Recombinant Human Epidermal Growth Factor (rhEGF)

Registered South African indications:

• Chronic advanced infection free diabetic foot ulcers

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy
• Breastfeeding
• Severe renal impairment  
  - Serum creatinine >200μmol/L
• Severe hepatic impairment (Child-Pugh Class C)
• Acute cardiovascular events (e.g. acute myocardial infarction, severe angina, acute stroke or transitory ischaemia) in the previous two months
• Thromboembolic events in the previous two months
• Severe congestive heart failure (NYHA III and IV)
• Severe atrial-ventricular block (grade III)
• Atrial fibrillation with uncontrolled rhythm
• Personal history or suspicion of malignancies
• Diabetic coma
• Diabetic ketoacidosis

Cautions

• Mild to moderate renal impairment
• Mild to moderate hepatic impairment (Child-Pugh Classes A&B)
• Elderly
• Ischaemic ulcers
• Pressure to the ulcer area during the treatment and healing period
• Infection
  - Infection of the ulcer and/or the exposed anatomical structures inside the ulcer
• Uncontrolled chronic disease, including cardiac failure and pulmonary failure
• Osteomyelitis
• Ischaemia due to peripheral macroangiopathy
• Haemoglobin levels <10g/dL
• History of underlying neurological or psychiatric disease
• History of acute cardiovascular events such as myocardial infarction, stroke or transient ischemia or thromboembolism
• Clinically significant valvular disease (i.e. calcified aortic valves)
• Severe hypertension
• History of venous thrombosis
• Diabetes mellitus
• Fructose intolerance
• Glucose-galactose malabsorption
• Sucrase-isomaltase insufficiency
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: inj 

Chronic advanced infection free diabetic foot ulcers 
- Wagner classification grades 3 or 4, or ulcer size of >1cm² with either a neuropathic and/or ischaemic component, to promote the formation of granulation tissue to allow for skin grafting and/or healing
- In hospitalised and well controlled diabetic patients who have failed other treatment options and are at risk of an amputation

• Intralesional (inj): 75μg, three times per week; Treatment duration: ≤8 weeks

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Use in combination with appropriate and meticulous wound and ulcer care practices to ensure an infection free ulcer

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Debridement of the lesions should be done if needed and pressure on the ulcer area should be avoided during the treatment and healing period

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Continue administration until complete granulation of the lesion is achieved, there is lesion closure by grafting, or a maximum of 8 weeks of treatment has been reached

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Discontinue treatment when granulation tissue covers the whole extent of the lesion or there is a reduction to <1cm² of the area is achieved (See additional prescribing points)

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Additionally, the treatment should be discontinued after 3 weeks of uninterrupted treatment if no useful granulation tissue has developed on the ulcer bed. Re-evaluation of the treatment and factors that could delay healing (such as osteomyelitis, local infection and metabolic unbalance) should be considered

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Injection vials should be diluted before use (See additional prescribing points)

Not established for use in children below 18 years

Pregnancy

• Contraindicated
• Recombinant human epidermal growth factor (rhEGF) should not be used during pregnancy
• Effective contraception must be used in women of childbearing potential as the potential risk to humans is unknown

Breastfeeding

• Contraindicated
• Recombinant human epidermal growth factor (rhEGF) should not be used whilst breastfeeding

Renal Impairment

• Mild to moderate: Caution; no information available
• Severe: Contraindicated
  The use of recombinant human epidermal growth factor (rhEGF) is contraindicated in patients with a serum creatinine of >200μmol/L

Hepatic Impairment

• Mild to moderate (Child-Pugh Classes A&B): Caution; no information available
• Severe (Child-Pugh Class C): Contraindicated

Elderly

• Caution; no information available 

Drugs in Sport

• Prohibited - At all times

Central Nervous System Disorders

• Headache
• Dizziness
• Loss of consciousness
• Seizures
• Incoherent speech
• Stability loss
• Muddle speech
• Fatigue

Cardiovascular Disorders

• Chest pain
• Decompensated hypertension
• Acute myocardial infarction
• Tachycardia
• Acute pulmonary oedema
• Sudden cardiac death
• Pulmonary embolism
• Distal cyanosis
• Ischaemic stroke
• Palpitations
• Cardiac arrest
• Decompensated heart failure
• Ventricular fibrillation
• Crisis vagal
• Generalised erythro-cyanosis

Respiratory Disorders

• Yawning
• Dyspnoea
  - Contraction of the thorax muscle with dyspnoea
• Respiratory distress
• Glottis oedema
• Respiratory failure

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea
• Desire to defecate
• Epigastric pain
• Upper gastrointestinal bleeding
• Acute gastro-enterocolitis
• Dry mouth
• Abdominal pain

Hepatobiliary Disorders

• Increased serum glutamic pyruvic transaminase (SGTP)

Genitourinary Disorders

• Decompensated chronic kidney disease

Endocrine and Metabolic Disorders

• Hypoglycaemia
• Diabetic ketoacidosis
• Thirst
• Chills
• Hypothermia
• Shivering

Musculoskeletal Disorders

• Low back pain
• Cramp

Skin and Subcutaneous Tissue Disorders

• Myiasis
• Pruritus
• Slough
• Profuse sweating
• Rash
• Pain at the injection site
• Burning sensation at the injection site
• Lesion pain
• Bleeding at the injection site
• Cellulitis
• Pallor
• Decay

Immune, Blood and Lymphatic System Disorders

• Local infection
• Septic shock
• Acute lymphangitis  
• Anaemia
• Purplish rash
• Anaphylactic reaction
• Fever

Others

• Worsening of disease
• Fainting
• Leg pain
• Bone exposure

• Topical medicines (See additional prescribing points)

• Haemoglobin level

Some cases may require

• Serum creatinine
• Blood glucose

Additional administration directions

• After the treatment is complete, the infiltrations should continue into the edges of the ulcers with 26G x 1⁄2" needles. In the case of deep lesions, use 24G x 1 1⁄2" or 24G x 3⁄4", for effective deep penetration of the lesion
• Initially, the cleanest zones of the lesions should be infiltrated (required needle changes are necessary to prevent the possibility of transmission of infection from one area to another within the lesion). The lesion must be covered afterwards with 0.9% sodium chloride dampened dressing gauze, ensuring a wet and clean environment in and around the lesion

Reconstitution instructions

• 75μg should be diluted in 5ml of Water for Injection (WFI) immediately before intralesional injection
• WFI should be injected into the vial and the vial swirled gently. Do not shake the vial

Instructions for handling

• Use each vial for the same patient only
• It is necessary to be careful to avoid deteriorations and bacterial contamination of the vials
• Health care professionals handling the product must wash their hands properly and wear sterile gloves before administration
• Care must be taken to avoid the dissemination of the infection in the lesions. A needle change (new needle) is recommended for each injection into different parts of the lesion
• After each treatment session, the unused portion of the reconstituted product must be discarded
• The reconstituted product must be used immediately and should not be stored

Coadministration with topical medicines

• It is not known if recombinant human epidermal growth factor (rhEGF) interacts with other topical medications and hence, its use is not recommended with other topical products

The mechanism of action of recombinant human epidermal growth factor (rhEGF) is based on an interaction with a glycoprotein located in the cell membrane of cells. This glycoprotein with tyrosine kinase activity possesses an extracellular binding domain, a transmembrane region and a cytoplasmic portion. The presence of these receptors has been reported in most human tissue, with a large amount in the skin. It stimulates the proliferation of fibroblasts as well as epithelial cells. It has in vivo mitogenic activity on the epidermal, vessel smooth muscular, fibroblasts and keratinocytes cells, among others. It regulates the growth, differentiation and metabolism of several cells and stimulates the migration and proliferation of fibroblasts, which allows collagen synthesis and deposit. It is also chemoattractant and mitogenic for endothelial and epithelial cells.

Injection (per 5ml) 75μg

• Heberprot-P (Kahma Biotech) originator