Frisium

clobazam

(kloe-ba-zam) ,

Frisium

(trade name),

Onfi

(trade name)

Classification

Therapeutic: anticonvulsants
Pharmacologic: benzodiazepines
Pregnancy Category: C

Indications

Adjunctive treatment of seizures associated with Lennox-Gestaut syndrome in patients ≥2 yr.

Action

Facilitates neurotransmission mediated by gamma-amino butyric acid (GABA) by binding to the benzodiazepine site of the GABAAreceptor.

Therapeutic effects

Decreased incidence and severity of seizures associated with Lennox-Gestaut syndrome.

Pharmacokinetics

Absorption: Well absorbed following oral administration.
Distribution: Rapidly distributes throughout the body; enters breast milk.
Metabolism and Excretion: Extensively metabolized by the liver; 2% excreted unchanged in urine, 1% in feces Mostly metabolized by CYP3A4, some metabolism by CYP2C19 and CYP2B6. Major circulating metabolite, desmethylclobazam, is 1/5 as active as the parent compound and is further metabolized by the CYP2C19. Metabolites of this process are renally eliminated. genetic implication Poor CYP2C19 metabolizers have significantly ↑ levels of desmethylclobazam.
Half-life: Clobazam—36–42 hr; desmethylclobazam—71–82 hr.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
POunknown0.5–4 hr12–24 hr

Contraindications/Precautions

Contraindicated in: None noted.
Use Cautiously in: Hepatic impairment (dosage adjustment recommended for mild to moderate impairment); History of substance abuse, suicidal behavior/ideation; Geriatric: Slow dosage escalation and weight-based dosing recommended due to higher blood levels; Obstetric: Use in pregnancy only if potential benefit outweighs fetal risk; Lactation: Clobazam enters breast milk, effects on infants are not known; Pediatric: Safe and effective use in children <2 yr has not been established.

Adverse Reactions/Side Effects

Central nervous system

  • sedation (most frequent)
  • somnolence (most frequent)
  • aggression
  • ataxia
  • dizziness
  • dysarthria
  • fatigue
  • insomnia
  • irritability
  • lethargy

Dermatologic

  • stevens-johnson syndrome (life-threatening)
  • toxic epidermal necrolysis (life-threatening)

Respiratory

  • cough

Gastrointestinal

  • constipation
  • drooling
  • dysphagia
  • ↑ appetite
  • vomiting

Interactions

Drug-Drug interaction

Alcohol ↑ blood levels by 50%.↑ risk of CNS depression with alcohol, someantidepressants, antihistamines, opioid analgesics and sedative/hypnotics.Concurrent use of strong/moderate inhibitors of the CYP2C19 enzyme system including fluconazole, fluvoxamine, ticlopidine and omeprazole ↑ levels and effects of N-desmethylclobazam; lower doses of clobazam may be necessary.

Route/Dosage

Oral (Adults and Children >30 kg) 5 mg twice daily initially, may be titrated after 1 wk to 20 mg/day in 2 divided doses and after another wk to a maximum of 40 mg/day in 2 divided doses.
Oral (Adults and Children ≤ 30 kg) 5 mg daily initially, may be titrated after 1 wk to 10 mg/day in 2 divided doses and after another wk to a maximum of 20 mg/day in 2 divided doses.
Oral (Geriatric Patients >30 kg) 5 mg daily initially, may be titrated weekly over 3 wk to a maximum of 40 mg/day in 2 divided doses.
Oral (Geriatric Patients ≤30 kg) 5 mg daily initially, may be titrated weekly over 3 wk to a maximum of 20 mg/day in 2 divided doses.

Hepatic Impairment

Oral (Adults and Children) Mild to moderate hepatic impairment and weight >30 kg—5 mg daily initially, may be titrated weekly over 3 wk to a maximum of 40 mg/day in 2 divided doses; Mild to moderate hepatic impairment and weight ≤30 kg—5 mg daily initially, may be titrated weekly over 3 wk to a maximum of 20 mg/day in 2 divided doses.
Oral (Adults and Children) Known CYP2C19 poor metabolizers >30 kg—5 mg daily initially, may be titrated weekly over 3 wk to a maximum of 40 mg/day in 2 divided doses; Known CYP2C19 poor metabolizers ≤30 kg—5 mg daily initially, may be titrated weekly over 3 wk to a maximum of 20 mg/day in 2 divided doses.

Availability

Tablets: 10 mg, 20 mg
Oral suspension: 2.5 mg/mL

Nursing implications

Nursing assessment

  • Assess location, duration, and characteristics of seizure activity. Institute seizure precautions.
  • Monitor closely for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.
  • Assess patient for skin rash frequently during therapy. Discontinue at first sign of rash; may be life-threatening.
  • Lab Test Considerations: May cause anemia, eosinophilia, leukopenia, thrombocytopenia.
    • May cause increased hepatic enzymes.

Potential Nursing Diagnoses

Risk for injury (Adverse Reactions)

Implementation

  • Oral: Administer without regard to meals. Tablets can be administered whole or crushed and mixed with applesauce.
    • Use provided measuring device and syringe for accurate measure of oral solution.
    • Do not escalate dose more rapidly than once/wk.

Patient/Family Teaching

  • Instruct patient to take clobazam around the clock, as directed. Do not stop taking clobazam without consulting health care professional. Medication should be gradually discontinued to prevent withdrawal symptoms (seizures, psychosis, hallucinations, behavioral disorder, tremor, anxiety). Advise patient to read the Medication Guide before starting therapy and with each Rx refill in case of changes.
  • May cause drowsiness, dizziness, ataxia, and incoordination. Caution patient to avoid driving or other activities requiring alertness until response to medication is known. Tell patient not to resume driving until physician gives clearance based on control of seizure disorder.
  • Inform patients and families of risk of suicidal thoughts and behavior and advise that behavioral changes, emergency or worsening signs and symptoms of depression, unusual changes in mood, or emergence of suicidal thoughts, behavior, or thoughts of self-harm, or rash should be reported to health care professional immediately.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications. Advise patient to avoid taking other CNS depressants or alcohol.
  • Instruct female patient to use a nonhormonal method of contraception during and for 28 days after clobazam use. Advise female patients to notify health care professional if pregnancy is planned or suspected or if breast feeding. Encourage pregnant patients to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334; information is available at www.aedpregnancyregistry.org.

Evaluation/Desired Outcomes

  • Decreased frequency and intensity of seizure activity.

Frisium

A brand name for CLOBAZAM.
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