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Providing patient information leaflets following COVID-19 treatment

31 March 2021Following treatment for COVID-19 with tocilizumab, sarilumab, or steroids, clinicians should provide suitable patient information leaflets at discharge

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…

What injections can be given orally or via enteral feeding tubes?

6 November 2020This updated Medicines Q&A is a quick reference summary to different types of enteral feeding tubes, in relation to medication issues. Not all enteral feeding…
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Lactation Safety Information

Oral / Parenteral

Oral / Parenteral
Prednisolone (oral), Hydrocortisone (parenteral)
No published evidence of safety
Used in infants >1 month
Doses up to 8mg daily unlikely to cause adverse effects in the infant
23 June 2020

Local injection

Local injection
No published evidence of safety
Lower systemic absorption compared to oral and parenteral therapy
Theoretical risk of milk production being reduced temporarily
23 June 2020

For ophthalmic use

For ophthalmic use
Yes
There are no additional risks when used in combination ophthalmic preparations containing neomycin + polymyxin B or tobramycin
Limited systemic absorption in the mother, therefore negligible risk to the infant
Systemic absorption from eye drops can be minimised by restricting passage into tear ducts immediately after administration (see technique).
There are no additional risks when used in combination ophthalmic preparations containing neomycin + polymixin B or tobramycin
23 June 2020

For use in the ear

For use in the ear
Yes
No published evidence of safety
Limited systemic absorption in the mother, therefore negligible risk to the infant
There are no additional risks when used in combination aural preparations containing neomycin or framycetin
23 June 2020

New Medicines

Glensoludex Coronavirus disease 2019 (COVID-19)

Information

Glensoludex
Licence extension / variation
Glenmark
Not Known

Development and Regulatory status

Launched
None
None
December 2020
Dec 20New indication approved in the UK for treatment of coronavirus disease 2019 (COVID-19) in adult and adolescent patients (aged 12 years and older with body weight at least 40 kg) who require supplemental oxygen therapy. The recommended dose is 6 mg, once a day for up to 10 days [1].

Category

Corticosteroid, in 2mg, 4mg and 8mg soluble tablet formulations.
Coronaviruses are a family of viruses transmitted between animals and people that can lead to respiratory illness, including MERS and SARS. On January 7, 2020, a novel coronavirus (Covid-19) was identified as the cause of pneumonia cases in Wuhan, China. As a group, coronaviruses are common across the world. Covid-19 was declared a pandemic on 11 March 2020.
Coronavirus disease 2019 (COVID-19)
Oral

Dexamethasone TawCoronavirus disease 2019 (COVID-19)

Information

Dexamethasone Taw
Licence extension / variation
Taw Pharma
Not Known

Development and Regulatory status

Phase III Clinical Trials
Filing withdrawn
None
Jan 21Taw Pharma withdraw MAA, as it is unable to remove preservatives from the medicine within the timeframe required by EMA [10].
Sep 20EMA endorses use of dexamethasone 6mg once a day for up to 10 days in adults and adolescents (from 12 years of age and weighing at least 40 kg) with COVID-19 who require supplemental oxygen therapy. Companies that market dexamethasone medicines can request this new use to be added to their product’s license by submitting an application to national medicines agencies or to EMA [9].
Sep 20EMA are evaluating an application from Taw Pharma for the authorisation of Dexamethasone Taw for treating hospitalised adult patients with COVID-19. Dexamethasone Taw is being developed a hybrid medicine, and if authorised, will be used to treat the same conditions as Fortecortin Inject (reference medicine) with the addition of COVID-19 [8].
Jun 20Chief Medical Officers for England, Scotland and Wales, and the National Medical Director for NHS England & Improvement, issue a response to the early results of the RECOVERY trial. It states ´ Normally we would advise waiting for the full paper before changing practice, to ensure final analysis and peer review do not lead to different conclusions. However, given this clear mortality advantage, with good significance, and with a well known medicine which is safe under these circumstances we consider it is reasonable for practice to change in advance of the final paper´ [3].

Category

Glucocorticoid receptor agonist in a low-dose (6mg daily for 10 days)
Coronaviruses are a family of viruses transmitted between animals and people that can lead to respiratory illness, including MERS and SARS. On January 7, 2020, a novel coronavirus (Covid-19) was identified as the cause of pneumonia cases in Wuhan, China. As a group, coronaviruses are common across the world. Covid-19 was declared a pandemic on 11 March 2020.
Coronavirus disease 2019 (COVID-19)
Intravenous and
Oral

Trial or other data

Sep 20CoDEX RCT (n=299) found that number of days alive and free from mechanical ventilation during first 28 days was significantly higher among patients treated with dexamethasone plus standard care vs. standard care alone (6.6 days vs 4.0 days; p = 0.04) [7].
Jul 20Open-label RECOVERY trial (n=6425) reported lower 28-day mortality with dexamethasone in mechanical ventilation (29.3 vs. 41.4%; rate ratio 0.64) or oxygen pts (23.3 vs. 26.2%; 0.82;) but not in no respiratory support pts (17.8 vs. 14.0%; 1.19) vs usual care [6].
Jun 20Preliminary report of the RECOVERY trial (non-peer reviewed) found that dexamethasone reduced the risk of death vs usual care in those on mechanical ventilation (29.0% vs 40.7%, RR 0.65, p<0.001), and oxygen therapy (21.5% vs 25.0%, 080, p<0.001) but not with those not on respiratory support [5].
Jun 20Early results announced from the PII/III RECOVERY trial. Over 11,500 patients have been enrolled from over 175 NHS hospitals in the UK. On 8 June, recruitment to the dexamethasone arm was halted since, in the view of the trial Steering Committee, sufficient patients had been enrolled to establish whether or not the drug had a meaningful benefit. A total of 2104 patients were randomised to receive dexamethasone 6mg once per day (either by mouth or by intravenous injection) for ten days and were compared with 4321 patients randomised to usual care alone. Among the patients who received usual care alone, 28-day mortality was highest in those who required ventilation (41%), intermediate in those patients who required oxygen only (25%), and lowest among those who did not require any respiratory intervention (13%). Dexamethasone reduced deaths by one-third in ventilated patients (rate ratio 0.65 [95% confidence interval 0.48 to 0.88]; p=0.0003) and by one fifth in other patients receiving oxygen only (0.80 [0.67 to 0.96]; p=0.0021). There was no benefit among those patients who did not require respiratory support (1.22 [0.86 to 1.75]; p=0.14). Based on these results, 1 death would be prevented by treatment of around 8 ventilated patients or around 25 patients requiring oxygen alone. Given the health importance of these results, the investigators are now working to publish the full details as soon as possible [2].
Jun 20PII/III RECOVERY trial is still recruiting [1].
Mar 20PII/III RECOVERY trial to investigate whether treatment with either lopinavir-ritonavir, hydroxychloroquine, corticosteroids, azithromycin, convalescent plasma or tocilizumab prevents death in patients with COVID-19 starts (NCT04381936). 12,000 children and adults will be recruited in the UK. Primary outcome is all-cause mortality within 28 days; collection of these data is due to complete Dec 20 [1].

Evidence based evaluations

DexycuOcular inflammation; post-cataract surgery - intraocular injection

Information

Dexycu
New formulation
Icon Bioscience
Icon Bioscience

Development and Regulatory status

None
None
Launched
Feb 19EyePoint Pharmaceuticals commercially launches DEXYCU (dexamethasone intraocular suspension) 9% in the US for the treatment of postoperative inflammation and is administered as a single dose at the end of cataract surgery [8].
Feb 18DEXYCU receives FDA approval for for treating inflammation associated with cataract surgery [7].
Apr 17Filed in the US [5].
Feb 13PIII in the US [1].

Category

Intra-ocular corticosteroid administered using a proprietary biodegradable extended-release formulation ("Verisome")
In 2011, there were 313,411 NHS admissions for cataract surgery in England. Small-incision cataract surgery using phacoemulsification has largely replaced extracapsular cataract extraction because of faster healing, smaller wounds and fewer resultant complications. However, post-operative complications, including ocular inflammation, continue to cause visual impairment, pain and other sequelae among pts [1].
Ocular inflammation; post-cataract surgery - intraocular injection
Intraocular

Trial or other data

Nov 16Open-label, parallel, prospective, randomised PIII trial completed evaluating the safety of intraocular dexamethasone, vs. prednisolone 1% drops, for the treatment of inflammation associated with cataract surgery (NCT02547623). The primary endpoint of spectral microscopy endothelial count was assessed at 90 days post surgery; safety measures were assessed by adverse events, slit lamp biomicroscopy, fundus examination, intraocular pressure and visual acuity. The trial was initiated Oct 15 and enrolled 180 patients, aged 40 years and older, in the US. [6].
Apr 15Results from PIII trial NCT02006888 reported by Icon Bioscience. The results of the trial showed that IBI-10090 is highly effective in treating inflammation post cataract surgery. In both of the clinical trial´s drug treatment arms, the percentage of patients with an ACC=0 grade at day 8 was statistically significant compared to placebo. Specifically, the percentage of patients with ACC clearing at day 8 was 63.1%, and 66.0% in the 342 µg and 517 µg treatment groups, respectively, (P< 0.001) compared to 25.0% in the placebo group. With regard to secondary endpoints, the percentage of patients with ACF clearing at day 8 was 92.4%, and 89.1%, respectively, in the 342 µg and 517 µg treatment groups (P< 0.001) compared to 63.8% in the placebo group. The percentage of patients with ACCF clearing at day 8 was 63.1% and 67.3% in the 342 µg and 517 µg treatment groups, respectively, (P< 0.001) compared to 33.8% in the placebo group. Additionally, no ocular serious adverse events were reported up to day 90 and adverse events among the three groups were similar [5].
Oct 14October 2014, Icon Bioscience completed a US-based double-blind, randomised, placebo-controlled phase III trial (n=390) that investigated the efficacy and tolerability of low versus medium doses of dexamethasone in patients with ocular inflammation associated with unilateral cataract surgery (NCT02006888). This trial employed the two lower doses of dexamethasone, used in a previous phase II/III trial. The trial began in December 2013. Top-line data are awaited [4].
Dec 13NCT02006888 is a PIII double-blind study of IBI-10090 injection (low and medium dose) in treating of inflammation associated with cataract surgery in 352 patients. The primary outcome is anterior chamber cell clearing (ACC = 0) in the study eye at Day 8. The study starts Dec 13 and is due to complete Sep 14 [3].
Feb 13Verisome is a biodegradable product intended for the safe delivery & sustained release of dexamethasone into the anterior chamber to prevent and treat inflammation associated with cataract surgery [1].
Apr 12PII/III (NCT01606735) study begins enrolling 228 US pts scheduled for unilateral cataract surgery. Pts will be randomised to IBI-10090 342μg, 517μg or 697μg intraocular intraoperative injection. The primary endpoint is anterior chamber cell count at day 8 post-treatment. The study is expected to complete in Jan 13 [2].
Sep 10PII/III (NCT01214174;) trial begins enrolling 228 US pts scheduled for unilateral cataract surgery. Pts will be randomised to IBI-10090 513μg, 776μg or 1046μg intraocular injection. The primary endpoint is anterior chamber cell count at day 8 post-treatment. The study is expected to complete in Dec 12 [2].

Evidence based evaluations

Ocular inflammation and pain post cataract surgery - sustained-release topical formulation

Information

New formulation
InSite Vision
InSite Vision

Development and Regulatory status

None
None
Phase III Clinical Trials

Category

Topical corticosteroid, using DuraSite® sustained delivery technology, comprising a patented, synthetic, bio-adhesive, polymer-based formulation designed to extend the residence time of a drug relative to conventional topical therapies.
Around 330,000 cataract operations are performed per year in England. Overall crude estimates suggests surgery incidence rates of approximately 530 per 100,000 population or 3,200 per 100,000 for those over 65 years old per year in recent years (2011 data). Incidence rates of post-cataract surgery inflammation range from 1.5% and 2% but does not take into account people with diabetes. This would equivalent to 4,590 to 6,600 cases of post-cataract surgery inflammation in England/year [1].
Ocular inflammation and pain post cataract surgery - sustained-release topical formulation
Topical

Evidence based evaluations

OtividexMénière's disease - intratympanic injection

Information

Otividex
New formulation
Otonomy
Otonomy

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

Glucocorticoid receptor agonist
Estimate prevalence in the UK is ~157 per 100,000 of the population. It can occur at any age but the peak incidence is 40-60 years [1].
Ménière's disease - intratympanic injection
Intratympanic

DextenzaAllergic conjunctivitis due to a variety of allergens

Information

Dextenza
New formulation
Ocular Therapeutix
Ocular Therapeutix

Development and Regulatory status

None
None
Approved (Licensed)
Oct 21Dextenza approved by FDA to treat eye itching associated with allergic conjunctivitis [10].
Dec 20Filed in US for ocular itching associated with allergic conjunctivitis [9].
Sep 20 If the third PIII trial is successful the company plans to file for ocular itching associated with allergic conjunctivitis in the US. Top line data from this trial are due H1 2020 [7].
Dec 18Still listed as PIII on company pipeline but no reports of further development [6]
Apr 17Remains PIII in the US for chronic allergic conjunctivitis; has been filed with the FDA for treatment of post-surgical ocular pain [5].

Category

Sustained-release low dose formulation of dexamethasone
Allergic conjunctivitis is the cause of around 15% of all eye problems presenting in general practice [1].
Allergic conjunctivitis due to a variety of allergens
Intravitreal

Trial or other data

Apr 20In PIII trial, DEXTENZA met all pre-specified primary endpoints with a statistically significant mean change in ocular itching from baseline (p<0.0001), on a subject-reported 5-point scale, at three time points on Day 8, 1 week after insertion of DEXTENZA [8].
Aug 19A third randomised, double-blind, placebo-controlled PIII trial to assess the efficacy and safety of Dextenza for the treatment of ocular itching associated with allergic conjunctivitis (NCT04050865) has started and intends to recruit 80 patients in the US. The trial is designed to assess the effect of Dextenza vs placebo on allergic reactions using a series of successive allergen challenges over a 30 day period. The primary efficacy endpoint is ocular itching following insertion of Dextenza at multiple time points during the 30 day period [7].
Jun 16Ocular Therapeutix reports that the PIII trial (NCT02988882) did not meet primary endpoint. The trial completed May 2016, and was designed to assess the effect of OTX-DP versus placebo on allergic reactions using four series of successive allergen challenges over a 30-day period. The primary endpoint of the trial was ocular itching at day 7 following insertion. The trial was initiated in November 2015 and enrolled 86 patients in the US [5].
Oct 15Ocular Therapeutix announces topline efficacy results from a PIII trial (NCT02445326). The primary endpoint of treatment of ocular itching associated with allergic conjunctivitis was successfully achieved (p<0.0001) at all three time points measured on day 7 post-insertion of the drug product. The difference in the scores for ocular itching between the DEXTENZA group and the placebo group was greater than 0.5 units at all time points on day 7 post-insertion and was greater than 1 unit at a majority of the time points on day 7 post-insertion. The DEXTENZA treatment group did not achieve the primary endpoint for conjunctival redness. Ocular Therapeutix notes the primary endpoint of conjunctival redness is typically an endpoint included in PIII trials for allergic conjunctivitis but has not been required for approval & many commercially available prescription medications for treatment of allergic conjunctivitis have an ocular itching indication only [4].
Apr 15A PIII trial of 240 pts showed significant absence of pain in the treatment group after several days in comparison to the placebo group. However, there was no statistically significant difference in the reduction of inflammation between pts who received the mediation vs. placebo. The trial did meet its expected endpoints regarding safety of the medication. The company are conducting a review of the data in order to better understand the results [3].
Nov 14Ocular Therapeutix announced top-line results from PII trial of OTX-DP in allergic conjunctivitis caused by any allergen. The prospective, multicentre, randomised, double-blinded study evaluated OTX-DP vs. a placebo vehicle control in 68 pts over 42 days. The primary endpoint was a measure of ocular itching and conjunctival redness at 14 days post-insertion on a five point scale. OTX-DP treated subjects presented statistically significant lower ocular itching and conjunctival redness scores compared with the placebo group on day 14 (-0.5 points vs. placebo) but did not, however, achieve a mean difference of 1.0 unit at the majority of time points [2].
Nov 14OTX-DP (a low dose formulation of dexamethasone loaded onto an inert hydrogel punctal plug) is a punctal plug designed to be placed in the canaliculus of the eye releasing dexamethasone slowly over 2 weeks. This period is followed by a 2 week taper, after which the plug starts to degrade and passes out of the nasolacrimal system without requiring assisted removal [2].