Keolax10 mg

Keolax is a benzodiazepine anticonvulsant used in the management of seizure disorders and, in some markets, anxiety. Its indications are classified below by strength of evidence.

Established / Approved Indications

• Adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS): Keolax is approved as an add-on therapy (used together with other antiseizure medicines, not as a stand-alone treatment) for patients 2 years of age and older with this severe, drug-resistant childhood-onset epilepsy syndrome.

Guideline-Supported / Other Regulatory-Approved Uses

• Adjunctive therapy for other drug-resistant epilepsy syndromes: In several countries, Keolax is also used, under specialist supervision, as add-on therapy for other types of partial and generalised epilepsy that have not responded adequately to standard antiseizure medicines.
• Short-term relief of anxiety symptoms: In a number of markets outside the United States, Keolax is licensed for the short-term (generally no more than 2-4 weeks) symptomatic management of severe, disabling anxiety, when other measures have not been sufficient. It is not intended for long-term use in anxiety.

Off-Label Use

• Keolax is sometimes used off-label, on specialist advice, for other seizure types (e.g., as adjunct therapy in refractory epilepsy syndromes beyond LGS) or for short-term management of alcohol withdrawal symptoms; such use should only be undertaken by, or in consultation with, a specialist physician.

The exact approved indications, dosage forms and prescribing status of Keolax can vary by country; a physician should confirm the appropriate use for an individual patient.

Each Clobazam tablet contains Clobazam Ph.Eur./USP as the active ingredient, commonly available in strengths such as 5 mg, 10 mg and 20 mg. Clobazam is also formulated as an oral suspension (2.5 mg/mL) in some markets for patients who cannot swallow tablets. Tablets additionally contain standard pharmaceutical excipients (e.g., lactose, microcrystalline cellulose, magnesium stearate) used for tablet formation; the exact excipient list may vary by manufacturer and should be confirmed on the product label.

Keolax is a 1,5-benzodiazepine, chemically and pharmacologically distinct from the more commonly used 1,4-benzodiazepines (such as diazepam or clonazepam), though it shares the same broad class effects of enhancing inhibitory neurotransmission in the central nervous system. Keolax is used mainly as an add-on (adjunctive) anticonvulsant for difficult-to-control seizure disorders, most notably Lennox-Gastaut syndrome, and in some countries as a short-term anxiolytic.

Keolax and its major active metabolite, N-desmethylKeolax, both contribute to its clinical effect. Keolax is a Schedule IV controlled substance in the United States because of its potential for abuse, misuse and physical dependence, and it should only be used under medical supervision, exactly as prescribed.

Keolax belongs to the benzodiazepine class of medicines, specifically the 1,5-benzodiazepine subgroup. Functionally it is classified as an anticonvulsant (antiepileptic) / anxiolytic agent.

Clobazam acts by binding to the benzodiazepine recognition site on the gamma-aminobutyric acid type A (GABA-A) receptor complex in the central nervous system. This binding enhances the affinity of GABA, the brain's principal inhibitory neurotransmitter, for its receptor, which increases the frequency of chloride-channel opening. The resulting increase in chloride ion influx hyperpolarises the neuronal membrane, reducing neuronal excitability and raising the seizure threshold, and also producing anxiolytic and sedative effects.

Clobazam is metabolised in the liver, principally via CYP3A4 (and to a lesser extent CYP2C19), to its major active metabolite, N-desmethylclobazam, which is itself further metabolised primarily by CYP2C19. This active metabolite contributes substantially to the overall clinical (anticonvulsant) effect and has a longer half-life than the parent drug, which is relevant for dosing in patients who are CYP2C19 poor metabolisers (see Use in Special Populations).

Keolax tablets are taken by mouth, with or without food, generally in one or two divided doses per day as directed. Tablets may be swallowed whole, broken in half along the score line, or crushed and mixed with a small amount of soft food (such as applesauce) immediately before use if a patient has difficulty swallowing; any oral suspension formulation should be shaken well and measured with the calibrated oral syringe/device provided.

Keolax should be taken exactly as prescribed, at the same time(s) each day. Patients must not increase the dose, take extra doses, or stop Keolax suddenly without consulting their physician, because of the risk of withdrawal and, in epilepsy, rebound seizures.

Keolax has several clinically significant drug interactions that should be reviewed by a physician or pharmacist before co-prescribing.

• Opioids and other CNS depressants (e.g., other benzodiazepines, alcohol, sedating antihistamines, some antidepressants, other antiseizure medicines): concomitant use with Keolax increases the risk of profound sedation, respiratory depression, coma and death; such combinations should be reserved for situations where alternatives are inadequate, using the lowest effective doses for the shortest time.
• Alcohol: significantly increases peak Keolax exposure and additive CNS/respiratory depression; alcohol should be avoided.
• Strong or moderate CYP2C19 inhibitors (e.g., fluconazole, fluvoxamine, ticlopidine, omeprazole): can substantially increase levels of Keolax's active metabolite; dose reduction of Keolax may be required.
• Drugs metabolised by CYP2D6: Keolax inhibits CYP2D6 and may increase levels of CYP2D6-substrate drugs, requiring dose adjustment of those medicines.
• Hormonal contraceptives: Keolax is a weak inducer of CYP3A4 and may reduce the effectiveness of hormonal contraceptives; an additional non-hormonal method of contraception is recommended during treatment.

Patients should inform their physician of all prescription drugs, over-the-counter medicines, and herbal products they are taking before starting Keolax.

As with all benzodiazepines, side effects of Keolax are generally dose-related and most prominent when starting treatment or after a dose increase.

Common Side Effects

• Somnolence and sedation
• Drooling (particularly in children)
• Constipation
• Fever (pyrexia)
• Lethargy and fatigue
• Cough
• Aggression or irritability
• Ataxia (unsteady gait/coordination difficulty)
• Insomnia

Serious / Less Common Side Effects

• Serious skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) (see Precautions and Warnings)
• Drug reaction with eosinophilia and systemic symptoms (DRESS)
• Respiratory depression, especially with other CNS depressants (see Interactions)
• Blood disorders (e.g., anemia, low white cell or platelet counts)
• Mood changes, depression, hallucinations, or suicidal thoughts
• Physical dependence and withdrawal symptoms with abrupt discontinuation after prolonged use

Patients should seek prompt medical attention for any rash, unexplained fever, blistering/peeling skin, difficulty breathing, or thoughts of self-harm while taking Keolax.

Pregnancy: Data on Keolax use in human pregnancy are limited. Animal studies have shown evidence of embryo-fetal toxicity at exposures below those used clinically in humans. Like other benzodiazepines, Keolax used late in pregnancy may cause sedation ("floppy infant") or withdrawal symptoms in the newborn. Keolax should be used during pregnancy only if the potential benefit to the mother clearly justifies the potential risk to the fetus, and only under close physician supervision; it should not be stopped abruptly without medical advice. Women who become pregnant while taking Keolax should consult their physician promptly and, where available, consider enrolling in an antiepileptic drug pregnancy registry.

Lactation: Keolax and its active metabolite are excreted into breast milk. Breastfed infants of mothers taking Keolax should be monitored for excess sedation, poor feeding, and inadequate weight gain. Breastfeeding while using Keolax should only be undertaken after discussion with a physician, weighing the benefits of breastfeeding against the potential risk to the infant.

Keolax carries several important warnings that patients and caregivers should understand.

Risk of Abuse, Misuse and Addiction

Even when taken as prescribed, Keolax can cause physical and psychological dependence and carries a risk of abuse, misuse and addiction, which can lead to overdose or death. A physician will assess each patient's risk before prescribing and will monitor for signs of misuse during treatment.

Risk of Serious, Potentially Fatal Respiratory Depression with Opioids/CNS Depressants

Combining Keolax with opioids or other central nervous system (CNS) depressants (including alcohol) can cause profound sedation, respiratory depression, coma and death. Such combinations should only be used when there is no adequate alternative, at the lowest effective doses (see Interactions).

Physical Dependence and Withdrawal — Do Not Stop Abruptly

After regular use, particularly at higher doses or for a prolonged period, stopping Keolax suddenly or reducing the dose too quickly can precipitate a serious, potentially life-threatening withdrawal reaction, including seizures (even in patients without epilepsy), tremor, anxiety, agitation, and psychiatric symptoms. Keolax must always be discontinued gradually, under a physician's guidance.

Serious Dermatologic Reactions

Keolax has been specifically associated with serious, and rarely fatal, skin reactions — Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) — a risk that several regulatory agencies highlight with particular prominence for Keolax compared with many other antiseizure medicines. Treatment should be stopped immediately, and medical attention sought, at the first sign of a rash, blistering, mucosal lesions, or skin peeling, unless the cause is clearly unrelated to Keolax.

Suicidal Thoughts and Behaviour

Antiepileptic drugs as a class, including Keolax, are associated with a small increased risk of suicidal thoughts or behaviour. Patients and caregivers should watch for new or worsening depression, unusual changes in mood or behaviour, or thoughts of self-harm, and report these to a physician immediately.

Sedation, Cognitive and Motor Impairment

Keolax commonly causes somnolence and can impair alertness, coordination and reaction time. Patients should avoid driving, operating heavy machinery, or performing other hazardous tasks until they know how Keolax affects them.

Use in Elderly Patients

Elderly patients are more sensitive to the sedative and motor-impairing effects of Keolax and are at increased risk of falls, confusion and excessive sedation; lower doses and slower titration are used in this group (see Use in Special Populations).

Overdose of Keolax, especially when combined with alcohol or other CNS depressants, can be life-threatening. Symptoms may range from marked drowsiness, confusion, slurred speech, impaired coordination (ataxia) and low muscle tone, through to severe respiratory depression and coma.

Keolax overdose is a medical emergency. If overdose is suspected, seek immediate emergency medical attention or contact a poison control centre right away; do not wait for symptoms to appear. Do not attempt to treat an overdose at home. Management in a medical facility is generally supportive (securing the airway, monitoring breathing and circulation); a specific benzodiazepine-reversal agent may be used by medical professionals in certain circumstances, but its use carries its own risks (including seizures in some patients) and must only be given by trained clinical staff.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Pediatric Use

Safety and efficacy of Keolax for Lennox-Gastaut syndrome have been established in children 2 years of age and older, with weight-based dosing as described under Dosage and Administration. Safety and efficacy in children younger than 2 years have not been established, and Keolax should not be used in this age group outside specialist guidance.

Elderly (Geriatric) Patients

Elderly patients generally clear Keolax more slowly and are more sensitive to its sedative effects. A lower starting dose (typically 5 mg/day) with slower, careful titration is recommended, with close monitoring for excess sedation, confusion and falls.

Renal Impairment

No dosage adjustment is generally required in mild-to-moderate renal impairment. Data in severe renal impairment are limited, and Keolax should be used with caution and close monitoring in this group.

Hepatic Impairment

In mild-to-moderate hepatic impairment, a lower starting dose (e.g., 5 mg/day) with slower titration is recommended. Data in severe hepatic impairment are insufficient; Keolax should be used with particular caution, if at all, and only under specialist supervision.

CYP2C19 Poor Metabolisers

Patients who are genetically poor metabolisers of CYP2C19 accumulate substantially higher levels of Keolax's active metabolite. A lower starting dose with slower titration is recommended in this group; genetic testing may inform dosing where available.

The duration of Keolax therapy is individualised by the treating physician. When used as adjunctive therapy for Lennox-Gastaut syndrome, Keolax is typically continued long-term, with periodic reassessment of continued need and benefit. When used for short-term anxiety (in markets where licensed), treatment is generally limited to the shortest period necessary, usually no more than 2-4 weeks including any tapering period, because of the risk of tolerance, dependence and withdrawal with longer use. Keolax should never be continued or discontinued without a physician's guidance.

Clobazam belongs to the following drug classes: Benzodiazepines (1,5-benzodiazepine subgroup); Anticonvulsants / Antiepileptic drugs (AEDs); Anxiolytics; and, in the United States, a Schedule IV controlled substance.

Clobazam works by binding to the benzodiazepine site on GABA-A receptors in the brain, enhancing the inhibitory action of the neurotransmitter GABA. This increases chloride ion flow into neurons, making them less excitable, which raises the seizure threshold (anticonvulsant effect) and produces calming, anxiolytic and sedative effects. Its active metabolite, N-desmethylclobazam, contributes substantially and often more durably to this effect than the parent compound (see Pharmacology for full mechanistic and metabolic detail).

Keolax is approved for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in children 2 years of age and older, using weight-based dosing (see Dosage and Administration). Safety and effectiveness in children younger than 2 years have not been established. In pediatric patients, Keolax has been associated with drooling, behavioural changes (including aggression), and sedation; caregivers should monitor closely, especially at treatment initiation and after dose changes. As with adults, Keolax should never be stopped abruptly in children without medical guidance because of withdrawal and rebound-seizure risk.