LOPRAZOLAM Tablets Ref.[9823] Active ingredients: Loprazolam

Disinhibiting effects may be manifested in various ways. Suicide may be precipitated in patients who are depressed and who exhibit aggressive behaviour towards self and others. Extreme caution should therefore be used in prescribing benzodiazepines in patients with personality disorders.

In general, the dependence potential of benzodiazepines is low but this increases when high doses are attained, especially when given over long periods and particularly in patients with a history of alcoholism or drug abuse. However, withdrawal symptoms occur even with normal therapeutic doses given for short periods of time. Withdrawal from benzodiazepines may be associated with physiological and psychological symptoms of withdrawal including depression, anxiety, tension, restlessness, confusion, irritability and headaches. Patients receiving benzodiazepines should be regularly monitored.

Rebound insomnia may also occur. It may be accompanied by other reactions such as changes in mood, anxiety, sleep disturbances and restlessness.

Loprazolam should be used with caution in chronic pulmonary insufficiency, cerebrovascular disease and chronic renal or hepatic impairment.

Risks from concomitant use of benzodiazepines and opioids

Concomitant use of benzodiazepines, including loprazolam, and opioids may result in sedation, respiratory depression, coma, and death. Because of these risks, reserve concomitant prescribing of benzodiazepines and opioids for use in patients for whom alternative treatment options are inadequate.

If a decision is made to prescribe loprazolam concomitantly with opioids, prescribe the lowest effective dosages and minimum durations of concomitant use, and follow patients closely for signs and symptoms of respiratory depression and sedation. (See Section 4.5)

Suicidality and depression

Several epidemiological studies show an increased incidence of suicide and suicide attempt in patients with or without depression, treated with benzodiazepines and other hypnotics, including loprazolam. A causal relationship has not been established.

Fall

Due to its pharmacological properties, loprazolam can cause drowsiness and a decreased level of consciousness, which may lead to falls and consequently to severe injuries, especially in elderly (see section 4.8).

Loprazolam may be potentiated by alcohol or other drugs acting on the CNS or with Cisapride. Additive synergy has been observed with neuromuscular depressants (curare-like drugs and muscle relaxants).

Combination with CNS depressants e.g. antipsychotics, hypnotics, anxiolytics/sedatives, antidepressant agents, narcotic analgesics, anti-epileptic drugs, anaesthetics and sedative antihistamines, causes enhancement of the central depressive effects of Loprazolam.

Concommitant intake with alcohol is not recommended. The sedative effects may be enhanced when the product is used in combination with alcohol. This affects the ability to drive or use machinery.

The risk of a withdrawal syndrome occurring is increased when loprazolam is combined with other benzodiazepines prescribed as anxiolytics or hypnotics.

Benzodiazepines and Opioids

The concomitant use of benzodiazepines and opioids increases the risk of sedation, respiratory depression, coma, and death, because of additive CNS depressant effect. Limit dosage and duration of concomitant use of benzodiazepines and opioids (see section 4.4).

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.

If, for compelling medical reasons, the product is administered during the late phase of pregnancy, or during labour at high doses, effects on the neonate, such as hypothermia, hypotonia and moderate respiratory depression can be expected due to the pharmacological action of the compound.

Moreover, infants born to mothers who took benzodiazepines chronically during the latter stages of pregnancy may have developed physical dependency and may be at some risk for developing withdrawal symptoms in the postnatal period.

Since benzodiazepines are found in the breast milk, they should not be given to breast feeding mothers.

Attention should be drawn to the risk of drowsiness, sedation, amnesia, impaired concentration and muscular weakness, especially in drivers of vehicles and operators of machines, when taking the product (see also “Interactions”).

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:

• The medicine is likely to affect your ability to 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:
  • The medicine has been prescribed to treat a medical or dental problem and
  • You have taken it according to the instructions given by the prescriber and in the information provided with the medicine and
  • It was not affecting your ability to drive safely.

In general, Loprazolam is very well tolerated. However, the common side effects of benzodiazepines, including headaches, nausea, drowsiness, hypotonia, blurring of vision, dizziness and ataxia may occur on the following day, particularly in unusually sensitive patients or when dosage has been excessive.

Rare behavioural adverse effects of benzodiazepines include paradoxical aggressive outbursts, excitement, confusion and the uncovering of depression with suicidal tendencies. If these reactions should occur, use of the drug should be discontinued. Even more rare side effects reported with some benzodiazepines have been hypotension, gastro-intestinal and visual disturbances, skin rashes, urinary retention, changes in libido, blood dyscrasias and jaundice.

Frequency not known: speech disorders

Benzodiazepines may induce cognitive disorders (anterograde amnesia). In cases of loss or bereavement, psychological adjustment may be inhibited by benzodiazepines.

Injury poisoning and procedural complications: Fall (see Section 4.4)

Reporting of suspected adverse reactions

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 Yellow Card Scheme at :www.mhra.gov.uk/yellowcard.

None.