Colchicine Lirka 1 mg tablets No. 60

Instructions Colchicine Lirka 1 mg tablets No. 60

Composition

active ingredient: colchicine;

1 tablet contains 1 mg of colchicine;

excipients: lactose monohydrate; sucrose; gum arabic; magnesium stearate.

Dosage form

Pills.

Main physicochemical properties: whitish (from white to yellowish) round tablets with a score on one side.

Pharmacotherapeutic group

Drugs affecting the musculoskeletal system. Drugs used for gout. Drugs that do not affect uric acid metabolism. Colchicine.

ATX code M04A C01.

Pharmacological properties

Pharmacodynamics.

The active ingredient of the drug Colchicine Lirka is colchicine, an alkaloid extracted from the seeds of autumn crocus, a herbaceous plant belonging to the lily family.

The extract of this plant has diuretic, analgesic, and anti-inflammatory properties, so it is used for rheumatism, arthritis, and especially as an anti-gout remedy.

Although the mechanism of colchicine's antigout action is not fully understood, it is thought that the drug reduces the inflammatory response to monosodium urate crystal deposition in tissues through its ability to inhibit the metabolism, motility, and chemotaxis of polymorphonuclear cells and/or other functions of leukocytes. Colchicine also directly affects monosodium urate deposition by reducing the production of lactic acid by polymorphonuclear leukocytes and indirectly by inhibiting phagocytosis.

In addition, colchicine inhibits cell division by preventing the formation of the division spindle at the metaphase level, which was observed in granulocytes.

These effects have been observed both in cell cultures and in cells from patients treated with colchicine. Colchicine has a potential for dose-dependent toxicity, and colchicine therapy should be adjusted according to individual tolerability, which varies widely, with early signs of toxicity in the form of gastrointestinal disturbances, particularly diarrhea, as an indicator.

Pharmacokinetics.

After oral administration, colchicine is rapidly absorbed. Maximum plasma concentrations are reached after 30 minutes to 2 hours.

After absorption, colchicine is partially transformed into oxycolchicine, which selectively accumulates in the kidneys, from where it is excreted rather slowly. Thus, in patients with impaired renal function, accumulation of colchicine and its metabolites is possible. The elimination half-life in healthy subjects (t1/2) is 65 ± 15 minutes, total clearance is 601 ± 155 ml/min, and the volume of distribution is 49 ± 9 l.

Enterohepatic recirculation occurs to a large extent, which can lead to gastrointestinal side effects when using higher doses. Colchicine is distributed in the tissues of the kidneys, liver, spleen and intestines and is concentrated mainly in leukocytes. Colchicine can be detected in leukocytes 10 days after administration. Colchicine is metabolized in the liver and in other tissues. The half-life in plasma is 3–5 minutes. The half-life is 1.7–20.9 hours in patients with normal renal function and is increased in patients with impaired renal function, therefore a dose reduction is recommended. Colchicine and its metabolites are excreted mainly in the feces, 10–20% is excreted in the urine unchanged.

Renal excretion may be increased in patients with liver disease.

Indication

Acute attack of gouty arthritis.

For the preventive treatment of recurrent gouty arthritis.

For the treatment of acute and recurrent pericarditis.

Contraindication

Hypersensitivity to the active substance or to any of the excipients.

Severe heart, kidney and/or gastrointestinal failure.

Patients with renal or hepatic impairment who are taking P-glycoprotein or CYP3A4 inhibitors (see section 4.5). Life-threatening and fatal toxicity of colchicine has been reported in these patients at therapeutic doses.

Pregnancy and breastfeeding.

Patients on dialysis.

Interaction with other medicinal products and other types of interactions

There is no data on incompatibility when using this medicinal product with typical drugs for the treatment of gout or on interactions with laboratory tests.

Colchicine is a substrate of CYP3A4 and the transport protein P-glycoprotein. In the presence of inhibitors of CYP3A4 or P-glycoprotein, the concentration of colchicine in the blood may increase.

Concomitant use of colchicine with cyclosporine, HMG-CoA reductase inhibitors (statins), fibrates, ketoconazole, some anti-HIV drugs, macrolide antibiotics, cimetidine, verapamil, diltiazem, ranolazine, digoxin, large amounts of grapefruit juice (1000 ml/day) and other CYP3A4 or P-glycoprotein inhibitors, especially in patients with renal insufficiency, may cause bone marrow depression, agranulocytosis, neuromyopathy, myopathy or rhabdomyolysis and other adverse effects, as well as high, potentially life-threatening levels of colchicine in the blood serum.

Life-threatening and fatal drug interactions have been reported in patients receiving colchicine in combination with strong P-glycoprotein and CYP3A4 inhibitors.

If treatment with a P-glycoprotein inhibitor or a strong CYP3A4 inhibitor is necessary, patients with normal renal or hepatic function may require adjustment of the colchicine dose.

The main drugs or drug classes that are metabolized by the same CYP3A isoenzyme are alprazolam, oral anticoagulants (e.g. warfarin), astemizole, carbamazepine, cilostazol, cisapride, clarithromycin, telithromycin, cyclosporine, disopyramide, ergot alkaloids, lovastatin, methylprednisolone, midazolam, omeprazole, pimozide, quinidine, rifabutin, rifapentine, sildenafil, simvastatin, tacrolimus, terfenadine, triazolam, vinblastine, ritonavir, atazanavir, indinavir, saquinavir, efavirenz, nevirapine, or zidovudine. Other drugs that interact by a similar mechanism through other cytochrome P450 isoenzymes are phenytoin, theophylline, valproate, and phenobarbital.

Concomitant use with P-gp inhibitors (such as amiodarone, verapamil, quinidine, ketoconazole, dronedarone, clarithromycin and ticagrelor) results in increased plasma concentrations of colchicine. Increased plasma levels of colchicine have been reported with single doses of ketoconazole, ritonavir, verapamil and diltiazem.

P-glycoprotein inhibitors or potent CYP3A4 inhibitors: Colchicine is contraindicated in patients with renal or hepatic impairment who are receiving P-glycoprotein inhibitors or potent CYP3A4 inhibitors.

Macrolides (e.g. clarithromycin and erythromycin), as well as CYP3A4 inhibitors, should not be used in patients with renal or hepatic impairment receiving colchicine. Concomitant use of colchicine and erythromycin/clarithromycin is contraindicated in such patients.

In patients with normal renal and hepatic function, a reduction in the dose of colchicine or temporary discontinuation of its use is recommended if treatment with a P-glycoprotein inhibitor or a potent CYP3A4 inhibitor is required (see section "Special warnings and precautions for use").

Statins: Cases of rhabdomyolysis have been reported in patients receiving concomitant statins. Patients should be advised to report muscle pain and weakness.

Concomitant use of atorvastatin, simvastatin, pravastatin, fluvastatin, gemfibrozil or fibrates (associated with myotoxicity) and cyclosporine with colchicine may lead to myopathy. Symptoms usually resolve after discontinuation of use within 1 week to several months.

Colchicine may impair the absorption of vitamin B12.

Application features

Colchicine is potentially toxic, so it is important not to exceed the dose prescribed by a specialist who has the necessary knowledge and experience.

Patients with renal impairment and cardiovascular disease.

Bone marrow disorders, agranulocytosis, neuromyopathy, myopathy and rhabdomyolysis may occur in patients with renal impairment.

Considerable caution is required in patients with more severe circulatory and renal disorders (dehydration, changes in blood pressure, impaired renal function).

Patients with gastrointestinal disorders.

In patients with gastrointestinal disorders, symptoms may be exacerbated due to the antimitotic effect of colchicine, which leads to diarrhea, nausea, vomiting, and stomach pain.

Treatment of acute gout attacks in patients with renal impairment.

For the treatment of gout attacks, the drug should be used with caution in patients with mild (creatinine clearance 50–80 ml/min) or moderate (creatinine clearance 30–50 ml/min) renal impairment. Patients with moderate renal impairment should have their dose reduced or their dosing interval increased. Treatment of such patients should be carried out under close supervision to avoid side effects.

Patients with severe renal impairment (creatinine clearance less than 30 ml/min) should initially take ½ tablet (0.5 mg) per day. The dosage should be increased under close supervision to avoid side effects. Although the dose does not need to be adjusted for the treatment of gout attacks, patients with severe renal impairment should not repeat the course of treatment more frequently than once every 2 weeks. Patients with gout attacks requiring repeated courses of treatment should consider alternative therapy.

Colchicine treatment is contraindicated in patients undergoing dialysis (see Contraindications).

For the treatment of gout attacks, no adjustment of the recommended dose is necessary in patients with mild to moderate hepatic impairment, but close monitoring for adverse effects is necessary. A dose reduction should be considered in patients with severe hepatic impairment.

Treatment of elderly patients.

Colchicine should be used with great caution in elderly and debilitated patients, especially in the presence of kidney, gastrointestinal, or heart disease.

If weakness, anorexia, nausea, vomiting, or diarrhea occur, the dose should be reduced.

Clarithromycin.

There have been post-marketing reports of toxicity with the concomitant use of colchicine and clarithromycin, particularly in elderly patients and occasionally in patients with renal impairment. Some of these patients have been fatal. If concomitant use of colchicine and clarithromycin is necessary, the patient should be closely monitored for symptoms of colchicine toxicity.

Excipients.

Colchicine Lira contains lactose, therefore patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Colchicine Lira contains sucrose, therefore patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

Allergic reactions are more common in patients with hypersensitivity to acetylsalicylic acid.

The medicine must be stored out of reach of others before and after use. Toxic medicine!

Use during pregnancy or breastfeeding

Pregnancy

Published animal data on reproductive and developmental effects indicate that colchicine exhibits embryofetal toxicity, teratogenicity, and alters postnatal development at exposures achieved after administration of the drug at or above the indicated therapeutic doses.

Use is contraindicated.

Breast-feeding

Colchicine is excreted in breast milk.

Physicochemical and available pharmacodynamic/toxicological data on colchicine indicate excretion of colchicine in breast milk and a risk to the infant, therefore a risk to the breastfed infant cannot be excluded.

Use is contraindicated.

Fertility

Published nonclinical data have shown that colchicine-induced disruption of microtubule formation affects meiosis and mitosis.

The use of colchicine causes morphological abnormalities of sperm and a decrease in sperm count in men, as well as disruption of the process of sperm penetration, the second meiotic division, and egg cell division in women taking colchicine.

Although male infertility due to colchicine is rare, there have been reports of azoospermia after discontinuation of the drug.

Clinical case reports and epidemiological studies in women treated with colchicine have not established a clear association between colchicine use and female infertility.

Ability to influence reaction speed when driving vehicles or other mechanisms

Colchicine Lirka does not affect the ability to drive vehicles and operate other mechanisms.

Method of administration and doses

Dosage

Gouty arthritis

Treatment of acute gout attacks should be started as soon as possible (within the first 12 hours of the onset of the gout attack). The expected effect will occur within 12 hours.

First, take 1 tablet (1 mg of the drug), then 1 hour later, take ½ tablet (0.5 mg of the drug). After that, do not take the tablet for 12 hours.

If necessary, the dose can be repeated after 12 hours. The maximum daily dose is ½ tablet (0.5 mg of the drug) every 8 hours until symptoms improve.

The course of treatment should be completed after symptoms have subsided or 6 tablets (6 mg) have been taken. No more than 6 tablets (6 mg) should be taken during the course of treatment.

A repeated course of treatment is carried out no earlier than 3 days (72 hours) after the end of the previous course.

Prevention of gout attacks: Adults should take ½–1 tablet (0.5–1 mg of the drug) per day for up to 6 months. The individual duration of treatment should be determined after assessing factors such as the frequency of exacerbations, the duration of the disease, and the presence and size of tophus.

Acute and recurrent pericarditis

The recommended daily dose of colchicine for acute and recurrent pericarditis is ½–1 tablet (0.5 mg–1 mg) per day: 0.5 mg twice daily for adult patients weighing > 70 kg or 0.5 mg once daily for adult patients weighing ≤ 70 kg, or for patients who cannot tolerate higher doses, for at least six months for recurrent pericarditis and at least three months for acute pericarditis.

In most clinical trials, the dose of colchicine used is 1 tablet (1 mg).

Method of application

The recommended dose may vary depending on the patient's kidney and liver function status.

Kidney dysfunction

Use with caution in patients with mild renal impairment. For patients with moderate renal impairment, the dose should be reduced or the dosing interval should be increased. Such patients should be carefully monitored for the occurrence of colchicine side effects. For information on the treatment of patients with severe renal impairment, see section 4.3.

Liver dysfunction

Use with caution in patients with mild/moderate hepatic impairment. Such patients should be closely monitored for colchicine side effects. For use in patients with severe hepatic impairment, see section "Contraindications".

Special patient groups

Concomitant use of colchicine with certain drugs, primarily cytochrome P450 3A4 (CYP3A4)/P-glycoprotein inhibitors, increases the risk of colchicine toxicity. If the patient is receiving concomitant therapy with a moderate or potent CYP3A4 inhibitor or P-glycoprotein inhibitor, the maximum recommended oral dose of colchicine should be reduced and the patient should be closely monitored for adverse effects.

Children.

The drug is not used in children.

Overdose

Overdose and disregard for drug interaction recommendations can cause poisoning, which is accompanied by severe pain and can also be fatal.

Colchicine has a narrow therapeutic range and is extremely toxic in overdose. Patients with renal or hepatic impairment, gastrointestinal or cardiac disease, and the elderly are at particular risk of toxicity. Patients with colchicine overdose, even in the absence of early symptoms, should seek immediate medical attention.

Acute intoxication may occur after oral ingestion of approximately 20 mg (20 tablets) of colchicine in adults and 5 mg (5 tablets) in children. Chronic intoxication may occur after repeated doses of the drug in patients with gout after taking doses of 10 mg or more over several days.

Because colchicine inhibits mitosis, organs with a higher rate of proliferation are more affected.

Symptoms

The exact dose of colchicine that is toxic is unknown. Fatalities have been reported after 7 mg of colchicine for 4 days, while other patients survived after taking more than 60 mg. A review of 150 patients after colchicine overdose found that those who took less than 0.5 mg/kg survived and tended to have milder toxicity, manifested by gastrointestinal upset, while those who took 0.5 mg to 0.8 mg/kg had more serious reactions, such as myelosuppression. There was a 100% mortality rate in those who took more than 0.8 mg/kg.

The first stage of acute colchicine poisoning begins within 24 hours of ingestion and includes gastrointestinal disorders such as dehydration, stomach pain, hemorrhagic gastroenteritis, hypovolemia, diarrhea, nausea, and vomiting, accompanied by electrolyte imbalance, leukocytosis, and hypotension in severe cases.

The second stage, with life-threatening complications, may be accompanied by symptoms such as multiorgan failure, acute renal failure, confusion, coma, peripheral motor and sensory neuropathy, myocardial depression, pancytopenia, arrhythmia, respiratory failure, and coagulopathy within 24 to 72 hours after ingestion.

Death can occur from respiratory and cardiovascular failure.

If the patient survives, recovery of affected organs may be accompanied by a return of leukocytosis and alopecia, beginning approximately 1 week after the initial overdose.

Therapy

There is no antidote.

In case of colchicine overdose, gastric lavage should be performed, preferably within 60 minutes after ingestion, and activated charcoal should be administered. Diarrhea does not need to be treated, as defecation is the main route of colchicine excretion.

In adults, vomiting can be induced, for example, with warm hypertonic sodium chloride solution (2–3 teaspoons per glass) or apomorphine (0.1–0.15 mg/kg body weight).

In children under 6 years of age, 1 tablespoon of syrup of ipecac in 100–200 mL of juice is used to induce vomiting, followed by gastric lavage and repeated or continuous administration of activated charcoal.

Hemodialysis is ineffective (due to the large volume of distribution).

Treatment is mainly symptomatic and supportive (control of breathing, maintenance of blood pressure and circulation, correction of fluid and electrolyte balance). Pain relief may be required with cautious use of analgesics and the use of atropine (if necessary), as well as benzodiazepines, papaverine or tanalbin if convulsions occur. Digoxin may be administered to support cardiac function.

Prophylactic antibiotic treatment is recommended. Dexamethasone is indicated for elevated cerebrospinal fluid pressure. Lumbar puncture may also be necessary. Oxygen therapy or mechanical ventilation may be required.

Hemodynamic, cardiac and respiratory parameters, as well as blood electrolyte levels, should be carefully monitored and controlled.

Side effects

In high doses, this drug can cause profuse diarrhea, gastrointestinal bleeding, rash, and kidney and liver damage. However, to obtain an adequate therapeutic effect, this drug must be used in full dose.

Colchicine may cause reversible impairment of vitamin B12 absorption, which impairs the function of the ileal mucosa. The table below summarizes the main adverse reactions of colchicine by frequency (MedDRA dictionary coding, version 16.1): very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1,000, < 1/100), rare (≥ 1/10,000, < 1/1,000), very rare (< 1/10,000), frequency unknown (cannot be estimated from the available data).

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after the approval of a medicinal product is important. This allows for continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national pharmacovigilance system.

Expiration date

5 years.

Storage conditions

Keep out of reach of children. No special storage conditions required.

Packaging

30 tablets in a blister; 2 blisters in a cardboard box.

Vacation category

According to the recipe.

Producer

Haupt Pharma Amareg GmbH.

Address

Donaustaufer Strasse 378, 93055 Regensburg, Germany.