The formula contains two active ingredients: Heparin and Allantoin.
Each substance contributes to the overall therapeutic effect to penetrate into the scar tissue, where they have a synergistic effect on scar healing and may help prevent excessive scar growth.
This combination formula has been clinically studied over 50 years and across 60 countries and has been shown to successfully diminish both keloid and hypertrophic scars.
Heparin/Allantoin is commonly compounded as a 50iu/10mg/ml gel.
Heparin. Heparin elicits a negative regulatory effect on collagen production through down-regulation of pro-alpha1(I) of the type I collagen gene, inhibiting polymerization of collagen and loosening the collagen structure.1
Further to heparin’s ability to soften the tissue structure, it has anti-inflammatory and anti-swelling properties, and 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.
Allantoin. The exact mechanism of action of allantoin is unknown. Studies suggest that it encourages wound healing and has a softening effect due to its keratolytic, hydrating, epithelizing, and anti-irritating effects.
Allantoin may also promote penetration through the skin and relieve itching often associated with scar formation. Its increased ability to hold moisture may act to smooth the skin surface and improve scar elasticity.
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/Allantoin/Extractum cepae 50iu/10mg/100mg/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
A multicenter, retrospective cohort study investigated the safety and efficacy of topical Heparin/Allantoin/Extractum cepae 50iu/10mg/100mg/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/Allantoin/Extractum cepae 50iu/10mg/100mg/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/Allantoin/ Extractum cepae 50iu/10mg/100mg/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/Allantoin/ Extractum cepae 50iu/10mg/100mg/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/Allantoin/Extractum cepae 50iu/10mg/100mg gel was significantly more effective than corticosteroid treatment.3
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
Heparin and Allantoin gels have be used to reduce the aesthetic appearance of various types of scars after the wounds have healed.
Its combination has been studied for its utility in both keloid1.5 hypertrophic3 scarring.
It has been used successfully to reduce the appearance of scars resulting from thoracic surgeries2 and c-sections.4
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.
Concurrent use of Heparin/Allantoin gel with other anticoagulant may precipitate overdose symptoms initially presenting as easy bruising or petechial formations. Concurrent use of Heparin/Allantoin with systemic anticoagulants is not recommended.
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
Patients with documented hypersensitivity should not use Heparin/Allantoin gel.
Do not use Heparin/Allantoin gel on open wounds or mucosa.
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.
Heparin is not excreted in human milk. No special precautions are required.6
Use of Heparin/Allantoin 50iu/10mg gel has been used in children and adolescents with good tolerability.
Not recommended. Concurrent use of Heparin/Allantoin/Extractum cepae may precipitate easy bruising or petechial formations. Falls in this population should be a primary concern.
Topical Heparin/Allantoin gel has not been assessed in this population.
Topical Heparin/Allantoin gel has not been assessed in this population.
Pharmacokinetics of topical heparin and cepae extract is unavailable.
In studies on human subjects, a recovery of 19% and 34% of allantoin in the urine was observed but only in two individuals and only after the administration of massive doses of allantoin.
Distribution: information not available
Elimination: Urinary clearance is the predominant excretion route
Metabolism: Allantoin is found endogenously and is part of basic, natural metabolic pathways, no accumulation is expected of it. Additionally, allantoin is not believed to be metabolized to a measurable extent in humans and animals
Excretion: Some studies suggest that the average renal clearance of allantoin in normal, healthy human subjects is approximately 123ml per minute. It is generally agreed upon that exogenously administered allantoin is rapidly excreted
Bleeding is a chief sign of heparin overdosage. Easy bruising or petechial formations should be monitored.
Do not store at a temperature higher than 25 °C (77 °F)
- 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
- 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.
- 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.
- 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.
- 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.
- Heparin. In: Drugs and Lactation Database (LactMed). Bethesda (MD): National Library of Medicine (US); 2006.
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