STESOLID(r) rectal tube Diazepam 5mg in 2.5ml and 10mg in 2.5ml solution.
Stesolid(r) is a clear colourless-to-slightly-yellowish aqueous liquid, in a yellow polyethylene tube. Stesolid(r) is available in a 5mg/2.5ml tube and 10mg/2.5ml tube, for rectal administration.
PHARMACOLOGICAL ACTIONS
Diazepam has anxiolytic, sedative, amnestic, hypnotic, anticonvulsant and muscle- relaxing activity. Diazepam acts centrally. As a benzodiazepine, it facilitates GABA-mediated synaptic inhibition. It is bound in the brain to specific benzodiazepine-receptors, which are found particularly in the limbic system, amygdaloid nucleus and the frontal cortex.
PHARMACOKINETICS
Absorption: diazepam is quickly absorbed from the rectal mucosa. The maximum serum concentration is reached within 17 minutes. Absorption by this route is 100%, and is therefore comparable in extent to an intravenous injection of diazepam formulated for IV injection. Diazepam is distributed systemically. In the blood it is 96-98% bound to plasma protein. It quickly passes the blood-brain barrier. It crosses the placenta and passes into breast milk. Diazepam is metabolised in the liver and its major metabolite, desmethyldiazepam, is pharmacologically active. The metabolites are excreted in the urine as glucuronide or sulphate. A very small amount is excreted via the bile. The plasma half-life of diazepam varies from person to person, and increases with age. The mean is about 50 hours. The half-life of desmethyldiazepam is about 100 hours.
INDICATIONS
For the treatment of febrile and childhood convulsions, where rapid onset of anticonvulsant activity is imperative.
For rectal administration only
| AGE GROUP | Dosage in mg | Number of 5mg/2.5mL tubes | OR | Number of 10mg/2.5mL tubes |
| Adults | 10-20mg | 2-4 | 1-2 | |
| Children(7-12 years): | 10mg | 2 | 1 | |
| Children(1-6 years) | 5mg | 1 | Not applicable |
If necessary, these doses may be repeated once only, after five minutes A maximum dose of 30 mg is recommended, unless adequate medical supervision and monitoring are available.
Administration
For rectal administration:
Position the patient with the buttocks raised. If a child, place the child across your knee.
Remove the tube cap and coat the opening of the nozzle with a little Vaseline.
Insert the entire length of the nozzle (about 5cm) into the anus.
In children less than three years of age, insert the nozzle half-way only. IMPORTANT: In order to empty the tube, the nozzle must point downwards. When the tube feels empty, keep squeezing it, while simultaneously withdrawing the nozzle. Keep the patient in the same position and press the buttocks together for a few minutes, to avoid seepage.
Hypersensitivity to diazepam or to benzodiazepines, or to any of the excipients listed later in this data sheet. Myasthenia gravis, severe respiratory insufficiency, sleep apnoea syndrome, severe hepatic insufficiency. Not for IV, IM or oral administration.
Benzodiazepines can cause blurred vision/dizziness and impair concentration. They can therefore affect ability to drive and to operate machinery.
Tolerance
After chronic use, tolerance will occur. For withdrawal of benzodiazepines, doses should be tapered off gradually, according to clinical response.
Dependence
Benzodiazepines can cause dependency, even in short-term use. Any course of treatment should be as brief as possible. The risk of dependence developing is greater in patients with a history of alcohol or drug abuse or with marked personality disorders. Extreme caution should be exercised when prescribing benzodiazepines to these individuals. Regular monitoring is essential, routine repeat prescriptions should be avoided and treatment should be withdrawn gradually.
Withdrawal and rebound insomnia
Once physical dependence has developed, abrupt termination of treatment will be accompanied by withdrawal symptoms (see 'Adverse effects'). Rebound insomnia and anxiety may also occur, especially after abrupt discontinuation of treatment. They may be accompanied by other reactions including mood changes or sleep disturbances and restlessness. Abrupt discontinuation may also result in convulsions and therefore particular care should be taken in patients with epilepsy, a history of seizures or a history of alcohol or drug abuse. Discontinuation should be gradual in order to minimise the risk of withdrawal symptoms or rebound insomnia. Diazepam should not be used together with alcohol as this can enhance the sedative effect of diazepam.
Amnesia
Benzodiazepines can cause anterograde amnesia, even if they are used within the normal dose range (though this is seen in particular at high dose levels).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. Amnestic effects may be associated with inappropriate behaviour.
Paradoxical reactions
Paradoxical reactions have been reported from the use of benzodiazepines (see 'Adverse effects'). Benzodiazepines should not be used alone to treat depression or anxiety associated with depression (suicide may be precipitated in such patients). Potentially suicidal individuals should not have access to large amounts of diazepam due to the risk of overdosing.
Pregnancy and Lactation:
Diazepam should only be used in pregnant women on compelling indication. Although there is no evidence that it induces teratogenic injury, diazepam, like other medicaments, should preferably not be used during pregnancy, especially during the first and last trimesters unless the benefit is considered to outweigh the potential risk. Data from animal experiments shows that the use of diazepam in the first trimester produces an increased risk of foetal abnormalities in the offspring. Since benzodiazepines are found in breast milk, benzodiazepines should not be given to breast feeding mothers.
The adverse effects of diazepam are usually mild and infrequent.
Common (>=1/100) Drowsiness, dizziness, balance disorders, ataxia, tremor, fatigue, confusion, impaired motor ability. Withdrawal symptoms are also considered a commonly occurring adverse effect after discontinuation of therapy. The likelihood and severity depends on the duration of treatment, dose level, and degree of dependency. Withdrawal symptoms include 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.
Uncommon (>1/1000 to <1/100)
Anterograde amnesia, concentration impairment, headache, slurred speech, respiratory depression, gastrointestinal disorders, increased salivation, allergic skin reactions, myasthenia.
Rare (>=1/10000 to <1/1000)
Unconsciousness, insomnia, respiratory arrest, increased bronchial secretion, bradycardia, heart failure including cardiac arrest, hypotension, syncope, dry mouth, increased appetite, jaundice, changes of hepatic parameters (elevation of ALT, AST, alkaline phosphatase), urinary retention, incontinence, gynaecomastia, impotence, changes in libido, dysarthria, emotional poverty, decreased alertness and depression (pre-existing depression may be unmasked with benzodiazepine use).Psychiatric and paradoxical reactions to benzodiazepines (provoking excitement instead of sedation) have been reported rarely. Reactions include restlessness, agitation, irritability, aggressiveness, delusion, rages, hallucinations, psychoses, memory loss, nightmares and inappropriate behaviour. In very rare cases anaphylaxis, leukopenia or elevation of transaminases may occur.
Post-marketing experience
Reversible vision disorders (blurred vision, diplopia and nystagmus) have also been reported during the post-marketing period.
Pharmacodynamic interactions
Diazepam, as a benzodiazepine, enhances the central depressive effects of other CNS-active agents, for example: alcohol, narcotic analgesics, anaesthetics (eg.ketamine), anti-epilepsy compounds (eg. phenobarbital), hypnotics, anxiolytics/sedatives, antidepressant agents, antipsychotics (eg. clozapine) and sedative antihistamines. Narcotic analgesics may also promote psychic dependency due to enhancement of euphorigenic effects. Concomitant use is not recommended with alcohol, phenobarbital or clozapine. Special caution is recommended for concomitant use with muscle relaxants such as suxamethonium or tubocurarin (where diazepam can enhance or reduce the intensity of the neuromuscular block) and for theophylline (competitive binding of theophylline to adenosine receptors may reduce the effect of diazepam).
Pharmacokinetic interactions
The effect of diazepam can be enhanced by agents that block or reduce its metabolism. Compounds that inhibit certain hepatic enzymes (particularly cytochrome P450, 2C19 and P3A4) can increase the effects of diazepam. Concomitant use is not recommended for antiviral agents (eg. atazanavir, ritonavir), azoles (eg. fluconazole, ketoconazole, itraconazole) and fluvoxamine. Special caution is recommended for concomitant use with disulfiram, omeprazole, esomeprazole, cimetidine, isoniazid, fluoxetine, oral contraceptives and grapefruit juice. Other compounds can induce hepatic enzyme activity and therefore decrease the effects of diazepam. Concomitant use is not recommended for rifamycins (eg. rifampicin), carbamazepine, phenytoin, phenobarbital. Special caution is recommended for concomitant use with corticosteroids. Special caution is also recommended in the use of cispride (which accelerates diazepam absorption) and valproic acid (which inhibits metabolism of diazepam). Agents on which diazepam exerts an effect include levodopa (diazepam causes a reduced effect of levodopa), and ketamine (diazepam blocks ketamine metabolism resulting in increased sedation).
Overdose of benzodiazepines usually presents as some degree of central nervous system depression, ranging from drowsiness to coma. In mild cases, symptoms include drowsiness, mental confusion and lethargy; in more severe cases, symptoms may include ataxia, hypotonia, hypotension, respiratory depression, hypothermia, bradycardia, dysarthria, rarely coma and very rarely death. Overdose of diazepam should not present a threat to life unless administered to a recipient affected by CNS depressants, including alcohol. Emergency management of overdosage: Gastric lavage and adequate airway maintenance may be necessary. Otherwise, management is symptomatic. Intravenous fluids may be administered and flumazenil may be useful as an antidote. For information on the management of overdose, contact the New Zealand Poison Information Centre on 0800 POISON (0800 764 766).
Benzoic acid, ethanol, propylene glycol, sodium benzoate, benzyl alcohol, purified water.
Store in a cool place below 25oC and away from light.
Prescription Medicine. CONTROLLED DRUG C5. PACKAGE QUANTITIES Boxes of five rectal tubes.
Nil
bioCSL (NZ) Ltd 666 Great South Road Penrose, Auckland 1061 New Zealand Phone 0800 502 757
Under licence from:
Actavis Group PTC ehf. Reykjavikurvegi 76-78
220 Hafnarfjordur Iceland
October 2013
Stesolid(r) is a trademark of Actavis Group PTC ehf. (Iceland).