RyR1 Structural Alterations Explain Statin-Associated Muscle Dysfunction
December 16, 2025
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Brand Name :
Ekterly
Synonyms :
sebetralstat
Class :
Kallikrein Inhibitors
Brand Name :
Ekterly
Synonyms :
sebetralstat
Class :
Kallikrein Inhibitors
Dosage Forms & Strengths
Tablet
300mg
Take 2 tablets (600 mg) at the first sign of an HAE attack.
If symptoms do not improve or return, a second dose of 2 tablets can be taken at least 3 hours later.
Do not exceed 4 tablets (1,200 mg) in a 24-hour period.
Dosage modification
Dosage adjustments when EKTERLY is used with CYP3A4 inhibitors:
Strong CYP3A4 inhibitors: Do not use EKTERLY at the same time.
Moderate CYP3A4 inhibitors: Lower the EKTERLY dose to 300 mg (1 tablet) at the first sign of an acute HAE attack. If symptoms do not improve, get worse, or come back, a second 300 mg dose may be taken at least 3 hours later.
Weak CYP3A4 inhibitors: No change to the EKTERLY dose is needed.
Dosage adjustments when EKTERLY is used with CYP3A4 inducers:
Strong or moderate CYP3A4 inducers: Do not use EKTERLY together with these medicines.
Weak CYP3A4 inducers: No change to the EKTERLY dose is needed.
Tablet
300mg
Approved for treatment of acute hereditary angioedema (HAE) attacks in patients 12 years and older.
Recommended dose: 600 mg by mouth at the first sign of an acute HAE attack.
If symptoms do not improve, worsen, or return, a second 600 mg dose can be taken at least 3 hours after the first.
Do not take more than 1,200 mg in a 24-hour period.
Dosage modifications
When given with CYP3A4 inhibitors or inducers:
Strong CYP3A4 inhibitors or strong/moderate inducers: Do not use together.
Moderate CYP3A4 inhibitors: Lower the starting and possible second dose to 300 mg.
Weak CYP3A4 inhibitors or inducers: No dose change needed.
For kidney function:
Mild impairment (eGFR 60–89): No meaningful difference in how the drug works.
Moderate to severe impairment (eGFR below 60): Effects are unknown.
For liver function:
Mild impairment (Child-Pugh A): No dose change needed.
Moderate impairment (Child-Pugh B): Reduce the initial and possible second dose to 300 mg.
Severe impairment (Child-Pugh C): Do not use.
Refer adult dosing
It acts as a competitive and reversible blocker of plasma kallikrein, preventing it from breaking down high molecular weight kininogen (HK). This stops the release of bradykinin, which would otherwise increase blood vessel permeability and lead to swelling.
It targets plasma kallikrein activity specifically, helping control bradykinin-mediated edema in conditions like hereditary angioedema.
Frequency defined:
1-10%
Headache
There is no Blackbox warning for this drug
Contraindication
None
Caution
Sebetralstat is highly affected by CYP3A4 interactions. Strong CYP3A4 inhibitors should not be used with sebetralstat, as they can raise drug levels by over five times and increase side effects. With moderate CYP3A4 inhibitors, the dose should be lowered to avoid excessive exposure. Strong or moderate CYP3A4 inducers should also be avoided since they can reduce sebetralstat levels and may make the drug less effective.
Pregnancy consideration:
There are no human data on use in pregnancy. Animal studies showed no harm to the fetus at exposures up to about 11–15 times the human dose, but higher doses caused fetal harm and pregnancy losses in rats.
Lactation:
It’s unknown if sebetralstat passes into human milk. Animal studies show it can be present in milk, so the benefits of breastfeeding should be weighed against the possible risks to the baby.
Pregnancy category:
Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester.
Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women.
Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women
Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits.
Category X: Drugs listed in this category outweigh risks over benefits These category drugs should be prohibited for pregnant women.
Category N: There is no data available for the drug under this category.
Pharmacology
Sebetralstat works by competitively and reversibly blocking plasma kallikrein, an enzyme that normally breaks down high molecular weight kininogen (HK) to release bradykinin. Bradykinin makes blood vessels more permeable, leading to swelling. By stopping HK from being cleaved, sebetralstat lowers bradykinin levels, helping relieve the symptoms of an acute HAE attack. In addition, it interrupts the kallikrein-kinin system’s positive feedback loop, which helps limit further activation of factor XIIa and reduces the formation of more plasma kallikrein.
Pharmacodynamics
Sebetralstat shows concentration-dependent blocking of plasma kallikrein activity, with exploratory tests showing over 90% average inhibition within 30 minutes of a single 600 mg dose in healthy people. This strong effect lasts for about 6 hours.
At a dose 2.5 times higher than the recommended maximum, sebetralstat caused an average QTc interval increase of about 10.4 milliseconds (with an upper limit of 15.3 milliseconds). This effect on heart rhythm was linked to the drug’s concentration.
Pharmacokinetics
Absorption
After taking a single 600 mg oral dose, peak blood levels are typically reached in about 1 hour. In patients with HAE, the average peak concentration (Cmax) is about 6,080 ng/mL, and total exposure (AUC) is around 17,600 ng•h/mL. Taking a second 600 mg dose three hours later can raise peak levels by about 10% and nearly double total exposure. Food has no significant effect on how the drug is absorbed.
Distribution
Sebetralstat has an estimated apparent volume of distribution of about 70 L, and about 77% of the drug binds to plasma proteins in lab tests.
Metabolism
The drug is mainly broken down by the CYP3A4 enzyme, with some involvement from CYP2C8.
Elimination/ Excretion
The average half-life ranges from about 5 to 9 hours. Clearance is estimated at roughly 30.7 L/hour.
After a single oral dose, around 63% of the drug is recovered in feces (with about 12.5% unchanged) and about 32% in urine (around 8.7% unchanged).
No major differences in these pharmacokinetic measures were seen between healthy individuals and people with HAE.
Take by mouth; can be taken with or without food. Keep at 20–25 °C (68–77 °F); brief temperature changes between 15–30 °C (59–86 °F) are acceptable.
Patient information leaflet
Generic Name: sebetralstat
Pronounced: se-be-TRAL-stat
Why do we use sebetralstat?
It is prescribed to treat sudden attacks of hereditary angioedema (HAE) in adults and children aged 12 and older. It is taken as soon as possible to help manage the pain and swelling caused by these acute, potentially serious episodes.
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