Diazepam 5mg/1ml Oral Concentrate
WARNING: This drug is a benzodiazepine. The use of a benzodiazepine drug along with opioid drugs has led to very bad side effects. Side effects that have happened include slowed or trouble breathing and death. Opioid drugs include drugs like codeine, oxycodone, and morphine. Opioid drugs are used to treat pain and some are used to treat cough. Talk with the doctor.If you are taking this drug with an opioid drug, get medical help right away if you feel very sleepy or dizzy; if you have slow, shallow, or trouble breathing; or if you pass out. Caregivers or others need to get medical help right away if the patient does not respond, does not answer or react like normal, or will not wake up. Benzodiazepines can put you at risk for drug use disorder. Misuse or abuse of this drug can lead to overdose or death, especially when used along with certain other drugs, alcohol, or street drugs. Drug use disorder can happen even if you take this drug as your doctor has told you. Get medical help right away if you have changes in mood or behavior, suicidal thoughts or actions, seizures, or trouble breathing.You will be watched closely to make sure you do not misuse this drug or develop drug use disorder.Benzodiazepines may cause dependence. Lowering the dose or stopping this drug all of a sudden may cause withdrawal. This can be life- threatening. The risk of dependence and withdrawal are raised the longer you take this drug and the higher the dose. Talk to your doctor before you lower the dose or stop this drug. You will need to follow your doctor's instructions. Get medical help right away if you have trouble controlling body movements, seizures, new or worse behavior or mood changes like depression or thoughts of suicide, thoughts of harming someone, hallucinations (seeing or hearing things that are not there), losing contact with reality, moving around or talking a lot, or any other bad effects.Sometimes, withdrawal signs can last for several weeks to more than 12 months. Tell your doctor if you have anxiety; trouble with memory, learning, or focusing; trouble sleeping; burning, numbness, or tingling; weakness; shaking; muscle twitching; ringing in the ears; or any other bad effects. @ COMMON USES: It is used to relax muscles.It is used to treat alcohol withdrawal.It is used to treat anxiety.It is used to help control certain kinds of seizures.It may be given to you for other reasons. Talk with the doctor.
Drug Class
Antianxiety agent, anticonvulsant, sedative-hypnotic, skeletal muscle relaxant
Pharmacologic Class
Benzodiazepine
Pregnancy Category
Category D
FDA Approved
Nov 1963
DEA Schedule
Schedule IV
Overview
What is this medicine?
Diazepam is a medication that belongs to a group of drugs called benzodiazepines. It works by calming the brain and nerves. It's used to treat anxiety, muscle spasms, and seizures, and also to help with alcohol withdrawal symptoms. It comes as a liquid concentrate that you take by mouth.
How to Use This Medicine
Taking Your Medication Correctly
To ensure you get the most out of your medication, follow these steps:
Take your medication exactly as directed by your doctor.
Read all the information provided with your medication and follow the instructions carefully.
You can take your medication with or without food. If it causes stomach upset, take it with food.
Make sure you have the correct liquid strength, as there are multiple strengths available.
Measure your liquid doses accurately using the measuring device that comes with your medication.
Mix the liquid with water, juice, soda, applesauce, or pudding before taking it. Swallow the mixture immediately and do not store it for later use.
Storing and Disposing of Your Medication
To keep your medication safe and effective:
Store it at room temperature, protected from light and moisture.
Keep it in a dry place, away from bathrooms.
Discard any unused medication after 3 months.
Store your medication in a secure location where children and pets cannot access it. Consider using a locked box or area to keep it safe.
Dispose of unused or expired medication properly. Do not flush it down the toilet or pour it down the drain unless instructed to do so. Check with your pharmacist for guidance on disposal or to see if there are any drug take-back programs in your area.
What to Do If You Miss a Dose
If you take your medication regularly and miss a dose:
Take the missed dose as soon as you remember.
If it's close to the time for your next dose, skip the missed dose and resume your regular schedule.
Do not take two doses at the same time or take extra doses.
* If you take your medication as needed, do not take it more frequently than directed by your doctor.
To ensure you get the most out of your medication, follow these steps:
Take your medication exactly as directed by your doctor.
Read all the information provided with your medication and follow the instructions carefully.
You can take your medication with or without food. If it causes stomach upset, take it with food.
Make sure you have the correct liquid strength, as there are multiple strengths available.
Measure your liquid doses accurately using the measuring device that comes with your medication.
Mix the liquid with water, juice, soda, applesauce, or pudding before taking it. Swallow the mixture immediately and do not store it for later use.
Storing and Disposing of Your Medication
To keep your medication safe and effective:
Store it at room temperature, protected from light and moisture.
Keep it in a dry place, away from bathrooms.
Discard any unused medication after 3 months.
Store your medication in a secure location where children and pets cannot access it. Consider using a locked box or area to keep it safe.
Dispose of unused or expired medication properly. Do not flush it down the toilet or pour it down the drain unless instructed to do so. Check with your pharmacist for guidance on disposal or to see if there are any drug take-back programs in your area.
What to Do If You Miss a Dose
If you take your medication regularly and miss a dose:
Take the missed dose as soon as you remember.
If it's close to the time for your next dose, skip the missed dose and resume your regular schedule.
Do not take two doses at the same time or take extra doses.
* If you take your medication as needed, do not take it more frequently than directed by your doctor.
Lifestyle & Tips
- Avoid alcohol and other sedating medications (e.g., opioids, sleeping pills) while taking diazepam, as this can lead to dangerous drowsiness and breathing problems.
- Do not drive or operate heavy machinery until you know how this medication affects you, as it can cause dizziness and drowsiness.
- Do not stop taking this medication suddenly, especially if you have been taking it regularly for a long time. This can cause serious withdrawal symptoms, including seizures. Your doctor will help you gradually reduce the dose.
- Store the oral concentrate properly, often in the refrigerator, and use the provided dropper for accurate dosing.
- Inform your doctor about all other medications, supplements, and herbal products you are taking.
Available Forms & Alternatives
Available Strengths:
- Diazepam 2mg Tablets
- Diazepam 5mg Tablets
- Diazepam 10mg Tablets
- Diazepam 5mg/5ml (1mg/1ml) Oral Sol
- Diazepam 5mg/1ml Oral Concentrate
- Diazepam 5mg/ml Inj, 2ml
- Diazepam 5mg/ml Inj, 10ml
- Diazepam 20mg Rectal Gel
- Diazepam 10mg Rectal Gel( 2 Pack)
- Diazepam 2.5mg Rectal Gel (2 Pack)
- Diazepam 5mg/ml Inj, 2ml
- Diazepam 10mg Rectal Gel (2 Pack)
- Diazepam 20mg Rectal Gel
- Diazepam 10mg/2ml Inj, 2ml
Dosing & Administration
Adult Dosing
Standard Dose:
Varies by indication. For anxiety: 2-10 mg orally 2-4 times daily. For acute alcohol withdrawal: 10 mg orally 3-4 times daily for the first 24 hours, then 5 mg 3-4 times daily as needed. For muscle spasm: 2-10 mg orally 3-4 times daily.
Dose Range:
2 - 40 mg
Condition-Specific Dosing:
Anxiety:
2-10 mg orally 2-4 times daily
Acute Alcohol Withdrawal:
10 mg orally 3-4 times daily for 24 hours, then 5 mg 3-4 times daily as needed
Muscle Spasm:
2-10 mg orally 3-4 times daily
Adjunct in Convulsive Disorders:
2-10 mg orally 2-4 times daily
Pediatric Dosing
Neonatal:
Not established (contraindicated in infants <30 days due to risk of gasping syndrome with parenteral benzyl alcohol, and general risk of CNS depression).
Infant:
Not established for infants <6 months. For infants >6 months: 1-2.5 mg orally 3-4 times daily, or 0.12-0.8 mg/kg/day in divided doses.
Child:
0.12-0.8 mg/kg/day orally in divided doses (e.g., 1-2.5 mg 3-4 times daily), not to exceed 10 mg/dose.
Adolescent:
Initial dose typically 2-5 mg orally 2-4 times daily, adjusted based on response and tolerability.
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment generally required, but use with caution.
Moderate:
No specific dose adjustment generally required, but use with caution.
Severe:
No specific dose adjustment generally required, but use with caution. Monitor for increased sedation due to accumulation of active metabolites.
Dialysis:
Diazepam and its active metabolites are not significantly removed by dialysis. Administer after dialysis if needed, or monitor closely.
Hepatic Impairment:
Mild:
Use with caution. Consider lower initial doses.
Moderate:
Reduce initial dose by 50% or more. Titrate slowly based on clinical response and tolerability. Monitor closely for sedation.
Severe:
Contraindicated or use with extreme caution and significantly reduced dosage (e.g., 2 mg once daily initially). Monitor closely for encephalopathy and profound sedation.
Pharmacology
Mechanism of Action
Diazepam binds to stereospecific benzodiazepine receptors on the postsynaptic GABA-A neuron at several sites within the central nervous system, including the limbic system, reticular formation, and cerebral cortex. This binding enhances the inhibitory effects of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, by increasing the frequency of chloride channel opening, leading to hyperpolarization of the neuronal membrane and decreased neuronal excitability.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 90-100% (oral)
Tmax:
Oral solution/concentrate: 1-1.5 hours; Tablets: 1-2 hours
FoodEffect:
Food can delay the rate of absorption (increase Tmax) but generally does not significantly affect the extent of absorption (AUC).
Distribution:
Vd:
0.8-1.0 L/kg (adults); higher in children and lower in elderly
ProteinBinding:
Approximately 98% (primarily to albumin)
CnssPenetration:
Yes
Elimination:
HalfLife:
Diazepam: 20-100 hours (highly variable, longer in elderly and liver disease); Desmethyldiazepam: 30-100 hours
Clearance:
Approximately 20-32 mL/min (adults)
ExcretionRoute:
Primarily renal (as metabolites), small amount in feces.
Unchanged:
<1% (renal)
Pharmacodynamics
OnsetOfAction:
Oral: 15-60 minutes
PeakEffect:
Oral: 1-2 hours
DurationOfAction:
6-8 hours (clinical effects), but active metabolites prolong effects and accumulation can occur with chronic dosing.
Safety & Warnings
BLACK BOX WARNING
Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation. The concomitant use of benzodiazepines, including diazepam, and opioids may result in profound sedation, respiratory depression, coma, and death. Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. If a decision is made to prescribe diazepam concomitantly with opioids, prescribe the lowest effective dosages and minimum durations of concomitant use, and follow patients closely for signs and symptoms of respiratory depression and sedation. Advise both patients and caregivers about the risks of respiratory depression and sedation when diazepam is used with opioids. Advise patients not to drive or operate heavy machinery until the effects of concomitant use with the opioid have been determined. The use of benzodiazepines, including diazepam, exposes patients to the risks of abuse, misuse, and addiction, which can lead to overdose or death. Before prescribing diazepam, assess each patient’s risk for abuse, misuse, and addiction. After diazepam has been prescribed, assess and monitor each patient regularly for these behaviors and conditions. The continued use of benzodiazepines, including diazepam, may lead to clinically significant physical dependence. The risks of dependence and withdrawal increase with longer treatment duration and higher daily dose. Abrupt discontinuation or rapid dosage reduction of diazepam after continued use may precipitate acute withdrawal reactions, which can be life-threatening. To reduce the risk of withdrawal reactions, use a gradual taper to discontinue diazepam or reduce the dosage.
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
While rare, some people may experience severe and potentially life-threatening side effects when taking this medication. If you experience any of the following symptoms, contact your doctor or seek medical attention immediately:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Shortness of breath
Change in balance
Feeling confused
Hallucinations (seeing or hearing things that are not there)
Memory problems or loss
Severe dizziness or passing out
Muscle spasm
Twitching
Trouble sleeping
Change in eyesight
Slurred speech
Severe upset stomach, vomiting, or loss of appetite that does not go away
Like other medications used to treat seizures, this drug may rarely increase the risk of suicidal thoughts or actions, especially in people who have had suicidal thoughts or actions in the past. If you experience any new or worsening symptoms, such as:
Depression
Feeling nervous, restless, or irritable
Panic attacks
Other changes in mood or behavior
contact your doctor right away. If you have suicidal thoughts or actions, seek medical help immediately.
Other Possible Side Effects
Most people do not experience significant side effects, but some may occur. If you experience any of the following side effects and they bother you or do not go away, contact your doctor:
Feeling sleepy
Feeling tired or weak
Muscle weakness
This is not a comprehensive list of all possible side effects. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
While rare, some people may experience severe and potentially life-threatening side effects when taking this medication. If you experience any of the following symptoms, contact your doctor or seek medical attention immediately:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Shortness of breath
Change in balance
Feeling confused
Hallucinations (seeing or hearing things that are not there)
Memory problems or loss
Severe dizziness or passing out
Muscle spasm
Twitching
Trouble sleeping
Change in eyesight
Slurred speech
Severe upset stomach, vomiting, or loss of appetite that does not go away
Like other medications used to treat seizures, this drug may rarely increase the risk of suicidal thoughts or actions, especially in people who have had suicidal thoughts or actions in the past. If you experience any new or worsening symptoms, such as:
Depression
Feeling nervous, restless, or irritable
Panic attacks
Other changes in mood or behavior
contact your doctor right away. If you have suicidal thoughts or actions, seek medical help immediately.
Other Possible Side Effects
Most people do not experience significant side effects, but some may occur. If you experience any of the following side effects and they bother you or do not go away, contact your doctor:
Feeling sleepy
Feeling tired or weak
Muscle weakness
This is not a comprehensive list of all possible side effects. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Extreme drowsiness or difficulty waking up
- Slow or shallow breathing
- Severe dizziness or lightheadedness
- Slurred speech
- Unusual confusion or disorientation
- Loss of coordination or balance (ataxia)
- Yellowing of the skin or eyes (jaundice)
- Signs of an allergic reaction (rash, itching, swelling, severe dizziness, trouble breathing)
- Paradoxical reactions (increased anxiety, agitation, aggression, hallucinations)
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following conditions to ensure safe treatment:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Describe the allergic reactions you have experienced.
Certain health conditions, including:
+ Breathing problems
+ Glaucoma
+ Liver disease
+ Myasthenia gravis
+ Sleep apnea
A history of psychosis
Recent consumption of large amounts of alcohol or use of medications that may slow your reactions, such as phenobarbital or certain pain medications like oxycodone
If you are breastfeeding or plan to breastfeed, as you may need to avoid nursing
Special Considerations for Children:
If the patient is under 6 months of age, do not administer this medication, as it is not suitable for infants younger than 6 months.
To ensure your safety, it is crucial to disclose all of the following to your doctor and pharmacist:
All medications you are taking, including prescription and over-the-counter drugs, natural products, and vitamins
Any health problems you have
Your doctor will assess the potential interactions between this medication and your other medications or health conditions to determine the safest course of treatment. Never start, stop, or change the dose of any medication without consulting your doctor.
It is essential to inform your doctor about the following conditions to ensure safe treatment:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Describe the allergic reactions you have experienced.
Certain health conditions, including:
+ Breathing problems
+ Glaucoma
+ Liver disease
+ Myasthenia gravis
+ Sleep apnea
A history of psychosis
Recent consumption of large amounts of alcohol or use of medications that may slow your reactions, such as phenobarbital or certain pain medications like oxycodone
If you are breastfeeding or plan to breastfeed, as you may need to avoid nursing
Special Considerations for Children:
If the patient is under 6 months of age, do not administer this medication, as it is not suitable for infants younger than 6 months.
To ensure your safety, it is crucial to disclose all of the following to your doctor and pharmacist:
All medications you are taking, including prescription and over-the-counter drugs, natural products, and vitamins
Any health problems you have
Your doctor will assess the potential interactions between this medication and your other medications or health conditions to determine the safest course of treatment. Never start, stop, or change the dose of any medication without consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
When starting this medication, be cautious when driving or performing tasks that require alertness and clear vision until you understand how it affects you.
To minimize potential risks, avoid consuming alcohol while taking this medication. Additionally, consult your doctor before using marijuana, other cannabis products, or prescription and over-the-counter (OTC) medications that may cause drowsiness or slow your reactions.
If you experience changes in your seizure patterns or if they worsen after initiating this medication, promptly discuss these changes with your doctor.
This medication can cause drowsiness and impaired alertness, increasing the risk of falls, particularly in older adults. If you have concerns, consult your doctor to discuss potential strategies to mitigate this risk.
Do not adjust the dosage or discontinue this medication without consulting your doctor, as this may lead to seizures. If you are taking this medication long-term, your doctor may recommend regular blood tests to monitor your condition.
Prolonged use of this medication or taking it at high doses may lead to tolerance, reducing its effectiveness. In such cases, you may require higher doses to achieve the same therapeutic effect. If you notice a decrease in the medication's efficacy, contact your doctor. However, do not exceed the prescribed dosage.
Older adults (65 years and older) should exercise caution when taking this medication, as they may be more susceptible to side effects. Similarly, children should be closely monitored, as they may have a higher risk of experiencing certain side effects.
If you are pregnant or become pregnant while taking this medication, immediately notify your doctor, as it may pose risks to the unborn baby. Taking this medication late in pregnancy can increase the likelihood of respiratory or feeding problems, low body temperature, or withdrawal symptoms in the newborn. Therefore, it is crucial to discuss the potential risks and benefits with your doctor.
When starting this medication, be cautious when driving or performing tasks that require alertness and clear vision until you understand how it affects you.
To minimize potential risks, avoid consuming alcohol while taking this medication. Additionally, consult your doctor before using marijuana, other cannabis products, or prescription and over-the-counter (OTC) medications that may cause drowsiness or slow your reactions.
If you experience changes in your seizure patterns or if they worsen after initiating this medication, promptly discuss these changes with your doctor.
This medication can cause drowsiness and impaired alertness, increasing the risk of falls, particularly in older adults. If you have concerns, consult your doctor to discuss potential strategies to mitigate this risk.
Do not adjust the dosage or discontinue this medication without consulting your doctor, as this may lead to seizures. If you are taking this medication long-term, your doctor may recommend regular blood tests to monitor your condition.
Prolonged use of this medication or taking it at high doses may lead to tolerance, reducing its effectiveness. In such cases, you may require higher doses to achieve the same therapeutic effect. If you notice a decrease in the medication's efficacy, contact your doctor. However, do not exceed the prescribed dosage.
Older adults (65 years and older) should exercise caution when taking this medication, as they may be more susceptible to side effects. Similarly, children should be closely monitored, as they may have a higher risk of experiencing certain side effects.
If you are pregnant or become pregnant while taking this medication, immediately notify your doctor, as it may pose risks to the unborn baby. Taking this medication late in pregnancy can increase the likelihood of respiratory or feeding problems, low body temperature, or withdrawal symptoms in the newborn. Therefore, it is crucial to discuss the potential risks and benefits with your doctor.
Overdose Information
Overdose Symptoms:
- Somnolence (extreme drowsiness)
- Confusion
- Diminished reflexes
- Coma
- Hypotension (low blood pressure)
- Respiratory depression (slow, shallow breathing)
What to Do:
Seek immediate medical attention. Call 911 or Poison Control at 1-800-222-1222. Flumazenil may be used as an antidote in a hospital setting, but it carries risks, especially in patients with chronic benzodiazepine use or seizure disorders.
Drug Interactions
Contraindicated Interactions
- Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir) in patients with severe respiratory insufficiency or sleep apnea, due to increased risk of profound sedation and respiratory depression.
- Opioids (concomitant use is a Black Box Warning, not an absolute contraindication, but requires extreme caution and dose reduction of one or both agents).
Major Interactions
- Opioids (e.g., fentanyl, oxycodone, hydrocodone): Increased risk of respiratory depression, profound sedation, coma, and death.
- Other CNS depressants (e.g., alcohol, barbiturates, other benzodiazepines, tricyclic antidepressants, antihistamines, general anesthetics): Additive CNS depression.
- Strong CYP3A4 inhibitors (e.g., azole antifungals, macrolide antibiotics like erythromycin, clarithromycin, protease inhibitors): Significantly increase diazepam plasma concentrations, leading to increased sedation and respiratory depression.
- Strong CYP2C19 inhibitors (e.g., fluvoxamine, omeprazole, fluoxetine): Increase diazepam plasma concentrations.
- Phenytoin: Diazepam may alter phenytoin levels; monitor phenytoin levels.
Moderate Interactions
- Moderate CYP3A4 inhibitors (e.g., diltiazem, verapamil, grapefruit juice): May increase diazepam levels.
- Moderate CYP2C19 inhibitors (e.g., cimetidine, esomeprazole): May increase diazepam levels.
- Digoxin: May increase serum digoxin concentrations.
- Theophylline: May antagonize the sedative effects of diazepam.
Minor Interactions
- Antacids: May delay the rate of diazepam absorption but not the extent.
Monitoring
Baseline Monitoring
Liver Function Tests (LFTs)
Rationale: Diazepam is extensively metabolized by the liver; hepatic impairment can significantly alter its pharmacokinetics and increase risk of adverse effects.
Timing: Prior to initiation, especially in patients with suspected or known liver disease.
Renal Function (BUN, Creatinine)
Rationale: Although primarily metabolized by the liver, metabolites are renally excreted. Severe renal impairment may lead to accumulation of active metabolites.
Timing: Prior to initiation, especially in patients with suspected or known renal disease.
Respiratory Status
Rationale: To assess baseline respiratory function, especially in patients with pre-existing respiratory compromise (e.g., COPD, sleep apnea) due to risk of respiratory depression.
Timing: Prior to initiation.
Mental Status/Cognitive Function
Rationale: To establish a baseline for assessing drug-induced sedation, cognitive impairment, and therapeutic response.
Timing: Prior to initiation.
Routine Monitoring
Level of Sedation/Alertness
Frequency: Daily during initiation/dose titration, then periodically as clinically indicated.
Target: Appropriate level of anxiolysis/sedation without excessive drowsiness or impairment.
Action Threshold: Excessive sedation, somnolence, slurred speech, ataxia; consider dose reduction or discontinuation.
Respiratory Rate and Depth
Frequency: Daily during initiation/dose titration, especially with concomitant opioid use, then periodically as clinically indicated.
Target: Normal respiratory rate and effort for the patient.
Action Threshold: Bradypnea, shallow breathing, hypoventilation; consider dose reduction, discontinuation, or respiratory support.
Therapeutic Response (e.g., anxiety reduction, seizure control, muscle spasm relief)
Frequency: Daily during acute treatment, then periodically to assess efficacy.
Target: Achievement of therapeutic goals with minimal side effects.
Action Threshold: Lack of efficacy or worsening symptoms; consider dose adjustment or alternative therapy.
Signs of Dependence/Withdrawal
Frequency: Periodically, especially with long-term use or during dose reduction/discontinuation.
Target: Absence of withdrawal symptoms (e.g., rebound anxiety, insomnia, seizures).
Action Threshold: Emergence of withdrawal symptoms; consider slower taper or re-evaluation of treatment plan.
Symptom Monitoring
- Excessive drowsiness
- Dizziness
- Ataxia (loss of coordination)
- Slurred speech
- Confusion
- Memory impairment
- Difficulty breathing or shallow breathing
- Unusual weakness
- Paradoxical reactions (e.g., excitement, aggression, hallucinations)
- Signs of withdrawal upon discontinuation (e.g., rebound anxiety, insomnia, irritability, tremors, seizures)
Special Patient Groups
Pregnancy
Diazepam is classified as Pregnancy Category D. It should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus. Benzodiazepines, including diazepam, can cross the placenta.
Trimester-Specific Risks:
First Trimester:
Increased risk of congenital malformations (e.g., cleft lip/palate) has been suggested in some studies, though data are conflicting and not definitively established.
Second Trimester:
Risk of fetal exposure and potential for adverse effects, though less data on specific malformations compared to first trimester.
Third Trimester:
Risk of 'floppy infant syndrome' (hypotonia, lethargy, hypothermia, respiratory depression, feeding difficulties) if used late in pregnancy or during labor. Risk of neonatal withdrawal symptoms (e.g., irritability, hypertonia, tremors, feeding difficulties) if used chronically during pregnancy.
Lactation
Diazepam and its active metabolites are excreted into breast milk. It is classified as L4 (Possibly Hazardous) by LactMed. Due to the long half-life of diazepam and its active metabolites, accumulation can occur in the infant, leading to sedation, lethargy, poor feeding, and weight loss.
Infant Risk:
High risk of sedation, lethargy, poor feeding, and potential for respiratory depression in the breastfed infant. Long-term effects on neurodevelopment are unknown. Breastfeeding is generally not recommended while taking diazepam, or if used, the infant should be closely monitored for adverse effects.
Pediatric Use
Not recommended for infants younger than 6 months due to potential for prolonged sedation and respiratory depression. Use with caution in older children, starting with the lowest effective dose and titrating slowly. Children may be more sensitive to CNS depressant effects. Paradoxical reactions (e.g., hyperactivity, agitation) may occur.
Geriatric Use
Elderly patients are more sensitive to the effects of benzodiazepines due to decreased metabolism, increased volume of distribution, and increased brain sensitivity. They are at increased risk for sedation, dizziness, ataxia, falls, and cognitive impairment. Initial doses should be significantly lower (e.g., 2 mg 2-4 times daily) and titrated slowly. Monitor closely for adverse effects.
Clinical Information
Clinical Pearls
- Diazepam oral concentrate (5mg/1ml) requires careful measurement with a calibrated dropper. Ensure patients understand how to measure the dose accurately.
- Due to its long half-life and active metabolites, diazepam can accumulate with chronic use, especially in elderly patients or those with liver impairment, leading to prolonged sedation.
- Abrupt discontinuation after prolonged use can lead to severe and potentially life-threatening withdrawal symptoms, including seizures. Always taper the dose gradually.
- Diazepam is a Schedule IV controlled substance due to its potential for abuse, misuse, and dependence. Prescribers should assess patient risk factors before prescribing and monitor for signs of abuse.
- The Black Box Warning regarding concomitant use with opioids is critical. Educate patients and caregivers about the risks of profound sedation and respiratory depression.
- Consider alternative, shorter-acting benzodiazepines or non-benzodiazepine options for anxiety or insomnia, especially in the elderly, to minimize accumulation and fall risk.
Alternative Therapies
- Other benzodiazepines (e.g., lorazepam, alprazolam, clonazepam for anxiety/seizures; midazolam for acute sedation)
- SSRIs/SNRIs (for anxiety disorders)
- Buspirone (for generalized anxiety disorder)
- Anticonvulsants (e.g., levetiracetam, valproic acid, phenytoin for seizure disorders)
- Skeletal muscle relaxants (e.g., cyclobenzaprine, tizanidine for muscle spasms)
- Beta-blockers (e.g., propranolol for situational anxiety)
- Non-pharmacological therapies (e.g., cognitive behavioral therapy, psychotherapy, exercise, mindfulness for anxiety)
Cost & Coverage
Average Cost:
Varies widely, typically $10-$50 per 30ml (5mg/ml) oral concentrate
Generic Available:
Yes
Insurance Coverage:
Tier 1 or Tier 2 (Generic)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe use, never share your medication with others or take someone else's medication. This medication is accompanied by a Medication Guide, which provides crucial information for patients. Please read this guide carefully and review it again whenever you receive a refill of this medication. If you have any questions or concerns about this medication, consult your doctor, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When reporting the incident, be prepared to provide details about the medication taken, the quantity, and the time it occurred.