Gerard Laboratories

Gerax Tablet 250 micrograms.

Gerax Tablet 500 micrograms.

Gerax Tablet 1 mg.

Gerax Tablets 250 micrograms

Each tablet contains 250 micrograms alprazolam (as active). Also contains 92.77mg lactose (as excipient).

Gerax Tablets 500 micrograms

Each tablet contains 500 micrograms alprazolam (as active). Also contains 92.465 mg lactose (as excipient).

Gerax Tablets 1 mg

Each tablet contains 1 mg alprazolam (as active). Also contains 92.00 mg lactose(as excipient).

For a full list of excipients, see section 6.1.

Gerax tablet 250 microgram:

White, oval tablets scored and marked “AL 0.25” on one side and “G” on the other.

Gerax tablet 500 microgram:

Pale pink oval tablets scored and marked “AL 0.50” on one side and “G” on the other.

Gerax tablet 1 mg:

Light blue, oval tablets, scored and marked “AL 1.0” on one side and “G” on the other.

The scoreline is only to facilitate breaking for ease of swallowing and not to divide into equal doses.

Anxiety

Benzodiazepines are only indicated when the disorder is severe, disabling or subjecting the individual to extreme distress.

Treatment should be as short as possible. The overall duration of treatment generally should not be more than 8-12 weeks, including a tapering off process. The patient should be reassessed regularly and the need for continued treatment should be evaluated, especially in case the patient is symptom free.

Anxiety:

250 microgram (0.25 mg) to 500 microgram (0.5 mg) three times daily increasing, if required, to a total of 3 mg daily.

Treatment should be started with the lower recommended dose. The maximum dose should not be exceeded.

Initial doses may be given at bedtime to minimise daytime lethargy. If side effects occur with the starting dose, the dose should be lowered.

In certain cases extension beyond the maximum treatment period may be necessary, if so, it should not take place without re-evaluation of the patient's status.

Gerax is contra-indicated in patients with known hypersensitivity to benzodiazepines and any component of the product formulation.

Myasthenia gravis

Severe respiratory insufficiency

Sleep apnoea syndrome

Severe hepatic insufficiency

Tolerance

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

Dependence

Use of benzodiazepines may lead to the development of physical and psychic dependence upon these products. The risk of dependence increases with dose and duration of treatment, it is also greater in patients with a history of alcohol or drug abuse.

Once physical dependence has developed, abrupt termination of treatment will be accompanied by withdrawal symptoms. These may consist of headaches, muscle pain, extreme anxiety, tension, restlessness, confusion and irritability. In severe cases the following symptoms may occur: derealisation, depresonalisation, hyperacusis, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact, hallucinations or epileptic seizures.

Rebound insomnia and anxiety: a transient syndrome whereby the symptoms that led to treatment with a benzodiazepine recur in an enhanced form may occur on withdrawal of treatment. It may be accompanied by other reactions including mood changes, mild dysphoria, anxiety or sleep disturbances, abdominal and muscle cramps, vomiting, sweating, tremor 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 section 4.3 Posology and method of administration) but should not exceed eight to twelve weeks including tapering off process. Extension beyond these periods should not take place without re-evaluation of the situation.

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.

During discontinuation of Gerax treatment, the dosage should be reduced slowly in keeping with good medical practice. It is suggested that the daily dosage of alprazolam be decreased by no more than 0.5 mg every three days. Some patients may require an even slower dosage reduction.

Amnesia

Benzodiazepines may induce anterograde amnesia. The condition occurs most often several hours after ingesting the product and therefore to reduce the risk patients should ensure that they will be able to have an uninterrupted sleep of 7-8 hours (see also section 4.8 undesirable effects).

Psychiatric and 'paradoxical'reactions

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. Should this occur, use of the drug should be discontinued.

They are more likely to occur in children and the elderly.

Specific patient groups

Benzodiazepines should not be given to children without careful assessment of the need to do so, the duration of treatment must be kept to a minimum. Elderly should be given a reduced dose (see section 4.2 Posology and method of administration). Use Gerax with caution in elderly patients as there is a risk of falls and consequently of hip fractures secondary to the myorelexant effects of benzodiapines.

A lower dose is also recommended for patients with chronic respiratory insufficiency due to the risk of respiratory depression. Benzodiazepines are not indicated to treat patients with severe hepatic insufficiency as they may precipitiate encephalopathy.

Benzodiazepines are not recommended for the primary treatment of psychotic illness.

Benzodiazepines should not be used alone to treat depression or anxiety associated with depression (suicide may be precipitated in such patients). Benzodiazepines should be used with extreme caution in patients with a history of alcohol or drug abuse.

Administration to severely depressed or suicidal patients should be done with appropriate precautions and appropriate size of the prescription.

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

Not recommended Concomitant intake with alcohol

The sedative effect may be enhanced when the product is used in combination with alcohol. This affects the ability to drive or use machines.

Take into account Concomitant with CNS depressants

Enhancement of the central depressive effect may occur in cases of concomitant use with antipsychotics (neuroleptics), hypnotics, anxiolytics/sedatives, antidepressant agents, narcotic analgesics, anti-epileptic drugs, anaesthetics and sedative antihistamines.

In the case of narcotic analgesics enhancement of the euphoria may also occur leading to an increase in psychic dependence.

Compounds which inhibit certain hepatic enzymes (particularly cytochrome P450) may enhance the activity of benzodiazepines. To a lesser degree this also applies to benzodiazepines that are metabolised only by conjugation. Based on the degree of interaction and the data available currently, the following recommendations are made:

• The coadministration of Gerax with ketoconazole, itraconazole, or other azole-type antifungals is not recommended.

• Caution and consideration of dose reduction is recommended when Gerax is co-administered with nefazodone, fluvoxamine, and cimetidine.

• Caution is recommended when Gerax is coadministered with fluoxetine, propoxyphene, oral contraceptives, diltiazem, or macrolide antibiotics such as erythromycin and troleandomycin.

• Interactions involving HIV protease inhibitors (eg ritonair) and Gerax are complex and time dependent . Low doses of ritonavir resulted in a large impairment of Gerax clearance, prolonged its elimination half life and enhanced clinical effects. However, upon extended exposure to ritonavir, CYP3A induction offset this inhibition. This interaction will require a dose adjustment or discontinuation of Gerax.

Benzodiazepines including Gerax should only be used during pregnancy or lactation if considered essential by the physician. Animal studies with benzodiazepines have shown minor effects on the foetus while a few studies have reported late behavioural disturbance in offspring exposed in utero.

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 she is pregnant. If for compelling medical reasons, the product is administered during the late phase of pregnancy, or during labour, 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 dependence and may be at some risk for developing withdrawal symptoms in the postnatal period.

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

Sedation, amnesia, impaired concentration and impaired muscular function may adversely affect the ability to drive or to use machines. If sufficient sleep duration occurs, the likelihood of impaired alertness may be increased (see section 4.5 interactions with other medicaments and other forms of interactions).

These effects are potentiated by alcohol (see section 4.5 interactions with other medicaments and other forms of interaction). Patients should be cautioned about operating motor vehicles or engaging in other dangerous activities while taking Gerax.

Sedation/drowsiness, light-headedness, numbed emotions, reduced alertness, confusion, fatigue, headache, dizziness, memory impairment, muscle weakness, ataxia, double or blurred vision, insomnia, nervousness/anxiety, tremor, change in weight. These phenomena occur predominantly at the start of therapy and usually disappear with repeated administration. Side effects also decrease with decreased dosage. Other side effects like gastrointestinal disturbances, changes in libido or skin reactions have been reported occasionally. In addition, the following adverse events have been reported in association with the use of Gerax: dystonia, anorexia, slurred speech, jaundice, sexual dysfunction/changes in libido, menstrual irregularities, incontinence, urinary retention, abnormal liver function and hyperprolactinaemia. Increased intraocular pressure have been rarely reported.

Withdrawal symptoms have occurred following rapid decrease or abrupt discontinuance of benzodiazepines including Gerax. These can range from mild dysphoria and insomnia to a major syndrome, which may include abdominal and muscle cramps, vomiting, sweating, tremor and convulsions. In addition, withdrawal seizures have occurred upon rapid decrease or abrupt discontinuation of therapy with Gerax.

Amnesia

Anterograde amnesia may occur using therapeutic dosages, the risk increasing at higher dosages. Amnesic effects may be associated with inappropriate behaviour. (see section 4.4 special warnings and precautions for use).

Depression

Pre-existing depression may be unmasked during benzodiazepine use.

Psychiatric and 'paradoxical' reactions

Reactions like restlessness, agitation, irritability, aggressiveness, delusion, rages, nightmares, hallucinations, psychoses, inappropriate behaviour and other adverse behavioural effects are known to occur when using benzodiazepine like agents. They may be quite severe with this product. They are more likely to occur in children and the elderly.

Dependence

Use (even at therapeutic doses) may lead to the development of physical dependence: discontinuation of the therapy may result in withdrawal or rebound phenomena (see section 4.4 special warnings and precautions for use). Psychic dependence may occur. Abuse of benzodiazepines has been reported.

Manifestations of Gerax overdosage include extensions of its pharmacological activity, namely ataxia and somnolence. Induced vomiting and/or gastric lavage are indicated. As in all cases of drug overdosage, respiration, pulse and blood pressure should be monitored and supported by general measures when necessary. Intravenous fluids may be administered and an adequate airway maintained. Animal experiments have suggested that forced diuresis or haemodialysis are probably of little value in treating overdosage. As with management of any overdosage, the physician should bear in mind that multiple agents may have been ingested.

Alprazolam, like other benzodiazepines, has a high affinity for the benzodiapine binding site to the brain. It facilitates the inhibitory neurotransmitter action of gamma-aminobutyric acid which mediates both pre- and post-synaptic inhibition in the central nervous system (CNS).

Following oral administration, peak plasma concentrations are reached in about 1.7 hours. After a single oral dose of 500 micrograms, the average maximal concentration was 7.1 nanograms/ml. There is a linear relationship between the dose and plasma concentration. At least 80% of the oral dose is absorbed. About 70% of the absorbed dose is bound to plasma proteins. Alprazolam is extensively metabolised in the liver, primarily to hydroxylated metabolites, but about 20% of the dose is excreted as unchanged alprazolam. Elimination occurs mostly via the kidneys: 80% of the dose is excreted into the urine and only 7% into the faeces. The mean elimination half-life is 10-12 hours.

None given

250 microgram Tablet:

Lactose Monohydrate, Microcrystalline Cellulose, Maize Starch, Sodium Benzoate, Docusate Sodium, Povidone, Silica colloidal anhydrous, Sodium Starch Glycollate (Type A), Magnesium Stearate.

500 microgram Tablet:

Lactose Monohydrate, Microcrystalline Cellulose, Maize Starch, Sodium Benzoate, Docusate Sodium, Povidone, Silica colloidal anhydrous, Sodium Starch Glycollate (Type A), Magnesium Stearate, FD and C Blue No 2 aluminium lake (certified) E132 [Indigo carmine (aluminium lake)], Erythrosine (aluminium lake ) E127

1 mg Tablet:

Lactose Monohydrate, Microcrystalline Cellulose, Maize Starch, Sodium Benzoate, Docusate Sodium, Povidone, Silica colloidal anhydrous, Sodium Starch Glycollate (Type A) , Magnesium Stearate, FD and C Blue No 2 aluminium lake (certified) E132 [Indigo carmine (aluminium lake)]

Not applicable.

3 years

Do not store above 25°C. Keep container in the outer carton.

Tamper evident polypropylene securitainers fitted with polyethylene white caps and Jayfilla ullage filler. Or alternatively, perforated blister packs of PVC/foil.

Pack size: 100

Not all pack sizes may be marketed.

No special requirements.

McDermott Laboratories

T/a Gerard Laboratories

35/36 Baldoyle Industrial Estate

Grange Road

DUBLIN 13

PA 577/10/1

PA 577/10/2

PA 577/10/3

8 January 1996/ 8 January 2006

October 2007