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Clonazepam / Epitril / Klonopin / Rivotril

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1 Clonazepam / Epitril / Klonopin / Rivotril on Wed Sep 30, 2009 3:01 pm


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 belongs to a group of medications called the benzodiazepines (BEN-zo-di-AZ-ah-peens). The use of benzodiazepines to treat epilepsy over a long period of time is controversial because tolerance often develops within weeks. Tolerance occurs when a person has to take larger and larger doses of a medication to achieve the same result.

Because clonazepam has a high degree of tolerance it will work well for brief periods of time, but its effectiveness may decrease over time. In addition, since the dosage must be increased to maintain the same degree of seizure control the side effects associated with clonazepam may increase too.

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.

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.

How well does it work?
Clonazepam is an effective medication but its side effects and problems with tolerance and withdrawal have kept it from being widely used as a first-line therapy for most kinds of seizures. Instead, it is usually used as an "add-on" medication for people who continue to have seizures while taking other seizure medicines, or sometimes as a medication of last resort after most others have failed. It sometimes loses its efficacy after a while.

Clonazepam has been available in the United States since 1975, so doctors have plenty of experience with its use, but few large, well-controlled studies of its effectiveness have been performed. It has been shown to work for many different seizure types.

It can be used to treat absence seizures, often in combination with Depakote (valproate). Clonazepam is particularly effective against some types of myoclonic seizures such as juvenile myoclonic epilepsy and progressive myoclonic epilepsy. Again, it is often used in combination with Depakote.

Clonazepam is useful for seizures brought on by flashing lights (photosensitivity).

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

Clonazepam is usually regarded as less effective against partial seizures than carbamazepine (Tegretol or Carbatrol) or phenytoin (Dilantin, Phenytek).

Factors influencing the decision about whether to add clonazepam to a regimen of seizure medicines that are not fully controlling a person's seizures may include potential interactions, side effects, and the mechanisms of action of the various medications. No single combination is perfect for everyone. Sometimes, a series of combinations must be tried before finding what is best for the individual.

Clonazepam belongs to a class of medications called benzodiazepines, which lower brain activity. As a result, common symptoms include:

•impaired attention and memory
•hyperactivity (in children)
•drooling (in children)
•depression (usually in adults)
•loss of appetite

Scientific studies show that about half of people 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. Problems with thinking and behavior are greater with clonazepam than with seizure medicines like Tegretol, Dilantin, and Depakote.

If these problems do not go away within several days, or are really bothersome, call the doctor. Sometimes the doctor can help with these side effects by changing the prescription:

•reducing the overall amount of clonazepam
•changing the amount taken at certain times, such as taking a greater proportion of the clonazepam at bedtime to reduce daytime sleepiness
•prescribing smaller doses, to be taken more often

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

People who have just started taking clonazepam (or who have just started taking a larger amount) should be careful during activities that might be dangerous, until they know whether they are having any side effects.

Most people who take clonazepam have no side effects or mild side effects that go away with no lasting harm. But a few people have serious reactions. Here's a list of symptoms that may be the start of one of these problems. If you notice any of these symptoms, call the doctor right away:

•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
•Hallucinations, severe confusion, or changes in vision
One of the great dangers in using medications like clonazepam is the tendency to increase the dose as tolerance develops. To a certain extent, dosage increases may be necessary, but adverse effects may be increased more than seizure control. If the dosage is increased gradually over a long period, subtle changes in personality (such as irritability, depression, or decreased motivation) or problems such as impaired memory may go unnoticed or be considered natural for that person.

High doses sometimes are prescribed, especially for 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.

An important concern when people with epilepsy take clonazepam or other benzodiazepines is the risk that seizures will become more frequent or more severe if the medicine is reduced or stopped. The longer the person has been taking clonazepam and the higher the dosage, the greater the tolerance and therefore the higher the risk of worsening seizure control. Even small, gradual dose reductions can temporarily increase seizure activity, but the long-term decrease in effects like drowsiness and depression often makes the change worthwhile.

Also, sometimes clonazepam makes people feel sleepy or uncoordinated. If you've just started taking clonazepam or have just had your dosage increased, especially if you tend to be sensitive to medications, be careful when doing things that could be dangerous until you know how it will affect you.

Finally, clonazepam and other benzodiazepines are the medicines that are most likely to cause psychological dependence. When someone takes a benzodiazepine at a certain dosage for more than 2 to 4 weeks, the body (or specifically, the brain's receptors for the neurotransmitter GABA) becomes accustomed to it. Then if a dose is missed or reduced, a withdrawal process starts and the person experiences:

•increased heart rate
•general unwell feeling
Taking another pill relieves all of these symptoms, confirming the person's belief that he or she "needs" the medication. This is a very dangerous cycle, since long-term use can cause long-lasting changes in the brain's GABA receptors that lead to significant problems such as impaired thinking, decreased motivation, and depression. In this setting, rapid dose reduction can cause severe symptoms of anxiety, insomnia, and illness, as well as seizures. In many of these cases, very gradual reduction of the benzodiazepine (often over many months or years) can lead to a dramatic improvement in attention, concentration, memory, and mood without worsening the seizures, insomnia, or anxiety for which the medication was originally prescribed.

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. The FDA has provided the following information for patients, family members, and caregivers at

•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.

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.

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

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