Drug Interaction:

Benzodiapines include- Alprozolam, Chlordiazepoxide, Clonazepam, Clorazepate,Diazepam, Halazepam, Lorazepam, Oxazepam, Prazazepam

Refer Diazepam

 Interacting drugs - Benzodiazepines - summary

 + Benzodiazepines -

Alcohol                                                                                                                               increased CNS effects CNS depresants +}

Antacids                                                                                                                              may alter rate but extent of GI absorption. Staggering admin. times may help avoid possible interaction

Contraceptives Oral                                                                                                             the clearance rate of benzodiapines increased

Digoxin                                                                                                                              serum concentration may be increased.

Levodopa                                                                                                                      antiparkinson efficacy decreased by coadmin.

Nondepolarizing +  Benzodiapines                                                                                          may potentiate, counteract, or have no actions Neuromuscular on NNBs Blockers( NNBs)

Phenytoin                                                                                                                          serum concentrations may be increased , resulting in toxicity,

Probenecid-                                                                                                                          may interfere with benzodiapine, more rapid onset or prolonged effect

Rantidine                                                                                                                             may reduce the GI absorption of diazepam

Rifampicin                                                                                                                   Pharmacologic effects of some benzodiazepine may be decreased

Scopolamine                                                                                                                      used concomittantly with parentral lorazepam may increase sedative effects

Theophylline                                                                                                                       may antogonise the sedative effect of benzodiazepine

 

   

Indication:

 

 

Anxiety

 

   

Adverse Reaction:

BENZODIAPINES- Discontinuation of therapy due to undesirable effects is rare. Transcient mild drowsiness is commonly seen in the first few days of therapy Drowsiness, ataxia and confusion have occured especially in the elderly and debilatated If persistent ruduce dosage, Ataxia is rare with oxazepam and does not appear to be specifically related to dose or age.

Other adverse reactions less frequently reported include-

CNS- Headache, nervousness, talkativeness, apprenhension, irritability, confusion, euphoria,relaxed feeling,weakness , tremor,lack of concentration, coordination disorders,confusional states/memory impairment, depression, dreaming/ nightmares, insomnia, paresthesis, restlessness, tiredness, dysesthesia.

Hallucinations, horizontal nystagmus,and paradoxixal reactions, including excitement, stimulation, and hyperactivity were rare. Dizziness, drowsiness, lightheadedness, staggering, ataxia, falling, particularly in elderly or debilated patients. Severe sedation lethargy, disoreientation and coma are probably indicative of drug tolerance or overdosage.

GI- Dyspepsia, decreased/increased appetite, flaatulance, gastritis, enterocolitis, melena, mouth ulceration.

Cardioavascular- Aerrhythmia, syncope

Dermatologic- Urticaria, acne,dru skin, photosentivity.

Respiratory- Cold symptoms, pharyngitis, astrhma, cough, dyspnea, rhinitis, sinusitis, epistaxis, hyperventilation, laryngitis.

Special senses- Easr pain, eye irritation/ pain/swelling, photophobia, decreased hearing, diplopia, nystagmus, scotoma

GU- Frequent urination, menstrual cramps, urinary hesistency, vaginal discharge/itching, hematuria, oliguria, penile discharge, urinary incontinence

Miscellaneous-Lower extremity /back/abdominal pain, stiffness, allergic reaction,chills, fever, neck/upper extremity pain, thirst, arthritis, muscle spasm,myalgia, edema, jaw pain, swollen breast, thyroid nodule, purpura, swollen lymph nodes, agranulocytosis, incresed AST, weight gain/loss, arthalgia

   

Contra-Indications:

Hypersensitivity, narrow angle glaucoma,myasthenia gravis, children under 6 months.

Special precautions:

Pregnancy, impaired renal and hepatic functions.Respiratory insufficiency.Organic cerebral changes.

Monitoring- When triazolam or estazolam treatment is protracted, obtain periodic blood counts, urinalysis, and blood chemistry analysis.

Minor ECG changes , usually low voltage activity, are of known significance.

Depression- Administer with caution in severly depressed patients or in those in whom there is evidence of latent depression or suicidal tendencies. Signs or symptoms of depressioin or suicida tendencies may be intensified by hypnotic drugs.

Protective measures may be required. Intentional overdosage is more common in these patients, and the least amount of drug that is feasible should be available to the patient at any one time.

Rebound sleep disorder- which is characterised by recurrence of insomnia to levels worse than before treatment began may occur following abrupt withdrawal of triazolam, usually during the first 1 to 3 nights. Gradual rather abrupt withdrawal of the drug may help avoid this syndrome

Rebound insomnia appears to be less likely after withdrawal of agents with intermediate or long half-lives (eg. estazolam, flurazepam, quazepam).

Disturbed nocturnal sleep- may occur for thr first or second night after discontinuing use.

Early morning insomnia- or early morning awakening appears to be more common with the use of short half-life agents (temazepam,triazolam) than agents with intermediate or long half-lives (flurazepam, quazepam). However day time sleep appears to be more prevalent with long half-life agents.

Respiratory depression and sleep apnea- observe caution in patients with compromised respiratory function, respiratory depression and sleep apnea have occured. Benzodiapines have the capacity to depress respiratory drive, although there are insufficient data to characterize the relative potency of these agents in depressing respiratory drive at clinically recommeded dose.

Drug abuse and dependence- Withdrwwal symptoms following abrupt discontinuatioin of benzodiapines have occured in patients receiving excessive doses over extended periods of time.

Excercise caution in admininisterting to individuals known to be addiction prone or those who may increase the dosage on their initiative. Limit repeated prescribtions without adequate medical supervision.

Hazardous tasks- Observe caution while driving or performing tasks requiring alerness.. be aware of potential impairment of performance of such activities the day following ingestion.

Warnings-

Anterodrade amnesia- of varying severity and paradoxical reactions have occured following therapeutic doses of Triazolam

Renal/Hepatic functionimpairment- observe usual precautions under these conditions Abnormal liver function tests as wellas blood dyscrasias have been reported with benzodiazepines

Elderly- the risk of developing oversedation , dizziness, confusion or ataxia increases substantially with larger doses of benzodiapines in elderly and debilated patients. Initiate with the lowest effective dose.

Pregnancy- if there a likelihood of the patient becoming pregnant while receiving benzodiazepines, warn of the potential risk to the fetus. Instruct the patient to discontinue the drug before becoming pregnant.

Lactation- safety fo use in nursing mother has not been established.

Children- Not for use in children < 15 years of age.

   

Dosages/ Overdosage Etc:

Indications:

Anxiety, acute alcohol withdrawal ,muscle relaxant, anticonvulsant, preoperative cases.

Dosage:

Individualise dose. Normal - 2 to 10mg 4 times daily. Children- 1 to 2.5mg 3 to 4 times daily.

Overdosage-

Symptoms Somnolonce, confusion with reduced or absent reflexes, respiratory depression, apnea, hypotension, impaired coordination, slurred speech, seizures, ultimately coma, Death has occured with overdoses of benzodiazepine alone and with alcohol.

Treatment

1. If excitation occurs.do not use barbiturates.

2. Consider the possibility that multiple agents may have been ingested.

3. Monitor respiration, pulse and blood presure

4. Employ general supportive measures.

5. Administer IV fluids and maintain an adequate airway.

6. Perform gastric lavage.

7. Hemodialysis and forced diuresis are of little value.

 Missed dose-

- 1. If you miss a dose of this medicine, take it as soon as possible.

2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

   

Other Information:

   

Patient Information:

1. Avoid alcohol and other CNS depressants.

2. Do not exceed the prescribed dose.

3. Do not discontinue medication abruptly after prolonged therapy

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

5.May cause dizziness or drowsiness, observe caution while driving or performing other tasks requiring alertness.

6. Inform your physcian if you are planning to become pregnant,if you are pregnant or if you become pregnant while taking the drug.

7. Trizoalam- Advise patients not to take trizolam in circimstances when a full nights sleep and clearance of the drug from the body are not posible before they would again need to be active and functional.

8.Allergies- Tell your doctor if you had any unusual or allergic reactions to benzodiazepines Tell your doctor if you are allergic to any other substances such as foods, or drinks

. 9. Pregnancy- Chlordiazepoxide and diazepam have been repored to increase the chance of birth defects when used during the first 3 months of pregnancy. Although similar problems haved not been reported with other benzidiazepines the chance always always exist since all benzodiazepines are interelated.

10. Breast feeding- Benzodiazepines pass into breast milk and cause drowsinwess , slow heart beat, shortness of breath, or troubled breathing in nursing babies of mothers taking this medicine.

11. Children- These patients are more sensitive than adults to the effects of benzodiazepines

12. Elderly- Taking benzodiazepines for trouble in sleeping are more likely to cause more day time drowsiness in elderlty than in younger adults.

13. Other medicines- Tell your doctor if you are taking any of the following medicines- CNS depressants- these effects of either of these medicines may be increased . Your doctor may want to change the dose of either or both medicines

14. Other medical problems- Tell your doctor if you have any other medical problems- Alcohol abuse or Drug abuse or depence on benzodiazepines may develop Brain disease- CNS depresion and other side effects of benzodiazepines may occur

Difficulty in swallowing or Emphysema, Asthma, bronchitis, or other chronic lung disease or Glaucoma or Hyperacidity or Mental illness or Myasthena gravis or Porphyria or Sleep apnea- benzodiazepines may make the condition worse.

Epilepsy- starting or suddenly stopping treatment with these medicines may increase seizures Kidney or liver disease- higher blood levels of benzodiapines may result, with increased side effects.

15. Missed dose- If you are taking this medicine regularly and miss a dose take it right away if you remember within an hour of the missed dose. However, if you do not remember until later, skip the missed dose and go back to your regular dosing schedule. Do not double doses

. 16. Storage - Keep out of reach of children. Store away from heat or direct sunlight. Do not store the capsule in bathroom, near the kitchen sink, or in other damp places.

17. Outdated medicines - Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of reach of children.

   

Pharmacology/ Pharmacokinetics:

   

Interaction with Food:

Not available

   

Pregnancy and lactation:

Refer nitrazepam

Pregnancy-

If there a likelihood of the patient becoming pregnant while receiving benzodiazepines, warn of the potential risk to the fetus. Instruct the patient to discontinue the drug before becoming pregnant.

Lactation-

Safety fo use in nursing mother has not been established.

Children-

Not for use in children < 15 years of age.