Drug Monograph

Heparin 50iu/ml Topical Gel

DESCRIPTION

Heparin is an ingredient of a topical gel which has been used for over 50 years and across 60 countries to reduce the appearance of new and old scars, including hypertrophic and keloid scars.

HOW SUPPLIED

Heparin is commonly compounded as a 50iu/ml Topical Gel.

CLINICAL PHARMACOLOGY

Heparin elicits a negative regulatory effect on collagen production through down-regulation of the pro-alpha1(I) of type I collagen gene, inhibiting polymerization of collagen loosening the collagen structure.1 Further to heparin’s ability to soften the tissue structure, it has anti-inflammatory and anti-swelling properties, supports cell and tissue regeneration. Heparin is also reported to relieve pain, reduce inflammation, prevent burn extension, and shorten healing, resulting in smooth and healed skin without scars or contractors. Heparin stimulates capillary endothelial cells to migrate into ischemic tissues where they multiply and form new capillary blood vessel systems which, on perfusion with blood, restore blood flow into the ischemic tissues. In response to heparin application, burn blisters, which are not removed and rarely become infected, function as natural skin grafts that require no further care. Reports show that smooth new skin is evident beneath the dried thin blister usually within 7-14 days.

CLINICAL EVIDENCE
Study 1 – Thoracic Surgery

Scar development was investigated in 45 young patients who underwent thoracic surgery. They were randomly assigned to either a group treated topically with a combination gel containing Heparin 50iu/ml or to a group receiving no treatment. Treatment began on average 26 days after surgery and was continued for one year. Scar development was assessed monthly by the physician and assessment included scar appearance, scar type, size, and color. A reduction of the increase of scar width was observed in the treatment group compared with the untreated group. Physiological scars and skin-colored scars were more frequent in the treated group than the untreated group. Hypertrophic or keloidal scars were less frequent in the treated group. No differences in scar length and scar height were seen.

At the end of the observation period, the clinical course of scar development was rated as "very good" or "good" in more than 90% of the treated patients, "good" in less than 40% and "moderate" or "bad" in more than 60% of the untreated cases. The tolerability of the drug was "good" or "very good" in all cases.2

Study 2 – Hypertrophic Scars

A multicenter, retrospective cohort study investigated the safety and efficacy of topical Heparin 50iu/ml gel on hypertrophic scars in routine out-patient practice and compared it to corticosteroid treatment. 771 patients were eligible for the per protocol treatment with Heparin 50iu/ml gel (n=555) and corticosteroid (n=216). At the end of defined treatment periods (minimum 28 days for local therapy with 1 intralesional corticosteroid application), normalization of the pre-treatment pathological parameters (erythema, pruritus, consistency) of hypertrophic scars was more frequent (42.5%) after Heparin 50iu/ml gel treatment as compared to corticosteroid treatment (22.2%). The time to normalization of erythema, pruritus and consistency was significantly (p=0.034) shorter with Heparin 50iu/ml gel treatment (median 344 days) than with corticosteroids (median 507 days). For the primary aim of this study (assessment of normalization of erythema, pruritus, and consistency of hypertrophic scars) and for time to normalization, local administration of Heparin 50iu/ml gel was significantly more effective than corticosteroid treatment.2

Study 3 – C-Section Scars

A total of 61 females, aged ≥18 years, who had given birth by elective C-section for the first time within the last 5-10 days, were included in this prospective, randomized, single-center study. Patients were advised to apply the topical scar gel twice daily (treatment group), or received no treatment (control group). Efficacy was evaluated at 6 and 12 weeks after a baseline visit using the Patient and Observer Scar Assessment Scale (POSAS), a validated scar assessment tool comprised of a Patient Scale and an Observer Scale. Analysis revealed a significant change in the POSAS Patient Scale total score, with a 14.2% improvement in the treatment group compared with a decline of similar magnitude (-14.8%) in the control group at week 6. Significant improvements were also seen for POSAS Patient Scale sub-items in the treatment group compared with the control group for scar color (13.6% vs -18.5%, respectively, P=0.0284), stiffness (12.5% vs -34.6%, respectively, P=0.0029), and irregularity (29.4% vs -46.2%, respectively, P=0.0140) after 6 weeks of treatment.4

INDICATIONS AND USAGE

Topical heparin gel has been clinically studied for the aesthetic appearance of various types of scars such as those resulting from burns and c-sections, in both keloid and hypertrophic scar formations.2,3,4,5

DOSING AND ADMINISTRATION

Apply to skin 2 to 3 times per day and gently massage in circular motion into the scar tissue until gel is absorbed. For best results, apply for at least 3 months on wound as soon as it is closed. In case of old hard scars, can also be applied overnight and covered with a bandage. For older scars, apply 3 times daily for minimum of 6 months.

Apply gel only to wounds that are already closed. Avoid contact with the eyes, the inside of the nose or mouth and other mucous membranes.

DRUG INTERACTIONS

Concurrent use of Heparin gel with other anticoagulant may precipitate overdose symptoms initially presenting as easy bruising or petechial formations. Concurrent use of Heparin with systemic anticoagulants is not recommended.

ADVERSE EFFECTS

Common: pruritus, redness (erythema), visible dilation of blood vessels (telangiectasia), scar lower than skin surface (scar atrophy)

Uncommon: Darkened skin (hyperpigmentation), thinned skin (skin atrophy)

Unknown: small pustules on the skin (pustular rash), allergic reaction (hypersensitivity), skin crawling (paraesthesia), swelling, pain in the application site, local skin reactions (contact dermatitis), hives (urticaria), rash, itching (pruritus), redness (erythema), skin irritations, small bumps (papules), skin inflammation, burning sensation on the skin, separation of skin layers in the application site, tight skin sensation

WARNINGS AND PRECAUTIONS
Hypersensitivity

Patients with documented hypersensitivity should not use Heparin gel.

Bleeding

Do not use heparin gel on open wounds or mucosa.

USE IN SPECIFIC POPULATION
Pregnancy

Teratogenic Effects – Pregnancy Category C Animal reproduction studies have not been conducted with heparin sodium. It is also not known whether heparin sodium can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.

Lactation

Heparin is not excreted in human milk. No special precautions are required.6

Pediatric

Use of Heparin 50iu/ml gel has been used in children and adolescents with good tolerability.

Geriatric

Not recommended. Concurrent use of Heparin may precipitate easy bruising or petechial formations. Falls in this population should be a primary concern.

Renal impairment

Topical Heparin gel has not been assessed in this population.

Hepatic impairment

Topical Heparin gel has not been assessed in this population.

PHARMACOKINETICS

Pharmacokinetics of topical heparin is unavailable.

TOXICITY

Bleeding is a chief sign of heparin overdosage. Easy bruising or petechial formations should be monitored.

STORAGE

Do not store at a temperature higher than 25 °C (77 °F)

REFERENCES
  1. Tan EM, Peltonen J. Endothelial cell growth factor and heparin regulate collagen gene expression in keloid fibroblasts. Biochem J. 1991;278 ( Pt 3)(Pt 3):863-869. doi:10.1042/bj2780863
  2. Willital GH, Heine H. Efficacy of Contractubex gel in the treatment of fresh scars after thoracic surgery in children and adolescents. Int J Clin Pharmacol Res. 1994;14(5-6):193-202.
  1. Beuth, J & Hunzelmann, N & Leendert, R & Basten, R & Noehle, M & Schneider, B. (2006). Safety and Efficacy of Local Administration of Contractubex® to Hypertrophic Scars in Comparison to Corticosteroid Treatment. Results of a Multicenter, Comparative Epidemiological Cohort Study in Germany. In vivo (Athens, Greece). 20. 277-83.
  2. Ocampo-Candiani J, Vázquez-Martínez OT, Iglesias Benavides JL, Buske K, Lehn A, Acker C. The prophylactic use of a topical scar gel containing extract of Allium cepae, allantoin, and heparin improves symptoms and appearance of cesarean-section scars compared with untreated scars. J Drugs Dermatol. 2014;13(2):176-182.
  3. Chadzyńska M. Leczenie bliznowców pooparzeniowych maścia Contractubex compositum firmy Merz [Treatment of post-burn keloid with Contractubex compositum ointment (Merz)]. Przegl Dermatol. 1987;74(1):55-61.
  4. Heparin. In: Drugs and Lactation Database (LactMed). Bethesda (MD): National Library of Medicine (US); 2006.
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