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Fulsed
Midazolam Maleate Tablets
COMPOSITION
FULSED TABLETS 7.5 MG
Each film-coated tablet contains
Midazolam Maleate equivalent to Midazolam 7.5 mg
FULSED TABLETS 15 MG
Each film-coated tablet contains
Midazolam Maleate equivalent to Midazolam 15 mg
PRODUCT DESCRIPTION
FULSED TABLETS 7.5 MG
White to off-white, round, biconvex film-coated tablets
FULSED TABLETS 15 MG
Blue to deep blue colored, round, biconvex film-coated tablets
DESCRIPTION
FULSED TABLET (Midazolam Maleate Tablet) contains Midazolam Maleate which is
a water-soluble benzodiazepine. Chemically, midazolam maleate is
8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a] [1,4] benzodiazepine
maleate. Midazolam maleate has the empirical formula C18H13CIFN3.C4H4O4 and
a calculated molecular weight of 441.84. Its structural formula is as
follows:
PHARMACOLOGY
• Mechanism of action
Midazolam is a short-acting benzodiazepine CNS depressant and binds to
specific receptors in the CNS. The benzodiazepine receptors in the CNS have
a close functional connection with receptors of the GABA-ergic transmitter
system. After binding to the benzodiazepine receptor, midazolam augments the
inhibitory effect of GABA-ergic transmission. The effects of midazolam on
the CNS are dependent on the dose administered, the route of administration,
and the presence or absence of other medications.
Midazolam is a sleep-inducing agent characterized by a rapid onset and short
duration of action. It also exerts an anxiolytic, anticonvulsant and
muscle-relaxant effect.
• Pharmacokinetics
Absorption
Midazolam is absorbed rapidly and completely after oral administration. With
a dose of 15 mg, maximum plasma concentrations of 70-120 ng/ml are reached
within one hour. Food prolongs the time to peak plasma concentration by one
hour, indicating a reduced absorption rate of midazolam. The absorption
half-life is 5-20 minutes.
Due to the substantial first-pass effect, absolute bioavailability is
30-50%. The pharmacokinetics of midazolam is linear in the 7.5-15 mg oral
dose range.
Distribution
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. Midazolam is 96-98% bound to plasma proteins mainly
albumin. There is a slow and insignificant passage of midazolam into
cerebrospinal fluid. In humans, midazolam has been shown to cross the
placenta slowly and enter into fetal circulation. Small quantities of
midazolam are found inhuman milk.
Metabolism
Midazolam is almost entirely eliminated by biotransformation. Midazolam is
hydroxylated by cytochrome P4503A4 isozyme. Alpha-hydroxy-midazolam
(1-hydroxy-midazolam) is the major urinary and plasma metabolite. Plasma
concentrations of alpha-hydroxymidazolam are 30-50% those of the parent
compound. After oral administration, there is a substantial first-pass
metabolism of 30-60%. The elimination half-life of the metabolite is shorter
than 1 hour. Alpha-hydroxy-midazolam is pharmacologically active and
contributes significantly (about 34%) to the effects of oral midazolam.
There is no evidence of a genetic polymorphism in the oxidative metabolism
of midazolam.
In young healthy volunteers, the elimination half-life is between 1.5 and
2.5 hours. Midazolam is anon-accumulating medicine when given once nightly.
Repeated administrations of midazolam do not induce drug-metabolizing
enzymes.
Elimination
Less than 1 % of the dose is recovered in urine as the unchanged substance.
Sixty to eighty percent of the dose is excreted in the urine as
glucuroconjugated α-hydroxymidazolam.
Pharmacokinetics in Special Populations
Elderly. Patients above 60 years of age has little or no influence on the
pharmacokinetics of oral midazolam.
Patients with hepatic impairment: Liver cirrhosis has no effect, or may
increase the absolute bioavailability of midazolam because of reduced
metabolism.
INDICATIONS
FULSED TABLET (Midazolam Maleate Tablet) is indicated for the short-term
treatment of insomnia.
Benzodiazepines are only indicated when the disorder is severe, disabling or
subjecting the individual to extreme distress. FULSED TABLET (Midazolam
Maleate Tablet) is also used for sedation in premedication before surgical
or diagnostic procedures.
DOSAGE AND ADMINISTRATION
In order to minimize the risk of dependence, benzodiazepines should only be
prescribed after careful consideration of the indication and should be taken
for the shortest possible duration. 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. The necessity of continuing treatment
should be closely monitored.
In certain cases extension beyond the maximum treatment period may be
necessary; it so, it should not take place without reevaluation of the
patients status. Owing to the rapid onset of action FULSED TABLETS should
betaken immediately before going to bed, and swallowed whole with fluid.
Standard dosage
Adults:
Initial dose : 7.5 mg
Dosage range : 7.5-15 mg.
In elderly and debilitated patients the recommended dose is 7.5 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.
Special dosage instructions
In patents with impaired liver function, the recommended dose is 7.5 mg.
FULSED TABLETS can betaken at any time of the day, provided the patient is
subsequently assured of at least 7-8 hours undisturbed sleep.
Premedication
In premedication,15mg of FULSED TABLETS should be given 30-60 minutes before
the procedure.
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