Patient leaflet - Co-zidocapt 25/12.5 mg tablets

1. What Co-zidocapt is and what it is used for

Co-zidocapt Tablets is a combination of two active substances, Captopril and Hydrochlorothiazide (HCT). Captopril belongs to a group of medicines known as ACE (Angiotensin-Converting Enzyme) Inhibitors. ACE inhibitors cause blood vessels to relax and the blood pressure to lower. Hydrochlorothiazide (HCT) is one of a group of medicines known as thiazide diuretics (also known as water tablets). They increase urine output and hence decrease blood pressure.

The two active substances in Co-zidocapt Tablets work together to decrease blood pressure further than if either was given alone.

Captopril + Hydrochlorothiazide Tablet (referred to as Co-zidocapt throughout this leaflet) is used in the treatment of high blood pressure (essential hypertension), if treatment with captopril or hydrochlorothiazide alone has not led to a sufficient decrease in blood pressure.

2. What you need to know before you take Co-zidocapt

Do not take Co-zidocapt if:

You are allergic to Captopril, Hydrochlorothiazide, other ACE Inhibitors, other Sulphonamides or any of the other ingredients of this medicine (listed in Section 6)
If you have already been treated with medicines from the same group of medicines as this medicine (ACE inhibitors) and have had allergic reactions that cause swelling of the arms, legs, ankles, lips, tongue and/or throat with difficulty swallowing or breathing (angioedema) or if a family member has had a similar reaction.
You are more than 3 months pregnant (It is also better to avoid Co-zidocapt in early pregnancy - see Pregnancy section)
You suffer from severe kidney problems
You suffer from severe liver problems
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 Co-zidocapt:

If you are due to have a surgical operation. You should make sure that the anaesthetist is aware you are taking Co-zidocapt
If you are due to take an anti-doping test, a bentiromide test, thyroid tests or a urine test for acetone (see “Other medicines and Co-zidocapt”)
If you are suffering from dehydration as a result of diuretic treatment, low salt diet, diarrhoea, vomiting (being sick) or dialysis. Symptoms of dehydration include: dry mouth, thirst, weakness, lack of energy, drowsiness, restlessness, muscle pain or cramps, low blood pressure (hypotension), decreased production of urine (oliguria), faster heartbeat (tachycardia), feeling (nausea) or being sick (vomiting)
If you suffer from heart failure or other heart problems
If you suffer from a condition that affects the circulation of blood to the brain
If you suffer from kidney problems or narrowing of the aorta (aortic stenosis) or renal artery (renal artery stenosis).
If you are black as black patients receiving ACE inhibitor treatment have been reported to have a higher incidence of angioedema (swelling of the deeper layers of the skin, caused by a build-up of fluid) than in non-black patients. Additionally, Co-zidocapt may be less effective in lowering blood pressure in black patients than in non-black patients
Patients with a history of angioedema (swelling of the deeper layers of the skin, caused by a build-up of fluid) unrelated to ACE inhibitor treatment may be at increased risk of developing angioedema while taking Co-zidocapt. sirolimus, everolimus, and other drugs in the mTOR inhibitor class (used to prevent rejection of transplanted organs).
If you are currently suffering from a dry, persistent cough (this will usually go after stopping treatment with Co-zidocapt)
If you suffer from liver problems
If you have high levels of potassium in the blood (hyperkalaemia), are currently taking potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes or other medicines associated with increases in potassium (e.g. heparin) (see “Other medicines and Co-zidocapt”)
If you are diabetic, especially if you take oral anti-diabetic medicines or insulin (see “Other medicines and Co-zidocapt”)
If you suffer from collagen vascular disease (disease where problems with the immune system cause inflammation or weakness of collagen [connective tissue])
If you are receiving treatment to reduce your immune response
If you are taking allopurinol &/or procainamide (see “Other medicines and Co-zidocapt”)
If you show signs of infection e.g. sore throat, fever
If you are receiving treatment to reduce the effects of an allergy to a bee or wasp sting. Allergic reactions have been reported in patients treated with this medicinal product together with desensitisation treatments. Check with your doctor before starting your treatment
If you are on dialysis, allergic reactions have been reported in patients treated with this medicine with certain dialysis membranes (called high-flow haemodialysis membranes or low-density lipoprotein apheresis with dextran sulfate absorption). Check with your doctor before your next dialysis treatment.
If you are having treatment to remove high levels of cholesterol by a procedure called Low-Density Lipoprotein (LDL) apheresis with dextran sulphate
If you are currently taking corticosteroids or ACTH [Adreno CorticoTropic Hormone] (see “Other medicines and Co-zidocapt”)
If you have high levels of calcium in the blood (hypercalcaemia)
If you have an abnormally low level of magnesium in the blood (hypomagnesaemia)
If you have a history of allergic reactions or suffer from bronchial asthma
If you suffer from Systemic Lupus Erythematosus (long-term inflammation of skin)
If you are taking lithium (see “Other medicines and Co-zidocapt”)
If you are taking any of the following medicines used to treat high blood pressure:
- an angiotensin II receptor blocker (ARBs) (also known as sartans - for example valsartan, telmisartan, irbesartan), 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 Co-zidocapt.
If you experience a decrease in vision or eye pain. These could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or an increase of pressure in your eye and can happen within hours to a week of taking Co-zidocapt. 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.
- 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 Co-zidocapt, seek medical attention immediately. 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 Co-zidocapt”.

You must tell your doctor if you think you are (or might become) pregnant. Co-zidocapt tablets are 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).

If you develop any of the following reactions, see your doctor immediately

swelling of the arms, legs, ankles, face, lips, tongue, and neck /or throat with difficulty swallowing or breathing. This can occur at any time during treatment.
any signs of infection (such as sore throat or fever) that do not respond quickly to usual treatment
dizziness or fainting
severe abdominal pain
unusually fast or irregular heartbeat
jaundice (yellowing eyes/skin)
any sudden, unexplained rash or burning, peeling or red skin

If this is the first time you have taken this medicine you may feel lightheaded or dizzy for a short time, in this case it may help to sit or lie down. However, it is unlikely to occur when you take the tablets regularly. If this situation worries you, consult your doctor.

Other medicines and Co-zidocapt

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including those obtained without prescription. This includes medicines for colds, coughs, allergies or sinusitis as they can increase your blood pressure.

Medicines which may interact or be affected by with Co-zidocapt:

If you are due to have a surgical procedure. You should make sure that the anaesthetist is aware you are taking Co-zidocapt
Clonidine, a medicine used to treat high blood pressure
Medicines used to increase frequency of urination e.g. spironolactone, triamterene, amiloride (Potassium-Sparing Diuretics), Thiazide Diuretics such as bendrofluazide and Loop Diuretics such as torasemide
Potassium-containing supplements or salt substitutes
Medicines used to treat high blood pressure such as propranolol (Beta Blockers), verapamil (Calcium Channel Blockers) and doxazosin (Alpha Blockers)
Medicines used to treat angina and heart failure e.g. nitroglycerine, other nitrates and other Vasodilators (medicines used to widen the blood vessels)
Medicines used to treat depression such as imipramine (Tricyclic Antidepressants)
Medicines used to treat mood disorders e.g. lithium (Anti-Psychotics)
Allopurinol, a medicine used to treat gout
Procainamide, digoxin a medicine used to treat irregular heartbeats (Cardiac Glycosides)
Medicines used to treat cancer such as cyclophosphamide and azathioprine (Cytostatics)
Medicines used to reduce the body’s immunity when receiving organ transplant e.g. ciclosporin sirolimus, everolimus, and other mTOR inhibitor class drugs). See the “Warnings and precautions” section.
(Immunosuppressants)
Medicines used to treat serious allergic reaction (anaphylaxis) such as epinephrine (Adrenaline) (Sympathomimetics)
Medicines used to treat diabetes e.g. insulin, sulphonylurea (Antidiabetics)
Amphotericin B, a medicine used to treat fungal infections
Carbenoxolone, a medicine used to treat inflammation of the gullet and oral ulcers
Medicines used to reduce inflammation such as prednisolone (Corticosteroids)
Corticotropin (AdrenoCorticoTropic Hormone - ACTH)
Medicines used to treat constipation e.g. senna (Stimulant Laxative)
Cholestyramine, Colestipol, medicines used to lower cholesterol. (Co-zidocapt should be taken at least 1 hour before or 4-6 hours after taking these medicines)
Tubocurarine, a muscle relaxant
Medicines known to induce Torsades de Pointes such as erythromycin. This may include some Anti-Arrhythmics such as amiodarone and some Anti-Psychotics such as chlorpromazine
Carbamazepine, a medicine used to treat epileptic seizures
Medicines used to treat certain rheumatic disorders e.g. indomethacin and ibuprofen (Non-Steroidal Anti-Inflammatory Drugs - NSAIDs)
Potassium supplements or salt substitutes containing potassium, diuretics (particularly so-called potassium-sparing), and other Medicines associated with increases in serum potassium e.g. heparin and co-trimoxazole, also called trimethoprim/sulfamethoxazole).
Calcium salts
Medicines that lower blood pressure by widening blood vessels (e.g. minoxidil),

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

If you are taking an angiotensin II receptor blocker (ARB) or aliskiren (see also information under the headings “Do not take Co-zidocapt” and “Warnings and precautions”) Tests
Hydrochlorothiazide (HCT) contained in this medicine could produce a positive analytical result in an anti-doping test
Hydrochlorothiazide (HCT) contained in this medicine may cause diagnostic interference of a Bentiromide Test
Hydrochlorothiazide (HCT) contained in this medicine may affect thyroid tests
Captopril contained in this medicine may cause a false-positive urine test for acetone

Co-zidocapt with food and drink and alcohol

Co-Zidocapt can be administered with or without food, tell your doctor if you take potassium supplements or eat a diet rich in potassium. During treatment with Co-Zidocapt, it is advisable not to drink alcohol.

Pregnancy and breast-feeding

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

Pregnancy

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

Your doctor will normally advise you to stop taking Co-zidocapt before you become pregnant or as soon as you know you are pregnant and will advise you to take another medicine instead of Co-zidocapt. Co-zidocapt 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 are going to

Feeling faint (Syncope)

start breast-feeding. This medicine is not recommended for use during breastfeeding.

Blurred vision
Heart abruptly stops beating (Cardiac Arrest)

Driving and using machines

The blood supply being pumped by the heart muscle needs oxygen (Cardiogenic Shock)

Caution is required when driving or using machines if you notice side effects such as lightheadedness, dizziness or tiredness. This is more likely to occur at the start of treatment, when the dose is changed or if you drink alcohol. Co-zidocapt contains lactose

Shortness of breath or difficulty in breathing (Bronchospasm/Allergic Alveolitis)
Cold-like symptoms: sneezing, itchiness, blocked/runny nose (Rhinitis)

If you have been told by your doctor that you have intolerance to some sugars, contact your doctor before taking this medicine.

Collective symptoms of cough, fever, difficulty breathing, and sweating at night (Eosinophilic Pneumonia)
Inflammation or infection of the tongue (Glossitis)

3. How to take Co-zidocapt

Inflammation of the pancreas that causes stomach pain (Pancreatitis)

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 Yellow Card Scheme at 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. Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

Liver failure or other liver disorders including Jaundice (yellowing of skin and eyes), hepatitis
Skin rashes with the formation of wheals (Urticaria)

Your doctor has prescribed this medicine as previous treatment for high blood pressure did not provide adequate lowering of blood pressure. Your doctor will tell you how to switch from previous treatments to this medicine. Method of administration

Abnormal sensitivity of the skin to sunlight (Photosensitivity)
Skin disorders - redness of the skin (Erythroderma), peeling skin (Exfoliative Dermatitis)
Rash all over the body (Steven Johnson syndrome)
These tablets are to be taken orally as a single dose in the morning.
Allergic rash that causes pink spots with a lighter center on the skin (erythema multiforme),
These tablets should be taken independently of meals and with a generous amount of fluid. It is important that you continue to take this medicine until your doctor advises you otherwise.
A series of reactions in which they can cause fluid-filled blisters (pemphigoid reactions)
Muscle and/or joint pain (Myalgia/Arthralgia)
Protein in the urine (Nephrotic Syndrome/Proteinuria)
The score line is only there to help you break the tablet if you have difficulty swallowing it whole.
Inability to maintain an erection (Impotence)
Excessive development of the male breast (Gynaecomastia)

The recommended dose for adults is:

The usual dose is one tablet daily (corresponding to 50mg captopril and 25mg hydrochlorothiazide). The maximum daily dose of one tablet should not be exceeded. Elderly patients

Fever
Frequent wheezing, breathlessness, stomach pain, diarrhoea, fever, cough and rashes due to an increase in certain white blood cells (Eosinophilia)
Acute respiratory distress (signs include severe shortness of breath, fever, weakness, and confusion).

The dose should be kept as low as possible to achieve adequate blood pressure control. In some patients, Co-zidocapt 25/12.5mg may be sufficient. If you think that the action of this medicine is too strong or weak, talk to your doctor or pharmacist.

Changes in laboratory test results.

Frequency not known (Frequency cannot be estimated from the available data)

Patients with severe kidney problems:

disorder of the blood glucose regulating hormones with pronounced lowering of blood sugar levels (insulin autoimmune syndrome)

If you have moderate kidney impairment, diabetes, or if you have a decrease in salt or water levels in your body, your doctor may prescribe a lower dose of this medicine, for example half a tablet a day (corresponding to 25mg captopril and 12.5mg hydrochlorothiazide).

The following side effects were observed with hydrochlorothiazide, the second active substance in this medicine:

Use in children

Serum sickness (a type of delayed allergic reaction)

Do not give this medicine to children.

Side effects affecting the blood and its components which can cause:

If you take more Co-zidocapt than you should

If you accidentally take too many tablets, contact your doctor or nearest emergency department immediately for advice. Remember to take this leaflet or any remaining tablets with you.

Decrease in functionality
Weariness
Infection
Sore throat or fever due to lack of white blood cells,
Reduced ability of the blood to clot which can cause bleeding or bruising

If you take more than you should you may experience the following: passing water more frequently, a change in the levels of some components in your blood, a large drop in your blood pressure, a reduced awareness of yourself or your surrounding (which includes coma), fits, a weakness in the muscles, an irregular or slower heartbeat or reduced kidney function.

Inflammation of the salivary glands (Sialadentitis)
loss of appetite (anorexia), sugar in the urine, abnormal changes in blood components such as sugar, uric acid (gout), sodium, potassium, high levels of cholesterol and other lipids in the blood,
Restlessness, depression, and sleep disturbances,

If another person has taken too many tablets and has fainted, lie down and raise their feet above their head. If you forget to take Co-zidocapt

Circulatory problems such as inflamed blood vessels including those in the skin and other organs (necrotising angiitis)

Take it as soon as you remember, unless it is nearly time for your next dose.

Lung and breathing problems such as shortness of breath
Gastric irritation, diarrhoea, constipation, pancreatitis,

If you miss a dose, do not take a double dose to make up for a forgotten dose.

Jaundice (yellowing of the skin and eyes),
Severe skin reactions such as:

If you stop taking Co-zidocapt

Sensitivity to light
Eruption

It is important that you keep taking Co-zidocapt for as long as your doctor has told you to. Do not stop taking the tablets even though you may feel better. Do not stop or change your treatment before talking to your doctor. If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

A rash around the nose and cheeks with red butterfly-shaped spots (lupus and lupus-like disorders),
Allergic reactions which cause itching and redness of the skin (hives),
An over-reaction of the body’s natural defences (hypersensitization reactions),

4. Possible side effects

Abnormal condition of the bone marrow in which it is unable to produce normal amounts of red blood cells, white blood cells, and platelets leaving the immune system in a weakened state and vulnerable to infection (Bone Marrow Depression)

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

Stop taking Co-zidocapt and seek medical advice immediately if you develop the following symptoms:

High blood sugar levels (Hyperglycaemia)
Swelling of the arms, legs, ankles, face, lips, tongue and/or throat with difficulty in swallowing or breathing, sore throat or fever,
Glucose in the urine (Glycosuria)
Abnormally high level of uric acid in the blood (Hyperuricaemia)
Severe dizziness or fainting,
Imbalance of fluids in the body. Symptoms include dry mouth, thirst, weakness, tiredness, drowsiness, restlessness, muscle pain, cramps, being/feeling sick (Electrolyte Imbalance)
Severe abdominal pain
Unusually fast or irregular heartbeat
Jaundice (yellowing eyes/skin)
Sudden unexplained skin reactions such as rash, burning, peeling or red skin.
Increased level of fats (cholesterol and triglyceride) in your blood

Below you will find side effects ranked in order of decreasing severity that were observed with captopril and/or other ACE inhibitors, in addition to the side effects observed with hydrochlorothiazide.

Restlessness
Eye disorders including objects appear yellow (Xanthopsia), near-sightedness in vision (Acute Myopia), sudden eye pain, red eyes and reduced vision caused by pressure inside the eye rising quickly (Acute Angle-Closure Glaucoma)

Common Side Effects (may affect up to at least 1 in 100 patients and less than 1 in 10 patients)

with captopril as well as other ACE inhibitors:

Feeling of dizziness or “spinning” (Vertigo)
Sleep disorders
Low blood pressure which may cause dizziness, tingling, light-headedness or fainting on standing up (Postural Hypotension), heart problems such as irregular pulse, circulation problems,
Taste impairment, dizziness, dry, irritating (non-productive) cough, breathing problems,
Nausea, vomiting, gastric irritations, abdominal pain, diarrhoea, constipation, dry mouth, peptic ulcer,
Inflammation of the blood vessels often with skin rash (Vasculitis)
Skin problems such as itchiness and rash, hair loss. Uncommon Side Effects (may affect at least 1 in 1,000 patients and less than 1 in 100 patients)
Muscle spasm
kidney problems,
Skin rash resulting from bleeding into the skin (Purpura)