Buccolam

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 

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1. NAME OF THE MEDICINAL PRODUCT 
 
BUCCOLAM 2.5 mg oromucosal solution  
BUCCOLAM 5 mg oromucosal solution 
BUCCOLAM 7.5 mg oromucosal solution 
BUCCOLAM 10 mg oromucosal solution 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
BUCCOLAM 2.5 mg oromucosal solution  
 
Each pre-filled oral syringe contains 2.5 mg midazolam (as hydrochloride) in 0.5 ml solution 
 
BUCCOLAM 5 mg oromucosal solution 
 
Each pre-filled oral syringe contains 5 mg midazolam (as hydrochloride) in 1 ml solution 
 
BUCCOLAM 7.5 mg oromucosal solution 
 
Each pre-filled oral syringe contains 7.5 mg midazolam (as hydrochloride) in 1.5 ml solution 
 
BUCCOLAM 10 mg oromucosal solution 
 
Each pre-filled oral syringe contains 10 mg midazolam (as hydrochloride) in 2 ml solution 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Oromucosal solution 
Clear colourless solution 
pH 2.9 to 3.7 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Treatment of prolonged, acute, convulsive seizures in infants, toddlers, children and adolescents (from 
3 months to < 18 years). 
 
BUCCOLAM must only be used by parents/carers where the patient has been diagnosed to have 
epilepsy. 
 
For infants between 3-6 months of age treatment should be in a hospital setting where monitoring is 
possible and resuscitation equipment is available. See section 4.2. 
 

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4.2 Posology and method of administration 
 
Posology 
 
Standard doses are indicated below:  
 

Age range Dose Label colour 

3 to 6 months hospital 
setting 

2.5 mg Yellow 

> 6 months to < 1 year 2.5 mg Yellow 

1 year to < 5 years 5 mg Blue 

5 years to < 10 years 7.5 mg Purple 

10 years to < 18 years 10 mg Orange 
 
Carers should only administer a single dose of midazolam. If the seizure has not stopped within 10 
minutes after administration of midazolam, emergency medical assistance must be sought and the 
empty syringe given to the healthcare professional to provide information on the dose received by the 
patient. 
 
A second or repeat dose when seizures re-occur after an initial response should not be given without 
prior medical advice (see section 5.2). 
 
Special populations 
 
Renal impairment 
No dose adjustment is required, however, BUCCOLAM should be used with caution in patients with 
chronic renal failure as elimination of midazolam may be delayed and the effects prolonged. (see 
section 4.4) 
 
Hepatic impairment 
Hepatic impairment reduces the clearance of midazolam with a subsequent increase in terminal half-
life. Therefore, the clinical effects may be stronger and prolonged, hence careful monitoring of the 
clinical effects and vital signs is recommended following administration of midazolam in patients with 
hepatic impairment (see section 4.4). 
 
BUCCOLAM is contraindicated in patients with severe hepatic impairment (see section 4.3). 
 
Paediatric population 
The safety and efficacy of midazolam in children aged 0 to 3 months has not been established. No data 
are available. 
 
Method of administration 
 
BUCCOLAM is for oromucosal use. The full amount of solution should be inserted slowly into the 
space between the gum and the cheek. Laryngo-tracheal insertion should be avoided to prevent 
accidental aspiration of the solution. If necessary (for larger volumes and/or smaller patients), 
approximately half the dose should be given slowly into one side of the mouth, then the other half 
given slowly into the other side.   
 
For detailed instructions on how to administer the medicinal product, see section 6.6.  
 

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Precautions to be taken before handling or administering the medicinal product 
 
No needle, intravenous tubing or any other device for parenteral administration should be attached to 
the oral syringe. 
 
BUCCOLAM is not for intravenous use. 
 
The oral syringe cap should be removed before use to avoid risk of choking. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance, benzodiazepines or to any of the excipients listed in section 
6.1 
Myasthenia gravis 
Severe respiratory insufficiency 
Sleep apnoea syndrome 
Severe hepatic impairment 
 
4.4 Special warnings and precautions for use 
 
Respiratory insufficiency 
 
Midazolam should be used with caution in patients with chronic respiratory insufficiency because 
midazolam may further depress respiration. 
 
Paediatric patients aged 3 to 6 months 
 
Given the higher metabolite to parent drug ratio in younger children, a delayed respiratory depression 
as a result of high active metabolite concentrations in the 3-6 months age group cannot be excluded. 
Therefore, the use of BUCCOLAM in the 3-6 month age group should be limited for use only under 
the supervision of a health care professional where resuscitation equipment is available and where 
respiratory function can be monitored and equipment for respiratory assistance, if needed, is available.  
 
Altered elimination of midazolam 
 
Midazolam should be used with caution in patients with chronic renal failure, impaired hepatic or 
cardiac function. Midazolam may accumulate in patients with chronic renal failure or impaired hepatic 
function whilst in patients with impaired cardiac function it may cause decreased clearance of 
midazolam. 
 
Concomitant use with other benzodiazepines 
 
Debilitated patients are more prone to the central nervous system (CNS) effects of benzodiazepines 
and, therefore, lower doses may be required. 
 
Medical history of alcohol or drug abuse 
 
Midazolam should be avoided in patients with a medical history of alcohol or drug abuse. 
 
Amnesia 
 
Midazolam may cause anterograde amnesia. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Midazolam is metabolized by CYP3A4. Inhibitors and inducers of CYP3A4 have the potential to 
respectively increase and decrease the plasma concentrations and, subsequently, the effects of 

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midazolam thus requiring dose adjustments accordingly. Pharmacokinetic interactions with CYP3A4 
inhibitors or inducers are more pronounced for oral as compared to oromucosal or parenteral 
midazolam as CYP3A4 enzymes are also present in the upper gastro-intestinal tract. After oromucosal 
administration, only systemic clearance will be affected. After a single dose of oromucosal 
midazolam, the consequence on the maximal clinical effect due to CYP3A4 inhibition will be minor 
while the duration of effect may be prolonged. Hence, a careful monitoring of the clinical effects and 
vital signs is recommended during the use of midazolam with a CYP3A4 inhibitor even after a single 
dose. 
 
Anaesthetics and narcotic analgesics  
 
Fentanyl may reduce midazolam clearance. 
 
Antiepileptics  
 
Co-administration with midazolam may cause enhanced sedation or respiratory or cardiovascular 
depression.  Midazolam may interact with other hepatically metabolised medicinal products, e.g. 
phenytoin, causing potentiation. 
 
Calcium-channel blockers 
 
Diltiazem and verapamil have been shown to reduce the clearance of midazolam and other 
benzodiazepines and may potentiate their actions. 
 
Ulcer-healing medicinal products 
 
Cimetidine, ranitidine and omeprazole have been shown to reduce the clearance of midazolam and 
other benzodiazepines and may potentiate their actions. 
 
Xanthines 
 
Metabolism of midazolam and other benzodiazepines is accelerated by xanthines. 
 
Dopaminergic medicinal products 
 
Midazolam may cause inhibition of levodopa. 
 
Muscle relaxants 
 
E.g. baclofen. Midazolam may cause potentiation of muscle relaxants, with increased CNS depressant 
effects. 
 
Nabilone 
 
Co-administration with midazolam may cause enhanced sedation or respiratory and cardiovascular 
depression. 
 
Medicinal products that inhibit CYP3A4 
 
Medicinal product interactions following oromucosal administration of midazolam are likely to be 
similar to those observed after intravenous midazolam rather than oral administration. 
 
Food 
Grapefruit juice reduces the clearance of midazolam and potentiates its action. 
 

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Azole antifungals 
Ketoconazole increased the plasma concentrations of intravenous midazolam by 5-fold while the 
terminal half-life increased by about 3-fold. 
 
Voriconazole increased the exposure of intravenous midazolam by 3-fold whereas its elimination half-
life increased by about 3-fold. 
 
Fluconazole and itraconazole both increased the plasma concentrations of intravenous midazolam by 2 
to 3-fold associated with an increase in terminal half-life by 2.4-fold for itraconazole and 1.5-fold for 
fluconazole. 
 
Posaconazole increased the plasma concentrations of intravenous midazolam by about 2-fold. 
 
Macrolide antibiotics 
Erythromycin resulted in an increase in the plasma concentrations of intravenous midazolam by about 
1.6 to 2 –fold associated with an increase of the terminal half-life of midazolam by 1.5 to 1.8-fold. 
 
Clarithromycin increased the plasma concentrations of intravenous midazolam by up to 2.5-fold 
associated with an increase in terminal half-life by 1.5 to 2-fold. 
 
HIV Protease inhibitors 
Co-administration with protease inhibitors (e.g. Saquinavir and other HIV protease inhibitors) may 
cause a large increase in the concentration of midazolam. Upon co-administration with ritonavir-
boosted lopinavir, the plasma concentrations of intravenous midazolam increased by 5.4-fold, 
associated with a similar increase in terminal half-life. 
 
Calcium-channel blockers 
A single dose of diltiazem increased the plasma concentrations of intravenous midazolam by about 
25% and the terminal half-life was prolonged by 43%. 
 
Various medicinal products 
Atorvastatin showed a 1.4-fold increase in plasma concentrations of intravenous midazolam compared 
to control group. 
 
Medicinal products that induce CYP3A4 
 
Rifampicin  
7 days of 600 mg once daily decreased the plasma concentrations of intravenous midazolam by about 
60%. The terminal half-life decreased by about 50-60%. 
 
Herbs 
St John’s Wort decreased plasma concentrations of midazolam by about 20-40% associated with a 
decrease in terminal half life of about 15-17%.  Depending on the specific St John's Wort extract, the 
CYP3A4-inducing effect may vary. 
 
Pharmacodynamic Drug-Drug Interactions (DDI) 
 
The co-administration of midazolam with other sedative/hypnotic medicinal products and CNS 
depressants, including alcohol, is likely to result in enhanced sedation and respiratory depression. 
 
Examples include opiate derivatives (used as analgesics, antitussives or substitutive treatments), 
antipsychotics, other benzodiazepines used as anxiolytics or hypnotics, barbiturates, propofol, 
ketamine, etomidate; sedative antidepressants, non-recent H1-antihistamines and centrally acting 
antihypertensive medicinal products. 
 

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Alcohol (including alcohol-containing medicinal products may markedly enhance the sedative effect 
of midazolam. Alcohol intake should be strongly avoided in case of midazolam administration (see 
section 4.4). 
 
Midazolam decreases the minimum alveolar concentration (MAC) of inhalation anaesthetics. 
 
The effect of CYP3A4 inhibitors may be larger in infants since part of the oromucosal dose is 
probably swallowed and absorbed in the gastro-intestinal tract. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no or limited amount of data from the use of midazolam in pregnant women. Animal studies 
do not indicate a teratogenic effect with respect to reproductive toxicity, but foetotoxicity has been 
observed in humans as with other benzodiazepines. No data on exposed pregnancies are available for 
the first two trimesters of pregnancy. 
 
The administration of high doses of midazolam in the last trimester of pregnancy or during labour has 
been reported to produce maternal or foetal adverse reactions (risk of aspiration of fluids and stomach 
contents during labour in the mother, irregularities in the foetal heart rate, hypotonia, poor suckling, 
hypothermia and respiratory depression in the new-born infant). 
 
Midazolam may be used during pregnancy if clearly necessary. The risk for new-born infants should 
be taken into account in the event of administration of midazolam in the third trimester of pregnancy. 
 
Breast-feeding 
 
Midazolam is excreted in low quantities (0.6%) in human milk. As a result it may not be necessary to 
stop breast feeding following a single dose of midazolam. 
 
Fertility 
 
Animal studies did not show an impairment of fertility (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Midazolam has a major influence on the ability to drive and use machines. 
 
Sedation, amnesia, impaired attention and impaired muscular function may adversely affect the ability 
to drive, ride a bicycle or use machines. After receiving midazolam, the patient should be warned not 
to drive a vehicle or operate a machine until completely recovered.  
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
Published clinical studies show that oromucosal midazolam was administered to approx 443 children 
with seizures. Respiratory depression occurs at a rate of up to 5%, although this is a known 
complication of convulsive seizures as well as being related to midazolam use. One episode of pruritus 
was possibly attributed to the use of buccal midazolam. 
 
Tabulated list of adverse reactions 
 
The table below lists the adverse reactions reported to occur when oromucosal midazolam was 
administered to children in clinical studies.  
 

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The frequency of adverse reactions is classified as follows: 
Common:  ≥ 1/100 to < 1/10 
Uncommon:  ≥ 1/1,000 to < 1/100 
Very rare: < 1/10,000 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness:  
 

System Organ Class Frequency: Adverse Drug Reaction 
Psychiatric disorders Very rare: 

Aggression**, agitation**, anger**, confusional state**, 
euphoric mood**, hallucination**, hostility**, movement 
disorder**, physical assault** 

Nervous system disorders 
 

Common: 
Sedation, somnolence, depressed levels of consciousness 
Respiratory depression 
Very rare: 
Anterograde amnesia**, ataxia**, dizziness**, headache**, 
seizure**, paradoxical reactions** 

Cardiac disorders Very rare: 
Bradycardia**, cardiac arrest**, hypotension**, 
vasodilatation** 

Respiratory, thoracic and 
mediastinal disorders 

Very rare: 
Apnoea**, dyspnea**, laryngospasm**, respiratory arrest** 

Gastrointestinal disorders Common: 
Nausea and vomiting 
Very rare: 
Constipation**, dry mouth** 

Skin and subcutaneous tissue 
disorders  

Uncommon: 
Pruritus, rash and urticarial 

General disorders and 
administration site conditions 

Very rare: 
Fatigue**, hiccups** 

**These adverse reactions have been reported to occur when midazolam is injected in children and/or 
adults, which may be of relevance to oromucosal administration. 
 
Description of selected adverse reactions 
 
An increased risk for falls and fractures has been recorded in elderly benzodiazepine users. 
 
Life-threatening incidents are more likely to occur in those with pre-existing respiratory insufficiency 
or impaired cardiac function, particularly when a high dosage is administered (see section 4.4).  
 
Reporting of suspected adverse reactions  
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
 
4.9 Overdose 
 
Symptoms 
 
Midazolam overdose can present a threat to life if the patient has pre-existing respiratory or cardiac 
insufficiency, or when combined with other CNS depressants (including alcohol). 
 
Overdose of benzodiazepines is usually manifested by degrees of central nervous system depression 
ranging from drowsiness to coma. In mild cases, symptoms include drowsiness, mental confusion and 

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lethargy, in more serious cases, symptoms may include ataxia, hypotonia, hypotension, respiratory 
depression, rarely coma and very rarely death. 
 
Management 
 
In the management of overdose with any medicinal product, it should be borne in mind that multiple 
agents may have been taken. 
 
Following overdose with oral midazolam, vomiting should be induced (within one hour) if the patient 
is conscious or gastric lavage undertaken with the airway protected if the patient is unconscious. If 
there is no advantage in emptying the stomach, activated charcoal should be given to reduce 
absorption. Special attention should be paid to respiratory and cardiovascular functions in intensive 
care. 
 
Flumazenil may be useful as an antidote. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Psycholeptics, benzodiazepine derivatives ATC code: N05CD08. 
 
Mechanism of action 
 
Midazolam is a derivative of the imidazobenzodiazepine group. The free base is a lipophilic substance 
with low solubility in water. The basic nitrogen in position 2 of the imidazobenzodiazepine ring 
system enables midazolam to form the hydrochloride salt with acids. These produce a stable solution 
suitable for oromucosal administration. 
 
Pharmacodynamic effects 
 
The pharmacological action of midazolam is characterized by short duration because of rapid 
metabolic transformation. Midazolam has an anticonvulsant effect.  It also exerts a sedative and sleep-
inducing effect of pronounced intensity, and an anxiolytic and a muscle-relaxant effect. 
 
Clinical efficacy and safety 
 
In 4 rectal diazepam controlled studies and one study versus intravenous diazepam, in a total of 688 
children, cessation of visible signs of seizures within 10 minutes was observed in 65% to 78% of 
children receiving oromucosal midazolam. Additionally, in 2 of the studies, cessation of visible signs 
of seizures within 10 minutes without recurrence within 1 hour after administration was observed in 
56% to 70% of children. The frequency and severity of adverse drug reactions reported for 
Oromucosal midazolam during published clinical trials were similar to the adverse drug reactions 
reported in the comparative group using rectal diazepam. 
 
The European Medicines Agency has waived the obligation to submit the results of studies with 
BUCCOLAM in the subset of the paediatric population < 3months old, on the grounds that the 
specific medicinal product does not represent a significant therapeutic benefit over existing treatments 
for these paediatric patients.  
 
5.2 Pharmacokinetic properties 
 
Simulated pharmacokinetic parameters for the recommended posology in children aged 3 months to 
less than 18 years, based on a population pharmacokinetic study are provided in tabulated format 
below: 
 

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Dose Age Parameter Mean SD 

2.5 mg 3 m  < 1 yr AUC0-inf  (ng.h/ml) 168 98 
Cmax (ng/ml) 104 46 

5 mg 1 yr  < 5 yrs AUC0-inf  (ng.h/ml) 242 116 
Cmax (ng/ml) 148 62 

7.5 mg 5 yrs  <10 yrs AUC0-inf  (ng.h/ml) 254 136 
Cmax (ng/ml) 140 60 

10 mg 10  yrs < 18 yrs AUC0-inf  (ng.h/ml) 189 96 
Cmax (ng/ml) 87 44 

 
Absorption 
 
After oromucosal administration midazolam is absorbed rapidly. Maximum plasma concentration is 
reached within 30 minutes in children. The absolute bioavailability of oromucosal midazolam is about 
75% in adults. The bioavailability of oromucosal midazolam has been estimated at 87% in children 
with severe malaria and convulsions. 
 
Distribution 
 
Midazolam is highly lipophilic and distributes extensively. The steady state volume of distribution 
following oromucosal administration is estimated to be 5.3 l/kg.  
 
Approximately 96-98% of midazolam is bound to plasma proteins. The major fraction of plasma 
protein binding is due to albumin. There is a slow and insignificant passage of midazolam into the 
cerebrospinal fluid. In humans, midazolam has been shown to cross the placenta slowly and to enter 
foetal circulation. Small quantities of midazolam are found in human milk. 
 
Biotransformation 
 
Midazolam is almost entirely eliminated by biotransformation.  The fraction of the dose extracted by 
the liver has been estimated to be 30-60%.  Midazolam is hydroxylated by the cytochrome P4503A4 
isozyme and the major urinary and plasma metabolite is alpha-hydroxy-midazolam.  Following 
oromucosal administration in children the area under the curve ratio for alpha-hydroxy midazolam to 
midazolam is 0.46.  
 
In a population pharmacokinetic study, the metabolite levels are shown to be higher in younger than 
older paediatric patients and thus likely to be of more importance in children than in adults. 
 
Elimination 
 
Plasma clearance of midazolam in children following oromucosal administration is 30 ml/kg/min. The 
initial and terminal elimination half-lives are 27 and 204 minutes, respectively.  Midazolam is excreted 
mainly by the renal route (60-80% of the injected dose) and recovered as glucuroconjugated alpha-
hydroxy-midazolam.  Less than 1% of the dose is recovered in urine as unchanged medicinal product.. 
 
Pharmacokinetics in special populations 
 
Obese 
The mean half-life is greater in obese than in non-obese patients (5.9 versus 2.3 hours). This is due to 
an increase of approximately 50% in the volume of distribution corrected for total body weight. The 
clearance is not significantly different in obese and non-obese patients. 
 
Hepatic impairment 
The elimination half-life in cirrhotic patients may be longer and the clearance lower as compared to 
those in healthy volunteers (see section 4.4). 
 

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Renal impairment 
The elimination half-life in patients with chronic renal failure is similar to that in healthy 
volunteers. 
 
The elimination half-life of midazolam is prolonged up to six times in the critically ill. 
 
Cardiac insufficiency 
The elimination half-life is longer in patients with congestive heart failure compared with that in 
healthy subjects (see section 4.4). 
 
Exposure following a second dose in the same seizure episode 
Simulated exposure data show that the overall AUC approximately doubles when a second dose is 
administered at 10, 30 and 60 minutes following the first dose. A second dose at 10 minutes results in 
a significant increase in mean Cmax of between 1.7 to 1.9 fold. At 30 and 60 minutes, significant 
elimination of midazolam has already occurred and therefore the increase in mean Cmax is less 
pronounced; 1.3 to 1.6 and 1.2 to 1.5 fold respectively. (see section 4.2). 
 
5.3 Preclinical safety data 
 
In a rat fertility study, animals dosed up to ten times the clinical dose, no adverse effects on fertility 
were observed. 
 
There are no other preclinical data of relevance to the prescriber which are additional to that already 
included in other sections of the SmPC. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sodium chloride 
Water for injections 
Hydrochloric acid (for pH adjustment and conversion of midazolam to the hydrochloride salt) 
Sodium hydroxide (for pH adjustment) 
 
6.2 Incompatibilities 
 
Not applicable 
 
6.3 Shelf life 
 
BUCCOLAM 2.5 mg oromucosal solution 
 
18 months 
 
BUCCOLAM 5 mg, 7.5 mg, 10 mg oromucosal solution 
 
2 years 
 
6.4 Special precautions for storage 
 
Keep the oral syringe in the protective plastic tube. 
Do not refrigerate or freeze. 
 

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6.5 Nature and contents of container 
 
Amber, pre-filled needle-free oral syringe (polypropylene) with plunger (polypropylene) and end cap 
(high density polyethylene) packed in a protective, capped plastic tube.  
 

Strength Volume of 
solution 

Syringe 
volume 

Age range Label colour 

2.5 mg 0.5 ml 1 ml 3 months to < 1 year Yellow 

5 mg 1 ml 3 ml 1 year to < 5 years Blue 

7.5 mg 1.5 ml 3 ml 5 years to < 10 years Purple 

10 mg 2 ml 3 ml 10 years to < 18 years Orange 
 
BUCCOLAM is available in cartons containing 4 pre-filled syringes. 
 
6.6 Special precautions for disposal and other handling 
 
Administration of BUCCOLAM 
 
BUCCOLAM is not for intravenous use. 
 
Step 1 

 

Hold the plastic tube, break the seal at one 
end and pull the cap off. Take the syringe out 
of the tube. 

 
Step 2 

 

Pull the red cap off the tip of the syringe and 
dispose of it safely. 

 

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Step 3 

 

Using the finger and thumb gently pinch and 
pull back the child’s cheek. Put the tip of the 
syringe into the back of the space between 
the inside of the cheek and the lower gum. 

 
Step 4 

 

Slowly press the syringe plunger until the 
plunger stops.  
 
The full amount of solution should be 
inserted slowly into the space between the 
gum and the cheek (buccal cavity). 
 
If necessary (for larger volumes and/or 
smaller patients), approximately half the 
dose should be given slowly into one side of 
the mouth, then the other half given slowly 
into the other side. 

 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.  
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Shire Services BVBA 
rue Montoyer 47 
1000 Brussels 
Belgium 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
BUCCOLAM 2.5 mg oromucosal solution  
 
EU/1/11/709/001 
 
BUCCOLAM 5 mg oromucosal solution 
 
EU/1/11/709/002 
 
BUCCOLAM 7.5 mg oromucosal solution 
 
EU/1/11/709/003 
 
BUCCOLAM 10 mg oromucosal solution 
 
EU/1/11/709/004 

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9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 05 September 2011 
Date of latest renewal: 26 May 2016 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 

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ANNEX II 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE  

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT 

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A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release 
 
Shire Pharmaceuticals Ireland Limited 
Block 2 & 3 Miesian Plaza 
50 – 58 Baggot Street Lower 
Dublin 2 
Ireland 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Strength 2.5 mg:  
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
Strengths 5 mg, 7.5 mg and 10  mg:  
 
Medicinal product subject to medical prescription. 
 
 
C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION  
 
• Periodic Safety Update Reports 
 
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list)) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
 
D.  CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT  
 
• Risk Management Plan (RMP) 
 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2. of the Marketing Authorisation and any agreed subsequent 
updates of the RMP. 
 
An updated RMP should be submitted: 
- At the request of the European Medicines Agency; 
- 2Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 
 
 
 

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ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 

17 



 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Carton (2.5 mg/0.5 ml) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
BUCCOLAM 2.5 mg oromucosal solution 
midazolam 
For children aged 3 months to less than 1 year 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled, oral syringe (0.5 ml) contains 2.5 mg midazolam (as hydrochloride) 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Oromucosal solution 
4 pre-filled oral syringes 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
For oromucosal use only. 
Each syringe is for single use only. 
Remove the oral syringe cap before use to avoid risk of choking. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH  OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not refrigerate or freeze. 
Keep the oral syringe in the protective plastic tube. 
 
 

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10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Shire Services BVBA 
rue Montoyer 47 
1000 Brussels 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/11/709/001 
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
BUCCOLAM 2.5 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
 

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
Plastic Tube Label 2.5 mg /0.5 ml 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
BUCCOLAM 2.5 mg oromucosal solution 
midazolam 
For children aged 3 months to less than 1 year 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Shire logo 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
BN 
 
 
5. OTHER 
 
For oromucosal use only 
Remove the oral syringe cap before use 
Keep the oral syringe in the protective plastic tube 

↘  Open Here 
 
How to give this medicine 
 
Buccolam must not be injected. Do not attach a needle to the syringe 
 
The dose is the full contents of one syringe. Do not give more than one dose 
 
Step 1 

 

Hold the plastic tube, break the seal at one 
end and pull the cap off. Take the syringe out 
of the tube. 

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Step 2 

 

Pull the red cap off the tip of the syringe and 
dispose of it safely. 

 
Step 3 

 

Using the finger and thumb gently pinch and 
pull back the child’s cheek. Put the tip of the 
syringe into the back of the space between 
the inside of the cheek and the lower gum. 

 
Step 4 

 

Slowly press the syringe plunger until the 
plunger stops. 
 
The full amount of solution should be 
inserted slowly into the space between the 
gum and the cheek (buccal cavity). 
 
If prescribed by your doctor (for larger 
volumes and/or smaller patients), you can 
give approximately half the dose slowly into 
one side of the mouth, then into the other 
side of the child’s mouth. 

 

22 



 

When to call an ambulance 
ALWAYS follow the treatment advice provided by the patient’s doctor or as explained by a 
healthcare professional. If in any doubt, call for immediate medical help if: 
• The seizure does not stop within 10 minutes 
• You’re unable to empty the syringe or you spill some of the contents 
• The child’s breathing slows down or stops e.g. slow or shallow breathing or blue lips 
• You observe signs of a heart attack which may include chest pain or pain that spreads 

to the neck and shoulders and down the left arm 
• The child is sick (vomits) and the seizure does not stop within 10 minutes 
• You give too much BUCCOLAM and there are signs of overdose which include: 

o Drowsiness, tiredness, fatigue 
o Confusion or feeling disorientated 
o Absence of knee reflex or a response to a pinch 
o Breathing difficulties (slow or shallow breathing) 
o Low blood pressure (giddiness and feeling faint) 
o Coma 

 
Keep the syringe to show to the ambulance staff or doctor. 
 
Do not give more than the amount of medicine prescribed by a doctor for the patient. 
 
 

23 



 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Plastic oral syringe 2.5 mg/0.5 ml 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
BUCCOLAM 2.5 mg oromucosal solution 
midazolam 
For children aged 3 months to less than 1 year 
For oromucosal use only. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
BN 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
2.5 mg 
 
 
6. OTHER 
 
Single use only 
Remove the oral syringe cap before use. 
 

24 



 

 
 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Carton (5 mg/1 ml) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
BUCCOLAM 5 mg oromucosal solution 
midazolam 
For children aged 1 year to less than 5 years 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled, oral syringe (1 ml) contains 5 mg midazolam (as hydrochloride) 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Oromucosal solution 
4 pre-filled oral syringes  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
For oromucosal use only 
Each syringe is for single use only 
Remove the oral syringe cap before use to avoid risk of choking 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH  OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not refrigerate or freeze. 
Keep the oral syringe in the protective plastic tube. 
 

25 



 

 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Shire Services BVBA 
rue Montoyer 47 
1000 Brussels 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/11/709/002 
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
BUCCOLAM 5 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 

26 



 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
Plastic Tube Label 5 mg /1 ml 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
BUCCOLAM 5 mg oromucosal solution 
midazolam 
For children aged 1 year to less than 5 years 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Shire logo 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
BN 
 
 
5. OTHER 
 
For oromucosal use only 
Remove the oral syringe cap before use 
Keep the oral syringe in the protective plastic tube 

↘  Open Here 
 
How to give this medicine 
 
Buccolam must not be injected. Do not attach a needle to the syringe 
 
The dose is the full contents of one syringe. Do not give more than one dose 
 
Step 1 

 

Hold the plastic tube, break the seal at one 
end and pull the cap off. Take the syringe out 
of the tube. 

27 



 

Step 2 

 

Pull the red cap off the tip of the syringe and 
dispose of it safely. 

 
Step 3 

 

Using the finger and thumb gently pinch and 
pull back the child’s cheek. Put the tip of the 
syringe into the back of the space between 
the inside of the cheek and the lower gum. 

 
Step 4 

 

Slowly press the syringe plunger until the 
plunger stops. 
 
The full amount of solution should be 
inserted slowly into the space between the 
gum and the cheek (buccal cavity). 
 
If prescribed by your doctor (for larger 
volumes and/or smaller patients), you can 
give approximately half the dose slowly into 
one side of the mouth, then into the other 
side of the child’s mouth. 

 

28 



 

When to call an ambulance 
ALWAYS follow the treatment advice provided by the patient’s doctor or as explained by a 
healthcare professional. If in any doubt, call for immediate medical help if: 
• The seizure does not stop within 10 minutes 
• You’re unable to empty the syringe or you spill some of the contents 
• The child’s breathing slows down or stops e.g. slow or shallow breathing or blue lips 
• You observe signs of a heart attack which may include chest pain or pain that spreads 

to the neck and shoulders and down the left arm 
• The child is sick (vomits) and the seizure does not stop within 10 minutes 
• You give too much BUCCOLAM and there are signs of overdose which include: 

o Drowsiness, tiredness, fatigue 
o Confusion or feeling disorientated 
o Absence of knee reflex or a response to a pinch 
o Breathing difficulties (slow or shallow breathing) 
o Low blood pressure (giddiness and feeling faint) 
o Coma 

 
Keep the syringe to show to the ambulance staff or doctor. 
 
Do not give more than the amount of medicine prescribed by a doctor for the patient. 
 

29 



 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Plastic oral syringe 5 mg/1 ml 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
BUCCOLAM 5 mg oromucosal solution 
midazolam 
 
For children aged 1 year to less than 5 years 
For oromucosal use only 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
BN 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
5 mg 
 
 
6. OTHER 
 
Single use only. 
Remove the oral syringe cap before use. 

30 



 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Carton (7.5 mg/1.5 ml) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
BUCCOLAM 7.5 mg oromucosal solution 
midazolam 
For children aged 5 years to less than 10 years 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled, oral syringe (1.5 ml) contains 7.5 mg midazolam (as hydrochloride) 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Oromucosal solution 
4 pre-filled oral syringes 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
For oromucosal use only 
Each syringe is for single use only 
Remove the oral syringe cap before use to avoid risk of choking 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not refrigerate or freeze. 
Keep the oral syringe in the protective plastic tube. 
 
 

31 



 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Shire Services BVBA 
rue Montoyer 47 
1000 Brussels 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/11/709/003 
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
BUCCOLAM 7.5 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 

32 



 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
Plastic Tube Label 7.5 mg /1.5 ml 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
BUCCOLAM 7.5 mg oromucosal solution 
midazolam 
For children aged 5 years to less than 10 years 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Shire logo 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
BN 
 
 
5. OTHER 
 
For oromucosal use only 
Remove the oral syringe cap before use 
Keep the oral syringe in the protective plastic tube 

↘  Open Here 
 
How to give this medicine 
 
Buccolam must not be injected. Do not attach a needle to the syringe 
 
The dose is the full contents of one syringe. Do not give more than one dose 
 
Step 1 

 

Hold the plastic tube, break the seal at one 
end and pull the cap off. Take the syringe out 
of the tube. 

33 



 

 
Step 2 

 

Pull the red cap off the tip of the syringe and 
dispose of it safely. 

 
Step 3 

 

Using the finger and thumb gently pinch and 
pull back the child’s cheek. Put the tip of the 
syringe into the back of the space between 
the inside of the cheek and the lower gum. 

 
Step 4 

 

Slowly press the syringe plunger until the 
plunger stops. 
 
The full amount of solution should be 
inserted slowly into the space between the 
gum and the cheek (buccal cavity). 
 
If prescribed by your doctor (for larger 
volumes and/or smaller patients), you can 
give approximately half the dose slowly into 
one side of the mouth, then into the other 
side of the child’s mouth. 

 

34 



 

When to call an ambulance 
ALWAYS follow the treatment advice provided by the patient’s doctor or as explained by a 
healthcare professional. If in any doubt, call for immediate medical help if: 
• The seizure does not stop within 10 minutes 
• You’re unable to empty the syringe or you spill some of the contents 
• The child’s breathing slows down or stops e.g. slow or shallow breathing or blue lips 
• You observe signs of a heart attack which may include chest pain or pain that spreads 

to the neck and shoulders and down the left arm 
• The child is sick (vomits) and the seizure does not stop within 10 minutes 
• You give too much BUCCOLAM and there are signs of overdose which include: 

o Drowsiness, tiredness, fatigue 
o Confusion or feeling disorientated 
o Absence of knee reflex or a response to a pinch 
o Breathing difficulties (slow or shallow breathing) 
o Low blood pressure (giddiness and feeling faint) 
o Coma 

 
Keep the syringe to show to the ambulance staff or doctor. 
 
Do not give more than the amount of medicine prescribed by a doctor for the patient. 
 

35 



 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Plastic oral syringe 7.5 mg/1.5 ml 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
BUCCOLAM 7.5 mg oromucosal solution 
midazolam 
For children aged 5 years to less than 10 years 
For oromucosal use only 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
BN 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
7.5 mg 
 
 
6. OTHER 
 
Single use only 
Remove the oral syringe cap before use. 

36 



 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Carton (10 mg/2 ml) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
BUCCOLAM 10 mg oromucosal solution 
midazolam 
For children aged 10 years to less than 18 years 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled, oral syringe (2 ml) contains 10 mg midazolam (as hydrochloride) 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Oromucosal solution 
4 pre-filled oral syringes 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
 
For oromucosal use only 
Each syringe is for single use only 
Remove the oral syringe cap before use to avoid risk of choking 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not refrigerate or freeze. 
Keep the oral syringe in the protective plastic tube. 
 
 

37 



 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Shire Services BVBA 
rue Montoyer 47 
1000 Brussels 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/11/709/004 
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
BUCCOLAM 10 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
 

38 



 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
Plastic Tube Label 10 mg /2 ml 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
BUCCOLAM 10 mg oromucosal solution 
midazolam 
For children aged 10 years to less than 18 years 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Shire logo 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
BN 
 
 
5. OTHER 
 
For oromucosal use only 
Remove the oral syringe cap before use 
Keep the oral syringe in the protective plastic tube 

↘  Open Here 
 
How to give this medicine 
 
Buccolam must not be injected. Do not attach a needle to the syringe 
 
The dose is the full contents of one syringe. Do not give more than one dose 
 
Step 1 

 

Hold the plastic tube, break the seal at one 
end and pull the cap off. Take the syringe out 
of the tube. 

39 



 

 
Step 2 

 

Pull the red cap off the tip of the syringe and 
dispose of it safely. 

 
Step 3 

 

Using the finger and thumb gently pinch and 
pull back the child’s cheek. Put the tip of the 
syringe into the back of the space between 
the inside of the cheek and the lower gum. 

 
Step 4 

 

Slowly press the syringe plunger until the 
plunger stops. 
 
The full amount of solution should be 
inserted slowly into the space between the 
gum and the cheek (buccal cavity). 
 
If prescribed by your doctor (for larger 
volumes and/or smaller patients), you can 
give approximately half the dose slowly into 
one side of the mouth, then into the other 
side of the child’s mouth. 

 

40 



 

When to call an ambulance 
ALWAYS follow the treatment advice provided by the patient’s doctor or as explained by a 
healthcare professional. If in any doubt, call for immediate medical help if: 
• The seizure does not stop within 10 minutes 
• You’re unable to empty the syringe or you spill some of the contents 
• The child’s breathing slows down or stops e.g. slow or shallow breathing or blue lips 
• You observe signs of a heart attack which may include chest pain or pain that spreads 

to the neck and shoulders and down the left arm 
• The child is sick (vomits) and the seizure does not stop within 10 minutes 
• You give too much BUCCOLAM and there are signs of overdose which include: 

o Drowsiness, tiredness, fatigue 
o Confusion or feeling disorientated 
o Absence of knee reflex or a response to a pinch 
o Breathing difficulties (slow or shallow breathing) 
o Low blood pressure (giddiness and feeling faint) 
o Coma 

 
Keep the syringe to show to the ambulance staff or doctor. 
 
Do not give more than the amount of medicine prescribed by a doctor for the patient. 
 

41 



 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Plastic oral syringe 10 mg/2 ml 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
BUCCOLAM 10 mg oromucosal solution 
midazolam 
For children aged 10 years to less than 18 years 
For oromucosal use only 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
BN 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
10 mg 
 
 
6. OTHER 
 
Single use only. 
Remove the oral syringe cap before use. 
 

42 



 

 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 

43 



 

Package leaflet: Information for the user 
 

BUCCOLAM 2.5 mg oromucosal solution 
For children aged 3 months to less than 1 year 

 
BUCCOLAM 5 mg oromucosal solution 

For children aged 1 year to less than 5 years 
 

BUCCOLAM 7.5 mg oromucosal solution 
For children aged 5 years to less than 10 years 

 
BUCCOLAM 10 mg oromucosal solution 

For children aged 10 years to less than 18 years 
 

Midazolam 
 
Read all of this leaflet carefully, before you start giving this medicine because it contains 
important information for you. 
• Keep this leaflet. You may need to read it again. 
• If you have any further questions, ask your doctor or pharmacist. 
• This medicine has been prescribed for your child. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as those of the child for whom this medicine has been 
prescribed. 

• If you see any side effects, talk to your doctor or pharmacist. This includes any possible side 
effects not listed in this leaflet.  See section 4. 

 
What is in this leaflet: 
1. What BUCCOLAM is and what it is used for 
2. What you need to know before you give BUCCOLAM 
3. How to give BUCCOLAM 
4. Possible side effects 
5. How to store BUCCOLAM 
6. Contents of the pack and other information 
 
 
1. What BUCCOLAM is and what it is used for 
 
BUCCOLAM contains a medicine called midazolam. Midazolam belongs to a group of medicines 
known as benzodiazepines. BUCCOLAM is used to stop a sudden, prolonged, convulsive, seizure in 
infants, toddlers, children and adolescents (from 3 months to less than 18 years of age). 
 
In infants from 3 months to less than 6 months it should only be used in a hospital setting where 
monitoring is possible and resuscitation equipment is available. 
 
This medicine must only be used by parents/carers where the child has been diagnosed to have 
epilepsy. 
 
 
2. What you need to know before you give BUCCOLAM 
 
Do not give BUCCOLAM if the patient has: 
• An allergy to midazolam, benzodiazepines (such as diazepam) or any of the other ingredients of 

this medicine (listed in section 6) 
• A disease of the nerves and muscles causing muscle weakness (myasthenia gravis) 
• Severe difficulty breathing at rest (BUCCOLAM can make breathing difficulties worse) 
• An illness causing frequent interruption of breathing during sleep (sleep apnoea syndrome) 
• Severe liver problems. 

44 



 

 
Warnings and precautions 
Talk to your doctor or pharmacist before giving BUCCOLAM if the patient has: 
• A kidney, liver or heart condition 
• A lung condition that causes difficulty breathing on a regular basis. 

 
This medicine may cause people to forget what happened after they have been given it. Patients should 
be observed carefully after being given the medicine. 
 
This medicine should be avoided in patients with a medical history of alcohol or drug abuse. 
 
Life threatening incidents are more likely in patients with breathing difficulties or heart problems, 
especially when higher doses of BUCCOLAM are given.  
 
Children younger than 3 months: BUCCOLAM should not be given to children younger than 3 
months since there is not enough information in this age group. 
 
If you are not sure if any of the above applies to the patient, talk to a doctor or pharmacist before 
giving this medicine. 
 
Other medicines and BUCCOLAM 
Tell your doctor or pharmacist if the patient is taking, or has recently taken, or might take any other 
medicines. If you have any doubt about whether any medicine the patient is taking may affect the use 
of BUCCOLAM, please speak to your doctor or pharmacist.  
 
This is extremely important, as using more than one medicine at the same time can strengthen or 
weaken the effect of the medicines involved.  
 
The effects of BUCCOLAM may be intensified by medicines such as: 
• antiepileptics, (for treating epilepsy) e.g. phenytoin 
• antibiotics, e.g. erythromycin, clarithromycin  
• antifungals, e.g. ketoconazole, voriconazole, fluconazole, itraconazole, pozaconazole  
• anti-ulcer medicines, e.g. cimetidine, ranitidine and omeprazole  
• medicines used to treat blood pressure, e.g. diltiazem, verapamil 
• some medicines used to treat HIV and AIDS, e.g. saquinavir, lopinavir/ritonavir combination 
• narcotic analgesics (very strong pain killers), e.g. fentanyl  
• medicines used to reduce fat in the blood, e.g. atorvastatin 
• medicines used to treat nausea, e.g. nabilone 
• hypnotics (sleep inducing medicines) 
• sedative antidepressants (medicines used to treat depression that make you sleepy) 
• sedatives (medicines that relax you) 
• anaesthetics (for pain relief) 
• antihistamines (to treat allergies). 
 
The effects of BUCCOLAM may be reduced by medicines such as: 
• rifampicin (used to treat tuberculosis) 
• xanthines (used to treat asthma)  
• St John’s Wort (a herbal medicine). This should be avoided in patients taking BUCCOLAM. 
 
BUCCOLAM may increase the effect of some muscle relaxants e.g. baclofen (causing increased 
drowsiness). This medicine may also stop some other medicines from working as well, e.g. levodopa 
(used to treat Parkinson’s disease). 
 
Talk to your doctor or pharmacist about medicines the patient should avoid whilst taking 
BUCCOLAM. 
 

45 



 

BUCCOLAM with food and drink 
The patient must not drink alcohol while taking BUCCOLAM. Alcohol may increase the sedative 
effects of this medicine and make them very sleepy. 
 
The patient must not drink grapefruit juice while taking BUCCOLAM. Grapefruit juice may increase 
the sedative effects of this medicine and make them very sleepy. 
 
Pregnancy 
If the patient who will be given this medicine is pregnant or breast-feeding, thinks she may be 
pregnant or is planning to have a baby, ask a doctor for advice before taking this medicine.   
 
Giving high doses of BUCCOLAM during the last 3 months of pregnancy can cause abnormal heart 
beat in the unborn child. Babies born after this medicine is administered during childbirth can also 
have poor suckling, breathing difficulties and poor muscle tone at birth. 
 
Breast-feeding  
Tell the doctor if the patient is breast-feeding. Even though small amounts of BUCCOLAM may pass 
into breast milk, it may not be necessary to stop breast-feeding. The doctor will advise if the patient 
should breast-feed after being given this medicine. 
 
Driving and using machines 
BUCCOLAM may make the patient sleepy, forgetful or affect their concentration and co-ordination. 
This may affect their performance at skilled tasks such as driving, riding a bicycle, or using machines. 
 
After receiving this medicine, the patient should not drive a vehicle, ride a bicycle or operate a 
machine until they have completely recovered. Please discuss with your doctor if you need further 
advice. 
 
 
3. How to give BUCCOLAM 
 
Always give this medicine exactly as a doctor has told you. Check with a doctor or pharmacist if you 
are not sure. 
 
Dosage 
Your doctor will prescribe the appropriate dose of BUCCOLAM your child needs, generally according 
to your child’s age. The different doses each have a different colour, which is shown on the carton, the 
tube and the syringe containing the medicine. 
 
Depending on age, your child will have received one of the following doses, in specifically colour 
labelled packaging:  
3 months to less than 1 year: 2.5 mg - yellow labelled packaging 
1 year to less than 5 years: 5 mg - blue labelled packaging 
5 years to less than 10 years: 7.5 mg - purple labelled packaging 
10 years to less than 18 years: 10 mg - orange labelled packaging 
The dose is the full contents of one oral syringe. Do not give more than one dose. 
 
Toddlers aged from 3 months to less than 6 months should only be treated in a hospital setting where 
monitoring is possible and resuscitation equipment is available.  
 
Preparing to give this medicine 
If the child is having a seizure, allow their body to move freely, do not try to restrain them. Only move 
them if they are in danger from, for example, deep water, fire or sharp objects. 
 
Support your child’s head with something soft, such as a cushion or your lap. 
 
Check that the medicine is the correct dose for your child, according to their age. 

46 



 

How to give this medicine 
Ask a doctor, pharmacist or nurse to show you how to take or administer this medicine. Always check 
with them if you are not sure. 
 
The information on how to give this medicine is also shown on the tube label. 
 
Buccolam must not be injected. Do not attach a needle to the syringe 
 
Step 1 

 

Hold the plastic tube, break the seal at one 
end and pull the cap off. Take the syringe out 
of the tube. 

 
Step 2 

 

Pull the red cap off the tip of the syringe and 
dispose of it safely. 

 
Step 3 

 

Using the finger and thumb gently pinch and 
pull back the child’s cheek. Put the tip of the 
syringe into the back of the space between 
the inside of the cheek and the lower gum. 

 

47 



 

Step 4 

 

Slowly press the syringe plunger until the 
plunger stops.  
 
The full amount of solution should be 
inserted slowly into the space between the 
gum and the cheek (buccal cavity). 
 
If prescribed by your doctor (for larger 
volumes and/or smaller patients), you can 
give approximately half the dose slowly into 
one side of the mouth, then into the other 
side of the child’s mouth. 

 
 
When to call an ambulance 
ALWAYS follow the treatment advice provided by the patient’s doctor or as explained by a healthcare 
professional. If in any doubt, call for immediate medical help if: 
• The seizure does not stop within 10 minutes 
• You’re unable to empty the syringe or you spill some of the contents 
• The child’s breathing slows down or stops e.g. slow or shallow breathing or blue lips 
• You observe signs of a heart attack which may include chest pain or pain that spreads to the 

neck and shoulders and down the left arm 
• The child is sick (vomits) and the seizure does not stop within 10 minutes 
• You give too much BUCCOLAM and there are signs of overdose which include: 

o Drowsiness, tiredness, fatigue 
o Confusion or feeling disorientated 
o Absence of knee reflex or a response to a pinch 
o Breathing difficulties (slow or shallow breathing) 
o Low blood pressure (giddiness and feeling faint) 
o Coma 

 
Keep the syringe to show to the ambulance staff or doctor. 
 
Do not give more than the amount of medicine prescribed by a doctor for the patient. 
 
If the child is sick (vomits) 
• Do not give the patient another dose of BUCCOLAM. 
• If the seizure does not stop within 10 minutes, call an ambulance. 
 
If you have any further questions on the use of this medicine, ask a doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Serious side effects 
Seek medical advice immediately or telephone for an ambulance if the patient experiences the 
following: 
• Severe breathing difficulties e.g. slow or shallow breathing or blue lips. In very rare cases 

breathing might stop. 
• Heart attack. Signs may include chest pain which may spread to the child’s neck and shoulders 

and down their left arm. 
 

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Other side effects 
If the patient gets any side effects, talk to their doctor, pharmacist or nurse. This includes any possible 
side effects not listed in this leaflet. 
 
Common side effects (may affect up to 1 in 10 people): 
• Feeling and being sick 
• Sleepiness or losing consciousness 
 
Uncommon side effects (may affect up to 1 in 100 people): 
• Rash, hives (lumpy rash), itchiness 
 
Very rare side effects (may affect up to 1 in 10,000 people):  
• Agitation, restlessness, hostility, rage or aggression, excitement, confusion, euphoria (an 

excessive feeling of happiness or excitement), or hallucinations (seeing and possibly hearing 
things that are not really there) 

• Muscle spasms and muscle tremors (shaking of your muscles that you cannot control) 
• Reduced alertness 
• Headache 
• Dizziness 
• Difficulty co-ordinating muscles 
• Fits (convulsions) 
• Temporary memory loss. How long this lasts depends on how much BUCCOLAM was given.. 
• Low blood pressure, slow heart rate, or redness of the face and neck (flushing) 
• Laryngospasm (tightening of the vocal cords causing difficult and noisy breathing) 
• Constipation 
• Dry mouth 
• Tiredness 
• Hiccups 
 
Reporting of side effects  
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store BUCCOLAM 
 
Keep this medicine out of the sight and reach of children. 
Do not give this medicine after the expiry date which is stated on the carton, tube and oral syringe 
labels after EXP. The expiry date refers to the last day of that month. 
 
Do not refrigerate or freeze. 
 
Keep the oral syringe in the protective plastic tube. 
 
Do not use this medicine if the packaging has been opened or damaged. 
 
Disposal of oral syringes 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use.  These measures will help to protect the environment. 
 
 

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6. Contents of the pack and other information 
 
What BUCCOLAM contains  
• The active substance is midazolam 
• Each 2.5 mg pre-filled oral syringe contains 2.5 mg midazolam (as hydrochloride) in 0.5 ml 

solution. 
• Each 5 mg pre-filled oral syringe contains 5 mg midazolam (as hydrochloride) in 1 ml solution. 
• Each 7.5 mg pre-filled oral syringe contains 7.5 mg midazolam (as hydrochloride) in 1.5 ml 

solution. 
• Each 10 mg pre-filled oral syringe contains 10 mg midazolam (as hydrochloride) in 2 ml 

solution. 
 
The other ingredients are sodium chloride, water for injections, hydrochloric acid and sodium 
hydroxide (for pH adjustment). 
 
What BUCCOLAM looks like and contents of the pack 
3 months to less than 1 year: 2.5 mg - yellow labelled packaging 
1 year to less than 5 years: 5 mg - blue labelled packaging 
5 years to less than 10 years: 7.5 mg - purple labelled packaging 
10 years to less than 18 years: 10 mg - orange labelled packaging 
 
BUCCOLAM oromucosal solution is a clear colourless liquid. It is supplied in an amber coloured pre-
filled, single-use oral syringe. Each oral syringe is individually packed in a protective plastic tube. 
BUCCOLAM is available in cartons containing 4 pre-filled oral syringes/tubes (of the same dose). 
 
Marketing Authorisation Holder 
 
Shire Services BVBA 
rue Montoyer 47 
1000 Brussels 
Belgium 
Tel: +44(0)1256 894 959 
E-mail: medinfoEMEA@shire.com 
 
Manufacturer 
 
Shire Pharmaceuticals Ireland Limited 
Block 2 & 3 Miesian Plaza 
50 – 58 Baggot Street Lower 
Dublin 2 
Ireland 
 
This leaflet was last revised in . 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
 

50 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D.  CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET