Therapeutic/ Pharmacologic Class of Drug
Dormicum Tablet is a sleep-inducing agent belonging to the
ATC code: N05CD08
Type of Dosage Form
Route of Administration
Sterile / Radioactive Statement
Qualitative and Quantitative Composition
Active ingredient: midazolam as the maleate.
Tablets containing midazolam maleate equivalent to 7.5 mg
and 15 mg of midazolam.
Excipients: described as per local requirements (Dormicum
Short-term treatment of insomnia
Benzodiazepines are only indicated when the disorder is
severe, disabling or subjecting the individual to extreme
Sedation in premedication before surgical or diagnostic
Dosage and Administration
Generally the duration of treatment varies from a few days to
a maximum of 2 weeks. The tapering-off process should be
tailored to the individual. Treatment with Dormicum should
In certain cases extension beyond the maximum treatment
period may be necessary; if so, it should not take place
without reevaluation of the patient’s status. Owing to the
immediately before going to sleep, and swallowed whole with
fluid. Dormicum can be taken any time of the day, provided
the patient is subsequently assured of at least 7 – 8 hours
Dosage range: 7.5 – 15 mg
Treatment should be started with the lowest recommended
dose. The maximum dose should not be exceeded because of
the increased risk of CNS adverse effects possibly including
clinically relevant respiratory and cardiovascular depression.
In premedication, Dormicum should be given 30 – 60 minutes
before the procedure.
Special Dosage Instructions
Elderly and/or debilitated patients
In elderly and/or debilitated patients the recommended dose is
Elderly patients showed a larger sedative effect, therefore
they may be at increased risk of cardio-respiratory depression
as well. Thus, Dormicum should be used very carefully in
Patients with hepatic impairment
In patients with impaired liver function, the recommended
dose is 7.5 mg. Dormicum should be used very carefully in
patients with hepatic impairment. If necessary a lower dose
should be considered (see 3.2.5 Pharmacokinetics in Special
Patients with renal impairment
In patients with severe renal impairment, accumulation of the
respiratory and cardiovascular depression. Dormicum should
therefore be dosed carefully in this patient population. The
recommended dose is 7.5 mg and when needed a lower dose
should be considered.
Severe respiratory insufficiency;
Severe hepatic insufficiency;
Sleep apnea syndrome;
benzodiazepines or to any component of the product;
itraconazole, voriconazole, HIV protease inhibitors
Medicinal Products and other Forms of Interaction).
Warnings and Precautions
Information should be given to the patients about following
warnings and precautions.
Some loss of efficacy to the hypnotic effects of short-acting
benzodiazepines may develop after repeated use for a few
Duration of treatment
Extension beyond this period should not take place without
reevaluation of the situation.
When discontinuing Dormicum therapy, insomnia may recur,
possibly with a higher severity than before starting treatment
sundrome, may be accompanied by other reactions including
mood changes, anxiety and restlessness. The risk of rebound
treatment. Therefore it is recommended that the dosage of
Dormicum is decreased gradually (see 2.4.2 Drug Abuse and
most frequently within the first few hours after ingesting the
product. In order to reduce the risk, patients should ensure
that they are able to have an uninterrupted sleep of 7 – 8 hours
(see 2.6 Undesirable effects).
Provided the oral dose of Dormicum is not larger than 15
mg/day and the patient is assured of at least 7 to 8 hours
undisturbed sleep, no residual effect is observed following
oral administration of Dormicum tablet in standard patients as
Psychiatric and ‘paradoxical’ reactions
behaviour and other adverse behavioural effects are known to
occur when using benzodiazepines. Should this be so, use of
the drug should be discontinued.
These effects are more likely to occur in the elderly.
Specific patient groups
In elderly and/or debilitated patients, as well as in patients
recommended dose is 7.5 mg. these patients may be more
sensitive to the clinical side effects of midazolam like cardio-
respiratory depression. Thus Dormicum should be used very
carefully in these patient populations and if needed a lower
Dosage instructions for patients with hepatic and/or renal
impairment are described in section 2.2.1 Special Dosage
Instructions. Benzodiazepines are contraindicated in patients
encephalopathy, see section 2.3 Contraindications.
treatment of psychotic illness. Benzodiazepines should not be
used alone to treat depression or anxiety associated
depression as suicide may occur in such patients.
Concomitant use of alcohol / CNS depressants
The concomitant use of Dormicum with alcohol or/and CNS
depressants should be avoided. Such concomitant use has the
potential to increase the clinical effects of Dormicum possibly
and/or cardio-vascular depression (see 2.4.4 Interactions with
other Medicinal Products and other Forms of Interaction).
Medical history of alcohol or drug abuse
history of alcohol or drug abuse.
Co-medication with drugs that later CYP3A activity
Midazolam pharmacokinetics is altered in patients receiving
increased or decreased respectively (see 2.4.4 Interactions
intolerance, the Lapp lactase deficiency or glucose-galactose
malabsoption should not take this medicine.
Drug Abuse and Dependence
Use of Dormicum may lead to the development of physical
and psychic dependence. The risk of dependence increases
with dose and duration of treatment; it is also greater in
patients with a medical history of alcohol and/or drug abuse.
pain, extreme anxiety, tension, restlessness, confusion and
numbness and tingling of the extermities, hypersensitivity to
Since the risk of withdrawal phenomena/ rebound insomnia is
recommended that the dosage be decreased gradually (see 2.2
Dosage and Administration and 2.4.1 General (Warnings and
Ability to Drive and Use Machines
muscular function may adversely affect the ability to drive or
likelihood of impaired alertness may be increased (see also
2.4.4 Interactions with Other Medicinal Products and other
Forms of Interaction).
Interactions with other Medicinal Products
and other Forms of Interaction
cytochrome P450 3 (CYP3A), modulators of CYP3A have the
potential to alter the plasma concentrations, and subsequently
the clinical effects of midazolam.
Combination of midazolam with strong and moderate CYP3A
condition that could make the patient in particular sensitive to
the potential clinical side effects of midazolam (see 2.4.1
General (Warnings and Precautions)).
Weak inhibitors: Midazolam AUC increased by 1.25 to
< 2-fold or C
increased by 1.25 to < 2-fold. The
following drugs and gerbals are included in this category:
concomitant use with midazolam.
Drugs that induce CYP3A
Patients receiving a combination of midazolam with CYP3A
inducers may require a higher midazolam dose in particular if
midazolam is co0administered with strong CYP3A inducers.
inducers include efavirenz and St John’s wort.
Pharmacodynamic Drug-Drug Interactions (DDI)
antipsychotics, other benzodiazepines used as anxiolytics or
sedative antidepressants, antihistamines and centrally acting
antihypertensive drugs. Midazolam decreases the minimum
alveolar concentration (MAC) of inhalational anaesthetics.
Enhanced side effects such as sedation and cardiorespiratory
administered with any centrally acting depressants including
alcohol. The combined influence of alcohol and midazolam
Please see section 2.7 Overdose for warning of other central
nervous system depressants, including alcohol.
Use in Special Populations
Insufficient data are available on midazolam to assess its
safety during pregnancy. Benzodiazepines should be avoided
during pregnancy unless there is no safer alternative. If the
product is prescribed to a woman of childbearing potential,
warned to contact her physician regarding
discontinuance of the product if she intends to become or
suspects that she is pregnant.
pregnancy or at high doses during labour has been reported to
produce irregularities in the foetal heart rate, hypotonia, poor
sucking and hypothermia and moderate respiratory depression
in the neonate.
Moreover, infants born to mothers who took benzodiazepines
chronically during the latter stages of pregnancy may have
developed physical dependence and may be at some risk of
developeing withdrawal symptoms in the postnatal period.
Labor and Delivery
See 2.5.1 Pregnancy.
Since midazolam passes into breast milk, Dormicum should
not be administered to breast-feeding mothers.
See 2.3 Contraindications.
(Warnings and Precautions).
See 2.2.1 Special Dosage Instructions.
See 2.2.1 Special Dosage Instructions.
Immune System Disorders: Hypersensitivity reactions may
occur in susceptible individuals.
Psychiatric Disorders: Confusional state, emotional disorder.
These phenomena occur predominantly at the start of therapy
and usually disappear with repeated administration. Libido
disorders have been reported occasionally.
Depression: pre-existing depression may be unmasked during
hallucinations, psychosis, inappropriate behaviour and other
benzodiazepines or benzodiazepine-like agents. Should this
be the case, the use of the drug should be discontinued. These
effects are more likely to occur in the elderly.
Dependence: Use (even at therapeutic doses) may lead to the
development of physical dependence: discontinuation of the
restlessness (see 2.4.1 General (Warnings and Precautions).
Psychic drug dependence may occur. Abuse has been reported
in poly-drug abusers.
phenomena occur predominantly at the start of the therapy
and usually disappear with repeated administration.
When used as premedication, this product may contribute to
Anterograde amnesia may occur with therapeutic doses, the
risk increasing at higher dosages. Amnestic effects may be
associated with inappropriate behaviour (see 2.4.1 General
(Warnings and Precautions)).
predominantly at the start of therapy and usually disappears
with repeated administration.
have been reported occasionally.
Skin and Subcutaneous Tissue Disorders: Skin reactions have
been reported occasionally.
Musculoskeletal and Connective Tissue Disorders: Muscle
weakness, this phenomenon occurs predominantly at the start
Fatigue, this phenomenon occurs predominantly at the start of
therapy and usually disappear with repeated administration.
Injury, Poisoning and Procedural Complications: There have
been reports of falls and fractures in benzodiazepine users.
The risk is increased in those taking concomitant sedatives
(including alcoholic beverages) and in the elderly.
Respiratory Disorders: Respiratory depression was reported.
Cardiac Disorders: Cardiac failure including cardiac arrest
dysarthria and nystagmus. Overdose of Dormicum is seldom
life-threatening, if the drug is taken alone, but may lead to
depression and rare cases to coma. Coma, if it occurs, usually
lasts a few hours but it may be more protracted and cyclical,
particularly in elderly patients. Benzodiazepine respiratory
Benzodiazepines increase the effects of other central nervous
system depressants, including alcohol.
particular, patients may require symptomatic treatment for
cardiorespiratory effects or central nervous system effects.
If taken orally further absorption should be prevented using
an appropriate method e.g. treatment within 1 – 2 hours with
protection is imperative for drowsy patients. In case of mixed
ingestion gastric lavage may be considered, however not as a
If CNS depression is severe consider the use of flumazenil
), a benzodiazepine antagonist. This should only be
administered under closely monitored conditions. It has a
short half-life (about an hour), therefore patients administered
flumazenil will require monitoring after its effects have worn
off. Flumazenil is to be used with extreme caution in the
presence of drugs that reduce seizure threshold (e.g. tricyclic
), for further information on the correct
use of this drug.
Mechanism of Action
Dormicum is a sleep-inducing agent characterized by a rapid
onset and short duration of action. It also exerts an anxiolytic,
Dormicum impairs psychomotor function after single and/or
multiple doses but causes minimal haemodynamic changes.
As for other benzodiazepines, it is believed that the effects of
gamma-aminobutyric acid receptors (GABA
) in the CNS.
receptors, but require the endogenous ligand,
i.e. GABA, to exert the effects.
bioavailability of oral midazolam ranges between is 30 –
50%. The pharmacokinetics of midazolam is linear in the 7.5
– 20 mg oral dose range.
After a dose of single administration of a Dormicum 15 mg
tablet, maximum plasma concentrations of 70 – 120 ng/ ml
are reached within one hour. Food prolongs the time to peak
reduced absorption rate of midazolam. The absorption half-
life is 5 – 20 minutes.
The tissue distribution of midazolam is very rapid and in most
cases a distribution phase is not apparent or is essentially
finished within 1 – 2 hours after oral administration. The
volume of distribution at steady state is 0.7 – 1.2 l / kg. 96 –
98% of midazolam is bound to plasma proteins. The major
fraction of plasma protein binding is due to albumin. There is
cerebrospinal fluid. In humans, midazolam has been shown to
cross the placenta slowly and to enter fetal circulation. Small
quantities of midazolam are found in human milk.
biotransformation. Less than 1% of the dose is recovered in
hepatic oxidative metabolism of midazolam.
hydroxymidazolam (also named α-hydroxymidazolam) and 4-
urinary and plasma metabolite. 60 – 80% of the dose is
hydroxymidazolam conjugate. Plasma concentrations of 1’-
hydroxymidazolam may reach 30 – 50% those of the parent
compound. 1’-hydroxymidazolam is pharmacologically active
and contributes significantly (about 34%) to the effects of oral
midazolam ranges between 1.5 to 2.5 hours. Midazolam is a
metabolite is shorter than 1 hour.
Pharmacokinetics in Special Populations
In elderly male subjects over 60 years of age, the elimination
half-life of midazolam was significantly prolonged by a factor
elderly subjects and the bioavailability of the oral tablet was
significantly increased. However no significant differences
Patients with hepatic impairment
advanced liver cirrhosis. In particular, as a consequence of a
prolonged and the absolute bioavailability of oral midazolam
was significantly increased in cirrhotic patients compared to
Patients with renal impairment
The pharmacokinetics of midazolam are not altered in patients
with chronic renal failure. However the major midazolam
excreted through the kidney, accumulates in patients with
severe chronic renal failure. This accumulation produces a
administered carefully in patients with renal impairment.
In obese patients the volume of distribution of midazolam is
increased. As a consequence, the mean elimination half-life of
midazolam is longer in obese than in non-obese patients (5.9
hours vs 2.3 hours). The oral bioavailability of the midazolam
tablet was not different in obese patients compared to non-
Dormicum Film-Coated Tablets 15 mg: Keep container in
outer carton in order to protect from light.
This medicine should not be used after the expiry date (EXP)
shown on the pack.
Tablets 7.5 mg (white) 10
Tablets 15 mg (blue) 10, 20, 30, 100
Not all pack sizes are available for sale.
Medicine: keep out of reach of children
Current at Jul 2013
Made for F. Hoffmann-La Roche Ltd,
By Productos Roche S.A. de C.V.