DIASTAT Dosage & Rx Info | Uses, Side Effects

Diastat Generic Name & Formulations

Legal Class

CIV

General Description

Diazepam 2.5mg, 10mg, 20mg; per applicator; rectal gel.

Pharmacological Class

Benzodiazepine.

How Supplied

Gel delivery system—2 (w. applicator + lubricant)

Manufacturer

Bausch Health Companies Inc.

Generic Availability

Mechanism of Action

Although the precise mechanism by which diazepam exerts its antiseizure effects is unknown, studies suggest that diazepam acts to suppress seizures through an interaction with γ-aminobutyric acid (GABA) receptors of the A-type (GABA_A). Also, it is believed that diazepam enhances the actions of GABA by causing GABA to bind more tightly to the GABA_A receptor.

Diastat Indications

Indications

Acute treatment of intermittent, stereotypic episodes of frequent seizure activity (eg, seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern in those with epilepsy.

Diastat Dosage and Administration

Adults and Children

Individualize. Calculate dose based on body weight (in kg) and round up to next available dosage strength. Treat no more than 1 episode every 5 days and no more than 5 episodes per month. <2yrs: not established. 2–5yrs: 0.5mg/kg. 6–11yrs: 0.3mg/kg. ≥12yrs: 0.2mg/kg. See full labeling for dosing chart. Elderly or debilitated: reduce dose. May give 2^nd dose 4–12hrs after 1^st dose. May use 2.5mg strength as supplemental dose.

Diastat Contraindications

Contraindications

Acute narrow-angle glaucoma.

Diastat Boxed Warnings

Boxed Warning

Risks from concomitant use with opioids. Abuse, misuse, and addiction. Dependence and withdrawal reactions.

Diastat Warnings/Precautions

Warnings/Precautions

Risks from concomitant use with opioids; see Interactions. Caregiver must be fully able to identify cluster seizures or prodrome, be able to decide when to treat, correctly administer rectal dose, monitor patient, and assess response. Monitor for CNS depressant effects. Untreated open-angle glaucoma. Renal or hepatic impairment. Compromised respiratory function. Neurologic damage. Chronic daily use of diazepam may increase tonic-clonic seizures; not recommended. Assess patient's risk for abuse, misuse, addiction prior to and during therapy. Avoid abrupt cessation. Drug or alcohol abusers. Elderly. Neonates <6mos: not recommended. Neonatal sedation and withdrawal syndrome; monitor neonates exposed during pregnancy or labor. Pregnancy (esp. late stage). Nursing mothers: monitor infants.

Diastat Pharmacokinetics

Absorption

Following rectal administration, reaching peak plasma concentrations in 1.5 hours. The absolute bioavailability of diazepam rectal gel relative to Valium injectable is 90%.

Distribution

The volume of distribution of diazepam rectal gel is calculated to be ~1 L/kg. Both diazepam and its major active metabolite desmethyldiazepam bind extensively to plasma proteins (95–98%).

Metabolism

Hepatic and involves demethylation (primarily CYP2C19 and CYP3A4) and 3-hydroxylation (primarily CYP3A4), followed by glucuronidation.

Elimination

The mean elimination half-life of diazepam and desmethyldiazepam following administration of a 15 mg dose of diazepam rectal gel was found to be about 46 hours (CV=43%) and 71 hours (CV=37%), respectively.

Diastat Interactions

Interactions

Increased sedation, respiratory depression, coma, and death with concomitant opioids; reserve use in those for whom alternative treatment options are inadequate; if needed, limit dosages/durations to minimum and monitor. CNS depression potentiated with valproate, alcohol, other CNS depressants. Caution with other psychotropics. May be potentiated by inhibitors of CYP2C19 (eg, cimetidine, quinidine) or CYP3A4 (eg, ketoconazole, troleandomycin, clotrimazole). May be antagonized by inducers of CYP2C19 (eg, rifampin) or CYP3A4 (eg, carbamazepine, phenytoin, dexamethasone, phenobarbital). Diazepam may potentiate or antagonize other drugs metabolized by these enzymes (eg, omeprazole, propranolol, imipramine, cyclosporine, paclitaxel, theophylline, warfarin).

Diastat Adverse Reactions

Adverse Reactions

Somnolence, dizziness, headache, pain, nervousness, vasodilation, diarrhea, ataxia, euphoria, incoordination, asthma, rhinitis, rash, hyperkinesia, hypoventilation, paradoxical excitement (discontinue if occurs), withdrawal reactions.

Diastat Clinical Trials

See Literature

Diastat Note

Not Applicable

Diastat Patient Counseling