Clonazepam – Uses, Risk Factors, and Side Effects

Background

Clonazepam is a long-acting benzodiazepine used to treat various seizures, including myotonic or atonic seizures, photosensitive epilepsy, and absence seizures, although tolerance may develop. The agent has also been indicated for treating panic disorder. The mechanism of action appears to involve the enhancement of gamma-aminobutyric acid receptor responses.

Since being first patented in 1960 and then released for sale from Roche in the US in 1975, clonazepam has experienced a storied history in the treatment of the aforementioned medical conditions. Now available as a generic medication, the agent continues to see exceptionally high use as millions of prescriptions are written for the medication internationally every year. Unfortunately, however, like most benzodiazepines, clonazepam use has also been associated with recreational use and drug abuse.

Properties and characteristics of Clonazepam

Drug class	Benzodiazepines
Brand Names	Clonapam, Klonopin, Rivotril
Synonyms	Clonazepam, Clonazepamum
Molecular Formula	C15H10ClN3O3
Molecular Weight	315.71 g/mol
IUPAC Name	5-(2-chlorophenyl)-7-nitro-1,3-dihydro-1,4-benzodiazepin-2-one
Structural formula of main components
Pure active ingredient	Clonazepam
Appearance	Off-white to light yellow crystalline powder
Melting point	237.5 °C
Solubility	In water, <100 mg/L at 25 °C
Excretion	Clonazepam is excreted via urine
Storage	Clonazepam tablets should be stored in air-tight, light-resistant containers at 25 °C
Available Forms	Tablet, Solution
Prescription	Do not consume without the doctors’ advice

What are the uses of Clonazepam?

Clonazepam functions by modulating the GABA-A receptors that help in inducing calming effects on the brain and reducing the excitability of neurons. Some of the uses of Clonazepam are:

• Management of seizure disorders (status epilepticus, minor motor seizures, myoclonic seizures, grand mal epilepsies, and infantile spasms) in both adults and children
• Management of panic disorders (as a short-term treatment) and agoraphobia
• Helps in regulating acute mania
• Other uses include akathisia, restless leg syndrome, and bruxism

What side effects can this medication cause?

Clonazepam may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• Drowsiness
• Dizziness
• Unsteadiness
• Problems with coordination
• Difficulty thinking or remembering
• Increased saliva
• Muscle or joint pain
• Frequent urination
• Blurred vision
• Changes in sex drive or ability

Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately or get emergency medical treatment:

• Rash
• Hives
• Swelling of the eyes, face, lips, tongue, or throat
• Difficulty breathing or swallowing
• Hoarseness
• Difficulty breathing

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration’s (FDA)

Mechanism of action

Gamma-Aminobutyric acid (GABA) is considered the principal inhibitory neurotransmitter in the human body. When GABA binds to GABA(a) receptors found in neuron synapses, chloride ions are conducted across neuron cell membranes via an ion channel in the receptors. With enough chloride ions conducted, the local, associated neuron membrane potentials are hyperpolarized – making it more difficult or less likely for action potentials to fire, ultimately resulting in less excitation of the neurons.

Subsequently, benzodiazepines like clonazepam can bind to benzodiazepine receptors that are components of various varieties of GABA(a) receptors. This binding act to enhance the effects of GABA by increasing GABA affinity for the GABA(a) receptor, which ultimately enhances GABA ligand binding at the receptors. This enhanced ligand binding of the inhibitory neurotransmitter GABA to the receptors increases the aforementioned chloride ion conduction (perhaps reportedly via an increase in the frequency of the chloride channel opening), resulting in a hyperpolarized cell membrane that prevents further excitation of the associated neuron cells. Combined with the notion that such benzodiazepine receptor associated GABA(a) receptors exist both peripherally and, in the CNS, this activity consequently facilitates various effects like sedation, hypnosis, skeletal muscle relaxation, anticonvulsant activity, and anxiolytic action.

In particular, when out of the ordinary rapid and repetitive electrical signals are released in the CNS, it is proposed that the brain can become over-stimulated and ordinary functions are disrupted – resulting in seizure activity 8. By enhancing the neuro-inhibitory activity of GABA, it is believed that clonazepam can facilitate in decreasing any excessive electrical nerve activity in the CNS that might be contributing to seizures 8. Concurrently, it is also believed that clonazepam’s actions in enhancing GABA effects may inhibit neuronal activity proposed to occur in amygdala-centered fear circuits – therefore assisting in the management of anxiety or panic.

Clonazepam may interact with other medications

Clonazepam can interact with several other medications. Different interactions can cause different effects. For instance, some can interfere with how well a drug works, while others can cause increased side effects.

Below is a list of medications that can interact with Clonazepam. This list does not contain all drugs that may interact with Clonazepam.

Before taking Clonazepam, a person should be sure to tell their doctor and pharmacist about all prescription, over-the-counter, and other drugs they take. They should also tell them about any vitamins, herbs, and supplements they use. Sharing this information can help avoid potential interactions.

If a person has questions about drug interactions that may affect them, they should ask their doctor or pharmacist.

What are Dosages of Clonazepam?

Dosages of Clonazepam:

Dosage Forms and Strengths

Tablet dispersible: Schedule IV

• 0.12 mg
• 0.25 mg
• 0.5 mg
• 1 mg
• 2 mg

Tablet: Schedule IV (Adult Only)

• 0.5 mg
• 1 mg
• 2 mg

Dosage Considerations – Should be Given as Follows:

Panic Disorder Treatment

• Dose 0.25 mg orally every 12 hours initially; may increase to 1 mg/day after 3 days (may increase up to 4 mg/day in some patients)

Treatment of Seizure Disorders

• Seizures in adults: 1.5 mg/day orally divided every 8 hours; increase by 0.5-1 mg every 3 days until the desired effect achieved; not to exceed 20 mg/day
• Maintenance for seizures in adults: 2-8 mg orally; not to exceed 20 mg/day
• Children younger than 6 years:
  • Potential toxic dose: 0.05 mg/kg
• Children younger than 10 years or less than 30 kg
  • Dose 0.01-0.03 mg/kg/day orally divided every 8 hours; increase by 0.25-0.5 mg/day every 3 days to maximum 0.1-0.2 mg/kg/day orally divided every 8 hours
  • Maintenance dose: 0.1-0.2 mg per kg per day orally divided every 8 hours; not to exceed 0.2 mg per kg per day
• Children younger than 10 years or more than 30 kg
  • 1.5 mg/day orally divided every 8 hours; increase by 0.5-1 mg every 3 days until the desired effect is achieved; not to exceed 20 mg/day
  • Maintenance: 2-8 mg orally; not to exceed 20 mg/day

Dosing Considerations

• Discontinuation of treatment (seizures in adults): Withdraw treatment gradually over time; decrease the dose once every 3 days by 0.125 mg orally every 12 hours until completely withdrawn
• Discontinuation of treatment (seizures in children)
  • Children younger than 10 years: Treatment should be withdrawn gradually over time, as necessary
  • Children older than 10 years: Withdraw treatment gradually over time; decrease the dose every 3 days by 0.125 mg orally every 12 hours until completely withdrawn

Dosing Modifications

• Renal impairment: Supplemental dose in haemodialysis not necessary

What if there is an overdose of Clonazepam?

In case of an overdose, visit your doctor immediately. Also, contact the nearest hospital as soon as possible. Some of the symptoms of overdose include:

• Tendency to sleep and drowsiness
• Double vision
• Slurred speck
• Impaired motor skills.

More serious side effects include:

• Respiratory depression and hypoxemia
• Apnoea
• Hypotension
• Cardiac arrest
• Bradycardia
• Coma

The possibility of these side effects is very rare. Consult your doctor to discuss them, especially if they last for a longer period of time.

Precautions

If you are allergic to clonazepam or other benzodiazepines (such as diazepam or lorazepam), or if you have some other reactions, tell your doctor or pharmacist until taking it. Inactive ingredients can be found in this product, triggering allergic reactions or other issues.

Tell your doctor or pharmacist about your medical history, particularly if you have: a particular form of eye problem (narrow-angle glaucoma), a specific blood disorder (porphyria), liver disease, kidney disease, lung/breathing issues, mental/mood problems (such as depression, thoughts of suicide), personal or family history of a drug use disorder (such as overuse of or addiction to), or a personal or family history of a substance use disorder (such as overuse

The effects of this medication, especially drowsiness and confusion, may be more pronounced in older adults. These side effects will make you more vulnerable to dropping.

This drug should only be taken during pregnancy if absolutely necessary. It has the ability to injure an unborn child. However, since untreated seizures are a severe disorder that can affect both the mother and the unborn child, you should not stop taking this drug until your doctor orders you to. If you’re considering pregnancy or believe you may be, speak to your doctor right away about the advantages and dangers of taking this drug while pregnant.

This medicine will pass into breast milk and have unfavorable effects on a nursing baby. Consult with your doctor.