Can Allopurinol and Colchicine Be Taken Together for Gout

November 27, 2022 at seven:30 AM

Colchicine (Colcrys) and Allopurinol (Zyloprim, Aloprim and generics) are used for gout treatment. This post compares their efficiency, dosage and intake methods, side furnishings and interactions in gout treatment when taking individually and together.

Colchicine

Colchicine is a drug which is normally used for the treatment of gout. It is quite a toxic product and a secondary metabolite which is extracted from plants of the genus Colchicum (1). This drug can lead to some adverse effects like gastrointestinal problems but these furnishings are simply seen at high doses of the drug. Colchicine is normally used for the treatment of gout but it is as well used for the treatment of several other diseases like Mediterranean fever, atrial fibrillation and pericarditis.

Contempo evidence has suggested that colchicine effectiveness in treating gout is greater than the similar medicines of this class. The researches have indicated the common side effects of other drugs and how colchicine overcomes those side furnishings.

In that location are a few things which the wellness care professionals need to continue in mind when recommending colchicine. These things are mentioned below:

• The healthcare professionals should exist aware of the recommended dosage of colchicine for treating gout.
• The wellness care professional should abjure from prescribing colchicine to those patients who have renal or hepatic impairment and those who are taking the drugs which react with colchicine.

Airsickness and diarrhea are the common side effects seen when colchicine is given repeatedly later 1 to 2 hours dosage gap (2).

These are the beginning indication of colchicine toxicity and many rare side effects may also occur similar neuropathy, musculus damage, bone marrow suppression and multiple organs failure.

Patients suffering from renal and hepatic damage are probable to suffer from colchicine toxicity.

Medical uses

Colchicine is ordinarily prescribed to those patients who are unable to tolerate NSAIDs in gout. The use of the drug is limited due to its side furnishings at high doses. But this drug is quite effective and tolerable at lower doses.

Colchicine is likewise used for the long term handling of Behcet's affliction. This drug has a limited effect in relapsing polychondritis considering information technology is only useful for the handling of chondritis and mild skin symptoms.

Colchicine is as well used for the constipation predominant irritable syndrome in women and too for the treatment of persistent or severe aphthous stomatis.

Colchicine is also used in the treatment of pericarditis (3). Pericarditis is the inflammation caused around pericardium which is a membranous sac surrounding the heart. The about common complication of acute pericarditis is recurrent pericarditis which causes severechest pain.

A study was recently done whose main objective was to review the effect of all randomized and controlled studies. The data bases of dissimilar inquiry companies was analyzed in the report. The researchers said in the conclusion of their report that colchicine is effective in reducing the number of pericarditis recurrences in patients suffering from acute pericarditis.

But the researchers also said that the study was washed on a limited number of subjects.

Colchicine also has anti-inflammatory properties and it is used to reduce the recurrence of atrial fibrillation of the cardiac tissue.

Colchicine is as well used for the treatment of familial Mediterranean fever (an inborn condition which causes several episodes of astringent hurting, fever and swelling of the lungs and joints) in adults with ages of 4 years and older (4).

You should know one thing here that colchicine isn't a pain reliever and shouldn't be used for the treatment of pain that isn't acquired by gout. Colchicine belongs to a class of medicines known equally anti-gout agents. The mechanism of gout is naturally stopping the natural processes which crusade swelling and other symptoms of gout.

Likewise at initial stages of gout in patients on Allopurinol medication, doctors may prescribe Colchicine. Taking Colchicine and Allopurinol together resulted in lower number of time to come gout attacks (5a, 5b) however still more than research should be washed to confirm whether Allopurinol and Colchicine should exist used together or not.

Dosage and intake methods

The proper dosage for colchicine is described below (6, 7, eight):

• Oral use – the initial dosage for gout flare is about 1.ii mg at the first signs of gout followed by a dose of 0.six mg nigh one hour later. The dosage with stiff CYP450 3A4 inhibitors is about 0.6 mg followed by 0.3 mg dose one 60 minutes afterward. The dose shouldn't be repeated earlier than 3 days. The dosage can also exist 1.2 mg orally for one dose only. The dose can also be 0.6 mg for one dose only.
• Dosage for familial mediterranean fever – the dosage is well-nigh 1.2 mg to 2.4 mg to be administered in 1 to 2 divided doses. The dose can be increased according to the specific needs. Sometimes you lot can develop tolerance to the drug. You lot shouldn't discontinue the drug at in one case in this example but the dosage should be decreased in increment of 0.three mg/24-hour interval.
• Dosage for gout – the dosage is about 0.five to 0.6 mg to be administered in one case a day for iii to 4 days a calendar week. Some severe cases require doses of 1 to ane.8 mg/day.

Intake methods

Colchicine comes but in the tablet course. The following things should exist kept in heed while taking colchicine:

• You should read the manufacturer'due south label carefully inside the box earlier starting the treatment. This will give you more information nigh the drug and provide you with a detailed description of the side furnishings of the drug.
• You lot must take the drug exactly as instructed by the doctor. Well-nigh doctors volition recommend to have the drug when severe gout arises. It is important that y'all shouldn't take more 12 tablets during i gout set on.
• The usual dosage for the handling of colchicine is most 1 tablet to be taken twice a twenty-four hour period.
• You should drink the colchicine tablets with a glass of water. It's your choice to have the tablet with or without nutrient.
• You lot should accept the dose immediately if you have missed a dose. But yous shouldn't take the dose if it's the time for your adjacent dose. Never double dose.

The dosage of colchicine is based on your medical condition and the other drugs which you are taking forth with information technology. You shouldn't increase the dose to reduce the risks of side effects. You lot shouldn't as well take the dose more ofttimes or more than that recommended by the doctor.

Mechanism of activity

Colchicine binds itself to tubulin and stops the microtubule polymerization. The availability of tubule is essential for mitosis. Therefore colchicine functions effectively every bit a spindle poison or mitotic poison (nine).

The mitosis-inhibiting office of colchicine has go of corking utilize in the written report of cellular genetics. If you lot want to see the chromosomes of the prison cell under a microscope then it is important that they should be viewed near the signal in the cell cycle in which they have the virtually density.

This happens in the middle of mitosis and that is why mitosis must be stopped earlier it is completed. The standard process for doing karyotype studies is to add colchicine in a civilization during mitosis.

Colchicine also stops the neutrophil mobility and activeness other than stopping the mitosis which leads to an anti-inflammatory upshot which is quite useful for the treatment of acute gout flares.

Action after intake – pharmacokinetics

The post-obit steps are involved in the pharmacokinetics of colchicine (10):

one. Assimilation

Colchicine is captivated when given orally to healthy subjects and reaches a hateful Cmax of two.5 ng/mL after ane or two hours following a single dosage given under fasting weather. Colchicine is readily absorbed when it is given orally as 1.8 mg colchicine over 1 hour to salubrious young subjects nether fasting conditions. Colchicine is readily absorbed in such a case and reaches a maximum plasma concentration of half-dozen.2 ng/mL with a median 1.81 hours. The mean plasma concentration later the oral administration of the drug at high dose was six.8 ng/mL with a median of iv.47 hours. The peak concentrations reach from 3.1 to 3.6 ng/mL after 10 days of giving 0.6 mg twice on daily basis.

Taking colchicine with nutrient has no effect on rate of the absorption of colchicine but it decreases the extent of colchicine by 15%.

ii. Distribution

The apparent hateful volume of distribution in healthy young adults is about 5 to 8 50/kg. The bounden of colchicine to serum protein is quite low which is 39+-v due to albumin, regardless of the concentration. Colchicine crosses the placenta. Information technology too distributes in the breast milk at concentrations like to those found in maternal serum.

three. Metabolism

Colchicine is metabolized to two important metabolites which are 2-O-demethylcolchicine and iii-O-demethylcolchicine and 1 small metabolite which is 10-O-demethylcolchicine. The vitro studies which involved the human being liver microsomes have shown that CYP3A4 is involved in the metabolism of colchicine to 2- and three-DMC. The plasma levels of these metabolites are at minimum levels.

4. Elimination

About twoscore% to 65% orally administered colchicine in healthy volunteers was recovered unchanged through the urine. A major office played in the colchicine elimination is past enterohepatic recirculation and biliary excretion. The hateful half lives in individuals after the oral administration becomes from 26.6 to 31.2 hours. Colchicine acts as a substrate of P-gp.

Colchicine overdosage

The exact dosage of colchicine which produces colchicine toxicity isn't yet known (11, 12, xiii). There have been many cases of deaths subsequently taking doses as low equally 7 mg over a four day time flow. Merely some patients accept even survived after consuming doses of more than 60 mg. The bloodshed rate in the patients who ingested more than than 0.8 mg/kg was 100%.

Some common signs and symptoms colchicine toxicity which occur in the first 24 hours are shown beneath:

• Gastrointestinal symptoms similar airsickness, diarrhea
• Significant fluid loss which leads to fluid depletion
• Peripheral leukocytosis
• Multi organs failure
• Death due to respiratory low and cardiovascular collapse

The handling of colchicine overdose starts with gastric lavage and measures taken to prevent daze. The treatment is as well symptomatic and supportive. At that place isn't a specific antidote of colchicine even so known. Colchicine isn't removed finer through the procedure of dialysis.

Colchicine side effects

Some major side effects of colchicine intake include diarrhea, nausea, abdominal pain, vomiting and cramping (14). You should inform your md at once if whatever of these side effects worsen.

You should remember i thing that the doctor has prescribed this medicine for you lot because he thinks that its benefits are greater than its side furnishings. Near people using this medication don't suffer from any serious side effects.

 You should stop taking this medicine and become medical aid if any of the following severe side furnishings occur:

• Severe vomiting or diarrhea
• Unusual bruising and bleeding
• Numbness in the fingers
• Muscle pain or weakness
• Unusual tiredness
• Tingling in the fingers or toes
• Shortening of jiff
• Alter in the amount of urine
• Fast heartbeat

Sometimes serious allergic reactions are besides caused due to this drug just it is quite rare.

Notwithstanding yous should seek help immediately if y'all detect the symptoms of a serious allergic reaction which include rashes, severe dizziness, trouble breathing and swelling or itching.

Sometimes nervous system side effects are besides caused due to the intake of colchicine which include seizures, mental state changes and neuropathy in patients. Neuromyopathy has been seen with or without the elevated muscle enzymes.

Some renal side effects of the intake of colchicine include the rare cases of rapid progressive glomerulonephritis. There have been several reports of chronic renal failure with a fatal outcome of colchicine toxicity. Acute renal failure with fatal issue has been observed in a 78 year one-time man after having a ten day form of 0.5 mg tablet 3 times a twenty-four hour period.

A instance of azoospermia (the absence of motile and feasible sperms in the semen) has been seen in patients treated with colchicine.  The sperm count of the patient returned to normal on the discontinuation of colchicine. Just the sperm levels once again decreased when the drug was connected.

Yous should annotation here that this isn't the complete list of side effects. Yous should immediately consult a medico or pharmacist if yous observe whatsoever other aberration.

Decreased efficiency causes

The following things reduce the overall efficiency of colchicine (xv):

• The efficiency of colchicine decreases when it reacts with other drugs. A total of 357 drugs are known to interact with colchicine. Some common drugs which can react with colchicine include aspirin low force, vitamin B12, Nexium, fish oi, Lasix and Lipitor.
• The efficiency of colchicine is decreased when liver patients take the drug. Therefore patients suffering from liver problems should avert the intake of colchicine.

Allopurinol

This drug is sold under the brand name Zyloprim and generics (16). This drug is mainly used to care for the high levels of uric acid in the claret and the complications associated with it which includes chronic gout. It is a xanthine oxidase inhibitor and is administered orally only. This drug is on the list of the Globe Health Organization's listing of Essential Medicines which is a list of important medications needed in the bones health care system (17).

This drug is also beneficial for people having uric acid and undergoing cancer treatment. Allopurinol has many other uses which will be discussed below.

Y'all should know about some important things relating to allopurinol before knowing about the medical uses of allopurinol. The outset thing is that you demand to terminate taking allopurinol if you previously had a potent allergic reaction to allopurinol. You should inform your doc at once if yous notice any symptoms and signs of rash even if they are mild. You should take each dose of allopurinol with a full glass of h2o. Y'all should also potable up to 8 to 10 glasses of fluid every twenty-four hour period to reduce kidney stones (eighteen).

Allopurinol can lower the blood cells in the body needed for fighting infection. This can make you bleed every bit soon every bit you have an allergy. Your blood needs to be tested ofttimes in these cases. Therefore, you should visit your doc oft.

You should avoid drinking alcohol as this tin make your condition worse than ever. Allopurinol can impair your thinking and reaction ability. And then you need to exist careful if you drive or practise anything which needs y'all to be warning.

Medical uses

There are a number of benefits of allopurinol which have been mentioned below (19):

• Hyperuricemia and gout – Allopurinol is used for the treatment of chronic gout to prevent any kind of futurity attacks. This drug doesn't rid oneself from the astute attacks of gout and correct now there is an ongoing controversy on whether it tin can really make the gout attacks worse.
• Tumor lysis syndrome – Allopurinol is used for the treatment of chronic tumor lysis syndrome in unlike chemotherapeutic treatments because information technology tin rapidly produce severe acute hyperuricemia. But now-a-days information technology has been replaced by the urate oxidase therapy.
• Reperfusion injury – Some major established indications for allopurinol therapy include kidney stones having a uric acid component and protozoal infections.
• Epilepsy – Allopurinol is too used for refractory epilepsy as an addition drug considering it is an adenosine agonist which stops the glutamine release from excitatory neurons and doesn't also change the concentration of plasma of other epilepsy drugs.
• Inflammatory bowel syndrome – The allopurinol cotherapy is used for the comeback of outcomes in people suffering from inflammatory bowel disease and Crohn's disease who don't answer to monotherapy (20). Cotherapy has greatly improved the hepatoxicity side effects in treatment of inflammatory bowel syndrome. The dose reduction of thiopurine is needed in cotherapy and the standard dose mainly depends upon the patient'south genetic status for thiopurine methyltransferase.

Dosage and intake methods

The dosage for allopurinol depends upon the specific patient and the specific problem. The dosing data of allopurinol has been mentioned below (21):

• The initial dosage of allopurinol for gout is 100 mg to be taken orally once a day. The maintenance dosage is nearly 200 to 300 k to exist taken in one case a day or 400 to 600 mg/twenty-four hours in divided doses.
• The usual dose for patient suffering from calcium oxalate calculi is about 200 to 300 mg daily. The maintenance dosage is about 300 mg or less per 24-hour interval.
• The usual dosage for patients suffering from congestive heart failure is about 300 mg orally for 1 month.
• The adult dosage for cardiothoracic surgery is about 600 mg orally before the surgery and another 600 mg on the twenty-four hour period of surgery.
• The usual dose of allopurinol for mania is about 300 mg orally every day.
• The usual pediatric dose for leishmaniasis is well-nigh xx mg/kg/solar day plus low-dose of meglumine antimoniate for 20 days.
• The usual dosage for hyperuricemia which is before chemotherapy is about 200 to 400 mg/day and a maximum of 600 mg/day. The maintenance dosage is 200 to 300 mg/day orally until the patient doesn't has a run a risk of developing hyperuricemia.

Intake methods

Allopurinol comes merely in the tablet to taken orally. Information technology is taken one time or twice a day generally subsequently meals. Only the choice depends upon you. You should take the medicine at the same fourth dimension every day to help you lot recall to have the medicine.

You should follow the direction on the label carefully and inquire the dr. annihilation which you don't understand. Take allopurinol exactly as directed past the doctor. Don't take the drug more than or less than that prescribed by the physician. The doc volition start from a depression dose of the drug and go on increasing the dose not more than in one case a week.

The drug may accept several weeks to take effect if yous are suffering from gout. You might have more than gout attacks for the first few months subsequently starting the medicine when the body withal removes the extra uric acrid. You should remember hither that allopurinol isn't a pain reliever. Yous should continue to take the medicine for gout attacks if yous want to relieve the hurting from gout.

It may accept you several months to see the full benefits of the drug. Allopurinol can increase the number of gout attacks in the first few months that yous take information technology and it might also foreclose the attacks. Your doctor might give yous some other medication like colchicine to forestall the gout attacks for the first few months that you lot take it. You should keep taking the medicine even if you experience well. Don't stop taking the medicine without consulting the doctor.

Machinery of action

Allopurinol is a purine analog which ways that information technology is a structural isomer of hypoxanthine and it inhibits the enzyme xanthine oxidase (22). Xanthine oxidase is responsible for the oxidation of hypoxanthine and xanthine which results in the production of uric acrid which is the production of human purine metabolism. The inhibition of xanthine oxidase also causes an increase in xanthine and hypoxanthine.

Mechanism of allopurinol – pharmacokinetics

The following steps accept identify after the intake of allopurinol (23):

ane. Assimilation

The peak plasma concentrations of allopurinol after 80 to 90 percent absorption are reached after 1.5 to iv hours. The infusion takes place over 30 minutes and the peak plasma concentration of allopurinol is reached in about 30 minutes.

The serum urate concentrations in patients suffering from gout decreases slowly within 24 to 48 hours. The minimum concentrations may not attain for nigh one to three weeks. The substantial uric acid may be delayed up to 6 to 12 hours because of the continuous mobilization of the urate deposits.

People who suffer from geriatric disease have greater peak plasma concentrations and the allopurinol dosage in such patients is 50 to threescore percent higher than in young adults which is related to the renal function in older population.

2. Distribution

Allopurinol is uniformly distributed throughout the torso except the brain where the concentrations are about 50% of the concentrations in other tissues. Allopurinol is distributed into the milk. Allopurinol isn't spring to plasma proteins.

three. Metabolism

Allopurinol is metabolized by xanthine oxidase and it is metabolized to an active metabolite known as oxypurinol.

4. Elimination

The drug is excreted through urine and feces every bit an unchanged drug inside 48 to 72 hours. Allopurinol is dialyzable. The half-life of allopurinol is almost 1-3 hours.

Allopurinol overdosage

It is possible that a person accidentally or intentionally overdoses on allopurinol. An allopurinol overdose is likely to cause the same side effects as those which are possible with this medication (24). Simply still the experts don't know exactly what to expect from allopurinol overdose. Some cases were reported in which no serious bug occurred.

There are a number of treatments of allopurinol overdose. The healthcare professional might provide yous with sure medications if the overdose was contempo. The md may besides identify a tube in your stomach to "pump the stomach".  Some other handling is supportive care in which the symptoms of allopurinol overdose are treated. Dialysis can as well be used to remove allopurinol from the blood.

It is very of import that you seek firsthand medical attention if you retrieve that you have overdosed on allopurinol.

Allopurinol side effects

Some mutual side effects of allopurinol overdose are nausea, airsickness, breadbasket upset and diarrhea. Yous should inform the md or chemist immediately if whatsoever of these side effects persist or worsen (25).

Y'all should remember that the medico has prescribed the medication for you because he thinks that its wellness benefits are greater than its side effects. Most people using this drug don't suffer from whatsoever serious kind of side effects.

You should inform your doc right away if any of the following serious side effects occur:

• Numbness
• Tingling in the hands and feet
• Signs of infection
• Unusual tiredness
• Painful urination
• Yellowing of skin and eyes
• Change in the amount of urine
• Persistent vomiting
• Night urine
• Vision changes
• Center pain
• Unusual weight loss

Sometimes an allergic reaction can too be caused due to the intake of allopurinol but it is quite rare. Simply you should inform the doc immediately if you find any symptoms of an allergic reaction like rashes, swelling, dizziness, itching and trouble animate.

Some patients are hypersensitive to this drug (26). Therefore information technology should be used advisedly.

Allopurinol should exist used in pregnancy only if clearly instructed by the md and it should exist used with caution by breast feeding women. The benefits and the harmful effects to the fetus should be considered before the intake of this drug. Allopurinol should also exist used with caution in certain patients with hyperuricemia.

Moderate side effects

The following is a list of less severe side effects of allopurinol consumption:

• Drowsiness
• Fever
• Feeling faint or giddy
• General feeling of weakness or tiredness
• Incoherent speech
• Itching
• Metal gustatory modality
• Sore throat
• Thirst
• Tightness in chest
• Sweating
• Hostility
• Dry mouth

Decreased efficiency causes

The following things reduce the overall efficiency of allopurinol (27):

• The efficiency of allopurinol is decreased when it reacts with other medicines. A full of 135 drugs are known to interact with allopurinol. Some mutual drugs which can interact with allopurinol include aspirin, Nexium, Vitamin B12, Synthroid, Lipitor and Lasix.
• Alcohol can reduce the overall efficiency of this drug. So you should quite booze as long as you are taking this drug.

Colchicine vs Allopurinol - final comparing and clinical trials

The following studies give a brief comparing betwixt colchicine and allopurinol:

• A randomized written report was washed which involved 184 patients having acute gout flares of less than 12 hours duration. The patients were divided into iii groups. Ane group was given high dose of colchicine whereas the second group was given a low dose of colchicine. The third group was the placebo group. The results showed that the depression dose showed comparable pinnacle plasma concentrations and efficacy and the side effects were quite similar to that of placebo. The researchers concluded in the results of the study that the side effects of colchicine are quite less. The half-life of the drug was found to be of 4 hours.
• A written report was recently washed to discover the effects of allopurinol for the treatment of gout. The patients were divided into ii groups. I group was given allopurinol whereas the other group was given colchicine. The results of the study showed that allopurinol was more than beneficial for the handling of gout as compared to the placebo. But information technology was constitute in the study that about 30% patients using allopurinol suffered from different side effects; the most common side effects were skin rashes and gastrointestinal intolerance. The half-life of allopurinol was found to be about 1 to 3 hours.

Determination

While Colchicine is unremarkably used for treatment of acute flares of gout, Allopurinol is usually used for chronic gout treatment as it is an uric acid lowering drug. Sometimes doctors prescribe Colchicine and Allopurinol together, mainly in patients on Allopurinol treatment at the initial stages to foreclose further gout attacks. Both drugs may take some serious side effects, therefore proper dosage is necessary and the drugs should not be overdosed as there is a adventure of renal impairment and other serious problems. Interactions of Allopurinol and Colchicine include some commonly used medicines (such as aspirin or fifty-fifty vitamin B12). Booze is reducing efficiency of Allopurinol as well as Colchicine.

Disclaimer: This postal service is non a medical advice neither it replaces a proper medical consultation. Always meet a doctor if you do non feel well and never rely on any information establish on the web!

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Source: https://medlicker.com/979-colchicine-vs-allopurinol

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