clobazam

Absorption: Well absorbed following oral administration.

Distribution: Rapidly distributes throughout the body.

Metabolism/Excretion: Primarily metabolized in the liver by the CYP3A4 isoenzyme, with some metabolism by the CYP2C19 and CYP2B6 isoenzymes. Major circulating metabolite, desmethylclobazam, is ⅕ as active as the parent compound and is further metabolized by the CYP2C19 isoenzyme. The CYP2C19 isoenzyme exhibits genetic polymorphism (2% of White patients, 4% of Black patients, and 14% of Asian patients may be poor metabolizers and may have significantly ↑ desmethylclobazam concentrations and an ↑ risk of adverse effects).2% excreted unchanged in urine, 1% in feces.

Half-Life: Clobazam: 36–42 hr; desmethylclobazam: 71–82 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	0.5–4 hr	12–24 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity.

Use Cautiously in:

Mild or moderate hepatic impairment (dose adjustment recommended);
History of substance abuse or suicidal behavior/ideation;
OB: Use late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, feeding difficulties) in neonates;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Children <2 yr (safety and effectiveness not established);
Geri: Appears on Beers list. ↑ risk of cognitive impairment, delirium, falls, fractures, and motor vehicle accidents. If possible, avoid use in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN)

GI: constipation, drooling, dysphagia, vomiting

Metab: ↑appetite

Neuro: sedation, somnolence, aggression, ataxia, dizziness, dysarthria, fatigue, insomnia, irritability, lethargy

Resp: cough

Misc:

physical dependence

psychological dependence

Interactions ⬆ ⬇

Drug-drug:

Alcohol↑ levels by 50%.
Use with opioids or other CNS depressants, including other benzodiazepines, nonbenzodiazepine sedative/hypnotics, anxiolytics, general anesthetics, muscle relaxants, antipsychotics, and alcohol, may cause profound sedation, respiratory depression, coma, and death; reserve concurrent use for when alternative treatment options are inadequate.
Strong or moderate CYP2C19 inhibitors, including fluconazole, fluvoxamine, and omeprazole, may ↑ levels and effects of N-desmethylclobazam; ↓ doses of clobazam may be necessary.
Cannabidiol may ↑ levels and risk of toxicity; ↓ doses of clobazam or cannabidiol may be necessary if adverse effects develop.

Route/Dosage ⬆ ⬇

PO (Adults and Children >30 kg): 5 mg twice daily initially; may be titrated after 1 wk to 10 mg twice daily and after another wk to a max of 20 mg twice daily; CYP2C19 poor metabolizers: 5 mg once daily initially; may be titrated weekly over 3 wk to a max of 20 mg twice daily.
PO (Adults and Children ≤30 kg): 5 mg once daily initially; may be titrated after 1 wk to 5 mg twice daily and after another wk to a max of 10 mg twice daily; CYP2C19 poor metabolizers: 5 mg once daily initially; may be titrated weekly over 3 wk to a max of 10 mg twice daily.
PO Geriatric Patients >30 kg): 5 mg once daily initially; may be titrated weekly over 3 wk to a max of 20 mg twice daily.
PO Geriatric Patients ≤30 kg): 5 mg once daily initially; may be titrated weekly over 3 wk to a max of 10 mg twice daily.

Hepatic Impairment

PO (Adults and Children >30 kg): Mild to moderate hepatic impairment: 5 mg once daily initially; may be titrated weekly over 3 wk to a max of 20 mg twice daily.

Hepatic Impairment

PO (Adults and Children ≤30 kg): Mild to moderate hepatic impairment: 5 mg once daily initially; may be titrated weekly over 3 wk to a max of 10 mg twice daily.

Availability ⬆ ⬇

(Generic available)

Tablets (Onfi): 10 mg; 20 mg
Oral suspension berry flavor (Onfi): 2.5 mg/mL
Oral film berry flavor (Sympazan): 5 mg; 10 mg; 20 mg

Assessment ⬆ ⬇

Assess location, duration, and characteristics of seizure activity. Institute seizure precautions.
Monitor closely for changes in behavior that may indicate emergence or worsening of suicidal thoughts or behavior or depression.
Assess patient for skin rash (skin blisters, rash, sores in the mouth, hives, any other allergic reaction), especially during first 8 wk or when reinitiating therapy, and frequently during therapy. May cause SJS or TEN. Discontinue at 1st sign of rash; may be life-threatening.
Monitor for signs and symptoms of DRESS (fever, rash, lymphadenopathy, facial swelling), associated with involvement of other organ systems (hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis) during therapy. May resemble an acute viral infection. Eosinophilia is often present. Discontinue therapy if signs occur.
Assess risk for addiction, abuse, or misuse prior to administration and periodically during therapy.
Prolonged high-dose therapy may lead to psychological or physical dependence. Assess regularly for continued need for treatment.

Lab Test Considerations:

May cause anemia, eosinophilia, leukopenia, or thrombocytopenia.
- May cause ↑ hepatic enzymes.

Implementation ⬆ ⬇

Do not confuse clobazam with clonazepam.
- Do not escalate dose more rapidly than once per wk.
PO: Administer without regard to meals. Tablets can be administered whole or crushed and mixed with applesauce.
- Shake oral suspension well before use. Use provided measuring device and syringe for accurate measure of oral suspension. Discard oral suspension 90 days after opening.
- Apply film on top of tongue where it adheres and dissolves. Administer only one oral film at a time; if 2nd film is needed to complete dose, do not take until 1st film completely dissolved.
- Gradually taper to discontinue or ↓ the dose to ↓ risk of withdrawal reactions, ↑ seizure frequency, and status epilepticus. Taper by ↓ total daily dose by 5–10 mg/day on a weekly basis until discontinued. If patient develops withdrawal symptoms, pause taper or ↑ dose to previous tapered dose level; ↓ dose more slowly. Some patients may require longer tapering period (weeks–>12 mo).

Patient/Family Teaching ⬆ ⬇

Instruct patient to take clobazam around the clock, as directed. Advise patient to read the Medication Guide before starting therapy and with each Rx refill in case of changes.
Caution patient not to stop taking clobazam without consulting health care provider. Abrupt withdrawal may cause sweating, vomiting, muscle cramps, tremors, and seizures; may be life-threatening.
Advise patient to avoid the use of alcohol or other CNS depressants, including opioids, concurrently with clobazam; may cause respiratory depression and overdose. Instruct patient to consult health care provider before taking Rx, OTC, or herbal products concurrently with this medication, especially St. John's wort.
Advise patient that clobazam is a drug with known abuse potential. Protect it from theft, and never give to anyone other than the individual for whom it was prescribed. Store out of sight and reach of children, and in a location not accessible by others.
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 health care provider 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; emergence of suicidal thoughts, behavior, or thoughts of self-harm; or rash should be reported to health care provider immediately.
Rep: May cause fetal harm. Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding. Monitor infants exposed to clobazam during 2nd and 3rd trimester or immediately prior to or during childbirth for decreased fetal movement and/or fetal heart rate variability, “floppy infant syndrome,” dependence, sedation (respiratory depression, lethargy, hypotonia), and symptoms of withdrawal (hypertonia, hyperreflexia, hypoventilation, irritability, tremors, diarrhea, vomiting, restlessness, inconsolable crying, feeding difficulties); may occur shortly after delivery up to 3 wk after birth. Monitor breastfed infants for sedation, poor sucking, poor feeding, and poor weight gain. Encourage pregnant patients to enroll in the North American Antiepileptic Drug Pregnancy Registry by calling 1-888-233-2334; information is available at www.aedpregnancyregistry.org.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇