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Bayer Limited

The Atrium, Blackthorn Road, Dublin 18,
Telephone: +353 1 2999 313
Fax: +353 1 2061 456
Summary of Product Characteristics last updated on medicines.ie: 08/11/2016
SPC Adalat Retard 20 mg

When a pharmaceutical company changes an SPC or PIL, 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 08/11/2016 and displayed until Current
Reasons for adding or 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 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 10 - Date of revision of the text
Date of revision of text on the SPC:   30-Sep-2016
Legal Category:   Product subject to medical prescription which may be renewed (B)

Free-text change information supplied by the pharmaceutical company



SPC Updates

4.2 Posology and method of administration

Method of administration

Oral Use

Dosage regimen

[…]

Patients with hepatic impairment

In patients with mild, moderate or severe impaired liver function, careful monitoring and, in severe cases a dose reduction may be necessary. The pharmacokinetics of nifedipine has not been investigated in patients with severe hepatic impairment (see “Special warnings and precautions for use” and “Pharmacokinetic properties”).

 

[…]

 

4.4 Special warnings and precautions for use

[…]

Patients with hepatic impairment

In patients with mild, moderate or severe impaired liver function, careful monitoring and, in severe cases, a dose reduction may be necessary (see section 5.2). The pharmacokinetics of nifedipine has not been investigated in patients with severe hepatic impairment (see “Dosage and method of administration” and “Pharmacokinetic properties”). Therefore, nifedipine should be used with caution in patients with severe hepatic impairment.

 

[…]

4.5 Interaction with other medicinal products and other forms of interactions

[…]

Effects of nifedipine on other drugs

Blood pressure lowering drugs

Nifedipine may increase the blood pressure lowering effect of concomitant applied antihypertensives, such as:

-diuretics

-beta-blockers

-ACE-inhibitors

-Angiotensin II 1 (AT 1)receptor- antagonists

-other calcium antagonists

-alpha-adrenergic blocking agents

-PDE5 inhibitors

-alpha-methyldopa

                   

[…]

 

4.8 Undesirable effects

[…]

Immune System Disorders

 

Allergic reaction

 

Allergic oedema / angioedema (incl. larynx oedema 1*)

Pruritus

Urticaria

Rash

Anaphylactic/ anaphylactoid reaction

[…]

                                                                                                                                                                                                               

[[1]]=May result in life threatening outcome

***The above line previously read as***

 

*= May result in life threatening outcome

                                                                                                                                                                                                               

[…]

5.2 Pharmacokinetic properties

Elimination

The terminal elimination half-life is 6 - 11 hours (Adalat retard), because of delayed absorption. No accumulation of the substance after the usual dose was reported during long-term treatment. In cases of impaired kidney function no substantial changes have been detected in comparison with healthy volunteers. In cases of impaired liver function the elimination half-life is distinctly prolonged and the total clearance is reduced. A dose reduction may be necessary in severe cases. In a non-blinded study among white subjects only (69% male), which compared the pharmacokinetics of single dose controlled-release nifedipine in patients with mild (Child Pugh A, n=8) or moderate (Child Pugh B, n=8) hepatic impairment with those in patients with normal liver function (n=8+8), oral clearance of nifedipine was reduced by on average 48% (Child Pugh A) and 72% (Child Pugh B). As a result AUC and Cmax of nifedipine increased on average by 93% (with 90% confidence interval 20.2%~ 209%) and 64% (with 90% confidence interval 14.3%~ 136%) for Child Pugh A, and by 253% (with 90% confidence interval 120%~ 466%) and 171% (with 90% confidence interval 88.7%~ 289%) for Child Pugh B, respectively, compared to patients with normal hepatic function. The pharmacokinetics of nifedipine has not been investigated in patients with severe hepatic impairment (see “Special warnings and precautions for use”). In a study comparing the pharmacokinetics of nifedipine in patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment with those in patients with normal liver function, oral clearance of nifedipine was reduced by on average 48% (Child Pugh A) and 72% (Child Pugh B). As a result AUC and Cmax of nifedipine increased on average by 93% and 64% (Child Pugh A) and by 253% and 171% (Child Pugh B), respectively, compared to patients with normal hepatic function. The pharmacokinetics of nifedipine has not been investigated in patients with severe hepatic impairment (see “Special warnings and precautions for use”.

 

[…]

10. Date of Revision of the Text

June 2016September 2016

 

Updated on 08/07/2016 and displayed until 08/11/2016
Reasons for adding or updating:
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text
Date of revision of text on the SPC:   30-Jun-2016
Legal Category:   Product subject to medical prescription which may be renewed (B)

Free-text change information supplied by the pharmaceutical company

In Section 4.6 Fertility, pregnancy and lactation

Acute pulmonary oedema has been observed when calcium channel blockers, among others nifedipine, have been used as a tocolytic agent during pregnancy (see section 4.8), especially in cases of multiple pregnancy (twins or more), with the intravenous route and/or concomitant use of beta-2 agonists. -was added.

In Section 4.8 Undesirable effects

Pulmonary oedema* -was added as a side effect. under the frequency 'Not Known', with the following condition* :
*cases have been reported when used as tocolytic during pregnancy (see section 4.6) -was added


10. Date of Revision of the Text
June 2016 -was added
Updated on 09/01/2015 and displayed until 08/07/2016
Reasons for adding or updating:
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 10 - Date of revision of the text
Date of revision of text on the SPC:   19-Dec-2014
Legal Category:   Product subject to medical prescription which may be renewed (B)

Free-text change information supplied by the pharmaceutical company

Section 4.8 was updated to include HPRA adverse effect reporting text
Updated on 10/03/2014 and displayed until 09/01/2015
Reasons for adding or updating:
  • 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
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 4.9 - Overdose
  • Change to section 10 - Date of revision of the text
Date of revision of text on the SPC:   18-Feb-2014
Legal Category:   Product subject to medical prescription which may be renewed (B)

Free-text change information supplied by the pharmaceutical company



4.2 Posology and method of administration

Additional information on special populations

Elderly (>65)Geriatric patients

 

The pharmacokinetics of Adalat capsules are altered in the elderly so that lower maintenance doses of nifedipine may be required compared to younger patients.

 

4.3          Contraindications

 

 

Adalat retard 20 mg should not be administered to patients with known hypersensitivity to nifedipine or other dihydropyridines because of the theoretical risk of cross-reactivity (see section 4.4, see section 6.1).

 

Adalat retard 20 mg should not be administered during pregnancy or to nursing mothers.

The safety of Adalat retard 20mg during pregnancy or in nursing mothers has not been established (see sections 4.4, 4.6 and 5.3).

 

Adalat retard 20 mg mustshould not be used in cardiogenic shock, clinically significant aortic stenosis, unstable angina pectoris, or during or within one month of a myocardial infarction.

 

Adalat retard 20 mg should not be used for the treatment of acute attacks of angina.

 

The safety of Adalat retard 20 mg in malignant hypertension has not been established.

 

Adalat retard 20 mg should not be used for secondary prevention of myocardial infarction.

 

Adalat retard 20 mg must should not be administered concomitantly with rifampicin since effective plasma levels of nifedipine may not be achieved owing to enzyme induction (see Section 4.5).

 

4.3               Special warnings and precautions for use

 

Caution should be exercised in patients with severe hypotension.

 

Adalat retard 20 mg should be used with caution in patients whose cardiac reserve is poor.  Deterioration of heart failure has occasionally been observed with nifedipine.

 

Care must be exercised in patients with very low blood pressure (severe hypotension with systolic pressure less than 90 mm HG), in cases of manifest heart failure and in the case of severe aortic stenosis.

 

 

Ischaemic pain has been reported in a small proportion of patients within one to four hours of the introduction of Adalat retard 20 mg therapy.  Although a "steal" effect has not been demonstrated, patients experiencing this effect should discontinue Adalat retard 20 mg.

 

Diabetic patients taking Adalat retard 20 mg may require adjustment of their control.

 

In dialysis patients with malignant hypertension and hypovolaemia, a marked decrease in blood pressure can occur.

 

There are no safety and efficacy data from well-controlled studies in pregnant women (see Section 4.6).

 

Animal studies have shown a variety of embryotoxic, placentotoxic and fetotoxic effects (see Section 5.3) when administered during and after the period of organogenesis.

 

Whilst nifedipine is contra-indicated in pregnancy, particular care must be exercised when administering nifedipine in combination with i.v. magnesium sulphate to pregnant women

 

Nifedipine should not be used during pregnancy unless the clinical condition of the woman requires treatment with nifedipine. Nifedipine should be reserved for women with severe hypertension who are unresponsive to standard therapy (see section 4.6).

 

Nifedipine is not recommended for use during breastfeeding because nifedipine has been reported to be excreted in human milk and the effects of oral absorption of small amounts of nifedipine are not known (see section 4.6).

 

Careful monitoring of blood pressure must be exercised, also when administered    nifedipine with i.v. magnesium sulfate, owing to the possibility of an excessive fall in blood pressure which could harm both mother and fetus.

 

 

Co-administration of nifedipine with erythromycin, ketoconazole, itraconazole, fluconazole, fluoxetine, indinavir, nelfinavir, ritonavir, amprenavir and saquinavir may theoretically result in an increase in nifedipine plasma concentrations. Upon co-administration with any of these cytochrome P450 3A4 inhibitors, blood pressure should be monitored and, if necessary, a reduction in the nifedipine dose considered (see Section 4.5).

 

Patients with hepatic impairment

 

In patients with impaired liver function, careful monitoring and, in severe cases, a dose reduction may be necessary (see section 5.2).

 

Nifedipine is metabolised via the cytochrome P450 3A4 system. Drugs that are known to either inhibit or to induce this enzyme system may therefore alter the first pass or the clearance of nifedipine (See Section 4.5)

 

Drugs, which are inhibitors of the cytochrome P450 3 A4 system, and which may therefore lead to increased plasma concentrations of nifedipine include, for example:

 

-macrolide antibiotics (e.g., erythromycin)

-anti-HIV protease inhibitors (e.g., ritonavir)

-azole antimycotics (e.g., ketoconazole)

-the antidepressants, nefazodone and fluoxetine

-quinupristin/dalfopristin

-valproic acid

-cimetidine

 

Upon co-administration with these drugs, the blood pressure should be monitored and, if necessary, a reduction of the nifedipine dose should be considered.

 

For use in special populations see section 4.2.

 

Since this medicinal product contains lactose, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

 

4.4               Interaction with other medicinal products and other forms of interactions

Macrolide antibiotics (e.g., erythromycin):

No interaction studies have been carried out between nifedipine and macrolide antibiotics.  Certain macrolide antibiotics are known to inhibit the cytochrome P450 3A4 mediated metabolism of other drugs. Therefore the potential for an increase of nifedipine plasma concentrations upon co-administration of both drugs cannot be excluded (see Section 4.4).

 

Anti-HIV protease inhibitors (e.g., ritonavir):

A clinical study investigating the potential of a drug interaction between nifedipine and certain anti-HIV protease inhibitors has not yet been performed. Drugs of this class are known to inhibit the cytochrome P450 3A4 system. In addition, dDrugs of this class have been shown to inhibit in vitro the cytochrome P450 3A4 mediated metabolism of nifedipine. When administered together with nifedipine, a substantial increase in plasma concentrations of nifedipine due to a decreased first pass metabolism and a decreased elimination cannot be excluded (see Section 4.4).

Azole anti-mycotics (e.g., ketoconazole):

A formal interaction study investigating the potential of a drug interaction between nifedipine and certain azole anti-mycotics has not yet been performed. Drugs of this class are known to inhibit the cytochrome P450 3A4 system. When administered orally together with nifedipine, a substantial increase in systemic bioavailability of nifedipine due to a decreased first pass metabolism cannot be excluded (see Section 4.4).

Fluoxetine:

A clinical study investigating the potential of a drug interaction between nifedipine and fluoxetine has not yet been performed. Fluoxetine has been shown to inhibit in vitro the cytochrome P450 3A4 mediated metabolism of nifedipine. Therefore an increase of nifedipine plasma concentrations upon co-administration of both drugs cannot be excluded (see Section 4.4).

 

Nefazodone:

A clinical study investigating the potential of a drug interaction between nifedipine and nefazodone has not yet been performed. Nefazodone is known to inhibit the cytochrome P450 3 A4 mediated metabolism of other drugs. Therefore an increase in nifedipine plasma concentrations upon co-administration of both drugs cannot be excluded (see Section 4.4).

 

Quinupristin/dalfopristin and cisapride:

Simultaneous administration of quinupristin / dalfopristin and nifedipine, or cisapride and nifedipine, may lead to increased plasma concentrations of nifedipine (see Section 4.4).

 

Valproic acid:

No formal studies have been performed to investigate the potential interaction between nifedipine and valproic acid. As valproic acid has been shown to increase the plasma concentrations of the structurally similar calcium channel blocker, nimodipine, due to enzyme inhibition, an increase in nifedipine plasma concentrations and hence an increase in efficacy cannot be excluded (see Section 4.4).

Cisapride

Simultaneous administration of cisapride and nifedipine may lead to increased plasma concentrations of nifedipine.

Effects of nifedipine on other drugs

Blood pressure lowering drugs

4.6          Fertility, pregnancy and lactation

 

Pregnancy

Adalat retard 20 mg is contra-indicated during pregnancy.

 

Nifedipine should not be used during pregnancy unless the clinical condition of the woman requires treatment with nifedipine. Nifedipine should be reserved for women with severe hypertension who are unresponsive to standard therapy (see section 4.4).

 

Adalat retard 20 mg should not be used by women who intend to get pregnant in the near future.

 

The safety of Adalat retard 20 mg for use in human pregnancy has not been established.  Evaluation of experimental animal studies has shown reproductive toxicity consisting of embryotoxicity and teratogenic effects at maternally toxic doses.

 

There are no adequate and well controlled studies in pregnant women.

 

 

The available information is inadequate to rule out adverse drug effects on the unborn and newborn child.

 

In animal studies nifedipine has been shown to produce embryotoxicity, fetotoxicity and teratogenicity (see section 5.3).

 

 

Evaluation of experimental animal studies has shown reproductive toxicity consisting of embryotoxicity and teratogenic effects at maternally toxic doses.

 

 

From the clinical evidence available a specific prenatal risk has not been identified. Although an increase in perinatal asphyxia, caesarean delivery as well as prematurity and intrauterine growth retardation has been reported. It is unclear whether these reports are due to the underlying hypertension, its treatment or to a specific drug effect.

 

 

Breast-feedingLactation

Adalat Retard 20mg is contra-indicated in breastfeeding. Nifedipine passes into the breast milk. As there is no experience of possible effects on infants, breastfeeding should first be stopped if nifedipine treatment becomes necessary during the breastfeeding period.

Nifedipine is excreted in the breast milk. The nifedipine concentration in the milk is almost comparable with mother serum concentration. For immediate release formulations, it is proposed to delay breastfeeding or milk expression for 3 to 4 hours after drug administration to decrease the nifedipine exposure to the infant (see section 4.4).

In- vitro fertilisation

Fertility

4.8          Undesirable effects

System Organ Class

(MedDRA)

Common

Uncommon

Rare

Not known

 

                                        Oedema (incl. peripheral oedema)

                                       Vasodilation

 

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 via the online reporting option (preferred method) accessible from the IMB homepage (www.imb.ie). A downloadable report form is also accessible from the IMB website, which may be completed manually and submitted to the IMB via ‘freepost’ (see details below). Alternatively, the traditional post-paid ‘yellow card’ option may also be used.

 

Ireland

IMB Pharmacovigilance

Earlsfort Terrace

IRL - Dublin 2

Tel: +353 1 6764971

Fax: +353 1 6762517

Website: www.imb.ie

e-mail: imbpharmacovigilance@imb.ie

 

 

10. Date of Revision of the Text

February 2014

June 2012To be inserted upon approval

Updated on 12/07/2012 and displayed until 10/03/2014
Reasons for adding or updating:
  • Change to paediatric information
  • Change to section 10 - Date of revision of the text
Date of revision of text on the SPC:   18-Jun-2012
Legal Category:   Product subject to medical prescription which may be renewed (B)

Free-text change information supplied by the pharmaceutical company

Update of paediatric information in section 4.2 and section 5.1. 
Updated on 03/10/2011 and displayed until 12/07/2012
Reasons for adding or updating:
  • Change to section 2 - Qualitative and quantitative composition
  • 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 4.5 - 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 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 6.1 - List of excipients
  • Change to section 10 - Date of revision of the text
Date of revision of text on the SPC:   26-Aug-2011
Legal Category:   Product subject to medical prescription which may be renewed (B)

Free-text change information supplied by the pharmaceutical company

Following approval of Company Core Data Sheet ( CCDS) version #22, the following SPC sections have been updated.

Section 2.0, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.1, 5.2, 6.1 and section 10.0.
Updated on 19/12/2008 and displayed until 03/10/2011
Reasons for adding or updating:
  • Correction of spelling/typing errors
Updated on 09/12/2008 and displayed until 19/12/2008
Reasons for adding or updating:
  • 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
Date of revision of text on the SPC:   11/2008
Legal Category:   prescription only

Free-text change information supplied by the pharmaceutical company

Changes to Scetion 4.3, 4.4 and 4.6.
Updated on 17/11/2008 and displayed until 09/12/2008
Reasons for adding or updating:
  • Correction of spelling/typing errors
Updated on 14/11/2008 and displayed until 17/11/2008
Reasons for adding or updating:
  • New individual SPC (was previously included in combined SPC)

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Active Ingredients

 
   Nifedipine