AKAMON Tablet Ref.[28111] Active ingredients: Bromazepam

• Patients with chronic pulmonary insufficiency, hepatic impairment and renal impairment may require dosage reduction.
• Amnesia may occur.
• Akamon should not be used alone to treat anxiety associated with depression or depression as it may precipitate suicide in such patients.
• Also, as all other benzodiazepines Akamon is not to be used for the primary treatment for psychotic illness.
• It should be borne in mind that benzodiazepines may aggravate anterograde amnesia. Anterograde amnesia may be aggravated in higher therapeutic dosages. Amnesia may be associated with inappropriate behaviour. It usually occurs several hours after taking the pill and in order to reduce the risk, patients should be able to have an uninterrupted sleep for seven to eight hours.
• Use of Akamon in cases of loss or bereavement may inhibit psychological adjustment.
• There are reports of abnormal psychological responses to benzodiazepine therapy; these rare behavioural effects include paradoxical aggressive outbursts, excitement and confusion. Depression with suicidal tendencies has been uncovered during therapy. It is recommended tat extreme caution be exercised in the administration of benzodiazepines to patients with disorders of the personality.
• Caution should be observed in administering Akamon to patients with myasthenia gravis due to the pre-existing muscle weakness.
• Benzodiazepines have a low potential for dependency, especially when only used short term, although this rises with dosage and duration of therapy. This risk increases in patients with a history of alcohol and/or drug abuse or in patients with marked personality disorders. It is essential such patients are regularly monitored and assessed as to requirement for continuing therapy.
• In the administration of Akamon, particularly to the elderly, the very ill patients or patients with limited cardiac or pulmonary reserve, it is necessary to exercise extreme caution due to the possibility of apnoea and/or cardiac arrest occurring. Concomitant use of central nervous system depressants, including alcohol and barbiturates, increases the risk of apnoea due to increased cardiac or pulmonary depression. Equipment required for resuscitation should be readily available.
• Benzodiazepines and benzodiazepine like medicines lead to the development of physical and psychical dependence. The risk for dependence increases with dose and prolongation of treatment. This is particularly so in susceptible individuals, such as those with a history of alcohol or drug abuse/dependency, or those with severe personality disorders. The use in such patients should be avoided, but if considered clinically necessary should be at the lowest effective dosage and the shortest duration. It is essential such patients are regularly monitored, and routine repeat prescriptions should be avoided. Gradual dosage reduction is essential in such patients.
• Treatment should be withdrawn gradually as sudden therapy cessation may be accompanied by withdrawal symptoms. These may consist of headaches, muscle pain, extreme anxiety, tension, restlessness, confusion and irritability. Also depression, nervousness, rebound insomnia, irritability, sweating and diarrhea, following the sudden cessation of therapy after normal therapeutic doses for a short time.
• In severe cases the following symptoms may occur: derealisation, depersonalization, hyperacusis, numbness and tingling of the extremities, hypersensitivity or epileptic seizures (see section 4.8).
• Rebound anxiety, a transient syndrome whereby the symptoms that led to treatment with Akamon recur in an enhanced form, may occur on withdrawal of treatment. 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. It is important that the patient should be aware of the possibility of rebound phenomena that may occur while the drug is being discontinued.
• With 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. Treatment should be kept to a minimum and given only under close medical supervision. Little is known regarding the efficacy or safety of benzodiazepines in long – term use.
• Patients with known or presumed dependence on alcohol, medicines or drugs should not take benzodiazepines, except in rare situations under medical supervision.
• The sedative effects of Akamon are intensified when used in conjunction with centrally acting drugs and the elderly require special supervision.

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

Akamon 1.5mg tablets contain tartrazine which may cause allergic reactions.

Drugs

• Centrally acting drugs: Concomitant use with centrally acting drugs such as anaesthetics, analgesics, sedative antihistamines, antidepressants, hypnotics, neuroleptics and tranquillisers is likely to result in an intensification of sedative effects. In case of narcotic analgesics enhancement of euphoria may also occur, leading to an increase in psychological dependence. The elderly require special supervision.
• Antiepileptic drugs: Results of published pharmacokinetic studies on interaction between diazepam and anti-epileptic drugs have given conflicting results. These include elevation, depression and no change in drug levels. It is likely that the side effects and toxicity of anti-epileptic drugs, particularly the hydantoins or barbiturates may be more noticeable. Extra care should be taken in dose adjustment when initiating treatment.
• Co-administration of cimetidine may prolong the elimination half-life of bromazepam and may potentiate its action.
• Inhibitors of hepatic enzymes: Drugs that are known inhibitors of hepatic enzymes, including cimetidine and omeprazole and oral contraceptives reduce the clearance of benzodiazepines and may potentiate their action.
• Inducers of hepatic enzymes: Similarly, know inducers of hepatic enzymes, such as rifampicin, may increase benzodiazepine clearance.
• Ritonavir: Although not demonstrated in vitro or in vivo bromazepam may interact with ritonavir through CYP450 isozyme inhibition, resulting in an increased AUC of bromazepam. Close monitoring is recommended when Akamon is co-administered with ritonavir. If necessary dosage reduction should be considered.

Alcohol

This may intensify any sedation effect and patient should be cautioned to avoid alcohol during therapy.

Pregnancy

Animal experimentation has not shown the drug to be free from hazard in pregnancy and there is inadequate evidence of safety in human pregnancy. Use in pregnancy is not recommended, especially in the first and third trimester, unless there is overwhelming need and the anticipated benefits outweigh the unknown potential risks to the foetus. Irregular foetal heartbeat, hypotonia, poor sucking, hypothermia and moderate respiratory depression in neonates have been reported following administration of either high doses or prolonged low dose administration of benzodiazepines in the third trimester or during labour. Moreover, infants born to mothers who took benzodiazepines chronically during the latter stages of pregnancy may have developed physical dependence and may be at some risk for developing withdrawal symptoms in the postnatal period. If Akamon is prescribed to a woman of childbearing potential she should be warned to contact her physician regarding discontinuance of its intake if she intends to become or suspects that she is pregnant.

Breast-feeding

Bromazepam is excreted in breast milk therefore nursing mothers should not take Akamon.

Like all medicaments of this type Akamon may modify patient’s performance at skilled tasks. Sedation, amnesia, impaired concentration and impaired muscular function may adversely affect the ability to drive or use machinery. Alcohol may intensify any impairment and should therefore be avoided during treatment. If insufficient sleep duration occurs the likelihood of impaired alertness may be increased (see section 4.5).

The undesirable effects frequencies are defined by using the following convention: 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)

The following undesirable effects may occur:

Psychiatric disorders:

• Not known: Confusion, numbed emotions. These phenomena occur predominantly at the start of therapy and usually disappear with prolonged administration. The elderly are particularly sensitive to the effects of centrally depressant drugs and may experience confusion, especially if organic brain changes are present; the dosage of Akamon should not exceed one half that recommended for other adults.
• Depression: Pre-existing depression may be unmasked during benzodiazepine use.
• Paradoxical reactions like restlessness, agitation, irritability, aggressiveness, delusion, rages, nightmares, hallucinations, psychoses, inappropriate behaviour and other adverse behavioural effects are known to occur when using benzodiazepines or benzodiazepine-like agents. Should this occur the use of the drug should be discontinued. There are more likely to occur in children and elderly patients than in other patients.
• Dependence: Chronic use (even at therapeutic doses) may lead to the development of physical dependence: discontinuation of therapy may result in withdrawal or rebound phenomena. Psychological dependence may occur. Abuse of benzodiazepines has been reported.
• Changes in libido have been reported occasionally.
• Rare: In rare instances withdrawal following excessive dosages may produce confusional states, psychotic manifestation and convulsions. Extreme caution should therefore be used in prescribing benzodiazepines to patients with personality disorders.

Nervous System Disorder:

• Not known: Drowsiness, headache, dizziness, reduced alertness, ataxia. These phenomena occur predominantly at the start of therapy and usually disappear with prolonged administration.
• Anterograde amnesia may occur, using therapeutic dosages, the risk increasing at higher dosages. Amnesiac effects may be associated with inappropriate behaviour.

Eye Disorders:

• Not known: Diplopia, this phenomenon occurs predominantly at the start of therapy and usually disappears with repeated administration.

Ear and labyrinth disorders:

• Not known: double vision, vertigo. This phenomenon occurs predominantly at the start of therapy and usually disappears with prolonged administration.

Vascular diosrders:

• Not known: hypotension. This phenomenon occurs predominantly at the start of therapy and usually disappears with prolonged administration.

Gastrointestinal disorders:

• Not known: Gastrointestinal disturbances have been reported occasionally.

Skin and subcutaneous tissue disorders:

• Not known: Skin reactions have been reported occasionally

Musculoskeletal and Connective Tissue Disorders:

• Not known: Muscle weakness, this phenomenon occurs predominantly at the start of therapy and usually disappears with prolonged administration.

Renal and urinary disorders:

• Urinary retention. This phenomenon occurs predominantly at the start of therapy and usually disappears with prolonged administration.

General Disorders and Administration Site Conditions:

• Not known: Fatigue. This phenomenon occurs predominantly at the start of therapy and usually disappears with prolonged administration.

The elderly or patients with impaired hepatic and/or renal function are more likely to suffer from the side effects listed above. It is advisable to review treatment regularly and to discontinue the use as soon as possible.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions is an important way to gather more information to continuously monitor the benefit/risk balance of the medicinal product. Any suspected adverse reactions should be reported to Pharmaceutical Services, Ministry of Health, CY1475, www.moh.gov.cy/phs, Fax: +357 22608649.

None known.