ADALAT 10 MG SOFT CAPSULES

Ireland - English - HPRA (Health Products Regulatory Authority)

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Active ingredient:
NIFEDIPINE
Available from:
Bayer Limited
ATC code:
C08CA05
INN (International Name):
NIFEDIPINE
Dosage:
10 Milligram
Pharmaceutical form:
Capsules, Soft
Prescription type:
Product subject to prescription which may be renewed (B)
Therapeutic area:
nifedipine
Authorization status:
Not Marketed
Authorization number:
PA1410/025/002
Authorization date:
1977-05-25

Package leaflet - information

for the user

Adalat® 10mg

soft capsules

Nifedipine

Read all of this leaflet carefully

before you start taking this

medicine.

Keep this leaflet. You may need

to read it again.

If you have more questions, ask

your doctor or pharmacist.

This medicine has been

prescribed for you.

Do not pass it on to others. It

may harm them, even if their

symptoms are the same as yours.

If any of the side effects gets

serious, or if you notice any side

effects not listed in this leaflet,

please tell your doctor or

pharmacist.

In this leaflet

1 What Adalat capsules are

2 Before you take Adalat

capsules

3 How you take Adalat

capsules

4 Possible side effects

5 How to store Adalat capsules

6 Further information

1 What Adalat capsules are

Adalat capsules contain

nifedipine, which belongs to a

group of medicines called

calcium antagonists.

Adalat capsules are used to

treat high blood pressure,

angina (chest pain) or a

condition called Raynaud’s

syndrome which causes

discolouration (often whitening)

of the fingers and toes.

For high blood pressure: Adalat

capsules work by relaxing and

expanding the blood vessels. This

makes the blood flow more easily

and lowers blood pressure.

Lower blood pressure reduces the

strain on your heart.

For angina: Adalat capsules work

by relaxing and expanding the

arteries supplying the heart. This

allows more blood and oxygen to

reach the heart and decreases the

strain on it. Your angina attacks

will be less severe and less

frequent if there is less strain on

the heart.

Adalat capsules can increase the

risk of serious heart problems in

patients with high blood pressure

or angina. Because of this, Adalat

capsules are only used in these

patients if no other treatments are

appropriate.

For Raynaud’s syndrome: Adalat

capsules work by relaxing and

expanding the blood vessels in

the fingers and toes. This helps

ensure a good blood supply.

2 Before you take Adalat

capsules

Do not take Adalat capsules:

If you have had a heart attack

within the last month.

If you get a sudden angina

attack. Adalat capsules will not

help relieve symptoms of angina

quickly.

If you have unstable angina

If you are allergic to the active

ingredient (nifedipine), to any

other similar medicines (known

as dihydropyridines) or to any of

the other ingredients. The

ingredients of Adalat capsules

are listed in section 6.

If you are taking rifampicin,

an antibiotic.

If you have been told that you

have a narrowing of the aortic

heart valve (stenosis).

If you have ever had a

collapse caused by a heart

problem (cardiogenic shock),

during which you became

breathless, pale and had a cold

sweat and dry mouth.

If your blood pressure

continues to rise despite

treatment (malignant

hypertension).

Tell your doctor and do not

take Adalat capsules if any of

these apply to you.

Your doctor will take special

care:

If you have low blood

pressure. Your blood pressure

may be decreased further by this

treatment.

If you have a heart condition

where your heart cannot cope

with increased strain (poor

cardiac reserve).

If you are pregnant

If you are breastfeeding

If you are a diabetic. The

treatment for your diabetes may

need to be adjusted. If you have

any questions about this, ask

your doctor.

If you are on kidney dialysis.

If you have a very high blood

pressure and a low blood volume,

you might experience a sudden

drop in blood pressure when you

take Adalat capsules.

If your liver is not working

properly. Your doctor may need

to do some blood tests. You may

also be given a lower dose of

Adalat capsules.

Talk to your doctor before

you take Adalat capsules if any

of these apply to you.

Tell your doctor:

If your chest pain (angina)

gets worse (comes on more often

or more severely) over a matter

of hours or days. You may be

advised not to take Adalat

capsules.

If you have chest pains after

taking your first dose of Adalat

capsules. Your doctor may wish

to change your treatment.

If you notice increased

breathlessness.

If you notice swelling of the

ankles.

Tell your doctor before you

take the next dose if any of

these apply to you.

Also tell your doctor:

If you are giving a urine

sample. Adalat capsules may

interfere with the results of

certain urine tests.

If you are a man who has

been unable to father a child by

in vitro fertilisation. Drugs like

Adalat capsules have been shown

to impair sperm function.

Other medicines and Adalat

capsules

Tell your doctor about any

other medicines that you are

taking, or took recently. This

includes any products you bought

without a prescription.

Some medicines may affect the

way Adalat capsules work. Tell

your doctor if you are taking:

Other medicines to treat high

blood pressure.

Rifampicin (an antibiotic)

Cimetidine (to treat stomach

ulcers).

Digoxin, diltiazem, quinidine

or beta-blockers (to treat heart

conditions).

Quinupristin/dalfopristin (a

combination antibiotic).

Phenytoin, carbamazepine or

valproic acid (to treat epilepsy).

Cisapride (to treat reduced

movements of the gullet and

stomach).

Magnesium sulphate

injections during pregnancy

(may cause a severe fall in blood

pressure).

Erythromycin (an antibiotic).

Ketoconazole, itraconazole or

fluconazole (antifungal

medicines).

Indinavir, nelfinavir,

ritonavir, saquinavir or

amprenavir (to treat HIV).

Fluoxetine or nefazodone (to

treat depression).

Tacrolimus (to prevent the

rejection of transplanted organs).

Phenobarbital (usually used to

treat insomnia or anxiety).

Food and drink with Adalat

capsules

You can take Adalat capsules

either with or without food.

Do not drink grapefruit juice

or eat grapefruit while taking

Adalat capsules.

Do not start taking Adalat

capsules within 3 days of

drinking grapefruit juice or

eating grapefruit. Tell your

doctor if you have had grapefruit

or grapefruit juice in this time.

Also, do not drink grapefruit

juice or eat grapefruit whilst

taking Adalat capsules.

Grapefruit juice is known to

increase the blood levels of the

active ingredient, nifedipine. This

effect can last for at least 3 days.

Pregnancy and breastfeeding

If you are pregnant, think you

might be pregnant or are

planning a family, tell your

doctor before taking Adalat

capsules.

If you need to take Adalat

capsules while breastfeeding, tell

your doctor before taking the

capsules.

Driving and using machines

Adalat capsules may make you

feel dizzy, faint, extremely tired

or have visual disturbances. Do

not drive or operate machinery if

you are affected in this way.

This may be more likely when

you first start treatment, if you

change capsules, or if you have

drunk alcohol.

3 How to take Adalat capsules

Take the capsules as prescribed

by your doctor.

Adalat capsules are not

recommended for use in children

and adolescents below 18 years

of age, because there is only

limited data on the safety and

efficacy in this population.

To start with, you may be

given a lower strength (5 mg)

capsule every 8 hours. This

allows your doctor to monitor

how you are responding so that

the best long term dose can be

identified.

The dose can be increased to a

maximum of 20 mg every 8

hours.

Leave at least two hours

between doses.

Lower doses may be prescribed

for elderly patients or for

patients who have liver

problems.

Swallow the capsules whole

with a little water.

Continue to take the capsules

for as long as your doctor has

told you to.

Do not take them with grapefruit

juice.

You can take Adalat capsules

either with or without food.

If you take too many capsules

Get medical help

immediately. If possible, take

your capsules or the box with

you to show the doctor.

Taking too many capsules may

cause your blood pressure to

become too low and your

heartbeats to speed up or slow

down. It may also lead to an

increase in your blood sugar level

or an increase in the acidity of

your blood, swelling in the lungs,

low blood oxygen levels and

disturbances in consciousness,

possibly leading to

unconsciousness.

If you forget to take the

capsules

Take your normal dose

immediately and continue taking

your capsules as prescribed,

waiting 8 hours before taking

your next dose.

Do not take a double dose to

make up for the missed dose.

4 Possible side effects

Like all medicines, Adalat

capsules can have side effects,

although not everybody gets

them.

Serious side effects

If you notice:

severe, sudden generalised

allergic reaction including very

rarely life-threatening shock (e.g.

difficulty in breathing, drop of

blood pressure, fast pulse) or

swelling (including potentially

life-threatening swelling of the

airway)

other allergic reactions causing

swelling under the skin (possibly

severe and including swelling of

the larynx that may result in a

life-threatening outcome)

fast heart beat (tachycardia)

shortness of breath or difficulty

breathing

mild to moderate allergic

reactions

itching (possibly severe), a rash

or hives

Contact your doctor

immediately and do not take

the next dose as these may be

the first signs of allergic reaction

which may become severe.

Less serious side effects

Apart from the side effects listed

above, these are the other side

effects of Adalat capsules,

starting with the more common

ones:

Common side effects

(These may affect up to 1 in 10

people)

headache

flushing

general feeling of being unwell

constipation

swelling, particularly of the

ankles and legs

Uncommon side effects

(These may affect up to 1 in 100

people)

stomach pain (abdominal pain)

unspecific pain

chills

low blood pressure when

standing up (symptoms include

fainting, dizziness, light

headedness, occasional

palpitations, blurred vision and

sometimes confusion)

fainting

irregular heartbeat

(palpitations)

dry mouth

indigestion or upset stomach

wind (flatulence)

feeling sick (nausea)

muscle cramps

joint swelling

sleep disorders

anxiety or nervousness

reddening of the skin

nose bleeds

nasal congestion

sensation of spinning or

whirling motion (vertigo)

migraine

dizziness

trembling

increase in the need to pass

water (urinate)

painful or difficult urination

inability to achieve or maintain

an erection (impotence)

blurred vision

temporary increase in certain

liver enzymes

Rare side effects

(These may affect up to 1 in

1,000 people)

pins and needles

unpleasant abnormal sensation

inflammation of the gums,

tender or swollen gums, bleeding

gums

Other side effects

(Frequency unknown)

vomiting.

eye pain

chest pain

lowered white blood cell count

high blood sugar level

reduction in skin sensitivity to

pain or touch

drowsiness or sleepiness

acid reflux

yellow discolouration of the

skin (jaundice)

life-threatening skin reaction

(toxic epidermal necrolysis)

allergic reaction to sunlight

purplish-red spots which can be

felt

muscle / joint pain.

shortness of breath

All of these symptoms usually go

away when treatment with Adalat

capsules is stopped.

Reporting of side effects

If you get any side effects, talk to

your doctor, pharmacist or nurse.

This includes any possible side

effects not listed in this leaflet.

You can also report side effects

directly via HPRA

Pharmacovigilance, Earlsfort

Terrace, IRL - Dublin 2; Tel:

+353 1 6764971; Fax: +353 1

6762517. Website: www.hpra.ie;

E-mail: medsafety@hpra.ie. By

reporting side effects you can

help provide more information

on the safety of this medicine.

5 How to store Adalat capsules

Keep this medicine out of the

reach and sight of children.

Store your medicine in its

original container. Protect from

strong light and only remove the

capsule from the blister strip

when you are about to take it.

Do not store above 30ºC.

Do not use after the expiry date

which is marked on both the

outer carton and on each blister

strip of capsules.

Do not dispose of medicines in

household rubbish. Any unused

Adalat capsules should be

returned to a pharmacist

(chemist) who will dispose of

them properly. This helps the

environment.

6 Further information

What Adalat capsules contain

Adalat capsules contain the

active ingredient, nifedipine.

Adalat capsules also contain

glycerol, purified water,

saccharin sodium, peppermint oil

and macrogol 400.

The capsule shell contains

gelatin, glycerol, titanium

dioxide (E171) and Sunset

yellow (E110).

Sunset yellow (E110) may cause

allergic reactions.

What’s in the pack

Each oval, soft gelatin capsule is

filled with a viscous yellow

liquid containing 10 mg of

nifedipine.

Each pack contains 90 capsules.

Marketing authorisation

holder: Bayer Limited, The

Atrium, Blackthorn Road, Dublin

Manufacturer: Bayer Pharma

AG, D-51368, Leverkusen,

Germany

Bayer HealthCare Manufacturing

S.r.l., Via Delle Groane, 126,

20024, Garbagnate Milanese,

Italy

This leaflet was last revised:

June 2016Product

Authorisation Number: PA

1410/25/2

Summary of Product Characteristics

1 NAME OF THE MEDICINAL PRODUCT

Adalat 10 mg soft capsules

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each capsule contains 10 mg nifedipine.

Excipients: Sunset yellow (E110) 0.27 mg per capsule

For full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Capsule, soft.

Orange, gelatin ovoid capsules containing a yellow viscous liquid.

4 CLINICAL PARTICULARS

4.1 Therapeutic Indications

For the management of chronic stable angina pectoris, the treatment of Raynaud’s syndrome and essential

hypertension.

For patients suffering from essential hypertension or chronic stable angina pectoris, and treated with fast release

forms of nifedipine (Adalat 5 mg and 10 mg capsules), a dose dependent increase in the risk of cardiovascular

complications (e.g., myocardial infarction) and mortality may occur.

Due to this, Adalat 5 mg and 10 mg capsules should only be used for treatment of patients with essential

hypertension or chronic stable angina pectoris if no other treatment is appropriate.

4.2 Posology and method of administration

Method of administration

Oral Use

Dosage regimen

As far as possible the treatment must be tailored to the needs of the individual according to the severity of the disease

and the patient's response.

Depending on the clinical picture in each case, the basic dose must be introduced gradually

Dose titration is recommended for hypertensives with severe cerebrovascular disease and for patients, who because of

low body weight or multiple therapies with other antihypertensive drugs, are likely to have an excessive reaction to

nifedipine. In addition, patients in whom side effects in response to the nifedipine treatment make a finer dose

adjustment desirable should be individually stabilized with Adalat 5 mg capsule.

Unless otherwise prescribed, the following dosage guidelines are recommended for adults:

In coronary heart disease:

Chronic stable angina pectoris

1 Adalat 5 mg capsule 3 times daily

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(Angina of effort)

(3 x 5 mg/day)

If the therapeutic result is inadequate after about 2 - 3 days of treatment with nifedipine 5 mg, the dose should be

increased individually.

1 Adalat 10 mg capsule 3 times daily

(3 x 10 mg/day)

Starting dose should be nifedipine 5 mg preferably.

If higher dosages are necessary, the dose can be increased in stages up to maximum 60

mg daily.

In hypertension:

1 Adalat 5 mg capsule 3 times daily

(3 x 5 mg/day)

If the therapeutic result is inadequate after about 2 - 3 days of treatment with nifedipine 5 mg the dose should be

increased individually.

1 Adalat 10 mg capsule 3 times daily

(3 x 10 mg/day)

Starting dose should be nifedipine 5 mg preferably.

If higher dosages are necessary, the dose can be increased in stages up to maximum 60 mg daily.

In Raynaud's syndrome

1 Adalat 5 mg capsule 3 times daily

(3 x 5 mg/day)

If the therapeutic result is inadequate after about 2 - 3 days of treatment with nifedipine 5 mg, the dose should be

increased individually.

1 Adalat 10 mg capsule 3 times daily

(3 x 10 mg/day)

Starting dose should be nifedipine 5 mg preferably.

If higher dosages are necessary, the dose can be increased in stages up to maximum 60 mg daily.

Co-administration with CYP 3A4 inhibitors or CYP 3A4 inducers may result in the recommendation to adapt the

nifedipine dose or not to use nifedipine at all (see “interaction with other medicinal products and other forms of

interaction").

Duration of Treatment

The attending doctor will determine the duration of use.

Due to their pronounced antiischemic and antihypertensive action, Adalat capsules should be discontinued gradually,

particularly when high doses are used.

Administration

As a rule Adalat capsules are swallowed whole with a little liquid, irrespective of meal times. Grapefruit juice is to be

avoided (see “interaction with other medicinal products and other forms of interaction“).

Patients taking 20 mg unit doses of immediate release formulations such as Adalat 5 mg capsule or Adalat 10 mg

capsule should allow an interval of at least 2 h between doses.

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2

Additional information on special populations

Paediatric population

The safety and efficacy of nifedipine in children below 18 years have not been established. Currently available data for

the use of nifedipine in hypertension are described in section 5.1.

Elderly (>65) patients

The pharmacokinetics of Adalat capsules are altered in the elderly so that lower maintenance doses of nifedipine may

be required.

Patients with hepatic impairment

In patients with mild, moderate or severe impaired liver function, careful monitoring and 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”).

Patients with renal impairment

Based on pharmacokinetic data no dosage adjustment is required in patients with renal impairment (see

“Pharmacokinetic properties”).

4.3 Contraindications

Adalat 10 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 10mg during pregnancy or in nursing mothers has not been established (see sections 4.4, 4.6 and

5.3).

Adalat 10 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 10 mg should not be used for the treatment of acute attacks of angina.

The safety of Adalat 10 mg in malignant hypertension has not been established.

Adalat 10 mg should not be used for secondary prevention of myocardial infarction.

Adalat 10 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).

4.4 Special warnings and precautions for use

Adalat 10 mg is not a beta-blocker and therefore gives no protection against the dangers of abrupt beta-blocker

withdrawal; any such withdrawal should be a gradual reduction of the dose of beta-blocker, preferably over 8-10 days.

Adalat 10 mg may be used in combination with beta-blocking drugs and other antihypertensive agents but the

possibility of an additive effect resulting in postural hypotension should be borne in mind. Adalat 10 mg will not

prevent possible rebound effects after cessation of other antihypertensive therapy.

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.

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3

Treatment with short-acting nifedipine may induce an exaggerated fall in blood pressure and reflex tachycardia, which

can cause cardiovascular complications such as myocardial and cerebrovascular ischaemia.

As with other vasoactive substances, angina pectoris may very rarely occur (data from spontaneous reports) with

immediate release nifedipine, especially at the start of the treatment. Data from clinical studies confirm that the

occurrence of angina pectoris attacks is uncommon.

In patients suffering from angina pectoris an increase in frequency, duration and severity of angina pectoris attacks may

occur, especially at the start of the treatment.

The occurrence of myocardial infarction has been described in isolated cases, although it was not possible to

distinguish this from the natural course of the underlying disease.

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.

In patients with mild, moderate or severe impaired liver function, careful monitoring anda 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.

Adalat 10 mg should be used with caution in patients whose cardiac reserve is poor. Deterioration of heart failure has

occasionally been observed with nifedipine.

At doses higher than those recommended, there is some concern about increased mortality and morbidity in the

treatment of ischaemic heart disease, in particular after myocardial infarction.

Ischaemic pain has been reported in a small proportion of patients within 30 to 60 minutes of the introduction of Adalat

10 mg therapy. Although a “steal” effect has not been demonstrated, patients experiencing this effect should

discontinue Adalat 10 mg.

The use of Adalat 10 mg in diabetic patients may require adjustment of their control.

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

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 moderate 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

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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.

Adalat 10mg capsules contain the excipient sunset yellow (E110) which may cause allergic reactions.

4.5 Interaction with other medicinal products and other forms of interaction

Drugs that affect nifedipine

Nifedipine is metabolised via the cytochrome P450 3A4 system, located both in the intestinal mucosa and in the liver.

Drugs that are known to either inhibit or to induce this enzyme system may therefore alter the first pass (after oral

administration) or the clearance of nifedipine (See Sections 4.4. Special warnings and precautions for use).

The extent as well as the duration of interactions should be taken into account when administering nifedipine together

with the following drugs:

Rifampicin: Rifampicin strongly induces the cytochrome P450 3A4 system. Upon co-administration with rifampicin,

the bioavailability of nifedipine is distinctly reduced and thus its efficacy weakened. The use of nifedipine in

combination with rifampicin is therefore contraindicated (See Section 4.3. Contraindications).

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

Section 4.2 and 4.4. 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.).

Azithromycin, although structurally related to the class of macrolide antibiotics is void of CYP3A4 inhibition.

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, drugs 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 3A4 mediated metabolism of other drugs.

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Therefore an increase in nifedipine plasma concentrations upon co-administration of both drugs cannot be excluded

(See section 4.4.).

Quinupristin/dalfopristin:

Simultaneous administration of quinupristin/dalfopristin 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).

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.).

Further studies

Cisapride

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

Cytochrome P450 3A4 system-inducing anti-epileptic drugs, such as phenytoin, carbamazepine and phenobarbital:

phenytoin induces the cytochrome P450 3A4 system. Upon co-administration with phenytoin, the bioavailability of

nifedipine is reduced and thus its efficacy weakened. When both drugs are administered concomitantly, the clinical

response to nifedipine should be monitored and, if necessary, an increase of the nifedipine dose considered. If the dose

of nifedipine is increased during co-administration of both drugs, a reduction of the nifedipine dose should be

considered when the treatment with phenytoin is discontinued.

No formal studies have been performed to investigate the potential interaction between nifedipine and carbamazepine

or phenobarbital. As both drugs have been shown to reduce the plasma concentrations of the structurally similar

calcium channel blocker, nimodipine, due to enzyme induction, a decrease in nifedipine plasma concentrations and

hence a decrease in efficacy cannot be excluded.

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 receptor-antagonists

-other calcium antagonists

-alpha-adrenergic blocking agents

-PDE5 inhibitors

-alpha-methyldopa

When nifedipine is administered simultaneously with beta-receptor blockers the patient should be carefully monitored,

since deterioration of heart failure is also known to develop in isolated cases.

Digoxin:

The simultaneous administration of nifedipine and digoxin may lead to reduced digoxin clearance and, hence, an

increase in the plasma digoxin level. The patient should therefore be checked for symptoms of digoxin overdosage as a

precaution and, if necessary, the glycoside dose should be reduced taking account of the plasma concentration of

digoxin.

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Quinidine:

When nifedipine and quinidine have been administered simultaneously, lowered quinidine levels, or after

discontinuation of nifedipine, a distinct increase in plasma concentrations of quinidine, have been observed in

individual cases. For this reason, when nifedipine is either additionally administered or discontinued, monitoring of the

quinidine plasma concentration, and if necessary, adjustment of the quinidine dose are recommended. Some authors

reported increased plasma concentrations of nifedipine upon co-administration of both drugs, while others did not

observe an alteration in the pharmacokinetics of nifedipine.

Therefore the blood pressure should be carefully monitored, if quinidine is added to an existing therapy with nifedipine.

If necessary, the dose of nifedipine should be decreased.

Tacrolimus:

Tacrolimus has been shown to be metabolised via the cytochrome P450 3A4 system. Data recently published indicate

that the dose of tacrolimus administered simultaneously with nifedipine may be reduced in individual cases. Upon co-

administration of both drugs, the tacrolimus plasma concentrations should be monitored and, if necessary, a reduction

in the tacrolimus dose considered.

Drug food interactions

Grapefruit juice inhibits the cytochrome P450 3A4 system. Administration of nifedipine together with grapefruit juice

thus results in elevated plasma concentrations and prolonged action of nifedipine due to a decreased first pass

metabolism or reduced clearance. As a consequence, the blood pressure lowering effect of nifedipine may be increased.

After regular intake of grapefruit juice, this effect may last for at least three days after the last ingestion of grapefruit

juice.

Ingestion of grapefruit/grapefruit juice is therefore to be avoided while taking nifedipine (See Section 4.2).

Drugs shown not to interact with nifedipine

The following drugs have been shown to have no effect on the pharmacokinetics of nifedipine when administered

concomitantly: ajmaline, aspirin, benazepril, candesartan cilexetil, debrisoquine, doxazosin, irbesartan, omeprazole,

orlistat, pantoprazole, ranitidine, rosiglitazone, talinolol and triamterene hydrochlorothiazide.

Other forms of interaction

Nifedipine may increase the spectrophotometric values of urinary vanillylmandelic acid falsely. However, HPLC

measurements are unaffected.

4.6 Fertility, pregnancy and lactation

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 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.

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.

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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.

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.

Breast-feeding

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).

Fertility

In single cases of in vitro fertilisation calcium antagonists like nifedipine have been associated with reversible

biochemical changes in the spermatozoa’s 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.

4.7 Effects on ability to drive and use machines

Reactions to the drug, which vary in intensity from individual to individual, can impair the ability to drive or to operate

machinery. This applies particularly at the start of treatment, on changing the medication and in combination with

alcohol.

4.8 Undesirable effects

Adverse drug reactions (ADRs) based on placebo-controlled studies with nifedipine sorted by CIOMS III categories of

frequency (clinical trial data base: nifedipine n=2,661; placebo n=1,486; status: 22 Feb 2006 and the ACTION study:

nifedipine n=3,825; placebo n=3,840) are listed below: ADRs listed under “common” were observed with a frequency

below 3% with the exception of oedema (9.9%) and headache (3.9%).

The frequencies of ADRs reported with nifedipine are summarised in the table below. Within each frequency grouping,

undesirable effects are presented in order of decreasing seriousness. Frequencies are defined as common (

1/100 to <

1/10), uncommon (

1/1,000 to < 1/100) and rare (

1/10,000 to < 1/1,000). The ADRs identified only during the

ongoing postmarketing surveillance, and for which a frequency could not be estimated, are listed under “Not known”.

System Organ

Class

(MedDRA)

Common

Uncommon

Rare

Not known

Blood and

lymphatic system

disorders

Agranulocytosis

Leukopenia

Immune system

disorders

Allergic reaction

Allergic oedema /

angioedema (incl.

larynx oedema

Pruritus

Urticaria

Rash

Anaphylactic/

anaphylactoid

reaction

Psychiatric

disorders

Anxiety reactions

Sleep disorders

Metabolism and

nutrition

disorders

Hyperglycaemia

Nervous system

disorders

Headache

Vertigo

Migraine

Dizziness

Par-/

Dysaesthesia

Hypoaesthesia

Somnolence

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*cases have been reported when used as tocolytic during pregnancy (see section 4.6)

[[1]] = may result in life-threatening outcome.

In dialysis patients with malignant hypertension and hypovolaemia a distinct fall in blood pressure can occur as a result

of vasodilation.

Tremor

Eye disorders

Visual

disturbances

Eye Pain

Cardiac

disorders

Tachycardia

Palpitations

Chest Pain

(Angina Pectoris)

Vascular

disorders

Oedema

(incl.

peripheral

oedema)

Vasodilatation

Hypotension

Syncope

Respiratory,

thoracic, and

mediastinal

disorders

Nosebleed

Nasal congestion

Dyspnea

Pulmonary

oedema*

Gastrointestinal

disorders

Constipation

Gastrointestinal

and abdominal

pain

Nausea

Dyspepsia

Flatulence

Dry mouth

Gingival

hyperplasia

Vomiting

Gastrooesophageal

sphincter

insufficiency

Hepatobiliary

disorders

Transient increase

in liver enzymes

Jaundice

Skin and

subcutaneous

tissue disorders

Erythema

Toxic Epidermal

Necrolysis

Photosensitivity

allergic reaction

Palpable

purpura

Musculoskeletal

and connective

tissue disorders

Muscle cramps

Joint swelling

Arthralgia

Myalgia

Renal and

urinary disorders

Polyuria

Dysuria

Reproductive

system and breast

disorders

Erectile

dysfunction

General

disorders and

administration

site conditions

Feeling unwell

Unspecific pain

Chills

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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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971;

Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

4.9 Overdose

Symptoms

The following symptoms are observed in cases of severe nifedipine intoxication:

Disturbances of consciousness to the point of coma, a drop in blood pressure, tachycardiac/bradycardiac heart rhythm

disturbances, hyperglycaemia, metabolic acidosis, hypoxia, cardiogenic shock with pulmonary oedema.

Management of Overdose

As far as treatment is concerned, elimination of the active substance and the restoration of stable cardiovascular

conditions have priority.

After oral ingestion, thorough gastric lavage is indicated, if necessary in combination with irrigation of the small intestine.

In case of intoxication with nifedipine, elimination must be as complete as possible, including the small intestine, to

prevent the otherwise inevitable subsequent absorption of the active substance.

Haemodialysis serves no purpose, as nifedipine is not dialysable, but plasmapheresis is advisable (high plasma protein

binding, relatively low volume of distribution).

Hypotension as a result of cardiogenic shock and arterial vasodilatation can be treated with calcium (10-20 ml of a 10 %

calcium gluconate solution administered slowly i.v. and repeated if necessary). As a result, the serum calcium can reach

the upper normal range to slightly elevated levels. If an insufficient increase in blood pressure is achieved with calcium,

vasoconstricting sympathomimetics such as dopamine or noradrenaline should be administered. The dosage of these

drugs should be determined by the patient's response.

Symptomatic bradycardia may be treated with beta-sympathomimetics, and in life- threatening bradycardiac disturbances

of heart rhythm, temporary pacemaker therapy can be advisable.

Additional liquid or volume must be administered with caution because of the danger of overloading the heart.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

ATC code: C08 CA05

Nifedipine is a calcium antagonist of the 1,4-dihydropyridine type. Calcium antagonists reduce the transmembranal

influx of calcium ions through the slow calcium channel into the cell. As a specific and potent calcium antagonist,

nifedipine acts particularly on the cells of the myocardium and the smooth muscle cells of the coronary arteries and the

peripheral resistance vessels.

The main action of Adalat 10 mg is to relax arterial smooth muscle both in the coronary

and peripheral circulation.

In angina pectoris, Adalat 10 mg relaxes peripheral arteries so reducing the load on the left ventricle. Additionally,

Adalat 10 mg dilates submaximally both clear and pre-stenotic coronary arteries, and stenotic and post-stenotic coronary

arteries, thus protecting the heart against coronary artery spasm and improving perfusion to the ischaemic myocardium.

Adalat 10 mg reduces the frequency of painful attacks and the ischaemic ECG changes irrespective of the relative

contribution from coronary artery spasm or atherosclerosis.

Adalat 10 mg causes a reduction in blood pressure such that the percentage lowering is directly related to its initial level.

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In normotensive individuals, Adalat 10 mg has little or no effect on blood pressure.

In Raynaud's syndrome nifedipine can prevent or reduce the occuring digital vasospasm.

Paediatric population

Limited information on comparison of nifedipine with other antihypertensives is available for both acute hypertension and

long-term hypertension with different formulations in different dosages. Antihypertensive effects of nifedipine have been

demonstrated but dose recommendations,

long term safety and effect on cardiovascular outcome remain unestablished.

Paediatric dosing forms are lacking.

5.2 Pharmacokinetic properties

Absorption

After oral administration nifedipine is immediately and almost completely absorbed. The systemic availability of orally

administered nifedipine immediate release formulations (Adalat capsules) is 45 - 56% owing to a first pass effect.

Maximum plasma and serum concentrations are reached at 30 to 60 minutes. Simultaneous food intake leads to

delayed, but not reduced absorption.

Distribution

Nifedipine is about 95% bound to plasma protein (albumin). The distribution half-life after intravenous administration

has been determined to be 5 to 6 minutes.

Biotransformation

After oral administration nifedipine is metabolised in the gut wall and in the liver, primarily by oxidative processes.

These metabolites show no pharmacodynamic activity. Nifedipine is excreted in the form of its metabolites

predominantly via the kidneys and about 5 - 15% via the bile in the faeces. The unchanged substance is recovered only

in traces (below 0.1%) in the urine.

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 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 C

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”).

5.3 Preclinical safety data

Preclinical data reveal no special hazard for humans based on conventional studies of single and repeated dose toxicity,

genotoxicity and carcinogenic potential.

Reproduction toxicology

Nifedipine has been shown to produce teratogenic findings in rats, mice and rabbits, including digital anomalies,

malformation of the extremities, cleft palates, cleft sternum, and malformation of the ribs. Digital anomalies and

malformation of the extremities are possibly a result of compromised uterine blood flow, but have also been observed

in animals treated with nifedipine solely after the end of the organogenesis period.

Nifedipine administration was associated with a variety of embryotoxic, placentotoxic and fetotoxic effects, including

stunted fetuses (rats, mice, rabbits), small placentas and underdeveloped chorionic villi (monkeys), embryonic and fetal

deaths (rats, mice, rabbits) and prolonged pregnancy/decreased neonatal survival (rats; not evaluated in other species).

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All of the doses associated with the teratogenic, embryotoxic or fetotoxic effects in animals were maternally toxic and

several times the recommended maximum dose for humans (See Section 4.6. Pregnancy and lactation).

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Glycerol

Purified water

Saccharin sodium

Peppermint oil

Macrogol 400

The capsule shell contains:

Gelatin

Glycerol (85 per cent)

Titanium dioxide (E171)

Sunset yellow (E110)

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

Store in the original package. Keep blister in the outer carton.

Do not store above 30°C.

6.5 Nature and contents of container

Blister strips of polypropylene foil backed with aluminium foil: 90 capsules.

6.6 Special precautions for disposal of a used medicinal product or waste materials derived from

such medicinal product and other handling of the product

No special requirements.

7 MARKETING AUTHORISATION HOLDER

Bayer Limited

The Atrium

Blackthorn Road

Dublin 18

8 MARKETING AUTHORISATION NUMBER

PA1410/025/002

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9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation:

25 May 1977

Date of last renewal:

25 May 2007

10 DATE OF REVISION OF THE TEXT

September 2016

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