PATIENT INFORMATION LEAFLET
HEBERPROT-P 75 µg vial containing lyophilised powder for injection
Sterile, Apyrogen
Applied to the wound and to the wound environment.
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Active ingredient: Recombinant Human Epidermal Growth Factor (rhEGF)
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Excipients: Sucrose, Dextran 40, Disodium hydrogen phosphate, Sodium dihydrogen
phosphate dihydrate, Water for injection
This medicine is subject to additional monitoring. This will allow quick identification of
new safety information. You can help by reporting any side effects you may get. See the end
of section 4 for how to report side effects.
Read all of this LEAFLET carefully before you start taking this medicine 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 or pharmacist..
 This medicine has been prescribed for you only. Do not pass it on to others.
 If you go to a doctor or a hospital during your therapy with this medicine, tell your doctor
that you use this drug.
 Exactly follow the instructions in this leaflet. Do not use higher or lower doses than
recommended
In this leaflet:
1. What HEBERPROT-P is and what it is used for
2. What you need to know before you take HEBERPROT-P
3. How to take HEBERPROT-P
4. Possible side effects?
5. Storing HEBERPROT-P
1. What HEBERPROT-P is and what it is used for
HEBERPROT-P is indicated in the treatment of patients with gangrene-free, open diabetic
foot ulcers whose osteomyelitis (a type of bone infection) and infection has been treated.
HEBERPROT-P is a white freeze-dried powder. It is used by reconstituting with 5 mL water
for injection. Each package contains 1 or 6 vials.
2. What you need to know before you take HEBERPROT-P
DO NOT take HEBERPROT-P
If
 you are hypersensitive to this product or its excipients
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sign of cancer is present near the injection site of HEBERPROT-P
you have malignant illness or if it is suspected
you have a severe condition related to diabetes (diabetic coma or diabetic ketoacidosis)
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you have experienced acute cardiovascular events such as acute heart attack, severe chest
pain, acute stroke or transitory ischaemia or thromboembolic events in the last two months
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you have severe congestive heart failure or severe heart rhythm disorder (atrioventricular
block, atrial fibrillation)
Take special care with HEBERPROT-P
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If you have a history of significant valvular disease, severe hypertension or venous
trombosis (forming of blood clot inside the vein)
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If you have a history of acute cardiovascular event such as heart attack, stroke or transient
ischemic attack or thromboembolism (obstruction of vein by the blood clot)
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If you have a history of kidney failure. If your creatinine levels are above 200 micromol/L
If these warnings are applicable for you, even for any period in the past, consult your doctor.
Taking HEBERPROT-P with food and drink
HEBERPROT-P is not used orally. It is injected into the wound or to the environment of the
wound. Therefore, foods and drinks taken concomitantly doest not affect HEBERPROT-P.
Pregnancy
Consult your doctor or your pharmacist before taking this medicine.
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HEBERPROT-P has not been tested in pregnant woman.
Tell your doctor if you are pregnant, if you think you are pregnant, or if you plan to
become pregnant. Your doctor will decide whether you should take this drug.
If you notice that you are pregnant during your treatment, consult your doctor or your
pharmacist immediately.
Breast-feeding
Consult your doctor or your pharmacist before taking this medicine.
It is not known whether HEBERPROT-P passes to mother’s milk. Therefore, it is not
recommended for nursing mothers.
Consult your doctor if you are a nursing mother or if you plan breastfeeding. Your doctor will
decide whether you should discontinue breastfeeding or treatment.
Driving and using machines
There are no reported effects on ability to drive and use machines.
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Important information about some of the ingredients of HEBERPROT-P
HEBERPROT-P contains 0.454 mg disodium hydrogen phosphate and 1.061 mg sodium
dihydrogen phosphate dihydrate as excipients. This medicinal product contains less than 1
mmol sodium (23 mg) per each ml, i.e. essentially ‘sodium- free’.
Using other medicines
It is not known whether HEBERPROT-P interacts with other topical medications. Therefore,
its use is not recommended with other topical products.
Inform your doctor or pharmacist if you are taking or have recently taken any other
prescription or non-prescription medicines.
3. How to take HEBERPROT-P?
HEBERPROT-P treatment must be performed especially by a specialized personnel that has
sufficient experience in the treatment of diabetic foot.
Instructions for appropriate use and dose/frequency of administration
HEBERPROT-P should be applied in doses of 75 µg dissolved in 5 ml of water for injection,
thrice weekly, through perilesional and intralesional route. Applications should be continued
until complete wound granulation, lesion closing by grafting or until a maximum period of 8
weeks of treatment is being reached. Duration of treatment is maximum 12 weeks. The
treatment should be discontinued when successful granulation tissue for wound closure is
obtained or a reduction of the wound area to less than 1 cm2 is achieved.
If useful tissue granulation is not observed in the ulcer after 3 weeks of continuous treatment,
your doctor will re-evaluate your treatment and consider other factors that affect wound
healing, such as osteomyelitis (a type of bone infection), local infections or metabolic
imbalance.
Route and method of administration:
In diabetic foot ulcers, HEBERPROT-P should always be administered together with
standardized care. Infarct area should be properly cleaned, pressurised areas should be
depressurised and a regular treatment should be administered. A suitable infection treatment
should be performed before starting to use HEBERPROT-P. In the case of suspected malign
lesions, biopsy should be taken before HEBERPROT-P use, to exclude the prescence of
cancer.
If you have additional questions about the use of this medicine ask your doctor, nurse or
pharmacist.
Use in children:
There are no sufficient data on the use of HEBERPROT-P in children. Risk/benefit balance
should be evaluated in each individual case.
Use in elderly:
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Posology and method of administration of HEBERPROT-P in elderly patients are similar to
that in adults.
Renal / hepatic impairment:
Caution should be taken in patients with a history of renal insufficiency and in patients with
creatinine levels above 200 micromol/L. Dose may be reduced to 25µg when needed.
There are no sufficient data on the use of HEBERPROT-P in patients with liver failure.
Risk/benefit balance should be evaluated in each individual case.
Talk to your doctor or pharmacist if you have an impression that the effect of HEBERPROT-P
is too strong or too weak.
If you take more HEBERPROT-P than you should:
If you take more HEBERPROT-P than you should, tell your doctor or pharmacist.
If you forget to take HEBERPROT-P
Do not take a double dose to make up the forgotten dose.
Possible effects after discontinuation of HEBERPROT-P
Do not discontinue treatment without consulting your doctor. If you have other problems on
the use of this medicine, ask you doctor.
4. Possible side effects?
Like all medicines, HEBERPROT-P can cause side effects in patients having sensitivity to its
ingredients. However, this does not mean that everybody gets them.
Side effects are listed in categories shown below:
Very common: Affects more than 1 users out of 10.
Common: Affects 1-10 users out of 100.
Uncommon: Affects 1-10 users out of 1000.
Rare: Affects 1-10 users out of 10000.
Not known: frequency cannot be estimated from the available data.
If you get any of following side effects, stop taking HEBERPROT-P and contact your doctor
or go to the emergency room of the nearest hospital:
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Anaphylactic shock (sudden swelling of the face, neck, lips and mouth. This may
cause shortness of breath and difficulty to swallow. Sudden swelling of the hands, feet
and ankles)
Shortness of breath or difficulty in breathing
You may require immediate medical treatment or hospitalization.
These very serious side effects are all very rare.
Tell your doctor if you notice any of the following side effects:
Very common:
 Burning sensation and pain at the site of injection
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Shivering
Chills
Common:
 Bleeding at the site of injection
 Anaemia
 Headache
 Nausea
 Vomiting
 Diarrhea
 Fever
 Swelling due to fluid accumulation (edema)
 Local infection
 Worsening of the disease
 Pain in the affected foot
Uncommon:
 Local blood accumulation (hematoma)
 Inflammation of the lymph vessel (lymphangitis)
 Swelling due to fluid accumulation in the lymph vessels, resulting from the
inflammation of the extremity
 Decrease in white blood cell count (leucopenia)
 Decrease in blood clotting cell count (thrombocytopenia)
 Increase in blood-platelet
 Decrease in hemoglobin
 Fungi on the skin (epidermophytosis)
 Decrease in blood sugar (hypoglycemia)
 Weight gain
 Increase in blood uric acid
 Increase in cholestrol and triglyceride
 Increase in glicosylated hemoglobin
 Insomnia or somnolence
 Depression
 Numbness of fingers
 Anorexia
 Pain and cramps in the lower extremity (foot, knee, ankle, hip)
 Dizziness
 Drowsiness
 Black-out
 Numbness
 Cramps in the affected extremity
 Pain and pressure sensation on the shoulder and on the lower area of the collar bone
 Loss of strength
 Immobility and tingling in toes
 Stinging sensation during the administration
 Facial paralysis
 Acute viral inflammation of the eye (conjunctivitis)
 Itching, redness and swelling of the eye
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Chest pain
Hypertension and hypotension
Ischemic cardiac disease (impairment of the blood-feeding of the heart)
Heart attack (acute myocardial infarctus)
Increase in the number of heart beat (tachycardia)
Inflammation of the veins (phlebitis)
Rash
Increased local temperature of the affected limb
Flu-like symptoms (Kataral syndrome)
Inflammation of the respiratory tract and the lungs (bronchopneumonia)
Shortness of breath
Bloody phlegm (hemoptysis)
Inflammation of the lungs (pneumonia)
Severe inflammation of the respiratory tract (respiratory sepsis)
Frequent colds
Feeling of fullness in the ear
Cough
Sore throat
Increase in the acidity of the gastrointestinal tract
Heartburn
Indigestion (dyspepsia)
Pain in the upper abdominal area and abdominal pain
Painful and bloody defecation
Constipation
Bowel inflammation (enterocolitis)
Toothache
Digestive problems
Increased transaminases
Increased glutamic pyruvic transaminase (GPT)
Forming of excessive healing tissue (hypergranulation)
Hardening of the muscles surrounding the shoulder (deltoid muscle)
Redness on the skin (erythema)
Discoloration of the toes
Blueish-pink colour of the toes with itching and burning sensation
Scabies
Boil
A disease caused by fly larva (myiasis)
Purulent inflammation of the sculp (pyoderma)
Rash
Skin inflammation (dermatitis)
Thickening of the walls of scar tissue
Pruritus
Skin peel
Excessive sweating
Nail inflammation (paronychia)
Nail loss
Traumatic congestion in the hip
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Pain in the bones and joints
Pain in the back, waist and hip
Cramps
Knee trauma
Kidney failure
Urinary tract inflammation (cystitis)
Increased creatinine
Interdigital mycosis
Buttock abscess
Swelling due to fluid accumulation in ankles, elbows and face
Allergic reactions (i.e. itchy rash, shortness of breath and swelling of the face or
tongue)
Shock
pale finger where the injury is located
Slight fever
Feeling of chest tightness
Transitory hypotension (vagal reaction)
Increase erythrocyte sedimentation rate
Fainting (lipothymia)
Bacterial infection (cellulitis)
Pain at resting
Fetid lesion
Pain in the lesion
Fatigue
Condition characterised by the decrease in body temperature (hypothermia)
Seizure (convulsion)
Uncontrolled hypertension
Excessive fluid accumulation in the lungs (acute pulmonary edema)
Yawning
Respiratory distress syndrome
Last stage (decompensated) chronic kidney disease
Sight impairments due to inflammation of the inner layers and iris muscles of the eye
(still disease)
Rare:
 Leg pain
 Black out with sweating and feeling faint, due to stimulation of the vagus nerve (vagal
crisis)
 Pallor
 Sphincter relaxation
 Tooth decay
 Bones vulnerable to conditions such as tissue loss and inflammation (bone exposure)
 A serious condition that can cause multiple organ failure and death due to severe
infection in the body and in the blood (septic shock)
 Incoherent speech
 Muddle speech
 Loss of stability
 Upper gastrointestinal bleedings
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Acute inflammation of the gastrointestinal tract (gastroenterocolitis)
Dry mouth
Cardiac arrest
Occlusion in veins of the lungs (pulmonary embolism)
Blue-purple colour of the hands and feet due to oxygen shortage
Blueish-pink colour of the skin with itching and burning sensation
Stroke caused by the embolisation of the veins to the brain (ischemic stroke)
Palpitation
Cardiac arrest
Failure of the heart in providing the needs, especially oxygen needs, of the tissues
(decompensated heart failure)
Insufficient blood in the organs due to irregular and fast heart rhythm (ventricular
fibrillation)
Swelling of the larynx mucosa characterised by cough, hoarseness and difficulty in
breathing (glottis edema)
Respiratory failure
Severe condition of diabetic patients characterised by excessive acid accumulation in
the blood in the fasting state (diabetic ketoacidosis)
Thirst
Purplish rash
Increased serum glutamic pyruvic transaminase (SGPT) enzyme
If you notice any side effects not listed in this leaflet, please inform your doctor or
pharmacist.
Reporting of the side effects
If you get any side effects listed or not listed in this leaflet, contact your doctor, pharmacist or
nurse. You can also report side effects you experienced directly to Turkish Pharmacovigilance
Center (TUFAM) by clicking “Drug Side Effect Reporting” icon on www.titck.gov.tr or by
calling side effect reporting line at 0 800 314 00 08. By reporting side effects, you help to
provide more information on the safety of this medicine.
5. Storing HEBERPROT-P
Keep HEBERPROT-P out of reach and sight of children and store in its package.
Store in the fridge between 2 to 8°C.
HEBERPROT-P should be used immediately after first opening and reconstitution.
Do not freeze. Do not defrost and do not use the frozen product.
Store in its original packaging.
Use in accordance with the expiration dates.
Do not use HEBERPROT-P after the expiry date stated on the label or packaging.
As a measure to help protecting the environment, do not throw away HEBERPROT-P via
wastewater or household waste. Ask your pharmacist how to throw away medicines you no
longer use.
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Marketing authorization holder: Hasbiotech İlaç San. ve Tic.A.Ş.
Hacılar / Kayseri
Manufacturer: Centro de Ingenieria Genetica y Biotecnologica (CIGB)
Havana/Küba.
Praxis Pharmaceutical SA Vitoria/İspanya
This leaflet was approved on 05.11.2014.
FOLLOWING INFORMATION IS FOR THE HEALTHCARE PERSONNEL TO
APPLY THIS MEDICINE
Each vial of HEBERPROT-P is for the same patient only.
Care should be taken to avoid deterioration and bacterial contamination of vials.
Product should be used after proper cleaning of the hands and after wearing sterile gloves.
Care should be taken to avoid dissemination of the infections in the lesions. It is
recommended to change the needles when HEBERPROT-P is injected in different parts of the
lesion.
Once the treatment is finished the remaining product should be discarded.
Needle 23Gx1½”
Needle 23Gx1½”
Needle 26Gx1½”
Needle 24Gx1½”
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