Diazepam
Tablets USP C-IV
Rx only
Diazepam is a benzodiazepine derivative.
Diazepam tablets are indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic.
In acute alcohol withdrawal, diazepam may be useful in the symptomatic relief of acute agitation, tremor, impending or acute delirium tremens and hallucinosis.
Diazepam is a useful adjunct for the relief of skeletal muscle spasm due to reflex spasm to local pathology (such as inflammation of the muscles or joints, or secondary to trauma); spasticity caused by upper motor neuron disorders (such as cerebral palsy and paraplegia); athetosis; and stiff-man syndrome.
Oral diazepam may be used adjunctively in convulsive disorders, although it has not proved useful as the sole therapy. The effectiveness of diazepam in long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies. The physician should periodically reassess the usefulness of the drug for the individual patient.
DESCRIPTION
Diazepam is a benzodiazepine derivative. Chemically, diazepam is 7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2 H -1,4-benzodiazepin-2-one. It is a colorless crystalline compound, and is insoluble in water. The structural formula is represented below:
C16H13ClN2O M.W. 284.74
C16H13ClN2O M.W. 284.74
Diazepam Tablets USP 2 mg, 5 mg and 10 mg, for oral administration, contain the following inactive ingredients: anhydrous lactose, magnesium stearate and microcrystalline cellulose.
Diazepam Tablets USP 5 mg also contain D&C Yellow No. 10.
Diazepam Tablets USP 10 mg also contain FD&C Blue No. 1.
PHARMACOLOGY
In animals, diazepam appears to act on parts of the limbic system, the thalamus and hypothalamus, and induces calming effects. Diazepam, unlike chlorpromazine and reserpine, has no demonstrable peripheral autonomic blocking action, nor does it produce extrapyramidal side effects; however, animals treated with diazepam do have a transient ataxia at higher doses. Diazepam was found to have transient cardiovascular depressor effects in dogs. Long-term experiments in rats revealed no disturbances of endocrine function.
Oral LD50 of diazepam is 720 mg/kg in mice and 1240 mg/kg in rats. Intraperitoneal administration of 400 mg/kg to a monkey resulted in death on the sixth day.
Reproduction Studies
A series of rat reproduction studies was performed with diazepam in oral doses of 1, 10, 80 and 100 mg/kg. At 100 mg/kg there was a decrease in the number of pregnancies and surviving offspring in these rats. Neonatal survival of rats at doses lower than 100 mg/kg was within normal limits. Several neonates in these rat reproduction studies showed skeletal or other defects. Further studies in rats at doses up to and including 80 mg/kg/day did not reveal teratological effects on the offspring.
In humans, measurable blood levels of diazepam were obtained in maternal and cord blood, indicating placental transfer of the drug.
INDICATIONS
Diazepam Tablets USP are indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic.
In acute alcohol withdrawal, diazepam may be useful in the symptomatic relief of acute agitation, tremor, impending or acute delirium tremens and hallucinosis.
Diazepam is a useful adjunct for the relief of skeletal muscle spasm due to reflex spasm to local pathology (such as inflammation of the muscles or joints, or secondary to trauma); spasticity caused by upper motor neuron disorders (such as cerebral palsy and paraplegia); athetosis; and stiff-man syndrome.
Oral diazepam may be used adjunctively in convulsive disorders, although it has not proved useful as the sole therapy.
The effectiveness of diazepam in long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies. The physician should periodically reassess the usefulness of the drug for the individual patient.
DOSAGE AND ADMINISTRATION
Dosage should be individualized for maximum beneficial effect. While the usual daily dosages given below will meet the needs of most patients, there will be some who may require higher doses. In such cases, dosage should be increased cautiously to avoid adverse effects.
Adults: Usual Daily Dose
Management of Anxiety Disorders and relief of Symptoms of Anxiety. Depending on severity of symptoms — 2 mg to 10 mg, 2 to 4 times daily
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 Spasm. 2 mg to 10 mg, 3 or 4 times daily
Adjunctively in Convulsive Disorders 2 mg to 10 mg, 2 to 4 times daily
Geriatric Patients, or in the presence of debilitating disease. 2 mg to 2 ½ mg, 1 or 2 times daily initially; increase gradually as needed and tolerated
Children:
Because of varied responses to CNS-acting drugs, initiate therapy with lowest dose and increase as required. Not for use in children under 6 months. 1 mg to 2 ½ mg, 3 or 4 times daily initially; increase gradually as needed and tolerated
HOW SUPPLIED
Diazepam Tablets USP 2 mg are scored, round, white tablets imprinted DAN 5621 and 2 supplied in bottles of 100, 500 and 1000.
Diazepam Tablets USP 5 mg are scored, round, yellow tablets imprinted DAN 5619 and 5 supplied in bottles of 100, 500 and 1000.
Diazepam Tablets USP 10 mg are scored, round, blue tablets imprinted DAN 5620 and 10 supplied in bottles of 100, 500 and 1000.
Dispense in tight, light-resistant container with child-resistant closure.
Store at 20°-25°C (68°-77°F). [See USP controlled room temperature.]
WARNINGS
Diazepam is not of value in the treatment of psychotic patients and should not be employed in lieu of appropriate treatment. As is true of most preparations containing CNS-acting drugs, patients receiving diazepam should be cautioned against engaging in hazardous occupations requiring complete mental alertness such as operating machinery or driving a motor vehicle.
As with other agents which have anticonvulsant activity, when diazepam is used as an adjunct in treating convulsive disorders, the possibility of an increase in the frequency and/or severity of grand mal seizures may require an increase in the dosage of standard anticonvulsant medication. Abrupt withdrawal of diazepam in such cases may also be associated with a temporary increase in the frequency and/or severity of seizures.
Since diazepam has a central nervous system depressant effect, patients should be advised against the simultaneous ingestion of alcohol and other CNS-depressant drugs during diazepam therapy.
Usage in Pregnancy
An increased risk of congenital malformations associated with the use of minor tranquilizers (diazepam, meprobamate and chlordiazepoxide) during the first trimester of pregnancy has been suggested in several studies. Because use of these drugs is rarely a matter of urgency, their use during this period should almost always be avoided. The possibility that a woman of childbearing potential may be pregnant at the time of institution of therapy should be considered. Patients should be advised that if they become pregnant during therapy or intend to become pregnant they should communicate with their physicians about the desirability of discontinuing the drug.
Management of Overdosage
Manifestations of diazepam overdosage include somnolence, confusion, coma and diminished reflexes. Respiration, pulse and blood pressure should be monitored, as in all cases of drug overdosage, although, in general, these effects have been minimal following overdosage. General supportive measures should be employed, along with immediate gastric lavage. Intravenous fluids should be administered and an adequate airway maintained. Hypotension may be combated by the use of norepinephrine or metaraminol. Dialysis is of limited value. As with the management of intentional overdosage with any drug, it should be borne in mind that multiple agents may have been ingested.
Flumazenil, a specific benzodiazepine receptor antagonist, is indicated for the complete or partial reversal of the sedative effects of benzodiazepines and may be used in situations when an overdose with a benzodiazepine is known or suspected. Prior to the administration of flumazenil, necessary measures should be instituted to secure airway, ventilation, and intravenous access. Flumazenil is intended as an adjunct to, not as a substitute for, proper management of benzodiazepine overdose. Patients treated with flumazenil should be monitored for re-sedation, respiratory depression, and other residual benzodiazepine effects for an appropriate period after treatment. The prescriber should be aware of a risk of seizure in association with flumazenil treatment, particularly in long-term benzodiazepine users and in cyclic antidepressant overdose. The complete flumazenil package insert including CONTRAINDICATIONS, WARNINGS and PRECAUTIONS should be consulted prior to use.
Withdrawal symptoms of the barbiturate type have occurred after the discontinuation of benzodiazepines (see DRUG ABUSE AND DEPENDENCE section).
PRECAUTIONS
If diazepam is to be combined with other psychotropic agents or anticonvulsant drugs, careful consideration should be given to the pharmacology of the agents to be employed — particularly with known compounds which may potentiate the action of diazepam, such as phenothiazines, narcotics, barbiturates, MAO inhibitors and other antidepressants. The usual precautions are indicated for severely depressed patients or those in whom there is any evidence of latent depression; particularly the recognition that suicidal tendencies may be present and protective measures may be necessary. The usual precautions in treating patients with impaired renal or hepatic function should be observed.
In elderly and debilitated patients, it is recommended that the dosage be limited to the smallest effective amount to preclude the development of ataxia or oversedation (2 mg to 2 ½ mg once or twice daily, initially, to be increased gradually as needed and tolerated).
The clearance of diazepam and certain other benzodiazepines can be delayed in association with Tagamet (cimetidine) administration. The clinical significance of this is unclear.
Information for Patients
To assure the safe and effective use of benzodiazepines, patients should be informed that, since benzodiazepines may produce psychological and physical dependence, it is advisable that they consult with their physician before either increasing the dose or abruptly discontinuing this drug.
ADVERSE REACTIONS
Side effects most commonly reported were drowsiness, fatigue and ataxia. Infrequently encountered were confusion, constipation, depression, diplopia, dysarthria, headache, hypotension, incontinence, jaundice, changes in libido, nausea, changes in salivation, skin rash, slurred speech, tremor, urinary retention, vertigo and blurred vision. Paradoxical reactions such as acute hyperexcited states, anxiety, hallucinations, increased muscle spasticity, insomnia, rage, sleep disturbances and stimulation have been reported; should these occur, use of the drug should be discontinued.
Because of isolated reports of neutropenia and jaundice, periodic blood counts and liver function tests are advisable during long-term therapy. Minor changes in EEG patterns, usually low-voltage fast activity, have been observed in patients during and after diazepam therapy and are of no known significance.
REPORTS OF SIDE EFFECTS / ADVERSE REACTIONS RELATED TO DIAZEPAM
Below is a sample of reports where side effects / adverse reactions may be related to Diazepam. The information is not vetted and should not be cosidered as verified clinical evidence.
Possible Diazepam side effects / adverse reactions in 35 year old female
Reported by a physician from United States on 2007-02-16
Patient: 35 year old female
Reactions: Glaucoma, Abdominal Pain Upper, Tarsal Tunnel Syndrome, Neuropathy Peripheral, Malaise, Thrombophlebitis Superficial, Dizziness, Bronchospasm, Resorption Bone Increased, Blood Creatinine Increased, Cough, Pain in Extremity, Cholelithiasis, Osteoarthritis, Renal Failure, Vestibular Disorder, Vasculitis, Purpura Senile, Bronchitis, Arthritis, Deep Vein Thrombosis, Arthropod Bite, Vertigo Positional
Adverse event resulted in: hospitalization, disablity
Suspect drug(s):
Advair Diskus 100/50
Indication: Drug USE FOR Unknown Indication
Augmentin '125'
Dosage: 1750mg per day
Indication: Drug USE FOR Unknown Indication
Fluticason
Indication: Drug USE FOR Unknown Indication
Bupropion Hydrochloride
Dosage: 300mg unknown
Xanax
Dosage: 1mg three times per day
Indication: Stress
Start date: 1985-01-01
Zyrtec
Indication: Multiple Allergies
Latanoprost
Indication: Drug USE FOR Unknown Indication
Dexamethasone
Indication: Drug USE FOR Unknown Indication
Carisoprodol
Administration route: Oral
Indication: Drug USE FOR Unknown Indication
Clotrimazole
Indication: Drug USE FOR Unknown Indication
Clonazepam
Trazodone Hydrochloride
Indication: Drug USE FOR Unknown Indication
Gabapentin
Fluoxetine Hydrochloride
Indication: Drug USE FOR Unknown Indication
Atenolol
Dosage: 50mg per day
Meloxicam
Indication: Drug USE FOR Unknown Indication
Zydone
Indication: Drug USE FOR Unknown Indication
Olmesartan Medoxomil
Dosage: 40mg per day
Allegra D 24 Hour
Indication: Drug USE FOR Unknown Indication
Mometasone Furoate
Indication: Drug USE FOR Unknown Indication
Candesartan Cilexetil
Indication: Drug USE FOR Unknown Indication
Lansoprazole
Indication: Drug USE FOR Unknown Indication
Fluconazole
Indication: Drug USE FOR Unknown Indication
Esomeprazole Magnesium
Indication: Drug USE FOR Unknown Indication
Lotrisone
Indication: Drug USE FOR Unknown Indication
Rizatriptan Benzoate
Indication: Drug USE FOR Unknown Indication
Lomotil
Indication: Drug USE FOR Unknown Indication
Ketoconazole
Dosage: 200mg per day
Indication: Drug USE FOR Unknown Indication
Sinemet
Indication: Drug USE FOR Unknown Indication
Tramadol HCL
Indication: Drug USE FOR Unknown Indication
Metaxalone
Bactrim DS
Dosage: 2u unknown
Indication: Drug USE FOR Unknown Indication
Pethidine Hydrochloride
Indication: Drug USE FOR Unknown Indication
Percocet
Indication: Drug USE FOR Unknown Indication
Codiclear
Indication: Drug USE FOR Unknown Indication
Quinine
Indication: Drug USE FOR Unknown Indication
Moxifloxacin Hydrochloride
Indication: Drug USE FOR Unknown Indication
Rofecoxib
Indication: Drug USE FOR Unknown Indication
Cefazolin
Dosage: 500mg per day
Administration route: Oral
Indication: Drug USE FOR Unknown Indication
Duratuss
Indication: Drug USE FOR Unknown Indication
Lortab
Indication: Drug USE FOR Unknown Indication
Erythromycin
Dosage: 500mg per day
Indication: Drug USE FOR Unknown Indication
Cephalexin Monohydrate
Dosage: 1500mg per day
Administration route: Oral
Indication: Drug USE FOR Unknown Indication
Mupirocin
Administration route: Topical
Indication: Drug USE FOR Unknown Indication
Oseltamivir
Dosage: 150mg per day
Indication: Drug USE FOR Unknown Indication
Endal-HD
Indication: Drug USE FOR Unknown Indication
Triamcinolone Acetonide
Indication: Drug USE FOR Unknown Indication
Omeprazole
Indication: Drug USE FOR Unknown Indication
Exgest LA
Dosage: 2u unknown
Administration route: Oral
Indication: Drug USE FOR Unknown Indication
Mescolor
Dosage: 2u unknown
Indication: Drug USE FOR Unknown Indication
Triazolam
Dosage: .25mg per day
Indication: Drug USE FOR Unknown Indication
Lorcet-HD
Dosage: 2u unknown
Administration route: Oral
Indication: Drug USE FOR Unknown Indication
Econazole Nitrate
Indication: Drug USE FOR Unknown Indication
Arthrotec
Dosage: 150mg per day
Indication: Drug USE FOR Unknown Indication
Diazepam
Indication: Drug USE FOR Unknown Indication
Celecoxib
Dosage: 200mg per day
Indication: Pain
Sucralfate
Indication: Drug USE FOR Unknown Indication
Lasix
Dosage: 40mg per day
Verapamil
Dosage: 120mg per day
Metoprolol Succinate
Lisinopril
Bisoprolol Fumarate
Amlodipine
Dosage: 5mg per day
Losartan Potassium
Covera-HS
Start date: 2002-01-01
Possible Diazepam side effects / adverse reactions in 26 year old female
Reported by a physician from Thailand on 2007-02-19
Patient: 26 year old female
Reactions: Neuroleptic Malignant Syndrome
Adverse event resulted in: hospitalization
Suspect drug(s):
Urecholine
Haloperidol
Indication: Delusion
Haloperidol
Indication: Tearfulness
Diazepam
Indication: Delusion
Diazepam
Diazepam
Indication: Tearfulness
Diazepam
Lorazepam
Other drugs received by patient: Fluoxetine; Imipramine Hydrochloride; Quetiapine Fumarate; Bromocriptine; Carbamazepine; Tianeptine
Possible Diazepam side effects / adverse reactions in 35 year old female
Reported by a health professional (non-physician/pharmacist) from United States on 2007-03-09
Patient: 35 year old female
Reactions: Glaucoma, Tarsal Tunnel Syndrome, Neuropathy Peripheral, Thrombophlebitis Superficial, Bronchospasm, Dizziness, Resorption Bone Increased, Condition Aggravated, Osteolysis, Cholelithiasis, Osteoarthritis, Renal Failure, Vestibular Disorder, Vasculitis, Bronchitis, Purpura Senile, Feeling Abnormal, Arthritis, Arthropod Bite, Deep Vein Thrombosis, Vertigo Positional
Adverse event resulted in: hospitalization, disablity
Suspect drug(s):
Zebeta
Advair(fluticasone Propionate, Salmeterol Xinaofate)
Dosage: inhalant
Allegra-D(pseudoephedrine Hydrochloride, Fexofenadine)
Alprazolam
Dosage: 3 mg, qd
Indication: Stress
Start date: 1985-01-01
Amlodipine
Dosage: 5 mg, qd
Indication: Hypertension
Amoxicillin W/clavulanate Potassium(amoxicillin, Clavulanate Potassium
Dosage: 170 mg, qd
Arthrotec
Dosage: 150 mg, qd
Atenolol
Dosage: 50 mg, qd
Indication: Hypertension
Avelox
Bactrim DS
Bupropion HCL
Dosage: 300 mg, qd
Candesartan Cilexetil(candesartan Cilexetil)
Carisoprodol
Dosage: oral
Administration route: Oral
Cefazolin Sodium
Dosage: 500 mg, qd, oral
Administration route: Oral
Celecoxib(celecoxib)
Dosage: 200 mg, qd
Indication: Pain
Cephalexin
Dosage: 1500 mg, qd, oral
Administration route: Oral
Cetirizine HCL
Indication: Hypersensitivity
Chlorpheniramine/pseudoephedrine(pseudoephedrine, Chlorphenamine)
Clonazepam
Indication: Muscle Spasms
Clotrimazole
Codiclear(guaifenesin, Hydrocodone Bitartrate)
Dexamethasone TAB
Diazepam
Duratuss(guaifenesin, Pseudoephedrine Hydrochloride)
Econazole Nitrate
Endal-Hd(phenylephrine Hydrochloride, Chlorphenamine Maleate, Hydrocod
Erythromycin
Dosage: 500 mg, qd
Esomeprazole(esomeprazole)
Fluconazole
Fluoxetine HCL
Fluticasone Propionate
Gabapentin
Indication: Muscle Spasms
Ketoconazole
Dosage: 200 mg, qd
Lansoprazole
Lasix
Dosage: 40 mg, qd
Indication: Hypertension
Latanoprost
Lisinopril
Indication: Hypertension
Lomotil
Lorcet Plus(hydrocodone Bitartrate, Acetaminophen)
Dosage: oral
Administration route: Oral
Lortab
Losartan Postassium
Indication: Hypertension
Lotrisone
Meloxicam
Metaxalone
Metoprolol Tartrate
Indication: Hypertension
Mometasone Furoate
Mupirocin
Dosage: topical
Administration route: Topical
Olmesartan Medoxomil
Dosage: 150 mg, qd
Zebeta
Advair HFA
Dosage: inhalant
Allegra-D 12 Hour
Alprazolam
Dosage: 3 mg, qd
Indication: Stress
Start date: 1985-01-01
Amlodipine
Dosage: 5 mg, qd
Indication: Hypertension
Amoxicillin + Clavulanate Potassium
Dosage: 170 mg, qd
Arthrotec
Dosage: 150 mg, qd
Atenolol
Dosage: 50 mg, qd
Indication: Hypertension
Avelox
Bactrim DS
Bupropion HCL
Dosage: 300 mg, qd
Candesartan Cilexetil
Carisoprodol
Dosage: oral
Administration route: Oral
Cefazolin Sodium
Dosage: 500 mg, qd, oral
Administration route: Oral
Celecoxib
Dosage: 200 mg, qd
Indication: Pain
Cephalexin
Dosage: 1500 mg, qd, oral
Administration route: Oral
Cetirizine HCL
Indication: Hypersensitivity
Pseudoephedrine Hcl/chlorpheniramine Maleate
Clonazepam
Indication: Muscle Spasms
Clotrimazole
Codiclear(guaifenesin, Hydrocodone Bitartrate)
Dexamethasone 0.5mg TAB
Diazepam
Duratuss(guaifenesin, Pseudoephedrine Hydrochloride)
Econazole Nitrate
Endal-Hd(phenylephrine Hydrochloride, Chlorphenamine Maleate, Hydrocod
Erythromycin
Dosage: 500 mg, qd
Esomeprazole Magnesium
Fluconazole
Fluoxetine Hydrochloride
Fluticasone Propionate
Gabapentin
Indication: Muscle Spasms
Ketoconazole
Dosage: 200 mg, qd
Lansoprazole
Lasix
Dosage: 40 mg, qd
Indication: Hypertension
Latanoprost
Lisinopril
Indication: Hypertension
Lomotil
Lorcet-HD
Dosage: oral
Administration route: Oral
Lortab
Losartan Potassium
Indication: Hypertension
Lotrisone
Meloxicam
Metaxalone
Metoprolol Tartrate
Indication: Hypertension
Mometasone Furoate
Mupirocin
Dosage: topical
Administration route: Topical
Olmesartan Medoxomil
Dosage: 150 mg, qd
DRUG INTERACTIONS
DIAZEPAM drug label information in our database does not contain a dedicated section on drug interactions. Please check subsections of WARNINGS AND PRECAUTIONS as well as other sources.
CONTRAINDICATIONS
Diazepam Tablets USP are contraindicated in patients with a known hypersensitivity to this drug and, because of lack of sufficient clinical experience, in children under 6 months of age. It may be used in patients with open angle glaucoma who are receiving appropriate therapy, but is contraindicated in acute narrow angle glaucoma.
