NORMISON (Temazepam) is a 1,4 benzodiazepine with the chemical name 7-chloro-1,3-dihydro-3-hydroxy-1-methyl-5-phenyl-2H-1-4-benzodiazepin-2-one. Its structural formula is:
Temazepam is a white, odourless crystalline powder; it is sparingly soluble in alcohol and freely soluble in chloroform, but insoluble in water. The molecular weight is 300.8.
NORMISON is available as soft gelatin capsules.
NORMISON 10 mg capsules also contain macrogol 400, gelatin, anidrisorb 85/70, titanium dioxide, sunset yellow and glycerol.
NORMISON 20 mg capsules also contain macrogol 400, gelatin, sodium ethyl hydroxybenzoate, sodium propyl hydroxybenzoate, titanium dioxide, sunset yellow and glycerol.
NORMISON hastens the onset of sleep and increases total sleeping time in short term use.
The exact mechanism of action of benzodiazepines has not yet been elucidated; however, benzodiazepines appear to work through several mechanisms. Benzodiazepines presumably exert their effects by binding to specific receptors at several sites within the central nervous system either by potentiating the effects of synaptic or pre-synaptic inhibition mediated by gamma-aminobutyric acid or by directly affecting the action potential generating mechanisms.
Pharmacokinetic studies have shown that NORMISON is well absorbed and has a relatively short elimination half-life of approximately 10 hours (range 5 - 15 hours). Peak plasma levels of the drug occur 35 to 65 minutes after administration of the capsules. , With multiple dosing, steady state is obtained by the third day, and there is little or no accumulation of parent drug or metabolites.
NORMISON is metabolised principally in the liver where most drug is directly conjugated to the glucuronide and excreted in the urine. Some drug is demethylated to oxazepam and eliminated as the glucuronide. The glucuronides of NORMISON have no demonstrable CNS activity. Following a single oral dose, 80% of the dose appears in the urine, mostly as the conjugates, and 12% of the dose appears in the faeces. Less than 2% of the dose is excreted unchanged in the urine. Approximately 96% of unchanged drug is bound to plasma proteins.
NORMISON is indicated for use as a hypnotic or night-time sedative. As a hypnotic, NORMISON is indicated for severe or disabling insomnia characterised by difficulty in falling asleep, frequent nocturnal awakenings and/or early morning awakening.
NORMISON is indicated for use as a premedicant taken 30-60 minutes prior to surgical or other procedures.
NORMISON is contraindicated in:
Rebound phenomena have been described in the context of benzodiazepine use. Rebound insomnia and anxiety mean an increase in the severity of these symptoms beyond pre-treatment levels following cessation of benzodiazepines. Rebound phenomena in general possibly reflect re-emergence of pre-existing symptoms combined with withdrawal symptoms described earlier. Some patients prescribed benzodiazepines with very short half-lives (in the order of 2 to 4 hours) may experience relatively mild rebound symptoms in between their regular doses. Withdrawal/rebound symptoms may follow high doses taken for relatively short periods.
Benzodiazepines cross the placenta and may cause hypotonia, reduced respiratory function and hypothermia in the newborn infant. Continuous treatment during pregnancy and administration of high doses in connection with delivery should be avoided. Withdrawal symptoms in newborn infants have been reported with this class of drugs.
The use of benzodiazepines during the first trimester of pregnancy should almost always be avoided. If the drug is prescribed to a woman of child-bearing potential, she should be warned to contact her physician regarding discontinuation of the drug if she intends to become or suspects that she is pregnant.
Non-Teratogenic Effects - The use of benzodiazepines during the last phase of pregnancy or at delivery may require ventilation of the infant at birth.
In animal studies an increased perinatal mortality has been seen following concomitant administration of temazepam and diphenhydramine to rabbits in the later stages of gestation compared with rabbits that received either drug alone. It is recommended that the use of temazepam be avoided in pregnant women receiving antihistamines.
Impairment of Fertility - Fertility in male and female rats was not adversely affected by temazepam.
Caution should be exercised when NORMISON is given to breast feeding women.
NORMISON is believed to be excreted in human breast milk and may cause drowsiness and feeding difficulties in the infant.
The safety and effectiveness of temazepam has not been established in children less than 16 years of age.
No interference with laboratory tests have been identified or reported with the use of temazepam.
All adverse reactions reported with temazepam are common with other benzodiazepine compounds.
Nervous System: dizziness, headache, vertigo.
Biochemical: elevated SAP, AST, BUN, bilirubin; proteinuria, neutrophil leucocytosis.
Cardiovascular: palpitation, tachycardia.
Dermatological: macular rash, pruritus.
Gastrointestinal: dry mouth, nausea, vomiting, gastrointestinal upset.
Miscellaneous: loss of taste.
Musculo-Skeletal: leg cramps, weakness.
Nervous System: confusion, disorientation, muzziness, sciatica, tremor, faintness.
Ocular: blurred vision.
Psychiatric: depression, irritability, vivid dreams.
Paradoxical reactions such as stimulation, excitement or rage rarely occur (see Precautions).
For use as a hypnotic, the usual adult dose is 20 mg taken one-half hour before retiring. In elderly or debilitated patients, 10 mg NORMISON is the initial recommended dosage.
The recommended dosage range in adults is 10 to 30 mg but dosage should be individualised to the lowest effective dose.
For use as a premedicant, the recommended adult dose is 20-30 mg taken 30-60 minutes prior to surgical or other procedures.
Since insomnia is often transient and intermittent, the prolonged administration of NORMISON is generally not necessary or recommended. In general, hypnotics should be prescribed for short periods only (not more than 2-4 weeks) unless the patient is already reliant on regular hypnotic use. Continuous long term use of NORMISON is not recommended, but intermittent use may be appropriate.
For patients already receiving long-term NORMISON, it is recommended that the need for continued therapy be reviewed periodically.
Overdosage of benzodiazepines is usually manifested by degrees of central nervous system depression ranging from drowsiness to coma. In mild cases, symptoms include drowsiness, mental confusion and lethargy. In more serious cases, symptoms may include ataxia, hypotonia, hypotension, respiratory depression, coma, and very rarely proves fatal.
Treatment: In the management of overdosage with any medication, it should be borne in mind that multiple agents may have been taken.
Following overdosage with oral benzodiazepines, vomiting should be induced (within one hour) if the patient is conscious or gastric lavage undertaken with the airways protected if the patient is comatose. If there is no advantage in emptying the stomach, activated charcoal should be given to reduce absorption. Hypotension and respiratory depression should be managed according to general principles.
Haemoperfusion and haemodialysis are not useful in benzodiazepine intoxication. The benzodiazepine antagonist flumazenil may be used in hospitalised patients for the reversal of acute benzodiazepine effects. Please consult the flumazenil product information prior to usage.
Capsules, 10 mg (soft gelatin, pale orange): 100's HDPE bottles
20 mg (soft gelatin, pale orange, marked WY20): 100's HDPE bottles
Controlled Drug C5
Capsules: Store below 25°C in a cool dry place.
Zuellig Pharma Limited
54 Carbine Road
Telephone: (09) 570 1080
19 May 2002