Clonazepam

Clonazepam is the generic name (non-brand name) of the seizure medicine Klonopin used in the United States, Canada, the UK and some other countries. In Canada and the UK, the brand name Rivotril is used for clonazepam. In India, the brand name is Epitril.

Clonazepam is the generic name (non-brand name) of the seizure medicine Klonopin used in the United States, Canada, the UK and some other countries. In Canada and the UK, the brand name Rivotril is used for clonazepam. In India, the brand name is Epitril.

Clonazepam has been available in the United States since 1975.

Clonazepam is a benzodiazepine; consequently, tolerance may potentially develop over time, causing a diminishment of efficacy.

Epitril
Klonopin
Tablet
Klonopin 0.5mg

0.5 mg: round, orange-colored tablet marked with K
 

Klonopin 1mg

1 mg: round, blue tablet marked with K

Klonopin 2mg

2 mg: round, white tablet marked with K

Wafers (orally disintegrating tablets) (not pictured)
White, round tablets packaged in a blister pack, at various doses:

0.125 mg (marked 1/8)
0.25 mg (marked 1/4)
0.5 mg (marked 1/2)
1 mg (marked 1)
2 mg (marked 2)

Rivotril

Indications

Clonazepam is used alone or with other seizure medicines to treat absence and myoclonic seizures (especially in Lennox Gastaut syndrome), and can help stop seizure clusters. (An example of a cluster might involve a person who has one complex partial seizure in the morning and three or four more seizures over the course of the day, just once a month.)

A person who typically has a prolonged warning before seizures (a particular symptom, an unusually long aura, or a series of small seizures) may be able to prevent the larger seizure by taking clonazepam when the warning begins.

For seizures that mainly occur during sleep or shortly after awakening, giving clonazepam or another benzodiazepine at bedtime can be very effective in controlling the seizures and improving sleep.

Forms

Generic clonazepam is manufactured in the United States by several different companies including TEVA pharmaceuticals, Watson Labs and Caraco Pharmaceutical Laboratories, Ltd. The name or appearance may differ in other countries. Clonazepam is available in tablet form in 0.5 mg,1.0 mg and 2.0 mg prescription strength.

Dosing

See package insert. 

How to take and store Clonazepam?

Regular clonazepam tablets should be swallowed whole, with a little water.

Clonazepam can be taken either with or without food. It is recommended that if the doses are not equally divided during the day, the largest dose should be taken at bedtime to minimize the possibility of daytime sedation.

Patients should be cautioned if you write a new prescription using a different strength of clonazepam. For example, if you've been prescribing 0.5-mg tablets and the new prescription is for 1-mg tablets, advise the patient about how many clonazepam tablets should now be taken. Clonazepam should be stored at room temperature.

Missed Doses

Advise patients to take a forgotten dose immediately unless it is almost time for the next dose. In that case, they should skip the forgotten dose (rather than taking a double dose) or call for further instructions.

Mechanisms of actions of Clonazepam

Although the precise mechanism of action of clonazepam is unknown, benzodiazepines appear to suppress seizures through enhancement of the actions of gamma-aminobutyric acid, the major inhibitory neurotransmitter in the central nervous system.

Clinical Pharmacology of Clonazepam

Clonazepam is metabolized in the liver by the cytochrome P-450 system and the metabolites are excreted by the kidneys. Clonazepam is approximately 85% protein bound.

Clonazepam is rapidly and nearly completely absorbed following oral administration. Peak serum concentrations are reached in approximately 1-4 hours. The half-life of clonazepam in multiple dose studies is approximately 30-40 hours. The effects of age, gender, hepatic dysfunction and renal dysfunction on the pharmacokinetics of clonazepam have not been well studied.

Efficacy of Clonazepam

Clonazepam is an effective medication but its side effects and problems with tolerance and withdrawal have kept it from being more widely used. Instead, it is usually used as an add-on medication for patients whose seizures do not completely respond to other seizure medicines.

Despite clonazepam becoming available in the United States in 1975, there have been few large, well-controlled studies of its effectiveness. It is generally used to treat absence seizures, often in combination with Depakote (valproate), and myoclonic seizures in patients with juvenile myoclonic epilepsy and progressive myoclonic epilepsy, typically in combination with Depakote. Clonazepam may also be useful for patients with photic-induced seizures.

Children with Lennox-Gastaut syndrome may benefit from its use, though not all studies have found it helpful for long-term treatment.

Common side effects of Clonazepam

The most common side effects of clonazepam are neurotoxic and dose-related. They include:

  • tiredness
  • dizziness
  • unsteadiness
  • impaired attention and memory
  • irritability
  • hyperactivity (in children)
  • drooling (in children)
  • depression (usually in adults)
  • nausea
  • loss of appetite

Up to half of patients treated for seizures with clonazepam experience drowsiness and about 30% have problems with coordination. In some cases, these problems diminish with time. About 25% have behavior problems such as hyperactivity in children.

Side effects may be lessened by:

  • reducing the total daily dosage
  • splitting the total daily dosage into more frequent doses shifting more of the total daily dosage to bedtime, especially for patients with nocturnal or early-morning seizures

Patients who have just started taking clonazepam (or who have just started taking a larger amount) should be cautioned about possible sedation and to avoid activities that require full vigilance until the effects of the drug are fully apparent.

No one should stop taking clonazepam or change the amount they take or when they take it without their doctor's guidance.

Serious Side effects of Clonazepam

Potentially serious or life-threatening reactions to clonazepam are rare. Symptoms that patients should report immediately to their doctor include:

Most patients who take clonazepam have no side effects or mild, transient side effects. Rarely, patients may develop any of the following serious side effects:

  • An allergic reaction (difficulty breathing; closing of the throat; swelling of the lips, face, or tongue; or hives)
  • Sores in the mouth or throat (could mean a blood problem)
  • Yellowing of the skin or eyes
  • Rash
  • Hallucinations, severe confusion, or changes in vision

Clonazepam, like other benzodiazepines, may cause psychological dependence. Withdrawal symptoms may occur if a dose is missed or reduced, including:

  • anxiety
  • increased heart rate
  • tremor
  • general unwell feeling

On July 10, 2008, an advisory panel was convened by the Food and Drug Administration (FDA) to review data that the FDA had previously collected from drug studies showing an association between many of the antiepileptic drugs (AEDs) and suicidal ideation and behavior, which together are called suicidality. According to the FDA’s Alert, among the patients with epilepsy in these drug studies, 1 out of 1000 people taking the placebo (inactive substance) showed suicidality compared to approximately 3.5 out of 1000 people who took an AED. The FDA advisory panel voted to accept the FDA's data at its meeting on July 10.

Taking antiepileptic medicines may increase the risk of having suicidal thoughts or actions;

  • Do not make any changes to the medication regimen without first talking with the responsible healthcare professional;
  • Pay close attention to any day-to-day changes in mood, behavior and actions. These changes can happen very quickly so it is important to be mindful of any sudden differences.

Be aware of common warning signs that might be a signal for risk of suicide. Some of these are:

  • Talking or thinking about wanting to hurt yourself or end your life
  • Withdrawing from friends and family
  • Becoming depressed or having your depression get worse
  • Becoming preoccupied with death and dying
  • Giving away prized possessions

We again urge patients and families to contact their doctor before stopping an epilepsy medication because this may possibly lead to seizures and worsening of mood.

Impact of Clonazepam on bone health

See package insert. 

Other Uses of Clonazepam

Clonazepam is indicated for the treatment of panic attack, with or without agoraphobia, as defined in DSM-IV. Clonazepam is sometimes used off-label to treat movement disorders such as Tourette syndrome.

Clonazepam Contraindications

Clonazepam should not be used in patients with a history of sensitivity to benzodiazepines or in patients with significant liver dysfunctioin. It is also contraindicated in patients with acute narrow angle glaucoma.

Clonazepam Interactions with other medications

See package insert. 

Clonazepam effects on Children

In children, drowsiness or hyperactivity can occur if clonazepam is started too quickly. Some children are very sensitive to these side effects, which can occur even if the clonazepam is introduced at very low doses. Children up to 10 years of age or up to 30 kilograms (about 65 pounds) of body weight generally start by taking no more than 0.01 to 0.02 mg per kg each day (a total of 0.25 to 0.75 mg per day for a child weighing 65 pounds or more). This amount is given in two or three doses per day.

Dosage should then increase by no more than 0.01 to 0.02 mg/kg every third day. The final daily maintenance dose is usually 0.1 to 0.2 mg/kg of body weight (depending on total weight and age).

If high doses are prescribed for children, especially those with developmental disabilities, problems with thinking and behavior may be the result. If the dose has been increased gradually over many months or years, it can be hard to separate the effects of the clonazepam (or other benzodiazepines) from the effects of other medications, seizures, and other neurological and psychological disorders.

Clonazepam and Pregnancy

As noted in the package insert for clonazepam, an increased risk of congenital malformations associated with the use of benzodiazepine drugs has been suggested in several studies.

In addition, there have been reports of neonatal flaccidity, respiratory and feeding difficulties, and hypothermia in children born to mothers who had received benzodiazepines late in pregnancy. Such children may also be at risk for withdrawal symptoms.

The risk of defects is higher for women who take several medicines, and for women with a family history of birth defects.

Women who are capable of becoming pregnant should be advised to take 400 mcg (0.4 mg) of folic acid (folate) daily to help prevent neural tube defects. Women at high risk, such as those with a history of a neural tube defect in a previous pregnancy, should take 4000 mcg (4 mg) daily, beginning before they become pregnant.

During the last month of pregnancy, the woman should take 10 mg per day of vitamin K to prevent a bleeding disorder that affects some babies born to mothers who are taking anticonvulsants.

No studies have been performed to demonstrate the effect of specific AEDs during labor and delivery. Possible causes of seizures include:

  • failure or inability to take medication
  • sleep deprivation
  • hyperventilation
  • stress
  • pain
Clonazepam effects on Seniors

Doctors do not often prescribe clonazepam to people over 65 because seniors are at greater risk for behavioral effects, as well as falls or other accidents resulting from side effects.

Clonazepam Dosing and titration

Clonazepam must be introduced gradually, and a low starting dose is advisable, such as 0.5 to 1.5 mg/day, which may be taken all at once or divided into two or three doses. The dosage can be increased by 0.5 to 1 mg every 3 to 7 days. The maximum daily dose recommended is 10 mg. In a survey of epilepsy specialists, most recommended no more than 4 mg per day and usually prescribed no more than 2 mg per day.

Special Concerns for Clonazepam

See package insert. 

Clonazepam Package insert

In the United States, companies that manufacture medicines are required to publish certain kinds of information about each product. This document is commonly known as a “package insert” because it is usually included with each package of the medicine.

You can also read these documents (also called "prescribing information") online. The U.S. package insert for Klonopin (clonazepam) is found at:

http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=9729

Some of the information may differ in other countries.

The summary of package characteristics can be obtained in any European language from:

    http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landing_page.jsp.

To learn how to read and understand a package insert, see "How to read a package insert."

Clonazepam References for Professionals

If you visit PubMed (http://www.ncbi.nlm.nih.gov/pubmed/), a service of the National Library of Medicine, you can read summaries of studies that have tested the effectiveness of clonazepam, as well as other reports about this medication.

Here is a link to one article related to clonazepam:

Mikkelsen B, Birket-Smith E, Bradt S, et al. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=817696&dopt=Abstract>Clonazepam in the treatment of epilepsy. A controlled clinical trial in simple absences, bilateral massive epileptic myoclonus, and atonic seizures. Arch Neurol. 1976;33(5):322-325. PMID: 817696

This small study reported very good results when clonazepam (Klonopin) was used as add-on therapy. Most patients experienced side effects, but they were usually tolerable.

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The mission of the Epilepsy Foundation is to lead the fight to overcome the challenges of living with epilepsy and to accelerate therapies to stop seizures, find cures, and save lives.

 
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