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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: 04/11/2016
SPC Adalat 10 mg capsules

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 04/11/2016 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 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



Summary of Changes

Deleted             Added

 4.2  Posology and method of administration

[…]

Additional information on special populations

[…]

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

[…]

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 Interactions with other medicinal products and other forms of interaction 

[…]

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

[…]

5.2 Pharmacokinetic Properties

Elimination

The terminal elimination half-life is 1.7 to 3.4 hours. 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 2016 September 2016

 

Updated on 08/07/2016 and displayed until 04/11/2016
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 11/03/2014 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 4.7 - Effects on ability to drive and use machines
  • 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 5 mg must not be administered to patients with known hypersensitivity to nifedipine or to other dihydropyridines because of the theoretical risk of cross-reactivity, or to any of the excipients (see section 4.4, see section 6.1).

 

The safety of Adalat 5mg during pregnancy or in nursing mothers has not been established (see sections 4.4, 4.6 and 5.3).

Adalat 5mg must not be administered to women during pregnancy or to nursing mothers.

 

There are no safety and efficacy data from well-controlled studies in pregnant women (see“Fertility, Pregnancy and lactation”).

 

Animal studies have shown a variety of embryotoxic, placentotoxic and fetotoxic effects when administered during and after the period of organogenesis. (see “Preclinical safety data”)

 

(See section 4.4, Special warnings and precautions for use, 4.6.Fertility, Pregnancy and lactation and 5.3. Preclinical safety data).

 

Adalat 5 mg must not be used in cases of cardiogenic shock, clinically significant aortic stenosis, unstable angina pectoris, or during or within 4 weeks of an acute myocardial infarction.

 

Adalat 5 mg should not be used for the treatment of acute attacks of angina.

 

The safety of Adalat 5 mg in malignant hypertension has not been established.

 

Adalat 5 mg should not be used for secondary prevention of myocardial infarction.

 

Adalat 5 mg must not be administered concomitantly with rifampicin since effective plasma levels of nifedipine may not be achieved owing to enzyme induction (See Section 4.5, Interaction with other medicinal products and other forms of interactions).

 

4.4 Special warnings and precautions for use

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).

 

There are no safety and efficacy data from well-controlled studies in pregnant women (See section 4.6. Fertility, Pregnancy and lactation).

 

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

 

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

 

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

 

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.

 

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

 

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), Interaction with other medicinal products and other forms of interactions).

 

Upon co-administration with these drugs, the blood pressure should be monitored and, if necessary, a reduction of the nifedipine dose should be considered (See Section 4.5, Interaction with other medicinal products and other forms of interactions)

 

 

4.5 Interaction with other medicinal products and other forms of interaction

Rifampicin

Upon co-administration of weak to moderate inhibitors of the cytochrome P450 3A4 system (listed immediately below), the blood pressure should be monitored and, if necessary, a reduction in the nifedipine dose considered (See Sections 4.2 and , Dosage  and method of administration and see section 4.4). , Special warnings and precautions for use). In the majority of these cases, no formal studies to assess the potential for a drug interaction between nifedipine and the drug(s) listed have been undertaken, thus far.

 

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, Special warnings and precautions for use).

 

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, Special warnings and precautions for use).

 

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, Special warnings and precautions for use).

 

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, Special warnings and precautions for use).

 

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 3A4 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, Special warnings and precautions for use).

 

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, Special warnings and precautions for use).

 

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, Special warnings and precautions for use).

 

Cimetidine:

Due to its inhibition of cytochrome P450 3A4, cimetidine elevates the plasma concentrations of nifedipine and may potentiate the antihypertensive effect (See Section 4.4, Special warnings and precautions for use).

 

Ingestion of grapefruit/grapefruit juice is therefore to be avoided while taking nifedipine (See Section 4.2, Dosage  and method of administration).

4.6 Fertility, pregnancy and lactation

Pregnancy

Adalat 5 mg is contra-indicated during pregnancy. (See Section 4.3. Contraindications).

 

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

 

The safety of Adalat 5 mg for use in human pregnancy has not been established.

 

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“Preclinical safety data”).

 

 

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.

 

 

Lactation

Breast-feeding

Adalat 5 mg 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

4.8 Undesirable effects

 

System Organ Class

(MedDRA)

Common

Uncommon

Rare

Not known

                                           Oedema (incl. peripheral oedema)

                                           Vasodilatation

 

 

 

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

4.9 Overdose

Management of Overdose

Treatment

Symptomatic bradycardia may be treated with beta-sympathomimetics, and in life- threatening bradycardiac disturbances of heart rhythm, temporary pacemaker therapy canmay be advisable.

10. DATE OF REVISION OF THE TEXT

 

June 2012To be inserted upon approval

February 2014

 

 

 

 

Updated on 05/07/2012 and displayed until 11/03/2014
Reasons for adding or updating:
  • Change to paediatric information
  • Change to section 4.2 - Posology and method of administration
  • Change to section 5.1 - Pharmacodynamic properties
  • 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

Section 4.2 has been updated with regards to the paediatric population information.
Section 5.1 has been updated with information regarding the paediatric population.
Updated on 04/01/2012 and displayed until 05/07/2012
Reasons for adding or updating:
  • Change to section 6.4 - Special precautions for storage
  • Change to section 10 - Date of revision of the text
Date of revision of text on the SPC:   09-Dec-2011
Legal Category:   Product subject to medical prescription which may be renewed (B)

Free-text change information supplied by the pharmaceutical company



Store in the original package. Keep blister in the outer carton. Do not store above 25°C.

was amended to:

 

Store in the original package. Keep blister in the outer carton. Do not store above 30°C.

New date if revision of text: December 2011

Updated on 07/07/2011 and displayed until 04/01/2012
Reasons for adding or 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 4.5 - 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 10 - Date of revision of the text
Date of revision of text on the SPC:   04-Jul-2011
Legal Category:   Product subject to medical prescription which may be renewed (B)

Free-text change information supplied by the pharmaceutical company

The following SPC sections have been updated following approval of Company Core Data Sheet (CCDS) # 24.

Section 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 5.1, 5.2, andsection 10.0.
Updated on 17/02/2009 and displayed until 07/07/2011
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
  • Change to section 10 - Date of revision of the text
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 Adalat 10mg SPC 17.02.09, BSP08126

 

Section: 4.3 Contraindications

Deleted:

Adalat 10mg capsules are contraindicated in pregnancy before week 20 and during breastfeeding (see Sections 4.4, 4.6 and 5.3)

Inserted:

Adalat 10mg should not be administered to women during pregnancy or to nursing mothers (see Sections 4.4, 4.6 and 5.3).

 

 

Section 4.4 Special warnings and precautions for use

Information regarding pregnancy and iv magnesium sulphate deleted and changed to:

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.

 

Section 4.6 Pregnancy and lactation

Text changed to:

Adalat 10 mg is contra-indicated during pregnancy. (See section 4.3. Contraindications).

 

Adalat 10 mg should not be used by women who intend to get pregnant in the near future.

 

The safety of Adalat 10 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.

 

Adalat 10 mg 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.

 

In single cases of in vitro fertilisation calcium antagonists like nifedipine have been associated with reversible biochemical changes in the spermatozoas head section that may result in impaired sperm function. In those men who are repeatedly unsuccessful in fathering a child by in vitro fertilisation, and where no other explanation can be found, calcium antagonists like nifedipine should be considered as possible causes.

 

10. Date of Revision of Text

Changed to

 November 2008

Updated on 05/12/2008 and displayed until 17/02/2009
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 Section 4.3, 4.4 and 4.6.
Updated on 26/11/2008 and displayed until 05/12/2008
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

Change to section 4.3 - Contra-indications
Change to section 4.4 - Special Warnings and Precautions for Use
Change to section 4.6 - Pregnancy and Lactation
Updated on 26/08/2008 and displayed until 26/11/2008
Reasons for adding or updating:
  • New SPC for medicines.ie

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Active Ingredients

 
   Nifedipine