Rasilamlo - patient leaflet, side effects, dosage

B. PACKAGE LEAFLET

Package leaflet: information for the user

Rasilamlo 150 mg/5 mg film-coated tablets

Rasilamlo 150 mg/10 mg film-coated tablets

Rasilamlo 300 mg/5 mg film-coated tablets

Rasilamlo 300 mg/10 mg film-coated tablets

Aliskiren/amlo­dipine

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• – Keep this leaflet. You may need to read it again.

• – If you have any further questions, ask your doctor or pharmacist.

• – This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,

even if their signs of illness are the same as yours.

• – If you get any side effects, talk to your doctor or pharmacist. This includes any possible side

effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What Rasilamlo is and what it is used for

• 2. What you need to know before you take Rasilamlo

• 3. How to take Rasilamlo

• 4. Possible side effects

• 5. How to store Rasilamlo

• 6. Contents of the pack and other information

1. What Rasilamlo is and what it is used for

What Rasilamlo is

Rasilamlo contains two active substances, called aliskiren and amlodipine. Both of these substances help to control high blood pressure (hypertension).

Aliskiren is a renin inhibitor. It reduces the amount of angiotensin II the body can make.

Angiotensin II causes blood vessels to tighten, which raises blood pressure. Lowering the amount of angiotensin II allows the blood vessels to relax; this lowers blood pressure.

Amlodipine belongs to a group of medicines known as calcium channel blockers, which help to control high blood pressure. Amlodipine causes blood vessels to dilate and relax, thus blood pressure is lowered.

High blood pressure increases the workload of the heart and arteries. If this continues for a long time, it can damage the blood vessels of the brain, heart and kidneys, and may result in a stroke, heart failure, heart attack or kidney failure. Lowering the blood pressure to a normal level reduces the risk of developing these disorders.

What Rasilamlo is used for

Rasilamlo is used to treat high blood pressure in adult patients whose blood pressure is not sufficiently controlled with aliskiren or amlodipine alone.

2. What you need to know before you take Rasilamlo

Do not take Rasilamlo

• – if you are allergic to aliskiren or amlodipine, to any of the other ingredients of this medicine

(listed in section 6) or to other dihydropyridine-derived medicines (known as calcium channel blockers)

• – if you have experienced the following forms of angioedema (difficulties in breathing or

swallowing, or swelling of the face, hands and feet, eyes, lips and/or tongue):

• – angioedema when taking aliskiren

• – hereditary angioedema

• – angioedema without any known cause

• – if you are between three and nine months pregnant

• – if you are taking any of the following medicines

– ciclosporin (a medicine used in transplantation to prevent organ rejection or for other

conditions, e.g. rheumatoid arthritis or atopic dermatitis)

• – itraconazole (a medicine used to treat fungal infections)

• – quinidine (a medicine used to correct heart rhythm)

– if you have diabetes or impaired kidney function and you are treated with either of the

following classes of medicines used to treat high blood pressure:

• – an angiotensin converting enzyme inhibitor such as enalapril, lisinopril, ramipril

or

• – an angiotensin II receptor blocker such as valsartan, telmisartan, irbesartan

• – if the patient is less than 2 years of age

• – if you have very low blood pressure

• – if you are suffering from shock, including cardiogenic shock

• – if you have a narrowing of the aortic heart valve (aortic stenosis)

• – if you have heart failure after an acute heart attack

If any of the above applies to you, do not take Rasilamlo and talk to your doctor.

Warnings and precautions

Talk to your doctor before taking Rasilamlo:

• – if you are suffering from vomiting or diarrhoea or if you are taking a diuretic (a medicine to

increase the amount of urine you produce)

• – if you have already experienced angioedema (difficulties in breathing or swallowing, or

swelling of the face, hands and feet, eyes, lips and/or tongue). If this happens, stop taking Rasilamlo and contact your doctor

• – if you are taking either of the following classes of medicines used to treat high blood pressure:

• – an angiotensin converting enzyme inhibitor such as enalapril, lisinopril, ramipril

or

• – an angiotensin II receptor blocker such as valsartan, telmisartan, irbesartan

• – if you have diabetes (high blood sugar)

• – if you suffer from heart problems

• – if you are on a low-salt diet

• – if your urine flow has decreased markedly for 24 hours or more and/or if you have serious

kidney problems (e.g. require dialysis) or a narrowing or blockage of the arteries that supply blood to your kidney

• – if you have impaired kidney function, your doctor will carefully consider whether Rasilamlo is

suitable for you and may wish to monitor you carefully

• – if you suffer from liver problems (impaired liver function)

• – if you have renal artery stenosis (narrowing of the blood vessels to one of both kidneys)

• – if you have serious congestive heart failure (a type of heart disease where the heart cannot

pump enough blood around the body)

Your doctor may check your kidney function, blood pressure and the amount of electrolytes (e.g. potassium) in your blood at regular intervals.

See also information under the heading “Do not take Rasilamlo”.

Children and adolescents

Rasilamlo is for use in adults.

Rasilamlo must not be used in children from birth to less than 2 years of age. It should not be used in children from 2 to less than 6 years of age, and is not recommended for use in children and adolescents from 6 to less than 18 years of age.

Elderly people

In the majority of patients aged 65 years or older, the 300 mg dose of aliskiren shows no additional benefit in reducing blood pressure compared to the 150 mg dose.

Other medicines and Rasilamlo

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Tell your doctor if you are using the following medicines:

• – an angiotensin II receptor blocker or an angiotensin converting enzyme inhibitor (see also

information under the headings “Do not take Rasilamlo” and “Warnings and precautions”)

• – medicines used to lower blood pressure, diuretics (medicines to increase the amount of urine

you produce), especially potassium-sparing medicines, potassium supplements, potassium-containing salt substitutes, or heparin

• – ketoconazole, a medicine used to treat fungal infections

• – verapamil, a medicine used to lower high blood pressure, to correct heart rhythm or to treat

angina pectoris

• – clarithromycin, telithromycin, erythromycin which are antibiotics used to treat infections

• – amiodarone, a medicine used to treat abnormal heart rhythms

• – atorvastatin, a medicine used to treat high cholesterol

• – furosemide or torasemide, medicines belonging to the type known as diuretics, which are used

to increase the amount of urine you produce and are also used to treat a certain kind of heart problem (heart failure) or oedema (swelling)

• – antiepileptics (e.g. carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone)

• – rifampicin, a medicine used to prevent or treat infections

• – St. John’ s wort (hypericum perforatum), a herbal medicine used to elevate mood

• – certain types of pain killers called non-steroidal anti-inflammatory medicines (NSAIDs) (used

especially in patients over 65 years old)

• – diltiazem, a medicine used to treat heart problems

• – ritonavir, a medicine used to treat viral infection

Your doctor may need to change your dose and/or take other precautions if you are taking one of the following medicines:

• – furosemide or torasemide, medicines belonging to the type known as diuretics, which are used

to increase the amount of urine you produce and are also used to treat a certain kind of heart problem (heart failure) or oedema (swelling)

• – some medicines used to treat infections, such as ketoconazole

Rasilamlo with food and drink

You should avoid taking this medicine together with fruit juice and/or drinks containing plant extracts (including herbal teas).

Pregnancy

Do not take this medicine if you are pregnant (see section Do not take Rasilamlo). If you become pregnant while taking this medicine, stop taking it immediately and talk to your doctor. If you think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. Your doctor will normally advise you to stop taking Rasilamlo before you become pregnant and will advise you to take another medicine instead of Rasilamlo. Rasilamlo is not recommended in early pregnancy, and must not be taken when more than 3 months pregnant, as it may cause serious harm to your baby if it is used after the third month of pregnancy.

Breast-feeding

Tell your doctor if you are breast-feeding or about to start breast-feeding. Rasilamlo is not recommended for mothers who are breast-feeding, and your doctor may choose another treatment for you if you wish to breast-feed, especially if your baby is newborn, or was born prematurely.

Driving and using machines

Amlodipine, one of the active substances in Rasilamlo, may make you feel dizzy and drowsy. If you experience this symptom, do not drive or use tools or machines.

3. How to take Rasilamlo

Always take this medicine exactly as your doctor has told you and do not exceed the recommended dose. Check with your doctor or pharmacist if you are not sure.

The usual dose of Rasilamlo is one tablet a day.

The effect on blood pressure is seen within 1 week and maximum effect is reached at around 4 weeks. If your blood pressure is not controlled after 4 to 6 weeks, your doctor may adjust your dose.

Method of administration

Swallow the tablet whole with some water. You should take this medicine with a light meal once a day, preferably at the same time each day. You should avoid taking this medicine together with fruit juice and/or drinks containing plant extracts (including herbal teas). During your treatment, your doctor may adjust your dose depending on your blood pressure response.

If you take more Rasilamlo than you should

If you have accidentally taken too many Rasilamlo tablets, talk to a doctor immediately. You may require medical attention.

If you forget to take Rasilamlo

If you forget to take a dose of this medicine, take it as soon as you remember and then take the next dose at its usual time. If you only remember the forgotten dose the next day, you should simply take the next tablet at the usual time. Do not take a double dose (two tablets at once) to make up for a forgotten tablet.

Do not stop taking this medicine , even if you are feeling well unless your doctor tells you to do so. People who have high blood pressure often do not notice any signs of the problem. Many may feel quite normal. It is very important that you take this medicine exactly as your doctor tells you to get the best results and reduce the risk of side effects. Keep your appointments with the doctor even if you are feeling well.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Fainting and/or light-headedness linked to low blood pressure could occur at the beginning of treatment with Rasilamlo. If you experience these, tell your doctor immediately.

As for any combination of two active substances, side effects associated with each individual component cannot be excluded. The adverse reactions previously reported with one or both of the two active substances (aliskiren and amlodipine) of Rasilamlo and listed below may occur with Rasilamlo.

Some side effects can be serious:

A few patients have experienced these serious side effects. If any of the following occur, tell your doctor straight away:

• Severe skin reactions (toxic epidermal necrolysis and/or oral mucosal reactions – red skin,

blistering of the lips, eyes or mouth, skin peeling, fever) (uncommon: may affect up to 1 in 100 people).

• Severe allergic reaction with symptoms such as rash, itching, swelling of face or lips or tongue,

difficulty breathing, dizziness (rare: may affect up to 1 in 1,000 people).

• Nausea, loss of appetite, dark coloured urine or yellowing of skin and eyes (may be signs of liver disorder) (frequency not known).

Other side effects may include:

Common (may affect up to 1 in 10 people):

• low blood pressure
• swelling, including swelling of hands, ankles or feet (peripheral oedema)
• diarrhoea
• joint pain (arthralgia)
• high level of potassium in the blood
• dizziness
• sleepiness
• headache
• hot flushes
• abdominal pain
• nausea
• tiredness
• palpitations (awareness of your heart beat)

Uncommon (may affect up to 1 in 100 people):

• skin rash (this may also be a sign of allergic reactions or angioedema – see “Rare” side effects below)
• kidney problems including acute renal failure (severely decreased urine output)
• severe skin reactions (toxic epidermal necrolysis and/or oral mucosal reactions – red skin,

blistering of the lips, eyes or mouth, skin peeling, fever)

• cough
• itching
• rash (including itchy rash and urticaria)
• increased liver enzymes
• insomnia
• mood changes (including anxiety)
• depression
• trembling
• disturbed sense of taste
• sudden, temporary loss of consciousness
• decreased skin sensitivity
• tingling or numbness
• vision disorder (including double vision)
• ringing noise in ears
• shortness of breath
• runny nose
• vomiting
• stomach discomfort after meal
• altered bowel habits (including diarrhoea and constipation)
• dry mouth
• hair loss
• purple skin patches
• skin discolouration
• excessive sweating
• generalised rash
• muscle pain
• muscle cramps
• back pain
• urination disorders
• urination at night
• frequent urination
• impotence
• breast enlargement in men
• chest pain
• weakness
• pain
• feeling unwell
• weight increase
• weight decrease

Rare (may affect up to 1 in 1,000 people):

• severe allergic reaction (anaphylactic reaction)
• allergic reactions (hypersensitivity) and angioedema (the symptoms of which can include

difficulties in breathing or swallowing, rash, itching, hives or swelling of the face, hands and feet, eyes, lips and/or tongue, dizziness)

• increased level of creatinine in the blood
• red skin (erythema)
• confusion

Very rare (may affect up to 1 in 10,000 people):

• low level of white blood cells and blood platelets
• high level of sugar in the blood
• increased muscle stiffness and inability to stretch
• sensation of numbness or tingling with sensation of burning in fingers and toes
• heart attack
• irregular heart beat
• inflammation of blood vessels
• severe upper stomach pain
• inflammation of the gastric lining
• bleeding, tender or enlarged gums
• inflammation of the liver
• abnormal liver function test
• skin reaction with skin reddening and peeling, blistering of lips, eyes or mouth
• dry skin, rash, itchy rash
• skin rash with flaking or peeling
• rash, red skin, blistering of the lips, eyes or mouth, skin peeling, fever
• swelling mainly of the face and throat
• increased sensitivity of the skin to sun

Not known (frequency cannot be estimated from the available data):

• dizziness with spinning sensation
• low level of sodium in the blood

If any of these affect you severely, tell your doctor. You may need to stop Rasilamlo.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed inBy reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Rasilamlo

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and blister after EXP. The expiry date refers to the last day of that month.

Do not store above 30°C.

Store in the original package in order to protect from moisture.

6. Contents of the pack and other information

What Rasilamlo contains

• – Each Rasilamlo 150 mg/5 mg film-coated tablet contains 150 mg aliskiren (as hemifumarate)

and 5 mg amlodipine (as besylate). The other ingredients are cellulose microcrystalline, crospovidone, povidone, magnesium stearate, silica colloidal anhydrous, hypromellose, titanium dioxide (E171), macrogol, talc, yellow iron oxide (E172) and red iron oxide (E172).

• – Each Rasilamlo 150 mg/10 mg film-coated tablet contains 150 mg aliskiren (as hemifumarate)

and 10 mg amlodipine (as besylate). The other ingredients are cellulose microcrystalline, crospovidone, povidone, magnesium stearate, silica colloidal anhydrous, hypromellose, titanium dioxide (E171), macrogol, talc and yellow iron oxide (E172).

• – Each Rasilamlo 300 mg/5 mg film-coated tablet contains 300 mg aliskiren (as hemifumarate)

and 5 mg amlodipine (as besylate). The other ingredients are cellulose microcrystalline, crospovidone, povidone, magnesium stearate, silica colloidal anhydrous, hypromellose, titanium dioxide (E171), macrogol, talc and yellow iron oxide (E172).

• – Each Rasilamlo 300 mg/10 mg film-coated tablet contains 300 mg aliskiren (as hemifumarate)

What Rasilamlo looks like and contents of the pack

Rasilamlo 150 mg/5 mg film-coated tablets are light yellow, convex, oval film-coated tablets, with “T2” debossed on one side and “NVR” on the other.

Rasilamlo 150 mg/10 mg film-coated tablets are yellow, convex, oval film-coated tablets, with “T7” debossed on one side and “NVR” on the other.

Rasilamlo 300 mg/5 mg film-coated tablets are dark yellow, convex, oval film-coated tablets, with “T11” debossed on one side and “NVR” on the other.

Rasilamlo 300 mg/10 mg film-coated tablets are brown-yellow, convex, oval film-coated tablets, with “T12” debossed on one side and “NVR” on the other.

Rasilamlo is available in packs containing 14, 28, 56 or 98 tablets (in calendar blisters), 30 or 90 tablets (in normal blisters) and 56×1 tablet (as perforated unit dose blisters).

It is also available in multi-packs of 98 tablets (2 packs of 49) and 280 tablets (20 packs of 14) in calendar blisters and 98×1 tablet (2 packs of 49×1) as perforated unit dose blisters.

Not all pack sizes or strengths may be available in your country.

Marketing Authorisation Holder

Novartis Europharm Limited

Frimley Business Park

Camberley GU16 7SR

United Kingdom

Manufacturer

Novartis Farma S.p.A.

Via Provinciale Schito 131

I-80058 Torre Annunziata/NA

Italy

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgiqu­e/Belgien Novartis Pharma N.V. Tél/Tel: +32 2 246 16 11 Etnrapwa Novartis Pharma Services Inc. Ten.: +359 2 489 98 28 Česká republika Novartis s.r.o. Tel: +420 225 775 111 Danmark Novartis Healthcare A/S Tlf: +45 39 16 84 00

Lietuva Novartis Pharma Services Inc. Tel: +370 5 269 16 50 Luxembourg/Lu­xemburg Novartis Pharma N.V. Tél/Tel: +32 2 246 16 11 Magyarorszag Novartis Hungaria Kft. Pharma Tel.: +36 1 457 65 00 Malta Novartis Pharma Services Inc. Tel: +356 2122 2872

Deutschland Novartis Pharma GmbH Tel: +49 911 273 0	Nederland Novartis Pharma B.V. Tel: +31 26 37 82 111
Eesti Novartis Pharma Services Inc. Tel: +372 66 30 810	Norge Novartis Norge AS Tlf: +47 23 05 20 00
EÀXàôa Novartis (Hellas) A.E.B.E. Tqk +30 210 281 17 12	Österreich Novartis Pharma GmbH Tel: +43 1 86 6570
España Novartis Farmacéutica, S.A. Tel: +34 93 306 42 00	Polska Novartis Poland Sp. z o.o. Tel.: +48 22 375 4888
France Novartis Pharma S.A.S. Tél: +33 1 55 47 66 00	Portugal Novartis Farma – Produtos Farmacêuticos, S.A. Tel: +351 21 000 8600
Hrvatska Novartis Hrvatska d.o.o. Tel. +385 1 6274 220	România Novartis Pharma Services Romania SRL Tel: +40 21 31299 01
Ireland Novartis Ireland Limited Tel: +353 1 260 12 55	Slovenija Novartis Pharma Services Inc. Tel: +386 1 300 75 50
Ísland Vistor hf. Sími: +354 535 7000	Slovenská republika Novartis Slovakia s.r.o. Tel: +421 2 5542 5439
Italia Novartis Farma S.p.A. Tel: +39 02 96 54 1	Suomi/Finland Novartis Finland Oy Puh/Tel: +358 (0)10 6133 200
Kúnpog Novartis Pharma Services Inc. Tqk +357 22 690 690	Sverige Novartis Sverige AB Tel: +46 8 732 32 00
Latvija Novartis Pharma Services Inc. Tel: +371 67 887 070	United Kingdom Novartis Pharmaceuticals UK Ltd. Tel: +44 1276 698370

This leaflet was last revised in

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website:

ANNEX IV

SCIENTIFIC CONCLUSIONS AND GROUNDS RECOMMENDING THE VARIATION TO THE TERMS OF THE MARKETING AUTHORISATION

Scientific conclusions

Taking into account the PRAC Assessment Report on the PSUR for aliskiren / aliskiren, amlodipine / aliskiren, hydrochlorothi­azide, the scientific conclusions of CHMP are as follows:

During the reporting a number of serious and non-serious adverse drug reactions (ADRs) from postmarketing data sources regarding “hyponatraemia” raised a concern that led to the submission of a cumulative review from the Marketing Authorisation Holder (MAH). The cumulative review retrieved 187 cases out of which 57 were sufficiently documented, in 8 of these cases a causal relationship could not be ruled out. In 3 additional cases where severe hyponatremia was associated with neurological symptoms such as brain oedema or major confusion and cerebral oedema, causality could also not be excluded.

The MAH submitted an analysis with 1407 cases of “dyspnoea”, in 13 of them there was positive dechallenge and three cases with positive rechallenge. The PRAC considered the cases of dechallenge and rechallenge to be important causal relationship information that contributes to confirm the safety signal.

Therefore, in view of available data regarding aliskiren/ aliskiren,amlo­dipine / aliskiren, hydrochlorothi­azide, the PRAC considered that changes to the product information were warranted. The CHMP agrees with the scientific conclusions made by the PRAC.

Grounds recommending the variation to the terms of the Marketing Authorisation

On the basis of the scientific conclusions for aliskiren / aliskiren, amlodipine / aliskiren, hydrochlorothiazide the CHMP is of the opinion that the benefit-risk balance of the medicinal product(s) containing aliskiren / aliskiren, amlodipine / aliskiren, hydrochlorothiazide is favourable subject to the proposed changes to the product information.

The CHMP recommends that the terms of the Marketing Authorisations should be varied.

145