Safety in Lactation: Anti-infective eye preparations

30 October 2020Anti-infective preparations for ophthalmic use have limited systemic absorption in the mother, and pose negligible risk to a breastfed infant. Systemic absorption from eye drops…

Safety in Lactation: Quinolones

21 October 2020Quinolones are generally accepted for use during breastfeeding, with caution. There have been concerns about adverse effects on infants’ developing joints, although this has only…

Raising the profile of medicines safety: Changing practice and sharing learning from medication incidents

22 August 2019The Patient Safety Alert: Improving medication error incident and reporting1,2  raised the profile of medicines safety in our Trust (CDDFT). Our evolving programme, focussing on…
Search Articles

Medicine Compliance Aid Stability

genericAccord Healthcare Ltd

Accord Healthcare Ltd
Tablets 250mg, 500mg, 750mg
A3 · Amber 3No stability data is available. There are theoretical concerns with use in CAs, which may be mitigated by risk minimisation.
Airtight container
Protect from moisture
Hygroscopic. Maximum 7 days in MCA.
5 August 2015

Lactation Safety Information

Cephalosporin/penicillin if microbiologically appropriate.
Limited published evidence of safety
Small amounts in breast milk
Case report of pseudomembranous colitis
17 September 2020

For ophthalmic use

For ophthalmic use
17 September 2020

New Medicines

LinhaliqBronchiectasis in non-cystic fibrosis patients with chronic respiratory infections due to Pseudomonas aeruginosa - first-line for prevention of pulmonary exacerbations (liposomal inhaled formulation)


New formulation

Development and Regulatory status

Nov 19CHMP meeting highlights indicate that at the time of the withdrawal, the EMA considered that the studies presented did not show convincingly that the medicine was effective, and also that more data were needed to show that its quality was consistent [20].
Oct 19Aradigm announce withdrawal of MAA [19].
Aug 19Company have filed for bankruptcy which is likely to impact on potential launch date [18].
Mar 18Aradigm has submitted its Marketing Authorisation Application to the EMA for Linhaliq™ for the treatment of non-cystic fibrosis bronchiectasis (NCFBE) patients with chronic lung infection with Pseudomonas aeruginosa [14].
Dec 16PIII studies (ORBIT-3 & 4) have now completed [13].
Jan 16PIII studies (ORBIT-3 & 4) are now due to complete Sep 16 [12].
Mar 15Two PIII studies (ORBIT-3 & 4) on-going and due to complete Jul 16 [11].
Mar 13No further update.
Mar 12PIII studies to start Jun 12 [7].
Mar 10Granted orphan drugs status in the US [5].
Jun 08PII trials starting [1].


Once-a-day inhaled formulation consisting of a mixture of unencapsulated ciprofloxacin and ciprofloxacin encapsulated in liposomes, delivering immediate and sustained release of the drug within the lung.
Bronchiectasis is a persistent or progressive condition characterised by dilated thick-walled bronchi. It may be widespread throughout the lungs or more localised. The incidence varies between populations from 3.7 per 100,000 children in New Zealand to 52 per 100,000 adults in the US. Features of bronchiectasis found in chest X-rays in the UK in the 1950s suggested a prevalence of 100 per 100,000 [8].
Bronchiectasis in non-cystic fibrosis patients with chronic respiratory infections due to Pseudomonas aeruginosa - first-line for prevention of pulmonary exacerbations (liposomal inhaled formulation)

Trial or other data

Jan 18PIII studies (ORBIT-3, NCT01515007 and ORBIT-4, NCT02104245) completed. [15] Top-line results of two PIII ORBIT-3 and ORBIT-4 trials in pts with non-CF bronchiectasis demonstrated a statistically significant reduction in Pseudomonas aeruginosa density at day 28, the end of the first on-treatment period (ORBIT-3 p = <0.0001, ORBIT-4 p = <0.0001). The magnitude of this antibiotic effect remained persistent throughout all on-treatment periods, in each study. In ORBIT-4 trial, the median time to first pulmonary exacerbation (PE) was 230 days in the inhaled ciprofloxacin treatment group vs. 158 days in the placebo group (p=0.0323). In ORBIT-3 study, the median time to first PE was 214 days in the inhaled ciprofloxacin treatment group vs. 136 days in the placebo group (p=0.9743).[16]
Apr 14NCT02104245 (ORBIT-4) is a PIII multicenter, randomized, double-blind, placebo-controlled of Pulmaquin® in the management of chronic lung infections with Ps. aeruginosa in 255 patients with non-cystic fibrosis bronchiectasis. The study will consist of a screening phase, a double-blind phase (6 cycles each consisting of 28-days once daily Pulmaquin or placebo, and 28 days off treatment) followed by open-label extension (28 days on Pulmaquin). The study starts Jun 14 and is due to complete Sep 16 [10].
May 13Grifols has agreed with Aradigm to fund PIII development of Pulmaquin and Lipoquin for non-cystic fibrosis bronchiectasis and is responsible for all commercialization activities. (Lipoquin is a liposomal formulation of ciprofloxacin. Pulmaquin is a dual release formulation that is a mixture of Lipoquin with unencapsulated ciprofloxacin.) [9].
Mar 12Plans for a PIII programme in patients with non-cystic fibrosis bronchiectasis (BE) have been cleared by the EMA and FDA. The program will consist of two identical placebo controlled trials enrolling 250 patients per trial with one year duration. The first study (NCT01515007) will begin in Jun 12. It is a multicentre, double-blind PIII RCT comparing Pulmaquin with placebo in patients with chronic lung infections with pseudomonas aeruginosa. The primary outcome is time to first exacerbation. Pulmaquin will be given once daily for 28 days on and 28 days off for six cycles. The study is due to complete Jul 14 [7]
Oct 10Company announced positive top line data from the 6-month P2b study (ORBIT-2) in patients with non-cystic fibrosis bronchiectasis. The primary endpoint - the mean change in Pseudomonas aeruginosa density in sputum from baseline to day 28 - was met; there was a mean reduction of 4.2 log10 units in the ciprofloxacin group vs 0.1 log10 units in the placebo group (p=0.004). 17 subjects on placebo required supplemental antibiotics for respiratory-related infections vs 8 subjects on ciprofloxacin (p=0.05), a secondary endpoint. The randomized, double-blind ORBIT-2 (Once-Daily Respiratory Bronchiectasis Inhalation Treatment) trial was conducted in Australia and New Zealand. Following a screening period, 42 patients, randomized into two equal sized groups, were treated once-a-day for 28 days with either the active drug or placebo, followed by a 28 day off-treatment period. This on-off sequence was repeated three times [6].
Feb 10ORBIT-1 (Once-daily Respiratory Bronchiectasis Inhalation Treatment) phase IIb study: Study will assess inhaled liposomal ciprofloxacin in 96 patients with non-cystic fibrosis bronchiectasis (BE). Pts will receive for four weeks either one of two different once-daily inhaled doses (100 or 150 mg ciprofloxacin delivered by inhalation as 2 or 3 mL of liposomal dispersion, respectively) or once-daily inhaled placebo. The main efficacy outcome = standard measure of antibacterial activity: the change from baseline in sputum Pseudomonas aeruginosa colony forming units (CFUs). Secondary outcomes will include quality of life measurements and improvement of outcomes with respect to exacerbations. Lung function changes will be monitored for safety. (4)
Jun 08Phase II, multicentre trial for inhaled liposomal ciprofloxacin in adult pts with non-cystic fibrosis bronchiectasis initiated. After an antibiotic washout period 36 pts will be recruited to receive daily inhaled liposomal ciprofloxacin for a period of 28 consecutive days. The primary efficacy endpoint will be therapy of respiratory infection measured as the change in the density of Pseudomonas Aeruginosa bacterial colony forming units (CFU) in the sputum over the therapy period. (2)

OtiprioBacterial infections in children undergoing tympanostomy tube-placement - intratympanic injection


New formulation
Not Known

Development and Regulatory status

Dec 19Launched in US. Plans for launch in EU/UK not documented.
01. Apr 15: Results from two identical PIII trials of AuriPro™ were presented at an annual American Society of Paediatric Otolaryngology (ASPO) meeting. These data supported a New Drug Application (NDA) submitted to the FDA in February 2015 for AuriPro for the treatment of middle ear effusion in paediatric pts undergoing TTP surgery. If approved, a commercial launch in the US is planned in the first quarter of 2016 [4].
02. Apr 15: US FDA accepts AuriPro for filing to treat middle ear effusion in paediatric pts undergoing tympanostomy tube placement (TTP) surgery [5].
03. Dec 15. Approved in US [6].
04. Dec 15: Otonomy is planning to get Otiprio on the US market in Q1 2016, & plans to look for a partner to commercialize the drug overseas [7].
05. Mar 18: No further information on company website.[8]


Sustained-release intratypmanic formulation of ciprofloxacin
Glue ear is common. By 10 years of age, 8 out of 10 children will have had at least one episode of OME. It is most common between the ages of 2 and 5 years. Boys are more commonly affected than girls. Most cases occur in winter. Glue ear persists for a year or more in a small number of cases (~1 in 10). In 2017/18 there were 24,670 finished consultant episodes for Myringotomy with insertion of ventilation tube through tympanic membrane. [10,11]
Bacterial infections in children undergoing tympanostomy tube-placement - intratympanic injection

Trial or other data

01. NCT01949142 and NCT01949155 are two similarly designed double-blind, sham-controlled, multicentre, PIII studies of OTO-201 given as a single intratympanic injection for intra-operative treatment of middle ear effusion in each in 264 paediatric subjects (6mo -12 years) requiring tympanostomy tube placement. The primary outcome is cumulative proportion of treatment failures over 1 month. The studies started Nov 13 and are due to complete Jul 14 [1].
02. Jul 14: In two PIII trials, AuriPro met its primary endpoint of 15-day freedom from ear drainage in patients aged 6 months to 17 years old [3].
03. Apr 15: Results from the two prospective, randomised, double-blind, sham-controlled PIII trials demonstrated that AuriPro achieved the primary efficacy endpoint, reduction in the incidence of treatment failures, with statistical significance (p<0.001) and that it was well tolerated. AuriPro reduced the risk of treatment failure (measured by the need for post-operative drainage or rescue antibiotics), by an average of 49% across the two trials. The studies enrolled a combined total of 532 paediatric pts [4].
04. Jun 17: Otonomy announced successful completion of an end-of-PII review with the FDA supporting that a single, placebo-controlled, pivotal PIII trial enrolling ~200 children with AOMT is sufficient to support approval of OTIPRIO for this indication. The timing for initiation of this trial has not yet been determined.[8]

Evidence based evaluations