Valium

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Diazepam is an oral medication that is used to treat anxiety. It belongs to the benzodiazepine family of drugs, the same family that includes:

• alprazolam (Xanax)
• clonazepam (Klonopin)
• lorazepam (Ativan)
•  flurazepam (Dalmane)

• Diazepam is used for the treatment of disorders with anxiety.
• Diazepam also is used for the treatment of agitation, tremors, delirium, seizures, and hallucinations resulting from alcohol withdrawal.
• It is used for the treatment of seizures, relief of muscle spasms in some neurological diseases, and for sedation during surgery.

Mechanism of Action

Modulates postsynaptic effects of GABA-A transmission, resulting in an increase in presynaptic inhibition. Appears to act on part of the limbic system, as well as on the thalamus and hypothalamus, to induce a calming effect

Absorption

Bioavailability: 90% (PR)

Duration: Variable, dependent on dose and frequency (PO [hypnotic action]); 15-60 min (IV [sedative action])

Peak plasma time: 30-90 min (PO), 5-90 min (PR)

Peak plasma concentration: 373 ng/mL (initial at 45 min); 447 ng/mL (second peak at 70 min)

Distribution

Protein bound: 98%

Vd: 0.8-1 L/kg

Metabolism

Metabolized by hepatic P450 enzymes CYP2C19, CYP3A4

Metabolites: N-desmethyldiazepam, 3-hydroxdiazepam, oxazepam

Elimination

Half-life: 20-70 hr (active metabolite)

Renal clearance: 20-30 mL/min

Excretion: Urine

Studies in women breastfeeding have demonstrated harmful infant effects. An alternative to this medication should be prescribed or you should stop breastfeeding while using this medicine.

Serious side effects have been reported with Valium. See the “Valium Precautions” section.

Common side effects include:

• drowsiness
• fatigue (a feeling of tiredness or exhaustion or a need to rest because of lack of energy or strength)
• muscle weakness
• poor coordination (ataxia)
• dry mouth
• diarrhea
• nausea
• changes in appetite
• changes in vision

This is not a complete list of Valium side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Diazepam is a benzodiazepine that exerts anxiolytic, sedative, muscle-relaxant, anticonvulsant and amnestic effects. Most of these effects are thought to result from a facilitation of the action of gamma aminobutyric acid (GABA), an inhibitory neurotransmitter in the central nervous system.

Pharmacokinetics

After oral administration >90% of diazepam is absorbed and the average time to achieve peak plasma concentrations is 1 – 1.5 hours with a range of 0.25 to 2.5 hours. Absorption is delayed and decreased when administered with a moderate fat meal. In the presence of food mean lag times are approximately 45 minutes as compared with 15 minutes when fasting. There is also an increase in the average time to achieve peak concentrations to about 2.5 hours in the presence of food as compared with 1.25 hours when fasting. This results in an average decrease in Cmax of 20% in addition to a 27% decrease in AUC (range 15% to 50%) when administered with food.

Diazepam and its metabolites are highly bound to plasma proteins (diazepam 98%). Diazepam and its metabolites cross the blood-brain and placental barriers and are also found in breast milk in concentrations approximately one tenth of those in maternal plasma (days 3 to 9 post-partum). In young healthy males, the volume of distribution at steady-state is 0.8 to 1.0 L/kg. The decline in the plasma concentration-time profile after oral administration is biphasic. The initial distribution phase has a half-life of approximately 1 hour, although it may range up to >3 hours.

Diazepam is N-demethylated by CYP3A4 and 2C19 to the active metabolite N-desmethyldiazepam, and is hydroxylated by CYP3A4 to the active metabolite temazepam. N-desmethyldiazepam and temazepam are both further metabolized to oxazepam. Temazepam and oxazepam are largely eliminated by glucuronidation.

The initial distribution phase is followed by a prolonged terminal elimination phase (half-life up to 48 hours). The terminal elimination half-life of the active metabolite N-desmethyldiazepam is up to 100 hours. Diazepam and its metabolites are excreted mainly in the urine, predominantly as their glucuronide conjugates. The clearance of diazepam is 20 to 30 mL/min in young adults. Diazepam accumulates upon multiple dosing and there is some evidence that the terminal elimination half-life is slightly prolonged.

Pharmacokinetics in Special Populations

In children 3 - 8 years old the mean half-life of diazepam has been reported to be 18 hours.

In full term infants, elimination half-lives around 30 hours have been reported, with a longer average half-life of 54 hours reported in premature infants of 28 - 34 weeks gestational age and 8 - 81 days post-partum. In both premature and full term infants the active metabolite desmethyldiazepam shows evidence of continued accumulation compared to children. Longer half-lives in infants may be due to incomplete maturation of metabolic pathways.

Elimination half-life increases by approximately 1 hour for each year of age beginning with a half-life of 20 hours at 20 years of age. This appears to be due to an increase in volume of distribution with age and a decrease in clearance. Consequently, the elderly may have lower peak concentrations, and on multiple dosing higher trough concentrations. It will also take longer to reach steady-state. Conflicting information has been published on changes of plasma protein binding in the elderly. Reported changes in free drug may be due to significant decreases in plasma proteins due to causes other than simply aging.

In mild and moderate cirrhosis, average half-life is increased. The average increase has been variously reported from 2-fold to 5-fold, with individual half-lives over 500 hours reported. There is also an increase in volume of distribution, and average clearance decreases by almost half. Mean half-life is also prolonged with hepatic fibrosis to 90 hours (range 66 - 104 hours), with chronic active hepatitis to 60 hours (range 26 - 76 hours), and with acute viral hepatitis to 74 hours (range 49 - 129). In chronic active hepatitis, clearance is decreased by almost half.

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.

For oral administration, Valium is supplied as round, flat-faced scored tablets with V-shaped perforation and beveled edges. Valium is available as follows: 2 mg, white - bottles of 100 (NDC 0140-0004-01); 5 mg, yellow - bottles of 100 (NDC 0140-0005-01) and 500 (NDC 0140-0005-14); 10 mg, blue - bottles of 100 (NDC 0140-0006-01) and 500 (NDC 0140-0006-14).

Engraved on tablets:

2 mg2 Valium® (front)

ROCHE (twice on scored side)   

5 mg5 Valium® (front)

ROCHE (twice on scored side)   

10 mg10 Valium® (front)

ROCHE (twice on scored side)   

STORAGE

Store at room temperature 59° to 86°F (15° to 30°C). Dispense in tight, light-resistant containers as defined in USP/NF.

Valium is a registered trademark of Hoffmann-La Roche, Inc.

Distributed by:

Roche Laboratories Inc. on behalf of Roche Products Inc.
150 Clove Road
Suite 8
Little Falls, NJ 07424

Revised: June 2017

© 2017 Genentech, Inc. All rights reserved.

Representative sample of labeling (see the HOW SUPPLIED section for complete listing):