EKTERLY sebetralstat 300 mg Tablet, 4-count
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Drugs used in hereditary angioedema class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
Sebetralstat is used to treat sudden attacks of hereditary angioedema (HAE; genetic condition causing recurrent severe swelling episodes). Sebetralstat is in a class of medications called plasma kallikrein inhibitors. It works by blocking a certain substance in the body that is responsible for producing the symptoms of angioedema.
Read the full MedlinePlus article ↗Patient education
Supplement & herbal interactions
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💊 What it looks like
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🧪 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.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII M28OL1HH48
Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
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UNII EX438O2MRT
Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
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UNII XM0M87F357
A dark iron oxide compound that gives medicines their black or dark color. It's used as a colorant in tablets and capsules to help identify the product and make it visually distinctive.
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UNII U72Q2I8C85
A mixture of fats derived from coconut oil that acts as an emulsifier and solubilizer. It helps blend oil and water-based ingredients together and improves how the body absorbs certain drugs.
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UNII E89I1637KE
Guar gum is a natural thickener made from guar bean seeds. It's used in medicines as a binder and thickening agent to hold ingredients together and create the right texture and consistency.
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UNII 3NXW29V3WO
Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII 7CVR7L4A2D
A starch-derived carbohydrate produced by breaking down corn, potato, or tapioca starch. It functions as a filler and binder to give the medicine bulk and texture, and sometimes as a mild sweetener or texture enhancer in powders and tablets.
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UNII C9H2L21V7U
A fat derived from coconut or palm oil containing shorter fatty acid chains. It serves as a solvent and carrier to help dissolve or suspend active ingredients, improving absorption and stability in liquid formulations.
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UNII 7T9FYH5QMK
A plant-derived powder that serves as a binder and filler in tablets and capsules. It helps hold ingredients together, adds bulk, and aids in smooth tablet disintegration when swallowed.
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UNII 23ZQ42JZZH
A synthetic polymer made by chemically linking polyvinyl alcohol to polyethylene glycol. It acts as a binder and film-former to hold tablet ingredients together and create smooth coatings on capsules or tablets.
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UNII 532B59J990
Polyvinyl alcohol is a synthetic polymer made from plant-derived materials. It's used as a binder to hold ingredients together, a film-former in coatings, and a thickener in liquid formulations.
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UNII U725QWY32X
Povidone K30 is a synthetic polymer made from petroleum. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in the stomach so the medicine can be absorbed.
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UNII 7SEV7J4R1U
A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
15 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 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 each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $8,309.32 | $33,237.29 / 4 tablet |
| Medicare drug plans payPart D · Q2 2026 | $8,942.18 | $35,768.71 / 4 tablet |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Ekterly 300 mgthis 82928-0300-04 | KalVista | 4 tablets | — | — | FDA listed | — |
Where does this data come from?
⏳ 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 11739068 ↗ | Method of use | U-4223 | Jun 23, 2037 |
| US 11234939 ↗ | Method of use | U-4223 | Jan 26, 2039 |
| US 11198691 ↗ | Method of use | U-4223 | Nov 26, 2035 |
| US 11084809 ↗ | Drug substance | U-4223 | Nov 26, 2035 |
| US 10611758 ↗ | Method of use | U-4223 | Nov 26, 2035 |
| US 10364238 ↗ | Drug substance | — | Nov 26, 2035 |
| US 11001578 ↗ | Drug substance | — | Nov 26, 2035 |
| US 11230537 ↗ | Drug substance | — | Dec 25, 2037 |
| Code | What it grants | Expires |
|---|---|---|
| NCE | New Chemical Entity (5-year) | Jul 3, 2030 |
| ODE-534 | Orphan Drug Exclusivity (7-year) | Jul 3, 2032 |
Is there a generic version of EKTERLY 300 MG TABLET?
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🗺️ Medicaid utilization & spend
💊 Medicaid utilization by pack size
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 82928-0300-04 You're viewing this | 4 BLISTER PACK in 1 CARTON (82928-300-04) / 1 TABLET in 1 BLISTER PACK (82928-300-01) | 2025-07-03 | Active |
| 82928-0300-05 | 2 BLISTER PACK in 1 CARTON (82928-300-05) / 2 TABLET in 1 BLISTER PACK (82928-300-02) | 2026-07-01 | Active |
Pack size FAQ
What quantity is in NDC 82928-0300-04?
What is the difference between NDC 82928-0300-04 and NDC 82928-0300-05?
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🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | ✓ Available |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE EKTERLY® is indicated for the treatment of acute attacks of hereditary angioedema (HAE) in adult and pediatric patients aged 12 years and older. EKTERLY ® is a plasma kallikrein inhibitor indicated for the treatment of acute attacks of hereditary angioedema (HAE) in adult and pediatric patients aged 12 years and older. ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Recommended Dosage : one dose of 600 mg (2 tablets) taken orally at the earliest recognition of an HAE attack. ( 2.1 ) A second dose of 600 mg (2 tablets) may be taken 3 hours after the first dose if response is inadequate, or if symptoms worsen or recur. ( 2.1 ) Maximum Recommended Dosage: 1,200 mg in any 24-hour period.
( 2.1 ) See full prescribing information for dosage modification for concomitant use with CYP3A4 inhibitors and inducers. ( 2.2 ) See full prescribing information for recommended dosage for patients with hepatic impairment. ( 2.3 )
2.1Recommended Dosage The recommended dosage of EKTERLY is one dose of 600 mg (two tablets) orally at the earliest recognition of an acute HAE attack. A second dose of 600 mg (two tablets) may be taken at least 3 hours after the first dose if response is inadequate, or if symptoms worsen or recur. Maximum recommended dosage is 1,200 mg (four tablets) in any 24-hour period.
2.2Dosage Modification for CYP3A4 Inhibitors and Inducers Refer to Table 1 for dosage modification of EKTERLY when used concomitantly with CYP3A4 inhibitors and inducers. Table 1: Dosage Modification of EKTERLY for Concomitant use with CYP3A4 Inhibitors and Inducers Dosage Modification for Concomitant use of EKTERLY with CYP3A4 Inhibitors Strong CYP3A4 Inhibitors Avoid concomitant use with EKTERLY. Moderate CYP3A4 Inhibitors Reduce EKTERLY dosage to 300 mg (one tablet) orally at earliest recognition of an acute HAE attack.
A second dose of 300 mg (one tablet) may be taken at least 3 hours after first dose if response is inadequate or if symptoms worsen or recur [ see Drug Interactions ( 7.1 ) and Clinical Pharmacology ( 12.3 ) ] . Weak CYP3A4 Inhibitors No dosage modification of EKTERLY [ see Dosage and Administration ( 2.1 ) ] . Dosage Modification for Concomitant use of EKTERLY with CYP3A4 Inducers Strong and Moderate CYP3A4 Inducers Avoid concomitant use with EKTERLY.
Weak CYP3A4 Inducers No dosage modification of EKTERLY [ see Dosage and Administration ( 2.1 ) ] .
2.3Recommended Dosage in Patients with Hepatic Impairment Refer to Table 2 for recommended dosage of EKTERLY in patients with hepatic impairment. Table 2: Recommended Dosage of EKTERLY in Patients with Hepatic Impairment Recommended Dosage of EKTERLY in Patients with Hepatic Impairment Severe Hepatic Impairment (Child-Pugh Class C) Avoid use of EKTERLY [ see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 ) ] . Moderate Hepatic Impairment (Child-Pugh Class B) Recommended dosage of EKTERLY is one dose of 300 mg (one tablet) orally at the earliest recognition of an acute HAE attack.
A second dose of 300 mg (one tablet) may be taken at least 3 hours after the first dose if response is inadequate, or if symptoms worsen or recur [ see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 ) ] . Mild Hepatic Impairment (Child-Pugh Class A) Recommended dosage is the same as the recommended dosage in patients with normal hepatic function [ see Dosage and Administration ( 2.1 ) ] .
2.1Recommended Dosage The recommended dosage of EKTERLY is one dose of 600 mg (two tablets) orally at the earliest recognition of an acute HAE attack. A second dose of 600 mg (two tablets) may be taken at least 3 hours after the first dose if response is inadequate, or if symptoms worsen or recur. Maximum recommended dosage is 1,200 mg (four tablets) in any 24-hour period.
2.2Dosage Modification for CYP3A4 Inhibitors and Inducers Refer to Table 1 for dosage modification of EKTERLY when used concomitantly with CYP3A4 inhibitors and inducers. Table 1: Dosage Modification of EKTERLY for Concomitant use with CYP3A4 Inhibitors and Inducers Dosage Modification for Concomitant use of EKTERLY with CYP3A4 Inhibitors Strong CYP3A4 Inhibitors Avoid concomitant use with EKTERLY. Moderate CYP3A4 Inhibitors Reduce EKTERLY dosage to 300 mg (one tablet) orally at earliest recognition of an acute HAE attack.
A second dose of 300…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Tablets: 300 mg, yellow, oval, biconvex, film-coated tablets debossed with on one side and “300” on the other side. Tablets: 300 mg ( 3 ) tab logo
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None ( 4 )
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The most common adverse reaction (incidence ≥2%) is headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact KalVista Pharmaceuticals, Inc. at 1-855-258-4782 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of EKTERLY is based on data from a double-blind, randomized, placebo-controlled, three-way, crossover clinical trial (KONFIDENT) [see Clinical Studies ( 14 )] . In KONFIDENT, a total of 110 patients aged 12 years and older with HAE treated 264 attacks.
In the safety population, 93 patients received EKTERLY 600 mg, 86 patients received EKTERLY 300 mg, and 83 patients received placebo. While EKTERLY 300 mg was included in KONFIDENT, the safety data is based on the recommended dosage of EKTERLY 600 mg. Table 3 displays adverse reaction(s) with an incidence of ≥2% in the EKTERLY 600 mg treated patients and more common than placebo.
Table 3: Adverse Reaction(s) with EKTERLY with Incidence ≥2% and More Common than Placebo in Patients with Hereditary Angioedema (KONFIDENT) a One (1) patient assigned to administer placebo actually received EKTERLY 600 mg. Safety results are presented by actual treatment received. Adverse Reaction EKTERLY 600 mg (N = 93) Placebo (N = 83) a n (%) n (%) Headache 3 (3.2) 1 (1.2)
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of EKTERLY is based on data from a double-blind, randomized, placebo-controlled, three-way, crossover clinical trial (KONFIDENT) [see Clinical Studies ( 14 )] . In KONFIDENT, a total of 110 patients aged 12 years and older with HAE treated 264 attacks.
In the safety population, 93 patients received EKTERLY 600 mg, 86 patients received EKTERLY 300 mg, and 83 patients received placebo. While EKTERLY 300 mg was included in KONFIDENT, the safety data is based on the recommended dosage of EKTERLY 600 mg. Table 3 displays adverse reaction(s) with an incidence of ≥2% in the EKTERLY 600 mg treated patients and more common than placebo.
Table 3: Adverse Reaction(s) with EKTERLY with Incidence ≥2% and More Common than Placebo in Patients with Hereditary Angioedema (KONFIDENT) a One (1) patient assigned to administer placebo actually received EKTERLY 600 mg. Safety results are presented by actual treatment received. Adverse Reaction EKTERLY 600 mg (N = 93) Placebo (N = 83) a n (%) n (%) Headache 3 (3.2) 1 (1.2)
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Strong and Moderate CYP3A4 Inhibitors : Avoid use with strong CYP3A4 inhibitors. In patients taking moderate CYP3A4 inhibitors, take one dose of 300 mg. A second dose of 300 mg may be taken at least 3 hours after the first dose if response is inadequate, or if symptoms worsen or recur. ( 2.2 , 7.1 , 12.3 ) CYP3A4 Inducers : Avoid use with moderate or strong CYP3A4 inducers. ( 2.2 , 7.1 , 12.3 )
7.1Effect of Other Drugs on EKTERLY Strong CYP3A4 Inhibitors Avoid use of EKTERLY with strong CYP3A4 inhibitors [see Clinical Pharmacology ( 12.3 )] . Sebetralstat is a substrate of CYP3A4. Concomitant use of sebetralstat with a strong CYP3A4 inhibitor increases sebetralstat exposure, which may increase the risk of sebetralstat adverse reactions.
Moderate and Weak CYP3A4 Inhibitors Reduce dose of EKTERLY to one dose of 300 mg (one tablet) orally at the earliest recognition of an HAE attack when used concomitantly with moderate CYP3A4 inhibitors. A second dose of 300 mg (one tablet) may be taken at least 3 hours after the first dose if response is inadequate, or if symptoms worsen or recur [see Dosage and Administration ( 2.2 ) and Clinical Pharmacology ( 12.3 )] . Sebetralstat is a substrate of CYP3A4.
Concomitant use of sebetralstat with a moderate CYP3A4 inhibitor increases sebetralstat exposure, which may increase the risk of sebetralstat adverse reactions. No dose modification is recommended when EKTERLY is used concomitantly with a weak CYP3A4 inhibitor [see Dosage and Administration ( 2.1 ) and Clinical Pharmacology ( 12.3 )] . Strong and Moderate CYP3A4 Inducers Use of EKTERLY with strong or moderate CYP3A4 inducers is not recommended.
Sebetralstat is a substrate of CYP3A4. Concomitant use of sebetralstat with a strong or moderate CYP3A4 inducer decreases sebetralstat exposure, which may decrease efficacy. Weak CYP3A4 Inducers No dose modification is recommended when EKTERLY is used concomitantly with weak CYP3A4 inducers [see Clinical Pharmacology ( 12.3 )] .
7.1Effect of Other Drugs on EKTERLY Strong CYP3A4 Inhibitors Avoid use of EKTERLY with strong CYP3A4 inhibitors [see Clinical Pharmacology ( 12.3 )] . Sebetralstat is a substrate of CYP3A4. Concomitant use of sebetralstat with a strong CYP3A4 inhibitor increases sebetralstat exposure, which may increase the risk of sebetralstat adverse reactions.
Moderate and Weak CYP3A4 Inhibitors Reduce dose of EKTERLY to one dose of 300 mg (one tablet) orally at the earliest recognition of an HAE attack when used concomitantly with moderate CYP3A4 inhibitors. A second dose of 300 mg (one tablet) may be taken at least 3 hours after the first dose if response is inadequate, or if symptoms worsen or recur [see Dosage and Administration ( 2.2 ) and Clinical Pharmacology ( 12.3 )] . Sebetralstat is a substrate of CYP3A4.
Concomitant use of sebetralstat with a moderate CYP3A4 inhibitor increases sebetralstat exposure, which may increase the risk of sebetralstat adverse reactions. No dose modification is recommended when EKTERLY is used concomitantly with a weak CYP3A4 inhibitor [see Dosage and Administration ( 2.1 ) and Clinical Pharmacology ( 12.3 )] . Strong and Moderate CYP3A4 Inducers Use of EKTERLY with strong or moderate CYP3A4 inducers is not recommended.
Sebetralstat is a substrate of CYP3A4. Concomitant use of sebetralstat with a strong or moderate CYP3A4 inducer decreases sebetralstat exposure, which may decrease efficacy. Weak CYP3A4 Inducers No dose modification is recommended when EKTERLY is used concomitantly with weak CYP3A4 inducers [see Clinical Pharmacology ( 12.3 )] .
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Hepatic Impairment : Avoid use of EKTERLY in patients with severe hepatic impairment (Child-Pugh Class C). In patients with moderate hepatic impairment (Child-Pugh Class B) take one dose of 300 mg. A second dose of 300 mg may be taken at least 3 hours after the first dose if response is inadequate, or if symptoms worsen or recur. ( 2.3 , 8.6 , 12.3 )
8.1Pregnancy Risk Summary There are no available data on EKTERLY in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of sebetralstat to pregnant rats and rabbits during organogenesis produced no evidence of fetal harm with dose exposures up to approximately 15 and 11 times, respectively, the human exposure at the maximum recommended human dose (MRHD) of up to 1,200 mg (on an area under the curve [AUC] basis).
Sebetralstat produced an increase in embryofetal losses and fetal malformations in rats at an exposure that was 60 times the MRHD (see Data) . The estimated 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 miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryofetal development study with pregnant rats dosed by the oral route during the period of organogenesis from gestation days 6 to 17, sebetralstat caused a dose-related increase in the incidence of external and visceral malformations, described as cleft palates and ventricular septal defects and an increase in embryofetal losses (early and late fetal deaths, mean number of live fetuses, and post-implantation loss at an exposure that was 60 times the MRHD (on an AUC basis with a maternal dose of 600 mg/kg/day)).
Maternal toxicity, as evidenced by decreased body weight gains, was observed at exposures 60 times the MRHD (on an AUC basis with a maternal oral dose of 600 mg/kg/day). No fetal or maternal toxicities were observed at exposures up to 15 times the MRHD (on an AUC basis with a maternal oral dose of 300 mg/kg/day). In an embryofetal development study with pregnant rabbits dosed by the oral route during the period of organogenesis from gestation days 6 to 18, maternal toxicity was evidenced by a decrease in body weight gain at an exposure that was 11 times the MRHD (on an AUC basis with a maternal dose of 300 mg/kg/day).
No adverse effects on maternal toxicity were observed at an exposure that was 2 times the MRHD (on an AUC basis with a maternal dose of 100 mg/kg/day). No adverse effects on fetal toxicity were observed at an exposure that was 11 times the MRHD (on an AUC basis with a maternal oral dose of 300 mg/kg/day). In a prenatal and postnatal development study with pregnant rats dosed by the oral route during the periods of gestation and lactation from gestation day 6 to lactation day 20, sebetralstat had no effects on the growth and development of offspring at an exposure that was 40 times the MRHD (on an AUC basis with a maternal oral dose of 450 mg/kg/day).
8.2Lactation Risk Summary There are no data on the presence of sebetralstat or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. Radioactivity is present in animal milk after dosing with radiolabeled sebetralstat. When a drug is present in animal milk, it is likely that the drug will be present in human milk.
Data in the rat have shown excretion of sebetralstat and/or its metabolites in milk (see Data) . The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for EKTERLY and any potential adverse effects on the breastfed child from EKTERLY or from the underlying maternal condition. Data Animal D…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary There are no available data on EKTERLY in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of sebetralstat to pregnant rats and rabbits during organogenesis produced no evidence of fetal harm with dose exposures up to approximately 15 and 11 times, respectively, the human exposure at the maximum recommended human dose (MRHD) of up to 1,200 mg (on an area under the curve [AUC] basis).
Sebetralstat produced an increase in embryofetal losses and fetal malformations in rats at an exposure that was 60 times the MRHD (see Data) . The estimated 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 miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryofetal development study with pregnant rats dosed by the oral route during the period of organogenesis from gestation days 6 to 17, sebetralstat caused a dose-related increase in the incidence of external and visceral malformations, described as cleft palates and ventricular septal defects and an increase in embryofetal losses (early and late fetal deaths, mean number of live fetuses, and post-implantation loss at an exposure that was 60 times the MRHD (on an AUC basis with a maternal dose of 600 mg/kg/day)).
Maternal toxicity, as evidenced by decreased body weight gains, was observed at exposures 60 times the MRHD (on an AUC basis with a maternal oral dose of 600 mg/kg/day). No fetal or maternal toxicities were observed at exposures up to 15 times the MRHD (on an AUC basis with a maternal oral dose of 300 mg/kg/day). In an embryofetal development study with pregnant rabbits dosed by the oral route during the period of organogenesis from gestation days 6 to 18, maternal toxicity was evidenced by a decrease in body weight gain at an exposure that was 11 times the MRHD (on an AUC basis with a maternal dose of 300 mg/kg/day).
No adverse effects on maternal toxicity were observed at an exposure that was 2 times the MRHD (on an AUC basis with a maternal dose of 100 mg/kg/day). No adverse effects on fetal toxicity were observed at an exposure that was 11 times the MRHD (on an AUC basis with a maternal oral dose of 300 mg/kg/day). In a prenatal and postnatal development study with pregnant rats dosed by the oral route during the periods of gestation and lactation from gestation day 6 to lactation day 20, sebetralstat had no effects on the growth and development of offspring at an exposure that was 40 times the MRHD (on an AUC basis with a maternal oral dose of 450 mg/kg/day).
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of EKTERLY for treatment of acute attacks of hereditary angioedema (HAE) have been established in pediatric patients aged 12 years and older. Use of EKTERLY for this indication is supported by evidence from an adequate and well-controlled study (KONFIDENT) in adults and pediatric patients aged 12 years and older with additional population pharmacokinetic (PK) analysis from adults and pediatric patients aged 12 years and older, which showed no clinically significant differences in PK based on body weight or age.
Results of the subgroup analysis for pediatric patients aged 12 years and older were consistent with study results for adult patients [see Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12.3 ), and Clinical Studies ( 14 )] . The safety and effectiveness of EKTERLY in pediatric patients aged <12 years of age have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical studies of EKTERLY did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients.
🆘 Overdosage ▾
10 OVERDOSAGE Consider contacting the poison control help line (1-800-222-1222) or medical toxicologist for overdose management recommendations.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Sebetralstat is a competitive, reversible inhibitor of plasma kallikrein. Plasma kallikrein is a serine protease that cleaves high molecular weight kininogen (HK) releasing bradykinin which increases vascular permeability through activation of bradykinin receptors causing edema. Sebetralstat inhibits the cleavage of HK and reduces production of bradykinin, thereby treating the clinical symptoms of an acute, episodic attack of HAE.
Sebetralstat also inhibits the positive feedback mechanism of the kallikrein kinin system by plasma kallikrein, thereby reducing factor XIIa and additional plasma kallikrein generation.
12.2Pharmacodynamics Concentration-dependent inhibition of plasma kallikrein, measured as a reduction from baseline of specific enzyme activity, was observed in exploratory assays. Following administration of a single oral dose of 600 mg sebetralstat to healthy subjects, greater than 90% mean inhibition of plasma kallikrein activity was observed beginning at 30 minutes after dosing and maintained through about 6 hours post-dose. Cardiac Electrophysiology The largest mean increase in QTc interval was 10.4 msec (upper confidence interval = 15.3 msec) after administration of sebetralstat (2.5 times the maximum recommended dose) in healthy subjects.
The increase in the QTc interval was concentration dependent.
12.3Pharmacokinetics Following a single oral dose of 600 mg sebetralstat in subjects with HAE, the geometric mean (CV%) C max is 6,080 ng/mL (40%) and AUC 0-inf is 17,600 ng•h/mL (36%). Following administration of a second oral dose of 600 mg sebetralstat 3 hours after the first dose, C max increases 10% and AUC 0-inf increases 90% when compared to those observed following a single dose. No clinically relevant differences in sebetralstat pharmacokinetics were observed between healthy subjects and patients with HAE.
Absorption After a single oral dose of 600 mg sebetralstat, the median time to peak plasma concentration is approximately 1 hour. Effect of Food No clinically relevant differences in sebetralstat pharmacokinetics were observed following administration of a high-fat meal (900-1,000 calories in total – 500-600, 250 and 150 calories from fat, carbohydrate and protein respectively). Distribution The estimated typical apparent volume of distribution (Vz/F) for sebetralstat is
70.1L (95% CI: 64.8, 75.4). Sebetralstat plasma protein binding is 77% in vitro . Elimination Following administration of a single oral dose of 600 mg sebetralstat, the mean (SD) elimination half-life of sebetralstat ranged from 5.3 (2.3) to 8.9 (5.1) hours. The estimated typical apparent clearance (CL/F) is
30.7L/h (95% CI: 29.1, 32.2). Metabolism Sebetralstat is primarily metabolized by CYP3A4 and to a lesser extent by CYP2C8. Excretion Following administration of a single oral dose of 600 mg radiolabeled sebetralstat to healthy male subjects, approximately 63% of the dose was recovered in feces (12.5% as unchanged sebetralstat) and 32% in urine (8.7% as unchanged sebetralstat).
Specific Populations No clinically relevant differences in the pharmacokinetics of sebetralstat were observed based on body weight (45-135 kg), age (19-68 years), sex, race (71% White, 17% Black, 11% Asian), and mild renal impairment (eGFR 60-89 mL/min/1.73 m 2 ). The effect of moderate and severe renal impairment (eGFR <60 mL/min/1.73 m 2 ) on sebetralstat pharmacokinetics is unknown. Patients with Hepatic Impairment The pharmacokinetics of sebetralstat were evaluated in subjects with mild (Child-Pugh Class A) and moderate (Child-Pugh Class B) hepatic impairment following administration of a single 600 mg dose.
In subjects with mild hepatic impairment C max was increased by 7% and AUC increased by 16% compared to subjects with normal hepatic function. In subjects with moderate hepatic impairment C max was increased by 63% and AUC was increased by 100% compared to subjects with normal hepatic function. The ef…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Sebetralstat is a competitive, reversible inhibitor of plasma kallikrein. Plasma kallikrein is a serine protease that cleaves high molecular weight kininogen (HK) releasing bradykinin which increases vascular permeability through activation of bradykinin receptors causing edema. Sebetralstat inhibits the cleavage of HK and reduces production of bradykinin, thereby treating the clinical symptoms of an acute, episodic attack of HAE.
Sebetralstat also inhibits the positive feedback mechanism of the kallikrein kinin system by plasma kallikrein, thereby reducing factor XIIa and additional plasma kallikrein generation.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING EKTERLY (sebetralstat) tablets: 300 mg, yellow, oval, biconvex, film-coated tablets debossed with on one side and “300” on the other side. EKTERLY is supplied as Carton of 4, containing four child-resistant blister cards. Each child-resistant blister card contains 1 x 300 mg tablet (NDC 82928-300-04).
Carton of 4, containing two child-resistant blister cards. Each child-resistant blister card contains 2 x 300 mg tablets (NDC 82928-300-05). Each carton contains a tamper evident seal.
Do not use if tamper evident seal is broken or missing. Store at 20°C to 25°C (68°F to 77°F). Excursions permitted between 15°C and 30°C (59°F to 86°F) [see USP Controlled Room Temperature] .
📋 Description ▾
11 DESCRIPTION The active ingredient of EKTERLY is sebetralstat, a plasma kallikrein inhibitor. The chemical name of sebetralstat is N-[(3-fluoro-4-methoxypyridin-2-yl) methyl]-3-(methoxymethyl)-1-({4-[(2-oxo-1,2-dihydropyridin-1-yl) methyl]phenyl}methyl)-1H-pyrazole-4-carboxamide. The chemical structure of sebetralstat is: The molecular formula is C 26 H 26 FN 5 O 4 and molecular weight is 491.5.
Sebetralstat is a white to off-white crystalline powder. It is slightly soluble in ethanol, acetone and isopropanol, and practically insoluble in water. EKTERLY is supplied as 300 mg film-coated tablets for oral administration.
Each tablet contains the active ingredient sebetralstat. The inactive ingredients include croscarmellose sodium, glycerol mono and dicaprylocaprate, guar gum/guar galactomannan, hypromellose, iron oxide black, iron oxide yellow, macrogol polyvinyl alcohol graft copolymer, magnesium stearate, maltodextrin, medium chain triglycerides, microcrystalline cellulose, polyvinyl alcohol, povidone, talc and titanium dioxide. mol structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise patients to read the FDA-approved patient labeling (Patient Information). Dosage Modification for Strong and Moderate CYP3A4 Inhibitors Advise patients not to use EKTERLY with strong CYP3A4 inhibitors [see Drug Interactions ( 7.1 ) and Clinical Pharmacology ( 12.3 )] . When used concomitantly with moderate CYP3A4 inhibitors, advise patients to reduce dose to one tablet of 300 mg (total dose 300 mg) at the earliest recognition of an HAE attack.
A second dose of 300 mg (one tablet) may be taken at least 3 hours after the first dose if response is inadequate, or if symptoms worsen or recur [see Dosage and Administration ( 2.2 ), Drug Interactions ( 7.1 ) and Clinical Pharmacology ( 12.3 )] . Recommended Dosage in Patients with Hepatic Impairment Advise patients with severe hepatic impairment to avoid use of EKTERLY. In patients with moderate hepatic impairment, advise patients to take one tablet of 300 mg (total dose 300 mg) at earliest recognition of an HAE attack.
A second dose of 300 mg (one tablet) may be taken at least 3 hours after the first dose if response is inadequate, or if symptoms worsen or recur [see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 )] . For more information, visit www.EKTERLY.com EKTERLY ® is a registered trademark of KalVista Pharmaceuticals Limited. Distributed by: KalVista Pharmaceuticals, Inc.
200 Crossing Boulevard Framingham, MA 01702