Coumarin

(rINN)

💊 Chemical information

1,2-Benzopyrone; 5,6-Benzoα-pyrone; Cumarin; Cumarina; Kumaryna; Tonka Bean Camphor. 2H-1-Benzopyran-2-one.
Chemical formula: C9H6O2 = 146.1.
CAS — 91-64-5.

Pharmacopoeias.

In Ger.

💊 Profile

Coumarin is the odorous principle of Tonka seed (Tonka or Tonquin bean); it may be prepared synthetically. Coumarin has been given to reduce excess tissue protein and associated fluid in the treatment of lymphoedema (see below). It has also been used as a fixative in perfumery and as a flavour. It is reported to be an immunostimulant and has been tried in the treatment of malignant neoplasms. Coumarin derivatives are used as anticoagulants; coumarin itself is not an active anticoagulant.

Effects on the liver.

Coumarin has been classified as hepatotoxic based on studies in animals and effects ranging from elevated liver enzymes to serious organ damage has been reported in humans. Seventeen of 2173 patients enrolled in a study of coumarin developed elevated liver enzyme values;1 the majority of patients were given 100 mg coumarin daily for 1 month followed by 50 mg daily for 2 years. However, none of the patients developed permanent liver damage and liver enzyme values returned to normal in 5 patients who continued taking coumarin. Results from 5 studies supported by the Lymphoedema Association of Australia, in which patients received 400 mg daily for a mean duration of 14.6 months, showed 2 cases of hepatotoxicity among 1106 patients.2 In the period of 14 months up to May 1995, the Australian Drug Evaluation Committee received 10 reports of suspected adverse reactions to coumarin,3 including 6 cases of jaundice in women who had taken 400 mg daily for 1 to 4 months. Periportal and lobular necrosis were found on biopsy in 1 case and another had a fatal outcome due to massive hepatic necrosis. Reports of hepatotoxicity have led to the withdrawal of coumarin in a number of countries.
1. Cox D, et al. The rarity of liver toxicity in patients treated with coumarin (1,2-benzopyrone). Hum Toxicol 1989; 8: 501–6
2. Casley-Smith JR, Casley-Smith JR. Frequency of coumarin hepatotoxicity. Med J Aust 1995; 162: 391
3. Anonymous. Lodema and the liver. Aust Adverse Drug React Bull 1995; 14: 11. Also available at: http://www.tga.gov.au/ adr/aadrb/aadr9508.htm (accessed 30/07/08)

Lymphoedema.

Benzopyrones such as coumarin are reported to reduce excess protein in tissues with high-protein oedema, hence the use of coumarin in lymphoedema of various causes, including postmastectomy, and filarial lymphoedema and elephantiasis.1-5 Evidence for its efficacy is, however, conflicting;4-6 at best the action is slow and treatment may need to be given for 6 months to 2 years before any benefit is seen.
1. Jamal S, et al. The effects of 5,6 benzo-[a]-pyrone (coumarin) and DEC on filaritic lymphoedema and elephantiasis in India: preliminary results. Ann Trop Med Parasitol 1989; 83: 287–90
2. Turner CS. Congenital lymphedema. JAMA 1990; 264: 518
3. Casley-Smith JR, et al. Treatment of lymphedema of the arms and legs with 5,6-benzo-[α]-pyrone. N Engl J Med 1993; 329: 1158–63
4. Casley-Smith JR, et al. Treatment of filarial lymphoedema and elephantiasis with 5,6-benzo-α-pyrone (coumarin). BMJ 1993; 307: 1037–41
5. Casley-Smith JR. Benzo-pyrones in the treatment of lymphoedema. Int Angiol 1999; 18: 31–41
6. Loprinzi CL, et al. Lack of effect of coumarin in women with lymphedema after treatment for breast cancer. N Engl J Med 1999; 340: 346–50.

💊 Preparations

Proprietary Preparations

Arg.: Esberiven; Ger.: Venalot mono†; Ital.: Linfovenodren. Multi-ingredient: Arg.: Esberiven; Microsuy; Braz.: Flebotrat†; Micotox†; Varicoss; Venalot; Venalot H; Ger.: Caye Rheuma-Balsam; Venalot; Venalot N†; Ital.: Flebolider; Mex.: Venalot.
Published May 08, 2019.