Download NOVERIL 240 MG TABLETS

‫פורמט עלון זה נקבע ע"י משרד הבריאות ותוכנו נבדק ואושר על ידו בנובמבר ‪05‬‬
‫‪NOVERIL® 240 MG TABLETS‬‬
‫)‪(dibenzepin‬‬
‫‪Prescribing Information‬‬
Novartis
NPI
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Noveril
Name of the medicinal product
NOVERIL® 240 mg tablets
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Qualitative and quantitative composition
Dibenzepin* hydrochloride 240 mg
* INN rec.
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Pharmaceutical form
Coated tablets
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Clinical particulars
4.1
Therapeutic indications
Adults
For the treatment of depression
Children and adolescents
In children and adolescents, there is not sufficient evidence of safety and efficacy of Noveril®
in the treatment of symptoms of depression. The use of Noveril in children and adolescents
(0-17 years of age) is therefore not recommended.
4.2
Posology and method of administration
Dosage
Doses must be adapted to individual requirements. Lower-than-usual doses are recommended
for elderly patients. The dosages are the following:
Oral administration
Age group
Average
Maximum
(mg per day)
(mg per day)
Adults
480
720
Elderly patients
240
480
The dose should be gradually increased up to an optimum therapeutic level and continued for
4 to 8 weeks. As with all tricyclic antidepressants, 1 to 3 weeks of treatment may be needed
until the optimal therapeutic effect is achieved. Following remission, the dose may usually be
reduced to one-half to one-third for maintenance therapy.
In adult patients, treatment should begin with Noveril 240 mg tablets, the daily dose being
given as a single dose or in 2 divided doses. (Note: tablet remnants of the Noveril 240 mg
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form may occasionally be passed with the feces. They contain no active substance.) If coated
tablets are used, the daily dose must be divided into 3 doses.
4.3
Contraindications
Known hypersensitivity to the drug, narrow-angle glaucoma.
4.4
Special warnings and special precautions for use
Risk of suicide is inherent to severe depression and may persist until significant remission
occurs. Patients with depressive disorders, both adult and paediatric, may experience
worsening of depression and/or suicidality or other psychiatric symptoms, whether or not they
are taking antidepressant medication. Antidepressants increased the risk of suicidal thinking
and behaviour (suicidality) in short-term studies in children and adolescents with depressive
disorders and other psychiatric disorders.
All patients being treated with Noveril for any indication should be observed closely for
clinical worsening, suicidality and other psychiatric symptoms (see section 4.8 Undesirable
effects), especially during the initial phase of therapy or at times of dose changes.
Modifying the therapeutic regimen, including possibly discontinuing the medication, should
be considered in these patients, especially if these changes are severe, abrupt in onset, or were
not part of the patient's presenting symptoms.
Families and caregivers of both paediatric and adult patients being treated with
antidepressants for both psychiatric and nonpsychiatric indications, should be alerted about
the need to monitor patients for the emergence of other psychiatric symptoms (see section 4.8
Undesirable effects), as well as the emergence of suicidality, and to report such symptoms
immediately to health care providers [2].
Prescriptions for Noveril should be written for the smallest quantity of tablets consistent with
good patient management, in order to reduce the risk of overdose.
Caution should be exercised in patients at risk of paralytic ileus, with prostatic enlargement,
heart failure, hyperthyroidism, bronchial asthma and impaired hepatic or renal function.
In epileptic patients, Noveril may lower seizure threshold. It should only be used if seizures
are adequately controlled under anti-epileptic medication.
Regular checks should be made on blood pressure if the patient is receiving antihypertensive
agents.
If the patient experiences difficulty in falling asleep, the evening dose should either be taken
before 4 p.m. or combined with a sedative.
Caution is indicated in patients with a history of thrombosis because Noveril may increase the
risk of thromboembolism due to sedation and immobilization of the patient.
4.5
Interactions with other medicinal products and other forms of
interaction
Tricyclic antidepressants may enhance:
• the response to alcohol especially during the first days of treatment (consumption of
alcohol should be avoided during treatment with Noveril)
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Noveril
the effects of CNS depressants and anticholinergics
the cardiovascular effects of sympathomimetics including amphetamine (concomitant
treatment may result in tachycardia, arrhythmia and hypertension)
the effects of oral anticoagulants, possibly by inhibiting enzymatic metabolism of the
anticoagulant.
Tricyclic antidepressants may decrease:
• the antihypertensive effect of methyldopa and guanethidine
• the effect of anticonvulsants (see section 4.4 Special warnings and special precautions for
use)
Effectiveness of tricyclic antidepressants may be reduced by concomitant intake of
barbiturates due to hepatic enzyme induction, whereas cimetidine may increase the
effectiveness due to inhibition of their metabolism.
Concomitant intake of MAO inhibitors may increase the risk of neuroleptic malignant
syndrome with hyperpyretic episodes, convulsions and hypertensive crises. 14 days should
elapse between the discontinuation of antidepressant and the initiation of MAO-inhibitor
therapy.
4.6
Pregnancy and lactation
Noveril should be used during pregnancy and lactation only under compelling circumstances.
4.7
Effects on ability to drive and use machines
Noveril can impair the patient's reactions, e.g. driving a vehicle and operating machinery.
4.8
Undesirable effects
In the initial stage of therapy, Noveril may cause headache, tiredness, drowsiness or agitation
and inner restlessness. Anticholinergic effects such as dry mouth, accommodation
disturbances, constipation and micturition disorders may also be observed.
Although therapeutic doses have little effect on blood pressure or the ECG, the following
cardiovascular symptoms may occur: tachycardia, hypotension, dizziness and, rarely,
arrhythmia.
On rare occasions, skin rashes, agranulocytosis, vasculitis have been reported.
4.9
Overdose
Symptoms: accommodation disturbances; dryness of mucosa; vertigo, dizziness, alternation
between excitation and apathy; hyperthermia; cramps, grand mal seizures, coma; tachycardia,
hypotension; AV-block, arrhythmia; cardiac arrest; respiratory depression.
Treatment: elimination of the drug from the gastrointestinal tract by gastric lavage (in case
of overdosage with Noveril 240 mg tablets use the stomach tube with the largest possible
lumen), administration of activated charcoal. Symptomatic treatment of the cardiovascular
and respiratory system. Cardiac arrhythmias may be controlled by alkalinization of blood or,
in refractory cases, by phenytoin under ECG monitoring. Administration of physostigmine to
control anticholinergic effects and of anticonvulsants to control convulsions. Special attention
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should be paid to metabolic acidosis. Close monitoring for not less than 5 days (because of
late effects!).
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Pharmacological properties
5.1
Pharmacodynamic properties
Pharmacotherapeutic group: Tricyclic antidepressant, non selective monoamine reuptake
inhibitors, ATC code: N06A A08
Noveril is a tricyclic antidepressant of the dibenzo-epine group. It is a selective noradrenaline
uptake inhibitor, which exhibits in vitro and in vivo imipramine-like effects. It is also
qualitatively comparable to desipramine, nortriptyline and maprotiline. It binds strongly to
histamine H1 receptors in the brain and, to a lesser extent, to cholinergic receptors. The
pharmacological profile of Noveril corresponds widely to its biochemical properties:
histamine antagonism, tetrabenazine antagonism, potentiation of various noradrenergic
effects and anticholinergic effects.
5.2
Pharmacokinetic properties
After oral administration of the 80 mg tablet, dibenzepin is absorbed with a half-life of
0.5 hours, giving rise to maximal plasma concentrations of about 100 ng/mL. The absolute
bioavailability does not exceed 25% due to first-pass metabolism. The volume of distribution
is approx. 300 L. Protein binding is 80%. Dibenzepin is mainly eliminated by metabolization,
with a terminal half-life of 5 hours. Only 1% of the dose is excreted unchanged in the urine.
The main metabolite in plasma arises from demethylation of dibenzepin in the side chain. Its
plasma concentration is approximately 1.5 times that of dibenzepin. This metabolite possesses
similar pharmacological properties as dibenzepin.
Once-a-day long-term dosing of the 240 mg tablet yields similar plasma concentrations as
t.i.d. administration of the 80 mg tablet.
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Pharmaceutical particulars
Noveril must be kept out of the reach and sight of children.
Manufacturer:
Novartis Farma S.p.A., Italy
for Novartis Pharma AG, Basel, Switzerland
License Holder:
PharmaExcel Ltd.
23 Hasivim St., Petach-Tikva
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