Nelurolen 1%

Nelurolen 1% Tablets should be used for short term treatment of insomnia only when it is severe, disabling, or subjecting the individual to extreme distress, where daytime sedation is acceptable.

Treatment should be as short as possible and should be started with the lowest effective dose.

Method of administration: For oral administration.

- Patients with known hypersensitivity to benzodiazepines or any of the excipients.

- Hypersensitivity reactions with benzodiazepines include rash, angioedema and hypertension been reported on rare occasions in susceptible patients.

- Acute pulmonary insufficiency, respiratory depression, as ventilatory failure may be exacerbated

- Acute Porphyria

- Myasthenia gravis, as the condition may be exacerbated

- Sleep apnoea syndrome, as the condition may be exacerbated

- Severe hepatic insufficiency (elimination half-life of Nelurolen 1% may be prolonged).

- Phobic or obsessional states and chronic psychosis

- Use in children.

- Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Nelurolen 1% tablets should not be used alone to treat depression or anxiety with depression, since suicide may be precipitated in such patients.

In patients with chronic pulmonary insufficiency, and in patients with chronic renal or hepatic disease, dosage may need to be reduced. Benzodiazepines are contraindicated in patients with severe hepatic insufficiency.

Benzodiazepines are not recommended for the primary treatment of psychotic illness. If the patient is awoken during the period of maximum drug activity, recall may be impaired.

In cases of loss or bereavement, psychological adjustment may be inhibited by benzodiazepines.

Insomnia

An underlying cause for insomnia should be sought before deciding upon the use of benzodiazepines for symptomatic relief.

Tolerance

Some loss of efficacy, due to the hypnotic effects of benzodiazepines, may develop after repeated use for a few weeks.

Dependence (including use with alcohol) and withdrawal

Use of benzodiazepines may lead to the development of physical and psychological dependence upon these products. The risk of dependence increases when high doses are used, especially when given over long periods. This is particularly so in patients with a history of alcoholism or drug abuse or in patients with marked personality disorders. Regular monitoring in such patients is essential; routine repeat prescriptions should be avoided and treatment should be withdrawn gradually. Symptoms such as depression, headaches, muscle weakness, nervousness, extreme anxiety, tension, restlessness, confusion, mood changes, rebound insomnia, irritability, sweating, and diarrhoea have been reported following abrupt cessation of treatment in patients receiving even normal therapeutic doses for short periods of time.

When benzodiazepines with a long duration of action are being used it is important to warn against changing to a benzodiazepine with a short duration of action, as withdrawal symptoms may develop.

In severe cases the following symptoms may occur: derealisation, depersonalisation, hyperacusis, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact and hallucinations or epileptic seizures. In rare instances, withdrawal following excessive dosages may produce confusional states and psychotic manifestations and convulsions. Abuse of the benzodiazepines has been reported.

Rebound insomnia and anxiety

This is a transient syndrome that may occur on withdrawal of treatment whereby the symptoms that led to treatment with a benzodiazepine recur in an enhanced form. It may be accompanied by other reactions including mood changes, anxiety or sleep disturbances and restlessness. Since the risk of withdrawal phenomena/rebound phenomena is greater after abrupt discontinuation of treatment, it is recommended that the dosage is decreased gradually.

Duration of treatment

The duration of treatment should be as short as possible (see 4.2 Posology and method of administration) depending on the indication, but should not exceed 4 weeks for insomnia, including tapering off process. Extension beyond these periods should not take place without re-evaluation of the situation. Routine prescriptions should therefore be avoided.

It may be useful to inform the patient when treatment is started that it will be of limited duration and to explain precisely how the dosage will be progressively decreased. Moreover it is important that the patient should be aware of the possibility of rebound phenomena, thereby minimising anxiety over such symptoms should they occur while the medicinal product is being discontinued.

There are indications that, in the case of benzodiazepines with a short duration of action, withdrawal phenomena can become manifest within the dosage interval, especially when the dosage is high.

When benzodiazepines with a long duration of action are being used it is important to warn against changing to a benzodiazepine with a short duration of action, as withdrawal symptoms may develop.

Amnesia

Benzodiazepines may induce anterograde amnesia. The condition occurs most often one to two hours after taking the product and may last several hours, therefore to reduce the risk patients should ensure that they will be able to have an uninterrupted sleep of 7-8 hours.

Psychiatric and paradoxical reactions

Extreme caution should be used in prescribing Nelurolen 1% to patients with personality disorders.

Reactions like restlessness, agitation, irritability, aggressiveness, excitement, confusion, delusion, rages, nightmares, hallucinations, psychoses, inappropriate behaviour and other adverse behavioural effects (such as the uncovering of depression with suicidal tendencies) are known to occur when using benzodiazepines. These reactions may be quite severe and are more likely to occur in the elderly and children. Should this occur, use of the medicinal product should be discontinued.

Specific patient groups

Due to the myorelaxant effect there is a risk of falls and consequently of hip fractures particularly for elderly patients when they get up at night.

Hypoalbuminaemia (may predispose patient to higher incidence of sedative side effects).

Care should be exercised in patients with epilepsy since there have been reports of rare paradoxical exacerbation of seizures in these patients.

Care should be taken in patients with chronic renal or hepatic disease as the elimination half-life of Nelurolen 1% may be prolonged.

Patients should be advised that, like all medicines of this type, Nelurolen 1% tablets may modify patients' performance at skilled tasks. Sedation, amnesia, impaired concentration and impaired muscular function may adversely affect the ability to drive or to use machinery. If insufficient sleep duration occurs, the likelihood of impaired alertness may be increased. Patients should further be advised that alcohol may intensify any impairment, and should, therefore, be avoided during treatment.

This medicine can impair cognitive function and can affect a patient's ability to drive safely. This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988. When prescribing this medicine, patients should be told:

- This medicine is likely to affect how you drive

- Do not drive until you know how the medicine affects you

- It is an offence to drive while under the influence of this medicine

- However, you would not be committing an offence (called 'statutory defence') if:

o The medicine has been prescribed to treat a medical or dental problem and

o You have taken it according to the instructions given by the prescriber and in the information provided with the medicine and

o It was not affecting your ability to drive safely

The following undesirable effects have been divided into the following categories: Very common:  1/10, Common:   1/100 to <1/10, Uncommon:   1/1,000 to <1/100 > Rare: 1/10,000 to <1/1,000, Very rare: <1/10,000, Not known (cannot be estimated > from the available data).

Blood and the lymphatic system disorders
Rare	Blood dyscrasias
Immune system disorders
Very rare	Hypersensitivity reactions (anaphylaxis and angioedema)
Psychiatric disorders
Uncommon	Confusion, sleeping disorders, including insomnia
Rare	Psychiatric and paradoxical reactions (1). Muscular cramps, libido fluctuations
Not known	Dependence and abuse of benzodiazepines, amnesia (2), depression (3), withdrawal symptoms (4)
Nervous system disorders
Common	Dizziness, sedation, unsteadiness, ataxia, drowsiness, numbed emotions, reduced alertness, fatigue
Uncommon	Disturbances in attention, tremor
Rare	Dystonia, headache
Not known	Dysarthria
Eye disorders
Rare	Visual disturbances
Not known	Double vision
Ear and labyrinth disorders
Rare	Vertigo
Vascular disorders
Rare	Hypotension
Respiratory, thoracic and mediastinal disorders
Rare	Respiratory depression
Gastrointestinal disorders
Rare	Nausea, gastrointestinal upsets
Hepato-biliary disorders
Rare	Jaundice
Skin and subcutaneous tissue disorders
Rare	Rash and other allergic skin reactions in the form of urticaria, pruritus, dermatitis, erythema multiforme, Stevens-Johnson syndrome
Renal and urinary disorders
Rare	Urinary retention
Musculoskeletal, connective tissue and bone disorders
Uncommon	Muscular weakness 4. Withdrawal effects on abrupt cessation of treatment - Depression, headaches, muscle weakness, nervousness, extreme anxiety, tension, restlessness, confusion, mood changes, rebound insomnia, irritability, sweating and diarrhoea have been reported following abrupt cessation of treatment. In rare cases, withdrawal following excessive dosages may produce confusional states, psychotic manifestations and convulsions. As with all benzodiazepines, withdrawal may be associated with physiological and psychological symptoms including depression. Reporting of suspected adverse reactions Reporting of suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report suspected adverse reactions via Yellow Card Scheme: www.mhra.gov.uk/yellowcard. Overdose The information provided in Overdose of Nelurolen 1% is based on data of another medicine with exactly the same composition as the Nelurolen 1%. . Be careful and be sure to specify the information on the section Overdose in the instructions to the drug Nelurolen 1% directly from the package or from the pharmacist at the pharmacy. more... As with other benzodiazepines, overdose should not present a threat to life unless combined with other CNS depressants (including alcohol). In the management of overdose with any medicinal product, it should be borne in mind that multiple agents may have been taken. Symptoms Overdose of benzodiazepines is usually manifested by degrees of central nervous system depression ranging from drowsiness to coma. In mild cases, symptoms include drowsiness, mental confusion, dysarthria and lethargy, in more serious cases, symptoms may include ataxia, hypotonia, hypotension, respiratory depression, rarely coma and very rarely death. Management Vomiting should be induced (within one hour) if the patient is conscious or gastric lavage undertaken with the airway protected if the patient is unconscious. If there is no advantage in emptying the stomach, activated charcoal should be given in adults or children who have taken more than 1 mg/kg within one hour to reduce absorption provided they are not too drowsy. Special attention should be paid to respiratory and cardiovascular functions in intensive care. The value of dialysis has not been determined. Flumazenil, a benzodiazepine antagonist, may be useful as an antidote in emergency situations. Patients requiring such intervention should be monitored closely in hospital. Flumazenil is not indicated in patients with epilepsy who have been treated with benzodiazepines. Antagonism of the benzodiazepine effect in such patients may trigger seizures. If excitation occurs, barbiturates should not be used. Pharmacodynamic properties The information provided in Pharmacodynamic properties of Nelurolen 1% is based on data of another medicine with exactly the same composition as the Nelurolen 1%. . Be careful and be sure to specify the information on the section Pharmacodynamic properties in the instructions to the drug Nelurolen 1% directly from the package or from the pharmacist at the pharmacy. more... Pharmacotherapeutic group: Hypnotics and Sedatives, Benzodiazepine derivatives, ATC Code: N05CD02 Nelurolen 1% is a benzodiazepine compound with sedative properties. It acts in 30 to 60 minutes to produce sleep lasting six to eight hours. Pharmacokinetic properties The information provided in Pharmacokinetic properties of Nelurolen 1% is based on data of another medicine with exactly the same composition as the Nelurolen 1%. . Be careful and be sure to specify the information on the section Pharmacokinetic properties in the instructions to the drug Nelurolen 1% directly from the package or from the pharmacist at the pharmacy. more... Nelurolen 1% is well absorbed with peak blood levels being achieved within two hours after administration. Two hours after administration, the concentration of Nelurolen 1% in the cerebrospinal fluid is about 8% and after 36 hours approximately 16% of the concentration in the plasma. The cerebrospinal fluid concentration thus corresponds to the non-protein-bound fraction of active ingredient in the plasma. The half-life of Nelurolen 1% is on average 24 hours. Steady-state levels are achieved within five days. Nelurolen 1% undergoes biotransformation to a number of metabolites none of which possesses significant clinical activity. About 5 % of metabolites are excreted unchanged in the urine together with less than 10% each of the 7-amino and 7-acetylamino metabolites in the first 48 hours. In younger persons the volume of distribution is 2L/kg, in elderly patients the volume of distribution is greater and the mean elimination half-life rises to 40 hours. Pharmacotherapeutic group The information provided in Pharmacotherapeutic group of Nelurolen 1% is based on data of another medicine with exactly the same composition as the Nelurolen 1%. . Be careful and be sure to specify the information on the section Pharmacotherapeutic group in the instructions to the drug Nelurolen 1% directly from the package or from the pharmacist at the pharmacy. more... Hypnotics and Sedatives, Benzodiazepine derivatives, Preclinical safety data The information provided in Preclinical safety data of Nelurolen 1% is based on data of another medicine with exactly the same composition as the Nelurolen 1%. . Be careful and be sure to specify the information on the section Preclinical safety data in the instructions to the drug Nelurolen 1% directly from the package or from the pharmacist at the pharmacy. more... There is no pre-clinical data of relevance to a prescriber, which is additional to that already included in other sections of the Summary of Product Characteristics. Incompatibilities The information provided in Incompatibilities of Nelurolen 1% is based on data of another medicine with exactly the same composition as the Nelurolen 1%. . Be careful and be sure to specify the information on the section Incompatibilities in the instructions to the drug Nelurolen 1% directly from the package or from the pharmacist at the pharmacy. more... None known. Special precautions for disposal and other handling The information provided in Special precautions for disposal and other handling of Nelurolen 1% is based on data of another medicine with exactly the same composition as the Nelurolen 1%. . Be careful and be sure to specify the information on the section Special precautions for disposal and other handling in the instructions to the drug Nelurolen 1% directly from the package or from the pharmacist at the pharmacy. more... No special instruction necessary. References: https://www.drugs.com/search.php?searchterm=nelurolen-1 https://pubmed.ncbi.nlm.nih.gov/?term=nelurolen-1 Available in countries Japan Find in a country: A B C D E F G H I J K L M N O P Q R S T U V Y Z