Diazepam (Rectal Solution)

What Is Diazepam and What Is It Used For?

Quick Answer: Diazepam belongs to the benzodiazepine class of medicines. In rectal solution form, it is primarily used for the emergency treatment of epileptic seizures and febrile convulsions, as a sedative before procedures, for muscle spasms in tetanus, and for severe, disabling anxiety when oral administration or injection is impractical.

Diazepam is one of the most widely recognized and extensively studied benzodiazepine medications in the world. Listed on the World Health Organization (WHO) Model List of Essential Medicines, it has been a cornerstone of acute seizure management and anxiolytic therapy since its introduction in the 1960s. The rectal solution formulation was developed to provide a rapid, non-invasive route of administration that can be used outside hospital settings, making it particularly valuable for the emergency treatment of seizures in children at home or in school settings.

The mechanism of action of diazepam involves enhancing the effect of gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system. By binding to specific sites on GABA-A receptors, diazepam increases the frequency of chloride ion channel opening, resulting in enhanced neuronal inhibition. This produces the drug's characteristic spectrum of pharmacological effects: anxiolytic (anxiety-reducing), sedative, muscle relaxant, anticonvulsant, and amnestic properties.

Primary Indications

Diazepam rectal solution is indicated for several clinical scenarios where rapid drug delivery is essential:

• Epileptic seizures and status epilepticus: The rectal solution provides a critical first-line option for managing prolonged tonic-clonic seizures lasting more than 5 minutes, or clusters of seizures occurring without full recovery between episodes. The International League Against Epilepsy (ILAE) recognizes rectal diazepam as an established rescue medication for community-based seizure management.
• Febrile convulsions in children: Fever-related seizures in young children can be rapidly terminated with rectal diazepam, making it an essential medication for parents and caregivers to have available. It is particularly useful for children aged 1–5 years who are most susceptible to febrile seizures.
• Pre-procedural sedation: When used before minor surgical or dental procedures, diazepam provides both anxiolysis and sedation, reducing patient distress and facilitating the procedure. The rectal route may be preferred when oral sedation is impractical, particularly in young children or uncooperative patients.
• Muscle spasms in tetanus: Severe tetanus-related muscle spasms can be life-threatening, and high-dose diazepam remains a key component of tetanus treatment protocols worldwide, as recommended by the WHO.
• Severe, disabling anxiety: In cases of acute, overwhelming anxiety or agitation where other routes of administration are unsuitable, rectal diazepam can provide rapid relief. However, it is not intended for routine anxiety management.

Pharmacokinetics

When administered rectally, diazepam is rapidly absorbed through the rectal mucosa, with bioavailability approaching 80–100%. Peak plasma concentrations are typically achieved within 10–30 minutes, although the onset of clinical anticonvulsant effect occurs within 5–15 minutes. This rapid onset makes rectal diazepam particularly suitable for emergency seizure management in community settings.

Diazepam is extensively metabolized in the liver, primarily by the cytochrome P450 enzymes CYP3A4 and CYP2C19, to pharmacologically active metabolites including desmethyldiazepam (nordiazepam), temazepam, and oxazepam. The parent compound has an elimination half-life of approximately 20–100 hours, while the active metabolite nordiazepam has a half-life of 36–200 hours. This prolonged elimination profile means that diazepam and its metabolites can accumulate with repeated dosing, particularly in elderly patients and those with hepatic impairment.

What Should You Know Before Taking Diazepam?

Quick Answer: Diazepam must not be used in patients with myasthenia gravis, severe respiratory insufficiency, sleep apnoea syndrome, or severe liver disease. It carries significant risks of dependence, withdrawal, and paradoxical reactions. Special caution is required in elderly patients, those with a history of substance abuse, and during pregnancy or breastfeeding.

Contraindications

Diazepam rectal solution must not be used in the following situations:

• Hypersensitivity: Known allergy to diazepam, other benzodiazepines, or any of the excipients. Allergic reactions may include skin rash, itching, difficulty breathing, or swelling of the face, lips, throat, or tongue.
• Myasthenia gravis: This autoimmune neuromuscular condition causes severe muscle weakness, and diazepam's muscle relaxant properties can dangerously worsen respiratory and skeletal muscle function.
• Sleep apnoea syndrome: Patients with obstructive or central sleep apnoea are at heightened risk of respiratory depression, as benzodiazepines suppress the respiratory drive during sleep.
• Severe hepatic insufficiency: Because diazepam is extensively metabolized by the liver, severe liver disease can lead to dangerous drug accumulation and may precipitate hepatic encephalopathy.
• Severe respiratory insufficiency: Pre-existing significant breathing problems can be critically worsened by diazepam's respiratory depressant effects.
• Premature infants: Diazepam should not be administered to premature neonates due to their immature hepatic metabolism and increased susceptibility to adverse effects.

Warnings and Precautions

Before using diazepam, discuss the following conditions with your healthcare provider, as dose adjustment or close monitoring may be required:

• Kidney or liver disease (even mild to moderate impairment requires dose reduction)
• Chronic respiratory conditions or breathing difficulties
• Cerebrovascular insufficiency or brain injury
• History of alcohol or substance abuse
• Mental health conditions including depression, phobias, or obsessive-compulsive disorder
• Patients in shock (hypovolaemia must be corrected before diazepam administration)

Withdrawal Symptoms

When physical dependence has developed, abrupt discontinuation can trigger potentially serious withdrawal symptoms. These may include:

• Common withdrawal symptoms: Vivid dreams, excessive sweating, tremor, headache, muscle pain, extreme anxiety, mood swings, tension, restlessness, confusion, and irritability.
• Severe withdrawal symptoms: Derealization (feeling that surroundings are not real), depersonalization (feeling detached from oneself), confusion, hypersensitivity to light, sound (hyperacusis), and touch, numbness and tingling in extremities, hallucinations, and epileptic seizures.

The symptoms that originally led to diazepam treatment may return in an intensified form when treatment is stopped (rebound phenomenon). Therefore, treatment should always be concluded with a gradual dose reduction rather than abrupt cessation. Your physician will create an individualized tapering schedule.

Memory Impairment

Diazepam can cause anterograde amnesia (inability to form new memories) at therapeutic doses. This means you may not remember actions performed after taking the medication. The risk increases with higher doses and decreases with adequate uninterrupted sleep of 7–8 hours after administration.

Paradoxical Reactions

In some patients, particularly children and the elderly, diazepam can produce paradoxical reactions — the opposite of the intended calming effect. These may include restlessness, agitation, irritability, aggressive behaviour, nightmares, hallucinations, delusions, rage, inappropriate behaviour, and psychosis. If any such reactions occur, treatment with diazepam should be discontinued immediately and your healthcare provider contacted.

Special Populations

Children and adolescents: Diazepam should only be given to children when a physician determines it is absolutely necessary, and all treatment courses should be kept to a minimum duration. Children are more susceptible to paradoxical reactions.

Elderly patients: Older adults should receive reduced doses due to increased sensitivity to benzodiazepines. The muscle-relaxant properties of diazepam increase the risk of falls and consequent fractures, particularly when rising during the night. Close supervision is recommended.

Patients with chronic respiratory insufficiency: A lower dose is recommended due to the risk of respiratory depression. Debilitated patients and those with impaired liver or kidney function should also receive reduced doses.

Patients with a history of substance abuse: Benzodiazepines should be used with the utmost caution in these patients due to their increased vulnerability to developing dependence.

Pregnancy and Breastfeeding

Pregnancy: Diazepam should not be used during pregnancy unless your doctor has specifically instructed you to do so after careful risk-benefit assessment. Studies have shown that benzodiazepine use during pregnancy may be associated with a slight increase in congenital malformations, particularly cleft lip and palate. Prolonged use during pregnancy can lead to neonatal withdrawal symptoms, and use during late pregnancy or delivery may cause “floppy infant syndrome” — characterized by low body temperature, poor muscle tone, breathing difficulties, and weak sucking reflex in the newborn.

Breastfeeding: Diazepam passes into breast milk and should not be used during breastfeeding. If treatment is unavoidable, breastfeeding must be discontinued to avoid adverse effects in the nursing infant, including sedation, poor feeding, and potential respiratory depression.

Driving and Operating Machinery

You must not drive or operate machinery for at least 24 hours after receiving the last dose of diazepam. If after 24 hours you still feel drowsy, have difficulty concentrating, notice muscle weakness, or experience periods of memory loss, you must not drive or use machinery and should consult your doctor.

How Does Diazepam Interact with Other Drugs?

Quick Answer: Diazepam interacts with numerous medications that affect the central nervous system. The most dangerous interactions are with opioids and alcohol, which can cause respiratory depression, coma, and death. Many common medications including antidepressants, antipsychotics, antifungals, and acid-reducing drugs can alter diazepam's effects.

Diazepam is metabolized primarily by the liver enzymes CYP3A4 and CYP2C19, making it susceptible to interactions with medications that inhibit or induce these enzymes. Additionally, any substance that depresses the central nervous system can have additive or synergistic effects with diazepam, potentially leading to excessive sedation, respiratory depression, or cardiovascular collapse.

Major Interactions

Moderate Interactions

Other Notable Interactions

• Rifampicin (antibiotic): A potent CYP enzyme inducer that can significantly reduce diazepam plasma levels, potentially rendering it ineffective.
• Theophylline (for asthma): May reduce the sedative effects of diazepam.
• St. John's Wort (herbal remedy): Can decrease diazepam levels through enzyme induction; do not combine.
• Nicotine (smoking): Cigarette smoking can reduce the effectiveness of diazepam by inducing its hepatic metabolism.

What Is the Correct Dosage of Diazepam?

Quick Answer: The standard dose is 0.25–0.5 mg/kg body weight administered rectally. For children aged 1–3 years (10–15 kg): one 5 mg tube. For children over 3 years (over 15 kg): one 10 mg tube. For adults: two 10 mg tubes. Treatment should be as brief as possible, and treatment duration should not exceed 4 weeks including tapering.

Always use diazepam exactly as prescribed by your doctor or pharmacist. The dose depends on the patient's age, body weight, and clinical condition. Diazepam rectal solution is intended for use in acute situations and is not intended for long-term treatment. If used continuously for too long, there is a risk of dependence or withdrawal problems upon discontinuation.

Adults

Children

Elderly and Special Populations

How to Administer Rectal Diazepam

The rectal tubes are for single use only. Follow these steps for correct administration:

1. Position the patient: If possible, turn the patient on their side or onto their stomach (especially for children).
2. Open the packaging: Tear open the foil wrapping.
3. Remove the cap: Twist or pull off the tube cap.
4. Insert the tip: Insert the tube tip fully into the rectum, pointing downwards. For children under 15 kg, insert only halfway.
5. Empty the tube: Squeeze the tube firmly between thumb and forefinger to dispense the contents.
6. Withdraw while squeezed: Keep the tube fully compressed while withdrawing it from the rectum.
7. Hold position: Maintain the patient's position and hold the buttocks pressed together for several minutes to prevent leakage.

Note: A small amount of solution will remain in the tube after the dose has been given. This is normal and the correct dose has been delivered.

Overdose

Symptoms of overdose range from mild to severe and may include:

• Mild to moderate: Drowsiness, sleepiness, confusion, lethargy, speech disturbances, involuntary eye movements (nystagmus)
• Severe: Low blood pressure (hypotension), loss of reflexes, respiratory depression, bluish discolouration of skin and mucous membranes (cyanosis), loss of consciousness, coordination problems (ataxia), muscle flaccidity, coma (rare), and death (very rare)

Overdose symptoms are significantly more severe when diazepam has been taken together with alcohol or other CNS depressants. During the recovery phase, severe agitation, insomnia, and potentially serious seizures may occur.

What Are the Side Effects of Diazepam?

Quick Answer: Common side effects include drowsiness, headache, dizziness, muscle weakness, fatigue, and next-day hangover effects. More serious but less common side effects include respiratory depression, cardiovascular effects, paradoxical reactions (especially in children and the elderly), and physical dependence with prolonged use.

Like all medicines, diazepam can cause side effects, although not everyone will experience them. Most side effects are dose-related and tend to be more pronounced in elderly patients, debilitated individuals, and those with hepatic impairment. If you experience any serious side effects or an allergic reaction (difficulty breathing, swollen eyelids, face or lips, skin rash or itching), seek immediate medical attention.

Reporting Side Effects

It is important to report suspected side effects after the medicine has been authorised. This enables continuous monitoring of the benefit-risk balance. Healthcare professionals and patients are encouraged to report any suspected adverse reactions to their national pharmacovigilance authority (e.g., the MHRA in the UK via the Yellow Card Scheme, the FDA MedWatch programme in the US, or the EMA for EU member states).

How Should You Store Diazepam?

Quick Answer: Store diazepam rectal solution at or below 25°C (77°F), out of sight and reach of children. Brief exposure to higher temperatures (e.g., in a car or emergency bag) does not affect the medication's quality. Do not use after the expiry date. Dispose of unused medicines through your pharmacy.

Proper storage is essential to maintain the effectiveness and safety of diazepam rectal solution. As a controlled substance, it should be stored securely to prevent accidental exposure or misuse.

• Temperature: Store at or below 25°C (77°F). Short-term exposure to higher temperatures (for example, in a car or emergency bag) is acceptable and does not affect the medication's quality.
• Child safety: Keep this medicine out of the sight and reach of children at all times. Accidental ingestion by a child is a medical emergency.
• Expiry date: Do not use after the expiry date printed on the packaging (after “EXP”). The expiry date refers to the last day of the stated month.
• Disposal: Do not dispose of medicines via wastewater or household waste. Return unused or expired medicines to your pharmacy for safe disposal. This helps protect the environment.
• Single-use tubes: Each rectal tube is for single use only. Discard any partially used tubes immediately after administration.

What Does Diazepam Contain?

Quick Answer: The active ingredient is diazepam (5 mg or 10 mg per 2.5 ml rectal tube). Inactive ingredients include benzyl alcohol, ethanol 96%, propylene glycol, benzoic acid, sodium benzoate, and purified water. Some of these excipients may cause allergic reactions or skin irritation in sensitive individuals.

Active Ingredient

Each 2.5 ml rectal tube contains diazepam 5 mg or diazepam 10 mg as the active ingredient.

Inactive Ingredients (Excipients)

• Benzyl alcohol (37.5 mg per tube, equivalent to 15 mg/ml) — may cause allergic reactions in some individuals
• Ethanol 96%
• Propylene glycol (1 mg per tube, equivalent to 400 mg/ml) — may cause skin irritation
• Benzoic acid (E210) (2.5 mg per tube, equivalent to 1 mg/ml) — may cause local irritation
• Sodium benzoate (E211) (122.5 mg per tube, equivalent to 49 mg/ml) — may cause local irritation
• Purified water

Appearance and Packaging

Diazepam rectal solution is a clear, colourless to slightly yellowish solution supplied in white plastic rectal tubes. Each pack contains 5 rectal tubes, with each tube holding 2.5 ml of solution.