Colchicine

Brand Names: ColBenemid

Clinical Names: Colchicine

Summary

generic name: Colchicine

trade name: ColBenemid®

type of drug: Anti-gout.

used to treat: Colchicine is used to treat gout and acute gouty arthritis, specifically relieving the pain of acute attacks. Colchicine can have a prophylactic, suppressive effect that helps reduce the incidence of acute attacks and relieve the residual pain and mild discomfort occasionally associated with gout. It is only occasionally effective in other types of arthritis. Colchicine is not an analgesic, and does not provide relief of other types of pain, nor will it prevent progression of gout to chronic gouty arthritis.

mechanism: The mode of action of colchicine in gout is unknown. However, it is thought to decrease lactic acid production by the leukocytes and thereby decrease urate crystal deposition and subsequent inflammatory response in gout and acute gouty arthritis.

overview of interactions:
• nutrient affected by drug: Vitamin B12

• nutrient affected by drug: Beta-Carotene

• nutrient affected by drug: Magnesium

• nutrient affected by drug: Potassium

• nutrient affected by drug: Sodium

• nutrient affected by drug: Dietary Fat

• nutrient affected by drug: Lactose

• herbs affecting drug performance: Salicylate-containing Herbs such as Betula lenta (Sweet Birch ), Cimicifuga racemosa (Black Cohosh rhizome), Filipendula ulmaria (Meadowsweet flower), Gaultheria procumbens (Wintergreen leaves), Populus canadensis (Poplar bark and/or buds), and Salix spp. (Willow bark)

• herbs affecting drug performance: Herbs containing Tannins such as Camellia sinensis (Green Tea and Black Tea), Arctostaphylos uva-ursi (Uva ursi), Juglans nigra (Black Walnut), Rubus idaeus (Red raspberry), Quercus spp. (Oak), and Hamamelis virginiana (Witch Hazel)



Interactions

nutrient affected by drug: Beta-Carotene

• mechanism: Colchicine has been linked to impaired absorption of these nutrients.
(Robinson C, Weigly E. 1984, 46-54.)

• nutritional support: Individuals taking colchicine would most likely benefit from taking a high-potency multivitamin/mineral supplement to compensate for these interactions.

nutrient affected by drug: Vitamin B12

• mechanism: Colchicine interferes with vitamin B12 metabolism by reducing intrinsic-factor-B12 receptors.

• research: Despite uncertainty about the exact relationship, caution is indicated in elderly individuals taking colchicine and experiencing nervous system symptoms.
(Kuncl, RW, et al. New Engl J Med 1987;317:1290-1291; Palopoli, JJ, Waxman J. N Engl J Med 1987 Nov 12;317(20):1290-1291; Ehrenfeld M, et al. Dig Dis Sci 1982 Aug;27(8):723-727; Robinson C, Weigly E. 1984, 46-54; Stopa EG, et al. Gastroenterology 1979 Feb;76(2):309-314.)

• clinical concerns: Any evidence of neuropathies following the use of colchicine warrants checking serum levels of B12 for deficiencies.

• nutritional support: B12 supplementation would be judicious prophylactically and administration is indicated when any deficiency is detected. A generous and wholly safe dosage of 10-25 mcg per day of vitamin B12 would compensate for the adverse effects of taking colchicine. Periods testing of serum levels would be appropriate for monitoring vitamin B12 status.

nutrient affected by drug: Magnesium

• mechanism: Colchicine has been linked to impaired absorption of Magnesium.
(Roe DA. 1985, 159-160.)

• nutritional support: Individuals taking colchicine would most likely benefit from taking a high-potency multivitamin/mineral supplement to compensate for these interactions.

nutrient affected by drug: Potassium

• mechanism: Colchicine has been linked to impaired absorption of Potassium.
(Roe DA. 1985, 159-160.)

• nutritional support: Individuals taking colchicine would most likely benefit from taking a high-potency multivitamin/mineral supplement to compensate for these interactions.

nutrient affected by drug: Sodium

• mechanism: Colchicine has been linked to impaired absorption of Sodium.
(Roe DA. 1985, 159-160.)

• nutritional support: Individuals taking colchicine would most likely benefit from taking a high-potency multivitamin/mineral supplement to compensate for these interactions.

nutrient affected by drug: Dietary Fat

• research: A variety of studies indicate that colchicine interferes with the intracellular phase of fat absorption.
(Arreaza-Plaza CA, et al. Biochim Biophys Acta 1976 May 27;431(2):297-302; Roe DA. 1985, 159-160; Pavelka M, Gangl A. Gastroenterology. 1983 Mar;84(3):544-555; Pavelka M, Gangl A. Verh Anat Ges. 1978;(72):687-689; Race TF, et al. Am J Med Sci 1970 Jan;259(1):32-41; Glickman RM, et al. Gastroenterology 1976 Mar;70(3):347-352; Miura S. Nippon Shokakibyo Gakkai Zasshi. 1980 Apr;77(4):572-82.)

nutrient affected by drug: Lactose

• mechanism: Colchicine has been linked to impaired absorption of lactose. In studies of patients with familial Mediterranean fever (FMF) Fradkin et al found that colchicine induces significant lactose malabsorption in FMF patients and concluded that this interaction was at least partially responsible for the gastrointestinal side effects of the drug.
(Roe DA. 1985, 159-160; Werbach, MR. 1997, 223-224; Race TF, et al. Am J Med Sci 1970 Jan;259(1):32-41; Fradkin A, et al. Isr J Med Sci. 1995 Oct;31(10):616-620.)

herbs affecting drug performance: Salicylate-containing Herbs such as Betula lenta (Sweet Birch bark), Cimicifuga racemosa (Black Cohosh rhizome), Filipendula ulmaria (Meadowsweet flower), Gaultheria procumbens (Wintergreen leaves), Populus canadensis (Poplar bark and/or buds), and Salix spp. (Willow bark)

• mechanism: Herbs high in salicylates (aspirin-like compounds) can precipitate herbal alkaloids and impair absorption of colchicine.
(Brinker, F. J Naturopathic Med 1997;7(2):14-20; Brinker F. 96, 99-100, 1999.)

• herbal concerns: Herbs high in salicylates should not be taken with colchicine.

herbs affecting drug performance: Herbs containing Tannins such as Camellia sinensis (Green Tea and Black Tea), Arctostaphylos uva-ursi (Uva ursi), Juglans nigra (Black Walnut), Rubus idaeus (Red raspberry), Quercus spp. (Oak), and Hamamelis virginiana (Witch Hazel)

• mechanism: Herbs high which yield tannins when extracted by hot water can precipitate alkaloids which can impair absorption of colchicine. Tannins will not precipitate low concentrations of alkaloidal salts in the presence of many gums present in plants such as Acacia, Agar, Aloe, Flax, Guar, Irish moss, Locust bean, Marshmallow root, Okra fruit, pectin powder, Psyllium seed husks and Slippery Elm bar.
(Brinker F. J Naturopathic Med 1997;7(2):14-20; Brinker F. 99-101, 1999.)

• herbal concerns: Herbs high in tannins should not be taken with colchicine.


Please read the disclaimer concerning the intent and limitations of the information provided here.
Do not rely solely on the information in this article.

The information presented in Interactions is for informational and educational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, case reports, and/or traditional usage with sources as cited in each topic. The results reported may not necessarily occur in all individuals and different individuals with the same medical conditions with the same symptoms will often require differing treatments. For many of the conditions discussed, treatment with conventional medical therapies, including prescription drugs or over-the-counter medications, is also available. Consult your physician, an appropriately trained healthcare practitioner, and/or pharmacist for any health concern or medical problem before using any herbal products or nutritional supplements or before making any changes in prescribed medications and/or before attempting to independently treat a medical condition using supplements, herbs, remedies, or other forms of self-care.



References

Arreaza-Plaza CA, Bosch V, Otayek MA. Lipid transport across the intestinal epithelial cell. Effect of colchicine. Biochim Biophys Acta 1976 May 27;431(2):297-302
Abstract: Rats injected with colchicine (0.5 mg/100 g of body weight) 1 h before ingestion of a margarine emulsion (1 g in 2 ml of saline) do not show the rise in plasma triacylglycerol concentration found in controls during the subsequent hours. The effect of colchicine is more dramatic when the experiment is performed after prior administration of Triton WR-1339, a substance known to inhibit the catabolism of lipoproteins. Colchicine-treated rats also showed a five-fold increase in the content of triacylglycerol in proximal jejunum, when compared to controls. These results are consistent with the idea that colchicine interferes with the intracellular phase of fat absorption, suggesting that the microtubular-microfilamentous system could be involved in the release of chylomicrons from the intestinal cell into the circulation.

Blok J, Ginsel LA, Mulder-Stapel AA, Onderwater JJ, Daems WT. The effect of colchicine on the intracellular transport of 3H-fucose-labelled glycoproteins in the absorptive cells of cultured human small-intestinal tissue. An autoradiographical and biochemical study. Cell Tissue Res 1981;215(1):1-12.

Brinker F. Interactions of pharmaceutical and botanical medicines. J Naturopathic Med 1997;7(2):14-20.

Brinker F. Herb Contraindications and Drug Interactions. 2nd edition. Sandy, OR: Eclectic Institute, Inc. 1999.

Ehrenfeld M, Levy M, Sharon P, Rachmilewitz D, Eliakim M. Gastrointestinal effects of long-term colchicine therapy in patients with recurrent polyserositis (familial mediterranean fever). Dig Dis Sci 1982 Aug;27(8):723-727.
Abstract: Twelve patients with recurrent polyserositis (RP, familial Mediterranean fever) on colchicine prophylaxis (1.0-2.0 mg daily) for three years or more were evaluated for the presence of gastrointestinal effects possibly attributable to the drug. Two patients had bulky stools, two others had transient diarrhea, and one had heartburn. Serum vitamin B12, calcium, and carotene levels were normal in all cases, and D-xylose absorption was normal in 11 of the 12. Three patients had mild steatorrhea (7.5, 7.9, and 9.9 g daily). Jejunal biopsies from these and a fourth patient with bulky stools but normal fecal fat excretion showed no abnormal histological changes. However, (Na + K)-ATPase activity was significantly decreased in all four cases. Colchicine had to be discontinued in only one of the 12 cases. It is concluded that mild steatorrhea and enzyme inhibition may occur in patients on long-term colchicine prophylaxis and that careful periodic observations for this and other adverse effects is imperative in such patients.

Fradkin A, Yahav J, Zemer D, Jonas A.  Colchicine-induced lactose malabsorption in patients with familial Mediterranean fever. Isr J Med Sci. 1995 Oct;31(10):616-620.
Abstract: Abdominal pain and diarrhea are frequent side effects of chronic colchicine therapy. Drug-induced lactose deficiency has been demonstrated in the experimental animal. Lactose malabsorption was assessed by the lactose breath test in 23 patients with familial Mediterranean fever (FMF) receiving colchicine for 0.25-15 years (mean 3.16). Twenty FMF patients not receiving colchicine and 38 non-FMF lactose malabsorbers served as controls. Patients receiving colchicine had a significantly higher percentage of lactose malabsorption (20/23, 87%) versus nontreated FMF patients (13/20, 65%; P < 0.05). Lactose intolerance was also more prevalent in colchicine-treated patients (17/23, 74%) versus nontreated FMF (5/20, 25%; P < 0.0005) and control lactose malabsorbers (16/38, 42%; P < 0.01). Of the 12 patients investigated before and 3 months after colchicine administration, 7 showed induction or aggravation of lactose malabsorption. The lactose-free diet resulted in partial improvement of symptoms. Colchicine induces significant lactose malabsorption in FMF patients and this is partially responsible for the gastrointestinal side effects of the drug.

Glickman RM, Perrotto JL, Kirsch K. Intestinal lipoprotein formation: effect of cholchicine. Gastroenterology 1976 Mar;70(3):347-352.
Abstract: The possibility that microtubules might be involved in intestinal lipoprotein formation or secretion was studied by determining the effect of colchicine, a known microtubule inhibitor, on intestinal lipid absorption. The effect of colchicine (0.5 mg per 100 g) in the lymphatic absorption of [14C]oleic acid was studied in rats with indwelling mesenteric lymph cannulas. Colchicine-treated animals showed a marked delay as well as a decrease in the lympatic absorption of [14C]oleic acid. Chylomicrons from colchicine-treated animals showed no difference in apoprotein content when examined on sodium dodecyl sulfate polyacrylamide gels. Micellar lipid absorption was next studied from in situ jejunal loops in animals pretreated with colchicine. Colchicine administration was associated with a 3-fold increase in residual mucosal lipid when compared with controls. Thin layer chromatography of residual lipid demonstrated that residual lipid was largely present as triglyceride, suggesting that the impairment in lipid transport induced by colchicine was at a site distal to triglyceride resynthesis. Electron microscopic examination of intestine from colchicine-treated animals revealed that most residual lipid was present within the endoplasmic reticulum and Golgi in numerous particles the size of chylomicrons (0.2 to 0.4 mu). These results suggest that the impairment in lipid transport induced by colchicine is distal and, in part, may represent an "exit block". These results suggest a possible role for microtubules in intestinal lipid transport. However, further studies are required to demonstrate directly the participation of microtubules in chylomicron secretion.

Goulston KJ, Skyring A. The effect of colchicine on the absorption of water and electrolytes by rat jejunum. Aust J Exp Biol Med Sci. 1966 Feb;44(1):93-100.

Kuncl RW, et al. Colchicine neuropathy or vitamin B12 deficiency neuropathy? New Engl J Med 1987;317:1290-1291. (Letter)

Kuncl RW, George EB. Toxic neuropathies and myopathies. Curr Opin Neurol 1993 Oct;6(5):695-704. (Review)

Longstreth GF, Newcomer AD. Drug-induced malabsorption. Mayo Clin Proc 1975 May;50(5):284-293.

Miura S. [Study on the fat absorption and transportation into intestinal lymph of rats--effect of colchicine on the absorption of long chain fatty acids and the role of intestinal alkaline phosphatase]. Nippon Shokakibyo Gakkai Zasshi. 1980 Apr;77(4):572-82. [Article in Japanese]

Palopoli JJ, Waxman J. Colchicine neuropathy or vitamin B12 deficiency neuropathy? N Engl J Med 1987 Nov 12;317(20):1290-1291. (Letter)

Pavelka M, Gangl A. Effects of colchicine on the intestinal transport of endogenous lipid. Ultrastructural, biochemical, and radiochemical studies in fasting rats. Gastroenterology. 1983 Mar;84(3):544-555.
Abstract: The involvement of microtubules in the transepithelial transport of exogenous lipid in intestinal absorptive cells has been suggested. Using electronmicroscopic, biochemical, and radiochemical methods, we have studied the effects of the antimicrotubular agent colchicine on the intestinal mucosa and on the intestinal transport of endogenous lipid of rats in the fasting state. After colchicine treatment, the concentration of triglycerides in intestinal mucosa of rats fasted for 24 h doubled, and electron microscopic studies showed a striking accumulation of lipid particles in absorptive epithelial cells of the tips of jejunal villi. These findings suggest that colchicine interferes with the intestinal transepithelial transport of endogenous lipoproteins. Additional studies, using an intraduodenal pulse injection of [14C]linoleic acid, showed that colchicine does not affect the uptake of fatty acids by intestinal mucosa. However, it had divergent effects on fatty acid esterification, enhancing their incorporation into triglycerides relative to phospholipids, and caused a significant accumulation of endogenous diglycerides, triglycerides, and cholesterol esters within the absorptive intestinal epithelium. Detailed ultrastructural and morphometric studies revealed a decrease of visible microtubules, and a displacement of the smooth and rough endoplasmic reticulum and Golgi apparatus. Furthermore, it is shown that after colchicine treatment, microvilli appear at the lateral plasma membrane of intestinal absorptive cells, a change not previously reported to our knowledge. Thus, our study shows that (a) colchicine causes significant changes in enterocyte ultrastructure and (b) colchicine perturbs the reesterification of absorbed endogenous fatty acids and their secretion in the form of triglyceride-rich lipoproteins from the enterocyte.

Pavelka M, Gangl A. [Ultrastructure of small intestine epithelial cells following administration of colchicine--studies in fasting condition and during fat absorption]. Verh Anat Ges. 1978;(72):687-689. [Article in German]

Polliotti BM, Panigel M, Miller RK. Free vitamin B12 and transcobalamin II-vitamin B12 complex uptake by the visceral yolk sac of the Sprague-Dawley rat: effect of inhibitors. Reprod Toxicol 1997 Jul;11(4):617-626.

Race TF, Paes IC, Faloon WW. Intestinal malabsorption induced by oral colchicine. Comparison with neomycin and cathartic agents. Am J Med Sci 1970 Jan;259(1):32-41.

Rachmilewitz D, Karmeli F. Colchicine and intestinal transport. Gastroenterology. 1982 Jul;83(1 Pt 1):159-60. (Letter)

Robinson C, Weigly E. Basic Nutrition and Diet Therapy. New York: MacMillan, 1984, 46-54.

Roe DA. Drug-induced Nutritional Deficiencies. 2nd ed. Westport, CT: Avi Publishing, 1985, 159-160.

Stopa EG, O'Brien R, Katz M. Effect of colchicine on guinea pig intrinsic factor-vitamin B12 receptor. Gastroenterology 1979 Feb;76(2):309-314.
Abstract: Colchicine can induce the malabsorption of vitamin B12 and other nutrients. Previous investigations have suggested but not proved that this malabsorption was due to a lesion in the ileal mucosa. Employing the receptor assay of M. Katz and B. A. Cooper (J Clin Invest 54:733-739, 1974), the authors have observed a dose-related, reversible reduction in the quantity of intrinsic factor-vitamin B12 (IF-B12) receptor (from 5.78 ng to 1.3 ng of B12 binding) in the intestinal mucosa of guinea pigs fed 0.05-0.25 mg/100 g colchicine/day for 3 days. Malabsorption of vitamin B12 was also demonstrated in vivo in similarly treated animals. Increasing intestinal motility with cascara sagrada had no effect on the IF-B12 receptor. The quantity of IF-B12 receptor and the amount of vitamin B12 absorbed increased markedly to greater than normal levels during recovery from a 3-day course of colchicine. The total number of intestinal cells decreased after colchicine administration and increased during recovery; however, the fluctuations observed were not sufficient to explain the changes in the quantity of receptor. Histologic examination of the ileal mucosa showed a decrease in the population of villus cells after colchicine. The correlation between the changes in receptor quantity and in vivo B12-absorption prove that the IF-B12 receptor is a critical limiting factor in B12 absorption.

Webb DI, Chodos RB, Mahar CQ, Faloon WW. Mechanism of vitamin B12 malabsorption in patients receiving colchicine. N Engl J Med 1968 Oct 17;279(16):845-850.

Wallace SL. Mechanism of action of colchicine. Arthritis Rheum. 1965 Oct;8(5):744-748.

Werbach MR. Foundations of Nutritional Medicine. Tarzana, CA: Third Line Press, 1997, 223-224. (Review).