COLCHICINE; PROBENECID - Generic Drug Details

What are the generic sources for colchicine; probenecid and what is the scope of patent protection?

Colchicine; probenecid is the generic ingredient in five branded drugs marketed by Watson Labs, Merck, Ani Pharms, Beecham, Impax Labs, Novast Labs, Rising, Sandoz, and Lederle, and is included in eleven NDAs. Additional information is available in the individual branded drug profile pages.

Three suppliers are listed for this compound.

Summary for COLCHICINE; PROBENECID

US Patents:	0
Tradenames:	5
Applicants:	9
NDAs:	11
Finished Product Suppliers / Packagers:	3
Clinical Trials:	2
DailyMed Link:	COLCHICINE; PROBENECID at DailyMed

Recent Clinical Trials for COLCHICINE; PROBENECID

Identify potential brand extensions & 505(b)(2) entrants

Sponsor	Phase
Chinese University of Hong Kong	Phase 2
Mutual Pharmaceutical Company, Inc.	Phase 1

See all COLCHICINE; PROBENECID clinical trials

Pharmacology for COLCHICINE; PROBENECID

Drug Class	Alkaloid
Mechanism of Action	Cytochrome P450 3A4 Inhibitors P-Glycoprotein Interactions

Anatomical Therapeutic Chemical (ATC) Classes for COLCHICINE; PROBENECID

M04AB	Preparations increasing uric acid excretion
M04A	ANTIGOUT PREPARATIONS
M04	ANTIGOUT PREPARATIONS
M	Musculo-skeletal system

M04AC	Preparations with no effect on uric acid metabolism
M04A	ANTIGOUT PREPARATIONS
M04	ANTIGOUT PREPARATIONS
M	Musculo-skeletal system

M04AC	Preparations with no effect on uric acid metabolism
M04A	ANTIGOUT PREPARATIONS
M04	ANTIGOUT PREPARATIONS
M	Musculo-skeletal system

US Patents and Regulatory Information for COLCHICINE; PROBENECID

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Ani Pharms	PROBENECID AND COLCHICINE	colchicine; probenecid	TABLET;ORAL	083734-001	Approved Prior to Jan 1, 1982		DISCN	No	No
Beecham	PROBENECID AND COLCHICINE	colchicine; probenecid	TABLET;ORAL	084321-001	Approved Prior to Jan 1, 1982		DISCN	No	No
Watson Labs	COL-PROBENECID	colchicine; probenecid	TABLET;ORAL	084279-001	Approved Prior to Jan 1, 1982	AB	RX	Yes	Yes
Novast Labs	PROBENECID AND COLCHICINE	colchicine; probenecid	TABLET;ORAL	040618-001	May 13, 2008	AB	RX	No	No
Sandoz	PROBENECID AND COLCHICINE	colchicine; probenecid	TABLET;ORAL	086130-001	Approved Prior to Jan 1, 1982		DISCN	No	No

COLCHICINE; PROBENECID Market Analysis and Financial Projection Experimental

The Market Dynamics and Financial Trajectory of Colchicine and Probenecid

Introduction

Colchicine, a centuries-old drug, has been a cornerstone in the treatment of gout and other inflammatory conditions. When combined with probenecid, it forms a potent therapeutic agent for managing uric acid levels and preventing gout attacks. However, the market dynamics and financial trajectory of these drugs have been marked by significant changes, particularly following regulatory interventions and market exclusivity.

Historical Context and Regulatory Impact

Before 2010, colchicine was available in unregulated and unapproved forms, priced very low, often less than $0.50 per pill[2][4].

• The FDA's Unapproved Drug Initiative in 2010 led to the approval of Colcrys, a brand-name version of colchicine, after a clinical trial. This approval resulted in the removal of other, much lower-priced versions of colchicine from the market[2][4].

Price Increases and Market Exclusivity

The approval of Colcrys and the subsequent market exclusivity granted to its manufacturer led to a dramatic increase in the price of colchicine.

• The price of a prescription for colchicine rose nearly 16-fold from $11.25 in 2009 to $190.49 in 2011[2].
• Medicaid unit prices for colchicine increased from $0.24 per pill in 2008 to $4.20 per pill in 2011 and peaked at $4.66 per pill in 2015[1][4].

Impact on Public Spending

The price increases had a profound impact on public spending on colchicine.

• Medicaid spending on single-ingredient colchicine rose by 2833% between 2008 and 2017, with 58% of this increase attributed to price increases alone. In 2017, spending totaled $32.2 million, compared to just $2.1 million if prices had remained at pre-Colcrys levels[1][4].

Effect on Patient Access and Health Outcomes

The sharp price increase led to reduced access to colchicine for many patients.

• Use of colchicine dropped by 17% between 2009 and 2011 and by 27% over the following decade. Patients turned to alternative medications like allopurinol and corticosteroids, which did not offer the same therapeutic benefits as colchicine. This shift resulted in worse disease control, with a 39.8% increase in emergency department visits and a 10.5% increase in rheumatology doctor visits for gout patients[2].

Authorized Generics and Their Impact

Authorized generics of colchicine entered the market in 2015 but were priced only marginally lower than the brand-name medication.

• These generics were still considerably more expensive than the previous unapproved formulations, contributing to the ongoing financial burden on patients and healthcare systems[1][4].

Global Market and Future Projections

The global colchicine market is expected to grow, driven by increasing demand for gout treatment.

• The market is projected to expand at a CAGR of 6.56% from 2024 to 2030, reaching a value of USD 1,558.9 million by 2030. The U.S. remains the largest market for colchicine, with a growing recognition of its efficacy in managing gout symptoms[3].

Additional Therapeutic Applications

Beyond gout, colchicine is being explored for other therapeutic uses, including cardiovascular applications.

• The Colchicine Cardiovascular Outcomes Trial (COLCOT) suggested that colchicine could be repurposed for cost-effective secondary prevention after myocardial infarction. However, the high prices in the U.S. market pose a significant barrier to its widespread adoption for these new indications[4].

Challenges and Limitations

The colchicine market faces several challenges, including price fluctuations and regulatory hurdles.

• Price volatility, driven by changes in manufacturing costs, regulatory developments, and market dynamics, affects both consumers and healthcare providers. This unpredictability can lead to budgeting uncertainties for healthcare organizations and financial strain for patients[3].

Probenecid and Colchicine Combination

The combination of probenecid and colchicine is used to enhance the efficacy of colchicine in treating gout.

• Probenecid acts as a uricosuric agent, increasing the urinary excretion of uric acid and reducing serum urate levels. When combined with colchicine, it provides a synergistic effect in managing gout symptoms[5].

Clinical Pharmacology and Precautions

The probenecid and colchicine combination has specific clinical pharmacology and precautions.

• Probenecid inhibits the tubular reabsorption of urate, while colchicine has antigout activity. The combination requires careful management to prevent side effects such as hematuria, renal colic, and the formation of uric acid stones[5].

Conclusion

The market dynamics and financial trajectory of colchicine and its combination with probenecid have been significantly influenced by regulatory decisions and market exclusivity. While these drugs remain crucial for managing gout and other conditions, the high prices and limited access pose substantial challenges for patients and healthcare systems.

Key Takeaways

• The FDA's approval of Colcrys led to a dramatic increase in colchicine prices.
• Public spending on colchicine has grown exponentially due to price increases.
• Patient access to colchicine has decreased, leading to worse disease control.
• The global colchicine market is expected to grow, driven by increasing demand for gout treatment.
• The combination of probenecid and colchicine is effective but requires careful management.

FAQs

Q: What led to the significant price increase of colchicine in the U.S.? A: The FDA's approval of Colcrys in 2010 and the subsequent market exclusivity granted to its manufacturer led to the removal of lower-priced, unapproved versions of colchicine from the market, resulting in a sharp price increase[2][4].

Q: How did the price increase affect patient access to colchicine? A: The price increase led to a 17% drop in colchicine use between 2009 and 2011 and a 27% drop over the following decade. Patients turned to alternative medications, which often did not provide the same therapeutic benefits[2].

Q: What are the additional therapeutic applications of colchicine being explored? A: Beyond gout, colchicine is being explored for cardiovascular applications, including secondary prevention after myocardial infarction, as suggested by the COLCOT trial[4].

Q: What is the role of probenecid in the combination with colchicine? A: Probenecid acts as a uricosuric agent, increasing the urinary excretion of uric acid and reducing serum urate levels, thereby enhancing the efficacy of colchicine in treating gout[5].

Q: What are the challenges faced by the colchicine market? A: The market faces challenges such as price fluctuations, regulatory hurdles, and the unpredictable pricing landscape, which can lead to budgeting uncertainties and financial strain for patients[3].

Sources

1. McCormick, N., et al. "Prolonged Increases in Public-Payer Spending and Prices After Approval of Colcrys (Colchicine) for Gout." JAMA Internal Medicine, 30 Nov. 2020.
2. Ly, D., et al. "A sharp increase in the price of the gout drug colchicine led to lower use and worse disease control." UCLA Health, 8 May 2023.
3. IndustryARC. "Colchicine Market - Forecast(2024 - 2030)." IndustryARC, 2023.
4. US Pharmacist. "Colchicine, Investigative Drug for COVID-19, Much More Expensive in US." US Pharmacist, 9 Dec. 2020.
5. DailyMed. "Label: PROBENECID AND COLCHICINE tablet." DailyMed, n.d.