Source: FDA, National Drug Code (US) Revision Year: 2021
Diazepam rectal gel is a gel formulation of diazepam intended for rectal administration in the management of selected, refractory, patients with epilepsy, on stable regimens of AEDs, who require intermittent use of diazepam to control bouts of increased seizure activity.
Evidence to support the use of diazepam rectal gel was adduced in two controlled trials (see CLINICAL PHARMACOLOGY, CLINICAL STUDIES) that enrolled patients with partial onset or generalized convulsive seizures who were identified jointly by their caregivers and physicians as suffering intermittent and periodic episodes of markedly increased seizure activity, sometimes heralded by nonconvulsive symptoms, that for the individual patient were characteristic and were deemed by the prescriber to be of a kind for which a benzodiazepine would ordinarily be administered acutely. Although these clusters or bouts of seizures differed among patients, for any individual patient the clusters of seizure activity were not only stereotypic but were judged by those conducting and participating in these studies to be distinguishable from other seizures suffered by that patient. The conclusion that a patient experienced such unique episodes of seizure activity was based on historical information.
This section is intended primarily for the prescriber; however, the prescriber should also be aware of the dosing information and directions for use provided in the patient package insert.
A decision to prescribe diazepam rectal gel involves more than the diagnosis and the selection of the correct dose for the patient.
First, the prescriber must be convinced from historical reports and/or personal observations that the patient exhibits the characteristic identifiable seizure cluster that can be distinguished from the patient’s usual seizure activity by the caregiver who will be responsible for administering diazepam rectal gel.
Second, because diazepam rectal gel is only intended for adjunctive use, the prescriber must ensure that the patient is receiving an optimal regimen of standard anti-epileptic drug treatment and is, nevertheless, continuing to experience these characteristic episodes.
Third, because a non-health professional will be obliged to identify episodes suitable for treatment, make the decision to administer treatment upon that identification, administer the drug, monitor the patient, and assess the adequacy of the response to treatment, a major component of the prescribing process involves the necessary instruction of this individual.
Fourth, the prescriber and caregiver must have a common understanding of what is and is not an episode of seizures that is appropriate for treatment, the timing of administration in relation to the onset of the episode, the mechanics of administering the drug, how and what to observe following administration, and what would constitute an outcome requiring immediate and direct medical attention.
The diazepam rectal gel dose should be individualized for maximum beneficial effect. The recommended dose of diazepam rectal gel is 0.2-0.5 mg/kg depending on age. See the dosing table for specific recommendations.
| Age (years) | Recommended Dose |
|---|---|
| 2 through 5 | 0.5 mg/kg |
| 6 through 11 | 0.3 mg/kg |
| 12 and older | 0.2 mg/kg |
Because diazepam rectal gel is provided as unit doses of 2.5, 5, 7.5, 10, 12.5, 15, 17.5, and 20 mg, the prescribed dose is obtained by rounding upward to the next available dose. The following table provides acceptable weight ranges for each dose and age category, such that patients will receive between 90% and 180% of the calculated recommended dose. The safety of this strategy has been established in clinical trials.
| 2-5 Years | 6-11 Years | 12+ Years | |||
|---|---|---|---|---|---|
| 0.5 mg/kg | 0.3 mg/kg | 0.2 mg/kg | |||
| Weight (kg) | Dose (mg) | Weight (kg) | Dose (mg) | Weight (kg) | Dose (mg) |
| 6 to 10 | 5 | 10 to 16 | 5 | 14 to 25 | 5 |
| 11 to 15 | 7.5 | 17 to 25 | 7.5 | 26 to 37 | 7.5 |
| 16 to 20 | 10 | 26 to 33 | 10 | 38 to 50 | 10 |
| 21 to 25 | 12.5 | 34 to 41 | 12.5 | 51 to 62 | 12.5 |
| 26 to 30 | 15 | 42 to 50 | 15 | 63 to 75 | 15 |
| 31 to 35 | 17.5 | 51 to 58 | 17.5 | 76 to 87 | 17.5 |
| 36 to 44 | 20 | 59 to 74 | 20 | 88 to 111 | 20 |
The rectal delivery system includes a plastic applicator with a flexible, molded tip available in two lengths. The DIASTAT ACUDIAL 10 mg syringe is available with a 4.4 cm tip and the DIASTAT ACUDIAL 20 mg syringe is available with a 6.0 cm tip. DIASTAT 2.5 mg is also available with a 4.4 cm tip.
In elderly and debilitated patients, it is recommended that the dosage be adjusted downward to reduce the likelihood of ataxia or oversedation.
The prescribed dose of diazepam rectal gel should be adjusted by the physician periodically to reflect changes in the patient’s age or weight.
The DIASTAT 2.5 mg dose may also be used as a partial replacement dose for patients who may expel a portion of the first dose.
The prescriber may wish to prescribe a second dose of diazepam rectal gel. A second dose, when required, may be given 4-12 hours after the first dose.
It is recommended that diazepam rectal gel be used to treat no more than five episodes per month and no more than one episode every five days.
Two patients in the clinical studies received more than twice the target dose; no adverse events were reported.
Previous reports of diazepam overdosage have shown that manifestations of diazepam overdosage include somnolence, confusion, coma, and diminished reflexes. Respiration, pulse and blood pressure should be monitored, as in all cases of drug overdosage, although, in general, these effects have been minimal. General supportive measures should be employed, along with intravenous fluids, and an adequate airway maintained. Hypotension may be combated by the use of levarterenol or metaraminol. Dialysis is of limited value.
Flumazenil, a specific benzodiazepine-receptor antagonist, is indicated for the complete or partial reversal of the sedative effects of benzodiazepines and may be used in situations when an overdose with a benzodiazepine is known or suspected. Prior to the administration of flumazenil, necessary measures should be instituted to secure airway, ventilation and intravenous access. Flumazenil is intended as an adjunct to, not as a substitute for, proper management of benzodiazepine overdose. Patients treated with flumazenil should be monitored for resedation, respiratory depression and other residual benzodiazepine effects for an appropriate period after treatment. The prescriber should be aware of a risk of seizure in association with flumazenil treatment, particularly in long-term benzodiazepine users and in cyclic antidepressant overdose. The complete flumazenil package insert, including CONTRAINDICATIONS, WARNINGS and PRECAUTIONS, should be consulted prior to use.
Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].
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