Drug Information

Drug Interaction:

Benzodiazepine ( Hypnotic ) include- Estozolam, Flurazepam, Quazepam, Triazolam

Refer - Flurazepam

Interacting drugs -summary

Benzodiazepine ( Hypnotic )

Alcohol /CNS depressants

additive CNS depression effects. Potential for this interaction

continues for several days following flurazepam withdrawal

Cimetidine / Contraceptives oral/ Disulfram / Isoniazid

the hepatic metabolism of benzodiapines may be inhibited

their half -life prolonged and their clearance decreased

possibly resulting in increased pharmacologic and CNS

depressant effects.

Probenecid

more rapid onset or more prolonged benzodiazepine effect

Rifampicin

increased clearance and decreased half-life of benzodiazepine

occur. Temazepam would probably not interact

Smoking

benzodiazepines clearance is increased in cigerrete smokers

probably due to enzyme induction

Theophylline

benzodiazepine pharmacologic effects may be antagonised

Macrolides + Tiazolam

bioavailabilty of triazolam may be increased

Benzodiazepine + Digoxin

digoxin serum levels and toxicity may increase

Benzodiaz + Neuromuscular blocking agents ( non depolarizing )

benzodiazepine may potentiate , counteract, or have no effect

on these agents

Benzodiazepine + Phenytoin

phenytoin serum levels may be increased, resulting in toxocity,

Indication:

Insomnia Anxiety

Adverse Reaction:

CNS-

somnolence (42% ) asthnia ( 11% ) hypokinesia ( 8% ) hangover ( 3%)

abnormal thinking ( 2% ) anxiety ( 1% ) agitation, amnesia, apathy, emotional lability, hostility, seizures, sleep disorder, stupor, twitch ( 0.1 to 1% )

ataxia, decreased libido, decreased refluexes, neuritis ( < 1% )

Cardiovascular-

arrhythmia, syncope ( < .0.1% )

Dermatologic -

urticaria ( 0.1 to 1% ) acne, dry skin, photosentivity ( < 0.1 % )

Respiratory -

cold symptoms ( 3% ) pharyngitis ( 1% ) asthma, cough, dyspnea, rhinitis, sinusitis ( 0.1 to 1% ) epistaxis.hyperventilation , laryngitis ( 0.1% )

Special senses-

ear pain, eye irritation/pain, swelling, photophobia, ( 0.1 to 1%)

decreased hearing, diplopia, nyastagmus, scotoma ( < 0.1 % )

GU -

frequent urination, menstrual cramps, urinary hesitancy/urgency ,

vaginal discharge/itching ( 0.1 to 1% )

hematuria, nocturia, oliguria, penile discharge, urinary incontinence ( < 0.1% )

Miscellaneous-

lower extremity /back/abdominal pain ( 1 to 3% ) stiffness ( 1% )

allergic reaction, chills, fever, neck/upper extremity pain, thrist, arthritis,

muscle spasm, myalgia ( 0.1 to 1% ) edema, jaw pain,

swollen breast, thyroid nodule, purpura, swollen lymph nodes,

agranulocytosis, increased AST , weight gain/loss, arthalgia ( < 0.1 % )

Contra-Indications:

Hypersensitivity to other benzodiazepines, pregnancy, established or suspected sleep apnea ( quazepam)

Warnings:

Triazolam -

Anterograde amnesia - of varying severity and paradoxical reactions has occured following therapeutic doses of triazolam. Although this effect generally occured with a dose of 0.5mg it has also been reported with 0.125 and -.25mg doses some other benzodiazepines., but data suggest that it may occur at higher rate of triazolam

Renal/hepatic function impairment- observe usual cautions under these conditions

Abnormal liver function tests as well as blood dyscrasis have been reported with benzodiazepines

Elderly- risk of developing oversedation, dizziness, confusion, or ataxia increase substantially with larger doses of benzodiazepines in eldrly and debilitated patients.

Initiate with a lowest effective dose.

Pregnancy - ( estozolam, quazepam temezepam, triazolam ) flurazepam is contraindicated in pregnancy

Lactation- safety for use in nursing mothers has not been established. Therfore admin to nursing mothers not recommended

Children- Flurazepam - not for use in children < 15 years of age

Estozolam, quazepam, temazepam, triazolam - not for use in children < 18 years of age

Precautions-

Monitoring- when triazolam or estrzolam treatment is protracted obtain periodic blood counts , urinalysis, and blood vchmistry analysis.

Depression- administer with caution in severely depressed patients or in those in whom is evidence or suicidal tendencies

Signs and symtpoms of depression may be intensified with hypnotic drugs

Protective measures may be reqd.

Intentional overdosage is more common in these patients , and the least amount of drugs

that is feasible should be available to patient at any one time.

Rebound sleep disorder - characterised by recurrence of insomnia following abrupt withdrawal usually during the first 1 to 3 nights

Gradual rather than abrupt discontinuation of the drug may help avoid this syndrome

Disturbed nocturnal sleep - may occur fr the first or second night after discontinuing use

Early morning insomnia- oe early morning awakening appears more common with the

use of short half-life agents-( temazepam, triazolam,) rather than intermediate or long half lives ( estazolam,flurazepam, quazepam )

Respiratory depression and sleep apnea- observe caution in patients with compromised respiratory function, respiratory depression and sleep apnea have occured

Estozolam may cause dose -related respiratory depressionthat is not ordinarily clinically relevent at recommended doses in patients with normal respiratory function

Drug abuse and dependence- withdrawal symptoms following discontinuation of benzodiazepines have occured in patients receiving excessive doses over extended periods of time.

Hazardous tasks- observe caution while driving or performing tasks requiring alertness. beware of potential impairment of performance of such activities following ingestion

Dosages/ Overdosage Etc:

Indications:

Anxiety, Insomnia

Dosage:

Adults- 30mg before bed time. In some cases 15mg may suffice.

Patient Information:

Benzodiazepine ( Hypnotic ) include- Estozolam, Flurazepam, Quazepam, Triazolam

Refer - Flurazepam

1. Avoid alcohol and other CNS depressants. Do not exceed the prescribed dose

2. Do not discontinue medication abruptly after prolonged therapy

3. Advise patients that they may experience disturbed nocturnal sleep for the first or second night after discontinuing the drug

4. May cause drowsiness or dizziness, observe cation while driving or performing other tasks requiring alertness.

5. Inform your physician if you are planning to become pregnant, if you pregnant, or if you become pregnant while taking this medicine

6. Troazolam- advice patients not to take triazolam in circumstances where a full nights sleep and clearance of the drug from the body are not possible before they would again need to be active and functional

Pharmacology/ Pharmacokinetics:

Ref- Drug Facts And Comparisons(2010)

Benzodiazepine ( Hypnotic ) include- Estozolam, Flurazepam, Quazepam, Triazolam, Temazepam

Refer - Flurazepam

Short Half life agents - Temazepam, Triazolam

Intermediate or long half life agents - Esazolam, Flurazepam, Quazepam

Pharmacology-

Estozolam, flurazepam, quazepam, temazepam and triazolam are benzodizepine derivatives useful as hynotics. Benzodizepines are believed to potentiate gamma aminobutyric acid GABA neuronal inhibition. The sedative and anticonvulsant actions involve GABA receptors located in limbic,neocortical and mesencephalic reticular systems

Pharmacokinetics-

These agents are rapidly absorbed within 1 to 3 hours after oral admin. Times to peak plasma conc,range from 0.5 to 6 hours Triazolam peak plasma conc, occurs within 1 hour, temazepam is slower. The major active metabolite reaches peak plasma conc. in 1 to 3 hours. Benzodiazepines are extensively metabolised in the liver

Nonbarbiturate Sedative/ Hypnotics Pharmacokinetic Parameters

Adult dose Onset Duration of Half-life Protein Urinary

Hypnotic Sedative min Action-hrs hrs binding excretn

% %

Drug

Imidazopyridines

Zolpedem

10mg na na nd ~2.5 92.5 0

Ureides

Acetylcabromal

nd 250-500mg nd nd nd nd nd

bid or tid

Tertiary Acetylenic Alcohols

Ethchlorvynol

500mg 100-200mg 15-60 5 10-20 nd 40

bid or tid

Piperidine Derivative

Glutethimide

250-500mg nd 30 4-8 10-12 50 <2

Benzodiazepine

Estazolam

1-2mg na nd nd 10-24 93 <5

Flurazepam

15-30mg na 17 7-8 50-100 97 <1

Quazepam

15mg na nd nd 24-41 >95 trace

Temazepam

15-30mg na nd nd 1-17 98 1.5

Trazolam

0.125-0.5mg na nd nd 1.5-5.5 90 2

Miscellaneous non barbiturates

Chloral hydrate

0.5- 1g 250mg tid 30 nd 7-10 35-41 nd

Paraldehyde

10-30ml 5-10ml 10-15 8-12 3.4- 9.8 nd small

Propiomazine

nd 10-20mg nd nd nd nd nd

Na- not applicable No data

Select Benzodiazepine (Hynotic) Pharmacokinetic Parameters

Usual adult Time to peak Half-life Protein Urinary excrtn

oral dose plasma level hrs binding unchanged

mg hrs % %

Drug

Estazolam

1.2 2 8.28 93 <5

Flunazepam

15-30 0.5-1 2-3 97 <1

(7.6- 13.6) (47-100)

Quazepam

7.5- 15 2 41 >95 trace

(1-2) (47-100)

Temazepam

15-30 1.2-1.6 3.5 -18.4 96 0.2

(9-15)

Triazolam

0.125-0.5 1-2 1.5 -5.5 78-89 2

Interaction with Food:

Not available.

Pregnancy and lactation:

Pregnancy -

( estozolam, quazepam temezepam, triazolam ) flurazepam is contraindicated in pregnancy

Lactation-

Safety for use in nursing mothers has not been established. Therfore admin to nursing mothers is not recommended

Flurazepam - @ Benzodiazepines ( Hypnotic)

Drug Interaction

Indication

Adverse Reaction

Contra-Indications

Dosages/ Overdosage Etc

Patient Information

Pharmacology/ Pharmacokinetics

Interaction with Food

Pregnancy and lactation