Temazepam

Temazepam (marketed under brand names Restoril®, Normison®, Tenox® and Temaze®) is a powerful hypnotic drug, which is a benzodiazepine derivative. It possesses powerful anxiolytic, hypnotic, anticonvulsant, amnestic, sedative and skeletal muscle relaxant properties.

History
Until recently temazepam was produced as a gel-filled capsule intended to be taken orally. However, it gained a certain notoriety in the United Kingdom, and especially Scotland, when it was discovered that if the capsules were melted and injected the effects were more potent and similar to alcohol. However, the liquid has a tendency to congeal in arteries and cause thrombosis and gangrene, in some cases requiring amputation.

Pharmacology
The pharmacological action of temazepam is thought to be the result of its facilitating the action of gamma aminobutyric acid (GABA), an inhibitor neurotransmitter.

Temazepam is an active benzodiazepine with powerful hypnotic properties. In sleep laboratory studies, temazepam dramatically decreased the number of nightly awakenings. Rebound insomnia was not observed after withdrawal of the drug. Temazepam decreased stage 3, and combined stage 3 and 4 sleep, accompanied by a compensatory increase in stage 2 sleep, but did not alter REM sleep.

Orally administered temazepam is well absorbed in humans. Temazepam has a half-life of about 8 to 10 hours in plasma (with considerable inter-individual variability). On multiple dosing, steady state is reached usually within 3 to 5 days with excretion of the drug mainly in the urine in the form of the inactive O-conjugate metabolite.

Indications
Temazepam is commonly prescribed for insomnia and other serious sleep disorders. Temazepam is considered to be one of the most addictive of the benzodiazepines and thus not suited for long-term treatment. Street terms include "rugby balls", "terms", "jellies", "mazzies", "beans", "eggs", and "yellow jackets".

Military Use
The United States Air Force uses temazepam under trade name Restoril as "no-go pills" to help pilots sleep after a mission (Cf. "go-pills"; dextroamphetamine, or recently modafinil, used as a stimulant for pilots). Another drug used for the same purpose is zolpidem.

Dosage


When used for treatment of insomnia, the usual dose is 7.5mg to 15mg taken at bedtime but can be used at doses up to 30mg.

In the United States, temazepam is available in 7.5mg, 15mg, 22.5mg and 30mg capsules.

It is available as 10 and 20mg tablets in the UK and Finland, but also in at least some countries in the rest of Europe.

In Australia it is only available in 10mg tablets. 20mg tablets and Temazepam in capsule or gelcap form is no longer available in that country.

Usual UK doses (from BNF) are 10-20mg at bedtime, max 30-40mg in exceptional circumstances.

Abuse potential
Studies suggest that temazepam is a particularily euphoric benzodiazepine, and along with other hypnotic benzodiazepines, particularily, flunitrazepam, nitrazepam, and nimetazepam, it is considered to have the highest abuse potential of all benzodiazepines. In the UK, temazepam has superseded diazepam, nitrazepam and flurazepam as the most commonly abused benzodiazepine, in line with the increase in temazepam prescriptions and possibly (until recently) because of the availability of easily injectable forms of temazepam from capsules, 'jellies', 'eggs' (Stark et al. 1987). Benzodiazepines have been injected but at present temazepam is mainly involved. Strang et al. (1994) conducted a questionnaire survey of subjects attending drug clinics in seven British cities. Of 208 subjects returning the questionnaire, 186 had used benzodiazepines and 103 had injected them intravenously. Temazepam was the most commonly used and had been injected from preparations of capsules, tablets and syrup.

Temazepam (whether obtained from capsules, tablets or elixir), is extremely irritating and likely to cause tissue damage. When arm veins become occluded due to local irritation, users may proceed to injecting in the groin, where inadvertent intra-arterial injection has led to amputation. The severity of the addiction which can develop to temazepam is illustrated by the case of a temazepam injector who needed his leg amputated but was later admitted for a second amputation since he had continued injecting into his remaining leg (Parrott 1995). A second subject, following a leg amputation, injected temazepam gel into his eye, resulting in bilateral blindness. 

Side effects
Common side effects include:
 * Somnolence
 * Impaired motor function
 * Impaired coordination
 * Impaired balance
 * Euphoria
 * Sluggishness
 * Anterograde amnesia
 * Confusion
 * Lack of concentration

Rare side effects include:
 * Neurological - Agitation, anxiety, headache, depression, hallucinations, hangover, increased dreaming, lack of coordination, loss of equilibrium, nightmares, restlessness, vertigo
 * Cardiovascular - Cardiac arrhythmia
 * Respiratory - Difficult or labored breathing, hypoventilation
 * Gastrointestinal - Abdominal discomfort, diarrhea, vomiting
 * Ocular - Blurred vision, burning sensation in eyes, nystagmus
 * Other - Abnormal sweating, backache, dry mouth, muscular weakness

Before taking temazepam, one should ensure that at least 8 hours are available to dedicate to sleep. Failing to do so can increase the side effects of the drug.

Long-term use of temazepam can result in psychological and physical dependence and the appearance of withdrawal symptoms when the drug is discontinued. Temazepam impairs cognitive and psychomotor functions, affecting reaction time and driving skill. The use of this drug in combination with alcohol potentiates these side effects, and can lead to toxicity and death.

From a research perspective, there are some data suggesting that temazepam may be more frequently involved in drug-related deaths than are some other benzodiazepines. Temazepam produced more sedation than did other benzodiazepines, in overdose situations. Thus, there is some reason to think that temazepam (once taken in overdose) may have greater toxicity than other benzodiazepines.

Interactions
See Diazepam.

Contraindications
Use of temazepam should be avoided, when possible, in individuals with the following conditions:
 * Ataxia
 * Severe hypoventilation
 * Acute narrow-angle glaucoma
 * Severe hepatic deficiencies (hepatitis and liver cirrhosis decrease elimination by a factor of 2)
 * Severe renal deficiencies (e.g. patients on dialysis)
 * Severe sleep apnea
 * Severe depression, particularly when accompanied by suicidal tendencies
 * Acute intoxication with alcohol, narcotics, or other psychoactive substances
 * Myasthenia gravis
 * Hypersensitivity or allergy to any drug in the benzodiazepine class

Special caution needed

 * Pregnant Women - temazepam may cause fetal damage when administered during pregnancy.
 * Pediatric patients
 * Less than 18 years of age - Safety and effectiveness have not been established; temazepam should generally not be given to individuals under 18 years of age
 * Under 6 months of age - Safety and effectiveness have not been established; temazepam should not be given to individuals in this age group.


 * Elderly and very ill patients - Possibility that apnea and/or cardiac arrest may occur. Concomitant use of other central nervous system depressants increases this risk. The smallest possible effective dose should be used for this group of patients.

Patients at a high risk for abuse and dependence
Temazepam can lead to physiological tolerance, and psychological and/or physical dependence. At a particularly high risk for temazepam misuse, abuse, and dependence are:
 * Patients with a history of alcohol or drug abuse or dependence
 * Emotionally unstable patients
 * Patients with severe personality disorders, such as Borderline Personality Disorder
 * Patients with chronic pain or other physical disorders

Patients from the aforementioned groups should be monitored very closely during therapy for signs of abuse and development of dependence. Discontinue therapy if any of these signs are noted. Long-term therapy in these patients is not recommended.

Overdose
Manifestations of acute overdosage of temazepam can be expected to reflect the increasing CNS effects of the drug and include:
 * Somnolence (difficulty staying awake)
 * Mental confusion
 * Respiratory depression
 * Hypotension
 * Impaired motor functions
 * Impaired or absent reflexes
 * Impaired coordination
 * Impaired balance
 * Dizziness
 * Coma

Temazepam overdose is considered a serious medical emergency and generally requires the immediate attention of medical personnel. The antidote for an overdose of temazepam (or any other benzodiazepine) is flumazenil (Anexate®).

If the patient is conscious, vomiting should be induced mechanically or with emetics (e.g., syrup of ipecac 20 to 30 mL). Gastric lavage should be employed as soon as possible, utilizing concurrently a cuffed endotracheal tube if the patient is unconscious, in order to prevent aspiration and pulmonary complications. Maintenance of adequate pulmonary ventilation is essential and fluids should be administered IV to encourage diuresis. The use of pressor agents IV, may be necessary to combat hypotension but only if considered essential. The value of dialysis in emergency therapy for benzodiazepine overdosage has not been determined. If excitation occurs, barbiturates should not be used. It should be borne in mind that multiple agents may have been ingested.

The oral LD50 of temazepam was 1963 mg/kg in mice, 1833 mg/kg in rats, and >2400 mg/kg in rabbits.

Legal Status
Temazepam is a Class C drug in the United Kingdom and possession is illegal without a prescription. Additionally, all manufacturers in the UK have replaced the gel-capsules with solid tablets.

In the US, temazepam is a Schedule IV drug and is only available by prescription. Certain states require specially coded prescriptions for this medication.

Internationally, temazepam is a Schedule IV drug under the Convention on Psychotropic Substances.

In Canada Temazepam can be issued as a standard prescription by any family doctor who sees a need for it.

In Australia Temazepam is Schedule 4 requiring a doctors prescription no repeats are allowed. All Schedule 4 drugs can only be obtained from a pharmacy in the same state or territory in which the prescription was issued.

Trivia
Temazepam tablets are called Jellies, Tems, Temazzies, Eggs, Green Eggs, Norries, and Rugby balls.

The recreational effects of the drug were documented in the Black Grape album, It's Great When You're Straight... Yeah. The track 'Tramazi Parti' contains the lyric: I got my boots on the back of my head / It's full of jellies in the good old bed / And no one knows what no one said. Although there is no medical research confirming this behaviour, it is not inconsistent with the known side effects of the drug.

On the BBC radio series The Archers, Jolyon Gibson's Christmas present to Kate was a bottle of temazepam capsules. Feeling depressed on New Year's Eve 1995, Kate took whisky and the "jellies" together and ended up in hospital.