Hydrocortisone

Articles · Refrigerated Storage · Medicine Compliance Aid Stability · Lactation Safety Information · New Medicines ·
16602005

Articles

Refrigerated Storage

Timodine · Alliance Pharmaceuticals

Alliance Pharmaceuticals
Timodine
Cream (contains nystatin, dimeticone, hydrocortisone and benzalkonium chloride)

Contact Alliance Pharmaceuticals in cases where additional stability data is required. Refer to the current BNF for company contact details.

Please also refer to the manufacturer’s product literature for recommended storage information at https://www.medicines.org.uk

17th April 2019
London MI Service

Medicine Compliance Aid Stability

generic · Amdipharm Mercury Co Ltd

Amdipharm Mercury Co Ltd
generic
Tablets 10mg, 20mg
A3 · Amber 3 · No stability data is available. There are theoretical concerns with use in CAs, which may be mitigated by risk minimisation.
Airtight container
Protect from light
Protect from light. Store in airtight containers.
19th February 2015

Plenadren · ViroPharma Ltd

ViroPharma Ltd
Plenadren
Tablets m/r 5mg, 20mg
A3 · Amber 3 · No stability data is available. There are theoretical concerns with use in CAs, which may be mitigated by risk minimisation.
Airtight container
Protect from light
Protect from light. Store in airtight containers.
19th February 2015

generic · Auden Mckenzie

Auden Mckenzie
generic
Tablets mucoadhesive buccal 2.5mg
R2 · Red 2 · Drug is not suitable for CAs due to theoretical reasons that cannot be mitigated.
Unsuitable
Mucoadhesive buccal tablets.
1st September 2015

Lactation Safety Information

Oral / parenteral

Oral / parenteral
No published evidence of safety
Normal component of breast-milk
Used in full-term neonates from birth
Doses up to 200mg daily unlikely to cause adverse effects in the infant

Local injection

Local injection

In the ear

In the ear
Only available in combination with gentamicin for which there are no additional risks

Orophayngeal - buccal tablets

Orophayngeal -
buccal tablets

Topical

Topical
Low potency
There are no additional risks when used in combination topical preparations containing antimicrobials or urea

Rectal for inflammatory bowel disease

Rectal
for inflammatory bowel disease
-
No published evidence of safety after rectal administration
Small amounts in breast milk after oral administration
Doses up to 50mg orally daily unlikely to cause adverse effects in the infant
19th May 2016

New Medicines

Alkindi · Adrenal insufficiency

Information

Alkindi
New formulation
Diurnal
Diurnal

Development and Regulatory status

Launched
Launched
None
September 2018
Sep 18 · Launched in UK. Price 500 microgram, 50=£33.75. 1mg, 50=£67.50. 2mg, 50=£135.00. 5mg, 50=£337.50 [9].
Feb 18 · Granted a marketing authorisation valid throughout the EU on 09/02/18 [8].
Dec 17 · Recommended for approval in the EU. Full indication is "Replacement therapy of adrenal insufficiency in infants, children and adolescents (from birth to < 18 years old)” [7].
Dec 16 · EMA accept Paediatric Use Marketing Authorisation (PUMA) application for Infacort [4].
May 15 · US FDA grants orphan designation for Infacort for treatment of paediatric adrenal insufficiency [2].
Jun 13 · Diurnal receives approval for a Paediatric Investigation Plan (PIP) from the EMA. Diurnal anticipates a Paediatric Use Medicine Authorisation (PUMA) filing to the EMA by end of 2016 [2].

Category

A granule formulation of hydrocortisone, designed to release hydrocortisone in a way that mimics the natural 24-hour production of cortisol in the body.
A study found that approximately one child in every 18,000 born in Great Britain has CAH. Similar numbers of boys and girls present clinically in the first year of life but boys present with more severe manifestations, such as salt-wasting crises. Salt-losing CAH accounts for about three quarters of cases reported and non-salt-losing CAH for one quarter [6].
Adrenal insufficiency
Replacement therapy of adrenal insufficiency in infants, children and adolescents (from birth to < 18 years old)
Oral

Trial or other data

Jan 17 · Estimated primary completion date of PIII Infacort004 (NCT02733367) is Aug 17 [5].
Oct 16 · Diurnal announce pivotal PIII trial (Infacort003) met its primary endpoint, demonstrating a statistically significant (p<0.0001) increase in cortisol values following administration of Infacort compared to pre-dose values. The median 60‑minute cortisol level achieved after Infacort treatment was 535 nmol/L, which is comparable to the mean peak morning cortisol of healthy children [3].
Oct 15 · Diurnal initiates the long-term follow-up PIII Infacort004 trial to assess safety and biochemical disease control of hydrocortisone granules in neonates, infants and children with CAH and adrenal insufficiency previously enrolled in the Infacort003 study (EudraCT2015-000458-40). The open-label trial is recruiting 24 patients in Germany [2].
Feb 15 · Diurnal initiates the open-label PIII Infacort003 study to evaluate safety, efficacy, pharmacokinetics and pharmacodynamics of Infacort® in congenital adrenal hyperplasia patients, aged 0-11 years (P01-2012; EudraCT2014-002265-30). Serum cortisol concentration after 240 minutes of administration will be evaluated as primary endpoint for the study. The study intends to enrol approximately 24 patients in Germany [2].
Dec 13 · Diurnal announces Infacort001 trial met its primary objective of demonstrating bioequivalence of Infacort® 10mg and marketed hydrocortisone tablets. The agent was safe, well-tolerated and was shown to be of neutral taste [2].
Nov 13 · A second PI trial of the paediatric hydrocortisone formulation was completed in the UK (Infacort002; NCT01960530). The trial investigated pharmacokinetics and oral bioavailability of immediate-release hydrocortisone tablets, and the relationship between drug concentrations and metabolic effect, in 14 healthy adult male volunteers [2].
Sep 13 · Diurnal completes a first-in-human PI trial in the UK, which compared pharmacokinetics of its immediate-release hydrocortisone formulation, Infacort® 10mg, and a marketed immediate-release formulation 10mg, in 16 healthy adult male volunteers (Infacort001; P031-2013; EudraCT 2013-000260-28). The randomised, crossover open-label trial also evaluated the dose-proportionality of Infacort® over the dose range 0.5, 2, 5 and 10mg. This trial is part of the Paediatric Investigation Plan [2].

Evidence based evaluations

Chronocort · Adrenal insufficiency due to congenital adrenal hyperplasia in adults - extended-release formulation

Information

Chronocort
New formulation
Diurnal
Diurnal

Development and Regulatory status

Pre-registration (Filed)
Pre-registration (Filed)
Phase III Clinical Trials
Yes
Yes
Dec 19 · Filed in the EU [13].
Nov 19 · Diurnal still expect to submit a MAA by end of 2019 [12].
Mar 19 · Diurnal report positive outcome from meeting with EMA to discuss regulatory pathway for Chronocort; no further trials are required. Diurnal intend to submit a EU MAA for Chronocort in Congenital Adrenal Hyperplasia (CAH) Q4 2019 [11].
Dec 18 · Diurnal submit a regulatory package for scientific advice in EU. Subject to the outcome of this advice, the company anticipate filing a MAA Q4 2019 [10].
Oct 18 · The manufacturer, following PIII trial results, said that "...we will now analyse the full data set from this trial, along with interim data from the ongoing Chronocort® long-term dosing study, to determine next steps in Chronocort development, and discuss these with the regulatory authorities.".[9]
Jan 18 · Diurnal expect to submit MAA by the end of 2018 [8].
Jan 18 · Two PIII studies in are ongoing in EU - EUDRA CT 2015-005448-32 and EUDRA CT 2015-000711-40 [7].
Jan 18 · Recruitment to two PIII trials (NCT03062280 and NCT02716818) is underway in US [6].
Feb 16 · Diurnal expect to submit a marketing authorisation application for Chronocort® by the end of 2017, with launch in 2018 [5].
Mar 15 · Diurnal are planning a pivotal large multi-centre PIII study, to start in 2015 [4].
Mar 15 · Granted orphan drug status in US [4].
Jul 05 · Granted orphan drug status in EU to treat CAH [3].

Category

A glucocorticoid receptor agonist providing delayed release of hydrocortisone to allow synchronisation with natural release of glucocorticoid in early hours of the morning.
Prevalence of congenital adrenal hyperplasia in the UK is 1 in 12,000 [1].
Adrenal insufficiency due to congenital adrenal hyperplasia in adults - extended-release formulation
Oral

Trial or other data

Oct 18 · Results from PIII trial (n=122) showed that chronocort was no better at controlling sex hormones than conventional glucocorticoid doses in pts with congenital adrenal hyperplasia (CAH). In the trial, pts and randomised to continue on standard-of-care regimes or switch to twice-daily doses of Chronocort. Over 24 weeks, investigators analysed the change in 17-hydroxyprogesterone levels.[9]
Dec 13 · PII (NCT01735617) study completes [2].
Dec 12 · PII (NCT01735617) study to gather safety and effectiveness information about Chronocort® to treat patients with CAH. The objective of the study is to measure levels of hydrocortisone that are absorbed into the bloodstream once Chronocort® is taken and what affects it has on other hormones in the body. Since Chronocort® is anticipated to mimic the same release pattern of cortisol in the body, it is hoped that patients with CAH will be treated more effectively to manage their disease. 16 patients will be recruited in the US [3].

Evidence based evaluations

SMC