Source: Υπουργείο Υγείας (CY) Revision Year: 2018 Publisher: Remedica Ltd, Aharnon Str., Limassol Industrial Estate, 3056 Limassol, Cyprus
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Hypersensitivity reactions with the benzodiazepines including rash, angioedema and hypertension have been reported on rare occasions in susceptible patients.
Use of this drug is also contraindicated in patients with acute pulmonary insufficiency; respiratory depression; phobic or obsessional states; chronic psychosis; myasthenia gravis; sleep apnoea syndrome; severe hepatic insufficiency; use in children.
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.
Nitredon should not be used alone to treat depression or anxiety associated with depression, since suicide may be precipitated in such patients. Benzodiazepines should be used with extreme caution in patients with a history of alcohol or drug abuse. 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.
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monitoring in such patients is essential; routine repeat prescriptions should be avoided and treatment should be withdrawn gradually.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.
Some loss of efficacy to the hypnotic effects of short-acting benzodiazepines may develop after repeated use for a few weeks.
Abnormal psychological reactions to benzodiazepines have been reported. Rare behavioral effects include paradoxical aggressive outburst, excitement, confusion, restlessness, agitation, irritability, delusion, rages, nightmares, hallucinations, psychoses, inappropriate behavior and the uncovering of depression with suicidal tendencies. Extreme caution should therefore be used in prescribing benzodiazepines to patients with personality disorders. If any of these reactions occur, use of the drug should be discontinued. These reactions may be quite severe and are more likely to occur in the elderly.
Benzodiazepines may induce anterograde amnesia. The condition usually occurs 1 to 2 hours after ingesting the product and may last up to several hours. Therefore, to reduce the risk, patients should ensure that they will be able to have an uninterrupted sleep of 7 to 8 hours.
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.
Risk from concomitant use of opioids: Concomitant use of Nitredon and opioids may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing of sedative medicines such as benzodiazepines or related drugs such as Nitredon with opioids should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe Nitredon concomitantly with opioids, the lowest effective dose should be used, and the duration of treatment should be as short as possible (see also general dose recommendation in section 4.2).
The patients should be followed closely for signs and symptoms of respiratory depression and sedation. In this respect, it is strongly recommended to inform patients and their caregivers (where applicable) to be aware of these symptoms (see section 4.5).
This product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Enhancement of the central depressive effect may occur if benzodiazepines are combined with centrally-acting drugs such as neuroleptics, tranquillisers, antidepressants, hypnotics, analgesics and anesthetics, anti-epileptics and sedative antihistamines. In the case of narcotic analgesics, enhancement of the euphoria may also occur, leading to an increase in psychological dependence. The elderly require special supervision.
When Nitredon is used in conjunction with anti-epileptic drugs, side-effects and toxicity may be more evident, particularly with hydantoins or barbiturates or combinations including them. This requires extra care in adjusting dosage in the initial stages of treatment.
Known inhibitors of hepatic enzymes, particularly cythochrome P450 have been shown to reduce the clearance of benzodiazepines and may potentiate their action and known inducers of hepatic enzymes, e.g. rifampicin, may increase the clearance of benzodiazepines.
Concomitant intake with alcohol should be avoided. The sedative effect may be enhanced when the product is used in combination with alcohol. This adversely affects the ability to drive or use machines.
The concomitant use of sedative medicines such as benzodiazepines or related drugs such as Nitredon with opioids increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. The dosage and duration of concomitant use should be limited (see section 4.4).
There is no evidence as to drug safety in human pregnancy, nor is there evidence from animal work that it is free from hazard. Do not use during pregnancy, especially during the first and last trimesters, unless there are compelling reasons.
If the product is prescribed to a woman of childbearing potential, she should be warned to contact her physician regarding discontinuance of the product if she intends to become or suspects that she is pregnant.
The administration of benzodiazepines in the last trimester of pregnancy or during labour has been reported to produce irregularities in the foetal heart rate, and hypotonia, poor sucking and hypothermia and moderate respiratory depression in the neonate.
Infants born to mothers who took benzodiazepines chronically in the latter stages of pregnancy may have developed physical dependence and may be at some risk of developing withdrawal symptoms in the postnatal period.
Since benzodiazepines are found in the breast milk, the use of nitrazepam in mothers who are breast-feeding should be avoided.
Patients should be advised that, like all medicaments of this type, nitrazepam may modify patients' performance at skilled tasks. Sedation, amnesia, impaired concentration and impaired muscle function may adversely affect the ability to drive or 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.
When prescribing this medicine, patients should be told:
Common adverse effects include drowsiness during the day, numbed emotions reduced alertness, confusion, fatigue, headache, dizziness, muscle weakness, ataxia and double vision. These phenomena are dose related and occur predominantly at the start of therapy, they usually disappear with repeated administration. The elderly are particularly sensitive to the effects of centrally-depressant drugs.
Anterograde amnesia may occur at therapeutic dosages, the risk increasing at higher dosages. Amnesia effects may be associated with inappropriate behaviour.
Pre-existing depression may be unmasked during benzodiazepine use.
Other adverse effects are rare and include headache, vertigo, hypotension, gastro- intestinal upsets, skin rashes, visual disturbances, changes in libido, and urinary retention. Isolated cases of blood dyscrasias and jaundice have also been reported.
Use (even at therapeutic doses) may lead to the development of physical and psychological dependence: discontinuation of the therapy may result in withdrawal or rebound phenomena, a transient syndrome whereby the symptoms that led to treatment with benzodiazepine or benzodiazepine-like agent recur in an enhanced form. It may be accompanied by other reactions including mood changes, anxiety and restlessness. Since the risk of withdrawal phenomena/rebound phenomena is greater after abrupt discontinuation of treatment, it is recommended that the dosage be decreased gradually.
Abuse of benzodiazepines has been reported.
Reporting 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 any suspected adverse reactions via the national reporting system:
Cyprus: Pharmaceutical Services, Ministry of Health, CY-1475 Nicosia, Fax: +357 22608649, Website: www.moh.gov.cy/phs
Not applicable.
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