List of Excipients in Branded Drug PACERONE

Generic Drugs Containing PACERONE

Company	Ingredient	NDC	Excipient
Upsher-Smith Laboratories LLC	amiodarone hydrochloride	0245-0144	FD&C YELLOW NO. 6
Upsher-Smith Laboratories LLC	amiodarone hydrochloride	0245-0144	LACTOSE MONOHYDRATE
Upsher-Smith Laboratories LLC	amiodarone hydrochloride	0245-0144	MAGNESIUM STEARATE
Upsher-Smith Laboratories LLC	amiodarone hydrochloride	0245-0144	POVIDONE

What are the Most Frequently-Used Excipients in PACERONE?

# Of NDCs	Excipient
1	D&C YELLOW NO. 10
4	FD&C RED NO. 40
6	FD&C YELLOW NO. 6
7	LACTOSE MONOHYDRATE

PACERONE Excipient Strategy and Commercial Opportunities

Last updated: August 22, 2026

PACERONE is an immediate-release oral amiodarone hydrochloride tablet used for life-threatening ventricular arrhythmias. Its commercial opportunity is not based on strong brand exclusivity or an active patent moat. The opportunity is in differentiated generic formulations, excipient risk reduction, dose flexibility, supply reliability, and hospital-focused packaging.

The most practical strategy is a low-risk tablet platform that preserves the established amiodarone profile while addressing lactose sensitivity, tablet usability, excipient variability, and manufacturing consistency. More advanced approaches, such as amorphous solid dispersions or lipid-based delivery systems, could improve dissolution but would carry higher bioequivalence, stability, and regulatory risk.

What is PACERONE and which dosage forms are commercially relevant?

PACERONE contains amiodarone hydrochloride, a Class III antiarrhythmic. FDA labeling covers oral tablets in 100 mg, 200 mg, and 400 mg strengths. The product is used primarily when other available treatments are inadequate or not tolerated because of its serious pulmonary, hepatic, thyroid, ocular, neurologic, and cardiac toxicities (FDA, 2023a).

Attribute	PACERONE profile
Active ingredient	Amiodarone hydrochloride
Drug class	Class III antiarrhythmic
Route	Oral
Dosage form	Immediate-release tablet
Commercial strengths	100 mg, 200 mg, 400 mg
Reference product sponsor	Upsher-Smith Laboratories
Regulatory pathway	NDA 021087
Primary substitutes	Generic amiodarone hydrochloride tablets
Biosimilar exposure	None; amiodarone is a small-molecule drug
Main commercial constraint	Mature generic market and narrow clinical use
Main formulation opportunity	Differentiated oral solid dosage forms

Amiodarone has a long terminal half-life, extensive tissue distribution, and variable oral absorption. Food increases the rate and extent of absorption, making product labeling, administration instructions, and formulation consistency commercially important (FDA, 2023a).

What excipients are used in PACERONE tablets?

PACERONE labeling identifies conventional tablet excipients, including lactose monohydrate, microcrystalline cellulose, povidone, magnesium stearate, sodium starch glycolate, colloidal silicon dioxide, and, depending on strength or presentation, crospovidone or related processing excipients (DailyMed, 2024).

The excipient architecture is consistent with a conventional wet- or dry-granulated immediate-release tablet:

Excipient category	Likely function
Lactose monohydrate	Diluent and tablet bulk
Microcrystalline cellulose	Diluent, binder, and compaction aid
Povidone	Binder
Sodium starch glycolate	Superdisintegrant
Crospovidone	Alternative or supplemental superdisintegrant
Colloidal silicon dioxide	Glidant and moisture-control aid
Magnesium stearate	Lubricant

The formulation is not protected by a complex delivery technology. That creates room for excipient substitution, but any change must preserve dissolution, content uniformity, mechanical strength, stability, and bioequivalence.

What excipient risks matter most?

Lactose is the most visible patient-facing issue. Although the quantity in a tablet is generally small, a lactose-free version could support institutional formulary positioning and patients who avoid lactose-containing medicines.

Magnesium stearate and colloidal silicon dioxide are standard excipients with broad regulatory precedent. The main development risks are manufacturing-related: over-lubrication can slow dissolution, while excessive glidant or disintegrant can affect tablet strength, friability, and dissolution performance.

Sodium-containing excipients are present at low levels, but a sodium-reduced formulation could have value in hospital systems with strict excipient and electrolyte review policies. The commercial benefit would likely be modest unless the product is paired with a broader "low-excipient" positioning.

How should a PACERONE excipient strategy be designed?

The preferred strategy is a staged platform rather than a single high-risk reformulation.

Platform 1: Lactose-free immediate-release tablet

A lactose-free tablet could replace lactose monohydrate with combinations of microcrystalline cellulose, mannitol, dibasic calcium phosphate, or directly compressible starch.

Mannitol can improve mouthfeel and support a cleaner excipient profile, but it may increase tablet size and affect hygroscopicity. Dibasic calcium phosphate can improve hardness and reduce moisture sensitivity, although it may alter dissolution and powder-flow behavior. A microcrystalline cellulose and mannitol system is likely to provide the best balance for conventional immediate-release development.

Commercial value:

• Supports lactose-free labeling.
• Uses familiar compendial excipients.
• Can remain within a conventional ANDA strategy.
• May qualify for institutional substitution if strength, scoring, and appearance match the reference product.

Key technical risks:

• Tablet weight may increase.
• Amiodarone content uniformity must be controlled because the active ingredient has a relatively high dose in the 200 mg and 400 mg strengths.
• Dissolution must remain comparable across pH conditions.
• The formulation must avoid excessive tablet hardness that delays disintegration.

Platform 2: Low-excipient or "clean-label" tablet

A reduced-excipient formulation could use microcrystalline cellulose, crospovidone, colloidal silicon dioxide, and magnesium stearate, with no lactose, colorants, or unnecessary coating components.

This approach is commercially credible for hospital and specialty-pharmacy channels. It is less compelling as a consumer product because amiodarone is usually prescribed for serious cardiac disease, not selected based on lifestyle preferences.

The value proposition is operational rather than promotional: fewer excipients, reduced allergen concerns, simplified sourcing, and lower risk of supply interruption.

Platform 3: Improved swallowability

Amiodarone tablets are administered over loading and maintenance regimens that can involve multiple tablets per day. A scored 200 mg tablet with strong dose flexibility could support titration and reduce pill burden.

Potential approaches include:

• A robust, functionally scored 200 mg tablet.
• A 100 mg tablet optimized for titration.
• A 400 mg tablet designed for loading regimens.
• A smaller high-density tablet using improved compaction excipients.
• A film-coated tablet with reduced surface roughness.

The regulatory risk is highest for tablet scoring and subdivision. Split-tablet performance, weight variation, and dose uniformity must be demonstrated if the product is labeled for splitting.

Platform 4: Modified dissolution without modified release

A conventional immediate-release product can still be optimized for rapid and reproducible disintegration. Candidate tools include:

• Crospovidone or sodium starch glycolate selection.
• Controlled granulation endpoint.
• Particle-size control for amiodarone hydrochloride.
• Improved wetting through surfactant selection.
• Reduced hydrophobic lubricant exposure.
• More consistent compression-force control.

A formulation that improves dissolution consistency without changing the labeled dosage form is more commercially practical than a true sustained-release product.

What formulation patents could protect a differentiated amiodarone product?

A conventional PACERONE-compatible tablet is unlikely to support a broad, durable patent position by itself. Patent value would depend on a specific and defensible technical limitation.

Potential patentable subjects include:

Potential protection	Commercial relevance	Patent strength
Lactose-free composition	Differentiated generic positioning	Low to moderate
Narrow excipient-ratio ranges	Manufacturing and dissolution control	Moderate if unexpected results exist
Particle-size or solid-state control	Bioavailability and stability	Moderate to strong
Amorphous amiodarone dispersion	Solubility and dissolution	Moderate to strong, but higher CMC risk
Taste-masked dosage form	More relevant to oral liquids or ODTs	Moderate
Scored tablet geometry	Dose flexibility	Low to moderate
Packaging with moisture and light control	Stability protection	Low unless technically unusual
Patient-specific dosing method	Clinical-use differentiation	Depends on claims and prior art

The strongest formulation patent opportunity would likely involve a defined solid-state form, particle-size distribution, or composition that produces a measurable dissolution or stability advantage. A claim directed only to replacing lactose with mannitol would face substantial obviousness risk because both are established tablet diluents.

Method-of-use claims could cover dosing regimens or monitoring strategies, but the clinical and legal value would be limited by the age of amiodarone, extensive prior art, and the need to avoid claims that conflict with established labeling.

When does PACERONE lose exclusivity?

PACERONE is a mature product. Its original regulatory exclusivity and any meaningful original-drug patent protection have expired. Generic amiodarone hydrochloride tablets are widely marketed through ANDAs.

Exclusivity element	PACERONE status
New chemical entity exclusivity	Expired
Five-year NCE exclusivity	Not commercially relevant
Orphan-drug exclusivity	Not the current commercial barrier
Pediatric exclusivity	No meaningful current barrier identified
Original compound patent	Expired
Generic competition	Established
Biosimilar pathway	Not applicable
Current moat	Brand recognition, supply, contracting, and formulation differentiation

FDA’s Orange Book is the controlling source for current listed patents and exclusivity. For a mature amiodarone tablet, the key regulatory question is generally not whether PACERONE has remaining exclusivity, but whether a proposed product can satisfy ANDA requirements and avoid any currently listed, enforceable patent claims (FDA, 2024).

What is the Orange Book status of PACERONE?

PACERONE is associated with NDA 021087. The commercial market includes generic amiodarone hydrochloride tablets approved under ANDAs. The product does not have a biosimilar framework because amiodarone is a synthetic small molecule.

A new applicant would typically evaluate:

1. The current reference-listed drug designation.
2. Approved strengths and dosage-form requirements.
3. Any current Orange Book patent listings.
4. Paragraph IV exposure, if a listed patent remains relevant.
5. Whether the proposed formulation is therapeutically equivalent to the reference product.
6. Whether inactive-ingredient differences require additional justification.

For a standard immediate-release tablet, the lowest-risk route is an ANDA that matches the reference product’s dosage form and demonstrates pharmaceutical equivalence and bioequivalence.

Which companies are challenging PACERONE?

Generic competition comes primarily from ANDA holders marketing amiodarone hydrochloride tablets. These products compete on:

• Wholesale acquisition cost.
• Hospital contract pricing.
• Availability of all three strengths.
• Backorder performance.
• Product substitution status.
• Packaging configuration.
• Tablet appearance and scoring.
• Regulatory reliability.

The key competitive threat is not a single Paragraph IV challenger. It is multi-source generic competition combined with institutional price pressure. A new entrant without a differentiated supply or formulation proposition would face limited pricing power.

What generic entry risks exist for a new PACERONE product?

The main risks are commercial and technical rather than patent-based.

Bioequivalence risk

Amiodarone has low aqueous solubility and variable absorption. Differences in particle size, wetting, granulation, compression, and lubricant level can affect dissolution. The applicant must establish that formulation changes do not produce clinically relevant exposure differences.

Food-effect risk

The PACERONE label states that food increases amiodarone absorption. A differentiated formulation that changes the food effect could create regulatory complications, even if average exposure appears acceptable.

Product-quality risk

Amiodarone tablets must meet strict content-uniformity, assay, dissolution, degradation, and stability requirements. Light, moisture, and packaging interactions require control.

Safety-monitoring risk

Because amiodarone carries serious organ-toxicity warnings, manufacturers and distributors face higher pharmacovigilance sensitivity than products for less complex chronic conditions. Packaging and labeling must preserve all FDA warnings and monitoring instructions.

Substitution risk

A product that is therapeutically equivalent but visually or physically different from common generic tablets may generate pharmacy and hospital verification work. Matching tablet dimensions, imprint strategy, and strength differentiation can reduce dispensing errors.

What manufacturing and intellectual-property barriers affect commercial entry?

Amiodarone itself is not difficult to source at the level of a novel biologic or complex injectable. The barriers are process control and regulatory reproducibility.

Important manufacturing controls include:

• API particle-size distribution.
• Blend uniformity.
• Granulation moisture.
• Lubrication time.
• Compression-force range.
• Disintegration and dissolution.
• Residual moisture.
• Light-protective packaging.
• Stability under accelerated and long-term conditions.

A formulation patent can support premium positioning only if it produces a measurable advantage. Manufacturing know-how may be more valuable than patent protection, particularly where the market is price-sensitive and standard generic entry is already established.

Trade-secret value can arise from:

• A robust low-dose blend process.
• Reduced tablet-weight variability.
• High-throughput compression.
• Stable lactose-free formulation.
• Improved dissolution after long-term storage.
• Reduced dependence on a single excipient supplier.

How does PACERONE compare with other amiodarone opportunities?

Opportunity	Development burden	Differentiation	Commercial outlook
Standard generic tablet	Low to moderate	Low	Price-driven
Lactose-free tablet	Moderate	Moderate	Institutional and specialty opportunity
Scored 200 mg tablet	Moderate	Moderate	Useful for titration
Orally disintegrating tablet	Moderate to high	Moderate	Niche adherence opportunity
Oral suspension	High	High	Pediatric and swallowing-related niche
Amorphous dispersion	High	High	Possible patent platform
Modified-release product	Very high	High	Clinical and regulatory uncertainty
Combination product	Very high	High	Limited due to interaction and safety complexity

An oral suspension or orally disintegrating tablet could address swallowing difficulty, but it would require stronger justification for stability, dose uniformity, palatability, and administration accuracy. A modified-release product would face the highest clinical and regulatory burden because amiodarone’s long half-life and complex toxicity profile make exposure control important.

What revenue exposure and commercial opportunities exist?

PACERONE is unlikely to support a large premium-priced franchise solely through excipient changes. The addressable opportunity is more attractive in targeted channels:

• Hospital and health-system contracting.
• Specialty pharmacy.
• Products with reliable supply during generic shortages.
• Lactose-free or low-excipient positioning.
• 100 mg and 200 mg dose-titration packs.
• Unit-dose packaging for inpatient use.
• Moisture- and light-protective bottles or blister packs.
• International markets with fewer established suppliers.

Revenue upside would depend on securing formulary access and maintaining supply rather than broad consumer demand. A differentiated product could command a modest premium if it reduces procurement risk or solves a documented excipient or administration problem.

Key Takeaways

• PACERONE is an immediate-release amiodarone hydrochloride tablet available in 100 mg, 200 mg, and 400 mg strengths.
• The original exclusivity and patent barriers are no longer the main commercial issue.
• Generic competition is established, making price and supply reliability central.
• A lactose-free tablet is the most practical excipient-led opportunity.
• Scoring, tablet-size reduction, and improved dose flexibility could create meaningful usability differentiation.
• Advanced solid-state or dispersion technologies offer stronger patent potential but carry greater bioequivalence and CMC risk.
• A formulation patent based only on routine excipient substitution would likely have limited strength.
• Biosimilar competition is irrelevant because amiodarone is a small-molecule drug.
• The strongest commercial strategy is a robust, low-excipient, lactose-free immediate-release tablet supported by reliable multi-strength supply.
• FDA Orange Book and Drugs@FDA records should control final patent, exclusivity, and reference-product determinations.

FAQs

Can amiodarone tablets be formulated without lactose?

Yes. Lactose can be replaced with mannitol, microcrystalline cellulose, dibasic calcium phosphate, starch, or combinations of these materials. The replacement must preserve dissolution, content uniformity, stability, and bioequivalence.

Is amiodarone a good candidate for an orally disintegrating tablet?

It is a possible niche candidate, particularly for patients with swallowing difficulty. The main barriers are the high dose, tablet size, taste, dose uniformity, and the need to demonstrate that rapid disintegration does not alter exposure.

Can excipient changes trigger a new clinical trial for amiodarone?

A conventional ANDA formulation generally relies on pharmaceutical equivalence and bioequivalence rather than a new efficacy trial. Major changes in release profile, dosage form, route, or exposure may require a more extensive regulatory package.

Does PACERONE have a biosimilar or interchangeable-product pathway?

No. Amiodarone is a synthetic small molecule. Competing products are approved as generic drugs under the ANDA framework, not as biosimilars under the Biologics Price Competition and Innovation Act.

What is the best patent strategy for a new amiodarone formulation?

The strongest strategy would focus on a defined solid-state form, particle-size distribution, excipient ratio, dissolution profile, or stability result that is difficult to replicate and supported by comparative data. Routine lactose replacement alone is unlikely to provide broad protection.

References

1. DailyMed. (2024). Pacerone: Amiodarone hydrochloride tablet prescribing information. U.S. National Library of Medicine.

2. U.S. Food and Drug Administration. (2023a). Pacerone (amiodarone hydrochloride) tablets: Prescribing information. FDA.

3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.

4. U.S. Food and Drug Administration. (2024). Drugs@FDA: FDA-approved drugs database. FDA.

5. U.S. Pharmacopeial Convention. (2024). United States Pharmacopeia and National Formulary. USP Convention.