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Articles
Administration of diazepam rectal tubes by registered Paramedics and Nurses for the management of seizures: PGD template
5 October 2021A PGD template developed by SPS and supported by NASMeD and JRCALC for ambulance services commissioned by NHS England.
Administration of diazepam emulsion for injection by registered Nurses for the management of seizures: National PGD
5 October 2021A national PGD developed by SPS and supported by NASMeD and JRCALC for ambulance services commissioned by NHS England.
Administration of diazepam solution for injection by registered Paramedics and Nurses for the management of seizures: National PGD
5 October 2021A national PGD developed by SPS and supported by NASMeD and JRCALC for ambulance services commissioned by NHS England.
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…
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
Libervant Treatment of seizures in epilepsy - buccal film formulation
Information
Libervant
New formulation
Aquestive Therapeutics
Aquestive Therapeutics
Development and Regulatory status
None
None
Pre-registration (Filed)
Yes
May 22A decision regarding filing was anticipated by the end of 2021 but this has now been delayed with no clear timeline whilst the FDA actively work on orphan-drug exclusivity issues related to the filing [10].
Nov 21Company is seeking a partner outside the US [9].
Jul 21Aquestive plans commercial launch of diazepam in USA in H1 22 [8].
Jul 21FDA accepts for filing the resubmission of the New Drug Application (NDA) for Libervant and sets a Prescription Drug User Fee Act (PDUFA) target goal date of Dec 23, 2021 [8].
Jun 21Re-filed in the US [8].
Dec 20Aquestive resubmits a revised weight-based dosing regimen along with modeling and simulations to the FDA in response to the Type A meeting held in Nov 20 [8].
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 in epilepsy - buccal film formulation
Buccal
Trial or other data
Jun 20Data from the PIII trial (NCT03428360) were previously presented at the 72nd Annual Meeting of the American Academy of Neurology (AAN-2020) in Apr 20. A total of 72 patients were included (adults, n=59; adolescents, n=7; pediatric, n=6). Five (6.9%) patients reported 7 treatment-related adverse events (AEs) over a mean of 192 days of follow-up; all were mild and none led to discontinuation. Local buccal discomfort (mild) was reported in 1 patient. Thirteen serious AEs were reported, none of which were considered treatment-related. Usability data were reported by 64 (88.9%) patients, representing 471 Libervant use occasions (mean 7.4 administrations/patient). Libervant was successfully administered during a first attempt on 443 of 471 (94.1%) use occasions and during a second attempt on 17 (3.6%) use occasions. All 64 patients had administration first-attempt success on ≥1 use occasion. Patients and caregivers reported no difficulty opening the outer or inner packaging in the majority of use occasions and almost all reported no difficulty removing Libervant from the inner packaging [8].
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].