LODOCO Colchicine Tablets 0.5 mg .5 mg Tablet, 30-count — NDC 82867-001-01 (Billing 82867-0001-01)
This is a package of 30 tablets of LODOCO Colchicine Tablets 0.5 mg .5 mg Tablet from AGEPHA Pharma USA, LLC, marketed since Jun 2023 and currently FDA-listed; retail pharmacies pay about $17.00 per tablet (NADAC). It is the main listing for this product, which comes in 2 package sizes.
NDC database record
One package, one record: these facts belong to NDC 82867-001-01 alone.
- Record
- FDA NDC Directory package listing · Human prescription drug
- Code segments
- 82867 labeler · 001 product · 01 package
- Package marketed since
- Jun 16, 2023
- Sample package
- No — commercial package
- Listing certified through
- Dec 31, 2027
- Billing quantity
- 30 EA per package
- Barcode (UPC)
- 0382867001018, 0382867001025
- Medicaid fills, this package
- 166 prescriptions in the last four reported quarters
- FDA record last changed
- Aug 27, 2026
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GSN (GCN sequence number): 085021
- GCN: 54457
- HICL (First Databank): 003717
- AHFS class code: 24:44.00.00
- RxCUI (RxNorm): 197540
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 5, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 1, 2026
RxNorm drug class
This medicine belongs to the Alkaloid class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 1, 2026
Clinical
Colchicine is used to prevent gout attacks (sudden, severe pain in one or more joints caused by abnormally high levels of a substance called uric acid in the blood) in adults. Colchicine is also used to relieve the pain of gout attacks when they occur. Colchicine is also used to treat familial Mediterranean fever (FMF; an inborn condition that causes episodes of fever, pain, and swelling of the stomach area, lungs, and joints) in adults and children 4 years of age and older. Colchicine (Lodoco®) is used to reduce the risk of heart attack, stroke, cardiovascular death, and needing certain ty...
Read the full MedlinePlus article ↗- It depends on the product. Most colchicine products — tablets, capsules, and the liquid Gloperba — are used to prevent gout flares in adults. Colcrys tablets and generic colchicine...
- Diarrhea is the most common side effect and it's a real nuisance for many people. Colchicine affects the lining of the gut, and nausea, cramping, and loose stools often come with i...
- Why does colchicine cause so much diarrhea?
- This is one of the most important questions you can ask. Colchicine has some serious drug interactions that have caused deaths — not just discomfort. Certain antibiotics (like clar...
Patient education
Supplement & herbal interactions
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 5, 2026
Ask a licensed pharmacist directly — free, answered by our team.
Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $17.000 | $509.99 / 30 tablets |
| Medicaid paysCMS SDUD · 12 mo | $16.77 | $503.03 / 30 tablets |
| Medicare drug plans payPart D · Q2 2026 | $17.77 | $532.97 / 30 tablets |
Where does this data come from?
- CMS NADAC weekly file · file of Sep 30, 2026
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · through Q4 2025
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Marketing end | Status |
|---|---|---|---|---|---|---|
| 82867-0001-01 You're viewing this Main listing | 1 BLISTER PACK in 1 CARTON / 30 TABLET in 1 BLISTER PACK | $17.00 / ea | $509.99 | 2023-06-16 | — | Active |
| 82867-0001-02 82867-001-02 | 1 BLISTER PACK in 1 CARTON / 30 TABLET in 1 BLISTER PACK Sample | — | — | 2023-06-16 | — | Active |
In Medicaid, this is the most-dispensed pack of this product — about 100% of fills over the last four reported quarters. See all packs ↓
Pack size FAQ
What quantity is in this package?
How does this package differ from NDC 82867-0001-02?
What NDC number is used to bill for this package of LODOCO Colchicine Tablets 0.5 mg .5 mg Tablet?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Lodoco .5 mgthis 82867-0001-01 | AGEPHA | 30 tablets | $17.000 | — | Availability likely | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA Orange Book · refreshed Oct 3, 2026
- CMS NADAC weekly file · file of Sep 30, 2026
Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 12364675 ↗ | Method of use | U-3639 | Nov 1, 2033 |
| US 12233035 ↗ | Method of use | U-4132 | Nov 1, 2033 |
| US 11026901 ↗ | Method of use | U-3638 | Nov 1, 2033 |
| US 11026900 ↗ | Method of use | U-3639 | Nov 1, 2033 |
| US 11026899 ↗ | Method of use | U-3639 | Nov 1, 2033 |
| US 10842762 ↗ | Method of use | U-3640 | Nov 1, 2033 |
| US 10265281 ↗ | Method of use | U-3639 | Nov 1, 2033 |
| US 10206891 ↗ | Method of use | U-3641 | Nov 1, 2033 |
| US 10130585 ↗ | Method of use | U-3642 | May 9, 2034 |
| US 9744144 ↗ | Method of use | U-3643 | Nov 1, 2033 |
| US 11944594 ↗ | Method of use | U-3864 | Nov 1, 2033 |
| US 12280025 ↗ | Method of use | U-4168 | Nov 1, 2033 |
| US 11944595 ↗ | Method of use | U-3867 | Nov 1, 2033 |
| US 11944595 ↗ | Method of use | U-3868 | Nov 1, 2033 |
Is there a generic version of LODOCO 0.5 MG TABLET?
The FDA approved a generic — why can’t I get it at my pharmacy yet?
Why do different websites show different generic release dates?
What does “FDA listed” mean?
What does a patent or protection date mean here?
What does “current Orange Book estimate” mean?
Can a generic come out before the last patent expires?
Can a generic come out after the listed dates?
What is the difference between patents and exclusivity?
Why are there multiple patent dates?
Where does this data come from?
- FDA Orange Book · refreshed Oct 3, 2026
What it looks like
Where does this data come from?
- FDA label on DailyMed · label index refreshed Oct 5, 2026
Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
🧪 Avoiding an ingredient? See Colchicine inactive ingredients by manufacturer: every current product's list side by side, so you can ask your pharmacy for the version that does not list it.
Where does this data come from?
IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.- FDA label on DailyMed · label index refreshed Oct 5, 2026
- FDA openFDA NDC Directory · synced Oct 1, 2026
Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
Manufacturer & labeler
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1. INDICATION AND USAGE LODOCO is indicated to reduce the risk of myocardial infarction (MI), stroke, coronary revascularization, and cardiovascular death in adult patients with established atherosclerotic disease or with multiple risk factors for cardiovascular disease. LODOCO is an alkaloid indicated: • to reduce the risk of myocardial infarction (MI), stroke, coronary revascularization, and cardiovascular death in adult patients with established atherosclerotic disease or with multiple risk factors for cardiovascular disease ( 1 ).
⏱️ Dosage and Administration ▾
2. DOSAGE AND ADMINISTRATION
2.1Recommended Dosage The recommended dosage is 0.5 mg orally once daily. If a dose of LODOCO is missed, the missed dose should be taken as soon as possible, and the patient should then return to the normal dosing schedule. If a dose is skipped, the patient should not double the next dose. The recommended dosage is 0.5 mg orally once daily ( 2.1 ).
💊 Dosage Forms and Strengths ▾
3. DOSAGE FORMS AND STRENGTHS Tablets: 0.5 mg - White to slightly yellow, round, biconvex tablets, debossed with ‘L1’ on one side and plain on the other side. Tablets: 0.5 mg ( 3 ).
⛔ Contraindications ▾
4. CONTRAINDICATIONS Concurrent use of strong CYP3A4 inhibitors or P-glycoprotein inhibitors with LODOCO is contraindicated, because life-threatening and fatal colchicine toxicity has been reported in these patients with colchicine taken in therapeutic doses [see Drug interactions (7)] . LODOCO use is contraindicated in patients with renal failure (Creatinine clearance less than 15 mL/minute) and severe hepatic impairment.
LODOCO is contraindicated in patients with pre-existing blood dyscrasias and in patients hypersensitive to this drug or any inactive ingredient of LODOCO [see Description (11)] . • Concurrent use of strong CYP3A4 inhibitors or P-gp inhibitors with LODOCO is contraindicated, including in patients with hepatic or renal impairment ( 4 ). • LODOCO is contraindicated in patients with pre-existing blood dyscrasias, renal failure, and severe hepatic impairment ( 4 ).
⚠️ Warnings and Cautions ▾
5. WARNINGS AND PRECAUTIONS
5.1Blood Dyscrasias LODOCO can cause myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, and aplastic anemia, which can be life-threatening or fatal [see Adverse Reactions (6)] . Gastrointestinal symptoms often are the first sign of colchicine toxicity, so new symptoms should prompt an evaluation for toxicity. Concomitant use of drugs that reduce the metabolism of colchicine or the presence of hepatic or renal impairment increases the risk of developing blood dyscrasias.
Use of LODOCO in patients with pre-existing blood dyscrasias, renal failure (Creatinine clearance less than 15 mL/minute), or severe hepatic dysfunction, and concomitant use of strong CYP3A4 inhibitors or P-glycoprotein inhibitors is contraindicated [see Contraindications (4)] . Concomitant use of moderate CYP3A4 inhibitors with LODOCO should be avoided in patients with risk factors for increased systemic exposure of colchicine. Monitor patients with any degree of renal impairment and hepatic impairment for colchicine toxicity [see Use in Specific Populations (8.6, 8.7)] .
5.2Neuromuscular Toxicity LODOCO can cause neuromuscular toxicity and rhabdomyolysis. Concomitant use of drugs that reduce the metabolism of colchicine or the presence of hepatic or renal impairment increases the risk of developing neuromuscular toxicity. Gastrointestinal symptoms often are the first sign of colchicine toxicity, so new symptoms should prompt evaluation for toxicity.
Use of LODOCO in patients with renal failure (Creatinine clearance less than 15 mL/minute), or severe hepatic dysfunction, and concomitant use of strong CYP3A4 inhibitors or P-glycoprotein inhibitors is contraindicated [see Contraindications (4)] . Concomitant use of moderate CYP3A4 inhibitors with LODOCO should be avoided in patients with risk factors for increased systemic exposure of colchicine [see Use in Specific Populations (8.6, 8.7) and Drug Interactions (7)] . If a patient develops signs of neuromuscular toxicity, discontinue LODOCO, investigate other causes, and treat appropriately.
Concomitant use of LODOCO and HMG CoA reductase inhibitors, gemfibrozil, and fenofibric acid or cyclosporine may potentiate the development of myopathy [see Drug interactions (7)] . Monitor patients with any degree of renal and hepatic impairment for adverse effects of LODOCO. • Blood dyscrasias : myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, and aplastic anemia have been reported ( 5.1 ). • Neuromuscular toxicity : Myotoxicity including rhabdomyolysis may occur, especially in combination with other drugs known to cause this effect.
Consider temporary interruption or discontinuation of LODOCO ( 5.2 ).
🤒 Adverse Reactions ▾
6. ADVERSE REACTIONS
6.1Clinical Trials Experience Because clinical studies are conducted under widely varying and controlled conditions, adverse reaction rates observed in clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not predict the rates observed in a broader patient population in clinical practice. In the LoDoCo2 trial, myalgia was reported for 21.2% of individuals randomized to colchicine and 18.5% of individuals randomized to matching placebo (hazard ratio 1.15, 95%CI 1.01-1.31).
6.2Postmarketing Experience The following adverse reactions have been identified with colchicine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or establish a causal relationship to drug exposure. These most often occur with excessive accumulation or overdosage [see Overdosage (10)] .
Neuromuscular : myotoxicity, weakness, numbness, paresthesia, rhabdomyolysis. Gastrointestinal : diarrhea, vomiting, abdominal cramping, abdominal pain. Renal : acute renal impairment Dermatology : rashes and alopecia Hematological : thrombocytopenia, leukopenia, pancytopenia The common side-effects reported in published clinical studies and literature with the use of colchicine are gastrointestinal symptoms (diarrhea; vomiting; abdominal cramping) and myalgia ( 6 ).
To report SUSPECTED ADVERSE REACTIONS, contact AGEPHA Pharma FZ LLC at 1 (800) 963-0353 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
🔄 Drug Interactions ▾
7. DRUG INTERACTIONS Colchicine is a substrate for the efflux transporter P-glycoprotein (P-gp). CYP3A4 is the primary enzyme involved in the metabolism of colchicine.
If LODOCO is administered with drugs that inhibit P-gp, most of which also inhibit CYP3A4, increased concentrations of colchicine are likely (Table 1). Table 1: Drug Interactions Drug class Outcome/effect Clinical comment Strong CYP3A4 Inhibitors † atazanavir clarithromycin darunavir/ritonavir indinavir itraconazole ketoconazole lopinavir/ritonavir nefazodone nelfinavir ritonavir saquinavir telithromycin tipranavir/ritonavir Significant increases in colchicine plasma levels [see Clinical Pharmacology (12.3)] . Concomitant use of LODOCO with strong CYP3A4 inhibitors is contraindicated [see Contraindications (4)] .
Moderate CYP3A4 Inhibitors amprenavir aprepitant diltiazem erythromycin fluconazole, fosamprenavir (prodrug of amprenavir) verapamil Significant increase in colchicine plasma concentration is anticipated. Monitor patients receiving moderate CYP3A4 inhibitors for signs of colchicine toxicity. Avoid use in patients with existing renal or hepatic impairment [see Warnings and Precautions (5)] .
Grapefruit grapefruit juice Grapefruit juice increases exposure to colchicine. Advise patients to avoid grapefruit or grapefruit juice when taking LODOCO. P- glycoprotein Inhibitors † cyclosporine ranolazine Significant increase in colchicine plasma levels is anticipated with P-gp inhibitors.
Concomitant use of LODOCO with strong P-gp inhibitors is contraindicated [see Contraindications (4)] . HMG-Co A Reductase Inhibitors Pharmacokinetic and/or pharmacodynamic interaction: the addition of one drug to a stable long term regimen of the other has resulted in myopathy and rhabdomyolysis (including fatality). Monitor patients for signs or symptoms of muscle pain toxicity.
Other Lipid Lowering drugs fibrates gemfibrozil Digitalis Glycosides digoxin P-gp substrate; rhabdomyolysis has been reported. Oral contraceptives Ethinyl estradiol and norethindrone (Ortho-Novum 1/35) In healthy female volunteers given coadministered with 0.6 mg colchicine twice daily, hormone concentrations are not affected [see Clinical Pharmacology (12.3)] . Colchicine can interact with oral contraceptives like norethindrone/ethinyl estradiol and can cause adverse events like diarrhea, nausea, upper abdominal pain, cold sweat etc.
Females using oral contraceptives should be prescribed LODOCO with caution and observed for adverse events. † Patients with renal or hepatic impairment should not be given LODOCO in conjunction with strong CYP3A4 or P-gp inhibitors [see Contraindications (4)] . Coadministration of P-gp and/or CYP3A4 inhibitors (e.g., cyclosporine or clarithromycin) have been demonstrated to alter the concentration of colchicine. The potential for drug-drug interactions must be considered prior to and during therapy.
See FPI for a complete list of reported and potential interactions ( 7 ).
👥 Use in Specific Populations ▾
8. USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk summary Available human data from published literature on colchicine use in pregnancy over several decades have not identified any drug associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data) . Colchicine crosses the human placenta. Although animal reproduction and developmental studies were not conducted with LODOCO (colchicine), published animal reproduction and development studies indicate that colchicine causes embryofetal toxicity and altered postnatal development at exposures within or above the clinical therapeutic range.
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Data Human Data Available data from published observational studies, case series, and case reports over several decades do not suggest an increased risk for major birth defects or miscarriage in pregnant women with rheumatic diseases (such as rheumatoid arthritis, Behcet’s disease, or Familial Mediterranean fever (FMF)) treated with colchicine at therapeutic doses during pregnancy. Limitations of these data include the lack of randomization and inability to control for confounders such as underlying maternal disease and maternal use of concomitant medications.
8.2Lactation Risk summary Colchicine is present in human milk (see Data) . Adverse events in breastfed infants have not been reported in the published literature after administration of colchicine to lactating women. There are no data on the effects of colchicine on milk production.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for LODOCO and any potential adverse effects on the breastfed infant from LODOCO or from the underlying maternal condition. Data Limited published data from case reports and a small lactation study demonstrate colchicine is present in breastmilk. A systematic review of literature reported no adverse effects in 149 breastfed children and advised to reconsider breastfeeding if the infant has diarrhea.
In a prospective observational cohort study, no gastrointestinal or other symptoms were reported in 38 colchicine-exposed breastfed infants.
8.3Females and Males of Reproductive Potential Infertility Case reports and epidemiology studies in human male subjects on colchicine therapy indicated that infertility from colchicine is rare and may be reversible.
8.4Pediatric Use Safety and effectiveness have not been established in pediatric patients.
8.5Geriatric Use The total number of subjects included in the LoDoCo2 study who were 65 and over and 75 and over were 3098 (56.1%). No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. This drug is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function.
Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function.
8.6Renal Impairment Colchicine is known to be excreted renally. In renally impaired patients, the total clearance of colchicine is significantly reduced. In patients, with renal impairment, elevated plasma concentrations of colchicine were observed, and may lead to the development of colchicine toxicity and adverse reactions like myeloneuropathy characterized by proximal weakness and elevated serum creatinine, and possibly rhabdomyolysis [see Warnings… [Excerpted — this section continues on DailyMed.]
🆘 Overdosage ▾
10. OVERDOSAGE Acute overdose exceeding 0.5 mg/kg (35 mg for a 70 kg average adult) is usually fatal. Fatalities have been reported with as little as 7 mg.
Symptoms : Colchicine poisoning presents in three sequential and usually overlapping phases. The first stage of acute colchicine toxicity typically occurs within 24 hours of ingestion and includes gastrointestinal symptoms such as abdominal pain, nausea, vomiting, and diarrhea, and significant fluid loss, leading to volume depletion. Peripheral leukocytosis may also be seen.
The second stage develops 24 to 72 hours after ingestion and is characterized by multi-organ failure. Death is usually a result of respiratory depression and cardiovascular collapse. Recovery may be accompanied by rebound leukocytosis about one week after the initial ingestion.
Treatment : No specific antidote is known. Elimination of toxins by gastric lavage followed by activated charcoal should be attempted within 1-2 hours of ingestion. Colchicine is not effectively removed by hemodialysis.
🧬 Clinical Pharmacology ▾
12. CLINICAL PHARMACOLOGY
12.1Mechanism of Action The mechanism of action of colchicine in the prevention of major cardiovascular events is not understood. However, it is known that colchicine disrupts cytoskeletal functions through inhibition of β-tubulin polymerization into microtubules and consequently prevents the activation, degranulation, and migration of neutrophils. Colchicine may also interfere with the intracellular assembly of the inflammasome complex in neutrophils and monocytes that mediates activation of interleukin-1β.
These anti-inflammatory effects are consistent with clinical data demonstrating that colchicine reduces high sensitivity C- reactive protein (hs-CRP).
12.2Pharmacodynamics The pharmacodynamics of colchicine in the intended indication is not completely understood.
12.3Pharmacokinetics In healthy adults, colchicine exhibits linear pharmacokinetics within a dose range of 0.5 to 1.5 mg. Mean pharmacokinetic parameter values of LODOCO in healthy adults are shown in table 2. Table 2: Summary of LODOCO Pharmacokinetic Parameters in Healthy Adults under Fasting and Fed Conditions BE studies C max ng/ml T max * hours t ½ hours AUC 0-t ng·h/ml Single dose of 0.5 mg (fasting) 2.1± 1.0 1.0 (Range 0.5-2.3) 31.9 18.6±
7.0Single dose of 0.5 mg (fed) 1.8± 0.4 1.7 (Range 0.7- 3.5) 31.0 16.4 ± 4.4 *Median and range are presented Absorption Oral colchicine intake undergoes an entero-hepatic recirculation. In healthy adults, LODOCO is absorbed when given orally, reaching a mean Cmax 2.1 ng/ml in approximately 1 hour after a single dose administered under fasting conditions. The mean absolute bioavailability of colchicine is reported to be approximately 45%.
Effect of food When LODOCO was administered with or following a high-fat, high-calorie meal in a bioavailability study, the results showed a lack of a significant food effect, see Table 2, above. LODOCO may be administered with or without food. The mean peak plasma concentration of LODOCO under fed conditions was found to be 1.8 ng/ml in approximately 1.75 hour.
Distribution The mean apparent volume of distribution in healthy volunteers is approximately 1300 L. Colchicine binding to serum protein is 39 ± 5%, primarily to albumin regardless of concentration. After reabsorption, is rapidly removed from the plasma and distributed to various tissues.
Colchicine is found in high concentrations in leucocytes, kidneys, the liver, and spleen. Colchicine crosses the placenta. Colchicine also distributes into breast milk.
Colchicine can also cross the blood-brain barrier and accumulate within the brain, which contains large amount of tubulin [see Use in Specific Populations (8.1, 8.2)] . Elimination Metabolism Colchicine is demethylated to two primary metabolites, 2-O-demethylcolchicine and 3-O-demethylcolchicine (2- and 3-DMC, respectively) and one minor metabolite, 10-O-demethylcolchicine (also known as colchiceine). In vitro studies using human liver microsomes have shown that CYP3A4 is involved in the metabolism of colchicine to 2- and 3-DMC.
Plasma levels of these metabolites are (less than 5% of parent drug). Excretion In healthy volunteers (n=12), 40 to 65% of 1 mg orally administered colchicine was recovered unchanged in urine. Enterohepatic recirculation and biliary excretion are also postulated to play a role in colchicine elimination.
Following single oral dose of 0.5 mg daily, the mean effective half-life in healthy volunteers is 19 hours. Colchicine is a substrate of P-gp. Colchicine is not removed by hemodialysis.
Specific Populations Geriatric Patients The pharmacokinetic studies of LODOCO were not conducted in elderly patients. In a study, conducted to compare the relative bioavailability in between 18 elderly subjects and 20 young subjects, the following pharmacokinetic parameter values (mean ± SD) were observed for colchicine in the young and elderly subjects, respectively: AUC (ng/.hr/mL) 22.4 ± 7.0 and 25.0 ± 6.9; C max (ng/mL) 2.6 ± 0.7 and 2.6 ± 1.… [Excerpted — this section continues on DailyMed.]
📦 How Supplied / Storage and Handling ▾
16. HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied LODOCO (colchicine) tablets 0.5 mg are white to slightly yellow, round, and biconvex and debossed with ‘L1’ on one side and plain on the other side and they are available as a single Aluminum/PVC blister pack of 30 tablets, which is secondary packaged in a carton: NDC 82867-001-01.
16.2Storage Store LODOCO at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F), [See USP Controlled Room Temperature]. Store LODOCO tablets in the original package in order to protect from light.
📋 Description ▾
11. DESCRIPTION LODOCO contains colchicine, which is an alkaloid chemically described as (S)-N-(5,6,7,9-tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo[a]heptalen-7-yl)acetamide with a molecular formula of C 22 H 25 NO 6 and a molecular weight of 399.4 g/mol. The structural formula of colchicine is given below.
Colchicine occurs as white to pale yellow powder, very soluble in water. LODOCO (colchicine) tablets are supplied for oral administration as white to slightly yellow, round, biconvex tablets debossed with ‘L1’ on one side and plain on the other side containing 0.5 mg of colchicine USP as the active ingredient and the following inactive ingredients: gelatin, lactose monohydrate, magnesium stearate, potato starch, and talc. Colchi-structure
🔬 Clinical Studies ▾
14. CLINICAL STUDIES The evidence for the efficacy of colchicine in patients with cardiovascular events is derived from published literature (LoDoCo2) along with other supportive studies. The LoDoCo2 trial was an investigator-initiated, randomized, placebo controlled, double-blind, event-driven trial conducted to assess the efficacy of colchicine 0.5mg once daily orally in patients with stable coronary artery disease.
The study included 5522 patients, in which 2762 were assigned to the colchicine group and 2760 to placebo. The baseline characteristics of the patients were balanced between the trial groups. Patients were treated for chronic coronary disease, with 99.7% taking an antiplatelet agent or an anticoagulant, 96.6% a lipid-lowering agent, 97.3% of which were statins, 62.1% a beta-blocker, and 71.7% an inhibitor of the renin–angiotensin system.
LoDoCo2 assessed the efficacy of colchicine 0.5 mg once daily in patients with stable coronary artery disease. Patients between 35-85 years were eligible for participation in the LoDoCo2 trial if they had proven coronary artery disease, were clinically stable for at least 6 months, without comorbidities that would preclude follow-up, or contraindication to colchicine use. The mean (±SD) age of the patients was 66±8.6 years, and 846 (15.3%) were female.
The median time on study medication was 28.6 months. The primary end point of LoDoCo2 trial was a composite of cardiovascular death, spontaneous (nonprocedural) myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization. In the LoDoCo2 trial, 0.5 mg of colchicine once daily resulted in a 31% lower relative risk (RRR) of the primary composite endpoint events compared to placebo (HR, 0.69; 95% [CI] 0.57 to 0.83; p<0.001) and the number needed to treat (NNT) was 36.
The results of the primary endpoint are summarized in Table 4. Table 4: Summary of efficacy results of LoDoCo2 trial LoDoCo2 Trial End Point Colchicine (N=2762) No. of patients (%) Placebo (N=2760) No. of patients (%) Hazard ratio (95% Cl) P value Primary end point Cardiovascular death, myocardial infarction, ischemic stroke, or ischemia driven coronary revascularization 187 (6.8) 264 (9.6) 0.69 (0.57–0.83) <0.001 Ischemia-driven coronary revascularization 135 (4.9) 177 (6.4) 0.75 (0.60–0.94) Myocardial infarction 83 (3.0) 116 (4.2) 0.70 (0.53–0.93) Ischemic stroke 16 (0.6) 24 (0.9) 0.66 (0.35–1.25) Cardiovascular death 20 (0.7) 25 (0.9) 0.80 (0.44–1.44) Myocardial infarction refers to spontaneous (non-procedural) myocardial infarction .
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🧪 Nonclinical Toxicology ▾
13. NONCLINICAL TOXICOLOGY
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Two-year studies were conducted in mice and rats to assess the carcinogenic potential of colchicine. No evidence of colchicine-related tumorigenicity was observed in mice or rats at colchicine oral doses up to 3 and 2 mg/kg/day, respectively, approximately 29 and 38 times, the recommended human dose of 0.5 mg on a mg/m 2 basis. Mutagenesis Colchicine was negative for mutagenicity in the bacterial reverse mutation assay.
In a chromosomal aberration assay in cultured human white blood cells, colchicine treatment resulted in the formation of micronuclei. Since published studies demonstrated that colchicine induces aneuploidy from the process of mitotic nondisjunction without structural DNA changes, colchicine is not considered clastogenic, although micronuclei are formed. Impairment of Fertility No studies of colchicine effects on fertility were conducted with LODOCO.
However, published nonclinical studies demonstrated that colchicine-induced disruption of microtubule formation affects meiosis and mitosis. Reproductive studies also reported abnormal sperm morphology and reduced sperm counts in males, and interference with sperm penetration, second meiotic division and normal cleavage in females when exposed to colchicine. Colchicine administered to pregnant animals resulted in fetal death and teratogenicity.
These effects were dose-dependent, with the timing of exposure critical for the effects on embryofetal development. The nonclinical doses evaluated were generally higher than an equivalent human therapeutic dose, but safety margins for reproductive and developmental toxicity could not be determined.
📄 Patient Package Insert ▾
PATIENT INFORMATION PATIENT INFORMATION LODOCO (Low-Doe-Co) (colchicine) tablets, for oral use What is LODOCO? LODOCO is a prescription medicine used to reduce the risk of heart attack, stroke, certain types of heart procedures, and cardiovascular death in adults with: known buildup of plaque inside the arteries (atherosclerotic disease), or with multiple risk factors for cardiovascular disease. Do not take LODOCO if you: take certain medicines called strong CYP3A4 inhibitors or P-glycoprotein inhibitors.
Ask your healthcare provider if you are not sure. Taking certain medicines with LODOCO may cause your level of LODOCO to be too high in your body and cause life-threatening side effects or death. have severe kidney or liver problems. have blood problems. are allergic to colchicine or any of the ingredients in LODOCO. See the end of this leaflet for a complete list of ingredients in LODOCO.
Before taking LODOCO, tell your healthcare provider about all your medical conditions, including if you: have liver or kidney problems. are pregnant or plan to become pregnant. It is not known if LODOCO will harm your unborn baby. are breastfeeding or plan to breastfeed. LODOCO can pass into your breast milk.
Talk to your healthcare provider about the best way to feed your baby during treatment with LODOCO. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you take: certain medicines called moderate CYP3A4 inhibitors cholesterol lowering medicines cyclosporine antibiotics Ask your healthcare provider or pharmacist if you are not sure if you take any of the medicines listed above.
This is not a complete list of all the medicines that can interact with LODOCO. Taking LODOCO with certain other medicines can affect each other and cause serious side effects or death. Do not start a new medicine without talking to your healthcare provider.
Your healthcare provider can tell you if it is safe to take LODOCO with other medicines. Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine.
How should I take LODOCO? Take LODOCO exactly as your healthcare provider tells you to take it. Do not change your dose or stop taking LODOCO without talking to your healthcare provider first.
Take LODOCO by mouth 1 time each day. If you miss a dose of LODOCO, take it as soon you remember and then take your next dose at your regular time. Do not take 2 doses of LODOCO at the same time to make up for a missed dose.
If you take too much LODOCO, go to the nearest hospital emergency room right away. What should I avoid while taking LODOCO? Avoid eating grapefruit or drinking grapefruit juice while taking LODOCO.
Grapefruit and grapefruit juice may increase your chance of side effects while taking LODOCO. What are the possible side effects of LODOCO? LODOCO may cause serious side effects, including: Blood problems.
LODOCO can cause low red blood cell counts, low white blood cell counts, and low platelet counts, which can be life-threatening or may lead to death. Muscle weakness (neuromuscular toxicity). LODOCO can cause muscle weakness and muscle problems.
Stop taking LODOCO and get medical help right away if you get muscle pain or weakness, or tingling or numbness in your fingers or toes. The most common side effects of LODOCO include: diarrhea, vomiting, and stomach-area (abdominal) cramping. Tell your healthcare provider right away if you develop any of these symptoms, they are often the first sign of having too much LODOCO in your body. muscle pain LODOCO may cause temporary fertility problems in males.
This may affect your ability to father a child. Talk to your healthcare provider if this is a concern for you. Tell your healthcare provider if you have any side effect that is new, that bothers you or that does not go away.
These are not all of the p… [Excerpted — this section continues on DailyMed.]
📄 Package Label / Principal Display Panel ▾
PRINCIPAL DISPLAY PANEL LODOCO-sample-panel-upd LODOCO-panel-upd