List of Excipients in Branded Drug REVONTO

Generic Drugs Containing REVONTO

Company	Ingredient	NDC	Excipient
US WorldMeds LLC	dantrolene sodium	27505-003	MANNITOL
US WorldMeds LLC	dantrolene sodium	27505-003	SODIUM HYDROXIDE
USWM LLC	dantrolene sodium	78670-003	MANNITOL
USWM LLC	dantrolene sodium	78670-003	SODIUM HYDROXIDE

What are the Most Frequently-Used Excipients in REVONTO?

# Of NDCs	Excipient
3	MANNITOL
3	SODIUM HYDROXIDE

REVONTO Excipient Strategy, Patent Position, and Commercial Opportunities

Last updated: September 5, 2026

Revonto is an injectable dantrolene sodium product used for the emergency treatment of malignant hyperthermia. Its commercial differentiation is driven less by active-ingredient exclusivity than by reconstitution speed, vial burden, storage, supply reliability, hospital purchasing, and the cost and performance of its excipient system. The core formulation uses dantrolene sodium, mannitol, sodium hydroxide, and sterile water for reconstitution. The principal opportunity is to improve emergency usability while preserving chemical stability and regulatory simplicity.

What is Revonto and how is it used?

Revonto contains dantrolene sodium for intravenous use in malignant hyperthermia, a rare but life-threatening reaction associated with certain anesthetic agents and depolarizing neuromuscular blockers. Treatment requires rapid administration and repeated dosing until clinical control is achieved.[1]

The labeled Revonto presentation is a 20-mg vial of dantrolene sodium. Each vial is reconstituted with 60 mL of sterile water for injection, producing a solution of approximately 0.333 mg/mL.[1] The initial recommended dose is 2.5 mg/kg, with additional doses administered as needed. A 70-kg patient may therefore require approximately nine 20-mg vials for the initial dose alone.

That vial burden creates the main commercial weakness of the traditional formulation. Hospitals must maintain substantial inventory, pharmacy or operating-room staff must reconstitute multiple vials, and the product generates significant packaging, compounding, waste, and administration costs.

Revonto formulation composition

Component	Function	Commercial relevance
Dantrolene sodium	Active pharmaceutical ingredient	Treats malignant hyperthermia by reducing calcium release from skeletal-muscle sarcoplasmic reticulum
Mannitol	Bulking agent and formulation excipient	Supports the lyophilized cake and contributes to product stability and reconstitution behavior
Sodium hydroxide	pH adjustment	Supports dantrolene sodium solubility in the reconstituted alkaline solution
Sterile water for injection	Reconstitution medium	Must be supplied separately and used according to labeling

Revonto is supplied as a lyophilized powder rather than a ready-to-use solution. The formulation choice reflects the poor practical suitability of maintaining dantrolene sodium as a concentrated aqueous injectable over the product shelf life.

What excipients protect Revonto’s commercial performance?

The excipient system is functional rather than ornamental. Mannitol and alkaline pH control are central to producing a stable, reconstitutable dantrolene product.

Mannitol’s role in the lyophilized formulation

Mannitol is used as a bulking agent in many sterile freeze-dried products. In Revonto, its quantity is substantial relative to the 20-mg active dose. The excipient helps create a physically acceptable lyophilized cake and supports consistent vial filling and powder recovery.

Mannitol also creates formulation constraints. Its crystallization behavior during freezing and drying can affect cake structure, reconstitution time, residual moisture, and batch-to-batch appearance. A reformulation that changes mannitol concentration or replaces it with another bulking agent would require comparative studies covering:

• Reconstitution time
• Cake appearance and collapse
• Residual moisture
• Dantrolene assay and degradation products
• Particulate matter
• Sterility and container-closure integrity
• Stability under labeled storage conditions

Potential substitutes include sucrose, trehalose, lactose, glycine, and combinations of crystalline and amorphous bulking agents. Each introduces different risks. Sugars can increase amorphous content and improve glass formation but may create moisture sensitivity. Glycine can improve cake structure but may crystallize unpredictably. A replacement program would need to balance fast dissolution against long-term solid-state stability.

Alkaline pH and sodium hydroxide

Dantrolene sodium is formulated in an alkaline environment. Sodium hydroxide adjusts pH and supports solubilization after reconstitution. The pH system is commercially important because changes can affect:

• Dantrolene solubility
• Color formation
• Degradation pathways
• Compatibility with infusion equipment
• Injection-site tolerability
• Reconstitution consistency

An excipient strategy that reduces alkalinity could improve handling or compatibility, but it may also reduce solubility and increase precipitation risk. A substitute buffer system would therefore carry a significant chemistry, manufacturing, and controls burden.

Reconstitution water is part of the product strategy

Revonto requires 60 mL of sterile water for injection per vial. The product cannot be reconstituted with standard saline or dextrose solutions unless specifically permitted by labeling or validated compatibility data.[1] This requirement creates an operational dependency. Hospitals must maintain sufficient sterile water alongside the drug, and emergency carts must have both components available.

A commercial reformulation that uses a smaller reconstitution volume would reduce preparation time and improve emergency deployment. The most valuable change would be a higher-concentration product that preserves stability without generating precipitation or unacceptable injection characteristics.

What formulations are protected by Revonto’s excipient strategy?

Revonto’s known formulation is a conventional lyophilized dantrolene sodium product. Its commercial protection is unlikely to depend on a currently active composition-of-matter patent. Dantrolene sodium has been used clinically for decades, and the principal competitive barriers are formulation know-how, manufacturing capability, regulatory approvals, distribution, and hospital purchasing arrangements.

Potential formulation claim categories

A new product could seek protection around:

1. A defined dantrolene sodium-to-mannitol ratio.
2. A specified alkaline pH range after reconstitution.
3. A lyophilized cake with defined residual moisture.
4. A reduced-volume reconstitution system.
5. A stable concentrated dantrolene solution or suspension.
6. A vial, transfer device, or emergency kit combining drug and diluent.
7. A formulation with reduced particulate formation.
8. A product with improved reconstitution time at room temperature.
9. A formulation with improved stability after partial reconstitution.
10. A ready-to-use or premixed presentation.

Patentability would depend on novelty, non-obviousness, enablement, and adequate data demonstrating an unexpected technical effect. A simple substitution of mannitol with another standard lyophilization excipient would face a higher obviousness risk unless it produced a measurable and unexpected improvement.

When does Revonto lose exclusivity?

Revonto’s active-ingredient and basic formulation protection is effectively mature. The FDA Orange Book should be reviewed for the current product-specific listing, patents, and exclusivity status, but no material period of new chemical entity exclusivity is expected for this legacy dantrolene product.[2]

Exclusivity category	Revonto position
New chemical entity exclusivity	Expired or not applicable
Orphan-drug exclusivity	No current exclusivity expected for the legacy product
Pediatric exclusivity	No current period expected
Basic active-ingredient patent	Expired
Core formulation patent	No current barrier identified in the cited public sources
Regulatory pathway for competitors	ANDA, 505(b)(2), or full NDA depending on formulation and clinical differences
Biosimilar pathway	Not applicable because dantrolene sodium is a small molecule

A competitor with the same active ingredient, dosage form, strength, route, and therapeutic use could potentially pursue an ANDA if it can establish pharmaceutical equivalence and bioequivalence or satisfy applicable waiver requirements. A materially different concentration, delivery system, or clinical use could require a 505(b)(2) application or a new NDA.

Are Paragraph IV challenges relevant to Revonto?

A Paragraph IV challenge is relevant only if a listed patent blocks an ANDA applicant. Because the core product is an old small-molecule injectable and the basic dantrolene formulation is mature, the main Paragraph IV risk would involve later-added formulation, device, process, or use patents rather than the dantrolene molecule itself.

A competitor could challenge a listed patent by alleging that it is invalid, unenforceable, or not infringed. The commercial value of such a challenge would depend on whether the patent covers the incumbent’s only commercially viable formulation or merely a narrow presentation.

No material Revonto-specific Paragraph IV litigation or settlement agreement is identified in the public sources cited here.

What is the Orange Book status of Revonto?

The Orange Book is the relevant FDA source for patents and regulatory exclusivity associated with approved small-molecule drug products.[2] Revonto should be assessed by:

• NDA number and approved sponsor
• Listed patents
• Patent-use codes
• Pediatric exclusivity
• Generic approvals
• Therapeutic-equivalence codes
• Current marketing status

For a legacy injectable such as Revonto, the key business question is not whether the active ingredient remains patent protected. It is whether a competing product can meet the practical requirements of emergency malignant-hyperthermia treatment at a lower total hospital cost.

The absence of meaningful Orange Book protection would shift competition toward manufacturing scale, supply continuity, formulation performance, contracting, and clinical workflow.

How does Revonto compare with Ryanodex?

Ryanodex is the most important branded formulation comparator because it was developed to reduce the preparation burden associated with conventional dantrolene injection. It uses a 250-mg vial and is reconstituted with 5 mL of sterile water, resulting in a substantially more concentrated product than Revonto.[3]

Attribute	Revonto	Ryanodex
Active ingredient	Dantrolene sodium	Dantrolene sodium
Vial strength	20 mg	250 mg
Reconstitution volume	60 mL per vial	5 mL per vial
Typical initial vial burden for a 70-kg patient	About 9 vials	About 2 vials
Main operational issue	High vial count and large reconstitution volume	Higher unit price and branded-product economics
Key differentiation	Established formulation and availability	Rapid preparation and lower injection volume
Biosimilar relevance	None	None

The comparison shows why excipient and presentation strategy can create commercial value even when the active ingredient is old. Ryanodex’s higher concentration changes the emergency workflow, reduces the number of vials, and may lower preparation time. Its commercial challenge is the price premium and the need for hospitals to justify the acquisition cost through reduced labor, lower waste, and faster treatment.

What commercial opportunities exist for Revonto excipient innovation?

The strongest opportunities are concentrated in emergency usability and total cost of ownership.

1. Reduced-volume reconstitution

A more concentrated formulation could reduce the quantity of sterile water and shorten reconstitution. The technical challenge is maintaining dantrolene solubility at higher concentrations while controlling pH, particulates, and stability.

A successful product could compete directly with high-concentration dantrolene products while using a lower-cost excipient system.

2. Faster-dissolving lyophilized cake

A formulation engineered for rapid dissolution could improve performance without changing the labeled dose. Opportunities include:

• Optimized cake porosity
• Controlled particle size
• Alternative bulking-agent ratios
• Modified freezing and primary-drying cycles
• Improved wetting after diluent addition
• Vial geometry designed for mixing

This approach may be easier to develop than a concentrated formulation because it preserves the established strength and route.

3. Integrated drug-and-diluent emergency kit

Revonto’s dependence on sterile water creates a packaging opportunity. A kit could combine:

• Dantrolene vials
• Sterile water
• Transfer devices
• Large-volume syringes
• Mixing instructions
• Emergency dosing references
• A tamper-evident or color-coded presentation

A kit may require a combination of drug, device, and packaging approvals. Its patent value would likely be strongest in the device configuration and workflow rather than the basic excipient composition.

4. Ready-to-use or premixed presentation

A stable ready-to-use product would offer the largest operational advantage. The barriers are substantial:

• Dantrolene chemical stability in water
• High concentration requirements
• Container compatibility
• Light sensitivity
• Particulate control
• Shelf-life expectations
• Sterilization strategy
• Cold-chain or special-storage requirements

A ready-to-use presentation could support premium pricing if it materially reduces preparation time and eliminates sterile-water handling.

5. Hospital emergency-cart optimization

A lower-volume product can reduce malignant-hyperthermia-cart size and storage requirements. Hospitals and ambulatory surgery centers may value products that:

• Fit existing emergency carts
• Reduce the number of stocked vials
• Simplify expiration management
• Reduce inventory discrepancies
• Improve readiness audits
• Lower pharmacy preparation workload

The relevant buyer is often the institution rather than the individual prescriber. Commercial messaging should quantify preparation time, storage footprint, and inventory cost.

What manufacturing and intellectual-property barriers affect new Revonto competitors?

The main barriers are technical and operational.

Manufacturing barriers

Dantrolene sodium injectable manufacturing requires control of:

• API particle characteristics
• Aseptic processing
• Lyophilization cycle reproducibility
• Residual moisture
• Reconstitution performance
• Alkaline solution stability
• Sterile water compatibility
• Container-closure integrity
• Extractables and leachables
• Particulate matter

The drug’s emergency use increases the commercial cost of supply interruption. Manufacturers must maintain reliable API sourcing and validated sterile capacity. A technically acceptable product may still fail commercially if it cannot support hospital stocking requirements.

IP barriers

A new entrant could encounter patents covering:

• Concentrated dantrolene formulations
• Stabilized aqueous compositions
• Reconstitution systems
• Emergency kits
• Transfer devices
• Specific dosing or administration methods
• Manufacturing processes
• Container-closure systems

The strongest patent estate would combine composition claims with device and method-of-use claims. Composition claims are more vulnerable when they rely on routine excipient substitutions. Device and workflow claims may provide narrower but more defensible protection if the product demonstrates a measurable reduction in preparation time or administration risk.

What method-of-use patents and litigation affect Revonto?

The core malignant-hyperthermia indication is established and does not create a meaningful new-use exclusivity opportunity for the legacy product. Potential method-of-use opportunities could involve:

• Prehospital treatment
• Ambulatory surgery center protocols
• Prophylactic use in selected high-risk patients
• Treatment of related hypermetabolic syndromes
• Protocolized use with specific anesthetic exposures
• Reduced-dose or repeat-dose administration algorithms

Such claims would face clinical and regulatory scrutiny. A method-of-use patent would be commercially valuable only if it supports a differentiated label or a recognized treatment protocol.

No material public litigation or settlement agreement involving Revonto’s excipient strategy is identified in the cited sources. Litigation risk is more likely to arise around a new competitor’s formulation or device patent than around the old dantrolene active ingredient.

What licensing opportunities exist for Revonto-related excipient technology?

Potential licensing targets include:

• Lyophilization platforms
• High-concentration injectable formulation technology
• Sterile single-use transfer devices
• Ready-to-use container systems
• Emergency drug-kit packaging
• Contract sterile manufacturing capacity
• Dantrolene API supply arrangements

No public licensing transaction tied specifically to Revonto’s mannitol or sodium-hydroxide formulation is identified in the cited sources. A company pursuing this market would more likely license enabling formulation or device technology than acquire rights to the legacy excipient combination.

The most attractive deal structure would link milestones to:

1. Proof of rapid reconstitution.
2. Completion of toxicology or compatibility work.
3. FDA acceptance of the development pathway.
4. Successful stability data.
5. Approval of the commercial presentation.
6. Hospital formulary conversion.

What FDA pathway should a new excipient-based dantrolene product use?

The regulatory pathway depends on how closely the product matches Revonto or another approved dantrolene product.

Product concept	Likely pathway
Same strength, dosage form, route, and formulation profile	ANDA, if pharmaceutical equivalence and applicable bioequivalence requirements are satisfied
New excipient system with meaningful formulation differences	505(b)(2) may be appropriate
New concentration or delivery system with clinical-use differences	505(b)(2) or NDA
Ready-to-use product with materially different stability and administration	Likely 505(b)(2) or NDA
Device-integrated emergency kit	Drug application plus device and combination-product review considerations
New therapeutic indication	505(b)(2) or NDA with supporting clinical evidence

Injectable products face heightened scrutiny for sterility, visible and subvisible particles, container compatibility, and dose-delivery reliability. A formulation that reduces reconstitution time but introduces new administration risks may not produce a favorable regulatory or commercial profile.

What generic launch risks exist for Revonto?

Generic entry risk is moderate for a conventional 20-mg dantrolene sodium injection because the molecule and basic dosage form are mature. The principal risks are:

• API supply constraints
• Aseptic manufacturing failures
• Difficulty matching reconstitution performance
• Low market volume relative to development cost
• Hospital contracts favoring established suppliers
• Inventory requirements for emergency readiness
• Product liability exposure from preparation or dosing errors
• Competition from higher-concentration branded products

A generic entrant may win on unit price but lose on total treatment cost if its product requires more vials, more sterile water, and more staff time than a concentrated alternative.

How strong is the Revonto patent estate?

Revonto’s patent estate is weak as a barrier to conventional generic entry but potentially valuable as a platform for formulation improvement.

Estate component	Strength assessment
Dantrolene molecule	Expired and commercially unprotective
Conventional mannitol lyophilized formulation	Mature technology with limited blocking value
Alkaline pH adjustment	Likely difficult to protect broadly
Fast-reconstitution formulation	Potentially protectable with supporting data
High-concentration composition	Potentially valuable if non-obvious and stable
Emergency kit or transfer device	Potentially protectable through combination and device claims
New method of use	Limited value unless supported by a differentiated label
Manufacturing process	Useful as a trade secret and potentially patentable if technically specific

The most defensible strategy is a layered estate covering composition, process, container, device, and workflow performance. A single narrow excipient claim is unlikely to create durable market control.

What is the revenue exposure and competitive outlook?

Drug-specific Revonto revenue is not separately disclosed in the public financial materials cited here. Market value is tied to the installed base of operating rooms, ambulatory surgery centers, hospitals, anesthesia providers, and emergency departments that must maintain malignant-hyperthermia treatment capability.

Demand is structurally unusual:

• Usage is low relative to inventory requirements.
• Purchases are driven by readiness, not routine prescription volume.
• Product expiration and replacement create recurring demand.
• Hospitals may stock multiple treatment doses despite rare clinical use.
• Supply shortages can rapidly increase commercial leverage for available manufacturers.
• Formulary decisions may prioritize response time over acquisition price.

The competitive landscape includes conventional dantrolene injections, high-concentration products such as Ryanodex, generic dantrolene products, and future combination kits. Product differentiation will depend on preparation time, vial count, storage efficiency, price per treated patient, and supply reliability.

Key Takeaways

• Revonto is a legacy dantrolene sodium injectable for malignant hyperthermia.
• Its core excipient system uses mannitol and sodium hydroxide in a lyophilized formulation.
• The major weakness is operational: 20-mg vials require substantial reconstitution volume and high vial counts.
• The strongest commercial opportunity is a faster, higher-concentration, lower-volume product.
• Ready-to-use presentations and integrated drug-and-diluent kits offer greater differentiation but carry higher development risk.
• Conventional active-ingredient patent protection is not a meaningful barrier.
• New entrants would compete through formulation performance, manufacturing reliability, hospital contracts, and emergency workflow economics.
• Biosimilar risk does not apply because dantrolene sodium is a small molecule.
• No material Revonto-specific Paragraph IV litigation or excipient-related settlement is identified in the cited public sources.
• The strongest future patent strategy would combine formulation, process, container, device, and method-of-use claims.

FAQs

Can mannitol be removed from the Revonto formulation?

Yes, but removal would require a new formulation development program. The replacement must maintain cake structure, stability, sterility, rapid dissolution, and acceptable residual moisture.

Is a premixed dantrolene injection commercially feasible?

It is technically possible, but high-concentration aqueous stability, container compatibility, particulate control, and shelf-life requirements make it substantially more difficult than a lyophilized presentation.

Does Revonto require sterile water for reconstitution?

Yes. The labeled Revonto product is reconstituted with sterile water for injection, and the required volume is materially larger than that used by high-concentration dantrolene products.[1]

Could a new dantrolene product qualify for an ANDA?

A close formulation and dosage-form copy may qualify for an ANDA. A substantially different concentration, excipient system, device, or administration method may require a 505(b)(2) application or NDA.

What is the most valuable excipient innovation for dantrolene injection?

A formulation that enables high drug concentration, rapid reconstitution, low particulate formation, and room-temperature stability would likely have the greatest commercial value.

References

1. U.S. Food and Drug Administration. (2023). Revonto: Dantrolene sodium for injection, USP prescribing information.
2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
3. U.S. Food and Drug Administration. (2023). Ryanodex: Dantrolene sodium for injectable suspension prescribing information.
4. Malignant Hyperthermia Association of the United States. (2024). Treatment of malignant hyperthermia and dantrolene stocking guidance.