Benzodiazepines (BDZs)
The benzodiazepines consist of the "Valium-like"¯ drugs such as Valium itself (diazepam), Klonopin (clonazepam), Ativan (lorazepam), Tranxene (clorazepate), alprazolam (Xanax).
These medicines are effective as quick-acting antiepileptic medications that work within minutes to hours, and do not require a loading dose. Therefore, injectable forms such as intravenous diazepam or intravenous lorazepam are typical drugs of choice for treatments of status epilepticus. Used chronically, their effectiveness tends to wear off after a few weeks of use.
In addition, increasing doses are sometimes required. Chronic use of benzodiazepines usually is discouraged, with the exception of treatment for atonic, myoclonic or completely intractable seizures, where few alternatives exist. Benzodiazepines can be useful as booster therapy for clusters of seizures, taken for a single dose or a day or two. This can happen when individuals know one seizure is likely to lead to another, or at times like the menstrual period for women.
A typical dose of diazepam (Valium) would be 2-5 mg every 4-6 hours for seizures. Clonazepam (Klonopin) usually is given as 0.5-2.0 mg orally three times per day. Ativan may be given in 0.5-1.0 mg boosters, repeated as needed to stop seizures up to about 4 mg per day.
Be aware of the sound-alike drug, clonidine, a blood pressure medicine, sometimes mistakenly substituted for Klonopin!
A rectal gel form of diazepam, called Diastat, is designed to be given for clusters of seizures ("¯serial seizures"¯). The rectal gel can be administered when swallowing pills is not possible. The gel is absorbed rapidly from the rectal mucosa.
Diastat comes packaged in syringes without needles, in doses of 2.5, 5, 10, 15, 20 mg. The usual adult does is 0.2 mg/kg (5-20 mg). Pediatric dose is 0.5 mg/kg for ages 2-5 and 0.3 mg/kg for 5-20 years. Maintenance is not relevant, since Diastat is an acute rescue medicine. However, the dose may be repeated once in 4-12 hours.
Summary Data for BDZs
Pill sizes
Klonopin 0.5, 1, 2 mg;
Ativan 0.5, 1. 2 mg; Valium 2, 5, 10 mg pills;
Tranxene 3.75, 15, 22.5 mg pills;
Tranxene slow release 11.25, 22.5 mg pills.
Liquid for oral: Valium solution 5 mg/ml
Injectable: Valium 5 mg/ml injectable; Ativan 2 mg/ml, 4 mg/ml injectable; Versed (midazolam) 1 mg/ml, 5 mg/ml injectable.
Typical adult dose: clonazepam or lorazepam, test dose of 0.5 mg hs, then 0.5 mg bid. Load in emergency: Diazepam and lorazepam can be given intravenously and midazolam i.v. or i.m. for emergencies - see texts and package insert for details. Increase to target for clonazepam or lorazepam of 1.5 - 3 mg/d divided into 3 doses; diazepam 6-15 mg/d divided into 3 doses; clorazepate 7.5 - 60 mg per day in 2 or 3 doses.
Typical pediatric dose of clonazepam: 3.75 - 20 mg/d in 2 or 3 divided doses.
Metabolism: various routes via liver and kidney.
Half-life: clonazepam - 24 to 48 hours; clorazepate - active metabolite about 48 hours; diazepam - 24 to 48 hours.
Therapeutic plasma concentrations: diazepam 150-700 nanograms/ml; clonazepam 20-80 nanograms/ml.
Pregnancy: Category D - believed able to cause birth defects in humans.
Clonazepam (Klonopin) will be used as an example of BDZ drug interactions.
Drugs that raise CLN levels: nafazodone
Drugs that lower CLN levels: rifampin
CLN increases sedative effects of: antihistamines, antipsychotics, antifungals, phenobarbital, other BDZs, opiates, trazodone, tricyclics.
CLN decreases effects of other drugs: none listed
Dangerous Side Effects
Respiratory depression or arrest, impairment of consciousness, low blood pressure (hypotension), blood or liver injury, birth defects.
Common Side Effects
Sedation, cognitive impairment, lightheadedness, dizziness.
Other Side Effects
Behavior and personality changes, attention deficit and hyperactivity, GI upset (rare), constipation, sexual dysfunction, rash or itching, headaches.