How colchicine works
Colchicine can effectively relieve the sometimes very severe pain of acute gout attacks.
Gout is a metabolic disease in which the concentration of uric acid in the blood is elevated. If it exceeds a certain limit, some of the uric acid precipitates in the form of crystals and is deposited in the tissue, for example in joint fluid. Over time, the joint cartilage is destroyed and the joint becomes inflamed: macrophages (“scavenger cells” that develop from monocytes) absorb the uric acid crystals that are classified as foreign and then release pro-inflammatory messenger substances.
With this inflammatory reaction in joints affected by gout, the body tries to do something about the uric acid crystals. The inflammatory process occurs in very painful episodes. Colchicine can help against these so-called gout attacks. It inhibits the phagocytosis activity of the macrophages. In addition, the active ingredient prevents the white blood cells from actively “firing up” the inflammatory reaction.
Dangerous mitotic poison
Colchicine inhibits certain proteins that enable the division of chromosomes into the new cells. As a result, the daughter cells are not viable and die.
Absorption, degradation and excretion
After ingestion, colchicine enters the bloodstream through the intestines, where it exerts its effects on blood cells. It is excreted through the kidneys in the urine as well as through the bile in the stool. The time it takes for half of the absorbed active ingredient to be excreted is between 20 and 50 hours – so it is highly variable. There are two reasons for this:
First, the active ingredient is subject to the so-called entero-hepatic cycle: that colchicine that passes through the liver into the bile and with it into the intestine can be reabsorbed from there into the blood, which then transports it again to the liver. This circulation between intestine (“entero”) and liver (“hepatic”) is also subject to some other substances (both other drugs and endogenous substances).
On the other hand, colchicine has a large volume of distribution, which means that it distributes well in the body.
When is colchicine used?
The areas of application of colchicine differ in Germany, Austria and Switzerland. In Germany and Switzerland, the approval is limited to:
- the treatment of acute gout attacks
- Treatment of acute gout attacks
- Prevention of a recurrent gout attack at the start of uric acid-lowering therapy
- Primary treatment of acute or recurrent pericarditis (inflammation of the heart sac) as an adjunct to non-steroidal anti-inflammatory drugs
- Treatment of familial Mediterranean fever (a rare genetic disorder)
- Seizure prophylaxis and prevention of amyloidosis (various rare diseases in which abnormally folded proteins are deposited in various tissues and organs)
Outside its scope of approval (“off-label” use), colchicine is also used in Germany and Switzerland to prevent gout attacks and to treat Familial Mediterranean Fever.
How colchicine is used
In the event of an acute gout attack, treatment with colchicine should be started as early as possible: Affected individuals first take one milligram (1 mg) of colchicine. If symptoms persist, another half milligram (0.5 mg) can be swallowed after one hour.
After that, no more colchicine tablets should be taken for twelve hours. After that, treatment can be continued with half a milligram (0.5 mg) every eight hours.
Treatment is stopped as soon as symptoms are relieved or a maximum of six milligrams (6 mg) of colchicine has been taken.
After such a treatment cycle, you must abstain from further colchicine for at least three days to allow the body to fully excrete the amount already administered and recover.
Stop treatment immediately if you experience diarrhea or vomiting, as these could be signs of an overdose.
The dosage for treating pericarditis or Familial Mediterranean Fever and for preventing a gout attack is determined on an individual basis. Usually it is between one to three milligrams per day.
The so-called therapeutic range of colchicine (dose range within which it is safe to use) is very small. If the average daily dose is two milligrams, as little as 20 milligrams can be fatal for an adult.
What are the side effects of colchicine?
The active ingredient colchicine acts primarily on tissue that is active in division. Apart from the desired effect on white blood cells, it particularly affects the intestinal mucosa, which explains the frequent side effects in the gastrointestinal tract.
Thus, one in ten to one hundred patients develops side effects in the form of nausea, abdominal pain and cramps, or vomiting. Drowsiness, muscle pain and muscle weakness occur with equal frequency.
What should be considered when using colchicine?
Contraindications
Colchicine must not be used in:
- severe renal impairment
- severe liver dysfunction
- patients with defective blood composition (blood dyscrasia)
Interactions
Because the active ingredient colchicine is transported and broken down in the body by enzyme systems that also break down and transport many other active ingredients, the combination of colchicine with other drugs must be closely monitored.
The brain protects itself from toxins that enter the blood through food by transport systems (P-glycoproteins) that actively “pump out” invading foreign substances. If this system fails, many substances that are actually well tolerated can have a very toxic effect.
Colchicine is also transported via these P-glycoproteins. The simultaneous use of drugs that inhibit this transport system can therefore massively increase its toxicity. Examples of such drugs are the antimalarial and anticonvulsant quinine, which is also contained in tonic water, antibiotics such as azithromycin or clarithromycin, and the antihypertensives verapamil and captopril.
Cytochrome inhibitors include some antibiotics (clarithromycin, erythromycin), antifungals (ketoconazole, itracomazole), HIV medications, and agents used to suppress the immune system after organ transplantation (ciclosporin).
The muscular side effects of statins (blood lipid-lowering drugs) may increase if taken at the same time as colchicine.
Grapefruit juice may increase the toxicity of colchicine.
Men who have taken colchicine should use safe contraception for at least six months after the last dose, since the gout drug’s mutagenic effects also damage sperm. Women should also use safe contraception during colchicine therapy and for up to three months afterward.
Age restriction
Colchicine may be used in children and adolescents with Familial Mediterranean Fever under the supervision of a specialist without age restriction. For the other indications, colchicine should be used only after the age of 18 years.
Pregnancy and lactation
In principle, colchicine is contraindicated during pregnancy and lactation and should be replaced by other agents. In women of childbearing age, an existing pregnancy must be excluded before use.
Studies of more than 1000 pregnant women (mostly with FMF) show no increase in malformation rates with colchicine therapy. Studies in breastfeeding women show no abnormalities in the breastfed infants. Breastfeeding is therefore acceptable with colchicine.
How to obtain medications containing colchicine
Colchicine is available by prescription in Germany, Austria, and Switzerland and can be obtained from pharmacies upon presentation of a valid prescription.
How long has colchicine been known?
The first written mention of a medicinal use of the colchicine-containing meadow saffron is found on an Egyptian papyrus that is more than 3000 years old. The plant was recommended on it for the treatment of rheumatic complaints and swellings.
Autumn crocus was also successfully used for these purposes in the Persian Empire and in Greece. Its active substance, colchicine, was first isolated and described in France in 1820.
However, its actual mode of action on cells was not deciphered until the second half of the 20th century. For many patients, preparations containing the active substance colchicine are the only effective treatment for an acute attack of gout.
