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Articles
Equivalent doses of oral benzodiazepines
6 July 2021Benzodiazepines are the most commonly used anxiolytics and hypnotics. There are major differences in potency between different benzodiazepines and this difference in potency is important…
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…
Safety in Lactation: Drugs used in status epilepticus
5 November 2020Choice of treatment will be influenced by the clinical situation. The evidence for these drugs in breastfeeding is based on their longer-term use rather than…
Safety in Lactation: Anxiolytics.
21 October 2020Additional information relating to breastfeeding To be used in conjunction with individual drug entries for specific information and guidance. Use of anxiolytics in breastfeeding mothers…
Safety in Lactation: Sedative and analgesic peri-operative drugs
25 September 2020Benzodiazepines are used for premedication and for conscious sedation during surgery. Following short–term therapy (1-2 doses) for these indications, it is considered that breastfeeding can…
Medicine Compliance Aid Stability
genericActavis UK Ltd
Actavis UK Ltd
generic
Tablets 2mg, 5mg, 10mg
A3 · Amber 3No stability data is available. There are theoretical concerns with use in CAs, which may be mitigated by risk minimisation.
Protect from light
Protect from light. Max 28 days in MCA.
1 October 2015
Lactation Safety Information
For anxiety
For anxiety
Lorazepam, Oxazepam
Limited published evidence of safety
Long half-life of diazepam and its active metabolites increases risk of accumulation in breastfed infants
Adverse effects reported include sedation and poor feeding
Monitor the infant closely for drowsiness, poor feeding and adequate weight gain
23 September 2020
Rectal / Parenteral For status epilepticus
Rectal / Parenteral
For status epilepticus
Midazolam (buccal) for rectal, Lorazepam/ clonazepam for parenteral
Long half-life increases risk of accumulation in breastfed infants with repeated doses
Adverse effects reported include sedation and poor feeding
Short-term therapy (1-2 doses) considered not to pose a risk to the infant
23 September 2020
For premedication / conscious sedation
For premedication / conscious sedation
Lorazepam
Long half-life increases risk of accumulation in breastfed infants with repeated doses
Adverse effects reported include sedation and poor feeding after prolonged use
Short-term therapy (1-2 doses) considered not to pose a risk to the infant
23 September 2020
For muscle spasm
For muscle spasm
Baclofen
Long half-life increases risk of accumulation in breastfed infants
Adverse effects reported include sedation and poor feeding
23 September 2020
New Medicines
Valtoco Epilepsy - intermittent use for acute repetitive or cluster seizures
Information
Valtoco
New formulation
Not Known
Neurelis
Development and Regulatory status
None
None
Launched
Yes
Sep 20Neurelis plans a clinical trial for epilepsy in children in the US and plans to file an sNDA to the FDA in 2021. The company does not currently appear to have plans to bring this product to EU/UK markets [6].
Mar 20Launched in US [5].
Jan 20Approved in US for acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e. seizure clusters, acute repetitive seizures) that are distinct from a patient ´s usual seizure pattern in adult and pediatric patients six years of age and older [5].
Sep 18Filed in the US with Fast Track designation as a treatment for epilepsy patients six years and older who experience increased bouts of seizure activity, also known as cluster or acute repetitive seizures [1].
Category
A proprietary formulation of diazepam delivered via a nasal formulation in a spray
The prevalence of acute repetitive seizures (ARS) is not well known. A population-based study of ARS in the UK estimated that the crude prevalence in the general population was 2.3 per 10,000. The prevalence was highest in the very young (ages 0–4) at 5.9 per 10,000, and declined with age to 0.5 per 10,000 in those aged ≥70. They estimated that ARS affect about 3% of the epilepsy population. There is evidence that the prevalence of ARS in an epilepsy-centre population is much higher [2].
Epilepsy - intermittent use for acute repetitive or cluster seizures
Intranasal
Trial or other data
Oct 19Neurelis releases updated results from PIII trial (NCT02721069). Previously they presented safety data at the 71th Annual Meeting of the American Academy of Neurology (AAN-2019) [4].
Apr 16Pivotal PIII trial initiated to evaluate the safety of repeated doses of diazepam intranasal (NRL-1) in epilepsy subjects who have frequent breakthrough seizures or Acute Repetitive Seizures (ARS), to support US filing (NCT02721069). The open-label, 12-month, repeat-dose study estimates enrolment of 80 patients in the US [3].
Evidence based evaluations
Libervant Treatment of seizures - buccal film formulation
Information
Libervant
New formulation
Not Known
Aquestive Therapeutics
Development and Regulatory status
None
None
Not recommended for approval (Negative opinion)
Yes
Nov 20After submitting a meeting package in October, the company announces that a review meeting with the FDA is set for November 12, 2020. The company does not believe additional studies are needed. At that Nov meeting, Aquestive will seek to confirm the pathway for approval and propose the immediate re-submission of the NDA for Libervant. If the FDA agrees with the proposal, then the Company plans on resubmitting the NDA before the end of the year. If the FDA does not agree, then the Company will seek to understand the best path forward for re-submission and approval [7].
Nov 20Diazepam buccal soluble film was awarded fast track status in US in Dec 18 [6].
Sep 20FDA issues a Complete Response for diazepam buccal film. In the letter, FDA cite that, in a study submitted with NDA, certain weight groups showed a lower drug exposure level than desired. Aquestive Therapeutics are asked to provide additional pharmacokinetic data to demonstrate that dose adjustments will obtain the desired exposure levels [5].
Nov 19Plans for EU development not discussed in company quarterly report [4].
Nov 19Aquestive Therapeutics intends to complete the rolling NDA submission by end of Nov 19, and launch in the US in 20 [3].
May 19Aquestive Therapeutics initiated a rolling new drug application (NDA) submission for diazepam buccal soluble film with the US FDA for the treatment of seizure [3].
Oct 18Has orphan drug status in US [2].
Category
GABA-A receptor stimulant in a buccal film formulation
The prevalence of active epilepsy is 5-10 cases per 1,000 - but with 5-30% of these misdiagnosed as having epilepsy [1].
Treatment of seizures - buccal film formulation
Buccal
Trial or other data
Jun 20PIII trial that evaluated the safety and tolerability of the buccal formulation of diazepam, patients aged two to 65 years, with epilepsy completes (42-1703; NCT03428360) [6].
Oct 18Pharmacokinetic epilepsy monitoring unit (EMU) study of diazepam buccal film demonstrates a comparable bioavailability when administered between seizures or during and shortly after seizures in adults with poorly controlled tonic-clonic seizures or focal seizures with impaired awareness [2].
Jan 18PIII trial to evaluate the safety and tolerability of the buccal formulation of diazepam, patients aged 2 to 65 years, with seizures starts (NCT03428360). The open label trial is intended to enrol 120 patients in the US [2].
Jul 17PII trial to evaluate the pharmacokinetics, tolerability and safety of diazepam buccal film for the treatment of patients with epilepsy starts (NCT03222349). 18 patients, aged 2 to 17 years, will be enrolled by invitation in the US [2].