Neuryl Plus

Neuryl Plus Uses, Dosage, Side Effects, Food Interaction and all others data.

Chemically, clonazepam is a benzodiazepine derivative. It exhibits several pharmacologic properties, which are characteristics of the benzodiazepine class of drugs. In human it is capable of suppressing the spike and wave discharge in absence seizure (petit mal) and decreasing the frequency, amplitude, duration and spread of discharge in minor motor seizure.

The pharmacodynamic properties of clonazepam are common among benzodiazepines and include anticonvulsive, sedative, muscle relaxing and anxiolytic effects . Animal data and electroencephalographic investigations in man have shown that clonazepam rapidly suppresses many types of paroxysmal activity including the spike and wave discharge in absence seizures (petit mal), slow spike wave, generalized spike wave, spikes with temporal or other locations, as well as irregular spikes and waves . Moreover, the agent can also decrease the frequency, amplitude, duration, and spread of discharge in minor motor seizures .

Generalized EEG abnormalities are more readily suppressed by clonazepam than are focal EEG abnormalities such as focal spikes . Neuryl Plus has beneficial effects in generalized and focal epilepsies .

Trade Name Neuryl Plus
Availability Prescription only
Generic Clonazepam
Clonazepam Other Names Clonazepam, Clonazepamum
Related Drugs gabapentin, sertraline, fluoxetine, alprazolam, Zoloft, Xanax, lamotrigine, diazepam, Prozac, pregabalin
Type
Formula C15H10ClN3O3
Weight Average: 315.711
Monoisotopic: 315.041068908
Protein binding

The recorded plasma protein binding of clonazepam ranges between 82–86% .

Groups Approved, Illicit
Therapeutic Class Adjunct anti-epileptic drugs, Benzodiazepine hypnotics
Manufacturer
Available Country Chile
Last Updated: September 19, 2023 at 7:00 am
Neuryl Plus
Neuryl Plus

Uses

Neuryl Plus (Oral) is used for:

Tablet:

• Anxiety disorders (Generalized, Phobic & Panic disorders)

• Insomnia and sleep disturbances

• Labile arterial hypertension

• Peri and Post menopausal anxiety (Anxiety in middle aged women)

• Burning Mouth Syndrome

• Peri and Post menopausal anxiety (Anxiety in middle aged women)

• Postoperative anxiety disorder

• Post traumatic stress disorder

• Anxiety in cancer patient (palliative treatment)

• Tension Headache

• Restless legs syndrome (RLS) or Wittmaack–Ekbom syndrome

• Nocturnal myoclonus

• Tourette's syndrome

• Bipolar affective disorder

• Resistant depression

• Drug-induced dyskinesia

• Choreiform movement

• Fulgurant pain

• Trigeminal neuralgia

• Epilespsy

Injection:

• Epilepsy

• Status epilepticus

• Myoclonic seizure

• Typical and atypical absences (Lennox-Gastaut syndrome)

• Infantile spasm

• Tonic-clonic seizure

• Partial seizure

• Absence seizure

• Focal seizure

Neuryl Plus is also used to associated treatment for these conditions: Akinetic seizures, Burning Mouth Syndrome, Gilles de la Tourette's Syndrome, Lennox-Gastaut Syndrome (LGS), Mixed manic depressive episode, Panic Disorder, Rapid Eye Movement Sleep Disorder, Restless Legs Syndrome (RLS), Tardive Dyskinesia (TD), Tremor, Essential, Acute Manic episode, Myoclonic seizures, Refractory absence Seizures

How Neuryl Plus works

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 acts 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 . 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 . 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 .

Dosage

Neuryl Plus dosage

Tablet:

Infants and children

Initial dose: 0.01 - 0.03 mg/kg/day. Up to 1 year: 0.25 mg daily in divided dose, not to exceed 0.05 mg/kg/days increase gradually to 0.5 - 1 mg.

Increment dose: not more than 0.25 - 0.5 mg 1 - 5 years: 0.25 mg daily in divided dose, at intervals of 3 days increase to 1 - 3 mg.

Maintenance dose: 0.1 - 0.2 mg/kg/day. 5 - 12 years: 0.5 mg daily in divided dose,

Dosing interval: b.i.d. / t.i.d. increase to 3 - 6 mg.

Adults and elderly

Initial dose: 1 mg daily in divided dose (Elderly 0.5 mg), not to exceed 1.5 mg/day

Increment dose: 0.5 - 1 mg at intervals of 3 days

Maintenance dose: 4 - 8 mg/day

Maximum dose: 20 mg/day should be administered with caution

Dosing interval: b.i.d. / t.i.d.

Initial dose should be low and increased gradually to a maintenance dose that controls seizure without toxic effects. During discontinuation, the dose should be tapered.

Injection:

Infants and children: half of a vial (0.5 mg) by slow IV injection or by IV infusion. Adults: 1 vial (1 mg) by slow IV injection or by IV infusion. This dose can be repeated as required (1 - 4 mg are usually sufficient to reverse the status). In adults, the rate of injection must not exceed 0.25 - 0.5 mg per minute (0.5 – 1.0 mL of the prepared solution) and a total dose of 10 mg should not be exceeded.

Slow intravenous injection: The contents of the vial must be diluted with 1 mL of water for injection prior to administration so as to avoid local irritation of the veins. The injection solution should be prepared immediately before use. IV injection should be administered slowly with continuous monitoring of EEG, respiration and blood pressure.

Intravenous infusion: Neuryl Plus (the vial) can be diluted for infusion in a ratio of 1 vial (1 mg) to at least 85 mL diluting media. The diluting media can be any of the following: sodium chloride 0.9%; sodium chloride 0.45% + glucose 2.5%; glucose 5% or glucose 10%. These mixtures are stable for 24 hours at room temperature. Infusion bags other than PVC should be used for infusing Neuryl Plus. If PVC infusion bags are used then the mixture should be infused immediately or within 4 hours. The infusion time should not exceed 8 hours. Do not prepare Neuryl Plus infusions using sodium bicarbonate solution, as precipitation of the solution may occur.

Intramuscular injection: The IM route should be used only in exceptional cases or if IV administration is not feasible.

Side Effects

Tablet:

The most frequently occurring side effects of clonazepam are referable to CNS depression, drowsiness, fatigue, dizziness, muscle hypotonia, co-ordination disturbance, hypersalivation in infants, paradoxical aggression, irritability and mental change.

Injection:

Some side effects, like: fatigue, muscle weakness, dizziness, somnolence, light-headedness, ataxia, restlessness, hypersalivation in infants, paradoxical aggression, reduced co-ordination may occur with Neuryl Plus therapy but these effects are transient and generally disappears in the course of the treatment. Respiratory depression may occur in patients with pre-existing airways obstruction, or brain damage, or if other medications which depress respiration have been given. As a rule, this effect can be avoided by careful adjustment of the dose to individual requirements.

Toxicity

Benzodiazepines like clonazepam commonly cause drowsiness, ataxia, dysarthria, and nystagmus. Overdose with clonazepam is generally not life-threatening if the drug is taken alone, but may lead to areflexia, apnea, hypotension, cardiorespiratory depression, and coma. Coma, if it does occur, usually lasts a few hours but it can become more protracted and cyclical, especially in elderly patients. Increased frequency of seizures may occur in patients at supratherapeutic plasma concentrations. Benzodiazepine respiratory depressant effects are more serious when compounded in patients with respiratory disease.

An increased risk of congenital malformations associated with the use of benzodiazepine drugs like clonazepam has been suggested in several studies . There may also be non-teratogenic risks associated with the use of benzodiazepines during pregnancy . There have been reports of neonatal flaccidity, respiratory and feeding difficulties, and hypothermia in children born to mothers who have been receiving benzodiazepines late in pregnancy . In addition, children born to mothers receiving benzodiazepines late in pregnancy may be at some risk of experiencing withdrawal symptoms during the postnatal period . In general, it is best for patients who are of childbearing potential and also use benzodiazepines like clonazepam to discuss such matters with their health care professionals as careful consideration must be undertaken regarding the intersection of the risks of untreated seizure potential in the patient and any possible toxicity to the fetus .

Although the active ingredient of clonazepam has been found to pass into the maternal milk in small amounts only, mothers receiving clonazepam should not breast-feed their infants .

Since the possibility that adverse effects on the physical or mental development of the child could become apparent only after a number of years, the risk-benefit consideration of the long-term use of clonazepam in pediatric patients younger than five years of age is important .

The pharmacological effects of benzodiazepines like clonazepam appear to be greater in elderly patients than in younger patients even at similar plasma benzodiazepine concentrations, possibly because of age-related changes in drug-receptor interactions, post-receptor mechanisms, and organ function . In general elderly patients should be started on the lowest possible dose of clonazepam and observed closely . There is an increased risk for falls and fractures among elderly and debilitated benzodiazepine users . The risk is increased in those taking concomitant sedatives, including substances like benzodiazepines, alcoholic beverages, and so on .

Some oral LD50 values documented are >4000 mg/kg for the mouse model, >4000 mg/kg for the adult rat model, and >2000 mg/kg for the rabbit model .

Precaution

Tablet:

When used in patients in whom several different types of seizure disorders coexist, clonazepam may increase the incidence or precipitate the onset of generalized tonic-clonic seizures (grand mal). This may require the addition of appropriate anticonvulsants or an increase in their dosages. The concomitant use of valproic acid and clonazepam may produce absence status. Periodic blood counts and liver function tests are advisable during long term therapy with clonazepam.

The abrupt withdrawal of clonazepam, particularly in those patients on long-term, high-dose therapy, may precipitate status epilepticus. Therefore when discontinuing clonazepam, gradual withdrawal is essential.

Neuryl Plus may produce an increase in salivation. This should be considered before giving the drug to patients who have difficulty handling secretions. Because of this and the possibility of respiratory depression, clonazepam should be used with caution in patients with chronic respiratory diseases.

Because of the possibility that adverse effects on physical or mental development could become apparent only after many years, a benefit-risk consideration of the long-term use of clonazepam is important in pediatric patients.

Injection:

The concomitant use of Neuryl Plus with alcohol and CNS depressants should be avoided. Such concomitant use has the potential to increase the clinical effects of Neuryl Plus, such as: severe sedation, respiratory and cardiac depression. In some cases, dose adjustment of other medications is necessary. Neuryl Plus may produce an increase in salivation. This should be considered before giving the drug to patients who have difficulty handling secretions. Neuryl Plus is adviced to use with caution in patients with chronic respiratory diseases. Because of the possibility that adverse effects on physical or mental development could become apparent only after many years, a benefit-risk consideration of the long-term use of clonazepam is important in pediatric patients.

Interaction

Interactions have been reported between some benzodiazepines and other anticonvulsants, with changes in the serum concentration of the benzodiazepine or anticonvulsant.

Food Interaction

  • Avoid alcohol.
  • Limit caffeine intake.
  • Take with or without food. The absorption is unaffected by food.

Neuryl Plus Alcohol interaction

[Moderate] GENERALLY AVOID:

Acute ethanol ingestion may potentiate the CNS effects of many benzodiazepines.

Tolerance may develop with chronic ethanol use.

The mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic enzyme inhibition.

Also, it has been suggested that the cognitive deficits induced by benzodiazepines may be increased in patients who chronically consume large amounts of alcohol.



Patients should be advised to avoid alcohol during benzodiazepine therapy.

Volume of Distribution

Neuryl Plus distributes very rapidly to various organs and body tissues with preferential uptake by brain structures . The apparent volume of distribution has been documented as approximately 3 L/kg .

Elimination Route

Neuryl Plus is rapidly and almost entirely absorbed after oral administration as tablets . Peak plasma concentrations of clonazepam administered by the oral route are reached within 1-4 hours and the associated absorption half-life is about 25 minutes . The absolute bioavailability is approximately 90% - but with substantially large differences between individuals .

Half Life

The mean elimination half-life determined for clonazepam is independent of the dose given and has been documented as being about 30-40 hours .

Clearance

The documented clearance for clonazepam is approximately 55 ml/min regardless of gender . Nevertheless, clearance values normalized by weight decline with increasing body weight .

Elimination Route

Approximately 50-70% of a clonazepam dose is excreted in the urine and 10-30% is excreted in the feces as metabolites . The excretion of unchanged clonazepam in the urine is typically less than 2% of the administered dose . Metabolites of clonazepam are present in urine as both free and conjugated (glucuronide and sulfate) compounds .

Pregnancy & Breastfeeding use

The use of clonazepam during pregnancy or lactation should be avoided. Neuryl Plus is excreted into the breast milk and should therefore be avoided in breast-feeding mothers.

Contraindication

Neuryl Plus should not be used in patients with a history of sensitivity to benzodiazepine, nor in patients with clinical or biochemical evidence of significant liver disease. It may be used in patients with open angle glaucoma who are receiving appropriate therapy, but is contraindicated in acute narrow angle glaucoma.

Acute Overdose

Tablet:

Symptoms of clonazepam overdosage, like those produced by other CNS depressants, include somnolence, confusion, coma and diminished reflexes.

Injection:

Symptoms of Neuryl Plus overdosage, like those produced by other CNS depressants, include: somnolence, confusion, coma and diminished reflexes.

Interaction with other Medicine

Tablet:

The CNS-depressant action of the benzodiazepine class of drugs may be potentiated by alcohol, narcotics, barbiturates, nonbarbiturate hypnotics, antianxiety agents, the phenothiazines, thioxanthene and butyrophenone classes of antipsychotic agents, monoamine oxidase inhibitors and the tricyclic antidepressants, and by other anticonvulsant drugs.

Injection:

The CNS-depressant action of the benzodiazepine class of drugs may be potentiated by alcohol, narcotics, barbiturates, nonbarbiturate hypnotics, antianxiety agents, the phenothiazines, thioxanthene and butyrophenone classes of antipsychotic agents, monoamine oxidase inhibitors and the tricyclic antidepressants, and by other anticonvulsant drugs.

Storage Condition

Store at 25°C.

Innovators Monograph

You find simplified version here Neuryl Plus

Neuryl Plus contains Clonazepam see full prescribing information from innovator Neuryl Plus Monograph, Neuryl Plus MSDS, Neuryl Plus FDA label

FAQ

What is Neuryl Plus used for?

Neuryl Plus is a medication used to prevent and treat seizures, panic disorder, anxiety, and the movement disorder known as akathisia. It's used to control seizures or fits due to epilepsy, involuntary muscle spasms and sometimes restless legs syndrome.

How safe is Neuryl Plus?

Neuryl Plus is a safe and effective medication when used as directed.

How does Neuryl Plus work?

Neuryl Plus works by increasing levels of a calming chemical in your brain.

What are the common side effects of Neuryl Plus?

Common side effects of Neuryl Plus are include:

  • 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

Is Neuryl Plus safe during pregnancy?

Taking Neuryl Plus during pregnancy is not recommended because it can create risks for the unborn baby.

Is Neuryl Plus safe during breastfeeding?

Neuryl Plus gets into the breast milk in small amounts. Because it can cause sedation and levels might build up in the infant's body, other medications may be preferred while breastfeeding a newborn or an exclusively breastfed infant.

Can Neuryl Plus cause weight loss?

Some people experience unintended weight loss on this bran, while other people find it more difficult to exercise when taking Neuryl Plus.

When should be taken of Neuryl Plus?

It usually is taken one to three times a day with or without food. Take Neuryl Plus at around the same time everyday.

How long does Neuryl Plus take to work?

Neuryl Plus takes approximately 20-60 minutes to start working. The peak effects of Neuryl Plus are reached in 1-4 hours.

Is Neuryl Plus fast acting?

Neuryl Plus is a fast-acting benzodiazepine. It relaxes your emotions and muscles by affecting chemicals in the brain.

Is Neuryl Plus the best for anxiety?

Neuryl Plus acts quickly on social anxiety symptoms, but the other potential benefits of the medication can take longer to appear.

Can I take Neuryl Plus for a long time?

Neuryl Plus is not generally recommended for long-term use because it is known to be a habit-forming substance. Over time, the patient's body tends to build a tolerance to Neuryl Plus.

What happens if I take Neuryl Plus every day?

Neuryl Plus is a safe and effective medication when used as directed. Neuryl Plus may produce emotional and/or physical dependence (addiction) even when used as recommended. Physical dependence may develop after 2 or more weeks of daily use.

Can I take Neuryl Plus for a long time?

Neuryl Plus is not generally recommended for long-term use because it is known to be a habit-forming substance. Over time, the patient's body tends to build a tolerance to Neuryl Plus.




Who should not take Neuryl Plus?

You should not take Neuryl Plus if you have liver problems, severe liver disease, sleep apnea, susceptible to breathing fluid into lungs.

What happens if I miss a dose?

Take Neuryl Plus as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

What happens if I overdose of Neuryl Plus?

Seek emergency medical attention or call the Poison Help line. An overdose of Neuryl Plus can be fatal if you take it with alcohol, opioid medicine, or other drugs that cause drowsiness or slow your breathing.Overdose symptoms may include extreme drowsiness, confusion, muscle weakness, or coma.

What happens when Neuryl Plus stops working?

Stopping Neuryl Plus abruptly may result in one or more of the following withdrawal symptoms: irritability, nausea, tremor, dizziness, blood pressure changes, rapid heart rate, and seizures.

Can Neuryl Plus cause heart problems?

They slow down heart and breath rate. If you take too much of a Neuryl Plus , you risk slowing your heart rate to damaging or fatal levels.

Can Neuryl Plus cause liver or kidney damage?

No cases of acute liver failure or chronic liver injury due to Neuryl Plus have been described. There is no information about cross reactivity with other benzodiazepines, but some degree of cross sensitivity should be assumed.

Can Neuryl Plus effect my fertility?

There's no evidence that Neuryl Plus will affect fertility in either men or women. If you're trying to get pregnant, or you're having problems getting pregnant while on Neuryl Plus, speak to a doctor.

*** Taking medicines without doctor's advice can cause long-term problems.
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