Temazepam Tablets 10mg
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Temazepam Tablets 10mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 10mg Temazepam PhEur.
3 PHARMACEUTICAL FORM
White to off-white uncoated tablets
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Indicated for:
1) The short-term treatment of insomnia only when it is severe, disabling, or subjecting the individual to extreme stress, especially for those patients in whom the persistence of a hypnotic effect would be undesirable.
2) The premedication before minor surgical and investigative procedures particularly when hospital admission is not essential.
4.2 Posology and method of administration
Posology
The lowest effective dose should be employed, and treatment should, if possible, be intermittent. Dosage regimes should not extend beyond 4 weeks and treatment should gradually be withdrawn. Patients who have received benzodiazepines for a long time may require an extended withdrawal period. Long-term chronic use is not recommended.
Adults:
Insomnia: 10-20mg on retiring. A dose of 20mg will be found satisfactory for most patients. This may be increased to 30-40mg in patients who do not respond to the lower dose.
Premedication: 20-40mg, half an hour to one hour prior to surgical or investigative procedures.
It is recommended that patients should be accompanied home after medication with Temazepam prior to surgical or investigative procedures.
Elderly and patients suffering from cerebrovascular disease: Dosage should be reduced to possibly half the normal adult dose. In general hypnotics should be avoided in the elderly as they are at risk of becoming ataxic and confused. This may lead to falls and injury.
Children: Not recommended for children. The safety and efficacy in children less than 18 years old has not be established.
Method of Administration For oral administration.
4.3 Contraindications
Known hypersensitivity to benzodiazepines and any other ingredients in temazepam tablets.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Children aged 18 years or under.
Phobic or obsessional states; chronic psychosis (paradoxical reactions may occur)
Mild anxiety states
Acute pulmonary insufficiency; severe respiratory insufficency (ventilatory failure may be exacerbated) or CNS depression.
Acute narrow angle glaucoma (due to anticholinergic effects of temazepam) Myasthenia gravis (condition may be exacerbated)
Sleep apnoea (condition may be exacerbated)
Severe hepatic insufficiency (elimination half-life of temazepam may be prolonged)
Temazepam should not be used as monotherapy in patients with depression or those with anxiety and depression as suicide may be precipitated in such patients.
4.4 Special warnings and precautions for use
An underlying cause for insomnia should be sought before deciding upon the use of benzodiazepines for symptomatic relief.
Duration of Treatment - The duration of treatment should be as short as possible (see Posology and method of administration) depending on the indication, but should not exceed 4 weeks for insomnia, including tapering off process. Extension beyond these periods should not take place without reevaluation 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 minimizing anxiety over such symptoms should they occur while temazepam is being discontinued.
There are indications that, in the case of benzodiazepines with a short duration of action such as temazepam, withdrawal phenomena can become manifest between doses, 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.
Dependence and Withdrawal - (see Section 4.8 Undesirable Effects).
Withdrawal symptoms occur with benzodiazepines following normal therapeutic doses given for short periods of time.
Use of temazepam may lead to the development of physical and psychological dependence. The risk of dependence increases with the dose and duration of treatment, it is also greater in patients with a history of alcoholism 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, depersonalisation, 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 temazepam may recur in an enhanced form on withdrawal of treatment. It may be accompanied by other reactions including mood changes, anxiety or sleep disturbances 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.
Tolerance - Limits of tolerance in patients with organic cerebral changes (particularly arteriosclerosis) or cardiorespiratory insufficiency may be very wide; care must be taken in adapting the dosage with such patients.
Some loss of efficacy to the hypnotic effects of temazepam may develop after repeated use for a few weeks.
Care should be taken in patients with chronic renal or hepatic disease (elimination half-life of temazepam may be prolonged). Sedatives given to patients with cirrhosis may precipitate encephalopathy.
Alcohol should be avoided during treatment with temazepam (additive CNS depression).
Amnesia
Temazepam 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 uninterrupted sleep of 7-8 hours (see undesirable effects section 4.8).
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 medicinal product should be discontinued.
They are more likely to occur in children and the elderly.
Specific patient groups
Elderly should be given a reduced dose. (see Posology and method of administration). A lower dose is also recommended for patients with chronic respiratory insufficiency due to the risk of respiratory depression.
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.
In case of loss or bereavement, psychological adjustment may be inhibited by benzodiazepines.
Extreme caution should be used in prescribing temazepam to patients with personality disorders.
4.5 Interaction with other medicinal products and other forms of interaction
The following drug interactions with temazepam should be considered:
Take in to account: combination with CNS depressants
Enhancement of other CNS depressant drugs such as antipsychotics (neuroleptics), anxiolytics and sedatives, anti-epileptic products, narcotic analgesics (enhancement of euphoria may also occur, leading to an increase in psychological dependence), antidepressants, MAOIs, hypnotics, anaesthetics, sedative antihistamines, lofexidine, nabilone.
Alcohol -concomitant intake with alcohol is not recommended. The sedative effects may be enhanced when temazepam is used in combination with alcohol. This further affects the ability to drive or use machines.
Antiepileptic drugs -plasma phenytoin concentrations increased or decreased by temazepam, Phenytoin levels may need monitoring during temazepam withdrawal. Side effects may be more evident with hydantoins or barbiturates.
Antihypertensives -enhanced hypotensive effects. Enhances sedative effect with alpha blockers or moxonidine.
Antivirals -Concurrent use of zidovudine with benzodiazepines may decrease Zidovudine clearance. Ritonavir may inhibit benzodiazepine hepatic metabolism.
Clozapine -reports of cardiorespiratory collapse. Also increase in hypersalivation with both drugs.
Disulfiram -inhibits the metabolism of benzodiazepines and enhances sedative effect. May cause temazepam toxicity.
Dopaminergics -concurrent use with benzodiazepines may decrease the therapeutic effects of levodopa.
Muscle relaxants - Baclofen and Tizanidine -enhanced sedative effect. 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.
4.6 Pregnancy and lactation
The safety of temazepam has not been evaluated in humans and therefore its use should be avoided, especially in the first and third trimester.
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 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.
4.7 Effects on ability to drive and use machines
Sedation, visual disturbances, impaired concentration, amnesia and impaired muscular function may adversely affect the ability to drive or use machines. If insufficient sleep occurs, the likelihood of impaired alertness may be increased (see also Interactions).
Impaired function and sedation may occur the following morning. This may not be apparent. Patients should make sure they are not affected before driving or operating machinery.
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
4.8 Undesirable effects
The following phenomena occur predominantly at the beginning of therapy and may disappear with repeated administration: drowsiness (when the product is used as a hypnotic it should be stated explicitly: drowsiness during the day), numbed emotions, reduced alertness, confusion, fatigue, headache, dizziness, muscle weakness, ataxia, double vision, respiratory depression or slurred speech. These phenomena occur predominantly at the start of therapy and usually disappear with repeated administration.
Other adverse reactions like gastrointestinal disturbances, hypotension, changes in libido, dry mouth, restless sleep, dreams/nightmares, dysarthria, tremor, visual disturbances, hypersalivation, hypersensitivity, skin rashes, incontinence, urinary retention, blood dyscrasias and jaundice have been reported occasionally.
Amnesia. Anterograde amnesia may occur using therapeutic dosages, the risk increasing at higher dosages. Amnesic effects may be associated with inappropriate behaviour (see warnings and precautions).
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 benzodiazepines or 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 Warnings and precautions).
Psychological dependence may occur. Abuse of benzodiazepines has been reported.
Withdrawal effects on abrupt cessation of treatment - Depression, anxiety, headache, dizziness, impaired concentration, tinnitus, loss of appetite, tremor, perceptual disturbances, nausea, vomiting, abdominal cramps, palpitations, mild systolic hypertension, tachycardia, orthostatic hypotension, photophobia, hyperacusis, confusion, tension, nervousness, rebound insomnia, irritability, sweating and diarrhoea have been reported following abrupt cessation of treatment. In rare cases, withdrawal following excessive dosages may produce confusional states, psychotic manifestations and convulsions. Broken sleep with vivid dreams may persist for some weeks after withdrawal.
4.9 Overdose
As with other benzodiazepines, overdose should not present a threat to life unless combined with other CNS depressants (including alcohol).
In the management of overdose with any medicinal product, it should be borne in mind that multiple agents may have been taken.
Following overdose with oral benzodiazepines, vomiting should be induced (within one hour) if the patient is conscious or gastric lavage undertaken with the airway protected if the patient is unconscious. If there is no advantage in emptying the stomach, activated charcoal should be given to reduce absorption. Special attention should be paid to respiratory and cardiovascular functions in intensive care.
Following overdose with oral benzodiazepines activated charcoal should be given to reduce absorption. 50g for adults and 10-15g for children if they have taken more than 1mg/kg within 1 hour, provided they are not too drowsy.
Overdose 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 seious cases, symptoms may include ataxia, hypotonia, hypotension, respiratory depression, rarely coma and very rarely death.
Flumazenil may be useful as an antidote providing the overdose is not with mixed drugs.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
ATC CODE; N05C D07
Temazepam is a benzodiazepine with hypnotic and sedative effects as well as anxiolytic activity.
Temazepam effects are likely to be due to potentiation of gamma-aminobutyric acid (GABA), although other neurotransmitters may also be affected. Evidence suggests a close molecular association between the sites and action for GABA and the benzodiazepines.
5.2 Pharmacokinetic properties
Absorption: Temazepam is readily absorbed from the gastro-intestinal tract, although the exact rate of absorption depends on the formulation. Peak plasma levels are reached within 50 minutes if given orally, with multidosing steady state reached by the third day.
Distribution: It is about 96% bound to plasma protein. Temazepam is also found in breast milk in small amounts and may exert its effects on the infant.
Metabolism: Temazepam is mainly metabolised in the liver with a terminal half-life of between 8 and15 hours. This half-life depends on time of dose (morning administration has longer half-life than evening) and age of patient (elderly patients experience a longer half-life).
Elimination: 80% is excreted in the urine in the form of its inactive glucuronide conjugate together with small amounts of the demethylated derivative, Oxazepam, also in conjugated form. Only approximately 12 % appears in the faeces.
5.3 Preclinical safety data
Not applicable
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Also contains:
Lactose
Magnesium stearate Maize starch Povidone Colloidal silica
6.2 Incompatibilities
None known
6.3 Shelf life
Shelf-life
Two years from the date of manufacture.
Shelf-life after dilution/reconstitution Not applicable.
Shelf-life after first opening Not applicable.
6.4 Special precautions for storage
250pm white PVC/60g/m2 PVdC with 20pm aluminium foil blister packs
Store below 25°C. Store in the original package to protect from moisture. Keep the blister in the outer carton to protect from light.
All other containers
Store below 25°C in a dry place. Protect from light.
6.5 Nature and contents of container
The product containers are rigid injection moulded polypropylene or injection blow-moulded polyethylene containers with snap-on polyethylene lids; in case any supply difficulties should arise the alternative is amber glass containers with screw caps.
The product may also be supplied in blister packs and cartons:
a) Carton: Printed carton manufactured from white folding box board.
b) Blister pack: (i) 250pm white rigid PVC. (ii) Surface printed 20pm hard temper aluminium foil with 5-6g/M2 PVC and PVdC compatible heat seal lacquer on the reverse side or:
c) Blister pack: 250pm white PVC/60g/m2 PVdC with 20pm aluminium foil
Pack sizes: 7s, 21s, 28s, 30s, 50s, 56s, 60s, 84s, 100s, 112s, 250s, 500s, 1000s Product may also be supplied in bulk packs, for reassembly purposes only, in polybags contained in tins, skillets or polybuckets filled with suitable cushioning material. Bulk packs are included for temporary storage of the finished product before final packaging into the proposed marketing containers.
Maximum size of bulk packs: 50,000.
6.6 Special precautions for disposal
Not applicable
7 MARKETING AUTHORISATION HOLDER
Actavis UK Limited (Trading style: Actavis)
Whiddon Valley Barnstaple
North Devon EX32 8NS
8 MARKETING AUTHORISATION NUMBER
PL 00142/0363
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
03/01/1995 / 05/10/2005
10 DATE OF REVISION OF THE TEXT
30/10/2014