Prograf 1mg Capsules

  • Name:

    Prograf 1mg Capsules

  • Company:
    info
  • Active Ingredients:

    Tacrolimus Monohydrate

  • Legal Category:

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

Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 23/09/19

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Summary of Product Characteristics last updated on medicines.ie: 23/9/2019

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Astellas Pharma Co. Ltd

Astellas Pharma Co

Company Products

Medicine NameActive Ingredients
Medicine Name Advagraf 0.5mg Prolonged-Release Capsules Active Ingredients Tacrolimus Monohydrate
Medicine Name Advagraf 1mg Prolonged-Release Capsules Active Ingredients Tacrolimus Monohydrate
Medicine Name Advagraf 3 mg prolonged-release hard capsules Active Ingredients Tacrolimus Monohydrate
Medicine Name Advagraf 5mg Prolonged-Release Capsules Active Ingredients Tacrolimus Monohydrate
Medicine Name Betmiga 25mg and 50mg prolonged-release tablets Active Ingredients Mirabegron
Medicine Name DIFICLIR 200 mg film-coated tablets Active Ingredients Fidaxomicin
Medicine Name Eligard 22.5mg Active Ingredients Leuprorelin Acetate
Medicine Name Eligard 45mg Active Ingredients Leuprorelin Acetate
Medicine Name Eligard 7.5mg Active Ingredients Leuprorelin Acetate
Medicine Name Modigraf 0.2mg & 1mg granules for oral suspension Active Ingredients Tacrolimus Monohydrate
Medicine Name Mycamine 50 & 100 mg powder for solution for infusion Active Ingredients Micafungin sodium
Medicine Name Omnexel Active Ingredients Tamsulosin Hydrochloride
Medicine Name Prograf 0.5 mg Capsules Active Ingredients Tacrolimus Monohydrate
Medicine Name Prograf 1mg Capsules Active Ingredients Tacrolimus Monohydrate
Medicine Name Prograf 5mg Capsules Active Ingredients Tacrolimus Monohydrate
Medicine Name Prograf Concentrate for Infusion Active Ingredients Tacrolimus
Medicine Name Vesitirim 1 mg/ml oral suspension Active Ingredients Solifenacin succinate
Medicine Name Vesitirim 10mg Film-coated Tablets Active Ingredients Solifenacin succinate
Medicine Name Vesitirim 5mg Film-Coated tablets Active Ingredients Solifenacin succinate
Medicine Name Vesomni 6 mg/0.4 mg modified release tablets Active Ingredients Solifenacin succinate, Tamsulosin Hydrochloride
Medicine Name Xtandi 40 mg soft capsules Active Ingredients enzalutamide
Medicine Name Zepholin SR 100mg Prolonged Release Capsules Active Ingredients Theophylline
Medicine Name Zepholin SR 200mg Prolonged Release Capsules Active Ingredients Theophylline
1 - 0 of 23 items.Total: Infinity 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 23 September 2019 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable effects

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

Updated on 23 September 2019 PIL

Reasons for updating

  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 2 - excipient warnings
  • Change to section 4 - possible side effects
  • Change to MA holder contact details

Updated on 10 June 2019 PIL

Reasons for updating

  • Individual PILs superseded by joint PIL

Updated on 25 February 2019 PIL

Reasons for updating

  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 4 - possible side effects

Updated on 22 February 2019 SmPC

Reasons for updating

  • 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 4.8 - Undesirable effects

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

Updated on 22 February 2019 SmPC

Reasons for updating

  • 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 4.8 - Undesirable effects

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

Updated on 13 February 2019 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use

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

Updated on 18 June 2018 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects

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

Free text change information supplied by the pharmaceutical company

Update section 4.8:

Musculoskeletal and connective tissue disorders

common:              arthralgia, back pain, muscle spasms, pain in limb extremity

Description of selected adverse reactions

Pain in extremity has been described in a number of published case reports as part of Calcineurin-Inhibitor Induced Pain Syndrome (CIPS). This typically presents as a bilateral and symmetrical, severe, ascending pain in the lower extremities and may be associated with supra-therapeutic levels of tacrolimus. The syndrome may respond to tacrolimus dose reduction. In some cases, it was necessary to switch to alternative immunosuppression

Updated on 18 June 2018 PIL

Reasons for updating

  • Change to section 4 - possible side effects

Updated on 17 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 17 July 2015 SmPC

Reasons for updating

  • 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 4.8 - 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

Section 4.4 & 4.5:

Addition of further information on the risk of interaction with herbal preparations including the Chinese herb Schisandra sphenanthera.

Section 4.8:

This section has been revised and now includes a section on “Investigations” which lists the side effects relating to investigations in a single section rather than throughout section 4.8.

The date of revision is updated to June 2015

Updated on 17 July 2015 PIL

Reasons for updating

  • 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 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Free text change information supplied by the pharmaceutical company

Section 4.4 & 4.5:

Addition of further information on the risk of interaction with herbal preparations including the Chinese herb Schisandra sphenanthera.

Section 4.8:

This section has been revised and now includes a section on “Investigations” which lists the side effects relating to investigations in a single section rather than throughout section 4.8.

The date of revision is updated to June 2015

Updated on 10 July 2015 PIL

Reasons for updating

  • New PIL for new product

Updated on 4 February 2015 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • 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 4.8 - Undesirable effects
  • Change to section 5.3 - Preclinical safety data
  • 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

 

2. Qualitative and quantitative composition, the following text has been added:

 

The printing ink used to mark the capsule contains trace amounts of soya lecithin (0.48% of total printing ink composition).

 

4.4     Special warnings and precautions for use

Section reformatted & the following text added:

 

High potassium intake or potassium-sparing diuretics should be avoided (see section 4.5).

 

Certain combinations of tacrolimus with drugs known to have nephrotoxic or neurotoxic effects may increase the risk of these effects (see section 4.5).

 

Vaccination

Immunosuppressants may affect the response to vaccination and vaccination during treatment with tacrolimus may be less effective. The use of live attenuated vaccines should be avoided.

 

Gastrointestinal disorders

Gastrointestinal perforation has been reported in patients treated with tacrolimus. As gastrointestinal perforation is a medically important event that may lead to a life-threatening or serious condition, adequate treatments should be considered immediately after suspected symptoms or signs occur.

 

Underlined text added:

Tacrolimus may prolong the QT interval and may cause Torsades de Pointes. Caution should be exercised in patients with risk factors for QT prolongation, including patients with a personal or family history of QT prolongation, congestive heart failure, bradyarrhythmias and electrolyte abnormalities. Caution should also be exercised in patients diagnosed or suspected to have Congenital Long QT Syndrome or acquired QT prolongation or patients on concomitant medications known to prolong the QT interval, induce electrolyte abnormalities or known to increase tacrolimus exposure (see section 4.5).

 

The printing ink used to mark Prograf capsules 1mg contains soya lecithin. In patients who are hypersensitive to peanut or soya, the risk and severity of hypersensitivity should be weighed against the benefit of using Prograf

 

4.5       Interaction with other medicinal products and other forms of interaction

Underlined text added

Systemically available tacrolimus is metabolised by hepatic CYP3A4. There is also evidence of gastrointestinal metabolism by CYP3A4 in the intestinal wall. Concomitant use of medicinal products or herbal remedies known to inhibit or induce CYP3A4 may affect the metabolism of tacrolimus and thereby increase or decrease tacrolimus blood levels. It is therefore strongly recommended to closely monitor tacrolimus blood levels, as well as QT prolongation (with ECG),

 

Other interactions potentially leading to increased tacrolimus blood levels

Tacrolimus is extensively bound to plasma proteins. Possible interactions with other medicinal products known to have high affinity for plasma proteins should be considered (e.g., NSAIDs, oral anticoagulants, or oral antidiabetics).

Other potential interactions that may increase systemic exposure of tacrolimus include the prokinetic agent metoclopramide, cimetidine and magnesium-aluminium-hydroxide.

 

 

Section 4.8 is updated throughout with the following added;

very rare:          echocardiogram abnormal, electrocardiogram QT prolonged, Torsades de Pointes

The information on reporting suspected adverse drug reactions hás also been added

5.3     Preclinical safety data, the following text is added:

 

When tacrolimus is administered intravenously as rapid infusion/bolus injection at a dose of 0.1 to 1.0 mg/kg, QTc prolongation has been observed in some animal species. Peak blood concentrations achieved with these doses were above 150 ng/mL which is more than 6-fold higher than mean peak concentrations observed with Prograf in clinical transplantation.

 

10. Date of Revision

Updated to January 2015

Updated on 4 February 2015 PIL

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • 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 4.8 - Undesirable effects
  • Change to section 5.3 - Preclinical safety data
  • Change to section 10 - Date of revision of the text

Free text change information supplied by the pharmaceutical company

 

2. Qualitative and quantitative composition, the following text has been added:

 

The printing ink used to mark the capsule contains trace amounts of soya lecithin (0.48% of total printing ink composition).

 

4.4     Special warnings and precautions for use

Section reformatted & the following text added:

 

High potassium intake or potassium-sparing diuretics should be avoided (see section 4.5).

 

Certain combinations of tacrolimus with drugs known to have nephrotoxic or neurotoxic effects may increase the risk of these effects (see section 4.5).

 

Vaccination

Immunosuppressants may affect the response to vaccination and vaccination during treatment with tacrolimus may be less effective. The use of live attenuated vaccines should be avoided.

 

Gastrointestinal disorders

Gastrointestinal perforation has been reported in patients treated with tacrolimus. As gastrointestinal perforation is a medically important event that may lead to a life-threatening or serious condition, adequate treatments should be considered immediately after suspected symptoms or signs occur.

 

Underlined text added:

Tacrolimus may prolong the QT interval and may cause Torsades de Pointes. Caution should be exercised in patients with risk factors for QT prolongation, including patients with a personal or family history of QT prolongation, congestive heart failure, bradyarrhythmias and electrolyte abnormalities. Caution should also be exercised in patients diagnosed or suspected to have Congenital Long QT Syndrome or acquired QT prolongation or patients on concomitant medications known to prolong the QT interval, induce electrolyte abnormalities or known to increase tacrolimus exposure (see section 4.5).

 

The printing ink used to mark Prograf capsules 1mg contains soya lecithin. In patients who are hypersensitive to peanut or soya, the risk and severity of hypersensitivity should be weighed against the benefit of using Prograf

 

4.5       Interaction with other medicinal products and other forms of interaction

Underlined text added

Systemically available tacrolimus is metabolised by hepatic CYP3A4. There is also evidence of gastrointestinal metabolism by CYP3A4 in the intestinal wall. Concomitant use of medicinal products or herbal remedies known to inhibit or induce CYP3A4 may affect the metabolism of tacrolimus and thereby increase or decrease tacrolimus blood levels. It is therefore strongly recommended to closely monitor tacrolimus blood levels, as well as QT prolongation (with ECG),

 

Other interactions potentially leading to increased tacrolimus blood levels

Tacrolimus is extensively bound to plasma proteins. Possible interactions with other medicinal products known to have high affinity for plasma proteins should be considered (e.g., NSAIDs, oral anticoagulants, or oral antidiabetics).

Other potential interactions that may increase systemic exposure of tacrolimus include the prokinetic agent metoclopramide, cimetidine and magnesium-aluminium-hydroxide.

 

 

Section 4.8 is updated throughout with the following added;

very rare:          echocardiogram abnormal, electrocardiogram QT prolonged, Torsades de Pointes

The information on reporting suspected adverse drug reactions hás also been added

5.3     Preclinical safety data, the following text is added:

 

When tacrolimus is administered intravenously as rapid infusion/bolus injection at a dose of 0.1 to 1.0 mg/kg, QTc prolongation has been observed in some animal species. Peak blood concentrations achieved with these doses were above 150 ng/mL which is more than 6-fold higher than mean peak concentrations observed with Prograf in clinical transplantation.

 

10. Date of Revision

Updated to January 2015

Updated on 18 November 2013 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.3 - Contraindications
  • 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 4.8 – Undesirable effects - how to report a side effect
  • Change to section 6.6 - Special precautions for disposal and other handling

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

Free text change information supplied by the pharmaceutical company



2.       Qualitative and quantitative composition

 

Each capsule contains 1 mg of tacrolimus (as monohydrate).

Excipient with known effect: 61.35 mg of lactose monohydrate

 

For thea full list of excipients, see section 6.1.

 

4.3     Contraindications

 

Hypersensitivity to tacrolimus or other macrolides.

Hypersensitivity to any of the excipients listed in section 6.1.

 

4.4     Special warnings and precautions for use

 

When substances with a potential for interaction (see section 4.5) - particularly strong inhibitors of

CYP3A4 (such as telaprevir, boceprevir, ritonavir, ketoconazole, voriconazole, itraconazole, telithromycin or clarithromycin) or inducers of CYP3A4 (such as rifampicin, rifabutin) – are being

combined with tacrolimus, tacrolimus blood levels should be monitored to adjust the tacrolimus dose

as appropriate in order to maintain similar tacrolimus exposure.

 

 

4.5       Interaction with other medicinal products and other forms of interaction

 

Metabolic interactions

Systemically available tacrolimus is metabolised by hepatic CYP3A4. There is also evidence of gastrointestinal metabolism by CYP3A4 in the intestinal wall. Concomitant use of medicinal products or herbal remedies known to inhibit or induce CYP3A4 may affect the metabolism of tacrolimus and thereby increase or decrease tacrolimus blood levels. It is therefore strongly recommended to closely monitor tacrolimus blood levels, as well as renal function and other side effects, whenever substances which have the potential to alter CYP3A4 metabolism are used concomitantly and to interrupt or adjust the tacrolimus dose as appropriate in order to maintain similar tacrolimus exposure (see sections 4.2 and 4.4).

 

Inhibitors of metabolism

Clinically the following substances have been shown to increase tacrolimus blood levels:

Strong interactions have been observed with antifungal agents such as ketoconazole, fluconazole, itraconazole and voriconazole, the macrolide antibiotic erythromycin, or HIV protease inhibitors (e.g. ritonavir, nelfinavir, saquinavir) or HCV protease inhibitors (e.g. telaprevir, boceprevir). Concomitant use of these substances may require decreased tacrolimus doses in nearly all patients.

Weaker interactions have been observed with clotrimazole, clarithromycin, josamycin, nifedipine, nicardipine, diltiazem, verapamil, amiodarone, danazol, ethinylestradiol, omeprazole and nefazodone.

 

 

4.6     Fertility, pPregnancy and lactation

 

In rats and rabbits, tacrolimus caused embryofoetal toxicity at doses which demonstrated maternal toxicity (see section 5.3). Tacrolimus affected male fertility in rats (see section 5.3).

 

Lactation

Human data demonstrate that tacrolimus is excreted into breast milk. As detrimental effects on the newborn cannot be excluded, women should not breast-feed whilst receiving Prograf.

 

Fertility

A negative effect of tacrolimus on male fertility in the form of reduced sperm counts and motility was observed in rats (see section 5.3).

 

 

 

4.8 Undesirable effects

 

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 preferably through the online reporting option accessible from the IMB homepage. A

downloadable report form is also accessible from the IMB website, which may be completed manually and submitted to the IMB via ‘freepost’. Alternatively, the traditional post-paid ‘yellow card’ option may also continue to be used.

 

 

FREEPOST

Pharmacovigilance Section

 

Irish Medicines Board

Irish Medicines Board

Kevin O’Malley House

Earlsfort Centre

Earlsfort Terrace

Dublin 2

Tel: +353 1 6764971

Fax: +353 1 6762517

Website: www.imb.ie

e-mail: imbpharmacovigilance@imb.ie

 

6.6     Special precautions for disposal and other handling

 

No special requirements.

 

 

 

 

 

Updated on 18 November 2013 PIL

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.3 - Contraindications
  • 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 4.8 – Undesirable effects - how to report a side effect
  • Change to section 6.6 - Special precautions for disposal and other handling

Free text change information supplied by the pharmaceutical company



2.       Qualitative and quantitative composition

 

Each capsule contains 1 mg of tacrolimus (as monohydrate).

Excipient with known effect: 61.35 mg of lactose monohydrate

 

For thea full list of excipients, see section 6.1.

 

4.3     Contraindications

 

Hypersensitivity to tacrolimus or other macrolides.

Hypersensitivity to any of the excipients listed in section 6.1.

 

4.4     Special warnings and precautions for use

 

When substances with a potential for interaction (see section 4.5) - particularly strong inhibitors of

CYP3A4 (such as telaprevir, boceprevir, ritonavir, ketoconazole, voriconazole, itraconazole, telithromycin or clarithromycin) or inducers of CYP3A4 (such as rifampicin, rifabutin) – are being

combined with tacrolimus, tacrolimus blood levels should be monitored to adjust the tacrolimus dose

as appropriate in order to maintain similar tacrolimus exposure.

 

 

4.5       Interaction with other medicinal products and other forms of interaction

 

Metabolic interactions

Systemically available tacrolimus is metabolised by hepatic CYP3A4. There is also evidence of gastrointestinal metabolism by CYP3A4 in the intestinal wall. Concomitant use of medicinal products or herbal remedies known to inhibit or induce CYP3A4 may affect the metabolism of tacrolimus and thereby increase or decrease tacrolimus blood levels. It is therefore strongly recommended to closely monitor tacrolimus blood levels, as well as renal function and other side effects, whenever substances which have the potential to alter CYP3A4 metabolism are used concomitantly and to interrupt or adjust the tacrolimus dose as appropriate in order to maintain similar tacrolimus exposure (see sections 4.2 and 4.4).

 

Inhibitors of metabolism

Clinically the following substances have been shown to increase tacrolimus blood levels:

Strong interactions have been observed with antifungal agents such as ketoconazole, fluconazole, itraconazole and voriconazole, the macrolide antibiotic erythromycin, or HIV protease inhibitors (e.g. ritonavir, nelfinavir, saquinavir) or HCV protease inhibitors (e.g. telaprevir, boceprevir). Concomitant use of these substances may require decreased tacrolimus doses in nearly all patients.

Weaker interactions have been observed with clotrimazole, clarithromycin, josamycin, nifedipine, nicardipine, diltiazem, verapamil, amiodarone, danazol, ethinylestradiol, omeprazole and nefazodone.

 

 

4.6     Fertility, pPregnancy and lactation

 

In rats and rabbits, tacrolimus caused embryofoetal toxicity at doses which demonstrated maternal toxicity (see section 5.3). Tacrolimus affected male fertility in rats (see section 5.3).

 

Lactation

Human data demonstrate that tacrolimus is excreted into breast milk. As detrimental effects on the newborn cannot be excluded, women should not breast-feed whilst receiving Prograf.

 

Fertility

A negative effect of tacrolimus on male fertility in the form of reduced sperm counts and motility was observed in rats (see section 5.3).

 

 

 

4.8 Undesirable effects

 

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 preferably through the online reporting option accessible from the IMB homepage. A

downloadable report form is also accessible from the IMB website, which may be completed manually and submitted to the IMB via ‘freepost’. Alternatively, the traditional post-paid ‘yellow card’ option may also continue to be used.

 

 

FREEPOST

Pharmacovigilance Section

 

Irish Medicines Board

Irish Medicines Board

Kevin O’Malley House

Earlsfort Centre

Earlsfort Terrace

Dublin 2

Tel: +353 1 6764971

Fax: +353 1 6762517

Website: www.imb.ie

e-mail: imbpharmacovigilance@imb.ie

 

6.6     Special precautions for disposal and other handling

 

No special requirements.

 

 

 

 

 

Updated on 3 July 2013 PIL

Reasons for updating

  • Change to improve clarity and readability

Free text change information supplied by the pharmaceutical company

correction of spacing errors

Updated on 3 July 2013 SmPC

Reasons for updating

  • Change to improve clarity and readability

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

Free text change information supplied by the pharmaceutical company

correction of spacing errors

Updated on 18 July 2012 PIL

Reasons for updating

  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects

Free text change information supplied by the pharmaceutical company

4.       CLINICAL PARTICULARS

 

4.6     Pregnancy and lactation

 

Human data show that tacrolimus is able to cross the placenta. Limited data from organ transplant recipients show no evidence of an increased risk of adverse effects on the course and outcome of pregnancy under tacrolimus treatment compared with other immunosuppressive medicinal products. However, cases of spontaneous abortion have been reported. To date, no other relevant epidemiological data are available. Due to the need of treatment, tacrolimus can be considered in pregnant women when there is no safer alternative and when the perceived benefit justifies the potential risk to the foetus. In case of in utero exposure, monitoring of the newborn for the potential adverse effects of tacrolimus is recommended (in particular the effects on the kidneys). There is a risk for premature delivery (<37 week) as well as for hyperkalaemia in the newborn, which, however, normalizes spontaneously.

 

4.8     Undesirable effects

 

The adverse drug reaction profile associated with immunosuppressive agents is often difficult to establish owing to the underlying disease and the concurrent use of multiple medications.

 

Many of the adverse drug reactions stated below are reversible and/or respond to dose reduction. Oral administration appears to be associated with a lower incidence of adverse drug reactions compared with intravenous use. Adverse drug reactions are listed below in descending order by frequency of occurrence: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).

 

Cardiac disorders

common:         ischaemic coronary artery disorders, tachycardia

uncommon:     ventricular arrhythmias and cardiac arrest, heart failures, cardiomyopathies, ventricular hypertrophy, supraventricular arrhythmias, palpitations, ECG investigations abnormal, heart rate and pulse investigations abnormal

rare:                             pericardial effusion

very rare:         echocardiogram abnormal

 

Blood and lymphatic system disorders

common:         anaemia, leukopenia, thrombocytopenia, leukocytosis, red blood cell analyses abnormal

uncommon:     coagulopathies, coagulation and bleeding analyses abnormal, pancytopenia, neutropenia

rare:                             thrombotic thrombocytopenic purpura, hypoprothrombinaemia

not known:      pure red cell aplasia, agranulocytosis, haemolytic anaemia

 

Updated on 18 July 2012 SmPC

Reasons for updating

  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects

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

Free text change information supplied by the pharmaceutical company

4.       CLINICAL PARTICULARS

 

4.6     Pregnancy and lactation

 

Human data show that tacrolimus is able to cross the placenta. Limited data from organ transplant recipients show no evidence of an increased risk of adverse effects on the course and outcome of pregnancy under tacrolimus treatment compared with other immunosuppressive medicinal products. However, cases of spontaneous abortion have been reported. To date, no other relevant epidemiological data are available. Due to the need of treatment, tacrolimus can be considered in pregnant women when there is no safer alternative and when the perceived benefit justifies the potential risk to the foetus. In case of in utero exposure, monitoring of the newborn for the potential adverse effects of tacrolimus is recommended (in particular the effects on the kidneys). There is a risk for premature delivery (<37 week) as well as for hyperkalaemia in the newborn, which, however, normalizes spontaneously.

 

4.8     Undesirable effects

 

The adverse drug reaction profile associated with immunosuppressive agents is often difficult to establish owing to the underlying disease and the concurrent use of multiple medications.

 

Many of the adverse drug reactions stated below are reversible and/or respond to dose reduction. Oral administration appears to be associated with a lower incidence of adverse drug reactions compared with intravenous use. Adverse drug reactions are listed below in descending order by frequency of occurrence: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).

 

Cardiac disorders

common:         ischaemic coronary artery disorders, tachycardia

uncommon:     ventricular arrhythmias and cardiac arrest, heart failures, cardiomyopathies, ventricular hypertrophy, supraventricular arrhythmias, palpitations, ECG investigations abnormal, heart rate and pulse investigations abnormal

rare:                             pericardial effusion

very rare:         echocardiogram abnormal

 

Blood and lymphatic system disorders

common:         anaemia, leukopenia, thrombocytopenia, leukocytosis, red blood cell analyses abnormal

uncommon:     coagulopathies, coagulation and bleeding analyses abnormal, pancytopenia, neutropenia

rare:                             thrombotic thrombocytopenic purpura, hypoprothrombinaemia

not known:      pure red cell aplasia, agranulocytosis, haemolytic anaemia

 

Updated on 15 November 2011 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 4.4 - Special warnings and precautions for use

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

Free text change information supplied by the pharmaceutical company

4.4       Special warnings and precautions for use

Cases of pure red cell aplasia (PRCA) have been reported in patients treated with tacrolimus. All patients reported risk factors for PRCA such as parvovirus B19 infection, underlying disease or concomitant medications associated with PRCA.







4.8     Undesirable effects


Blood and lymphatic system disorders

common:         anaemia, leukopenia, thrombocytopenia, leukocytosis, red blood cell analyses abnormal

uncommon:     coagulopathies, coagulation and bleeding analyses abnormal, pancytopenia, neutropenia

rare:                             thrombotic thrombocytopenic purpura, hypoprothrombinaemia

not known:      pure red cell aplasia

Updated on 15 November 2011 PIL

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 4.4 - Special warnings and precautions for use

Free text change information supplied by the pharmaceutical company

4.4       Special warnings and precautions for use

Cases of pure red cell aplasia (PRCA) have been reported in patients treated with tacrolimus. All patients reported risk factors for PRCA such as parvovirus B19 infection, underlying disease or concomitant medications associated with PRCA.







4.8     Undesirable effects


Blood and lymphatic system disorders

common:         anaemia, leukopenia, thrombocytopenia, leukocytosis, red blood cell analyses abnormal

uncommon:     coagulopathies, coagulation and bleeding analyses abnormal, pancytopenia, neutropenia

rare:                             thrombotic thrombocytopenic purpura, hypoprothrombinaemia

not known:      pure red cell aplasia

Updated on 18 March 2011 PIL

Reasons for updating

  • Change to section 10 - Date of revision of the text

Free text change information supplied by the pharmaceutical company

August 2010

Updated on 18 March 2011 SmPC

Reasons for updating

  • 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

August 2010

Updated on 12 August 2010 SmPC

Reasons for updating

  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 6.5 - Nature and contents of container
  • 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

Change detail

 

Prograf 1mgHard Capsules

 

 July 2010

 

Changes in Red

 

 

4.5     Interaction with other medicinal products and other forms of interaction

Inhibitors of metabolism

Clinically the following substances have been shown to increase tacrolimus blood levels:

Strong interactions have been observed with antifungal agents such as ketoconazole, fluconazole, itraconazole and voriconazole, the macrolide antibiotic erythromycin or HIV protease inhibitors (e.g. ritonavir). Concomitant use of these substances may require decreased tacrolimus doses in nearly all patients.

Weaker interactions have been observed with clotrimazole, clarithromycin, josamycin, nifedipine, nicardipine, diltiazem, verapamil, danazol, ethinylestradiol, omeprazole and nefazodone.

In vitro the following substances have been shown to be potential inhibitors of tacrolimus metabolism: bromocriptine, cortisone, dapsone, ergotamine, gestodene, lidocaine, mephenytoin, miconazole, midazolam, nilvadipine, norethisterone, quinidine, tamoxifen, troleandomycin.

Grapefruit juice has been reported to increase the blood level of tacrolimus and should therefore be avoided.

Lansoprazole and ciclosporin may potentially inhibit CYP3A4-mediated metabolism of tacrolimus and thereby increase tacrolimus whole blood concentrations.

 

 

6.5     Nature and contents of container

 

PVC/PVDC/Aluminium blisters or perforated unit-dose blisters. Ten capsules per blister. Two, three, five, six, nine or ten blisters with a desiccant in an aluminium wrapper.

 

Packs of 20, 30, 50, 60 and 100 hard capsules in blisters.

Packs of 20×1, 30×1, 50×1, 60×1 and 100×1 hard capsules in perforated unit-dose blisters.

 

 

Not all pack sizes may be marketed.

 

10.   Date of revision of the text

 

July 2010

 

 

 

Updated on 12 August 2010 PIL

Reasons for updating

  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 6.5 - Nature and contents of container
  • Change to section 10 - Date of revision of the text

Free text change information supplied by the pharmaceutical company

Change detail

 

Prograf 1mgHard Capsules

 

 July 2010

 

Changes in Red

 

 

4.5     Interaction with other medicinal products and other forms of interaction

Inhibitors of metabolism

Clinically the following substances have been shown to increase tacrolimus blood levels:

Strong interactions have been observed with antifungal agents such as ketoconazole, fluconazole, itraconazole and voriconazole, the macrolide antibiotic erythromycin or HIV protease inhibitors (e.g. ritonavir). Concomitant use of these substances may require decreased tacrolimus doses in nearly all patients.

Weaker interactions have been observed with clotrimazole, clarithromycin, josamycin, nifedipine, nicardipine, diltiazem, verapamil, danazol, ethinylestradiol, omeprazole and nefazodone.

In vitro the following substances have been shown to be potential inhibitors of tacrolimus metabolism: bromocriptine, cortisone, dapsone, ergotamine, gestodene, lidocaine, mephenytoin, miconazole, midazolam, nilvadipine, norethisterone, quinidine, tamoxifen, troleandomycin.

Grapefruit juice has been reported to increase the blood level of tacrolimus and should therefore be avoided.

Lansoprazole and ciclosporin may potentially inhibit CYP3A4-mediated metabolism of tacrolimus and thereby increase tacrolimus whole blood concentrations.

 

 

6.5     Nature and contents of container

 

PVC/PVDC/Aluminium blisters or perforated unit-dose blisters. Ten capsules per blister. Two, three, five, six, nine or ten blisters with a desiccant in an aluminium wrapper.

 

Packs of 20, 30, 50, 60 and 100 hard capsules in blisters.

Packs of 20×1, 30×1, 50×1, 60×1 and 100×1 hard capsules in perforated unit-dose blisters.

 

 

Not all pack sizes may be marketed.

 

10.   Date of revision of the text

 

July 2010

 

 

 

Updated on 12 June 2009 PIL

Reasons for updating

  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects

Free text change information supplied by the pharmaceutical company



Section 4.2      Posology and method of administration

Inserted

 

Inadvertent, unintentional or unsupervised switching of immediate- or prolonged-release formulations of tacrolimus is unsafe. This can lead to graft rejection or increased incidence of side effects, including under- or overimmunosuppression, due to clinically relevant differences in systemic exposure to tacrolimus. Patients should be maintained on a single formulation of tacrolimus with the corresponding daily dosing regimen; alterations in formulation or regimen should only take place under the close supervision of a transplant specialist (see sections 4.4 and 4.8). Following conversion to any alternative formulation, therapeutic drug monitoring must be performed and dose adjustments made to ensure that systemic exposure to tacrolimus is maintained.

 

 

Section 4.4      Special warnings and precautions for use

 

Inserted

 

Medication errors, including inadvertent, unintentional or unsupervised substitution of immediate- or prolonged-release tacrolimus formulations, have been observed. This has led to serious adverse events, including graft rejection, or other side effects which could be a consequence of either under- or over-exposure to tacrolimus. Patients should be maintained on a single formulation of tacrolimus with the corresponding daily dosing regimen; alterations in formulation or regimen should only take place under the close supervision of a transplant specialist (see sections 4.2 and 4.8).

 

Patients treated with tacrolimus have been reported to develop posterior reversible encephalopathy syndrome (PRES). If patients taking tacrolimus present with symptoms indicating PRES such as headache, altered mental status, seizures, and visual disturbances, a radiological procedure (e.g. MRI) should be performed. If PRES is diagnosed, adequate blood pressure control and immediate discontinuation of systemic tacrolimus is advised. Most patients completely recover after appropriate measures are taken.

 

Patients treated with immunosuppressants, including Prograf are at increased risk of opportunistic infections (bacterial, fungal, viral and protozoal). Among these conditions are BK virus associated nephropathy and JC virus associated progressive multifocal leukoencephalopathy (PML). These infections are often related to a high total immunosuppressive burden and may lead to serious or fatal conditions that physicians should consider in patients with deteriorating renal function or neurological symptoms.

 

 

 

Section 4.8      Undesirable effects

 

Inserted

Infections and infestations

Cases of BK virus associated nephropathy, as well as cases of JC virus associated progressive multifocal leukoencephalopathy (PML), have been reported in patients treated with immunosuppressants, including Prograf.

 

 

Injury, poisoning and procedural complications

Medication errors, including inadvertent, unintentional or unsupervised substitution of immediate- or prolonged-release tacrolimus formulations, have been observed. A number of associated cases of transplant rejection have been reported (frequency cannot be estimated from available data).

 

Section 5.1      Pharmacodynamic properties

 

Pharmacotherapeutic group: Macrolide immunosuppressant, ATC code: L04A A05

 

Changed to read:

Pharmacotherapeutic group: Calcineurin inhibitors, ATC code: L04AD02

 

 

section 10. Date of revision of the text

 

February 2008 updated to April 2009

 

 

Updated on 12 June 2009 SmPC

Reasons for updating

  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects

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

Free text change information supplied by the pharmaceutical company



Section 4.2      Posology and method of administration

Inserted

 

Inadvertent, unintentional or unsupervised switching of immediate- or prolonged-release formulations of tacrolimus is unsafe. This can lead to graft rejection or increased incidence of side effects, including under- or overimmunosuppression, due to clinically relevant differences in systemic exposure to tacrolimus. Patients should be maintained on a single formulation of tacrolimus with the corresponding daily dosing regimen; alterations in formulation or regimen should only take place under the close supervision of a transplant specialist (see sections 4.4 and 4.8). Following conversion to any alternative formulation, therapeutic drug monitoring must be performed and dose adjustments made to ensure that systemic exposure to tacrolimus is maintained.

 

 

Section 4.4      Special warnings and precautions for use

 

Inserted

 

Medication errors, including inadvertent, unintentional or unsupervised substitution of immediate- or prolonged-release tacrolimus formulations, have been observed. This has led to serious adverse events, including graft rejection, or other side effects which could be a consequence of either under- or over-exposure to tacrolimus. Patients should be maintained on a single formulation of tacrolimus with the corresponding daily dosing regimen; alterations in formulation or regimen should only take place under the close supervision of a transplant specialist (see sections 4.2 and 4.8).

 

Patients treated with tacrolimus have been reported to develop posterior reversible encephalopathy syndrome (PRES). If patients taking tacrolimus present with symptoms indicating PRES such as headache, altered mental status, seizures, and visual disturbances, a radiological procedure (e.g. MRI) should be performed. If PRES is diagnosed, adequate blood pressure control and immediate discontinuation of systemic tacrolimus is advised. Most patients completely recover after appropriate measures are taken.

 

Patients treated with immunosuppressants, including Prograf are at increased risk of opportunistic infections (bacterial, fungal, viral and protozoal). Among these conditions are BK virus associated nephropathy and JC virus associated progressive multifocal leukoencephalopathy (PML). These infections are often related to a high total immunosuppressive burden and may lead to serious or fatal conditions that physicians should consider in patients with deteriorating renal function or neurological symptoms.

 

 

 

Section 4.8      Undesirable effects

 

Inserted

Infections and infestations

Cases of BK virus associated nephropathy, as well as cases of JC virus associated progressive multifocal leukoencephalopathy (PML), have been reported in patients treated with immunosuppressants, including Prograf.

 

 

Injury, poisoning and procedural complications

Medication errors, including inadvertent, unintentional or unsupervised substitution of immediate- or prolonged-release tacrolimus formulations, have been observed. A number of associated cases of transplant rejection have been reported (frequency cannot be estimated from available data).

 

Section 5.1      Pharmacodynamic properties

 

Pharmacotherapeutic group: Macrolide immunosuppressant, ATC code: L04A A05

 

Changed to read:

Pharmacotherapeutic group: Calcineurin inhibitors, ATC code: L04AD02

 

 

section 10. Date of revision of the text

 

February 2008 updated to April 2009

 

 

Updated on 29 May 2008 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • 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 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.1 - List of excipients
  • Change to section 6.2 - Incompatibilities
  • Change to section 6.4 - Special precautions for storage
  • 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

   

Section 2: ¡°For a full list of excipients, see 6.1¡± has been changed to read ¡°For a full list of excipients, see section 6.1¡±

 

Section 4.4: last paragraph, ¡°1mg Hard Capsules¡± has been removed ¡°contain¡± has been changed to ¡°contains¡±

 

Section 4.5:

Inhibitors of metabolism: ¡°(triacetyl)oleandomycin¡± has been changed to ¡°troleandomycin¡±, ¡°norethindrone¡± has been changed to ¡°norethisterone¡±

 

Effect of tacrolimus on the metabolism of other medicinal products         :

¡°antipyrine¡± changed to ¡°phenazone¡±

 

Other interactions which have led to clinically detrimental effects:

¡°cotrimoxazole¡± changed to ¡°sulfamethoxazole + trimethoprim¡±

 

Section 4.8: Undersirable effects:

 

First paragraph is no longer underlined in bold.

 

Frequency of occurrence ¡°>¡± has been changed to read ¡°¡Ý¡±, ¡°including isolated reports¡± has been removed. ¡°not known (cannot be estimated form the available data¡± has been inserted.

 

The order of undesirable effects has been changed.

 

Section 5.1: ¡°Pharmacotherapeutic group Macrolide immunosuppressant¡± has been changed to read ¡°Pharmacotherapeutic group: Macrolide immunosuppressant. ATC code: L04A A05¡±.

 

Section 6.1: The words ¡°Capsule content¡± and ¡°Capsule shell¡± are no longer

underlined. ¡°hydroxyypropylcellulose¡± has been changed to read ¡°hydroxypropyl cellulose¡±.

 

Section 6.2: ¡°a suspension of Prograf 1 mg hard capsule contents¡± has been changed to read ¡° a suspension of Prograf capsule contents¡±

 

 

Section 6.4: Inserted the following sentence ¡°This medicinal product does not require any special temperature storage conditions¡±.

 

Section 6.5: The word ¡°strips¡± and the sentence ¡°Pack sizes: 50 and 100 capsules¡± have been removed.

 

Section 9: (DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION) Updated to read

¡°Date of first authorisation: 16th February 1996¡±

¡°Date of last renewal: 27th November 2007¡±

 

Section 10: (DATE OF REVISION OF THE TEXT) updated to February 2008.

 

 

Updated on 29 May 2008 PIL

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • 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 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.1 - List of excipients
  • Change to section 6.2 - Incompatibilities
  • Change to section 6.4 - Special precautions for storage
  • 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

Free text change information supplied by the pharmaceutical company

   

Section 2: ¡°For a full list of excipients, see 6.1¡± has been changed to read ¡°For a full list of excipients, see section 6.1¡±

 

Section 4.4: last paragraph, ¡°1mg Hard Capsules¡± has been removed ¡°contain¡± has been changed to ¡°contains¡±

 

Section 4.5:

Inhibitors of metabolism: ¡°(triacetyl)oleandomycin¡± has been changed to ¡°troleandomycin¡±, ¡°norethindrone¡± has been changed to ¡°norethisterone¡±

 

Effect of tacrolimus on the metabolism of other medicinal products         :

¡°antipyrine¡± changed to ¡°phenazone¡±

 

Other interactions which have led to clinically detrimental effects:

¡°cotrimoxazole¡± changed to ¡°sulfamethoxazole + trimethoprim¡±

 

Section 4.8: Undersirable effects:

 

First paragraph is no longer underlined in bold.

 

Frequency of occurrence ¡°>¡± has been changed to read ¡°¡Ý¡±, ¡°including isolated reports¡± has been removed. ¡°not known (cannot be estimated form the available data¡± has been inserted.

 

The order of undesirable effects has been changed.

 

Section 5.1: ¡°Pharmacotherapeutic group Macrolide immunosuppressant¡± has been changed to read ¡°Pharmacotherapeutic group: Macrolide immunosuppressant. ATC code: L04A A05¡±.

 

Section 6.1: The words ¡°Capsule content¡± and ¡°Capsule shell¡± are no longer

underlined. ¡°hydroxyypropylcellulose¡± has been changed to read ¡°hydroxypropyl cellulose¡±.

 

Section 6.2: ¡°a suspension of Prograf 1 mg hard capsule contents¡± has been changed to read ¡° a suspension of Prograf capsule contents¡±

 

 

Section 6.4: Inserted the following sentence ¡°This medicinal product does not require any special temperature storage conditions¡±.

 

Section 6.5: The word ¡°strips¡± and the sentence ¡°Pack sizes: 50 and 100 capsules¡± have been removed.

 

Section 9: (DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION) Updated to read

¡°Date of first authorisation: 16th February 1996¡±

¡°Date of last renewal: 27th November 2007¡±

 

Section 10: (DATE OF REVISION OF THE TEXT) updated to February 2008.

 

 

Updated on 7 August 2007 PIL

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.1 - List of excipients
  • Change to section 6.2 - Incompatibilities
  • Change to section 6.3 - Shelf life
  • Change to section 6.4 - Special precautions for storage
  • 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

Free text change information supplied by the pharmaceutical company

 

Prograf Capsules SPCs

Changes from April 2006 v April 2007

 

Reason for updates: Harmonisation of quality dossier in Europe.

 

2.       Qualitative and quantitative composition

New text added:

 

0.5mg SPC:  “…(as monohydrate). Excipient: 62.85mg of lactose monohydrate.“

1mg SPC: “(as monohydrate). Excipient: 61.35mg of lactose monohydrate.“

5mg SPC: “...(as monohydrate). Excipient: 123.60mg of lactose monohydrate.“

 

3.       Pharmaceutical form

 

New text added (shown underlined here):

 

0.5mg SPC: “Capsule hard. Opaque light yellow, hard gelatin capsule imprinted in red with “0.5 mg” and “[F] 607” containing white powder.

 

1mg SPC: “Capsule hard. Opaque white hard gelatin capsules imprinted in red with “1mg” and “[f] 617”, containing white powder.”

 

5mg SPC: “Capsule, hard. Opaque grayish red gelatin capsules imprinted in white with “5mg” and “[f] 657”, containing white powder.”

 

 

4.2     Posology and method of administration

Method of administration

New text added: “Patients should be advised not to swallow the desiccant.”

 

4.4     Special warnings and precautions for use

New text added: “As Prograf 0.5mg hard capsules contain lactose, special care should be taken in patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.”

Note: “0.5mg” reads “1mg” or “5mg” as appropriate in each SPC.

 

5.1       Pharmacodynamic properties

Deleted text: “ATC code: LO4A A05.”

 

6.1         List of excipients

Excipients split into Capsule Content, Capsule Shell and Printing Ink.

 

“Ferric oxide red (E172)” rephrased to “red iron oxide (E172).”

 

0.5mg SPC only:

“Ferric oxide yellow E172” rephrased and E number corrected to “Yellow iron oxide (E173)”.

0.5mg and 1mg SPC:

“Dimethicone” changed to “Simethicone”.

New excipient added: “hydroxypropylcellulose”.

 

6.2     Incompatibilities

Deleted text “not applicable” and replaced with new text: “Tacrolimus is not compatible with PVC. Tubing, syringes and other equipment used to prepare or administer a suspension of Prograf 0.5 mg hard capsule contents should not contain PVC.”

Note: “0.5mg” reads “1mg” or “5mg” as appropriate in each SPC.

 

6.3     Shelf life

Unopened shelf life extended from 2 to 3 years.

 

6.4     Special precautions for storage

Deleted text: “Do not store above 30°C.”

New text added (underlined here): “Store in the original package in order to protect from moisture. Hard capsules should be taken immediately following removal from the blister.”

 

6.5     Nature and contents of container

Additional packs of  2, 3, 6 or 9 blisters.

0.5mg SPC: Additional pack sizes of 20, 30 and 60 capsules.

1mg SPC: Additional pack sizes of 20, 30, 60 and 90 capsules.

5mg SPC: Additional pack sizes of 30, 60 and 100 capsules.

 

9.       Date of first authorisation/RENEWAL OF THE AUTHORISATION

Updated to: “15th February 2011”

 

10.       Date of revision of the text

Updated to: “April 2007”

Updated on 7 August 2007 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.1 - List of excipients
  • Change to section 6.2 - Incompatibilities
  • Change to section 6.3 - Shelf life
  • Change to section 6.4 - Special precautions for storage
  • 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

 

Prograf Capsules SPCs

Changes from April 2006 v April 2007

 

Reason for updates: Harmonisation of quality dossier in Europe.

 

2.       Qualitative and quantitative composition

New text added:

 

0.5mg SPC:  “…(as monohydrate). Excipient: 62.85mg of lactose monohydrate.“

1mg SPC: “(as monohydrate). Excipient: 61.35mg of lactose monohydrate.“

5mg SPC: “...(as monohydrate). Excipient: 123.60mg of lactose monohydrate.“

 

3.       Pharmaceutical form

 

New text added (shown underlined here):

 

0.5mg SPC: “Capsule hard. Opaque light yellow, hard gelatin capsule imprinted in red with “0.5 mg” and “[F] 607” containing white powder.

 

1mg SPC: “Capsule hard. Opaque white hard gelatin capsules imprinted in red with “1mg” and “[f] 617”, containing white powder.”

 

5mg SPC: “Capsule, hard. Opaque grayish red gelatin capsules imprinted in white with “5mg” and “[f] 657”, containing white powder.”

 

 

4.2     Posology and method of administration

Method of administration

New text added: “Patients should be advised not to swallow the desiccant.”

 

4.4     Special warnings and precautions for use

New text added: “As Prograf 0.5mg hard capsules contain lactose, special care should be taken in patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.”

Note: “0.5mg” reads “1mg” or “5mg” as appropriate in each SPC.

 

5.1       Pharmacodynamic properties

Deleted text: “ATC code: LO4A A05.”

 

6.1         List of excipients

Excipients split into Capsule Content, Capsule Shell and Printing Ink.

 

“Ferric oxide red (E172)” rephrased to “red iron oxide (E172).”

 

0.5mg SPC only:

“Ferric oxide yellow E172” rephrased and E number corrected to “Yellow iron oxide (E173)”.

0.5mg and 1mg SPC:

“Dimethicone” changed to “Simethicone”.

New excipient added: “hydroxypropylcellulose”.

 

6.2     Incompatibilities

Deleted text “not applicable” and replaced with new text: “Tacrolimus is not compatible with PVC. Tubing, syringes and other equipment used to prepare or administer a suspension of Prograf 0.5 mg hard capsule contents should not contain PVC.”

Note: “0.5mg” reads “1mg” or “5mg” as appropriate in each SPC.

 

6.3     Shelf life

Unopened shelf life extended from 2 to 3 years.

 

6.4     Special precautions for storage

Deleted text: “Do not store above 30°C.”

New text added (underlined here): “Store in the original package in order to protect from moisture. Hard capsules should be taken immediately following removal from the blister.”

 

6.5     Nature and contents of container

Additional packs of  2, 3, 6 or 9 blisters.

0.5mg SPC: Additional pack sizes of 20, 30 and 60 capsules.

1mg SPC: Additional pack sizes of 20, 30, 60 and 90 capsules.

5mg SPC: Additional pack sizes of 30, 60 and 100 capsules.

 

9.       Date of first authorisation/RENEWAL OF THE AUTHORISATION

Updated to: “15th February 2011”

 

10.       Date of revision of the text

Updated to: “April 2007”

Updated on 10 July 2006 PIL

Reasons for updating

  • New SPC for medicines.ie

Updated on 10 July 2006 SmPC

Reasons for updating

  • New SPC for medicines.ie

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