Side Effects of Valium (diazepam)

Valium (diazepam) is a benzodiazepine used to treat anxiety. Valium also is used to treat 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.

Common side effects of Valium include

• drowsiness,
• fatigue,
• diarrhea,
• rash,
• euphoria,
• loss of balance,
• paradoxical reactions with excitability,
• muscle spasm,
• lack of sleep,
• rage,
• confusion,
• speech problems, and
• double vision.

Serious side effects of Valium include

• respiratory depression,
• low white blood cell counts (neutropenia), and
• depression.

Valium can lead to addiction (dependency), especially when higher dosages are used over prolonged periods of time. Abrupt discontinuation of Valium may cause symptoms of withdrawal such as

• insomnia,
• headaches,
• nausea,
• vomiting,
• lightheadedness,
• sweating,
• anxiety,
• fatigue, and
• seizures in severe cases.

Drug interactions of Valium include alcohol or medications that cause sedation because they may add to the sedative effects of Valium.

• Cimetidine, ketoconazole, itraconazole, omeprazole, erythromycin, clarithromycin, darunavir, fluvoxamine, and fluoxetine may prolong the effects of Valium by inhibiting liver enzymes that eliminate Valium.
• Dosages may need to be decreased when these drugs are used with Valium. Carbamazepine, rifampin, and St. John's wort decrease levels of Valium by increasing the elimination of Valium by liver enzymes.

Benzodiazepines, including Valium, can cause fetal abnormalities and should not be used during pregnancy.

Valium is excreted in breast milk and can affect nursing infants. Valium should not be used by women who are breastfeeding.

The most common side effects of diazepam are:

• Drowsiness
• Fatigue
• Diarrhea
• Rash
• Euphoria
• Ataxia (loss of balance)

Other important side effects include:

• Paradoxical reactions with excitability
• Muscle spasm
• Lack of sleep
• Rage
• Confusion
• Speech problems
• Double vision

Possible serious side effects:

• Respiratory depression
• Neutropenia
• Depression

Side effects most commonly reported were drowsiness, fatigue, muscle weakness, and ataxia. The following have also been reported:

• Central Nervous System: confusion, depression, dysarthria, headache, slurred speech, tremor, vertigo
• Gastrointestinal System: constipation, nausea, gastrointestinal disturbances
• Special Senses: blurred vision, diplopia, dizziness
• Cardiovascular System: hypotension
• Psychiatric and Paradoxical Reactions: stimulation, restlessness, acute hyperexcited states, anxiety, agitation, aggressiveness, irritability, rage, hallucinations, psychoses, delusions, increased muscle spasticity, insomnia, sleep disturbances, and nightmares. Inappropriate behavior and other adverse behavioral effects have been reported when using benzodiazepines. Should these occur, use of the drug should be discontinued. They are more likely to occur in children and in the elderly.
• Urogenital System: incontinence, changes in libido, urinary retention
• Skin and Appendages: skin reactions
• Laboratories: elevated transaminases and alkaline phosphatase
• Other: changes in salivation, including dry mouth, hypersalivation
• Antegrade amnesia may occur using therapeutic dosages, the risk increasing at higher dosages. Amnestic effects may be associated with inappropriate behavior.
• Minor changes in EEG patterns, usually low-voltage fast activity, have been observed in patients during and after Valium therapy and are of no known significance.
• Because of isolated reports of neutropenia and jaundice, periodic blood counts and liver function tests are advisable during long-term therapy.

Postmarketing Experience

• Injury, Poisoning and Procedural Complications: There have been reports of falls and fractures in benzodiazepine users. The risk is increased in those taking concomitant sedatives (including alcohol), and in the elderly.

Centrally Acting Agents

• If Valium is to be combined with other centrally acting agents, careful consideration should be given to the pharmacology of the agents employed particularly with compounds that may potentiate or be potentiated by the action of Valium, such as
  • phenothiazines,
  • antipsychotics,
  • anxiolytics/sedatives,
  • hypnotics,
  • anticonvulsants,
  • narcotic analgesics,
  • anesthetics,
  • sedative antihistamines,
  • narcotics,
  • barbiturates,
  • MAO inhibitors and
  • other antidepressants.

Alcohol

• Concomitant use with alcohol is not recommended due to enhancement of the sedative effect.

Antacids

• Diazepam peak concentrations are 30% lower when antacids are administered concurrently.
• However, there is no effect on the extent of absorption.
• The lower peak concentrations appear due to a slower rate of absorption, with the time required to achieve peak concentrations on average 20 - 25 minutes greater in the presence of antacids.
• However, this difference was not statistically significant.

Compounds Which Inhibit Certain Hepatic Enzymes

• There is a potentially relevant interaction between diazepam and compounds which inhibit certain hepatic enzymes (particularly cytochrome P450 3A and 2C19).
• Data indicate that these compounds influence the pharmacokinetics of diazepam and may lead to increased and prolonged sedation.
• At present, this reaction is known to occur with
  • cimetidine,
  • ketoconazole,
  • fluvoxamine,
  • fluoxetine, and
  • omeprazole.

Phenytoin

• There have also been reports that the metabolic elimination of phenytoin is decreased by diazepam.

Drug Abuse And Dependence

• Diazepam is subject to Schedule IV control under the Controlled Substances Act of 1970.
• Abuse and dependence of benzodiazepines have been reported.
• Addiction-prone individuals (such as drug addicts or alcoholics) should be under careful surveillance when receiving diazepam or other psychotropic agents because of the predisposition of such patients to habituation and dependence.
• Once physical dependence to benzodiazepines has developed, termination of treatment will be accompanied by withdrawal symptoms.
• The risk is more pronounced in patients on long-term therapy.
• Withdrawal symptoms, similar in character to those noted with barbiturates and alcohol have occurred following abrupt discontinuance of diazepam.
• These withdrawal symptoms may consist of tremor, abdominal and muscle cramps, vomiting, sweating, headache, muscle pain, extreme anxiety, tension, restlessness, confusion and irritability.
• In severe cases, the following symptoms may occur:
  • derealization,
  • depersonalization,
  • hyperacusis,
  • numbness and tingling of the extremities,
  • hypersensitivity to light, noise and physical contact,
  • hallucinations or
  • epileptic seizures.
• The more severe withdrawal symptoms have usually been limited to those patients who had received excessive doses over an extended period of time.
• Generally milder withdrawal symptoms (e.g., dysphoria and insomnia) have been reported following abrupt discontinuance of benzodiazepines taken continuously at therapeutic levels for several months.
• Consequently, after extended therapy, abrupt discontinuation should generally be avoided and a gradual dosage tapering schedule followed.
• Chronic use (even at therapeutic doses) may lead to the development of physical dependence: discontinuation of the therapy may result in withdrawal or rebound phenomena.
• Rebound Anxiety: A transient syndrome whereby the symptoms that led to treatment with Valium recur in an enhanced form. This may occur upon discontinuation of treatment. It may be accompanied by other reactions including mood changes, anxiety, and restlessness.
• Since the risk of withdrawal phenomena and rebound phenomena is greater after abrupt discontinuation of treatment, it is recommended that the dosage be decreased gradually.