INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
HALCION 0,125 mg (Tablets)
HALCION 0,25 mg (Tablets)

SCHEDULING STATUS:
S5

PROPRIETARY NAME
(and dosage form):

HALCION 0,125 mg (Tablets)
HALCION 0,25 mg (Tablets)

COMPOSITION:
Each tablet contains 0,125 mg or 0,25 mg triazolam.

PHARMACOLOGICAL CLASSIFICATION:
A 2.2 Sedatives, hypnotics

PHARMACOLOGICAL ACTION:
HALCION is a short-acting benzodiazepine type hypnotic agent which significantly affects REM or stage III and IV sleep. Latency to stage REM I increases significantly.
Triazolam is rapidly and nearly completely absorbed. Peak plasma concentrations are achieved within one hour of administration by mouth. Triazolam has a short elimination half life ranging 2-4 hours.

INDICATIONS:
HALCION is indicated for transient and short-term treatment of insomnia. HALCION is only indicated when the disorder is severe, disabling or subjecting the individual to extreme stress.

CONTRA-INDICATIONS:
HALCION is contra-indicated in patients with known sensitivity to benzodiazepines.
It is contra-indicated in mental depression (unless there is a marked component of anxiety in their illness), pre-existing central nervous system depression or coma and psychiatric patients with suicidal tendencies. (See SIDE-EFFECTS AND SPECIAL PRECAUTIONS)
HALCION should not be used for long-term treatment of insomnia.
HALCION is contra-indicated in pregnant women and women at risk of pregnancy due to insufficient clinical data at this stage.
HALCION should not be given during labour because it crosses the placenta and can cause the floppy-infant syndrome characterised by central respiratory depression, hypothermia and poor sucking. HALCION should not be used by nursing mothers because metabolites are excreted in the milk.
The safety and efficacy in patients under the age of 18 years have not been established.

WARNINGS:
Patients should be cautioned against hazardous occupations requiring mental alertness such as operating machinery or driving a motor vehicle, the day after a night time dose of triazolam, until it is established that they do not exhibit daytime drowsiness or dizziness.
When HALCION is used at recommended doses for short-term treatment, the dependence potential is low. However, the risk of dependence with benzodiazepines increases with higher doses and long term use and is further increased in patients with a history of alcoholism and drug abuse. Once physical dependence has developed after long periods of ordinary therapeutic doses or multiple daily doses of HALCION, abrupt termination will be accompanied by withdrawal symptoms which may consist of headaches, muscle pain, extreme anxiety, tension, restlessness, confusion and irritability. In severe cases the following symptoms may occur : derealisation, depersonalisation, hyperacusis, numbness and tingling of extremities, hypersensitivity to light, noise and physical contact, hallucinations or epileptic seizures. Patients with a history of seizures should not be abruptly withdrawn from HALCION.

DOSAGE AND DIRECTIONS FOR USE:
It is important to individualise the dosage of HALCION tablets for maximum beneficial effect and to help avoid significant adverse effects. The recommended dose for adults is 0,25 mg before retiring. A dose of 0,5 mg should be reserved for those patients who do not respond adequately to a lower dose.
A dose of 0,125 mg may be found to be sufficient for selected, geriatric and/or debilitated patients. Therapy should be initiated at 0,125 mg in this group until individual response is determined and can then be increased to 0,25 mg if necessary. The lowest effective dose should be used.
Treatment should be as short as possible . Generally the duration of treatment varies from a few days to two weeks, with a maximum, including tapering off process, of four weeks. In certain cases extension beyond the recommended treatment period may be necessary; if so, it should not take place without re-evaluation of the patient’s status.

SIDE EFFECTS AND SPECIAL PRECAUTIONS:
Dose related side-effects:
Sedation (drowsiness, grogginess, dizziness, light-headedness, amnesia, ataxia and/or impaired co-ordination), considered to be an extension of the pharmacology activity of the medicine. The incidence and severity of these pharmacological events are generally dose related. The relationship of dose with the risk of other adverse actions has not been established. In accordance with good medical practice, it is recommended that therapy be initiated at the lowest effective dose.
Severe sedation and impaired co-ordination are indicative of drug intolerance or overdosage. (See KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT)
Most frequently occurring side-effects:
Headache may occur.
Less frequently occurring side-effects:
Less frequent adverse reactions which have been reported are taste alteration, euphoria, memory impairment and central nervous system depression. Adverse reactions which have been reported are blurred vision, hiccups, palpitations, epigastric discomfort, diarrhoea and burning eyes. Other side effects noted are agitation, paresis, somnambulism, changes in libido, changes in salivation, tremor, dysarthria, urinary retention, vertigo, hypotension, incontinence, slurred speech, and mental depression.
Rarely reported side-effects:
Aggressiveness, dizziness and falling, transient insomnia after drug discontinuance, hallucinations, syncope, jaundice, blood disorders, hypersensitivity reactions (pruritus, skin rash).As with other benzodiazepines and central nervous system active medicines, the idiosyncratic symptom clusters, which may overlap, have been reported rarely with triazolam: amnesic symptoms (anterograde amnesia of varying severity, with appropriate or inappropriate behaviour); confusional states (disorientation, derealisation, depersonalisation, and/or clouding of consciousness); and an agitational state (restlessness, irritability and excitation).
Frequently, other factors may contribute to these idiosyncratic reactions, e.g. concomitant intake of alcohol or other medicines, sleep depravation, an abnormal premorbid state, etc. Paradoxical or inappropriate behaviour (including dissociation and depersonalization) and acute transient psychotic episodes, have occasionally been reported following therapeutic doses of triazolam.
Precautions:
In elderly and/or debilitated patients, it is recommended that treatment with triazolam be initiated at 0,125 mg to decrease the possibility of development of over-sedation, dizziness or impaired co-ordination. In other adults the recommended dose is 0,25 mg.
A transient syndrome, whereby the symptoms that led to treatment with triazolam recur in an enhanced form, may occur on withdrawal of treatment. 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 (See WARNINGS).
The duration of treatment should be as short as possible. (See DOSAGE AND DIRECTIONS FOR USE), but should not exceed 4 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 be aware of the possibility of rebound phenomena, thereby minimising anxiety over such symptoms, should they occur while the product is being discontinued.
Triazolam is not recommended for the primary treatment of psychotic illness. Triazolam should not be used alone to treat depression or anxiety with depression (suicide may be precipitated in such patients). It should be used with extreme caution in patients with history of alcohol or drug abuse.
Clinical trials in depressed patients have not shown exacerbation of depression by triazolam; however, caution should be exercised if the patient is in a depressed state or reveals evidence of a latent depression since these conditions may be intensified by hypnotic agents. Although benzodiazepines are not depressogenic, they may be associated with mental depression which may or may not be associated with ideas of suicide or suicidal attempts. This occurs in a rare or unpredictable fashion. The prescription size must be limited in patients with signs and/or symptoms of a depressive disorder or suicidal tendencies, also in addiction prone individuals and for patients who are not under medical supervision. (See WARNINGS)
Caution must also be exercised in pulmonary insufficiency. In patients with compromised respiratory function, respiratory depression and apnoea have been reported infrequently. Caution is required in patients with organic brain changes, particularly arteriosclerosis.
Triazolam is mainly excreted after metabolism by the liver; therefore caution is required in patients with impaired liver and kidney function.
Interactions:
If HALCION is to be combined with other drugs having known hypnotic properties or central nervous system depressant effects, consideration should be given to potential additive effects.
HALCION plasma concentrations may approximately double when cimetidine is co-administered. The co-administration of triazolam and cimetidine results in a reduction of triazolam clearance without a change in elimination half-life in most subjects. The elimination half-life may be prolonged in some subjects, but does not result in drug accumulation on once-daily dosing.
Triazolam plasma concentrations may double when erythromycin is co-administered. The co-administration of triazolam and erythromycin or clarithromycin results in a reduction of triazolam clearance without an increase in elimination half-life.
Caution and consideration of dose reduction is recommended when HALCION is co-administered with troleandomycin
It is recommended that HALCION not be taken for sleep of less than 7-8 hours, since amnestic episodes have been reported.
Interactions with drugs involve antibacterial agents, antimycobacterial agents, gastro-intestinal agents and oral contraceptives.
Compounds which inhibit certain hepatic enzymes (particularly cytochrome P450IIIA4) may increase concentration of triazolam and enhance its activity. Varying degrees of interaction and possible interaction with triazolam for a number of medicine was reported. Based on the degree of interaction and type of data available the following recommendations are made:
The co-administration with ketoconazole , itraconazole and nefazodone is contra-indicated. Co-administration with other azole-type antifungals is not recommended.
Caution is recommended when triazolam is co-administered with isoniazid, fluvoxamine, paroxetine, diltiazem, verapamil, sertraline.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Manifestations of HALCION (triazolam) overdosage include extensions of its pharmacological action, namely somnolence and hypnosis. Other symptoms of overdosage include impaired co-ordination, slurred speech, confusion and ultimately coma . Respiratory and cardiovascular depression, apnoea and hypotension have been reported with overdosage of HALCION. Seizures have occasionally been reported after overdosage.
As in all cases of drug overdosage, respiration, pulse and blood pressure should be monitored and supported by general measures when necessary. Immediate gastric lavage should be performed. Intravenous fluids should be administered and an adequate airway maintained. Treatment for overdosage is generally symptomatic and supportive.
Experiments in animals have indicated that cardio-pulmonary collapse can occur with massive intravenous doses (over 100 mg/kg –500 times the maximum daily human dose) of HALCION. This could be reversed with positive mechanical respiration and the intravenous infusion of levarterenol or metaraminol. Other animal experiments have suggested that haemodialysis and forced diuresis are probably of little value. As with the management of intentional overdosage with any drug, the physician should bear in mind that multiple agents may have been ingested by the patient.

IDENTIFICATION:

HALCION 0,125 mg	-	Lavender elliptical, flat, bevelled tablet with "Upjohn 10" on the one side.
HALCION 0,25 mg	-	Powder blue elliptical tablet, scored on the one side and "Upjohn 17" impressed on the other side.

PRESENTATION:
HALCION 0,125 mg tablets are available in blister packs of 10, 30 and 100 tablets.
HALCION 0,25 mg tablets are available in blister packs of 10, 30 and 100 tablets and in glass bottles of 500 tablets.

STORAGE INSTRUCTIONS:
Store at room temperature (15 - 30°C)
Protect from moisture and light.
Keep out of reach of children.

REGISTRATION NUMBERS:

HALCION 0,125 mg tablets -	T/2.2/99
HALCION 0,25 mg tablets -	J/2.2/320

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
Pharmacia South Africa (Pty) Ltd
Alphen West G
George Street
Midrand 1685

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
21 May 1997

New addition to this site: January 2005
Source: Pharmaceutical Industry
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