dm+d
108622005
Articles
Safety in Lactation: Corticosteroids
9 November 2020There is very limited information on the use of corticosteroids during breastfeeding, although they are likely to be present in milk. Avoid prolonged high dose…
Safety in Lactation: Drugs used in nasal allergy
27 October 2020Drugs used for nasal allergy have limited systemic absorption in the mother, and pose negligible risk to a breastfed infant. There is no published evidence…
Safety in Lactation: Drugs for obstructive airways disease
25 September 2020Additional information relating to breastfeeding To be used in conjunction with individual drug entries for specific information and guidance. Bronchodilators Most bronchodilators are considered to…
Safety in lactation: Drugs for chronic bowel disorders
21 September 2020Additional information relating to breastfeeding To be used in conjunction with individual drug entries for specific information and guidance. Aminosalicylates for chronic bowel disorders Mesalazine…
Budesonide + salbutamol
13 September 2020Enteric coated granules containing the corticosteroid, budesonide
Medicine Compliance Aid Stability
EntocortAstraZeneca UK Ltd
AstraZeneca UK Ltd
Entocort
Capsules 3mg e/c m/r granules
A1 · Amber 1Stability data is available in an alternative container (not CAs) that may be extrapolated to support storage in CAs.
Airtight container
Protect from light
Protect from light and store in airtight containers. SPC states store in original packaging, which contains a desiccant. Company have stability studies that demonstrate stability in open storage for 3 months
22 October 2015
BudenofalkDr Falk Pharma UK Ltd
Dr Falk Pharma UK Ltd
Budenofalk
Capsules 3mg e/c granules
A2 · Amber 2No stability data is available, the manufacturer does not, or cannot recommend use in CAs but there are no theoretical concerns with the product.
Airtight container
Protect from light
Protect from light and store in airtight containers.
22 October 2015
Lactation Safety Information
Inhalation
Inhalation
-
Limited published evidence of safety
Only negligible amounts in breast milk
Used in infants >1 month
18 September 2020
Intranasal
Intranasal
18 September 2020
Oral/rectal for inflammatory bowel disease
Oral/rectal
for inflammatory bowel disease
-
No published evidence of safety after oral or rectal administration
Low levels anticipated in milk due to the drug’s properties
18 September 2020
New Medicines
BudenofalkMicroscopic colitis in adults - 3mg gastro-resistant capsule formulation
Information
Budenofalk
Licence extension / variation
Dr Falk
Dr Falk
Development and Regulatory status
Launched
Launched
None
December 2019
Jan 20Budenofalk 3mg gastro-resistant capsules are now licensed for use in microscopic colitis, both induction and maintenance of remission (previously licensed for induction of remission of active collagenous colitis, a form of microscopic colitis) [6].
Dec 19Licence change approved via the EU decentralised procedure, including in the UK. The SPC has been updated with the change in indication from collagenous colitis to microscopic colitis, with consequential changes to the posology and clinical efficacy and safety section to include data on the maintenance of remission in collagenous colitis [6].
Jan 19Currently pre-registration in EU. Has been filed via the decentralised procedure [5].
Apr 17Currently in PIII trials. Will be filed in the EU using the decentralised procedure [2].
Category
Enteric coated granules containing the corticosteroid, budesonide
Microscopic colitis (MC) is a chronic inflammatory condition characterized by chronic diarrhea, normal colonic mucosa, and abnormal histologic hallmarks. Two distinct disease phenotypes exist, collagenous colitis (CC) and lymphocytic colitis (LC). Reported prevalence rates of CC and LC are 42 and 69 per 100,000 persons, respectively [1].
Microscopic colitis in adults - 3mg gastro-resistant capsule formulation
Oral
Trial or other data
Sep 13Dr Falk Pharma in collaboration with the Swedish Organization for Studies on Inflammatory Bowel Disease completed the PIII SOIBD Collagenous Colitis Maintenance Study (SCCMS) to investigate efficacy and tolerability of budesonide gastro-resistant granule in patients with microscopic colitis. Patients underwent an 8-week induction phase followed by maintenance treatment phase (NCT01278082). The trial enrolled 92 patients in Belgium, the Czech Republic, Denmark, Germany, Hungary and Sweden [2,4].
Cortiment (EU), Uceris (US) Active microscopic colitis - induction of remission in adults
Information
Cortiment (EU), Uceris (US)
Licence extension / variation
Ferring
Salix Pharmaceuticals
Development and Regulatory status
Launched
None
None
November 2020
Nov 20Licence extension approved by the MHRA for induction of remission in adults with active microscopic colitis, in a dose of one 9mg tablet once daily for up to 8 weeks [2].
Category
Locally acting corticosteroid in a controlled-release tablet formulation. he specific drug dissolution profile increases the colonic specific bioavailability of budesonide and reduces the pre-colonic systemic absorption.
Microscopic colitis is an inflammatory bowel disease (IBD) that affects the large bowel - the colon and rectum. At least 1 in 1000 people are thought to have microscopic colitis in the UK, but the real number could be a lot higher because it is often underreported and misdiagnosed [1].
Active microscopic colitis - induction of remission in adults
Oral
Trial or other data
Nov 20Evidence for the indication microscopic colitis (collagenous colitis and lymphocytic colitis) comes from studies on budesonide product Entocort. The systemic availability of this product is similar to that of budesonide product Cortiment. Two randomised, double-blind, placebo-controlled induction studies of six and eight weeks duration investigated the clinical and histological effects of budesonide 9 mg/day in the treatment of collagenous colitis. In the first study, 23 patients were randomised to budesonide 9 mg/day and 22 patients to placebo for 6 weeks. The rate of clinical remission was significantly higher (p<0.001) in the budesonide group than in the placebo group 86.9% vs. 13.6%. Histologic improvement was observed in 14 patients of the budesonide group (60.9%) and in one patient of the placebo group (4.5%; p<0.001). In the second study, 10 patients were randomised to budesonide for 8 weeks (9 mg/day 4 weeks, 6 mg/day 2 weeks, and 3 mg/day 2 weeks) and ten to placebo. All 10 patients receiving budesonide had a clinical response compared with two in the placebo group (p<0.001). Two open-label studies (run-in phase of randomised, double-blind, placebo-controlled maintenance studies) investigated the efficacy of budesonide 9 mg/day during 6 weeks. In the first study, 46 patients (96%) achieved clinical remission within 2–30 (mean 6.4) days, with marked improvements in stool consistency. In the second study, of the 42 patients who commenced the study, 34 patients (81%) were in clinical remission (mean stool frequency of three or fewer per day) at week 6. Evidence for lymphocytic colitis is limited. One randomised, double-blind placebo-controlled study was carried out in 15 lymphocytic colitis patients. Eleven subjects were treated with budesonide 9 mg/day and four patients received placebo for 8 weeks. A clinical response (defined as at least 50% improvement in the frequency of bowel movements) was seen in 25% of the placebo group vs. 91% in the budesonide group (p=0.03) [2].
JorvezaEosinophilic oesophagitis - new 0.5mg tablet formulation
Information
Jorveza
New formulation
Dr Falk
Dr Falk
Development and Regulatory status
Approved (Licensed)
Approved (Licensed)
None
May 20New 0.5mg strength of the orodispersible Jorveza formulation and licence extension for maintenance therapy approved in EU [4].
Mar 20CHMP issues a positive opinion recommending a change to the duration of treatment allowing the use of Jorveza as maintenance therapy for eosinophilic esophagitis in adults (older than 18 years of age) with a new strength (0.5 mg orodispersible tablet). The recommendation for maintenance therapy is as follows: The recommended daily dose is 1 mg budesonide as one 0.5‑mg-tablet in the morning and one 0.5‑mg-tablet in the evening or 2 mg budesonide as one 1‑mg-tablet in the morning and one 1‑mg-tablet in the evening, depending on the individual clinical requirement of the patient. A maintenance dose of 1 mg budesonide twice daily is recommended for patients with a long standing disease history and/or high extent of esophageal inflammation in their acute disease state. The duration of maintenance therapy is determined by the treating physician [3].
Category
Oral corticosteroid in an orodispersible tablet that is designed to coat the oesophagus, enabling local anti-inflammatory action of the drug
In 2013, eosinophilic oesophagitis was considered to affect less than 5 in 10,000 people in the EU [1]. Studies suggest that the prevalence is rising, but it is uncertain whether this is a true increase or due to better diagnosis; it is most common in middle-aged men [2].
Eosinophilic oesophagitis - new 0.5mg tablet formulation
Oral
Further information
Yes
June 2021
Evidence based evaluations
BudenofalkMicroscopic colitis, induction of remission in adults, first-line (9mg EC-coated granule formulation)
Information
Budenofalk
Licence extension / variation
Dr Falk
Dr Falk
Development and Regulatory status
Launched
Launched
Phase III Clinical Trials
February 2021
Feb 21Licensed in UK and EU for induction of remission in adults with active microscopic colitis [10].
May 20Filing via the EU mutual recognition procedure is still planned [9].
Jan 20Still listed as PIII in Dr Falk pipeline [8].
May 14Will be filed via the EU Mutual Recognition procedure [3].
Category
Enteric coated granules containing the corticosteroid, budesonide
Microscopic colitis is characterised by chronic watery diarrhoea of unknown origin. Colonoscopy shows an essentially normal colonic mucosa, however abnormal histopathology on biopsy helps establish the correct diagnosis. Collagenous colitis and lymphocytic colitis are the two major subtypes. True incidence not known.
Microscopic colitis, induction of remission in adults, first-line (9mg EC-coated granule formulation)
Oral
Trial or other data
Sep 18Phase III trial (NCT01209208) published in Gastroenterology [7].
Jan 17Phase 3 study (NCT01209208) completed [6].
May 16NCT01209208 study still recruiting patients. Expected to complete collection of primary outcome data in December 2016 [5].
Nov 13PIII NCT01209208 study continue to recruit pts [1].
Mar 12PIII NCT00217022 study is closed early, because of low enrollment [1].
May 10PIII (NCT01209208) study to compare budesonide and mesalazine in the treatment of lymphocytic colitis begins. 75 pts will be recruited in Germany. Primary outcome is rate of clinical remission. Study is expected to complete in April 15 (primary outcome data collection complete in Dec 14) [1].
Aug 07PIII NCT00180050 study completes. Approx 40 pts were recruited in Germany to assess whether budesonide is effective in the treatment of lymphocytic colitis. Primary outcome was proportion of patients in clinical remission after 6 weeks [1].
Jun 03PII/III (NCT00217022) study begins recruiting pts in the US to assess efficacy and safety of budesonide compared with placebo for the treatment of diarrhoea in lymphocytic colitis. Primary outcome is satisfactory control of diarrhea during at least 3 of the last 4 weeks [1].
Evidence based evaluations
Budenofalk Ulcerative proctitis - first-line
Information
Budenofalk
New formulation
Dr Falk
Not Known
Development and Regulatory status
None
Phase III Clinical Trials
None
Category
Suppository containing the corticosteroid, budesonide
Ulcerative colitis (UC) is an idiopathic chronic inflammatory disease of the colon that follows a course of relapse and remission. In distal disease (left-sided colitis), colitis is confined to the rectum (proctitis) or rectum and sigmoid colon (proctosigmoiditis). UC has an incidence in the UK of approximately 10 per 100,000 people annually and a prevalence of approximately 240 per 100,000 [1].
Ulcerative proctitis - first-line
Rectal
Evidence based evaluations
NefeconImmunoglobulin A (IgA) nephropathy (Berger disease), 16mg EC formulation
Information
Nefecon
New formulation
Calliditas Therapeutics
Calliditas Therapeutics
Development and Regulatory status
Phase III Clinical Trials
Phase III Clinical Trials
Pre-registration (Filed)
Yes
Yes
Apr 21FDA grants Priority Review and sets a Prescription Drug User Fee Act (PDUFA) goal date of 15/09/21 [6].
Apr 21Calliditas plans to launch its first product, Nefecon in H1 2022 after getting agreement from the EMA for an accelerated review by the EMA. The company aims to file Nefecon for approval in Q4 2021 to the EU regulator, which will review the dossier in 150 days rather than the usual 210, as Nefecon could become the first ever approved therapy for IgAN [5].
Mar 21Filed in US. Calliditas is seeking accelerated approval from the FDA under Subpart H for their New Drug Application [4].
Nov 20Calliditas plan to file for accelerated approval with US FDA Q1 2021, followed by a submission for conditional approval with the EMA H1 2021 [3].
Nov 20Calliditas intend to commercialise Nefecon by itself in US and through collaborations in other regions [3].
Nov 20Granted orphan medicinal product designation for treatment of IgA nephropathy in EU and US, prior to Nov 20 [2].
Category
Glucocorticoid receptor agonist
IgA nephropathry is the most common primary glomerular disease with approximately 30% to 40% of patients progressing to end-stage kidney disease (ESKD) within 20 years. It is uncommon below the age of 10 and 80% of cases are diagnosed between the ages of 16 and 35 [1].
Immunoglobulin A (IgA) nephropathy (Berger disease), 16mg EC formulation
Oral
Trial or other data
Nov 20Calliditas report positive topline data from PIII NefIgArd trial (NCT03643965]. RCT (n=199) met primary objective of demonstrating statistically significant reduction in urine protein creatinine ratio (UPCR or proteinuria), after 9 months of treatment with 16mg dose vs. placebo, with continued improvement at 12 months [3].
Jorveza Eosinophilic oesophagitis in children - new oral suspension formulation
Information
Jorveza
New formulation
Dr Falk
Dr Falk
Development and Regulatory status
Phase III Clinical Trials
Phase III Clinical Trials
None
Yes
Category
Oral corticosteroid in an oral suspension that is designed to coat the oesophagus, enabling local anti-inflammatory action of the drug
In 2013, eosinophilic oesophagitis was considered to affect less than 5 in 10,000 people in the EU [1]. Studies suggest that the prevalence is rising, but it is uncertain whether this is a true increase or due to better diagnosis; it is most common in middle-aged men [2].
Eosinophilic oesophagitis in children - new oral suspension formulation
Oral
Eohilia (US)Active eosinophilic oesophagitis in adults and adolescents
Information
Eohilia (US)
New formulation
Takeda
Takeda
Development and Regulatory status
None
None
Pre-registration (Filed)
Yes
Dec 20FDA has accepted for review the company’s New Drug Application and granted Priority Review for the investigational therapy budesonide oral suspension (TAK-721)[9].
Feb 20According to its latest financial results, Takeda is only developing TAK-721 for the US market [8].
Category
Oral corticosteroid in an oral suspension that is designed to coat the oesophagus, enabling local anti-inflammatory action of the drug
Eosinophilic oesophagitis affects less than 5 in 10,000 people in the EU [1].
Active eosinophilic oesophagitis in adults and adolescents
Oral
Trial or other data
Oct 19PIII study of budesonide oral suspension in eosinophilic oesophagitis completes meets co-primary efficacy endpoints; the RCT (NCT02605837; n=318) found significantly more histologic responders and dysphagia symptom responders in the budesonide oral suspension treated group versus the placebo-treated group (53.1% vs 1.0%, p<0.001; 52.6% vs 39.1%, p=0.024, respectively) after an initial 12 weeks of therapy [6].
Apr 19PIII extension study (NCT02736409) is ongoing and has completed recruitment. Collection of primary outcome data is expected to complete Nov 19 [5].
Jan 19PIII study (NCT02605837) completes [5].
Jan 18PIII study (NCT02605837) is still recruiting, & expects to complete collection of primary outcome data in Jun 18 [3]
Oct 17PIII extension trial to study safety of budesonide oral suspension in patients with eosinophilic oesophagitis and participated in SHP621-302 study starts (SHP621-303; NCT03245840). The open-label trial intends to enrol approximately 100 patients in the US [2].
Apr 16PIII ORBIT2 extension trial to assess the maintenance of efficacy of budesonide oral suspension (10ml of 0.2 mg/ml) in adolescent and adult patients with EoE and who have completed the SHP621-301/NCT02605837 induction study starts (SHP621-302; NCT02736409). The trial is recruiting 200 patients (aged 11 to 55 years) in the US [2].
Nov 15PIII trial to assess the safety and efficacy of budesonide oral suspension (10ml of 0.2 mg/ml) in adolescent and adult patients with eosinophilic oesophagitis (EoE) dysphagia starts (NCT02605837). Histologic response and dysphagia symptom response will be assessed after 16 weeks of treatment as the primary endpoints. The trial is expected to enrol approximately 300 patients (aged 11 to 55 years) in the US [2].