Patient leaflet - Irbesartan and Hydrochlorothiazide Milpharm 150 mg / 12.5 mg film-coated tablets

1. What Irbesartan/ Hydrochlorothiazide is and what it is used for

Irbesartan and Hydrochlorothiazide is a combination of two active substances, irbesartan and hydrochlorothiazide.

Irbesartan belongs to a group of medicines known as angiotensin-II receptor antagonists. Angiotensin-II is a substance produced in the body that binds to receptors in blood vessels causing them to tighten. This results in an increase in blood pressure. Irbesartan prevents the binding of angiotensin-II to these receptors, causing the blood vessels to relax and the blood pressure to lower. Hydrochlorothiazide is one of a group of medicines (called thiazide diuretics) that causes increased urine output and so causes a lowering of blood pressure.

The two active ingredients in Irbesartan and Hydrochlorothiazide work together to lower blood pressure further than if either was given alone.

Irbesartan and Hydrochlorothiazide is used to treat high blood pressure, when treatment with irbesartan or hydrochlorothiazide alone did not provide adequate control of your blood pressure.

2. What you need to know before you take Irbesartan/ Hydrochlorothiazide

Do not take Irbesartan and Hydrochlorothiazide

if you are allergic to irbesartan or any of the
other ingredients of this medicine (listed in section 6)
if you are allergic to hydrochlorothiazide or any
other sulfonamide-derived medicines • if you are more than 3 months pregnant.
(It is also better to avoid Irbesartan and Hydrochlorothiazide in early pregnancy – see pregnancy section)
if you have severe liver or kidney problems • if you have difficulty in producing urine • if your doctor determines that you have
persistently high calcium or low potassium levels in your blood
if you have diabetes or impaired kidney function
and you are treated with a blood pressure lowering medicine containing aliskiren

Warnings and precautions

Talk to your doctor before taking Irbesartan/ Hydrochlorothiazide and if any of the following apply to you:

if you get excessive vomiting or diarrhoea • if you suffer from kidney problems or have a
kidney transplant
if you suffer from heart problems
if you suffer from liver problems
if you suffer from diabetes
if you develop low blood sugar levels (symptoms
may include sweating, weakness, hunger, dizziness, trembling, headache, flushing or paleness, numbness, having a fast, pounding heart beat), particularly if you are being treated for diabetes.
if you suffer from lupus erythematosus (also
known as lupus or SLE)
if you suffer from primary aldosteronism
(a condition related to high production of the hormone aldosterone, which causes sodium retention and, in turn, an increase in blood pressure).
if you are taking any of the following medicines
used to treat high blood pressure:
- an ACE-inhibitor (for example enalapril,
  lisinopril, ramipril), in particular if you have diabetes-related kidney problems. - aliskiren
if you have had skin cancer or if you develop
an unexpected skin lesion during the treatment. Treatment with hydrochlorothiazide, particularly long term use with high doses, may increase the risk of some types of skin and lip cancer (non-melanoma skin cancer). Protect your skin from sun exposure and UV rays while taking Irbesartan/ Hydrochlorothiazide
if you experienced breathing or lung problems
(including inflammation or fluid in the lungs) following hydrochlorothiazide intake in the past. If you develop any severe shortness of breath or difficulty breathing after taking Irbesartan and Hydrochlorothiazide, seek medical attention immediately.

Talk to your doctor if you experience abdominal pain, nausea, vomiting or diarrhoea after taking Irbesartan/ Hydrochlorothiazide . Your doctor will decide on further treatment. Do not stop taking Irbesartan/ Hydrochlorothiazide on your own.

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 Irbesartan/ Hydrochlorothiazide”

You must tell your doctor if you think you are (or might become) pregnant. Irbesartan and Hydrochlorothiazide is not recommended in early pregnancy, and must not be taken if you are more than 3 months pregnant, as it may cause serious harm to your baby if used at that stage (see pregnancy section).

Package leaflet: Information for the user

Irbesartan and Hydrochlorothiazide 150 mg/ 12.5 mg film-coated tablets Irbesartan and Hydrochlorothiazide 300 mg/ 12.5 mg film-coated tablets Irbesartan and Hydrochlorothiazide 300 mg/ 25 mg film-coated tablets irbesartan/ hydrochlorothiazide

You should also tell your doctor:

if you are on a low-salt diet
if you have signs such as abnormal thirst, dry mouth, general weakness, drowsiness, muscle pain or cramps, nausea, vomiting, or an abnormally fast heart beat which may indicate an excessive effect of hydrochlorothiazide (contained in Irbesartan and Hydrochlorothiazide) • if you experience an increased sensitivity of the skin to the sun with symptoms of sunburn (such as redness, itching, swelling, blistering) occurring more quickly than normal
if you are going to have an operation (surgery)
or be given anaesthetics
if you have decrease in your vision or pain in one or both of your eyes while taking Irbesartan and Hydrochlorothiazide. These could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or an increase of pressure in your eye (glaucoma) and can happen within hours to a week of taking Irbesartan and Hydrochlorothiazide. This can lead to permanent vision loss, if not treated. If you earlier have had a penicillin or sulfonamide allergy, you can be at higher risk of developing this. You should discontinue Irbesartan and Hydrochlorothiazide treatment and seek prompt medical attention.

The hydrochlorothiazide contained in this medicine could produce a positive result in an anti-doping test.

Children and adolescents

Irbesartan/ Hydrochlorothiazide should not be given to children and adolescents (under 18 years).

Other medicines and Irbesartan/ Hydrochlorothiazide

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

Diuretic agents such as the hydrochlorothiazide contained in Irbesartan and Hydrochlorothiazide may have an effect on other medicines. Preparations containing lithium should not be taken with Irbesartan and Hydrochlorothiazide without close supervision by your doctor.

Your doctor may need to change your dose and/or to take other precautions:

If you are taking an ACE-inhibitor or aliskiren (see also information under the headings “Do not take Irbesartan/ Hydrochlorothiazide” and “Warnings and precautions”)

You may need to have blood checks if you take:

potassium supplements
salt substitutes containing potassium • potassium-sparing medicines or other diuretics
(water tablets)
some laxatives
medicines for the treatment of gout
therapeutic vitamin D supplements
medicines to control heart rhythm
medicines for diabetes (oral agents as repaglinide or insulins)
carbamazepine (a medicine for the treatment of epilepsy)

It is also important to tell your doctor if you are taking other medicines to reduce your blood pressure, steroids, medicines to treat cancer, pain killers, arthritis medicines, or colestyramine and colestipol resins for lowering blood cholesterol.

Irbesartan and Hydrochlorothiazide with food and drink and alcohol

Irbesartan and Hydrochlorothiazide can be taken with or without food.

Due to the hydrochlorothiazide contained in Irbesartan and Hydrochlorothiazide, if you drink alcohol while on treatment with this medicine, you may have an increased feeling of dizziness on standing up, specially when getting up from a sitting position.

Pregnancy, breast-feeding and fertility Pregnancy

You must tell your doctor if you think you are (or might become) pregnant. Your doctor will normally advise you to stop taking Irbesartan and Hydrochlorothiazide before you become pregnant or as soon as you know you are pregnant and will advise you to take another medicine instead of Irbesartan and Hydrochlorothiazide. Irbesartan and Hydrochlorothiazide is not recommended during pregnancy, and must not be taken when more than 3 months pregnant, as it may cause serious harm to your baby if used after the third month of pregnancy.

Breast-feeding

Tell your doctor if you are breast-feeding or about to start breast-feeding. Irbesartan and Hydrochlorothiazide 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.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines

Irbesartan and Hydrochlorothiazide is unlikely to affect your ability to drive or use machines. However, occasionally dizziness or weariness may occur during treatment of high blood pressure. If you experience these, talk to your doctor before attempting to drive or use machines.

Irbesartan and Hydrochlorothiazide contains lactose

Irbesartan/ Hydrochlorothiazide contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

Irbesartan contain Sodium:

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

Black A/s : 165 x 500 mm

3. How to take Irbesartan/ Hydrochlorothiazide

Always take this medicine exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

Dosage

The recommended dose of Irbesartan and Hydrochlorothiazide is one or two tablets a day. Irbesartan and Hydrochlorothiazide will usually be prescribed by your doctor when your previous treatment did not reduce your blood pressure enough. Your doctor will instruct you how to switch from the previous treatment to Irbesartan and Hydrochlorothiazide.

Method of administration

Irbesartan and Hydrochlorothiazide is for oral use. Swallow the tablets with a sufficient amount of fluid (e.g. one glass of water). You can take Irbesartan and Hydrochlorothiazide with or without food. Try to take your daily dose at about the same time each day. It is important that you continue to take Irbesartan and Hydrochlorothiazide until your doctor tells you otherwise.

The maximal blood pressure lowering effect should be reached 6-8 weeks after beginning treatment.

If you take more Irbesartan and Hydrochlorothiazide than you should

If you accidentally take too many tablets, contact your doctor immediately.

Children should not take Irbesartan and Hydrochlorothiazide

Irbesartan and Hydrochlorothiazide should not be given to children under 18 years of age. If a child swallows some tablets, contact your doctor immediately.

If you forget to take Irbesartan and Hydrochlorothiazide

If you accidentally miss a daily dose, just take the next dose as normal. Do not take a double dose to make up for a forgotten dose.

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. Some of these effects may be serious and may require medical attention.

Rare cases of allergic skin reactions (rash, urticaria), as well as localised swelling of the face, lips and/ or tongue have been reported in patients taking irbesartan.

If you get any of the above symptoms or get short of breath, stop taking Irbesartan and Hydrochlorothiazide and contact your doctor immediately.

The frequency of the side effects listed below is defined using the following convention:

Common: may affect up to 1 in 10 people Uncommon: may affect up to 1 in 100 people

Side effects reported in clinical studies for patients treated with irbesartan/ hydrochlorothiazide were: Common side effects (may affect up to 1 in 10 people):

nausea/vomiting
abnormal urination
fatigue
dizziness (including when getting up from a lying
or sitting position)
blood tests may show raised levels of an enzyme
that measures the muscle and heart function (creatine kinase) or raised levels of substances that measure kidney function (blood urea nitrogen, creatinine).

If any of these side effects causes you problems, talk to your doctor.

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

diarrhoea
low blood pressure
fainting
heart rate increased
flushing
swelling
sexual dysfunction (problems with sexual
performance)
blood tests may show lowered levels of potassium
and sodium in your blood.

If any of these side effects causes you problems, talk to your doctor.

Side effects reported since the launch of Irbesartan/ Hydrochlorothiazide

Some undesirable effects have been reported since marketing of Irbesartan/ Hydrochlorothiazide. Undesirable effects where the frequency is not known are: headache, ringing in the ears, cough, taste disturbance, indigestion, pain in joints and muscles, liver function abnormal and impaired kidney function, increased level of potassium in your blood and allergic reactions such as rash, hives, swelling of the face, lips, mouth, tongue or throat. Uncommon cases of jaundice (yellowing of the skin and/or whites of the eyes) have also been reported.

As for any combination of two active substances, side effects associated with each individual component cannot be excluded.

Side effects associated with irbesartan alone

In addition to the side effects listed above, chest pain, severe allergic reactions (anaphylactic shock), decreased number of red blood cells (anaemia – symptoms may include tiredness, headaches, being short of breath when exercising, dizziness and looking pale) and decrease in the number of platelets (a blood cell essential for the clotting of the blood) and low blood sugar levels have also been reported.

Rare (may affect up to 1 in 1,000 people): Intestinal angioedema: a swelling in the gut presenting with symptoms like abdominal pain, nausea, vomiting and diarrhoea.

Side effects associated with hydrochlorothiazide alone

Loss of appetite; stomach irritation; stomach cramps; constipation; jaundice (yellowing of the skin and/or whites of the eyes); inflammation of the pancreas characterised by severe upper stomach pain, often with nausea and vomiting; sleep disorders; depression; blurred vision; lack of white blood cells, which can result in frequent infections, fever;

decrease in the number of platelets (a blood cell essential for the clotting of the blood), decreased number of red blood cells (anaemia) characterised by tiredness, headaches, being short of breath when exercising, dizziness and looking pale; kidney disease; lung problems including pneumonia or build-up of fluid in the lungs; increased sensitivity of the skin to the sun; inflammation of blood vessels; a skin disease characterized by the peeling of the skin all over the body; cutaneous lupus erythematosus, which is identified by a rash that may appear on the face, neck, and scalp; allergic reactions; weakness and muscle spasm; altered heart rate; reduced blood pressure after a change in body position; swelling of the salivary glands; high sugar levels in the blood; sugar in the urine; increases in some kinds of blood fat; high uric acid levels in the blood, which may cause gout.

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

Acute respiratory distress (signs include severe shortness of breath, fever, weakness, and confusion).

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

skin and lip cancer (non-melanoma skin cancer), decrease in vision or pain in your eyes due to high pressure (possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion) or acute angle-closure glaucoma).

It is known that side effects associated with hydrochlorothiazide may increase with higher doses of hydrochlorothiazide.

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 Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard. or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Irbesartan/ Hydrochlorothiazide

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 on the blister/label of the bottle after EXP. The expiry date refers to the last day of that month.

Store below 30⁰C.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Irbesartan and Hydrochlorothiazide contains

The active substance is irbesartan &
hydrochlorothiazide.
Each film-coated tablet contains 150 mg of irbesartan and 12.5 mg of hydrochlorothiazide. Each film-coated tablet contains 300 mg of irbesartan and 12.5 mg of hydrochlorothiazide. Each film-coated tablet contains 300 mg of irbesartan and 25 mg of hydrochlorothiazide.
The other ingredients are
Tablet core: Lactose monohydrate, Sodium Starch
Glycolate (Type A), Povidone K30, Silica Colloidal Anhydrous, Talc, Sodium stearyl fumarate.

Tablet coat:

150mg/12.5mg & 300mg/12.5mg film-coated tablets Lactose monohydrate

Hypromellose (E464)

Titanium dioxide (E171)

Macrogol 4000

Iron oxide yellow (E172)

Iron oxide red (E172)

300 mg/25 mg film-coated tablets

Hypromellose (E464)

Titanium dioxide (E171)

Macrogol 4000

Iron oxide red (E172)

Iron oxide black (E172)

What Irbesartan and Hydrochlorothiazide looks like and contents of the pack

Film-coated Tablet.

150 mg/ 12.5 mg

Peach coloured film-coated biconvex oval shaped tablets, debossed with “H 35” on one side and plain on other side.

300 mg/ 12.5 mg

Peach coloured film-coated biconvex oval shaped tablets, debossed with “H 36” on one side and plain on other side.

300 mg/ 25 mg

Pink coloured film-coated biconvex oval shaped tablets, debossed with “H 37” on one side and plain on other side.

Tablets are available in Polyamide/Aluminium/PVC/ Aluminium blister pack and white opaque HDPE bottle with white opaque polypropylene closure pack.

Pack size:

Blister pack: 1, 14, 28, 30, 56, 90, 98, 100 & 500 tablets

Bottle pack: 30 & 90 tablets

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Milpharm Limited

1 Roundwood Avenue

Stockley Park, Uxbridge

UB11 1AF

United Kingdom

Manufacturer

APL Swift Services (Malta) Limited

HF26, Hal Far Industrial Estate, Hal Far Birzebbugia, BBG 3000

Malta