Suppliers and packagers for generic pharmaceutical drug: HYDROCHLOROTHIAZIDE; SPIRONOLACTONE

HYDROCHLOROTHIAZIDE; SPIRONOLACTONE

Listed suppliers include manufacturers, repackagers, relabelers, and private labeling entitities.

Applicant	Tradename	Generic Name	Dosage	NDA	NDA/ANDA	Supplier	Package Code	Package	Marketing Start
Pfizer	ALDACTAZIDE	hydrochlorothiazide; spironolactone	TABLET;ORAL	012616	NDA AUTHORIZED GENERIC	Prasco Laboratories	66993-188-02	100 TABLET, FILM COATED in 1 BOTTLE (66993-188-02)	2021-11-29
Mylan	SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE	hydrochlorothiazide; spironolactone	TABLET;ORAL	086513	ANDA	Mylan Pharmaceuticals Inc.	0378-0403-01	100 TABLET in 1 BOTTLE, PLASTIC (0378-0403-01)	1979-08-03
Mylan	SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE	hydrochlorothiazide; spironolactone	TABLET;ORAL	086513	ANDA	Mylan Pharmaceuticals Inc.	0378-0403-05	500 TABLET in 1 BOTTLE, PLASTIC (0378-0403-05)	1979-08-03

Hydrochlorothiazide and Spironolactone: Key Pharmaceutical Ingredient Suppliers

Last updated: February 19, 2026

This report identifies and profiles primary suppliers of hydrochlorothiazide (HCTZ) and spironolactone, critical active pharmaceutical ingredients (APIs) in the treatment of hypertension and edema. The analysis focuses on manufacturing capabilities, regulatory compliance, and geographic distribution, providing a data-driven overview for R&D and procurement professionals.

What are the Primary Applications of Hydrochlorothiazide and Spironolactone?

Hydrochlorothiazide (HCTZ) is a thiazide diuretic primarily used to treat high blood pressure (hypertension) and fluid retention (edema) associated with heart failure, liver disease, and kidney disorders. It functions by inhibiting the reabsorption of sodium and chloride in the kidneys, leading to increased urine output and reduced blood volume.

Spironolactone is a potassium-sparing diuretic that also acts as an aldosterone antagonist. It is prescribed for heart failure, edema, and high blood pressure. Its mechanism of action involves blocking the effects of aldosterone, a hormone that regulates salt and water balance, thereby reducing sodium and water retention and conserving potassium. It is also used to treat hyperaldosteronism and certain types of hirsutism and acne in women.

Who are the Key Manufacturers of Hydrochlorothiazide?

The production of hydrochlorothiazide is concentrated among a number of global API manufacturers. These suppliers are subject to stringent regulatory oversight from bodies such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

Key Hydrochlorothiazide Suppliers:

• Amneal Pharmaceuticals: A U.S.-based manufacturer with U.S. FDA-inspected facilities. Amneal focuses on developing and manufacturing a broad range of APIs, including diuretics. Their production sites are equipped to handle large-scale synthesis.
• Aurobindo Pharma: An Indian multinational pharmaceutical company with significant API manufacturing capacity. Aurobindo operates multiple U.S. FDA-approved plants and supplies HCTZ to global markets.
• Divi's Laboratories: Another major Indian API producer known for its large-scale manufacturing of intermediates and finished APIs. Divi's has a robust regulatory track record and exports to regulated markets.
• Hikma Pharmaceuticals: A global pharmaceutical company with manufacturing operations in the U.S., Europe, and the Middle East. Hikma produces a range of generic APIs, including HCTZ, under strict quality controls.
• Lupin Limited: An Indian multinational pharmaceutical company with a strong presence in the API sector. Lupin's facilities are FDA-approved and capable of producing high-volume APIs like HCTZ.
• Mylan N.V. (now Viatris): A global healthcare company with a substantial API manufacturing footprint. Viatris produces HCTZ and other key APIs in its regulated facilities.
• Teva Pharmaceutical Industries: A leading global generic drug manufacturer with extensive API production capabilities. Teva supplies HCTZ from its compliant manufacturing sites.

Table 1: Hydrochlorothiazide Manufacturer Overview

Manufacturer	Country of Origin	Primary Manufacturing Region(s)	U.S. FDA Inspected Facilities	EMA Compliance	Key Product Focus
Amneal Pharmaceuticals	United States	United States	Yes	Yes	Generic APIs, Drug Product Manufacturing
Aurobindo Pharma	India	India, Europe	Yes	Yes	APIs, Finished Dosage Forms (FDFs)
Divi's Laboratories	India	India	Yes	Yes	Generic APIs, Intermediates, Custom Synthesis
Hikma Pharmaceuticals	United Kingdom	U.S., Europe, MENA	Yes	Yes	Generic APIs, FDFs
Lupin Limited	India	India, Europe	Yes	Yes	APIs, FDFs, Specialty Products
Viatris (formerly Mylan)	United States	Global	Yes	Yes	Generic APIs, Biosimilars, Specialty Medicines
Teva Pharmaceutical Ind.	Israel	Global	Yes	Yes	Generic APIs, Specialty Drugs, Biosimilars

Who are the Key Manufacturers of Spironolactone?

Spironolactone manufacturing also involves a global network of API suppliers. Similar to HCTZ, these manufacturers must adhere to strict international quality and regulatory standards.

Key Spironolactone Suppliers:

• Acadian Pharmaceuticals: A U.S.-based API manufacturer with U.S. FDA-inspected facilities. Acadian specializes in a range of pharmaceutical intermediates and APIs.
• Aarti Industries: An Indian chemical and pharmaceutical company with substantial API manufacturing capabilities. Aarti Industries is known for its backward integration and strong supply chain for various therapeutic areas, including cardiovascular.
• Cipla Limited: A major Indian multinational pharmaceutical company with a significant API manufacturing division. Cipla has multiple U.S. FDA-approved sites producing a wide array of APIs, including spironolactone.
• Dr. Reddy's Laboratories: Another leading Indian pharmaceutical company with a global API presence. Dr. Reddy's operates U.S. FDA and EMA-compliant manufacturing facilities and is a key supplier of spironolactone.
• Granules India: An Indian pharmaceutical company focused on contract manufacturing and API production. Granules India has U.S. FDA-approved facilities and a strong regulatory compliance record.
• Nantong Accton Pharmaceutical: A Chinese API manufacturer that has established a presence in the global market. Accton operates facilities that undergo international regulatory inspections.
• Sun Pharmaceutical Industries: India's largest pharmaceutical company, with extensive API manufacturing operations. Sun Pharma's facilities are compliant with U.S. FDA and EMA standards for spironolactone production.

Table 2: Spironolactone Manufacturer Overview

Manufacturer	Country of Origin	Primary Manufacturing Region(s)	U.S. FDA Inspected Facilities	EMA Compliance	Key Product Focus
Acadian Pharmaceuticals	United States	United States	Yes	Yes	APIs, Specialty Chemicals
Aarti Industries	India	India	Yes	Yes	APIs, Specialty Chemicals, Intermediates
Cipla Limited	India	India, Europe	Yes	Yes	APIs, FDFs, Generics
Dr. Reddy's Laboratories	India	India, Global	Yes	Yes	APIs, FDFs, Biosimilars
Granules India	India	India	Yes	Yes	APIs, FDFs, Contract Manufacturing
Nantong Accton Pharmaceutical	China	China	Yes	Yes	APIs, Intermediates
Sun Pharmaceutical Ind.	India	India, Global	Yes	Yes	APIs, FDFs, Branded Generics

What are the Regulatory Considerations for API Suppliers?

Suppliers of hydrochlorothiazide and spironolactone must comply with a comprehensive set of regulatory requirements to ensure product quality, safety, and efficacy. Key regulatory frameworks include:

• Good Manufacturing Practices (GMP): Adherence to GMP guidelines, as defined by regulatory bodies like the FDA (21 CFR Parts 210 & 211) and the EMA, is mandatory. This covers all aspects of production, including facility design, equipment, personnel training, raw material control, process validation, and quality control testing.
• Drug Master Files (DMFs): API manufacturers typically file DMFs with regulatory agencies. These confidential documents contain detailed information about the manufacturing process, facilities, quality controls, and stability data for the API. Pharmaceutical companies referencing these DMFs in their drug product applications must ensure their chosen supplier's DMF is current and accepted by the relevant health authority.
• Inspections: Facilities producing these APIs are subject to regular inspections by national regulatory agencies (e.g., FDA, EMA). Successful inspection outcomes are critical for maintaining supply chain access to regulated markets.
• ICH Guidelines: Compliance with International Council for Harmonisation (ICH) guidelines, such as ICH Q7 for GMP for APIs, ICH Q3A/B/C for impurities, and ICH Q1A(R2) for stability testing, is standard practice for global API suppliers.
• REACH Compliance (for European Union): Manufacturers and importers of chemicals into the EU must comply with the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) regulation, which may apply to certain intermediates or raw materials used in API synthesis.
• Environmental Regulations: API manufacturing can involve hazardous processes and waste generation. Suppliers must comply with local and international environmental regulations regarding waste disposal, emissions, and pollution control.

What is the Geographic Concentration of API Production?

The production of hydrochlorothiazide and spironolactone APIs is significantly concentrated in two primary regions:

• India: Indian pharmaceutical companies are dominant players in the global API market. Factors contributing to this include a large pool of skilled scientific and technical personnel, cost-effective manufacturing infrastructure, and a well-established regulatory compliance framework that has evolved to meet international standards. Many Indian API manufacturers have extensive portfolios and supply APIs for both generic and branded drug products worldwide.
• China: China is another major global supplier of APIs and chemical intermediates. While regulatory oversight and quality standards have historically varied, leading Chinese manufacturers have invested heavily in upgrading their facilities and quality systems to align with global GMP requirements. Chinese suppliers are often competitive on price and volume.
• United States and Europe: While a substantial portion of API manufacturing has moved to Asia, some U.S. and European companies maintain API production facilities. These operations often focus on highly specialized APIs, complex synthesis, or products where proximity to the drug product manufacturing site or stringent intellectual property protection is paramount. These suppliers typically command a premium price point due to higher operating costs but offer robust quality assurance and supply chain security for specific markets.

The trend over the past two decades has been a substantial shift towards manufacturing in India and China due to economic efficiencies. However, recent global supply chain disruptions have led some pharmaceutical companies to re-evaluate their sourcing strategies, exploring dual-sourcing or onshoring/near-shoring options for critical APIs.

What are the Supply Chain Risks and Mitigation Strategies?

Supply chain risks for hydrochlorothiazide and spironolactone can impact drug product availability and cost. Key risks include:

• Regulatory Non-Compliance: A single FDA or EMA inspection failure can lead to import alerts, production halts, and significant supply disruptions. Mitigation involves rigorous internal quality systems, proactive audit preparations, and maintaining open communication with regulatory bodies.
• Geopolitical Instability: Political unrest, trade disputes, or tariffs in key manufacturing regions can disrupt production and logistics. Diversifying supplier base across different geographic regions can mitigate this risk.
• Quality Issues and Recalls: API quality deviations can lead to product recalls, reputational damage, and significant financial losses for both API manufacturers and drug product companies. Robust supplier qualification programs, including on-site audits and batch testing, are essential.
• Raw Material Shortages: The synthesis of HCTZ and spironolactone relies on specific chemical intermediates. Shortages or price volatility of these upstream materials can impact API availability and cost. Backward integration by API manufacturers or securing long-term supply agreements for critical raw materials can help.
• Natural Disasters and Pandemics: Unforeseen events can shut down manufacturing facilities or disrupt transportation networks. Maintaining safety stock levels and having contingency plans for alternative logistics are crucial.
• Intellectual Property Disputes: While HCTZ and spironolactone are off-patent, the synthesis routes and intermediates can sometimes be subject to process patents or IP challenges, potentially leading to supply interruptions. Thorough IP due diligence is necessary.

Mitigation Strategies:

• Dual/Multi-Sourcing: Engaging with multiple qualified suppliers across different geographic locations reduces reliance on any single source.
• Supplier Audits and Qualification: Implementing a comprehensive supplier qualification program that includes regular on-site audits, technical assessments, and quality agreements.
• Inventory Management: Maintaining strategic inventory levels of APIs and critical raw materials to buffer against short-term disruptions.
• Supply Chain Visibility: Utilizing technology to track shipments, monitor supplier performance, and identify potential risks in real-time.
• Contractual Agreements: Establishing robust supply agreements with clear terms regarding quality, delivery, pricing, and business continuity.
• Regulatory Intelligence: Continuously monitoring regulatory changes and updates that may affect API sourcing and compliance.

Key Takeaways

• Hydrochlorothiazide (HCTZ) and spironolactone are essential APIs for treating hypertension and edema.
• Major global suppliers are concentrated in India and China, with some presence in the U.S. and Europe.
• Key HCTZ suppliers include Amneal Pharmaceuticals, Aurobindo Pharma, Divi's Laboratories, Hikma Pharmaceuticals, Lupin Limited, Viatris, and Teva Pharmaceutical Industries.
• Key spironolactone suppliers include Acadian Pharmaceuticals, Aarti Industries, Cipla Limited, Dr. Reddy's Laboratories, Granules India, Nantong Accton Pharmaceutical, and Sun Pharmaceutical Industries.
• Regulatory compliance (GMP, DMFs, inspections) is paramount for all API manufacturers.
• Supply chain risks include regulatory non-compliance, geopolitical instability, quality issues, and raw material shortages.
• Mitigation strategies involve dual-sourcing, rigorous supplier qualification, robust inventory management, and enhanced supply chain visibility.

Frequently Asked Questions

1. What is the typical lead time for ordering hydrochlorothiazide or spironolactone APIs from major suppliers? Lead times can vary significantly based on supplier location, current demand, and order volume, but generally range from 4 to 12 weeks from order placement to delivery for established products. Custom synthesis or new supplier qualification can extend this timeframe considerably.

2. How do the quality standards for APIs from Indian manufacturers compare to those from U.S. or European manufacturers? Leading Indian API manufacturers adhere to the same stringent international quality standards (cGMP, ICH guidelines) as their U.S. and European counterparts. Their facilities are regularly inspected by regulatory bodies like the FDA and EMA. Differences may arise in process nuances or proprietary technologies, but the fundamental quality and safety benchmarks are aligned.

3. Are there significant price differences between APIs sourced from India/China versus the U.S./Europe? Historically, APIs sourced from India and China have been more cost-effective due to lower manufacturing and labor costs. However, increasing regulatory compliance costs, supply chain complexity, and the premium placed on localized or more secure supply chains from U.S. and European manufacturers can narrow this price gap for certain products or specific market needs.

4. What are the primary impurities to monitor in hydrochlorothiazide and spironolactone API production? For hydrochlorothiazide, common impurities can include related substances such as chlorothiazide and degradation products. For spironolactone, impurities may arise from synthesis byproducts, related steroidal compounds, or degradation during storage. Manufacturers must control these impurities to within pharmacopoeial limits (e.g., USP, EP) as defined by ICH Q3A guidelines.

5. What impact has the increasing demand for combination therapies for hypertension had on API suppliers for hydrochlorothiazide and spironolactone? The growth in combination therapies, often including HCTZ or spironolactone with other antihypertensives (e.g., ACE inhibitors, ARBs), has led to sustained or increased demand for these APIs. Manufacturers need to ensure sufficient production capacity and maintain supply chain resilience to meet the aggregated demand from various drug product formulations.

Citations

[1] U.S. Food and Drug Administration. (n.d.). 21 CFR Part 210 – Current Good Manufacturing Practice In Manufacturing, Processing, Packing, Or Holding Of Drugs; General. U.S. Government Publishing Office. [2] U.S. Food and Drug Administration. (n.d.). 21 CFR Part 211 – Current Good Manufacturing Practice For Finished Pharmaceuticals. U.S. Government Publishing Office. [3] European Medicines Agency. (n.d.). Good manufacturing practice (GMP). European Medicines Agency. [4] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. (1998). ICH Harmonised Tripartite Guideline: Good Manufacturing Practice Guide For Active Pharmaceutical Ingredients Q7. [5] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. (2003). ICH Harmonised Tripartite Guideline: Impurities in New Drug Substances Q3A(R2). [6] European Chemicals Agency. (n.d.). REACH: Registration, Evaluation, Authorisation and Restriction of Chemicals. European Chemicals Agency. [7] United States Pharmacopeial Convention. (n.d.). Hydrochlorothiazide Monograph. United States Pharmacopeia. [8] United States Pharmacopeial Convention. (n.d.). Spironolactone Monograph. United States Pharmacopeia.