Clorazepate (Tranxene)

When is clorazepate used ?

Clorazepate is a benzodiazepine that can be used as an add-on therapy in the treatment of partial seizures.

In what conditions besides epilepsy is clorazepate used ?

Clorazepate is actually rarely used for seizures, and is much more often prescribed for anxiety and alcohol withdrawal.

Some doctors prescribe clorazepate for irritable bowel syndrome.

What are the most common side effects of clorazepate ?

As with other benzodiazepines, the side effects of clorazepate are generally mild and usually disappear if the dose is reduced. The side effects most often reported are:

  • drowsiness
  • dizziness
  • poor coordination
  • drooling
  • restlessness or aggressiveness

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 clorazepate
  • changing the amount taken at certain times, such as taking a greater proportion of the drug at bedtime to reduce daytime sleepiness
  • prescribing smaller doses at more frequent intervals

No one should stop taking clorazepate or change the amount or time of taking the medication without their doctor's guidance. Suddenly stopping the medication can be associated with repetitive breakthrough seizures.

People who have just started taking clorazepate (or who have just started taking a larger amount) should be careful during activities that require their full attention to ensure that they don’t become too sleepy on the new or higher dosage.

What are the most serious side effects of clorazepate ?

Most people who take clorazepate have either no or mild side effects that generally disappear within a short time without lasting harm. Serious reactions, such as a drug-related skin rash, are extremely rare. Call your doctor right away if you notice a rash after starting clorazepate.

Like many other seizure medicines, clorazepate makes some people feel sleepy or uncoordinated. If you've just started taking clorazepate or have just had your dosage increased, be careful when doing things that could be dangerous until you know how it will affect you. Be especially cautious if you tend to be sensitive to medications or if you are taking another medicine that could make you sleepy.

One of the great dangers in using medications like clorazepate is tolerance, or lessening of the effect at the same dose over time. Therefore, there is a tendency to increase the dose as tolerance develops. To a certain extent, this is 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 normal for that person.

High doses sometimes are prescribed for children and adults, 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 clorazepate (or other benzodiazepines) from the effects of other medications, seizures, and other neurological and psychological disorders.

An important concern when people with epilepsy take clorazepate or other benzodiazepines is the risk of “withdrawal seizures” or increased, repetitive or more severe seizures if the medicine is reduced or stopped. Withdrawal symptoms usually begin upon stopping the medicine and last for 8 to 10 days. Early symptoms might be agitation, anxiety, restlessness or even fast heart rate, though seizures might begin immediately as well. The longer the person has been taking clorazepate and the higher the dose, the greater the tolerance and therefore the higher the risk of withdrawal seizures. Even small, gradual dose reductions can temporarily increase seizure activity, but your doctor may suggest these changes since the long-term decrease in effects like drowsiness and depression often makes this worthwhile.

Besides increased seizure activity, other symptoms of withdrawal include:

  • drowsiness
  • dizziness
  • poor coordination
  • drooling
  • restlessness, aggression, anxiety or agitation

Tell your doctor if you notice any of these symptoms when your dosage is being reduced.

Are there long-term side effects of taking clorazepate ?

Clorazepate 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, characterized by:

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

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 cognition, 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.

Who should not take clorazepate ?

Do not take clorazepate if you have narrow-angle glaucoma. Clorazepate may worsen this condition.

You may not be able to take clorazepate, or may require a dosage adjustment or special monitoring during treatment, if:

  • You have kidney disease
  • You have liver disease
  • You have asthma, bronchitis, emphysema or any other respiratory disease
  • You are depressed or have suicidal thoughts

Clorazepate is not approved for use by children younger than 9 years of age.

If a woman takes clorazepate during pregnancy, will it hurt the baby ?

Clorazepate is in the FDA pregnancy category D. This means that clorazepate is known to increase the risk of birth defects, but the benefits to the mother’s seizure control may outweigh these risks. Do not take this medication without first talking to your doctor if you are pregnant. It is not known whether clorazepate passes into breast milk. Do not take clorazepate without first talking to your doctor if you are breast-feeding a baby.