Clonazepam (Iktorivil)

What Is Clonazepam and What Is It Used For?

Quick Answer: Clonazepam belongs to the benzodiazepine class of medicines and is primarily used as an anticonvulsant for the treatment of various forms of epilepsy. It works by enhancing the activity of gamma-aminobutyric acid (GABA) in the brain, preventing the spread of seizure-triggering signals and thereby suppressing ongoing seizures and preventing new ones from occurring.

Clonazepam is one of the most widely prescribed benzodiazepine anticonvulsants in the world. First synthesized in 1964 and approved for medical use in 1975, it has become an established treatment option for several types of epilepsy that are difficult to manage with other anticonvulsant medications alone. The drug is listed by the World Health Organization (WHO) as an essential medicine for epilepsy management, underscoring its importance in global healthcare.

Unlike many other benzodiazepines that are primarily used for anxiety or sedation, clonazepam was specifically developed and classified as an anticonvulsant, reflected in its Anatomical Therapeutic Chemical (ATC) code N03AE01, placing it within the antiepileptic drug category rather than the anxiolytic category. This distinction is clinically significant because clonazepam demonstrates particularly potent anticonvulsant properties at doses that produce relatively less sedation compared to other benzodiazepines used for seizure control.

The mechanism of action of clonazepam involves enhancing the effect of gamma-aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the central nervous system. By binding to the benzodiazepine site on GABA-A receptors, clonazepam increases the frequency of chloride ion channel opening, resulting in enhanced neuronal inhibition. This hyperpolarization of neuronal membranes prevents the spread of abnormal electrical activity that characterizes epileptic seizures. Clonazepam has a particularly strong affinity for GABA-A receptors containing the α1 and α2 subunits, which are thought to mediate its prominent anticonvulsant and anxiolytic effects respectively.

Primary Indications

Clonazepam is indicated for the treatment of several forms of epilepsy where other first-line anticonvulsants have proven insufficient or are not suitable:

• Absence seizures (petit mal): These brief episodes of staring and unresponsiveness, most common in children, can often be effectively controlled with clonazepam when ethosuximide or valproic acid are inadequate or contraindicated. The International League Against Epilepsy (ILAE) recognizes clonazepam as a treatment option for refractory absence epilepsy.
• Myoclonic seizures: Characterized by sudden, brief involuntary muscle jerks, myoclonic seizures respond particularly well to clonazepam. It is considered one of the most effective treatments for cortical myoclonus and is recommended in multiple international guidelines for myoclonic epilepsy syndromes.
• Lennox–Gastaut syndrome: This severe childhood-onset epilepsy syndrome involves multiple seizure types, cognitive impairment, and characteristic EEG patterns. Clonazepam can be a valuable adjunctive treatment, helping to reduce the frequency and severity of the various seizure types associated with this condition.
• Akinetic seizures (drop attacks): Sudden loss of muscle tone causing falls can be reduced with clonazepam therapy, helping to prevent the injuries frequently associated with these seizure types.
• Infantile spasms (West syndrome): In some treatment protocols, clonazepam is used as adjunctive therapy for infantile spasms when first-line treatments such as vigabatrin or adrenocorticotropic hormone (ACTH) are insufficient.

In some countries, clonazepam is also approved for the treatment of panic disorder with or without agoraphobia. However, due to the risk of dependence, it is generally reserved for cases where other treatments, such as selective serotonin reuptake inhibitors (SSRIs), have been ineffective. Additional off-label uses include certain movement disorders such as restless legs syndrome, rapid eye movement (REM) sleep behaviour disorder, and essential tremor.

Pharmacokinetics

Clonazepam is rapidly and completely absorbed after oral administration, with a bioavailability of approximately 90%. Peak plasma concentrations are typically achieved within 1–4 hours after ingestion. The drug is extensively distributed throughout the body and crosses the blood–brain barrier efficiently, which accounts for its rapid onset of central nervous system effects.

The drug is extensively metabolized in the liver, primarily by the cytochrome P450 enzyme CYP3A4, through nitroreduction and acetylation to pharmacologically inactive metabolites, including 7-aminoclonazepam and 7-acetaminoclonazepam. Unlike diazepam, clonazepam does not produce pharmacologically active metabolites, which simplifies its pharmacokinetic profile. The elimination half-life in adults is approximately 30–40 hours, allowing for sustained anticonvulsant activity and typically permitting twice- or thrice-daily dosing. In neonates, the half-life can be considerably longer (up to 80 hours) due to immature hepatic metabolism.

Approximately 85% of a dose is excreted renally as metabolites, with less than 2% appearing unchanged in urine. The long half-life means that steady-state plasma concentrations are not achieved until approximately 5–7 days after initiation or dose changes, which is an important consideration when titrating doses for seizure control.

What Should You Know Before Taking Clonazepam?

Quick Answer: Clonazepam must not be used in patients with known hypersensitivity to benzodiazepines, severe respiratory insufficiency, severe liver disease, or a history of substance abuse disorders. Special caution is required in elderly patients, those with depression, sleep apnoea, or respiratory diseases, and during pregnancy or breastfeeding. A small number of patients may experience suicidal thoughts.

Contraindications

Clonazepam must not be used in the following situations:

• Hypersensitivity: Known allergy to clonazepam, other benzodiazepines, or any of the excipients in the formulation. Allergic reactions to benzodiazepines may manifest as skin rash, urticaria, itching, or in rare cases, anaphylaxis.
• Severe respiratory insufficiency: Patients with significant breathing difficulties are at heightened risk of respiratory depression, as clonazepam suppresses respiratory drive. This includes conditions such as severe chronic obstructive pulmonary disease (COPD) and acute respiratory failure.
• Severe hepatic impairment: Because clonazepam is extensively metabolized by the liver, severe liver disease can lead to dangerous drug accumulation, prolonged sedation, and may precipitate hepatic encephalopathy.
• Substance abuse disorders: Patients with current substance abuse problems involving medications, drugs, or alcohol should not be prescribed clonazepam due to the extremely high risk of developing dependence and misuse.
• Comatose patients: Clonazepam must not be administered to patients who are in a coma, as it can further suppress consciousness and respiratory function.

Warnings and Precautions

Before using clonazepam, discuss the following conditions with your healthcare provider, as dose adjustment or close monitoring may be required:

• Elderly patients or those with reduced general health (increased sensitivity to benzodiazepine effects)
• Significantly impaired liver function (even moderate impairment requires dose reduction and monitoring)
• Sleep apnoea (respiratory pauses during sleep can be worsened)
• Respiratory tract diseases including chronic lung conditions
• Brain injury or cerebrovascular disease
• Concurrent use of medications that suppress breathing
• Movement coordination difficulties (ataxia)
• Current or history of depression
• Severe muscle weakness (myasthenia gravis)
• Acute poisoning caused by alcohol or drugs
• Porphyria (metabolic disorder affecting haem biosynthesis)

Special Populations

Children: Extra caution should be exercised when treating infants, as clonazepam can cause increased production of saliva and mucus in the airways, potentially leading to breathing difficulties. Infants and young children should be monitored closely, particularly during the initiation of treatment. Children are also more susceptible to paradoxical reactions such as hyperactivity and agitation.

Elderly patients: Older adults typically require lower doses due to increased sensitivity to the central nervous system effects of benzodiazepines. The muscle-relaxant properties of clonazepam increase the risk of falls and consequent fractures, particularly when getting up during the night. Close supervision and careful dose titration are essential in this population.

Patients with depression: Clonazepam should be used with particular caution in patients with current or historical depression, as benzodiazepines may worsen depressive symptoms in some individuals. Regular monitoring of mood is recommended throughout treatment.

Pregnancy and Breastfeeding

Pregnancy: There is a risk of harm to the unborn child. Clonazepam should not be used during pregnancy unless your doctor has specifically instructed you to do so after careful evaluation of the risks and benefits. Benzodiazepine use during pregnancy has been associated with potential adverse effects on fetal development. Use during late pregnancy or near delivery can cause neonatal symptoms including hypothermia, hypotonia (poor muscle tone), respiratory depression, and feeding difficulties. Women of childbearing age should discuss reliable contraception with their prescribing physician.

Breastfeeding: Clonazepam passes into breast milk and can affect the nursing infant. Effects may include excessive sedation, poor feeding, and impaired weight gain. Therefore, clonazepam should not be used while breastfeeding. If treatment with clonazepam is considered essential, breastfeeding must be discontinued.

Driving and Operating Machinery

Clonazepam can cause drowsiness, dizziness, seizures, and concentration difficulties. You should not drive or operate machinery until you are confident that your ability to perform these activities is not impaired. Discuss with your doctor whether it is safe for you to drive or perform work that requires sharp attention. The sedative effects are most pronounced at the start of treatment and after dose increases, but may persist throughout the treatment course.

Important Information About Excipients

Clonazepam tablets contain lactose. If you have been told by your doctor that you have an intolerance to certain sugars, contact your doctor before taking this medicine. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose–galactose malabsorption should not take this medicine.

How Does Clonazepam Interact with Other Drugs?

Quick Answer: Clonazepam interacts with numerous medications, including other antiepileptic drugs (phenytoin, carbamazepine, valproic acid), opioid painkillers, sedatives, and herbal supplements like St. John’s wort. The most dangerous interactions involve opioids and alcohol, which can cause respiratory depression, coma, and death. Several antiepileptic drugs can reduce clonazepam’s effectiveness by accelerating its metabolism.

Clonazepam is metabolized primarily by the liver enzyme CYP3A4, making it susceptible to interactions with medications that inhibit or induce this enzyme system. Additionally, any substance that depresses the central nervous system can have additive or synergistic effects with clonazepam, potentially leading to excessive sedation, respiratory depression, or cardiovascular collapse. Patients taking clonazepam should always inform their healthcare provider about all medications, supplements, and herbal remedies they use.

Major Interactions

Moderate Interactions

What Is the Correct Dosage of Clonazepam?

Quick Answer: Clonazepam dosage is individually determined by the prescribing physician. The usual adult maintenance dose for epilepsy is 4–8 mg per day, divided into 3–4 doses. Treatment is always started at a low dose and gradually increased. Children’s doses are calculated based on age and body weight. Never change your dose or stop treatment without consulting your doctor.

Clonazepam must always be taken exactly as prescribed by your doctor. The dose is individualized based on the type and severity of seizures, patient age, response to treatment, and tolerability. Treatment is always initiated with a low dose that is gradually increased over several days or weeks to minimize side effects, particularly drowsiness and dizziness. This gradual titration approach, known as “start low, go slow,” is essential for optimal tolerability and effectiveness.

Adults

Children

Elderly

Dosage Overview Table

Missed Dose

If you forget to take a dose of clonazepam, continue with your regular dosing schedule. Do not take a double dose to make up for the missed one. Taking an extra dose can increase the risk of side effects including excessive drowsiness, confusion, and impaired coordination. If you frequently forget doses, consider using a pill organizer or setting reminders. Missing multiple consecutive doses can affect seizure control, so inform your doctor if this occurs.

Overdose

If you have taken more clonazepam than prescribed, or if a child has accidentally ingested the medication, contact emergency services or your local poison control centre immediately. Symptoms of overdose may include extreme drowsiness, confusion, impaired coordination, diminished reflexes, respiratory depression, and in severe cases, coma. Overdose is particularly dangerous when clonazepam is combined with other central nervous system depressants such as alcohol, opioids, or other sedatives.

The benzodiazepine antagonist flumazenil is available as a specific antidote in hospital settings. However, its use requires careful medical judgement, particularly in patients taking clonazepam for epilepsy, as flumazenil can precipitate seizures in benzodiazepine-dependent patients.

What Are the Side Effects of Clonazepam?

Quick Answer: The most common side effect of clonazepam is involuntary eye movements (nystagmus). Other well-known effects include drowsiness, fatigue, dizziness, impaired coordination, and muscle weakness, which are typically most pronounced at the start of treatment and often improve with continued use. Rare but serious side effects include respiratory depression, paradoxical behavioural reactions, and severe allergic reactions. Starting treatment at a low dose helps minimize initial side effects.

Like all medicines, clonazepam can cause side effects, although not everyone experiences them. Many of the common side effects are related to the central nervous system depression that is inherent to the drug’s mechanism of action. These effects are generally most noticeable during the initial phase of treatment and tend to diminish as the body develops tolerance to the sedative properties while maintaining the anticonvulsant effect. Starting with a low dose and increasing gradually is the most effective strategy for minimizing these initial side effects.

It is important to distinguish between expected, manageable side effects and those that require urgent medical attention. If you experience any side effects that are severe, persistent, or concerning, contact your healthcare provider. Do not stop taking clonazepam abruptly, as this can trigger withdrawal symptoms and potentially dangerous seizures.

Side effects such as fatigue, drowsiness, coordination difficulties, dizziness, and muscle weakness are generally transient and tend to resolve with continued treatment. They are most prominent at the start of treatment and can largely be avoided by initiating therapy at a low dose and increasing gradually.

Paradoxical reactions such as confusion, aggression, irritability, and overactivity may resolve if the dose is reduced. If they persist, treatment should be discontinued under medical supervision.

At high doses or during long-term treatment, speech disorders, coordination difficulties, or visual disturbances (double vision) may occur. Respiratory depression may occur, particularly with intravenous administration, and can be avoided through careful dose titration.

There have been reports of falls and fractures in patients using benzodiazepines. The risk is increased in patients who concurrently take other sedating medications (including alcoholic beverages) and in elderly patients.

Additional Side Effects in Children

In addition to the effects listed above, the following have been reported in children:

• Incomplete and early puberty: Reported in isolated cases during long-term treatment.
• Increased saliva production and airway secretions: Particularly in infants and young children, which can potentially compromise breathing. Close monitoring is required in this age group.

How Should You Store Clonazepam?

Quick Answer: Store clonazepam in its original packaging, protected from light, at room temperature. Keep it out of the sight and reach of children. Do not use the medicine after the expiry date printed on the packaging. Dispose of unused or expired medicine properly through a pharmacy take-back programme.

Proper storage of medications is essential to maintain their effectiveness and safety. Clonazepam is sensitive to light degradation, which means exposure to light can reduce the potency and stability of the medication over time. Following these storage guidelines helps ensure that each dose provides the intended therapeutic effect.

• Keep out of reach and sight of children. Store the medication in a secure location, preferably a locked medicine cabinet, to prevent accidental ingestion by children.
• Store in original packaging. The original container is designed to protect the tablets from light. Do not transfer tablets to another container.
• Protect from light. Clonazepam is light-sensitive. Keep the container tightly closed when not in use.
• Room temperature storage. Store at controlled room temperature (below 25°C / 77°F) unless otherwise directed by the packaging.
• Check expiry date. Do not use clonazepam after the expiry date printed on the label. The expiry date refers to the last day of that month.
• Proper disposal. Medicines should not be disposed of via wastewater or household waste. Return unused or expired medicines to a pharmacy for safe disposal. These measures help protect the environment.

What Does Clonazepam Contain?

Quick Answer: The active ingredient is clonazepam, available in 0.5 mg and 2 mg tablet strengths. Inactive ingredients include lactose, maize starch, potato starch, iron oxide colourants (0.5 mg tablets), magnesium stearate, talc, and microcrystalline cellulose (2 mg tablets).

0.5 mg Tablets

Active ingredient: Clonazepam 0.5 mg per tablet.

Inactive ingredients (excipients): Lactose monohydrate (40 mg), maize starch, pregelatinised potato starch, red iron oxide (E172), yellow iron oxide (E172), talc, magnesium stearate.

Appearance: 8 mm, beige, flat tablets with a single score line on one side and marked “0.5” on the other side. The score line can be used to divide the tablet into two equal halves.

2 mg Tablets

Active ingredient: Clonazepam 2 mg per tablet.

Inactive ingredients (excipients): Anhydrous lactose (122 mg), pregelatinised starch, magnesium stearate, microcrystalline cellulose.

Appearance: 8 mm, white, flat tablets with a cross score line on one side and marked “2” on the other side. The cross score line allows the tablet to be divided into two or four equal parts.