Zismirt orotab 15 mg, 30 mg & 45 mg Orodispersible Tablets

  • Name:

    Zismirt orotab 15 mg, 30 mg & 45 mg Orodispersible Tablets

  • Company:
    info
  • Active Ingredients:

    Mirtazapine

  • Legal Category:

    Product subject to medical prescription which may not be renewed (A)

Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 12/11/15

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Summary of Product Characteristics last updated on medicines.ie: 28/7/2015
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Gerard Laboratories

Gerard Laboratories

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101 - 117 of 117 items.Total: 5 pages

When a pharmaceutical company changes any document, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 12 November 2015 PIL

Reasons for updating

  • Change of trade or active ingredient name

Updated on 12 November 2015 PIL

Reasons for updating

  • New PIL for new product

Updated on 28 July 2015 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 5.3 - Preclinical safety data
  • Change to section 6.1 - List of excipients
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.1:
Treatment of episodes of major depression in adults.

Section 4.2:
Posology

Adults
The effective daily dose is usually between 15 and 45 mg; the starting dose is 15 or 30 mg. Zismirt orotab begins to exert its effect in general after 1-2 weeks of treatment. Treatment with an adequate dose should result in a positive response within 2-4 weeks. With an insufficient response, the dose can be increased up to the maximum dose. If there is no response within a further 2-4 weeks, then treatment should be stopped.
Patients with depression should be treated for a sufficient period of at least 6 months to ensure that they are free from symptoms.
It is recommended to discontinue treatment with mirtazapine gradually to avoid withdrawal symptoms (see section 4.4).

Elderly
The recommended dose is the same as that for adults. In elderly patients an increase in dosing should be done under close supervision to elicit a satisfactory and safe response.

Paediatric population
Zismirt orotab should not be used in children and adolescents under the age of 18 years as efficacy was not demonstrated in two short-term clinical trials (see section 5.1) and because of safety concerns (see sections 4.4, 4.8 and 5.1).

Patients with renalRenal impairment
The clearance of mirtazapine may be decreased in patients with moderate to severe renal impairment (creatinine clearance < 40 ml/min). This should be taken into account when prescribing Zismirt orotabmirtazapine to this category of patients (see section 4.4).

Patients with Hepatic hepatic impairment
The clearance of mirtazapine may be decreased in patients with hepatic impairment. This should be taken into account when prescribing Zismirt orotabmirtazapine to this category of patients, particularly with severe hepatic impairment, as patients with severe hepatic impairment have not been investigated (see section 4.4).

Paediatric population
Zismirt orotab should not be used in children and adolescents under the age of 18 years as efficacy was not demonstrated in two short-term clinical trials (see section 5.1) and because of safety concerns (see sections 4.4, 4.8 and 5.1).

Method of Administrationadministration
Mirtazapine has an elimination half-life of 20-40 hours and therefore Zismirt orotabmirtazapine is suitable for once daily administration. It should be taken preferably as a single night-time dose before going to bed.

Zismirt orotabMirtazapine may also be given in two divided doses (once in the morning and once at night-time, the higher dose should be taken at night).

The tablets should be taken orally. The tablet will rapidly disintegrate and can be swallowed without water.

Patients with depression should be treated for a sufficient period of at least 6 months to ensure that they are free from symptoms.
It is recommended to discontinue treatment with mirtazapine gradually to avoid withdrawal symptoms (see section 4.4).

Section 4.4
[...]

With regard to the chance of suicide, in particular at the beginning of treatment, only a limited number the smallest amount of Zismirt orotab orodispersible tabletsmirtazapine should be given to the patient consistent with good patient management, in order to reduce the risk of overdose.

Like with other antidepressants, the following should be taken into account:
[...]
- QT prolongation: Cases of QT prolongation, torsades de pointes, ventricular tachycardia, and sudden death, have been reported during the post-marketing use of mirtazapine. The majority of reports occurred in association with overdose or in patients with other risk factors for QT prolongation, including concomitant use of QTc prolonging medicines (see sections 4.5 and 4.9). Caution should be exercised when mirtazapine is prescribed in patients with known cardiovascular disease or family history of QT prolongation, and in concomitant use with other medicinal products thought to prolong the QTc interval.

Section 4.5

Pharmacodynamic interactions
[...]
- The risk of QT prolongation and/or ventricular arrhythmias (e.g. torsades de pointes) may be increased with concomitant use of medicines which prolong the QTc interval (e.g. some antipsychotics and antibiotics)

 

Paediatric population

Interaction studies have only been performed in adults.

Section 4.6
Pregnancy
Limited data of the use of mirtazapine in pregnant women do not indicate an increased risk for congenital malformations. Studies in animals have not shown any teratogenic effects of clinical relevance, however developmental toxicity has been observed (see section 5.3). Caution should be exercised when prescribing to pregnant women. If Zismirt orotab is used until, or shortly before birth, postnatal monitoring of the newborn is recommended to account for possible discontinuation effects.

Epidemiological data have suggested that the use of SSRIs in pregnancy, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). Although no studies have been investigated an the association of PPHN to mirtazapine treatment, this potential risk cannot be ruled out taking in to account the related mechanism of action (increase in serotonin concentrations).

Caution should be exercised when prescribing to pregnant women. If mirtazapine is used until, or shortly before birth, postnatal monitoring of the newborn is recommended to account for possible discontinuation effects.

Breast-feeding
Animal studies and limited human data have shown excretion of mirtazapine in breast milk only in very small amounts. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with Zismirt orotab mirtazapine should be made taking into account the benefit of breast- feeding to the child and the benefit of Zismirt orotab mirtazapine therapy to the woman.

Fertility
Non-clinical reproductive toxicity studies in animals did not show any effect on fertility.

Section 4.7
Zismirt orotab Mirtazapine has minor or moderate influence on the ability to drive and use machines. Zismirt orotab Mirtazapine may impair concentration and alertness (particularly in the initial phase of treatment). Patients should avoid the performance of potentially dangerous tasks, which require alertness and good concentration, such as driving a motor vehicle or operating machinery, at any time when affected.

Section 4.8
Gastrointestinal disorders: Constipation added under column 'common'.
Musculoskeletal and connective tissue disorders: Rhabdomyolysis added under column 'not known'.
Renal and urinary disorders: Urinary retention added under column 'not known'.
General disorders and administration site conditions: Generalised oedema and Localised oedema added under column 'not known'.
Investigations: Increased creatinine kinase added under column 'not known'.
[...]
Reporting of suspected adverse reactions: IMB contact details updated to HPRA.

Section 4.9:
Present experience concerning overdose with Mirtazapine mirtazapine alone indicates that symptoms are usually mild. Depression of the central nervous system with disorientation and prolonged sedation have been reported, together with tachycardia and mild hyper- or hypotension. However, there is a possibility of more serious outcomes (including fatalities) at dosages much higher than the therapeutic dose, especially with mixed overdoses. In these cases QT prolongation and torsade de pointes have also been reported.
Cases of overdose should receive appropriate symptomatic and supportive therapy for vital functions. ECG monitoring should be undertaken. Activated charcoal or gastric lavage should also be considered.

Paediatric population
The appropriate actions as described for adults should be taken in case of an overdose in paediatrics.

Section 5.1
Pharmacotherapeutic group: other antidepressants, ATC code: N06AX11

Mechanism of action/pharmacodynamic effects
Mirtazapine is a centrally active presynaptic α2-antagonist, which increases central noradrenergic and serotonergic neurotransmission. The enhancement of serotonergic neurotransmission is specifically mediated via 5-HT1 receptors, because 5-HT2 and 5-HT3 receptors are blocked by mirtazapine. Both enantiomers of mirtazapine are presumed to contribute to the antidepressant activity, the S(+)enantiomer by blocking α2 and 5-HT2 receptors and the R(-) enantiomer by blocking 5-HT3 receptors.

Clinical efficacy and safety
The histamine H1-antagonistic activity of mirtazapine is associated with its sedative properties. It has practically no anticholinergic activity and, at therapeutic doses, has only limited practically no effects (e.g. orthostatic hypotension) on the cardiovascular system.

Section 5.2
Absorption
After oral administration of Mirtazapine mirtazapine, the active substance mirtazapine is rapidly and well absorbed (bioavailability ≈ 50 %), reaching peak plasma levels after approx. two hours.
Food intake has no influence on the pharmacokinetics of mirtazapine.

Distribution
Binding of mirtazapine to plasma proteins is approx. 85 %.
The mean half-life of elimination is 20-40 hours; longer half-lives, up to 65 hours, have occasionally been recorded and shorter half-lives have been seen in young men. The half-life of elimination is sufficient to justify once-a-day dosing. Steady state is reached after 3-4 days, after which there is no further accumulation. Mirtazapine displays linear pharmacokinetics within the recommended dose range. Food intake has no influence on the pharmacokinetics of mirtazapine.
Biotransformation
Major pathways of biotransformation are demethylation and oxidation, followed by conjugation. In vitro data from human liver microsomes indicate that cytochrome P450 enzymes CYP2D6 and CYP1A2 are involved in the formation of the 8-hydroxy metabolite of mirtazapine, whereas CYP3A4 is considered to be responsible for the formation of the N-demethyl and N-oxide metabolites. The demethyl metabolite is pharmacologically active and appears to have the same pharmacokinetic profile as the parent compound.

Elimination
Mirtazapine is extensively metabolized metabolised and eliminated via the urine and faeces within a few days.
Major pathways of biotransformation are demethylation and oxidation, followed by conjugation. In vitro data from human liver microsomes indicate that cytochrome P450 enzymes CYP2D6 and CYP1A2 are involved in the formation of the 8-hydroxy metabolite of mirtazapine, whereas CYP3A4 is considered to be responsible for the formation of the N-demethyl and N-oxide metabolites. The demethyl metabolite is pharmacologically active and appears to have the same pharmacokinetic profile as the parent compound.
The mean half-life of elimination is 20-40 hours; longer half-lives, up to 65 hours, have occasionally been recorded and shorter half-lives have been seen in young men. The half-life of elimination is sufficient to justify once-a-day dosing. Steady state is reached after 3-4 days, after which there is no further accumulation.

Linearity/non-linearity
Mirtazapine displays linear pharmacokinetics within the recommended dose range.

Other special populations
The clearance of mirtazapine may be decreased as a result of renal or hepatic impairment.

Section 5.3
Preclinical Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, carcinogenicity or genotoxicity,
carcinogenic potential, toxicity to reproduction and development.

 

Updated on 28 July 2015 SmPC

Reasons for updating

  • New SmPC for new product

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 24 July 2015 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change of contraindications
  • Change to instructions about missed dose
  • Change to instructions about overdose
  • Change to storage instructions
  • Change to side-effects
  • Change to drug interactions
  • Change to information about drinking alcohol
  • Change to information about pregnancy or lactation
  • Change to further information section
  • Change to date of revision
  • Changes to therapeutic indications

Updated on 19 August 2014 PIL

Reasons for updating

  • Change to date of revision
  • Addition of manufacturer

Updated on 19 December 2013 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to side-effects
  • Change to drug interactions
  • Change to information about pregnancy or lactation
  • Addition of information on reporting a side effect.

Updated on 19 December 2013 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 2 - Qualitative and quantitative composition

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Update SmPC with PRAC recommendation on Pancreatitis and QRD.

Updated on 24 January 2013 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Sections 4.4 and 4.8 updated in line with the Core Safety Profile.

Updated on 24 January 2013 PIL

Reasons for updating

  • Change to side-effects
  • Change to further information section
  • Change to date of revision

Updated on 8 February 2012 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to side-effects
  • Change to further information section

Updated on 26 January 2012 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.3 - Shelf life
  • Change to section 6.5 - Nature and contents of container
  • Change to section 9 - Date of renewal of authorisation
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Sections 4.2, 4.8 and 5.1: Information in regards to children and adolescents updated in accordance with Article 45/46.

Section 4.6: Information in regards pregnancy and lactation updated in accordance with PhVWP CMDh decision on risk of pulmonary hypotention in NeonatesPPHN (SNRI's).

Section 6.3: Shelf life updated from 2 years to 3 years.

Section 6.5: Update to blister configuration.

Updated on 16 March 2010 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Sections 4.2, 4.4, 4.6, 4.7, 4.8, 4.9 & 5.2 of the SmPC text in line with the Article 30 Commission Decision for medicinal products containing the active substance “Mirtazapine”.

Updated on 12 March 2010 PIL

Reasons for updating

  • Change due to harmonisation of patient information leaflet

Updated on 31 March 2009 PIL

Reasons for updating

  • Change of trade or active ingredient name
  • Change to date of revision

Updated on 30 September 2008 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

 following approval of type II variation to update SPC and PIL with regard to suicidal thoughts

Updated on 30 September 2008 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to side-effects
  • Change to date of revision

Updated on 30 June 2008 SmPC

Reasons for updating

  • New SPC for medicines.ie

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 30 June 2008 PIL

Reasons for updating

  • New PIL for medicines.ie