dm+d

27196008

Articles

Safety in Lactation: Local anaesthesia

25 September 2020Local anaesthetics are generally considered to be compatible with breastfeeding. They are used in a variety of clinical situations (surgery including Caesarean sections, labour and…

Bupivacaine + meloxicam

12 July 2019Sustained release local anaesthetic formulation
Search Articles

Lactation Safety Information

Yes
Limited published evidence of safety
Small amounts in breast milk and minimal absorption from the infant’s GI tract
24 September 2020

New Medicines

ExparelPostoperative pain in adults

Information

Exparel
New formulation
Patheon/Pacira
Pacira

Development and Regulatory status

Approved (Licensed)
Approved (Licensed)
Launched
Dec 20Approved in EU (and UK) [20].
Sep 20Recommended for EU approval by CHMP - the full indication is "as a brachial plexus block or femoral nerve block for treatment of post-operative pain in adults, and as a field block for treatment of somatic post-operative pain from small- to medium-sized surgical wounds in adults (see section 5.1). The medicine should be administered in a setting where trained personnel and appropriate equipment are available" [19].
Jun 19Marketing Authorization Application (MAA) for EXPAREL (bupivacaine liposome injectable suspension) for postsurgical analgesia validated by the EMA. CHMP opinion expected in H2 2020 [16].
Apr 18Company still states that it is "pursuing commercial partnerships in regions outside of the United States." [15] Partnership with Patheon is purely for manufacturing.
Mar 15Reported as in PII developent in the EU and UK, with plan to file in EU [14].
May 14Supplemental New Drug Application (sNDA) filed in the US for a nerve block indication for Exparel. The sNDA is based on positive data from a PIII study in femoral nerve block for total knee arthroplasty, and also includes additional safety data from a PIII study of Exparel used to perform an intercostal nerve block for thoracotomy. If the FDA accepts the sNDA filing, a PDUFA target date of March 5, 2015 is expected [12].
Apr 14Dedicated manufacturing unit being constructed in UK [15]
Aug 13Pacira plans to file in the US in early 2014 with safety data from the ongoing femoral and the intercostal nerve block study [10].
Apr 12Launched in the US [9].
Oct 11Approved in US for administration into the surgical site to produce postsurgical analgesia [8].
Jun 11US FDA have extended the Prescription Drug User Fee Act (PDUFA) goal date for its review of the New Drug Application for Exparel (Bupivacaine Extended-Release Liposome Injection) in pain management by three months to 28 October 2011. The FDA requested additional information from Pacira, which the company has submitted. The FDA determined that this information constituted a major amendment. [6]
Dec 10US filing submitted Sep 10 and accepted Dec 10 by the FDA. A decision is expected July 28, 2011 [3]
Nov 09EU and US filings expected 2010 [1].

Category

Sustained release local anaesthetic formulation
In UK hospitals around two thirds of patients experience pain during their admission and 20% of all inpatients may be suffering with moderate to severe pain at any time. Almost 60% of patients experience severe pain in the post-operative period [17]. In 2018-19 there were 12,164,264 recorded procedures in England [18].
Postoperative pain in adults
Infiltration

Further information

NICE has decided it will not appraise bupivacaine in this indication

Trial or other data

Oct 14Pacira Pharmaceuticals annouced additional data supporting safety of Exparel in Peripheral Nerve Block. The analysis was based on a review of six Phase 1-3 clinical trials. Exparel at doses up to 266 mg as a femoral, intercostal or ankle block exhibited a similar rate of adverse events to both placebo and bupivacaine groups (76% for Eexparel vs. 76% for placebo vs. 61% for bupivacaine). The most common events were gastrointestinal disorders, administration site events, cardiac and nervous system disorders [13].
Feb 14A PIII trial assessing the safety and efficacy of EXPAREL 266mg vs placebo in 183 patients having femoral nerve block for total knee arthroplasty met its primary efficacy endpoint for cumulative pain scores over 72 hours as measured by the area under the curve (AUC) (P<0.0001). The preliminary safety analysis was comparable between the two groups [11].
Aug 13Exparel failed to meet the primary endpoint of reduction of cumulative pain scores over 72 hours vs placebo in a PIII intercostal nerve block study in 180 patients who had had posterolateral thoracotomy. The study was carried out in the US, Bulgaria, Georgia, Poland and the Czech Republic and results varied according to country [10].
Oct 11A pooled analysis of data from 5 active-control RCTs with > 700 patients across variety of surgical models (hemorrhoidectomy, total knee arthroplasty and herniorrhaphy) compared depobupivacaine at doses ≤300 mg and bupivacaine HCl at doses ≤150 mg administered via wound infiltration. Depobupivacaine resulted in longer time to first opioid use (9.9 vs 2.7 hours), a reduced overall consumption of opioids (7.9 vs 15.8mg), fewer opioid-related AEs (mean 0.25 vs 0.46) and better pain control (AUC0-72 315 vs 427 over 72 hours); each finding was statistically significant (P<0.0001) [7].
May 11Positive data from a Phase III, multicentre, randomised, double-blind, parallel-group, placebo-controlled trial assessing depobupivacaine in 189 patients following haemorrhoidectomy. Patients experienced less pain and a reduction in opioid use for 72 hours following a single injection of depobupivacaine (Exparel) at the end of the surgical procedure. A statistically significant reduction in cumulative pain score was seen in patients receiving Exparel vs. placebo. The median time to first opioid rescue was 14 hours and 20 minutes in the Exparel group vs 70 minutes in the placebo group. Exparel was well tolerated with a similar incidence of side effects to placebo. The most common AEs experienced were gastrointestinal in nature, occurring in 8.4% of Exparel patients and 13.8% of placebo patients. Overall, 94.7% of patients treated with Exparel were "satisfied" or "extremely satisfied" with their postsurgical analgesia at 72 hours vs. 73.9% in the placebo group. [5]
Jan 11Additional data from the PIII study in 193 subjects undergoing first metatarsal osteotomy (bunionectomy) were reported at the Orthopaedic Research Society meeting. Median time to first use of opioid rescue medication was 7.2 hours for patients treated with EXPAREL vs 4.3 hours for patients treated with placebo (p<0.0001) and a greater proportion avoided opioid rescue medication during the first 24 hours after surgery (7% vs. 1%; p<0.05) [4].
Dec 09Results from the second PIII study of DepoBupivacaine reported. The study in 189 patients undergoing haemorrhoidectomy, met its primary endpoint, showing a statistically significant redu,ction in AUC of the NRS pain scores vs placebo up to 72 hours (p<0.0001). Opioid sparing effects were also demonstrated [2].
Nov 09Two ongoing PIII SIMPLE trials will evaluate the safety and efficacy of a single intraoperative administration of EXPAREL for prolonged postoperative analgesia following haemorrhoidectomy and in total knee arthroplasty [1].
Nov 09The formulation uses the proprietary sustained-release DepoFoam multivesicular liposomal particles which release the drug over a desired period of time [1].
Oct 09Results reported from a PIII study in 193 subjects of a single administration of EXPAREL for postoperative analgesia following first metatarsal osteotomy (bunionectomy). The study met its primary endpoint showing a statistically significant reduction in AUC analysis of the NRS scores in patients receiving EXPAREL vs placebo (p=0.0005) over the first 24 hours; the difference continued to be statistically significant to 36 hours. Pain scores in both groups declined after 36 hours. Secondary endpoints also favoured Exparel including: the % of patients who were pain free at 8 hours and at 48 hours; the % of patients who received no rescue medication upto 24 hours. EXPAREL appeared to be well tolerated, with the incidence of AE similar to placebo [1].

Evidence based evaluations

ExparelPostoperative pain in children aged 6 to 17 years old undergoing spine and/or cardiac surgeries

Information

Exparel
Licence extension / variation
Patheon/Pacira
Pacira

Development and Regulatory status

None
None
Phase III Clinical Trials

Category

Sustained release local anaesthetic formulation
According to a review in 2012, approximately half a million children and young people undergo anaesthesia and surgery each year in England and Wales [1]. In 2018/19, there were 7,599 procedures of the spinal cord and other contents of the spinal canal (A44-A57) in children aged 5 to 17 years old; there were 2,313 procedures on the heart [2].
Postoperative pain in children aged 6 to 17 years old undergoing spine and/or cardiac surgeries
Infiltration

Evidence based evaluations

XaraCollPostoperative pain

Information

XaraColl
New formulation
Innocoll, Inc
Innocoll, Inc

Development and Regulatory status

None
None
Pre-registration (Filed)

Apr 18: Innocoll resubmits the new drug application to the US FDA [5].


Dec 16: US FDA issues a Refusal to File letter regarding the new drug application for bupivacaine implant for Postoperative pain [5].


May 16: Innocoll have announced that the two pivotal PIII placebo-controlled trials met primary endpoints, and based on these the company intends to submit a New Drug Application to the US FDA [3].


Mar 15. PIII development appears only to be in US at present

Category

XaraColl is a biodegradable and fully resorbable collagen-bupivacaine matrix formulated and manufactured using Innocolls proprietary collagen-based drug delivery technology, CollaRx.
Postoperative pain
Implantation

Trial or other data

Aug 17: A PIII trial (NCT03262688) to evaluate the safety, tolerability, pharmacokinetics and analgesic effect of bupivacaine collagen implant for post-operative pain relief after open inguinal hernia repair is currently recruiting patients. This randomised, single-dose, controlled trial is aiming to recruit 159 patients aged 2 to 17 years in the US [6].


Apr 16: NCT02523599 (MATRIX-1) and NCT02525133 (MATRIX 2) met their primary end-points demonstrating significant post-operative pain relief after open abdominal hernia repair [5]


Aug 15: two PIII placebo-controlled trials start (MATRIX-1, NCT02523599; MATRIX-2, NCT02525133). The studies have identical design and both are taking place in the US; they involve adults who are scheduled for unilateral inguinal hernioplasty via open laparotomy (total enrolment 624) and the primary outcome is the difference in patient-assessed pain intensity from 0 to 24 hours [4].


Mar 15.. A phase III efficacy programme in the planned for the second quarter of 2015. The FDA has confirmed that the proposed phase III studies would be sufficient to support an NDA filing. [2]


XaraColl is a biodegradable and fully resorbable collagen/bupivacaine matrix formulated and manufactured using Innocoll´s proprietary collagen-based drug delivery technology, CollaRx®. This technology achieves a high concentration of drug at the target tissue, while maintaining low systemic levels. XaraColl is intended to provide pain control directly at the surgical site and thus reduce the level of additional analgesia required following surgery. XaraColl is easy to use and can be cut or rolled depending on the surgical setting and can be used laparoscopically. [1]