Clobazam

Clobazam is used with other medication(s) to control seizures in adults and children 2 years of age and older who have Lennox-Gastaut syndrome (a disorder that causes seizures and often causes developmental delays). Clobazam is in a class of medications called benzodiazepines. It works by decreasing abnormal electrical activity in the brain.

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store clobazam in a safe place so that no one else can take it accidentally or on purpose. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Store clobazam suspension (liquid) in an upright position. Do not use any remaining liquid more than 90 days after first opening the bottle. Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

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Clobazam is a prescription medicine used along with other medicines to treat seizures associated with Lennox-Gastaut syndrome in people 2 years of age or older. Lennox-Gasaut is a type of epilepsy that starts in childhood and causes several types of seizures, developmental delays, and behavioral changes.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Clobazam is a benzodiazepine (ben-zoe-dye-AZE-eh-peen). Clobazam affects chemicals in the brain that may be unbalanced in people with anxiety.

Clobazam is used in combination with other medications to treat seizures caused by Lennox-Gastaut syndrome, a severe form of childhood epilepsy that also causes developmental and behavior problems.

Clobazam may also be used for purposes not listed in this medication guide.

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Clobazam may be habit forming. Never share clobazam with another person, especially someone with a history of drug abuse or addiction. Keep the medication in a place where others cannot get to it.

You may crush the clobazam tablet and mix the medicine into a spoonful of applesauce to make swallowing easier. Swallow right away without chewing. Do not save the mixture for later use.

Shake the oral suspension (liquid) well just before you measure a dose. Measure the liquid with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.

Do not stop using clobazam suddenly, even if you feel fine. Stopping suddenly may cause increased seizures or unpleasant withdrawal symptoms. Follow your doctor's instructions about tapering your dose.

Use clobazam regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely. Contact your doctor if your seizures get worse or you have them more often while taking clobazam.

Store at room temperature away from moisture and heat.

Keep track of the amount of medicine used from each new bottle. Clobazam is a drug of abuse and you should be aware if anyone is using your medicine improperly or without a prescription.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For clobazam, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to clobazam or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of clobazam in children younger than 2 years of age. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of clobazam in the elderly. However, elderly patients are more likely to have age-related liver problems, which may require caution and an adjustment in the dose for patients receiving clobazam.

Pregnancy

Breast Feeding

Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking clobazam, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using clobazam with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Flumazenil
• Thioridazine

Using clobazam with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Alfentanil
• Amobarbital
• Bromazepam
• Buprenorphine
• Butabarbital
• Butalbital
• Butorphanol
• Calcifediol
• Carbinoxamine
• Carisoprodol
• Chloral Hydrate
• Chlorzoxazone
• Codeine
• Dantrolene
• Dihydrocodeine
• Donepezil
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Doxylamine
• Eliglustat
• Eslicarbazepine Acetate
• Ethchlorvynol
• Fentanyl
• Flibanserin
• Hydrocodone
• Hydromorphone
• Levorphanol
• Meperidine
• Mephenesin
• Mephobarbital
• Meprobamate
• Metaxalone
• Methadone
• Methocarbamol
• Methohexital
• Mirtazapine
• Morphine
• Morphine Sulfate Liposome
• Nalbuphine
• Nifedipine
• Orlistat
• Oxycodone
• Oxymorphone
• Pentazocine
• Pentobarbital
• Periciazine
• Phenobarbital
• Piperaquine
• Primidone
• Secobarbital
• Sodium Oxybate
• Sufentanil
• Tamoxifen
• Tapentadol
• Thiopental
• Tramadol
• Zolpidem

Using clobazam with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Dextromethorphan
• Etravirine
• Felbamate
• Fosphenytoin
• Ginkgo
• Ketoconazole
• Phenytoin
• Theophylline

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using clobazam with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use clobazam, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Other Medical Problems

The presence of other medical problems may affect the use of clobazam. Make sure you tell your doctor if you have any other medical problems, especially:

• Alcohol abuse, or history of or
• Depression, history of or
• Drug abuse or dependence, or history of or
• Lung or breathing problems (eg, respiratory depression) or
• Mood or behavior disorder, history of—Use with caution. May make these conditions worse.

• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Difficulty with swallowing
• fever
• shakiness and unsteady walk
• unsteadiness, trembling, or other problems with muscle control or coordination

• Change in speech pattern
• restlessness
• slurred speech
• trouble sitting still
• trouble speaking

• Agitation
• black, tarry stools
• bleeding gums
• blistering, peeling, or loosening of the skin
• blood in the urine or stools
• chest pain
• chills
• confusion as to time, place, or person
• cough
• diarrhea
• difficult or troubled breathing
• holding false beliefs that cannot be changed by fact
• irregular, fast or slow, or shallow breathing
• itching
• joint or muscle pain
• lack of feeling or emotion
• painful or difficult urination
• pale or blue lips, fingernails, or skin
• pinpoint red spots on the skin
• red skin lesions, often with a purple center
• red, irritated eyes
• seeing, hearing, or feeling things that are not there
• sore throat
• sores, ulcers, or white spots in the mouth or on the lips
• swollen glands
• troubled breathing with exertion
• unusual bleeding or bruising
• unusual excitement, nervousness, or restlessness
• unusual tiredness or weakness

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Aggressive
• body aches or pain
• decreased appetite
• difficulty having a bowel movement (stool)
• drooling
• ear congestion
• irritability
• loss of voice
• nasal congestion
• runny nose
• sleepiness or unusual drowsiness
• sneezing
• vomiting

• Bladder pain
• cloudy urine
• cough with mucus
• frequent urge to urinate
• increased appetite
• lower back or side pain

• Double vision
• full or bloated feeling
• headache
• muscle spasms
• pressure in the stomach
• rash, hives, or welts
• red skin
• swelling of the stomach area

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

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Maximum effect: 5 to 9 days

Time to Peak

Tablet: 0.5 to 4 hours; Oral suspension: 0.5 to 2 hours

Half-Life Elimination

Children: Clobazam: 16 hours (Ng 2007); Adults: Clobazam: 36 to 42 hours; N-desmethyl (active): 71 to 82 hours

Protein Binding

Clobazam: 80% to 90%; N-desmethylclobazam (NCLB): 70%

Hypersensitivity to clobazam or any component of the formulation.

Canadian labeling: Additional contraindications (not in US labeling): Myasthenia gravis; narrow-angle glaucoma; severe hepatic or respiratory disease; sleep apnea; history of substance abuse; use in the first trimester of pregnancy; breast-feeding

US labeling:

Lennox-Gastaut (adjunctive): Oral: Note: Dose should be titrated according to patient tolerability and response.

≤30 kg: Initial: 5 mg once daily for ≥1 week, then increase to 5 mg twice daily for ≥1 week, then increase to 10 mg twice daily thereafter

>30 kg: Initial: 5 mg twice daily for ≥1 week, then increase to 10 mg twice daily for ≥1 week, then increase to 20 mg twice daily thereafter

CYP2C19 poor metabolizers:

≤30 kg: Initial: 5 mg once daily for ≥1 week, then increase to 5 mg twice daily; after ≥1 week may increase to 10 mg twice daily

>30 kg: Initial: 5 mg once daily for ≥1 week, then increase to 5 mg twice daily for ≥1 week, then increase to 10 mg twice daily; after ≥1 week may increase to 20 mg twice daily

Canadian labeling:

Epilepsy (adjunctive): Oral: Initial: 5 to 15 mg/day; dosage may be gradually adjusted (based on tolerance and seizure control) to a maximum of 80 mg/day. Note: Daily doses of up to 30 mg may be taken as a single dose at bedtime; higher doses should be divided.

CYP2C19 poor metabolizers: Initiate at lowest recommended doses; titrate slowly as tolerated to half of usual recommended maximum dose. If needed, dose may be further increased as tolerated to usual recommended maximum dose beginning day 21.

Catamenial epilepsy (off-label use): Oral: 20 to 30 mg daily for 10 days during the perimenstrual period (Feely 1984)

Discontinuation of therapy: Withdraw gradually by decreasing the total daily dosage by 5 to 10 mg/day on a weekly basis until discontinued.

US labeling:

Lennox-Gastaut (adjunctive): Oral:

≤30 kg: Initial: 5 mg once daily for ≥1 week, then increase to 5 mg twice daily; after ≥1 week may increase to 10 mg twice daily based on patient tolerability and response; maximum 20 mg/day

>30 kg: Initial: 5 mg once daily for ≥1 week, then increase to 5 mg twice daily for ≥1 week, then increase to 10 mg twice daily; after ≥1 week may increase to 20 mg twice daily based on patient tolerability and response; maximum 40 mg/day

Canadian labeling:

Epilepsy (adjunctive): Oral: Refer to adult dosing. Initiate therapy at lowest possible dose and titrate slowly; monitor closely.

US labeling:

Mild to moderate impairment:

≤30 kg: Initial: 5 mg once daily for ≥1 week, then increase to 5 mg twice daily; after ≥1 week may increase to 10 mg twice daily based on patient tolerability and response; maximum: 20 mg/day

>30 kg: Initial: 5 mg once daily for ≥1 week, then increase to 5 mg twice daily for ≥1 week, then increase to 10 mg twice daily; after ≥1 week may increase to 20 mg twice daily based on patient tolerability and response; maximum: 40 mg/day

Severe impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). Use with caution; undergoes extensive hepatic metabolism.

Canadian labeling:

Mild to moderate impairment: Initiate at lowest recommended doses; titrate slowly as tolerated to half of usual recommended age-based maximum dose. If needed, dose may be further increased as tolerated to usual recommended age-based maximum dose beginning day 21.

Severe impairment: Use is contraindicated.

Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.

Adverse events were observed in animal reproduction studies. Clobazam crosses the placenta. An increased risk of fetal malformations may be associated with first trimester exposure. Exposure to benzodiazepines immediately prior to or during birth may result in hypothermia, hypotonia, respiratory depression, and difficulty feeding in the neonate; neonates exposed to benzodiazepines late in pregnancy may develop dependence and withdrawal. The incidence of premature birth and low birth weights may be increased following maternal use of benzodiazepines; hypoglycemia and respiratory problems in the neonate may occur following exposure late in pregnancy. Neonatal withdrawal symptoms may occur within days to weeks after birth and “floppy infant syndrome” (which also includes withdrawal symptoms) has been reported with some benzodiazepines (Bergman 1992; Iqbal 2002; Wikner 2007). A combination of factors influences the potential teratogenicity of anticonvulsant therapy. When treating women with epilepsy, monotherapy with the lowest effective dose and avoidance medications known to have a high incidence of teratogenic effects is recommended (Harden 2009; Wlodarczyk 2012).

Patients exposed to clobazam during pregnancy are encouraged to enroll themselves into the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334. Additional information is available at www.aedpregnancyregistry.org.

Data not available