Diazepam

Registered South African indications:

• Anxiety
• Pre-operative medication
• Alcohol withdrawal syndrome
• Muscle relaxation

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Known history of hypersensitivity to benzodiazepines
• Severe respiratory insufficiency
• Severe hepatic insufficiency
• Sleep apnoea syndrome
• Myasthenia gravis
• Diazepam is not recommended for the primary treatment of psychotic illness
• Diazepam should not be used alone to treat depression or anxiety associated with depression as suicide may occur in such patients
• Dependence on other CNS depressants including alcohol, except in the acute withdrawal reactions

• Pregnancy
• Breastfeeding
• Renal impairment
• Mild to moderate hepatic impairment
• Elderly
• Marked personality disorder 
• Abrupt withdrawal
• Epilepsy or history of seizures 
• Prolonged duration of treatment
• Bereavement
• Monotherapy in psychotic illness
• Coma
• Organic brain changes, particularly arteriosclerosis
• Tolerance
• Children
• Debilitated patients  
• History of alcohol or drug abuse
• Personality disorders
• Galactose intolerance (tab)
• Lapp lactase deficiency (tab)
• Glucose-galactose malabsorption (tab)
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: tab

South African registered indications and dosages
Anxiety
- Symptomatic relief of anxiety, tension, and other somatic or psychological complaints associated with the anxiety syndrome
- Adjunct to the treatment of anxiety or excitation associated with psychiatric disorders
Anxiety in neurotic patients, pre-operative medication, and relief of acute symptoms of alcohol withdrawal syndrome
Muscle relaxation
- Adjunct for the relief of reflex muscle spasm due to local trauma (injury, inflammation)
- Combat spasticity from damage to spinal and supraspinal interneurons, cerebral palsy, paraplegia, athetosis, and stiff-man syndrome

• Oral (tab): Initial dose: 5-10mg; Depending on symptom severity, usual dose: 5-20mg daily; Maximum single dose: 10mg

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Diazepam is only indicated when the disorder is severe, disabling, or subject to extreme stress

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For optimal effect, the dosage should be carefully individualised. Treatment should begin at the lowest effective dose appropriate to the particular condition and the maximum dose should not be exceeded

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Duration of treatment: Should be as short as possible, not exceeding 8-12 weeks for anxiety treatment, including a tapering off process. Treatment should not exceed 2-3 months overall, including the tapering-off period. Extension beyond this period requires re-evaluation

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Treatment should be started with an understanding that it will be of limited duration. Informing the patient about the dosage tapering process can help minimize anxiety during withdrawal

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Rebound phenomena can manifest during withdrawal. This is especially true for short-acting benzodiazepines and can be evident within the dosage interval, especially at high doses. When transitioning from long-acting benzodiazepines like diazepam, it's crucial to warn against switching to short-acting benzodiazepines to prevent withdrawal symptoms

Paed. forms avail. in SA and covered in this monograph: tab

South African registered indications and dosages
Anxiety
- Symptomatic relief of anxiety, tension, and other somatic or psychological complaints associated with the anxiety syndrome
- Adjunct to the treatment of anxiety or excitation associated with psychiatric disorders
Anxiety in neurotic patients, pre-operative medication, and relief of acute symptoms of alcohol withdrawal syndrome
Muscle relaxation
- Adjunct for the relief of reflex muscle spasm due to local trauma (injury, inflammation)
- Combat spasticity from damage to spinal and supraspinal interneurons, cerebral palsy, paraplegia, athetosis, and stiff-man syndrome

Younger than 6 months

• Not established for use

Older than 6 months

• Oral (tab): 0.1-0.3mg/kg bodyweight, daily

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Only indicated when the disorder is severe, disabling, or subject to extreme stress

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Diazepam should not be given to children without careful assessment of the indication; the duration of treatment must be kept to a minimum

Pregnancy 

South African recommendations

• Caution; positive evidence of risk
• The safety of diazepam during pregnancy has not been established
• An increased risk of congenital malformation has been suggested when benzodiazepines are used during the first trimester of pregnancy
• Continuous administration of benzodiazepines during pregnancy might lead to the floppy-infant syndrome, characterized by hypotension, reduced respiratory function, and hypothermia in the newborn
• Withdrawal symptoms in newborn infants have been associated with diazepam
• Special care is required when diazepam is used during labour and delivery. High single doses can cause irregularities in the fetal heart rate and lead to symptoms such as hypotonia, poor sucking, hypothermia, and moderate respiratory depression in the neonate
• It's important to note that the enzyme system responsible for breaking down the medication is not fully developed in newborns, especially in premature infants

Breastfeeding

South African recommendations

• Caution; not recommended
• Diazepam is excreted into breast milk and should not be administered to breastfeeding mothers

Fertility

South African recommendations

• No information available

South African recommendations

• Caution; no dose adjustment recommended
  The usual precautions in treating patients with impaired renal function should be observed

South African recommendations

• Mild to moderate: Caution; dose adjustment recommended
  Patients with impaired hepatic function should be given a reduced dose
• Severe: Contraindicated

South African recommendations

• Caution; dose adjustment recommended
  Elderly and debilitated patients who are at particular risk of over sedation, respiratory depression and ataxia should be given half of the usual adult dose
  These patients should be checked regularly at the start of treatment in order to minimise the dosage and/or frequency of administration to prevent overdose due to accumulation

Central Nervous System Disorders

• Confusion
• Paradoxical reactions 
• Emotional poverty
• Depression
• Drowsiness
• Ataxia
• Impaired motor ability
• Tremor
• Anterograde amnesia
• Concentration difficulties
• Balance disorders
• Dizziness
• Headache
• Slurred speech
• Unconsciousness
• Insomnia
• Dysarthria
• Fatigue

Cardiovascular Disorders

• Bradycardia
• Cardiac failure 
• Cardiac arrest
• Hypotension
• Syncope

Respiratory Disorders

• Respiratory depression
• Respiratory arrest
• Increased bronchial secretions
• Apnoea

Gastrointestinal Disorders

• Nausea and vomiting
• Constipation
• Diarrhoea
• Increased salivary secretion
• Dry mouth 
• Increased appetite

Hepatobiliary Disorders

• Jaundice
• Changes of hepatic parameters

Genitourinary Disorders

• Urinary retention
• Incontinence
• Gynaecomastia
• Impotence
• Increased or reduced libido

Musculoskeletal Disorders

• Myasthenia 

Skin and Subcutaneous Tissue Disorders

• Allergic skin reactions 

Immune, Blood and Lymphatic System Disorders

• Blood dyscrasias
• Leukopenia
• Anaphylaxis

Sensory Disorders

• Blurred vision
• Diplopia
• Nystagmus

Others

• Withdrawal 

• Central nervous system depressants
• Narcotic analgesics
• CYP450 inhibitors
• CYP450 inducers
• Sodium oxybate
• HIV protease inhibitors
• Cisapride
• Zidovudine
• Antibacterials
• Antihypertensives
• Lofexidine
• Digoxin
• Disulfiram
• Levodopa
• Muscle-relaxants 
• Nabilone
• Nicotine
• Oral contraceptives
• Theophylline
• Ketamine
• Caffeine
• Omeprazole

Other interactions

• Alcohol

None routine. Specific cases may require

• Mental status
• Hepatic function
• Vital signs
• Respiratory function

Diazepam binds nonspecifically to benzodiazepine receptors and facilitates the action of gamma aminobutyric acid, an inhibitory neurotransmitter in the central nervous system. It is found in high concentrations in the cortex and limbic system.

Tablet 5mg

• Betapam (Ranbaxy Pharmaceuticals)
• Doval (Innovata)
• Pax (Pharmacare) Discontinued
• Sandoz Diazepam (Sandoz)
• Valium (Roche) originator

Tablet 10mg

• Pax (Pharmacare)
• Valium (Roche) originator