BUCCOLAM (Midazolam)

What Is BUCCOLAM and What Is It Used For?

BUCCOLAM is a prescription medicine containing midazolam, a short-acting benzodiazepine, used to stop sudden, prolonged convulsive seizures (status epilepticus) in patients aged 3 months to adults with diagnosed epilepsy. It is given as an oromucosal solution by parents or caregivers during a seizure emergency.

BUCCOLAM belongs to a group of medications called benzodiazepines, which work by enhancing the activity of gamma-aminobutyric acid (GABA), the brain's primary inhibitory neurotransmitter. By increasing GABA activity at the GABA-A receptor, midazolam produces anticonvulsant, sedative, muscle relaxant, and anxiolytic effects. In the context of acute seizures, this mechanism rapidly suppresses the abnormal electrical activity in the brain that causes convulsions.

The oromucosal route of administration (placing the solution between the cheek and gum) allows midazolam to be absorbed directly through the oral mucosa into the bloodstream. This provides rapid onset of action, typically within 5 to 10 minutes, which is critical during a seizure emergency. The buccal route is particularly advantageous because it can be administered even when the patient is convulsing and unable to swallow oral medications, and it does not require intravenous access like hospital-based treatments.

BUCCOLAM is specifically indicated for the treatment of prolonged, acute, convulsive seizures in patients who have received a diagnosis of epilepsy. It is a rescue medication — meaning it is not used for daily seizure prevention, but rather kept on hand for emergency use when a seizure occurs and does not stop on its own within a few minutes. The medication is designed to be used by trained parents, family members, or caregivers in community settings, schools, or at home.

BUCCOLAM was approved by the European Medicines Agency (EMA) as an orphan medicinal product and has become a standard rescue medication for seizure emergencies across Europe. Prior to its approval, buccal midazolam was prepared extemporaneously from injection solutions, which led to dosing errors and safety concerns. The pre-filled, age-specific syringes of BUCCOLAM address these issues by providing accurate, ready-to-use doses.

What Should You Know Before Taking BUCCOLAM?

BUCCOLAM must not be given to patients with myasthenia gravis, severe respiratory insufficiency, sleep apnea syndrome, severe liver impairment, or known allergy to midazolam or benzodiazepines. Special caution is required for patients with kidney, liver, heart, or lung conditions.

Contraindications

BUCCOLAM must not be used in certain situations. Understanding these contraindications is essential for the safe use of this medication. Do not give BUCCOLAM to the patient if they have any of the following conditions:

• Allergy to midazolam, other benzodiazepines (such as diazepam), or any excipient in the formulation. An allergic reaction could include skin rash, swelling, or breathing difficulties.
• Myasthenia gravis — a neuromuscular disease that causes muscle weakness. Benzodiazepines can worsen muscle weakness and respiratory compromise in these patients.
• Severe respiratory insufficiency at rest — BUCCOLAM can further depress breathing, which could be life-threatening in patients who already have significant breathing difficulties even when resting.
• Sleep apnea syndrome — a condition causing frequent pauses in breathing during sleep. Midazolam can worsen these breathing pauses and increase the risk of hypoxia.
• Severe hepatic (liver) impairment — midazolam is extensively metabolized by the liver, and severe liver disease can dramatically increase drug levels, leading to prolonged sedation and respiratory depression.

Warnings and Precautions

Even when BUCCOLAM is not strictly contraindicated, certain patient populations require special care and closer monitoring. Talk to a doctor or pharmacist before giving BUCCOLAM if the patient has any of the following:

For children:

• A disease affecting the kidneys, liver, or heart
• A lung disease that regularly causes breathing difficulties
• Age under 3 months — there is insufficient safety data for this age group

For adults:

• Age over 60 years — elderly patients are more sensitive to the effects of benzodiazepines and may require lower doses or closer monitoring
• Chronic disease, including respiratory problems, kidney disease, liver disease, or heart conditions
• Debilitation — patients who are generally weakened or frail

Pregnancy and Breastfeeding

Consult a doctor before giving BUCCOLAM if the patient is pregnant, breastfeeding, thinks she may be pregnant, or is planning to become pregnant. As a rescue medication for seizure emergencies, the benefits of stopping a prolonged seizure must be weighed against potential risks to the fetus or infant.

Pregnancy: High doses of midazolam administered during the last three months of pregnancy may cause abnormal heart rhythm (irregular heartbeat) in the fetus. Babies born when this medication has been given during labor may have poor sucking ability, breathing difficulties, low body temperature, and reduced muscle tone at birth. These effects are typically temporary but require monitoring.

Breastfeeding: Small amounts of midazolam are transferred to breast milk, but this does not necessarily preclude breastfeeding. The treating physician should determine whether the patient should temporarily stop breastfeeding after receiving this medication. Given that BUCCOLAM is used as an emergency rescue medication rather than a regular treatment, brief interruption of breastfeeding may be sufficient.

Driving and Operating Machinery

BUCCOLAM can cause significant drowsiness, memory impairment, and reduced coordination. These effects can impair the ability to perform complex tasks safely. After receiving this medication, the patient should not drive a vehicle, ride a bicycle, or operate machinery until they have fully recovered. The duration of impairment varies depending on the dose given and individual patient factors, but effects can last several hours.

How Does BUCCOLAM Interact with Other Drugs?

BUCCOLAM interacts with many medications. CYP3A4 inhibitors (ketoconazole, erythromycin, HIV protease inhibitors) increase its effects, while CYP3A4 inducers (rifampicin, St John's wort) decrease them. Combining with other CNS depressants (opioids, sedatives, alcohol) can cause dangerous respiratory depression.

Drug interactions are a critical safety consideration with BUCCOLAM. Midazolam is primarily metabolized by the cytochrome P450 enzyme CYP3A4 in the liver. Medications that inhibit or induce this enzyme can significantly alter midazolam blood levels, either increasing the risk of side effects or reducing therapeutic efficacy. Additionally, combining midazolam with other central nervous system (CNS) depressants can produce additive or synergistic sedation and respiratory depression.

Always inform the prescribing doctor about all medications the patient is currently taking, has recently taken, or might take. This includes prescription medications, over-the-counter drugs, and herbal supplements.

Drugs That Increase BUCCOLAM Effects

The following medications can enhance the effects of BUCCOLAM, potentially leading to excessive sedation, prolonged drowsiness, or respiratory depression:

Drugs That Decrease BUCCOLAM Effects

The following medications can reduce the effectiveness of BUCCOLAM, potentially making it less effective at stopping seizures:

• Rifampicin (used for tuberculosis) — a powerful CYP3A4 inducer that can reduce midazolam blood levels by up to 96%, effectively making BUCCOLAM ineffective
• Xanthines (used for asthma, such as theophylline) — may counteract the sedative effects of benzodiazepines
• St John's wort (herbal supplement for depression) — a CYP3A4 inducer that should be avoided in patients who use BUCCOLAM, as it can significantly reduce midazolam effectiveness

Other Important Interactions

BUCCOLAM can enhance the effects of certain muscle relaxants such as baclofen, leading to increased drowsiness and muscle relaxation. It may also interfere with the action of levodopa, a medication used for Parkinson's disease. Patients should not drink alcohol while taking BUCCOLAM, as alcohol significantly enhances the sedative effects and can cause dangerous drowsiness. Similarly, grapefruit juice should be avoided as it inhibits CYP3A4 and can increase midazolam blood levels.

What Is the Correct Dosage of BUCCOLAM?

BUCCOLAM dosing is based on patient age: 2.5 mg (3 months to <1 year), 5 mg (1 to <5 years), 7.5 mg (5 to <10 years), and 10 mg (10 years to adults). Each pre-filled syringe contains one complete dose. Only one dose should be given per seizure episode.

BUCCOLAM is available in four age-specific doses, each supplied in a color-coded pre-filled oral syringe. The prescribing doctor selects the appropriate dose based on the patient's age. It is essential to use only the dose prescribed and to verify that the color coding on the packaging matches the patient's age group.

How to Administer BUCCOLAM

Proper administration technique is critical for BUCCOLAM to work effectively. Before an emergency occurs, ask your doctor, pharmacist, or nurse to demonstrate the correct technique. The following steps outline the administration procedure:

During a seizure, ensure the patient's safety first. Do not try to restrain the patient or stop their movements. Remove dangerous objects from nearby (sharp items, hot surfaces, deep water). Support their head with something soft, such as a pillow or your knee.

1. Step 1: Hold the protective plastic case, pull off the cap, and remove the pre-filled oral syringe from the case.
2. Step 2: Remove the red cap from the syringe tip and discard it safely. Do not attach a needle to the syringe.
3. Step 3: Gently pull back the patient's cheek with your thumb and forefinger. Insert the syringe tip into the space between the inside of the cheek and the lower gum.
4. Step 4: Slowly push the plunger until it stops. The entire dose should be squeezed slowly into the buccal cavity (the space between the gum and the inside of the cheek).

For larger volumes or smaller patients, the prescribing doctor may advise giving approximately half the dose slowly on one side of the mouth and then the remaining dose on the other side. This can help ensure better absorption and reduce the risk of the patient swallowing the solution.

Elderly Patients

Elderly patients (over 60 years) are more sensitive to the effects of benzodiazepines. The same age-based adult dose (10 mg) applies, but these patients should be monitored more closely for respiratory depression and prolonged sedation. The prescribing doctor may provide specific instructions for elderly patients.

What to Do If the Patient Vomits

If the patient vomits after receiving BUCCOLAM, do not give an additional dose. If the seizure does not stop within 10 minutes, call emergency services immediately. The empty syringe should be saved to show the paramedics or attending physician.

Overdose

If too much BUCCOLAM has been given, seek emergency medical help immediately. Signs and symptoms of overdose may include:

• Excessive drowsiness or difficulty waking the patient
• Confusion or disorientation
• Loss of reflexes (no knee-jerk reflex or no reaction to a pinch)
• Respiratory depression (slow, shallow breathing)
• Low blood pressure (dizziness, feeling faint)
• Coma in severe cases

In a hospital setting, the benzodiazepine antagonist flumazenil may be used to reverse the effects of midazolam overdose. However, flumazenil should be used with caution in patients with epilepsy, as rapid benzodiazepine reversal can trigger seizures.

What Are the Side Effects of BUCCOLAM?

The most common side effects of BUCCOLAM are nausea, vomiting, and drowsiness (up to 1 in 10 patients). Uncommon effects include skin rash and hives. Very rare but serious effects include respiratory depression, paradoxical agitation, and laryngospasm. Seek immediate medical help for breathing difficulties or severe allergic reactions.

Like all medications, BUCCOLAM can cause side effects, although not everyone experiences them. Most side effects are mild and temporary. However, some side effects can be serious and require immediate medical attention. It is important for caregivers to be aware of both common and serious adverse effects so they can respond appropriately.

Paradoxical Reactions

Paradoxical reactions are a well-documented but rare phenomenon with benzodiazepines. Instead of the expected calming and anticonvulsant effect, some patients — particularly children and elderly individuals — may experience the opposite: increased agitation, restlessness, irritability, aggression, or even hallucinations. These reactions are more common in children and in patients with pre-existing psychiatric conditions. If a paradoxical reaction occurs, the prescribing doctor should be informed, as alternative seizure rescue medications may need to be considered.

Anterograde Amnesia

Midazolam commonly causes anterograde amnesia, meaning the patient may not remember events that occurred after the medication was administered. The duration of amnesia depends on the dose given and individual patient factors. This is a known pharmacological effect of benzodiazepines and is usually temporary. Caregivers should be prepared to explain to the patient what happened during and after the seizure, as the patient may have no recollection of the event.

Reporting Side Effects

Reporting suspected side effects after a medicine has been authorized is important for ongoing safety monitoring. Healthcare professionals and patients are encouraged to report any suspected adverse reactions to their national pharmacovigilance authority.

How Should You Store BUCCOLAM?

Store BUCCOLAM at room temperature, away from cold and freezing. Keep the oral syringe in its protective plastic case. Do not use if the packaging is opened or damaged. Check the expiry date regularly and replace as needed. Keep out of sight and reach of children.

Proper storage of BUCCOLAM is essential to ensure the medication remains effective when needed in an emergency. Since this is a rescue medication that may be stored for extended periods before use, regular checks of storage conditions and expiry dates are particularly important.

• Keep out of sight and reach of children — although BUCCOLAM is intended for use in children, it should be stored where a child cannot access it unsupervised.
• Do not use after the expiry date printed on the carton, case, and oral syringe label (after "EXP"). The expiry date refers to the last day of the stated month.
• Protect from cold and do not freeze — unlike some medications, BUCCOLAM should not be refrigerated. Freezing can damage the pre-filled syringe and alter the solution.
• Keep the oral syringe in its protective plastic case until ready for use. The case protects the syringe from light and physical damage.
• Do not use if the packaging is opened or appears damaged.

Disposal of used or expired syringes should follow local pharmaceutical waste guidelines. Do not dispose of medications via household waste or drain. Ask your pharmacist about proper disposal methods to protect the environment.

What Does BUCCOLAM Contain?

BUCCOLAM contains midazolam (as hydrochloride) as the active ingredient, at a concentration of 5 mg/mL. Inactive ingredients include sodium chloride, water for injections, hydrochloric acid, and sodium hydroxide (for pH adjustment). The solution is clear, colorless to slightly yellow.

Understanding the full composition of a medication is important for patients and caregivers, particularly to identify potential allergens or excipients that could cause adverse reactions.

Active Ingredient

The active substance is midazolam (present as midazolam hydrochloride). The concentration is 5 mg/mL across all dose strengths. The four available pre-filled oral syringes contain:

• 2.5 mg syringe: 2.5 mg midazolam in 0.5 mL solution
• 5 mg syringe: 5 mg midazolam in 1 mL solution
• 7.5 mg syringe: 7.5 mg midazolam in 1.5 mL solution
• 10 mg syringe: 10 mg midazolam in 2 mL solution

Inactive Ingredients (Excipients)

• Sodium chloride — used to adjust the osmolality (salt balance) of the solution
• Water for injections — the purified water base
• Hydrochloric acid and sodium hydroxide — used for pH adjustment to ensure stability and optimal absorption through the oral mucosa

Appearance and Packaging

BUCCOLAM oromucosal solution is a clear, colorless to slightly yellowish liquid. It is supplied in a yellow-colored, single-use, pre-filled oral syringe. Each syringe is individually sealed in a protective plastic case. Packs contain 2 or 4 pre-filled oral syringes (all of the same dose strength). Not all pack sizes may be available in every market.