Clonazepam

Clonazepam is a drug with anxiolytic, anticonvulsant, muscle relaxant and sedative properties. From the chemical point of view, clonazepam is a benzodiazepine. It is sold under the trade name Rivotril®.

Clonazepam - Chemical Structure

Indications

For what it uses

The use of clonazepam is indicated for the treatment of the following epileptic clinical forms in infants and children:

Small evil, typical or atypical;
Generalized tonic-clonic crises, primary or secondary;
State of evil in all its clinical expressions.

Furthermore, clonazepam is also used for the treatment of epilepsy and focal seizures in adults.

Off-label therapeutic indications

In Italy, clonazepam is approved exclusively for the treatment of epilepsy. However, it can be used as an off-label drug for the treatment of other diseases, including:

Anxiety;
Panic attacks;
Social phobia;
Restless legs syndrome;
Post-traumatic stress disorder;
Tourette syndrome.

The term "off-label" means the use of drugs known and used for a long time, for which scientific evidence suggests their use in clinical situations not expressly indicated on the illustrative leaflet of the drug itself.

Warnings

Patients with a history of depression and / or attempted suicide should be closely monitored during treatment with clonazepam.

Clonazepam can cause hypersalivation, therefore attention must be paid to the prescription of the drug in patients with difficulty in controlling secretions.

Since clonazepam can cause respiratory depression, caution should be used when administering the drug in patients with chronic respiratory diseases.

Clonazepam is mainly excreted via the urine, therefore attention must be paid to the administration of the drug in patients with impaired renal function.

Abrupt discontinuation of clonazepam treatment may induce seizures, therefore, discontinuation of therapy should occur gradually.

In children and newborns, clonazepam can cause hypersalivation and increased bronchial secretions, so it is important to carry out regular checks to check that the airways are free.

For the duration of treatment with clonazepam, regular checks of liver function and regular blood tests are recommended.

Caution should be used when administering clonazepam in patients with porphyria (a rare condition characterized by the lack of an enzyme involved in heme group synthesis).

Alcohol can cause epileptic seizures, therefore patients on clonazepam therapy should definitely avoid consumption.

Extreme caution should be used when administering clonazepam in patients with a history of alcohol and / or drug abuse.

Because of the side effects that clonazepam can induce, driving vehicles or using machines during treatment with the drug is not recommended.

Interactions

The elimination rate of clonazepam can be increased - and, therefore, its therapeutic efficacy can be decreased - by concomitant administration of other antiepileptic drugs, including phenytoin, carbamazepine, phenobarbital and valproate .

Furthermore, the concomitant administration of clonazepam and phenytoin or primidone may cause an increase in the plasma concentration of these two antiepileptics.

Depressive action on the central nervous system (CNS) and on respiration induced by clonazepam, can be increased by the concomitant administration of substances or drugs also capable of depressing the CNS. These drugs include amphetamines, methylphenidate (a drug used in the treatment of attention deficit hyperactivity disorder), anxiolytic drugs, antipsychotics and alcohol .

Side effects

Clonazepam can trigger various types of side effects, although not all patients experience them.

The following are the main side effects that may occur following treatment with the drug.

Addiction

The use of clonazepam may result in the development of physical and mental dependence.

Prolonged treatment and / or high-dose clonazepam, can cause irreversible disorders, such as:

Dysarthria;
Decreased coordination of movements;
Ataxia;
nystagmus;
Diplopia.

Anterograde amnesia

Clonazepam therapy can cause anterograde amnesia.

The risk of developing this type of amnesia increases with increasing dose of clonazepam administered. Amnesia may be accompanied by behavioral abnormalities and, in some cases, by an increase in the frequency of convulsions.

Endocrine disorders

Some children treated with clonazepam may experience incomplete precocious puberty.

Psychiatric disorders

Treatment with clonazepam may cause:

agitation;
Hallucinations;
Memory and concentration disorders;
Confusion;
Disorientation;
Depression.

In addition, the following paradoxical symptoms may occur:

Restlessness;
Irritability;
Aggression;
Nervousness;
Hostility;
Anxiety;
Sleep disorders;
Nightmares and vivid dreams.

Nervous system disorders

Clonazepam therapy may cause:

Drowsiness;
Tremors;
Dizziness;
Ataxia;
Muscular hypotonia;
Slow down of reactions;
Headache;
Increased frequency of seizures in some types of epilepsy.

Cardiac disorders

Treatment with clonazepam can cause palpitations, heart failure and cardiac arrest.

Gastrointestinal disorders

Treatment with clonazepam can cause nausea, dry mouth and changes in the mouth.

Hepatobiliary disorders

Treatment with clonazepam may cause hepatomegaly, temporary increases in blood levels of transaminases and alkaline phosphatase.

Skin and skin tissue disorders

Clonazepam therapy can cause hives, itching, skin rash, alteration of skin pigmentation and temporary hair loss.

Blood and lymphatic system disorders

Treatment with clonazepam can cause disorders in the system responsible for the synthesis of blood cells (hemolymphopoietic system). These disorders can cause anemia (reduced amount of hemoglobin in the blood), leukopenia (reduced amount of white blood cells in the bloodstream), thrombocytopenia (reduction in the number of platelets in the blood) and eosinophilia (high concentration of eosinophils in the blood).

Other side effects

Other adverse effects that may occur during therapy with clonazepam are:

Allergic reactions - even serious - in sensitive subjects;
hypersalivation;
Diplopia;
nystagmus;
Respiratory depression;
Muscle weakness;
Urinary incontinence;
Erectile dysfunction;
Dehydration;
Changes in body weight.

Overdose

Overdose with clonazepam should not be life-threatening unless other drugs have been used that can depress the central nervous system, drugs or alcohol.

The symptoms that may arise from taking an overdose are:

Drowsiness;
Ataxia;
Dysarthria;
nystagmus;
areflexia;
Apnea;
Hypotension;
Cardiorespiratory depression;
Coma.

The coma usually lasts a few hours, but could last even for a longer period.

In case of overdose of clonazepam it could be useful the administration of activated charcoal.

If necessary, a benzodiazepine antagonist can be given, flumazenil .

In any case, if you suspect you have taken an overdose of medication, you must contact a doctor immediately and contact the nearest hospital.

Action mechanism

The anticonvulsant action of clonazepam is due to its ability to stimulate the GABAergic system, ie the γ-aminobuttiric acid system (GABA).

GABA is the main inhibitory neurotransmitter of the brain and carries out its biological functions by binding to its specific receptors: GABA-A, GABA-B and GABA-C.

A binding site for benzodiazepines is present on the GABA-A receptor.

Clonazepam binds to this specific site and activates the receptor, thus promoting the cascade of inhibitory signals induced by GABA.

Mode of Use - Posology

Clonazepam is available for oral administration in the form of tablets and oral drops.

The dosage of clonazepam must be established on a strictly individual basis, depending on the age of the patient and his response to therapy.

It is advisable to administer a low initial dose, which is then gradually increased until the ideal maintenance dose is reached.

In elderly patients, in patients with chronic pulmonary insufficiency, in patients suffering from sleep apnea or with impaired hepatic and / or renal function, a reduction in the usual dose of clonazepam may be necessary.

Pregnancy and breastfeeding

Clonazepam should not be given to women in the first trimester of pregnancy.

During the rest of the pregnancy, the drug can only be used in cases where it is actually necessary and only under the strict supervision of the doctor.

Because clonazepam is excreted in breast milk, mothers taking the drug should not breast-feed.