PP (niacin)

46 mg

CERNEVIT also contains: Glycine, Glycocholic acid, Soybean phosphatides, Sodium

hydroxide and Hydrochloric acid.

Indications

Supply of vitamins corresponding to the daily needs of adults and children over

11 years requiring multi-vitamin supplementation by the parenteral route when

oral nutrition is contraindicated, impossible or insufficient (e.g. due to malnutrition,

gastrointestinal malabsorption, parenteral nutrition, etc).

Dosage

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

Method of administration

Intravenous route: By slow intravenous injection (at least 10 minutes) or by infusion in

a solution of 5% glucose or 0.9% sodium chloride solution for infusion.

Nature and Contents of Container

Type I Ph.Eur. brown glass vial, containing an orange-yellow sterile cake of powder,

with an elastomeric stopper fitted with an aluminium closure.

Box of 1, 10 or 20 vials of lyophilised powder. Not all pack sizes may be marketed

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Preparation of Solution

Using a syringe, inject 5 ml of water for injections into the vial. Mix gently to dissolve

the powder. The obtained solution is yellow-orange in colour.

Do not use unless the reconstituted solution is clear, the original seal is intact and the

container is undamaged. The reconstituted product is a clear yellow-orange solution.

After addition of Cernevit to a parenteral nutrition solution, check for any abnormal

color change and/or the appearance of precipitates, insoluble complexes, or crystals.

Mix the final solution thoroughly when Cernevit is used as an admixture in parenteral

nutrition.

For single use only. Any unused portion of reconstituted Cernevit should be discarded

and should not be stored for subsequent admixing.

Parenteral drug products should be inspected visually for particulate matter and

abnormal discoloration prior to administration, whenever solution and container permit.

Use of a final filter is recommended during administration of all parenteral nutrition

solutions.

CERNEVIT may be included in the composition of nutritive mixtures combining

carbohydrates, lipids, amino acids and electrolytes provided that compatibility and

stability have been confirmed for each nutritive mixture.

Contraindications

CERNEVIT must not be used in:

hypersensitivity to the active substances, especially vitamin B1 or to any of the

excipients listed in section 6.1, including soy protein/products (lecithin in mixed

micelle is soy derived) or peanut protein/products,hypervitaminosis from any

vitamin contained in this formulation.

Special Warnings and Special Precautions for Use

WARNINGS

Hypersensitivity Reactions

Severe systemic hypersensitivity reactions have been reported with Cernevit, other

multivitamin preparations, and individual vitamins (including B1, B2, B12 and folic

acid). Reactions with fatal outcome have been reported with Cernevit and other

parenteral vitamin products.

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

In some cases, the manifestations of a hypersensitivity reaction during intravenous

administration of multivitamins may be rate related. If infused intravenously,

Cernevit should be administered slowly.

The infusion or injection must be stopped immediately if signs or symptoms of a

hypersensitivity reaction develop.

Vitamin Toxicity

The patient’s clinical status and blood vitamin concentrations should be monitored

to avoid overdose and toxic effects, especially with vitamins A, D and E, and in

particular in patients who receive additional vitamins from other sources or use

other agents that increase the risk of vitamin toxicity.

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Caution should be exercised when administering CERNEVIT to patients with

symptomatic hypercalcemia that results from excess vitamin D levels. Due to the risk

of hypercalcemia complication, CERNEVIT should be administered with caution to

patients suffering from primary hyperparathyroidism or malignancy with secondary

hypercalcemia. Administration of calcium and vitamin D to these patients should be

closely monitored.

Monitoring is particularly important in patients receiving long-term

supplementation.

Hypervitaminosis A

The risk for hypervitaminosis A and vitamin A toxicity (e.g., skin and bone

abnormalities, diplopia, cirrhosis) is increased in, for example:

– patients with protein malnutrition,

– patients with renal impairment (even in the absence of vitamin A

supplementation),

– patients with hepatic impairment,

– patients with small body size (e.g., paediatric patients), and

– patients on chronic therapy.

Acute hepatic disease in patients with saturated hepatic vitamin A stores can lead

to the manifestation of vitamin A toxicity.

Refeeding Syndrome in Patients Receiving Parenteral Nutrition

Refeeding severely undernourished patients may result in refeeding syndrome that is

characterized by the shift of potassium, phosphorus, and magnesium intracellularly

as the patient becomes anabolic. Thiamine deficiency and fluid retention may also

develop. Careful monitoring and slowly increasing nutrient intakes while avoiding

overfeeding can prevent these complications. Should nutrient deficiencies occur,

appropriate supplementation may be warranted.

Precipitates in Patients Receiving Parenteral Nutrition

Pulmonary vascular precipitates have been reported in patients receiving parenteral

nutrition. In some cases, fatal outcomes have occurred. Excessive addition of calcium

and phosphate increases the risk of the formation of calcium phosphate precipitates.

Precipitates have been reported even in the absence of phosphate salt in the solution.

Precipitation distal to the in-line filter and suspected precipitate formation in the blood

stream have also been reported.

In addition to inspection of the solution, the infusion set and catheter should also

periodically be checked for precipitates.

If signs of pulmonary distress occur, the infusion should be stopped and medical

evaluation initiated.

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PRECAUTIONS

Hepatic Effects

Monitoring of liver function parameters is recommended in patients receiving

Cernevit. Particularly close monitoring is recommended in patients with hepatic

jaundice or other evidence of cholestasis.

In patients receiving Cernevit, instances of liver enzyme increases have been

reported, including isolated alanine aminotransferase (ALT) increases in patients

with inflammatory bowel disease.

In addition, an increase in bile acid levels (total and individual bile acids including

glycocholic acid) have been reported in patients receiving Cernevit.

Hepatobiliary disorders including cholestasis, hepatic steatosis, fibrosis and

cirrhosis, possibly leading to hepatic failure, as well as cholecystitis and

cholelithiasis are known to develop in some patients on parenteral nutrition

(including vitamin supplemented parenteral nutrition). The etiology of these

disorders is thought to be multifactorial and may differ between patients. Patients

developing abnormal laboratory parameters or other signs of hepatobiliary

disorders should be assessed early by a clinician knowledgeable in liver diseases

in order to identify possible causative and contributory factors, and possible

therapeutic and prophylactic interventions.

Use in Patients with Impaired Hepatic Function

Patients with hepatic impairment may need individualized vitamin supplementation.

Particular attention should be placed on preventing vitamin A toxicity, because the

presence of liver disease is associated with increased susceptibility to vitamin A

toxicity, in particular in combination with chronic excessive alcohol consumption (See

also Hypervitaminosis A and Hepatic Effects above).

Use in Patients with Impaired Renal Function

Patients with renal impairment may need individualized vitamin supplementation,

depending on the degree of renal impairment and the presence of concomitant

medical conditions. In patients with severe renal impairment, particular attention

should be placed on maintaining adequate vitamin D status and preventing vitamin A

toxicity, which may develop in such patients with low-dose vitamin A supplementation

or even without supplementation.

Pyridoxine (vitamin B6) hypervitaminosis and toxicity (peripheral neuropathy, involuntary

movements) have been reported in patients on chronic haemodialysis receiving

intravenous multivitamins containing 4 mg pyridoxine administered three times a week.

General Monitoring

Clinical status and vitamin levels should be monitored in patients receiving parenteral

multivitamins as the only source of vitamins for extended periods of time. It is

particularly important to monitor for adequate supplementation of, for example:

Vitamin A in patients with pressure ulcers, wounds, burns, short bowel syndrome or

cystic fibrosis

Vitamin B1 in dialysis patients

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Vitamin B2 in cancer patients

Vitamin B6 in patients with renal impairment

Individual vitamins whose requirements may be increased due to interactions with

other medicines.

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

Vitamin K

CERNEVIT does not contain Vitamin K. Vitamin K must be administered separately if

necessary.

Use in Patients with Vitamin B12 Deficiency

Evaluation of vitamin B12 status is recommended before starting supplementation

with Cernevit in patients at risk for vitamin B12 deficiency and/or when

supplementation with Cernevit over several weeks is planned.

After several days of administration, both the individual amounts of cyanocobalamin

(vitamin B12) and folic acid in Cernevit may be sufficient to result in an increase in

red blood cell count, reticulocyte count, and haemoglobin values in some patients with

vitamin B12 deficiency-associated megaloblastic anaemia. This may be masking an

existing vitamin B12 deficiency. Effective treatment of vitamin B12 deficiency requires

higher doses of cyanocobalamin than provided in Cernevit.

Folic acid supplementation in patients with vitamin B12 deficiency, who do not also

receive vitamin B12, does not prevent the development or progression of neurologic

manifestations associated with the vitamin B12 deficiency. It has been suggested that

neurologic deterioration may even be accelerated.

When interpreting levels of vitamin B12, it should be taken into account that recent

intake of vitamin B12 may result in normal levels despite a tissue deficiency.

Laboratory Test Interferences

Depending on the reagents used, the presence of ascorbic acid in blood and urine

may cause false high or low glucose readings in some urine and blood glucose testing

systems, including test strips and handheld glucose meters. The technical information

for any laboratory test should be consulted to determine the potential interference

from vitamins.

Sodium Content

This medicinal product contains 24 mg (1.04 mmol) sodium per dose. To be taken into

consideration by patients on a controlled sodium diet.

Paediatric Use

Cernevit is indicated in paediatric patients over 11 years of age (see also Section 4.4:

Hypervitaminosis A above).

Geriatric Use

In general, dosage adjustments for an elderly patient should be considered (reducing

the dose and/or extending the dosing intervals) reflecting the greater frequency of

decreased hepatic, renal, or cardiac function, and of concomitant disease or drug

therapy.

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Interaction with Other Medicaments and Other Forms of Interactions

Interactions between specific vitamins in Cernevit and other agents should be

managed accordingly.

Such interactions include:

Agents that can cause pseudotumor cerebri (including certain tetracyclines):

Increased risk for pseudotumor cerebri by concomitant administration of Vitamin A

Alcohol (chronic excessive consumption): Increases the risk of vitamin A

hepatotoxicity

Anticonvulsants (phenytoin, fosphenytoin, phenobarbital, primidone): Folic acid

supplementation can decrease the anticonvulsant serum concentration and

increase seizure risk. Plasma concentrations of anticonvulsants should be

monitored with concurrent use of folate. Clinical surveillance, eventually plasma

level monitoring, and, if necessary, adjustment of the dose of the anticonvulsant

may be necessary during folic supplementation and after it is withdrawn.

Antiplatelet agents (e.g., aspirin): Vitamin E can add to the inhibition of platelet

function

Aspirin (high dose therapy): Can reduce folic acid levels by increasing urinary

excretion

Certain anticonvulsants (e.g., phenytoin, carbamazepine, phenobarbital, valproate):

Can cause folate, pyridoxine and vitamin D deficiencies

Certain antiretroviral agents: Decreased vitamin D levels have been associated

with, e.g., efavirenz and zidovudine. Decreased formation of the active vitamin D

metabolite has been associated with protease inhibitors.

Chloramphenicol: Can inhibit the haematological response to vitamin B12 therapy

Deferoxamine: Increased risk of iron-induced cardiac failure due to increased

iron mobilization by supraphysiologic vitamin C supplementation. For specific

precautions, refer to deferoxamine product information.

Ethionamide: Can cause pyridoxine deficiency

Fluoropyrimidines (5-fluorouracil, capecitabine, tegafur): Increased 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 folate to its

active metabolites and reduce the effectiveness of supplementation

Folate antimetabolites (methotrexate, raltitrexed): Folic acid supplementation can

decrease the antimetabolite effects

Levodopa: The content of pyridoxine may interfere with the effects of concurrent

levodopa therapy.

Pyridoxine antagonists, including cycloserine, hydralazine, isoniazid, penicillamine,

phenelzine: Can cause pyridoxine deficiency

Retinoids, including bexarotene: Increase the risk of toxicity when used

concomitantly with vitamin A (also see Hypervitaminosis A)

Theophylline: Can cause pyridoxine deficiency

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Tipranavir oral solution: Contains 116 IU/mL of vitamin E, which is in excess of the

daily recommended intake

Vitamin K antagonists (e.g., warfarin): Enhanced anticoagulant effect by vitamin E

Drugs that Bind to alpha1-Acid Glycoprotein (AAG):

In an in vitro study using human serum, concentrations of glycocholic acid

approximately 4 times higher than the glycocholic acid serum concentration that

would result from a bolus injection of Cernevit in adults, increased the unbound

fraction of selected drugs known to bind to alpha1-acid glycoprotein (AAG) by

50 – 80%.

It is not known whether this effect is clinically relevant if the amount of glycocholic

acid contained in a standard Cernevit dose (as a component of the mixed micelles) is

administered by slow intravenous injection, intramuscular injection, or infused over a

longer period of time.

Patients receiving Cernevit as well as drugs that bind to AAG should be closely

monitored for increases in response of these drugs. These include propranolol,

prazosin, and numerous others.

Interactions with Additional Vitamin Supplementation:

Some medications can interact with certain vitamins at doses markedly higher than

those provided with Cernevit. This should be taken into consideration in patients

receiving vitamins from multiple sources, and when applicable, patients should be

monitored for such interactions and managed accordingly.

Such interactions include:

Amiodarone: Concomitant use of vitamin B6 can enhance amiodarone-induced

photosensitivity.

Agents with anticoagulant effects (e.g., such as abciximab, clopidogrel, heparin,

warfarin): Increased bleeding risk due to additional risk of bleeding associated with

high vitamin A doses

Carbamazepine: Inhibition of metabolism associated with large nicotinamide doses

Chemotherapeutic agents that rely on the production of reactive oxygen species for

their activity: Possible inhibition of chemotherapy activity by the antioxidant effects

of high doses of vitamin E

Insulin, antidiabetic agents: Decreased insulin sensitivity associated with large

nicotinamide doses

Iron: High dose-supplementation with vitamin E may reduce the haematological

response to iron in anaemic patients

Oral contraceptives (combination hormone types): High doses of vitamin C have

been associated with breakthrough bleeding and contraceptive failure

Phenobarbital: Increased metabolism/lower serum levels and reduced effect

associated with large pyridoxine doses

Phenytoin, fosphenytoin: Lower serum levels associated with large pyridoxine

doses

Primidone: Decreased metabolism to phenobarbital and increased primidone levels

associated with large nicotinamide doses

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Fertility, Pregnancy and Lactation

Physicians should carefully consider the potential risks and benefits for each specific

patient before prescribing Cernevit.

Pregnancy

No safety data are available for Cernevit administered during pregnancy or in

breastfeeding women. This medicinal product may be prescribed during pregnancy if

required, providing the indication and dosages are observed in order to avoid vitamin

overdose.

Lactation

Use is not recommended during breastfeeding because of the risk of vitamin A

overdose in the neonate.

Fertility

There are no adequate data from the use of Cernevit with regards to fertility in male

or female patients.

Overdose

Acute or chronic overdose of vitamins (in particular A, B6, D, and E) can cause

symptomatic hypervitaminosis.

The risk of overdose is particularly high if a patient receives vitamins from multiple

sources and overall supplementation of a vitamin does not match the patient’s individual

requirements, and in patients with increased susceptibility to hypervitaminosis.

Treatment of vitamin overdose usually consists of withdrawal of the vitamin and other

measures as clinically indicated.

Incompatibilities

Additives may be incompatible with parenteral nutrition containing Cernevit.

Do not add other medicinal products or substances without first confirming their

compatibility and the stability of the resulting preparation.

If co-administration of drugs that are incompatible at the Y-site is necessary,

administer via separate IV lines.

Vitamin A and thiamine in Cernevit may react with bisulfites in parenteral nutrition

solutions (e.g., as a result of admixtures) leading to degradation of vitamin A and

thiamine.

An increase in pH of a solution may increase the degradation of some vitamins. This

should be considered when adding alkaline solutions to the admixture containing

Cernevit.

Folic acid stability can be impaired with increased calcium concentrations in an

admixture.

Numerous other incompatibilities between vitamins and other medicinal products,

including certain antibiotics, and trace elements have been described.

Refer to appropriate compatibility references and guidelines as needed.

BE-30-03-043

Storage and Stability

Do not store above 25°C. Keep the vial in the outer carton.

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

Shelf life unopened: 2 years.

Shelf life after reconstitution for intravenous administration: Chemical and Physical

in-use stability has been demonstrated for CERNEVIT for 24 hours at 25°C when

reconstituted with 5 ml of Water for Injections.

From a microbiological point of view, the product should be used immediately. If not

used immediately, in use storage times and conditions prior to use are the responsibility

of the user and would normally not be longer than 24 hours at 2 to 8°C, unless

reconstitution/dilution etc. has taken place in controlled and validated aseptic conditions.

Marketing Authorisation Holder

Baxter Healthcare Ltd. Caxton Way, Thetford, Norfolk, IP24 3SE, United Kingdom

Marketing Authorisation Number

PA 167/97/1

Further information on CERNEVIT is available from:

Baxter Healthcare Ltd. Caxton Way, Thetford, Norfolk, IP24 3SE, United Kingdom

Telephone: +44 1635 206345

Baxter and Cernevit are trademarks of Baxter International Inc.

BE-30-03-043

Summary of Product Characteristics

1 NAME OF THE MEDICINAL PRODUCT

Cernevit, Powder for Solution for Injection or Infusion

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each vial of powder contains:

Excipients: Each vial contains 24mg sodium and less than 112.5mg soya oil.

For a full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Powder for solution for injection or infusion

Orange-yellow sterile cake of lyophilised powder.

4 CLINICAL PARTICULARS

4.1 Therapeutic Indications

Supply of vitamins corresponding to the daily needs of adults and children over 11 years requiring multi-vitamin

supplementation by the parenteral route when oral nutrition is contraindicated, impossible or insufficient (e.g. due to

malnutrition, gastrointestinal malabsorption, parenteral nutrition, etc).

Retinol Palmitate (Vit A)

3500

Colecalciferol (Vit D

tocopherol (Vit E)

10.20

- corresponding to

-tocopherol

11.200

Ascorbic acid (Vit C)

Cocarboxylase tetrahydrate

5.80

- corresponding to Thiamine (Vit B

3.510

Riboflavin dihydrated sodium phosphate (Vit B

5.67

- corresponding to Riboflavin

4.14

Pyridoxine hydrochloride (Vit B

5.50

- corresponding to Pyridoxine

4.53

Cyanocobalamin (Vit B

micrograms

Folic acid

micrograms

Dexpanthenol

16.15

- corresponding to pantothenic acid

17.25

D-Biotin

micrograms

Nicotinamide

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4.2 Posology and method of administration

Dosage

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

Administration

Method of reconstitution: see 6.6 Instruction for use and handling

If infused intravenously, CERNEVIT should be administered slowly. If injected intravenously, the injection must be

administered slowly (over at least 10 minutes).

Cernevit may be included in the composition of nutritive mixtures combining carbohydrates, lipids, amino acids and

electrolytes provided that compatibility and stability have been confirmed for each nutritive mixture, to meet nutrient

needs and prevent deficiencies and complications from developing.

The total vitamin amounts from all sources such as nutritional sources, other vitamin supplements, or medications that

contain vitamins as inactive ingredients (see Section 4.5) should be considered.

It should be taken into account that some vitamins, especially A, B2, and B6 are sensitive to ultraviolet light (e.g.,

direct or indirect sun light). In addition, loss of vitamins A, B1, C, and E may increase with higher levels of oxygen in

the solution. These factors should be considered if adequate vitamin levels are not achieved.

4.3 Contraindications

CERNEVIT must not be used in:

hypersensitivity to the active substances, especially vitamin B1 or to any of the excipients listed in section 6.1,

including soy protein/products (lecithin in mixed micelle is soy-derived) or peanuts, protein/products.

hypervitaminosis from any vitamin contained in this formulation.

4.4 Special warnings and precautions for use

WARNINGS

Hypersensitivity Reactions

Severe systemic hypersensitivity reactions have been reported with Cernevit, other multivitamin preparations,

and individual vitamins (including B1, B2, B12 and folic acid). Reactions with fatal outcome have been reported

with Cernevit and other parenteral vitamin products (See Section 4.8).

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

In some cases, the manifestations of a hypersensitivity reaction during intravenous administration of

multivitamins may be rate related. If infused intravenously, Cernevit should be administered slowly.

The infusion or injection must be stopped immediately if signs or symptoms of a hypersensitivity reaction

develop.

Vitamin Toxicity

The patient’s clinical status and blood vitamin concentrations should be monitored to avoid overdose and toxic

effects, especially with vitamins A, D and E, and in particular in patients who receive additional vitamins from

other sources or use other agents that increase the risk of vitamin toxicity.

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Caution should be exercised when administering Cernevit to patients with symptomatic hypercalcaemia (e.g. calcium

stones, encephalopathy) that results from excess vitamin D levels. Due to the risk of hypercalcaemia complication,

Cernevit should be administered with caution to patients suffering from primary hyperparathyroidism or malignancy

with secondary hypercalcaemia. Administration of calcium and vitamin D to these patients should be closely

monitored.

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

Hypervitaminosis A

The risk for hypervitaminosis A and vitamin A toxicity (e.g., skin and bone abnormalities, diplopia, cirrhosis) is

increased in, for example:

- patients with protein malnutrition,

- patients with renal impairment (even in the absence of vitamin A supplementation),

- patients with hepatic impairment,

- patients with small body size (e.g., paediatric patients), and

- patients on chronic therapy.

Acute hepatic disease in patients with saturated hepatic vitamin A stores can lead to the manifestation of vitamin

A toxicity.

Refeeding Syndrome in Patients Receiving Parenteral Nutrition

Refeeding severely undernourished patients may result in refeeding syndrome that is characterized by the shift of

potassium, phosphorus, and magnesium intracellularly as the patient becomes anabolic. Thiamine deficiency and fluid

retention may also develop. Careful monitoring and slowly increasing nutrient intakes while avoiding overfeeding can

prevent these complications. Should nutrient deficiencies occur, appropriate supplementation may be warranted.

Precipitates in Patients Receiving Parenteral Nutrition

Pulmonary vascular precipitates have been reported in patients receiving parenteral nutrition. In some cases, fatal

outcomes have occurred. Excessive addition of calcium and phosphate increases the risk of the formation of calcium

phosphate precipitates. Precipitates have been reported even in the absence of phosphate salt in the solution.

Precipitation distal to the in-line filter and suspected precipitate formation in the blood stream have also been reported.

In addition to inspection of the solution, the infusion set and catheter should also periodically be checked for

precipitates.

If signs of pulmonary distress occur, the infusion should be stopped and medical evaluation initiated.

PRECAUTIONS

Hepatic Effects

Monitoring of liver function parameters is recommended in patients receiving Cernevit. Particularly close

monitoring is recommended in patients with hepatic jaundice or other evidence of cholestasis.

In patients receiving Cernevit, instances of liver enzyme increases have been reported, including isolated alanine

aminotransferase (ALT) increases in patients with inflammatory bowel disease (see Section 4.8).

In addition, an increase in bile acid levels (total and individual bile acids including glycocholic acid) have been

reported in patients receiving Cernevit.

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Hepatobiliary disorders including cholestasis, hepatic steatosis, fibrosis and cirrhosis, possibly leading to hepatic

failure, as well as cholecystitis and cholelithiasis are known to develop in some patients on parenteral nutrition

(including vitamin supplemented parenteral nutrition). The etiology of these disorders is thought to be

multifactorial and may differ between patients. Patients developing abnormal laboratory parameters or other

signs of hepatobiliary disorders should be assessed early by a clinician knowledgeable in liver diseases in order

to identify possible causative and contributory factors, and possible therapeutic and prophylactic interventions.

Use in Patients with Impaired Hepatic Function

Patients with hepatic impairment may need individualized vitamin supplementation. Particular attention should be

placed on preventing vitamin A toxicity, because the presence of liver disease is associated with increased

susceptibility to vitamin A toxicity, in particular in combination with chronic excessive alcohol consumption (See also

Hypervitaminosis A and Hepatic Effects above).

Use in Patients with Impaired Renal Function

Patients with renal impairment may need individualized vitamin supplementation, depending on the degree of renal

impairment and the presence of concomitant medical conditions. In patients with severe renal impairment, particular

attention should be placed on maintaining adequate vitamin D status and preventing vitamin A toxicity, which may

develop in such patients with low-dose vitamin A supplementation or even without supplementation.

Pyridoxine (vitamin B6) hypervitaminosis and toxicity (peripheral neuropathy, involuntary movements) have been

reported in patients on chronic haemodialysis receiving intravenous multivitamins containing 4 mg pyridoxine

administered three times a week.

General Monitoring

Clinical status and vitamin levels should be monitored in patients receiving parenteral multivitamins as the only source

of vitamins for extended periods of time. It is particularly important to monitor for adequate supplementation of, for

example:

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

Vitamin B1 in dialysis patients

Vitamin B2 in cancer patients

Vitamin B6 in patients with renal impairment

Individual vitamins whose requirements may be increased due to interactions with other medicines (see Section

4.5).

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

Vitamin K

Cernevit does not contain Vitamin K. Vitamin K must be administered separately if necessary.

Use in Patients with Vitamin B12 Deficiency

Evaluation of vitamin B12 status is recommended before starting supplementation with Cernevit in patients at risk for

vitamin B12 deficiency and/or when supplementation with Cernevit over several weeks is planned.

After several days of administration, both the individual amounts of cyanocobalamin (vitamin B12) and folic acid in

Cernevit may be sufficient to result in an increase in red blood cell count, reticulocyte count, and haemoglobin values

in some patients with vitamin B12 deficiency-associated megaloblastic anaemia. This may be masking an existing

vitamin B12 deficiency. Effective treatment of vitamin B12 deficiency requires higher doses of cyanocobalamin than

provided in Cernevit.

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Folic acid supplementation in patients with vitamin B12 deficiency, who do not also receive vitamin B12, does not

prevent the development or progression of neurologic manifestations associated with the vitamin B12 deficiency. It has

been suggested that neurologic deterioration may even be accelerated.

When interpreting levels of vitamin B12, it should be taken into account that recent intake of vitamin B12 may result in

normal levels despite a tissue deficiency.

Laboratory Test Interferences

Depending on the reagents used, the presence of ascorbic acid in blood and urine may cause false high or low glucose

readings in some urine and blood glucose testing systems, including test strips and handheld glucose meters. The

technical information for any laboratory test should be consulted to determine the potential interference from vitamins.

Sodium Content

This medicinal product contains 24 mg (1.04 mmol) sodium per dose. To be taken into consideration by patients on a

controlled sodium diet.

Paediatric Use

Cernevit is indicated in paediatric patients over 11 years of age (see also Section 4.4: Hypervitaminosis A above).

Geriatric Use

In general, dosage adjustments for an elderly patient should be considered (reducing the dose and/or extending the

dosing intervals) reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant

disease or drug therapy.

4.5 Interaction with other medicinal products and other forms of interaction

Interactions between specific vitamins in Cernevit and other agents should be managed accordingly.

Such interactions include:

Agents that can cause benign/idiopathic intracranial hypertension (including certain tetracyclines): Increased risk

for benign/idiopathic intracranial hypertension by concomitant administration of Vitamin A

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

Anticonvulsants (phenytoin, fosphenytoin, phenobarbital, primidone): Folic acid supplementation can decrease

the anticonvulsant serum concentration and increase seizure risk. Plasma concentrations of anticonvulsants

should be monitored with concurrent use of folate. Clinical surveillance, eventually plasma level monitoring,

and, if necessary, adjustment of the dose of the anticonvulsant may be necessary during folic supplementation

and after it is withdrawn.

Antiplatelet agents (e.g., aspirin): Vitamin E can add to the inhibition of platelet function

Aspirin (high dose therapy): Can reduce folic acid levels by increasing urinary excretion

Certain anticonvulsants (e.g., phenytoin, carbamazepine, phenobarbital, valproate): Can cause folate, pyridoxine

and vitamin D deficiencies

Certain antiretroviral agents: Decreased vitamin D levels have been associated with, e.g., efavirenz and

zidovudine. Decreased formation of the active vitamin D metabolite has been associated with protease inhibitors.

Chloramphenicol: Can inhibit the haematological response to vitamin B12 therapy

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Deferoxamine: Increased risk of iron-induced cardiac failure due to increased iron mobilization by

supraphysiologic vitamin C supplementation. For specific precautions, refer to deferoxamine product

information.

Ethionamide: Can cause pyridoxine deficiency

Fluoropyrimidines (5-fluorouracil, capecitabine, tegafur): Increased 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 folate to its active metabolites and reduce the effectiveness of

supplementation

Folate antimetabolites (methotrexate, raltitrexed): Folic acid supplementation can decrease the antimetabolite

effects

Levodopa: The content of pyridoxine may interfere with the effects of concurrent levodopa therapy.

Pyridoxine antagonists, including cycloserine, hydralazine, isoniazid, penicillamine, phenelzine: Can cause

pyridoxine deficiency

Retinoids, including bexarotene: Increase the risk of toxicity when used concomitantly with vitamin A (see

Section 4.4: Hypervitaminosis A)

Theophylline: Can cause pyridoxine deficiency

Tipranavir oral solution: Contains 116 IU/mL of vitamin E, which is in excess of the daily recommended intake

Vitamin K antagonists (e.g., warfarin): Enhanced anticoagulant effect by vitamin E

Drugs that Bind to alpha1-Acid Glycoprotein (AAG):

In an in vitro study using human serum, concentrations of glycocholic acid approximately 4 times higher than the

glycocholic acid serum concentration that would result from a bolus injection of Cernevit in adults, increased the

unbound fraction of selected drugs known to bind to alpha1-acid glycoprotein (AAG) by 50-80%.

It is not known whether this effect is clinically relevant if the amount of glycocholic acid contained in a standard

Cernevit dose (as a component of the mixed micelles) is administered by slow intravenous injection, intramuscular

injection, or infused over a longer period of time.

Patients receiving Cernevit as well as drugs that bind to AAG should be closely monitored for increases in response of

these drugs. These include propranolol, prazosin, and numerous others.

Interactions with Additional Vitamin Supplementation:

Some medications can interact with certain vitamins at doses markedly higher than those provided with Cernevit. This

should be taken into consideration in patients receiving vitamins from multiple sources, and when applicable, patients

should be monitored for such interactions and managed accordingly.

Such interactions include:

Amiodarone: Concomitant use of vitamin B

can enhance amiodarone-induced photosensitivity.

Agents with anticoagulant effects (e.g., such as abciximab, clopidogrel, heparin, warfarin): Increased bleeding

risk due to additional risk of bleeding associated with high vitamin A doses

Carbamazepine: Inhibition of metabolism associated with large nicotinamide doses

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Chemotherapeutic agents that rely on the production of reactive oxygen species for their activity: Possible

inhibition of chemotherapy activity by the antioxidant effects of high doses of vitamin E

Insulin, antidiabetic agents: Decreased insulin sensitivity associated with large nicotinamide doses

Iron: High dose-supplementation with vitamin E may reduce the haematological response to iron in anaemic

patients

Oral contraceptives (combination hormone types): High doses of vitamin C have been associated with

breakthrough bleeding and contraceptive failure

Phenobarbital: Increased metabolism/lower serum levels and reduced effect associated with large pyridoxine

doses

Phenytoin, fosphenytoin: Lower serum levels associated with large pyridoxine doses

Primidone: Decreased metabolism to phenobarbital and increased primidone levels associated with large

nicotinamide doses

4.6 Fertility, pregnancy and lactation

Physicians should carefully consider the potential risks and benefits for each specific patient before prescribing

Cernevit.

Pregnancy

No safety data are available for Cernevit administered during pregnancy or in breastfeeding women. This medicinal

product may be prescribed during pregnancy if required, providing the indication and dosages are observed in order to

avoid vitamin overdose.

Lactation

Use is not recommended during breastfeeding because of the risk of vitamin A overdose in the neonate.

Fertility

There are no adequate data from the use of Cernevit with regards to fertility in male or female patients.

4.7 Effects on ability to drive and use machines

There is no information on the effects of Cernevit on the ability to operate an automobile or other heavy machinery.

4.8 Undesirable effects

Adverse drug reactions (ADRs) that occurred after administration of Cernevit are presented with their relative

frequencies; these include ADRs documented in clinical trials and those from post-marketing reports. Cernevit was

administered during 3 clinical trials to 267 adult patients requiring a parenteral vitamin supplement.

Frequencies of ARs are reported, using the following convention: 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); and unknown (cannot be estimated

from the available data).

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Clinical Trial and Post-Marketing Adverse Drug Reactions Reported for Cernevit:

The frequency either cannot be determined or the overall number of patients in the individual studies is too

small to permit a valid estimation of frequency.

No symptoms of hypervitaminosis A were reported

Elevated plasma vitamin A levels have been reported in 8 of 20 patients receiving Cernevit in parenteral

nutrition at day 45 of administration. From day 45 to day 90 of product administration the high values of

vitamin A remained stable (maximum observed value of 3.6 µmol/L at day 90; normal values: 1 to 2.6 µmol/L).

In addition, an average increase in retinol binding protein (RBP) was also identified. A maximum observed

RBP value of 60 mg/L at day 90 (normal values: 30 to 50 mg/L), was reported.

Isolated alanine aminotransferase increases was reported in the presence of inflammatory bowel disease.

Cernevit was administered by intravenous injection in the absence of parenteral nutrition.

An increase in total and individual bile acids including glycocholic acid has been reported to develop early in

the course of parenteral nutrition administration in patients receiving Cernevit.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued

monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any

suspected adverse reactions via

HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2. el: +353 1 6764971; Fax: +353 1 6762517. ebsite:

www.hpra.ie; E-mail: medsafety@hpra.ie.

System Organ Class

Preferred MedDRA Term

Frequency

Immune system disorders

Systemic hypersensitivity reactions with

manifestations such as respiratory

distress, chest discomfort,

throat

tightness, urticaria, rash, erythema,

epigastric discomfort, as well as cardiac

arrest with fatal outcome anaphylactic

reaction

Unknown

Metabolism and nutrition

disorders

Vitamin A increased

Retinol binding protein increased

Unknown

Nervous system disorders

Dysgeusia (metallic taste)

Unknown

Cardiac disorders

Tachycardia

Unknown

Respiratory, thoracic and

mediastinal disorders

Tachypnea

Unknown

Gastrointestinal disorders

Nausea

Vomiting

Uncommon

Diarrhoea

Unknown

Hepatobiliary disorders

Transaminases increased,

Isolated alanine aminotransferase

increased

, Glutamate dehydrogenase

increased, lood alkaline phosphatase

increased, ile acids increased

Gamma-glutamyltransferase increased

Unknown

Skin and subcutaneous

tissue disorders

Pruritus

Unknown

General disorders and

administration site

conditions

Injection/Infusion Site Pain

Common

Pyrexia,

Generalized aching,

infusion site reactions, i.e., burning

sensation, rash

Unknown

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4.9 Overdose

Acute or chronic overdose of vitamins (in particular A, B6, D, and E) can cause symptomatic hypervitaminosis.

The risk of overdose is particularly high if a patient receives vitamins from multiple sources and overall

supplementation of a vitamin does not match the patient’s individual requirements, and in patients with increased

susceptibility to hypervitaminosis (see Section 4.4).

Treatment of vitamin overdose usually consists of withdrawal of the vitamin and other measures as clinically indicated.

See also Section 4.5.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Balanced association of all water soluble and fat soluble, vitamins essential for the metabolism of the adult and the

child aged over 11 years, with the exception of Vitamin K.

5.2 Pharmacokinetic properties

Not applicable.

5.3 Preclinical safety data

Not applicable.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Glycine

Glycocholic acid

Soybean phosphatides

Sodium hydroxide (for pH adjustment)

Hydrochloric Acid (for pH adjustment)

6.2 Incompatibilities

Additives may be incompatible with parenteral nutrition containing Cernevit.

Do not add other medicinal products or substances without first confirming their compatibility and the stability of

the resulting preparation.

If co-administration of drugs that are incompatible at the Y-site is necessary, administer via separate IV lines.

Vitamin A and thiamine in Cernevit may react with bisulfites in parenteral nutrition solutions (e.g., as a result of

admixtures) leading to degradation of vitamin A and thiamine.

An increase in pH of a solution may increase the degradation of some vitamins. This should be considered when

adding alkaline solutions to the admixture containing Cernevit.

Folic acid stability can be impaired with increased calcium concentrations in an admixture.

Numerous other incompatibilities between vitamins and other medicinal products, including certain antibiotics,

and trace elements have been described.

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Refer to appropriate compatibility references and guidelines as needed.

6.3 Shelf life

Unopened: 2 years

Once reconstituted: Chemical and Physical in-use stability has been demonstrated for Cernevit for 24 hours at 25°C

when reconstituted with 5ml of Water for Injections.

From a microbiological point of view, the product should be used immediately.

If not used immediately, in use storage times and conditions prior to use are the responsibility of the user and would

normally not be longer than 24 hours at 2 to 8°C, unless reconstitution/dilution etc has taken place in controlled and

validated aseptic conditions.

6.4 Special precautions for storage

Do not store above 25°C.

Keep the vial in the outer carton.

6.5 Nature and contents of container

Type I Ph.Eur. brown glass vial with an elastomer stopper containing an orange-yellow sterile cake of powder.

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

Not all pack sizes may be marketed.

6.6 Special precautions for disposal of a used medicinal product or waste materials derived from

such medicinal product and other handling of the product

Aseptic conditions must be followed during reconstitution and when used as part of an admixture in parenteral

nutrition.

Reconstitution - Using a syringe, inject 5ml of water for injections into the vial.

Mix gently to dissolve the lyophilised powder.

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

Do not use unless the reconstituted solution is clear, the original seal is intact and the container is undamaged.

Dilution - Cernevit can be diluted in a solution of 5% glucose or 0.9% sodium chloride solution for infusion or

included in the composition of nutritive mixtures carbohydrates, lipids, amino acids and electrolytes provided that

compatibility and stability have been confirmed for each nutritive mixture.

After addition of Cernevit to a parenteral nutrition solution or other compatible intravenous solution, check for any

abnormal color change and/or the appearance of precipitates, insoluble complexes, or crystals.

Mix the final solution thoroughly when Cernevit is used as an admixture in parenteral nutrition.

For single use only.

Any unused portion of reconstituted Cernevit should be discarded and should not be stored for

subsequent admixing.

Parenteral drug products should be inspected visually for particulate matter and abnormal discoloration prior to

administration, whenever solution and container permit.

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To reduce the risk of particulate matter, a 0.2 micron filter should be used during administration of non-lipid

containing parenteral nutrition solutions and a 1.2 micron filter should be used for the delivery of lipid-containing

emulsions.

7 MARKETING AUTHORISATION HOLDER

Baxter Healthcare Ltd.

Caxton Way

Thetford

Norfolk

IP24 3SE

United Kingdom

8 MARKETING AUTHORISATION NUMBER

PA0167/097/001

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 04 January 1993

Date of last renewal: 04 January 2008

10 DATE OF REVISION OF THE TEXT

July 2018

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