Brand name: T-Quil, Valium
Diazepam
Brand name: T-Quil, Valium |
|
Anxiolytic - Sedative - Muscle Relaxant
Diazepam is a benzodiazepine with CNS depressant properties and a somewhat flatter dose-response slope than the sedative-hypnotic drugs. In laboratory animals, it produces, in varying doses, taming, disinhibitory, sedative, anticonvulsant, muscle relaxant, ataxic and hypnotic effects.
Diazepam is relatively devoid of autonomic effects and does not significantly reduce locomotor activity at low doses, or depress amphetamine-induced excitation. In high doses, it activates the drug metabolizing enzymes in the liver. Diazepam also possesses dependence liability and may produce withdrawal symptoms, but has a wide margin of safety against poisoning.
Metabolism studies in animals and man have indicated that oral diazepam is rapidly absorbed from the gastrointestinal tract. Peak blood levels are reached within 1-2 hours after administration. The acute half-life is 6-8 hours with a slower decline thereafter, possibly due to tissue storage.
In humans, comparable blood levels of diazepam were obtained in maternal and cord blood indicating placental transfer of the drug. Diazepam may appear in human breast milk.
With the parenteral form, peak blood levels are reached within 15 minutes after i.v. administration and are of the same magnitude as after oral administration. The respective half-life is approximately 2-3 hours.
The distribution and fate of tritium-labeled diazepam in man has indicated that the drug has a rapid and extensive uptake by tissues. Although the radioactivity in the blood appears to represent mainly the intact drug, diazepam was shown to be excreted exclusively in the form of its metabolites. The two major metabolites are oxazepam glucuronide and N-desmethylated diazepam.
The short-term symptomatic management of mild to moderate degrees of anxiety in conditions dominated by tension, excitation, agitation, fear or aggressiveness, such as may occur in psychoneurosis, anxiety reactions due to stress conditions and anxiety states with somatic expression.
In acute alcoholic withdrawal, diazepam may be useful in the symptomatic relief of acute agitation, tremor and impending acute delirium tremens.
As an adjunct for the relief of skeletal muscle spasm due to reflex spasm to local pathology, such as inflammation of the muscle and joints or secondary to trauma; spasticity caused by upper motor neuron disorders, such as cerebral palsy and paraplegia; athetosis and the rare stiff man syndrome.
Myasthenia gravis, known hypersensitivity to benzodiazepines. Not recommended for children under 6 months of age.
Pregnancy:
Several studies have suggested an increased risk of congenital malformations
associated with the use of diazepam, chlordiazepoxide and meprobamate
during the first trimester of pregnancy. Therefore, the administration
of diazepam is rarely justified in women of childbearing potential. If
the drug is prescribed for a woman of childbearing 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.
Geriatrics:
Elderly and debilitated patients or those with organic brain disorders
have been found to be prone to CNS depression following even low doses.
For these patients it is recommended that the dosage be limited to the
smallest effective amount to preclude development of ataxia, oversedation
or other possible adverse effects.
Use in emotional disorders:
Diazepam is not recommended in the treatment of psychotic or severely depressed
patients. Precautions are indicated for severely depressed patients or
those who show evidence of impending depression, particularly the recognition
that suicidal tendencies may be present and protective measures may be
necessary. Since excitement and other paradoxical reactions may result
from the use of the drug in psychotic patients, it should not be used
in ambulatory patients suspected of having psychotic tendencies.
Use in epileptic patients:
Since diazepam may exacerbate grand mal seizures in some patients, caution
is required when it is used in epileptic patients. An adjustment may be
necessary in their anticonvulsive medication. Abrupt withdrawal of diazepam
in these patients should also be avoided.
Potentiation of drug effects:
Patients should be advised to abstain from alcohol and other CNS depressant
drugs during treatment with diazepam. Phenothiazines, barbiturates, MAO
inhibitors and other psychoactive drugs may potentiate the action of the
drug and should not usually be given concurrently.
Drug dependence:
Abrupt cessation of large doses of diazepam after prolonged periods may
precipitate acute withdrawal symptoms and, in these cases, the drug should
be discontinued gradually. Caution should be exercised when it is considered
necessary to administer diazepam to addiction prone individuals.
Occupational Hazards:
Patients receiving diazepam should be advised to proceed cautiously whenever
mental alertness and physical coordination are required.
The usual precautions in treating patients with impaired renal and hepatic functions should be observed. If diazepam is administered for protracted periods, periodic blood counts and liver function tests would be highly advisable.
The most common adverse effects reported are drowsiness and ataxia. Other reactions noted less frequently are fatigue, dizziness, nausea, blurred vision, diplopia, vertigo, headache, slurred speech, tremors, hypoactivity, dysarthria, euphoria, impairment of memory, confusion, depression, incontinence or urinary retention, constipation, skin rash, generalized exfoliative dermatitis, hypotension, changes in libido.
The more serious adverse reactions occasionally reported are leukopenia, jaundice, hypersensitivity and paradoxical reactions.
Paradoxical reactions such as hyperexcited states, anxiety, excitement, hallucinations, increased muscle spasticity, insomnia, rage, as well as sleep disturbances and stimulation, have been reported; should these occur, the drug should be discontinued.
Minor changes in EEG patterns have been observed in patients on diazepam therapy. These changes consist of low to moderate voltage fast activity, 20 to 30 cycles/second and are of no known significance.
Symptoms:
Drowsiness, oversedation and ataxia. When the effects of drug overdosage
begin to wear off, the patient exhibits some jitteriness and overstimulation.
The cardinal manifestations of overdosage are drowsiness and confusion,
reduced reflexes and coma. There are minimum effects on respiration, pulse
and blood pressure unless the overdosage is extreme.
Treatment:
Gastric lavage may be beneficial if performed soon after oral ingestion
of diazepam. If necessary, a CNS stimulant such as caffeine or methylphenidate
may be administered with caution. Supportive measures should be instituted
as indicated, such as, maintenance of an adequate airway, levarterenol
for hypotension. Dialysis appears to be of little value.
Must be individualized according to diagnosis, severity of symptoms and degree of response. While the usual daily dosages given below will meet the needs of most patients, there will be some who may require higher doses. In the first few days of administration a cumulative effect of the drug may occur, and therefore the dosage should be increased only after stabilization is evident.
Adults:
Symptomatic relief of anxiety and tension in psychoneurosis and anxiety
reactions: 2 to 10 mg, 2 to 4 times daily depending upon severity of symptoms.
Symptomatic relief in acute alcohol withdrawal: 10 mg, 3 or 4 times during the first 24 hours, reducing to 5 mg, 3 or 4 times daily as needed.
Adjunctively for relief of skeletal muscle spasms: 2 to 10 mg, 3 to 4 times daily.
Elderly and debilitated patients, or in
the presence of debilitating disease:
2 mg, 1 or 2 times daily initially; increase gradually as needed and tolerated.
Children (Because of varied responses,
initiate therapy with lowest dose and increase as required. Not for use
in children under 6 months):
1 to 2.5 mg, 3 or 4 times daily initially; increase gradually as needed
and tolerated.
Do not prescribe or administer diazepam for periods in excess of 6 weeks, unless a definite need for utilizing this medication has been established by a followup medical examination.
2 mg:
Each white cylindrical, biplane tablet with edges bevelled, single scored
on one side and engraved {ROCHEover2} on unscored side contains: Diazepam
2 mg. Also contains lactose 100 mg. Nonmedicinal ingredients: Cornstarch
and magnesium stearate. Energy: 2.8 kJ (0.7 kcal). Gluten-free, paraben-free,
sodium-free, sulfite-free and tartrazine-free. Bottles of 100.
5 mg:
Each yellow cylindrical, biplane tablet with edges bevelled, single scored
on one side engraved ROCHE above and C below the score line and engraved
{VALIUMover5} on unscored side contains: Diazepam 5 mg. Nonmedicinal ingredients:
Cornstarch, iron oxide, lactose, magnesium stearate and quinoline yellow
WS. Energy: 2.8 kJ (0.7 kcal). Gluten-free, paraben-free, sodium-free,
sulfite-free and tartrazine-free. Bottles of 100 and 1000.
10 mg:
Each light blue cylindrical, biplane tablet with edges bevelled, single
scored on one side and engraved {ROCHEover10} on unscored side contains:
Diazepam 10 mg. Also contains lactose 100 mg. Nonmedicinal ingredients:
Cornstarch, indigotine and magnesium stearate. Energy: 2.8 kJ (0.7 kcal).
Gluten-free, paraben-free, sodium-free, sulfite-free and tartrazine-free.
Bottles of 100.
Store between 15 and 30°C. Keep in a tightly closed, light-resistant container.
The research information is available separately on Internet Mental Health.
Note: This information is from a Canadian monograph. There can be differences in indications, dosage forms and warnings for this drug in other countries.
Internet Mental Health (www.mentalhealth.com) copyright © 1995-2009 by Phillip W. Long, M.D.