Colchicine (Oral)

An extract of the autumn crocus flower, colchicine is used to prevent attacks of gout and alleviate pain caused by too much uric acid in the bloodstream.

Overview:

Colchicine is a naturally occurring compound extracted from the autumn crocus (also known as œmeadow saffron ). It is primarily used to alleviate and prevent painful symptoms of gout, most notably in those who are unable to tolerate non-steroidal anti-inflammatory drugs (NSAIDs) to treat the condition.

This commonly-occurring, widely-used plant extract has been used historically to treat rheumatism and swelling of the joints, with documented evidence that it has been revered as a useful natural treatment in ancient Egypt from the year 1500BC right up until present day.

As a gout treatment, the use of colchicine can most notably be traced back to approximately 500AD, where the bulb-like corms of the plant were used to treat the condition. The plant first appeared in the London Pharmacopoeia in 1618 and its use in the Western world has been widespread since then.

In the US, this medication is marketed under the brand names Colcrys and Mitigare. It can also be used as an anti-inflammatory agent in the long-term treatments of familial Mediterranean fever and Behçet's disease, a disorder which affects various parts of the body with symptoms that include arthritis, painful sores in the mouth, genital sores and inflammation of the eye.

The use of colchicine at high doses is inhibited by its propensity to cause gastrointestinal upset. It is much more effective and tolerated by the body at lower doses. Despite having been used for centuries, with numerous modern studies suggesting that the medicine is effective in the treatment of acute flares of gout-related pain, the drug is not currently formally approved by the US Food & Drug Administration (FDA).

Although it functions by breaking down and flushing out uric acid which has collected in the joints and the bloodstream, colchicine does not actually have any analgesic (pain-killing) properties. Instead, it works by halting the natural processes which cause swelling and other symptoms related to gout.

Conditions treated:

  • Gout
  • Behçet's disease
  • Familial Mediterranean fever

Type of medicine:

  • Anti-inflammatory agent

Side effects:

Along with the desired effects, orally-administered colchicine can cause some unwanted side effects. The propensity for side effects to occur is increased when colchicine is taken at particularly high doses. Some of the most common symptoms reported by individuals taking this medicine include: diarrhea, nausea, vomiting and/or stomach pain.

Most patients will only experience minimal side effects when taking colchicine, especially when taking it in small doses. Some patients will experience no side effects at all. Many doctors agree that the benefits of alleviating the causes of painful gout attacks outweigh the risk of experiencing side effects related to this medication.

Other side effects experienced less frequently, albeit often enough to warrant a mention, include the following: tarry, black stools, blood in stools or urine, tingling/crawling/burning sensation in the skin, difficulty breathing while exercising, fever (with or without chills), headache, muscle weakness, hive-like swellings on the face, generalized pain, peeling of the skin, skin rash, sores and ulcers or white spots in the mouth or on the lips, sore throat, tenderness, unusual bleeding, bruising, and/or unusual weakness or tiredness. Patients who experience any of these rare side effects to the point of discomfort when taking colchicine should seek medical attention as soon as possible. In some instances, a doctor or healthcare professional may be able to advise on how to alleviate symptoms associated with certain side effects by using over the counter or natural remedies.

Patients who experience the following side effects should seek medical attention immediately: convulsions (seizures), severe or bloody diarrhea, shallow and fast breathing, a burning feeling in the stomach/throat/skin, bleeding. These symptoms are associated with overdose and if left untreated could be potentially serious or even fatal.

Very small numbers of patients experienced hair loss and loss of appetite when using colchicine, although experiencing either of these symptoms is very unlikely (occurring in less than 0.1 per cent of patients).

Although many gastrointestinal, nervous system, musculoskeletal, hematologic, hypersensitivity, hepatic, respiratory, ocular, genitourinary, endocrine and dermatologic side effects have been widely documented in patients undergoing treatment with colchicine, some side effects may not yet be reported. Patients who feel they may be experiencing unreported side effects should contact their doctor for medical advice, and report their findings to the FDA.

Dosage:

As with all medicines, it is important for patients to take colchicine only as prescribed by a doctor or qualified healthcare professional. This means that patients must avoid taking more of this medication than advised, both in terms of frequency and dose size. In addition to this, patients should cease taking colchicine if advised to do so by their doctor - even if they still have a supply of the medication remaining.

Doses of colchicine are typically prescribed to prevent attacks of gout (severe, sudden-onset joint pain, caused by usually high levels of uric acid within the body). It can also be used to alleviate pain associated with gout attacks after they occur. Colchicine can also be used to treat FMF (familial Mediterranean fever) - a condition which causes pain, fever, swelling of the stomach, joints and lungs in patients aged four and over. This medicine belongs to a class of medications known as anti-gout agents, and it functions by stopping processes which result in swelling and other symptoms associated with gout and FMF.

Colchicine is available as a tablet which is taken orally. It can be taken with or without food. As a preventative, colchicine is typically taken once or twice a day. When used to relieve the symptoms of a gout attack, a larger dose is typically taken when pain is first noticed, with a smaller dose taken one hour afterwards.

The starting dose of colchicine will depend upon the patient's condition, height, weight, and diet among other factors. Although the manufacturer provides dosage recommendations in the literature supplied with the medication, it should be reiterated that these are merely guidelines which can be adjusted by a doctor as they see fit. Many patients continue to take colchicine at a maintenance level to keep gout under control, as well as using it at higher doses to combat flare-ups of the condition. Patients should not stop taking this medicine without first speaking to a doctor.

Adult dosage for gout:

Adults who experience the first signs of a flare-up of gout should take 1.2mg of colchicine orally followed by 0.6mg, one after the initial dose. Patients should not exceed more than 1.8mg orally over a one-hour period, as higher doses are no more effective and simply contribute to more uncomfortable gastrointestinal side effects.

Adult dosage for prevention of gout:

Adults who wish to prevent potential flare-ups of gout are advised to take 0.6mg of colchicine once or twice per day. Patients taking colchicine for preventative reasons should avoid taking any more than 1.2mg of the medicine per day.

Adult dosage for FMF:

Adults suffering from Familial Mediterranean fever should take 1.2mg 2.4mg colchicine daily, which can be administered in one or two divided doses throughout the day. If required, the dose can be increased at increments of 0.3mg per day as required to control the disease, provided the patient can tolerate the increase. If unbearable side effects develop, the dosage should be similarly be decreased at increments of 0.3mg per day. Patients suffering from this condition are advised to take no more than 2.4mg of this medicine per day.

Pediatric dose for FMF:

This medicine is unsuitable for children under the age of four. Children aged four and above should take colchicine at a reduced dosage. Guidelines are as follows:

  • Aged 4 to 6 years: 0.3mg to 1.8mg taken orally each day, in one or two divided doses.
  • Aged 6 to 12 years: 0.9mg to 1.8mg taken orally each day, in one or two divided doses.
  • Aged 12 years and above: 1.2mg to 2.4mg taken orally each day, in one or two divided doses.

Renal dose adjustments (gout):

Patients with renal issues are advised to avoid taking colchicine in conjuction with any medicines which inhibit both P-glycoprotein and CYP450 3A4. When patients with renal issues experience gout flares, their dose of colchicine should be adjusted to the following, based on their renal condition:

  • Mild-moderate renal impairment (CrCl 30 to 80mL/min) patient should proceed with standard dosage with caution. Adjustments only necessary if patient experiences adverse effects.
  • Sever renal impairment (CrCl less-than 30mL/min dose reduction required dependent on patient reaction. Treatment with colchicine should be repeated no more than once every two weeks. Patients with recurring gout flare-ups may require alternative therapy.

Renal dose adjustments (FMF):

  • Mild-moderate renal impairment (CrCl 30 to 80mL/min patient should proceed with standard dosage with caution. Adjustments only necessary if the patient experiences adverse effects.
  • Sever renal impairment (CrCl less-than 30mL/min patient should start at a dose of 0.3mg per day, which can be increased provided the patient is adequately monitored for adverse effects.

Hepatic adjustments:

In some instances, colchicine may not be suitable for use by patients with liver impairment. Patients with liver issues should always consult their doctor or healthcare provider before undergoing treatment with colchicine.

Live dose adjustments (gout):

  • Mild-moderate hepatic impairment patient should proceed with standard dosage with caution during gout-flare ups. Adjustments only necessary if the patient experiences adverse effects.
  • Sever hepatic impairment standard dose should be administered with caution, and a treatment course should not be repeated more than once a fortnight. Doctors should consider offering alternative therapies to patients who require repeated courses.
  • For the prevention of gout, large dose reductions of alternative treatments should be considered.

Liver dose adjustments (FMF):

  • Mild-moderate hepatic impairment patient should proceed with standard dosage with caution. Adjustments only necessary if the patient experiences adverse effects.
  • Sever hepatic impairment dose reduction is advised. The patient should be monitored to ascertain the safety of colchicine use.

Taking too much of this medication can result in colchicine toxicity. In the event of a patient experiencing this, interruption or discontinuation of treatment with this medicine will be necessary.

If a patient misses a dose, he or she should take it as soon as they remember. If the patient takes colchicine on a regular basis and enough time has elapsed so that it is nearer the time for the next dose, they should skip the missed dose and continue with the regular dose schedule from here on in. However, patients who are taking colchicine to treat a gout flare-up which occurred while they were already taking the medicine to prevent gout attacks should take a missed dose as soon as possible, waiting at least 12 hours before taking the next scheduled preventative dose.

Patients who experience signs of overdose as a result of taking too much colchicine (slow or fast heartbeat, shallow or fast breathing, unconsciousness, loss of coordination or seizures) are advised to contact their local poison control center on 1800-222-1222 immediately, or alternatively to contact emergency services on 911.

Interactions:

All medications have the potential to interact with other chemicals or drugs within the human body, and these interactions can change how one or more of the involved medicines work. In some instances, an interaction can cause a medicine to become ineffective. In other circumstances, interactions can cause potentially serious or even fatal side effects. Because of this risk, patients are advised to keep a full, detailed list of all drugs they are currently taking. This extends to vitamins, herbal supplements, over the counter remedies and complementary medicines as well as prescription medications.

Below is a partial list of medicines known to interact negatively with colchicine. Patients who are currently undergoing therapy with any of these medications are advised to inform their doctor prior to taking their first dose of colchicine:

  • Addyi (flibanserin)
  • Advicor (lovastatin / niacin)
  • Agenerase (amprenavir)
  • Akynzeo (netupitant / palonosetron)
  • Aldactazide (hydrochlorothiazide / spironolactone)
  • Aldactone (spironolactone)
  • atorvastatin / ezetimibe
  • Baycol (cerivastatin)
  • Belsomra (suvorexant)
  • bepridil
  • CaroSpir (spironolactone)
  • Cartia XT (diltiazem)
  • carvedilol
  • Cerdelga (eliglustat)
  • ceritinib
  • cerivastatin
  • Cinvanti (aprepitant)
  • clarithromycin
  • Clopine (clozapine)
  • Diflucan (fluconazole)
  • Dilacor XR (diltiazem)
  • Dilt-XR (diltiazem)
  • Diltia XT (diltiazem)
  • diltiazem
  • Diltiazem Hydrochloride CD (diltiazem)
  • Diltiazem Hydrochloride SR (diltiazem)
  • Diltiazem Hydrochloride XR (diltiazem)
  • Diltiazem Hydrochloride XT (diltiazem)
  • diltiazem / enalapril
  • Diltzac (diltiazem)
  • dronedarone
  • E S P (erythromycin / sulfisoxazole)
  • E-Mycin (erythromycin)
  • E.E.S. Granules (erythromycin)
  • E.E.S.-200 (erythromycin)
  • E.E.S.-400 (erythromycin)
  • FloLipid (simvastatin)
  • fluconazole
  • fluvastatin
  • Fortovase (saquinavir)
  • fosamprenavir
  • fosaprepitant
  • Gengraf (cyclosporine)
  • Genox (tamoxifen)
  • Invirase (saquinavir)
  • isavuconazonium
  • Isoptin (verapamil)
  • Isoptin IV (verapamil)
  • Isoptin SR (verapamil)
  • itraconazole
  • ivacaftor
  • ivacaftor / lumacaftor
  • Juvisync (simvastatin / sitagliptin)
  • Juxtapid (lomitapide)
  • Kaletra (lopinavir / ritonavir)
  • Kalydeco (ivacaftor)
  • Ketek (telithromycin)
  • Ketek Pak (telithromycin)
  • ketoconazole
  • Kisqali (ribociclib)
  • lopinavir / ritonavir
  • lovastatin
  • lovastatin / niacin
  • Matzim LA (diltiazem)
  • Mavyret (glecaprevir / pibrentasvir)
  • Mevacor (lovastatin)
  • mibefradil
  • Mifeprex (mifepristone)
  • Norvir (ritonavir)
  • Noxafil (posaconazole)
  • Nuedexta (dextromethorphan / quinidine)
  • ombitasvir / paritaprevir / ritonavir
  • Omeclamox-Pak (amoxicillin / clarithromycin / omeprazole)
  • Onmel (itraconazole)
  • Orkambi (ivacaftor / lumacaftor)
  • Pacerone (amiodarone)
  • PCE Dispertab (erythromycin)
  • Pediazole (erythromycin / sulfisoxazole)
  • Prezista (darunavir)
  • Prograf (tacrolimus)
  • propafenone
  • QM-260 (quinine)
  • Qualaquin (quinine)
  • Quin-G (quinidine)
  • Quin-Release (quinidine)
  • Quinaglute Dura-Tabs (quinidine)
  • Quinidex Extentabs (quinidine)
  • quinidine
  • quinine
  • Quinora (quinidine)
  • Ranexa (ranolazine)
  • ranolazine
  • red yeast rice
  • Rescriptor (delavirdine)
  • Reyataz (atazanavir)
  • ribociclib
  • ritonavir
  • Robimycin (erythromycin)
  • rolapitant
  • rosuvastatin
  • Rythmol (propafenone)
  • Rythmol SR (propafenone)
  • Samsca (tolvaptan)
  • Sandimmune (cyclosporine)
  • saquinavir
  • Serzone (nefazodone)
  • Simcor (niacin / simvastatin)
  • simvastatin
  • simvastatin / sitagliptin
  • sofosbuvir / velpatasvir
  • Synercid (dalfopristin / quinupristin)
  • tacrolimus
  • Tamofen (tamoxifen)
  • Tamone (tamoxifen)
  • Tamosin (tamoxifen)
  • Tamoxen (tamoxifen)
  • tamoxifen
  • Tamoxifen Hexal (tamoxifen)
  • Tao (troleandomycin)
  • Tiazac (diltiazem)
  • tolvaptan
  • trandolapril / verapamil
  • troleandomycin
  • Tybost (cobicistat)
  • Tykerb (lapatinib)
  • ulipristal
  • Vaprisol (conivaptan)
  • Varubi (rolapitant)
  • Varubi IV (rolapitant)
  • Vascor (bepridil)
  • vemurafenib
  • Zocor (simvastatin)
  • Zydelig (idelalisib)
  • Zykadia (ceritinib)
  • Zypitamag (pitavastatin)

As well as drug interactions, various food interactions also exist with colchicine. Patients undergoing treatment with this medicine are advised against consuming large quantities of grapefruit or grapefruit juice, as this food contains enzymes which can cause the medicine to be absorbed into the body at a much greater rate, potentially running the risk of exposing the body to dangerous levels of the medication. Patients who consume grapefruit in conjunction with colchicine should contact their doctor immediately if they experienced nausea, vomiting, diarrhea, muscle pain, fever, fatigue, weakness, numbness and/or tingling in the hands or feets, as these could potentially be early signs of colchicine toxicity brought on by grapefruit consumption.

Warnings:

In some patients, colchicine can potentially cause a severe allergic reaction. Symptoms can include difficulty breathing and a swelling of the tongue or throat. Patients who experience an allergic reaction are advised to visit their nearest emergency room and to avoid taking colchicine in the future, as reactions can potentially be fatal.

Long-term preventative use of oral colchicine has been demonstrated to caused problems in patients with advanced renal failure. Approximately 10-20 per cent of colchicine is excreted unchanged by the kidneys, and is not removed by hemodialysis. As a result, the probability of cumulative toxicity is reasonably high in those with kidney issues, resulting in the progressive onset of proximal weakness, sensorimotor polyneuropathy and elevated creatine kinase.

The concomitant use of drugs designed to lower cholesterol (such as fibrates or statins) can contribute towards colchicine toxicity, which can potentially culminate in hypercapnic respiratory failure and even death.

Colchicine is classed by the FDA as a category C pregnancy drug. This means that research undertaken on animals has revealed that the fetus suffers adverse effects when a pregnant mother takes the drug, or that there have been insufficient studies performed in humans to be certain as to how this medicine might affect a developing fetus. Patients who are pregnant or intending on becoming pregnant should contact their doctor, who may advise that colchicine should only be used if the potential benefits of the medicine justify the risks of undergoing treatment with it.

Colchicine can potentially be excreted into breast milk and could cause side effects in children who are breastfed. Breastfeeding mothers may, therefore, wish to stop breastfeeding while undergoing treatment with colchicine, or to avoid taking colchicine and seek an alternative treatment instead.

Older patients may be at an increased risk of experiencing side effects when being treated with colchicine. This is because the kidneys of older people may not function as well as they used to. As a result, the body is unable to process the medicine, causing more of it to stay in the body for a longer period of time.

Storage:

This medicine should be kept in the container it was dispensed in, tightly closed and out of the reach of children and/or pets. It should be stored at room temperature and away from sources of excess heat or moisture (it is therefore not suitable for storage in the bathroom, and should instead be kept in a dedicated, locked medicine cabinet where available).

Unwanted or unused medicines should be disposed of in a safe and hygienic manner, with the patient ensuring that pets, children or other people cannot inadvertently consume them. Colchicine should not be disposed of down the toilet or drain. The best means of disposing of this medicine is via a take-back program. Most pharmacies offer community take-back programs where they will safely dispose of or recycle unwanted or unused medications.

Summary:

Colchicine is an incredibly effective treatment for gout, as it helps to reduce the levels of uric acid in the blood which cause painful inflammation of the joints. It is a particularly useful medication for patients who are allergic to or otherwise unsuited to NSAIDs. It is also useful in the treatment of familial Mediterranean fever, and can potentially be used off-label for a number of other unapproved uses at the discretion of a doctor, including post-pericardiotomy syndrome.

Despite its effectiveness in treating certain painful conditions, colchicine can also pose a risk to patients who fail to communicate with their physician. Gastrointestinal side effects can impair the day-to-day functioning of the body, and at high doses, this medication can put the patient at risk particularly if they are currently taking medicines or imbibing foodstuffs known to interact with colchicine.

For these reasons, it is imperative that the patient tells his or her doctor as much about their medical history as possible. When taken correctly, colchicine provides the relief of symptoms which can cause great pain and are often difficult to treat. At the correct dosage, colchicine facilitates greater flexibility and even provides patients with the ability to walk (something which many who experience gout in the lower extremities struggle to do during flare-ups).

To achieve the best possible results with this medicine, patient and doctor are encouraged to work together to find out the most appropriate dose levels and optimum frequency of use. In some instances, a doctor may even recommend combining colchicine with other medications, treatments or remedies in order to combat gout.