Leaflet VEDROP 50mg / ml oral solution
Indicated for: vitamin E deficiency
Route of administration: oral
Substance: tocopherol (vitamin)
ATC: A11HA08 (Alimentary tract and metabolism | Other plain vitamin preparations)
Tocopherol, also known as vitamin E, is an essential antioxidant that helps maintain cellular health and protects the body against oxidative stress. It neutralizes free radicals, preventing damage to lipids, proteins, and DNA.
Tocopherol is available as oral supplements or included in various food and cosmetic products. It is used to support skin health, immune function, and cardiovascular health.
Side effects are rare but may include nausea, diarrhea, or gastric discomfort when taken in high doses. In very rare cases, overdose can lead to coagulation disorders. It is important for patients to follow the recommended dosage provided by their doctor or the manufacturer.
Tocopherol is an essential nutrient for overall health, contributing to the prevention of premature aging and protecting the body from the harmful effects of oxidative stress.
General data about VEDROP 50mg / ml
- Substance: tocopherol
- Date of latest medicines list: 01-01-2019
- Product code: W54567002
- Concentration: 50mg / ml
- Pharmaceutical form: oral solution
- Packing volume: 20 ml
- Product type: Original
- Prescription status: P-RF - Medicines dispensed with a medical prescription that is retained by the pharmacy and cannot be renewed.
Pharmaceutical forms available for tocopherol
Concentrations available for tocopherol
- 100mg
- 200mg
- 30mg/ml
- 400mg
- 50mg/ml
Leaflet VEDROP 50mg/ml
Contents of the package leaflet for the medicine VEDROP 50mg / ml oral solution
1. NAME OF THE MEDICINAL PRODUCT
Vedrop 50 mg/ml oral solution
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each ml contains 50 mg of d-alpha-tocopherol, in the form of tocofersolan, corresponding to 74.5 IU oftocopherol.
Excipients:Each ml contains 6 mg sodium methyl parahydroxybenzoate (E219), 4 mg sodium ethylparahydroxybenzoate (E215) and 0.18 mmoles (4.1 mg) of sodium.
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Oral solution.
Slightly viscous, pale yellow solution.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Vedrop is indicated in vitamin E deficiency due to digestive malabsorption in paediatric patients withcongenital chronic cholestasis or hereditary chronic cholestasis, from birth (full term newborns) up to 18years of age.
4.2 Posology and method of administration
The treatment with Vedrop should be initiated and supervised by a physician experienced in themanagement of patients suffering from congenital chronic cholestasis or hereditary chronic cholestasis.
Bioavailability of vitamin E from Vedrop differs from that of other medicinal products. The dose should beprescribed in mg of d-alpha-tocopherol in the form of tocofersolan. Plasma vitamin E level should bemonitored monthly for at least the first few months of therapy, thereafter at regular intervals and the doseadjusted accordingly if necessary.
PosologyThe recommended total daily dose in paediatric patients suffering from congenital chronic cholestasis orhereditary chronic cholestasis is 0.34 ml/kg/day (17 mg/kg of d-alpha-tocopherol in the form oftocofersolan). The dose should be prescribed in ml.
The dose should be adjusted according to plasma vitamin E level.
To calculate the dose of Vedrop to be administered, divide the prescribed dose of d-alpha-tocopherol (in mg)by 50. The result is the volume of Vedrop in ml:
Dose of Vedrop (in ml) = dose of d-alpha-tocopherol (in mg)
The following table gives the volume of oral solution in function of patients’ weights.
Weight (kg) Oral solution volume (ml)3 1.04 1.45 1.76 2.07 2.48 2.79 3.110 3.415 5.1
Special populationsHepatic or renal impairment
Experience with tocofersolan therapy in patients with renal impairment or underlying liver impairment hasdemonstrated no need to adapt the dose regimen of Vedrop (see section 4.4).
Method of administrationVedrop is administered orally with or without water. The 1-ml or 2-ml oral syringes included in thecontainer are designed to assist in measuring out the exact dose in accordance with the prescribed posology.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Vedrop must not be used in preterm newborn infants.
4.4 Special warnings and precautions for use
As large doses of vitamin E have been reported to increase bleeding tendency in vitamin-K deficient patientsor those taking oral anti-vitamins K treatment, it is therefore recommended to monitor the prothrombin timeand international normalised ratio (INR). A possible adjustment of the dose of oral anticoagulant during andafter treatment with Vedrop may be necessary.
As data on patients with renal impairment are limited, Vedrop should be administered with caution andunder close monitoring of the renal function in patients with renal impairment e.g. dehydrated patients (seesection 4.2).
Vedrop should be administered with caution in patients with underlying liver impairment and under closemonitoring of the hepatic functions in such patients (see section 4.2).
Vedrop contains sodium methyl parahydroxybenzoate (E219) and sodium ethyl parahydroxybenzoate(E215) which may cause allergic reactions (possibly delayed).
This medicinal product contains sodium. It should be taken into consideration by patients on a controlledsodium diet.
4.5 Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed.
It is recommended to monitor the coagulation function when administered with anti-vitamins K treatment(see section 4.4).
Due to inhibition of P-Glycoprotein transporter, tocofersolan may also enhance intestinal absorption of otherconcomitant fat-soluble vitamins (A, D, E, K) or that of highly lipophilic medicinal products (such assteroids, antibiotics, antihistamines, cyclosporine, tacrolimus). Therefore, monitoring should be performedand, when necessary, doses should be adjusted.
4.6 Fertility, pregnancy and lactation
For tocofersolan no clinical data on exposed pregnancies are available. Animal studies do not indicate director indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or post-natal development (see section 5.3). Caution should be exercised when prescribing to pregnant women.
Breast-feedingIt is unknown whether tocofersolan is excreted in human breast milk. The excretion of tocofersolan in milkhas not been studied in animals. A decision on whether to continue/discontinue breast-feeding or tocontinue/discontinue therapy with Vedrop should be made taking into account the benefit of breast-feedingto the child and the benefit of tocofersolan therapy to the woman.
FertilityNo data is available
4.7 Effects on ability to drive and use machines
Vedrop has no or negligible influence on the ability to drive and use machines.
4.8 Undesirable effects
The most commonly reported adverse reaction during treatment is diarrhoea.
Tabulated list of adverse reactionsReported adverse reactions are listed below, by system organ class and by frequency.
Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to< 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from theavailable data).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
System organ class Adverse reactions
Gastrointestinal disorders Common: diarrhoea
Not known: abdominal pain
Skin and subcutaneous tissue disorders Uncommon: alopecia, pruritus, rash
General disorders and administration site Uncommon: asthenia, headacheconditions
Investigations Uncommon: serum sodium abnormal, serum potassiumabnormal, transaminases increase
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allowscontinued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals areasked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
4.9 Overdose
Large vitamin E doses may cause diarrhoea, abdominal pain, and other gastrointestinal disturbances.
In case of overdose, a symptomatic treatment should be proposed.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Vitamins, Other plain vitamin preparations; ATC code: A11HA08
Vitamin E is the principal lipo-soluble antioxidant in the organism. It acts as a free radical chain breakingmolecule, stopping the peroxidation of polyunsaturated fatty acids and it is involved in maintaining thestability and integrity of cell membranes.
This medicinal product has been authorised under “exceptional circumstances”. This means that due to therarity of the disease it has not been possible to obtain complete information on this medicinal product.
The European Medicines Agency will review any new information which may become available every yearand this SmPC will be updated as necessary.
5.2 Pharmacokinetic properties
The active substance d-alpha-tocopherol-polyethylene glycol 1000 succinate (tocofersolan) is a pro-drug; theactive metabolite is the d-alpha-tocopherol. At low concentrations, tocofersolan forms micelles whichenhance absorption of non-polar lipids such as fat-soluble vitamins. Its critical micellar concentration is low(0.04 to 0.06 mmol/l).
The hydrolysis of tocofersolan occurs in the gut lumen. Taken up by cells, the alpha-tocopherol moietyappears in chylomicrons in the lymph in a manner identical to vitamin E absorbed from the diet. Cellularuptake does not require receptors, binding proteins or metabolic processes and does not occur bypinocytosis. Absorption of deuterated tocofersolan showed a normal pattern in lipoproteins: alpha-tocopherol peaked first in chylomicrons, then in very low- density lipoproteins (VLDL) and finally in low-density lipoproteins (LDL) and high-density lipoproteins (HDL), and the disappearance portions of thecurves paralleled those in control subjects.
A study in 12 healthy volunteers compared tocofersolan with a water-miscible reference vitamin E after asingle oral loading dose of 1200 IU. The relative bioavailability of tocofersolan tended to be higher (Frel of1.01 ± 1.74) with AUC0-t of 0.383 ± 0.203µM.h/mg, Cmax of 0.013 ± 0.006, tmax of 6.0 h (6.0 - 24.0), and t1/2of 29.7 h (16.0 - 59.5).
In a similar study tocofersolan showed a higher bioavailability than a water-miscible reference vitamin E inpaediatric patients with chronic cholestasis (n=6), absorption was significantly higher on both plasmaconcentration maximum increase (p=0.008) and AUC (p=0.0026).
DistributionLocated principally on cell membranes, within mitochondria and microsomes, vitamin E is ubiquitouslydistributed (red blood cells, brain, muscle, liver, platelets) and fat tissues are its major reservoir.
EliminationVitamin E is mainly eliminated in the bile (75%) and stools, either as free tocopherol or as oxidized forms.
Urine represents a minor elimination route of vitamin E (as glucuro-conjugate).
5.3 Preclinical safety data
Non-clinical data in the literature reveal no special hazard for humans based on conventional studies ofrepeated dose toxicity, genotoxicity and toxicity to reproduction.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Potassium sorbate
Sodium methyl parahydroxybenzoate (E219)
Sodium ethyl parahydroxybenzoate (E215)
Glycerol
Disodium phosphate dodecahydrate
Concentrated hydrochloric acid
Purified water
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinalproducts.
6.3 Shelf life
2 years.
After first opening the bottle: 1 month.
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
Type III brown glass bottle with a child-resistant screw cap of HDPE and LDPE seal. Oral syringes withhousing of LDPE and piston of polystyrol. Each bottle contains 10 ml, 20 ml or 60 ml of oral solution.
Boxes containing: one 10 ml bottle and one 1 ml oral syringe one 20 ml bottle and one 1 ml oral syringe one 60 ml and one 2 ml oral syringe
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
Doses for administration should be extracted from the bottle using the oral syringes which are provided inthe pack.
The 1 ml oral syringe is graduated from 0.05 to 1 ml in steps of 0.05 ml. One graduation of the 1 ml oralsyringe corresponds to 2.5 mg of d-alpha-tocopherol in the form of tocofersolan.
The 2 ml oral syringe is graduated from 0.1 to 2 ml in steps of 0.1 ml. One graduation of the 2-ml oralsyringe corresponds to 5 mg of d-alpha-tocopherol in the form of tocofersolan.
10. DATE OF REVISION OF THE TEXT
Detailed information on this medicinal product is available on the website of the European Medicines
Agency http://www.ema.europa.eu