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Articles

Safety in Lactation: Drugs for hypertension

23 September 2020Additional information relating to breastfeeding To be used in conjunction with individual drug entries for specific information and guidance. Many of the drugs covered by…
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Medicine Compliance Aid Stability

CelectolZentiva

Zentiva
Celectol
Tablets f/c 200mg, 400mg
A3 · Amber 3No stability data is available. There are theoretical concerns with use in CAs, which may be mitigated by risk minimisation.
Protect from light
Protect from light.
9 November 2015

Lactation Safety Information

Propranolol
No published evidence of safety
Monitor breastfed infants for signs of beta blockade, especially bradycardia
16 January 2017

New Medicines

Edsivo Vascular Ehlers-Danlos syndrome (vEDS), associated with collagen mutation

Information

Edsivo
Repurposed drug
Acer Therapeutics Inc
Acer Therapeutics Inc

Development and Regulatory status

None
Phase IV Clinical Trials
Pre-registration (Filed)
Yes

Dec 18: No information on Acer website to indicate plans for licensing celiprolol for vEDS in Europe. Corporate presentation indicates company is focussed on US launch. If approved, Edsivo will be the only FDA-approved therapy to treat vEDS patients [6].


Dec 18: Has orphan drug status in US [5].


Dec 18: FDA grants priority review with a Prescription Drug User Fee Act (PDUFA) target action date of 25 Jun 19 [2].


Dec 18: FDA has accepted for review EDSIVO™ for the treatment of vascular Ehlers-Danlos syndrome (vEDS) in patients with a confirmed type III collagen (COL3A1) mutation [1].


Dec 16: Acer Therapeutics announces the signing of an agreement with the Greater Paris University Hospital, granting the company exclusive rights to access and use data from a randomized controlled clinical study of celiprolol. Acer Therapeutics will use this pivotal clinical data to support a New Drug Application (NDA) regulatory filing for its lead product, VASEBRA™ (celiprolol), for the treatment of vascular Ehlers-Danlos Syndrome (vEDS) [2].

Category

Beta-blocker. Celiprolol is believed to provide clinical benefit for people with vEDS by promoting normal collagen synthesis in the blood vessels, and by shifting the pressure load away from the vessels most prone to dissection and rupture.
Ehlers-Danlos Syndrome (EDS) is a group of hereditary disorders of connective tissue. vEDS is the most severe subtype where patients suffer from life threatening arterial dissections and ruptures, as well as intestinal and uterine ruptures. The average mortality is 51 years of age [1].
Vascular Ehlers-Danlos syndrome (vEDS), associated with collagen mutation
Oral

Trial or other data

Dec 18: Phase IV study, which has been published in the Lancet in 2010, was stopped early for treatment benefit. The primary endpoints were reached by five (20%) in the celiprolol group and by 14 (50%) controls (hazard ratio [HR] 0·36; 95% CI 0·15-0·88; p=0·040). Adverse events were severe fatigue in one patient after starting 100 mg celiprolol and mild fatigue in two patients related to dose uptitration [4].


Apr 11: PIV study (NCT00190411) recruited 54 patients aged 15 to 65 years old in France and Belgium. Patients were randomised to either celiprolol (50 to 400 mg BID) or no treatment. Patients who are not randomized enter a longitudinal survey of events. Primary outcome is rate of major cardiovascular events in the treated group during a 5 years follow-up. The hypothesis is a 50% reduction in the occurrence of cardiovascular events under treatment, assessed by a blinded, independent events committee [3].


2010: Prospective randomized open trial completed in 2010 (NCT00190411) [1].