Captor-HCT 50mg/25mg Tablets

Ireland - English - HPRA (Health Products Regulatory Authority)

Buy It Now

Active ingredient:
Captopril; Hydrochlorothiazide
Available from:
Rowex Ltd
ATC code:
C09BA; C09BA01
INN (International Name):
Captopril; Hydrochlorothiazide
Dosage:
50/25mg milligram(s)
Pharmaceutical form:
Tablet
Prescription type:
Product subject to prescription which may be renewed (B)
Therapeutic area:
ACE inhibitors and diuretics; captopril and diuretics
Authorization status:
Not marketed
Authorization number:
PA0711/025/003
Authorization date:
1998-10-16

Package leaflet: Information for the user

Captor-HCT 25mg/12.5mg & 50mg/25mg Tablets

captopril & hydrochlorothiazide

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 Captor-HCT is and what it is used for

2. What you need to know before you take Captor-HCT

3. How to take Captor-HCT

4. Possible side effects

5. How to store Captor-HCT

6. Contents of the pack and other information

1 What Captor-HCT is and what it is used for

Captor-HCT is used to treat:

high blood pressure

This medication is made up of two different active substances: captopril and hydrochlorothiazide.

Captopril belongs to the ACE inhibitors medicine group (angiotensin-converting enzyme inhibitors).

Captopril expands your blood vessels. This reduces your blood pressure and makes it easier for your

heart to pump blood to all body parts.

Hydrochlorothiazide is a water pill (diuretic). It increases the amount of salt and water you lose in

your urine. This also results in a fall in blood pressure.

2 What you need to know before you take Captor-HCT

Do not take Captor-HCT:

if you are allergic to

- captopril, hydrochlorothiazide or

- any of the other ingredients of this medicine (listed in section 6) or

- other ACE inhibitors or to any other sulphonamide derivatives

if during earlier ACE inhibitor use you had swelling of the face, lips, tongue and/or throat with

difficulty swallowing or breathing

Do not take Captor-HCT if you had any of these reactions

- without a known cause or

- if it has been confirmed that you have a hereditary or

- other form of fluid accumulation (angioedema)

if you have severely reduced kidney function

if you have severely reduced liver function

if you have diabetes or impaired kidney function and you are treated with a blood pressure lowering

medicine containing aliskiren

if you are more than 3 months pregnant. (It is also better to avoid Captor-HCT in early pregnancy

– see pregnancy section).

if you have taken or are currently taking sacubitril/valsartan, a medicine used to treat a type of long-

term (chronic) heart failure in adults, as the risk of angioedema (rapid swelling under the skin in an

area such as the throat) is increased.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before taking Captor-HCT if you:

suffer from dehydration due to treatment with ‘water tablets’ (diuretics), dialysis, a low salt diet,

vomiting or diarrhoea. After starting medication, a large drop in blood pressure may frequently

occur and feeling faint or light-headed.

suffer from heart disorders such as heart failure, narrowing of the aortic or mitral valves (aortic or

mitral stenosis) or an increase in the thickness of the heart muscle (hypertrophic cardiomyopathy or

‘HOCM’) or if you have a condition involving the blood vessels in the brain

have kidney problems

are undergoing dialysis treatment

- with high flux membranes

- blood separation treatment to remove cholesterol from your blood by machine with dextran sulphate

desensitisation treatment to reduce the effects of an allergy to a bee or wasp sting.

In these cases tell your doctor that you are taking Captor-HCT. He/She may wish to interrupt your

treatment to prevent a possible allergic reaction.

have liver problems. If you develop jaundice during use of Captor-HCT stop taking it and consult

your doctor.

have blood vessel disease, known as collagen vascular disease

black people of afro-Caribbean origin have a higher risk of the effect of Captor-HCT being

reduced

have a cough inform your doctor if this becomes worse

have symptoms of intestinal angiodema such as abdominal pain, nausea, vomiting and bloating

have systemic lupus erythematosus

are undergoing an operation with a general anaesthetic, inform your doctor about Captor-

are taking other medicines, such as potassium supplements, lithium (for mental disorders) or

medicines against diabetes

are taking any of the following medicines, the risk of angioedema may be increased:

- racecadotril, a medicine used to treat diarrhoea;

- medicines used to prevent organ transplant rejection and for cancer (e.g., temsirolimus,

sirolimus, everolimus).

- vildagliptin, a medicine used to treat diabetes.

are taking any of the following medicines used to treat high blood pressure:

- an angiotensin II receptor blocker (ARB) (also known as sartans - for example valsartan,

telmisartan, irbesartan), in particular if you have diabetes-related kidney problems

- aliskiren.

In particular, talk to your doctor or pharmacist if you are taking, have recently taken or might take

any of the following medicines:

potassium supplements (including salt substitutes), potassium-sparing diuretics and other

medicines that can increase the amount of potassium in your blood (e.g. trimethoprim and co-

trimoxazole for infections caused by bacteria; ciclosporin, an immunosuppressant medicine used to

prevent organ transplant rejection; and heparin, a medicine used to thin blood to prevent clots)

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 Captor-HCT’.

if you experience an infection with symptoms such as fever and serious deterioration of your

general condition, or fever with local infection symptoms such as sore throat/pharynx/mouth or

urinary problems you should see your doctor immediately.

if you have changes in your vision or pain in one or both of your eyes while taking this medicine.

This could be a sign that you are developing glaucoma, increased pressure in your eye(s). You

should discontinue this medicine and seek medical attention.

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 Captor-HCT.

You must tell your doctor if you think you are (or might become) pregnant. Captor-HCT 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).

While taking this medicine you should be aware of the following:

If you have to undergo an anti-doping test hydrochlorothiazide can produce a positive result

If you undergo a so called bentiromide test for your thyroid gland, hydrochlorothiazide can produce

a false result.

If you are unsure if any of the above apply to you, please discuss this with your doctor.

Other medicines and Captor-HCT

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

medicines, including medicines obtained without a prescription.

This applies in particular if you are also taking:

diuretics (‘water tablets’) which are used to treat high blood pressure including potassium-sparing

diuretics such as spironolactone, triamterene or amiloride

other medicines used to treat high blood pressure

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 Captor-HCT’ and ‘Warnings and precautions’)

medicines to treat arthritis or muscle pain, such as ibuprofen or indomethacin

medicines for mental disorders or depressions such as

- lithium

- medicines to treat psychoses

- tricyclic antidepressants, such as amitriptyline

medicines which are most often used to avoid rejection of transplanted organs (sirolimus,

temsirolimus, everolimus and other medicines belonging to the class of mTOR inhibitors).

See section ‘Warnings and precautions’.

potassium supplements or salt substitutes containing potassium, diuretics (water tablets, in

particular those so called potassium sparing), other drugs which can increase potassium in your

body (such as heparin, ciclosporin and co-trimoxazole also known as

trimethoprim/sulfamethoxazole)

blood sugar lowering medicines, such as insulin or those taken orally.

The antidiabetic medicine dose may need adjusting.

central nervous system stimulative medicines, such as

- ephedrine or pseudoephedrine, which could be included in decongestants or cough/cold remedies

- salbutamol, a medicine for treating asthma

m

edicines to suppress the body’s immune

system

allopurinol, a medicine to treat gout

procainamide, used to treat abnormal heartbeats

medicines used in cancer (cytostatics)

medicines against high cholesterol (colestyramine, colestipol resins). These medicines should be

taken 1 hour before or 4-6 hours after Captor-HCT.

amphotericin B (medicine for fungal infections)

carbenoxolone (medicine for gastrointestinal diseases)

corticosteroids (anti-inflammatory hormone

–like substances from the adrenal gland)

ACTH (to test whether your adrenal glands are working properly)

medicines to promote defaecation (laxatives)

the concentration of calcium in the blood can be increased by calcium salts

medicines that promote the pumping power of the heart (cardiac glycosides)

tubocurarine chloride, muscle-relaxants that are used in operations

drugs associated with torsades de pointes

carbamazepine (medicine to treat seizures)

sacubitril/valsartan, a medicine used to treat a type of long-term (chronic) heart failure in adults

(see section 2 ‘Do not take Captor-HCT’)

vildagliptin, a medicine used to treat diabetes

racecadotril, a medicine used to treat diarrhoea.

Pregnancy and breast-feeding

Pregnancy

You must tell your doctor if you think you are (or might become) pregnant. Your doctor will normally

advise you to stop taking Captor-HCT before you become pregnant or as soon as you know you are

pregnant and will advise you to take another medicine instead of Captor-HCT. Captor-HCT 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 used after the third month of pregnancy.

Breast-feeding

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

Captor-HCT is not recommended for mothers who are breast-feeding.

Ask your doctor or pharmacist for advice before taking any medicines.

Driving and using machines

Captor-HCT can affect your ability to drive, usually when you first start taking your medicine, if your

doctor changes your dose or in combination with alcohol. If you feel light-headed or dizzy, you

should not drive or operate machinery.

Captor-HCT contains lactose monohydrate.

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor

before taking this medicinal product.

3 How to take Captor-HCT

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist

if you are not sure.

Take the tablets before, during or after meals with a glass of water.

The tablets can be divided into equal halves.

The recommended dose is:

Adults

The usual dosage is 50mg/25mg once a day in the morning. The maximum daily dose is 50mg

/25mg.

Diabetic patients

The usual starting dose is 25mg/12.5mg once a day.

Patients with reduced kidney function

If you suffer from a kidney disorder your doctor may reduce the dose. Captor-HCT should not be

used if you have severely impaired kidney function.

Elderly

The usual starting dose is 25mg/12.5mg once a day.

Children

Not recommended.

If you take more Captor-HCT than you should

Contact your doctor or the nearest hospital casualty department immediately.

Take this leaflet or some tablets with you so that people will know what you have taken.

If you forget to take Captor-HCT

Take the missed dose as soon as you remember but never take two doses in one day.

If you stop taking Captor-HCT

Do not stop treatment before talking to your doctor, as this will reduce the treatment’s effect.

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

4

Possible side effects

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

Allergic reaction signs and symptoms are:

difficulties in breathing

swelling of the face, hands, feet, lips, tongue and/or throat

severe skin itch with raised lumps.

Stop taking Captor-HCT and seek medical advice immediately, if you develop any of the allergic

reaction signs.

Other possible side effects of captopril:

Common: may affect up to 1 in 10 people

sleep problems

taste abnormalities

dizziness

dry, irritating cough

shortness of breath

feeling sick (nausea)

vomiting

upset stomach

abdominal pain

diarrhoea

constipation

dry mouth

peptic ulcer

itching

rash

hair loss.

Uncommon: may affect up to 1 in 100 people

headache

the sensation of pins and needles

loss of appetite

increased heart rate

angina

heart palpitations

low blood pressure

numbness or tingling in the fingers and toes

flushing

looking pale

swelling of the eyes and lips (angioedema)

chest pain

tiredness

general weakness.

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

drowsiness

mouth ulcers

kidney disorders or failure

changes in frequency of passing urine

symptoms of intestinal angiodema such as abdominal pain, nausea, vomiting and bloating.

Very Rare: may affect up to 1 in 10,000 people

deficiency of red blood cells with signs such as looking pale or feeling tired

unexpected bruising

blood abnormality and abnormalities of the lymph glands

high levels of potassium in the blood

low blood sugar levels

confusion

depression

cerebrovascular incidents, including stroke, cerebrovascular insufficiency and lapse of

consciousness

blurred vision

heart problems, including heart attack

difficulty in breathing, stuffy nose, certain forms of pneumonia

swollen tongue

inflammation of the pancreas

impaired liver function and raised liver enzymes

liver damage, inflammation of the liver or jaundice (yellowing of the skin and/or the whites of the

eyes)

severe skin disorders including Stevens-Johnson syndrome

sensitivity of the skin to light

muscle pain

joint pain

an abnormal condition of the kidney known as nephrotic syndrome

inability to maintain an erection (impotence)

enlargement of one or both breasts in men

fever

proteinuria

eosinophilia

increase of serum potassium

decrease of serum sodium

elevation of BUN, serum creatinine and serum bilirubin

decreases in haemoglobin, haematocrit, leucocytes, thrombocytes

positive ANA titre

elevated ESR.

Other possible side effects of hydrochlorothiazide:

inflammation of a salivary gland

blood abnormality

high blood levels of: sugar, uric acid (as in the case of gout), cholesterol, triglycerides

low blood level of potassium which can cause muscle weakness, twitching or abnormal heart rhythm

low blood levels of sodium which can cause tiredness and confusion, muscle twitching, fits or coma

restlessness

depression

sleep disturbances

temporary blurred vision and visual changes which can make a colourless object look tinged with

yellow, near sightedness, glaucoma (increased eye pressure)

vertigo

dizziness and fainting on standing up, irregular heart beat

loss of appetite

the sensation of pins and needles

feeling of light-headedness

inflammation of blood vessels, often with skin rash

difficulty breathing, wheezing caused by inflammation of the lungs, fluid in the lungs

gastric irritation, diarrhoea, constipation

inflammation of the pancreas

jaundice (yellowing of the skin and/or the whites of the eyes)

hypersensitivity to light, rash, hives, a skin condition with red scaly patches over the nose and

cheeks (lupus erythematosus) this condition may be worsened in patients who already have it, a skin

disease known as toxic epidermal necrolysis

muscle spasm

kidney problems

fever

weakness.

Frequency ‘not known’

skin and lip cancer (Non-melanoma skin cancer)

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 Captor-HCT

Do not store above 25°C.

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 blister and on the carton after

‘Exp’. The expiry date refers to the last day of that month.

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 to protect the environment.

6 Contents of the pack and other information

What Captor-HCT contains

The active substances are captopril and hydrochlorothiazide.

One Captor-HCT 25mg/12.5mg tablet contains 25mg captopril and 12.5mg hydrochlorothiazide.

One Captor-HCT 50mg/25mg tablet contains 50mg captopril and 25mg hydrochlorothiazide.

The other ingredients are microcrystalline cellulose, lactose monohydrate, pregelatinised maize

starch, stearic acid and magnesium stearate.

What Captor-HCT looks like and contents of the pack

Captor-HCT 25mg/12.5mg is a white, round tablet with a score notch on one side. The opposite

convex side is engraved with ‘Cc’. It is available in the following pack size: 30 tablets.

Captor-HCT 50mg/25mg is a white, octagonal tablet with a crossed score notch on one side. The

opposite convex side is engraved with ‘Cc’. It is available in the following pack size: 30 tablets.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Rowex Ltd., Bantry, Co. Cork, Ireland.

Manufacturers:

Salutas Pharma GmbH, Otto-von-Guericke Allee 1, 39179 Barleben, Germany.

Rowa Pharmaceuticals Ltd., Bantry, Co. Cork, Ireland.

This leaflet was last approved 06/2019

Health Products Regulatory Authority

24 November 2019

CRN008X7G

Page 1 of 14

Summary of Product Characteristics

1 NAME OF THE MEDICINAL PRODUCT

Captor-HCT 50mg/25mg Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains captopril 50 mg and hydrochlorothiazide 25 mg.

Excipient(s) with known effect: contains lactose monohydrate 68.7mg

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Tablet.

White octagonal tablets with a one-sided crossed score notch and the opposite convex side has the mark ‘Cc’ engraved on it.

The score-notch allows the tablet to be divided into equal halves or quarters.

4 CLINICAL PARTICULARS

4.1 Therapeutic Indications

Treatment of essential hypertension. This fixed dose combination is indicated in patients whose blood pressure is not

adequately controlled by captopril alone or hydrochlorothiazide alone.

4.2 Posology and method of administration

CAPTOR-HCT can be administered in a single or two divided doses/day with or without food in patients whose blood pressure

is not adequately controlled by captopril alone or hydrochlorothiazide alone. A maximum daily dose of 50 mg captopril/25 mg

hydrochlorothiazide should not be exceeded. If satisfactory reduction of blood pressure has not been achieved, additional

antihypertensive medication may be added (see sections 4.3, 4.4, 4.5 and 5.1).

Adults: the administration of the fixed combination of captopril and hydrochlorothiazide is usually recommended after dosage

titration with the individual components. The usual maintenance dose is 50/25 mg, once a day, in the morning. When clinically

appropriate a direct change from monotherapy to the fixed combination may be considered.

Renal impairment: Creatinine clearance between 30 and 80 mL/min: the initial dose is usually 25/12.5 mg once a day, in the

morning.

The combination captopril/hydrochlorothiazide is contraindicated in patients with severe renal impairment (creatinine

clearance <30 mL/min).

Special populations: in salt/volume depleted patients, elderly patients, and diabetic patients, the usual starting dose is 25/12.5

mg once a day.

Paediatric population: There is no relevant indication for use of CAPTOR-HCT in children.

Health Products Regulatory Authority

24 November 2019

CRN008X7G

Page 2 of 14

4.3 Contraindications

-Hypersensitivity to the active substances or to any of the excipients listed in section 6.1 or to any other ACE inhibitor or to any

other sulphonamide-derived drugs.

- History of angioedema associated with previous ACE inhibitor therapy.

- Hereditary/idiopathic angioneurotic oedema.

- Severe renal impairment (creatinine clearance <30 mL/min).

- Severe hepatic impairment

- Second and third trimester of pregnancy (see sections 4.4 and 4.6).

- The concomitant use of Captor-HCT with aliskiren-containing products is contraindicated in patients with diabetes mellitus or

renal impairment (GFR < 60 mL/min/1.73 m

) (see sections 4.5 and 5.1).

- Concomitant use with sacubitril/valsartan therapy. Captor-HCT must not be initiated earlier than 36 hours after the last dose

of sacubitril/valsartan (see also sections 4.4 and 4.5).

4.4 Special warnings and precautions for use

CAPTOPRIL

Hypotension: rarely hypotension is observed in uncomplicated hypertensive patients. Symptomatic hypotension is more likely

to occur in hypertensive patients who are volume and/or sodium depleted by vigorous diuretic therapy, dietary salt restriction,

diarrhoea, vomiting, or haemodialysis. Volume and/or sodium depletion should be corrected before the administration of an

ACE inhibitor and a lower starting dose should be considered. As with any antihypertensive agent, excessive blood pressure

lowering in patients with ischaemic cardiovascular or cerebrovascular disease may increase the risk of myocardial infarction or

stroke. If hypotension develops, the patient should be placed in a supine position.

Volume repletion with intravenous normal saline may be required.

Renovascular hypertension: there is an increased risk of hypotension and renal insufficiency when patients with bilateral renal

artery stenosis or stenosis of the artery to a single functioning kidney are treated with ACE inhibitors. Loss of renal function

may occur with only mild changes in serum creatinine. In these patients, therapy should be initiated under close medical

supervision with low doses, careful titration, and monitoring of renal function.

Hypersensitivity/angioedema:

Concomitant use of ACE inhibitors with sacubitril/valsartan is contraindicated due to the increased risk of angioedema.

Treatment with sacubitril/valsartan must not be initiated earlier than 36 hours after the last dose of captopril. Treatment with

captopril must not be initiated earlier than 36 hours after the last dose of sacubitril/valsartan (see sections 4.3 and 4.5).

Concomitant use of ACE inhibitors with racecadotril, mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus) and vildagliptin

may lead to an increased risk of angioedema (e.g. swelling of the airways or tongue, with or without respiratory impairment)

(see section 4.5). Caution should be used when starting racecadotril, mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus)

and vildagliptin in a patient already taking an ACE inhibitor.

Angioedema

Angioneurotic oedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported in patients treated with

angiotensin converting enzyme inhibitors, including captopril. This may occur at any time during treatment. In such cases,

captopril should be discontinued promptly and appropriate monitoring should be instituted to ensure complete resolution of

symptoms prior to dismissing the patient. In those instances where swelling has been confined to the face and lips the

condition generally resolved without treatment, although antihistamines have been useful in relieving symptoms.

Angioneurotic oedema associated with laryngeal oedema may be fatal. Where there is involvement of the tongue, glottis or

larynx, likely to cause airway obstruction, appropriate therapy, which may include subcutaneous epinephrine solution 1:1000

(0.3mL to 0.5mL) and/or measures to ensure a patent airway, should be administered promptly.

Black patients receiving ACE inhibitors have been reported to have a higher incidence of angiodema compared to non- blacks.

Patients with a history of angiodema unrelated to ACE inhibitor therapy may be at increased risk of angiodema while receiving

an ACE inhibitor (see section 4.3 Contraindications).

Health Products Regulatory Authority

24 November 2019

CRN008X7G

Page 3 of 14

Intestinal angiodema has been reported rarely in patients treated with ACE inhibitors. These patients presented with abdominal

pain (with or without nausea or vomiting); in some cases there was no prior facial angioedema and C-1 esterase levels were

normal.

The angioedema was diagnosed by procedures including abdominal CT scan, or ultrasound or at surgery and symptoms

resolved after stopping the ACE inhibitor. Intestinal angiodema should be included in the differential diagnosis of patients on

ACE inhibitors presenting with abdominal pain. (See section 4.8).

Concomitant use of mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus): patients taking concomitant mTOR inhibitors

(e.g. sirolimus, everolimus, temsirolimus) therapy may be at increased risk for angioedema (e.g. swelling of the airways or

tongue, with or without respiratory impairment) (see section 4.5).

Cough: cough has been reported with the use of ACE inhibitors. Characteristically, the cough is non-productive, persistent and

resolves after discontinuation of therapy.

Hepatic failure: rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and

progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not understood. Patients

receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor

and receive appropriate medical follow-up.

Hyperkalaemia:

ACE inhibitors can cause hyperkalemia because they inhibit the release of aldosterone. The effect is usually not significant in

patients with normal renal function. However, in patients with impaired renal function and/or in patients taking potassium

supplements (including salt substitutes), potassium-sparing diuretics, trimethoprim or co-trimoxazole also known as

trimethoprim/sulfamethoxazole and especially aldosterone antagonists or angiotensin-receptor blockers, hyperkalemia can

occur. Potassium-sparing diuretics and angiotensin-receptor blockers should be used with caution in patients receiving ACE

inhibitors, and serum potassium and renal function should be monitored (see section 4.5).

Aortic and mitral valve stenosis/obstructive hypertrophic cardiomyopathy/cardiogenic shock: ACE inhibitors should be used

with caution in patients with left ventricular valvular and outflow tract obstruction and avoided in cases of cardiogenic shock

and haemodynamically significant obstruction.

Neutropenia/agranulocytosis: neutropenia/agranulocytosis, thrombocytopenia and anaemia have been reported in patients

receiving ACE inhibitors, including captopril. In patients with normal renal function and no other complicating factors,

neutropenia occurs rarely. Captopril should be used with extreme caution in patients with collagen vascular disease,

immunosuppressant therapy, treatment with allopurinol or procainamide, or a combination of these complicating factors,

especially if there is pre-existing impaired renal function. Some of these patients developed serious infections which in a few

instances did not respond to intensive antibiotic therapy. If captopril is used in such patients, it is advised that white blood cell

count and differential counts should be performed prior to therapy, every 2 weeks during the first 3 months of captopril

therapy, and periodically thereafter. During treatment all patients should be instructed to report any sign of infection (e.g. sore

throat, fever) when a differential white blood cell count should be performed. Captopril and other concomitant medication (see

section 4.5) should be withdrawn if neutropenia (neutrophils less than 1000/mm

) is detected or suspected.

In most patients neutrophil counts rapidly return to normal upon discontinuing captopril.

Proteinuria: proteinuria may occur particularly in patients with existing renal function impairment or on relatively high doses

of ACE inhibitors. Total urinary proteins greater than 1 g per day were seen in about 0.7% of patients receiving captopril. The

majority of patients had evidence of prior renal disease or had received relatively high doses of captopril (in excess of 150

mg/day), or both. Nephrotic syndrome occurred in about one-fifth of proteinuric patients. In most cases, proteinuria subsided

or cleared within six months whether or not captopril was continued. Parameters of renal function, such as BUN and creatinine,

were seldom altered in the patients with proteinuria. Patients with prior renal disease should have urinary protein estimations

(dip-stick on first morning urine) prior to treatment, and periodically thereafter.

Anaphylactoid reactions during desensitisation: sustained life-threatening anaphylactoid reactions have been rarely

reported for patients undergoing desensitising treatment with hymenoptera venom while receiving another ACE inhibitor. In

the same patients, these reactions were avoided when the ACE inhibitor was temporarily withheld, but they reappeared upon

inadvertent rechallenge. Therefore, caution should be used in patients treated with ACE inhibitors undergoing such

desensitisation procedures. Anaphylactoid reactions during high-flux dialysis/lipoprotein apheresis membrane exposure:

anaphylactoid reactions have been reported in patients haemodialysed with high-flux dialysis membranes or undergoing

Health Products Regulatory Authority

24 November 2019

CRN008X7G

Page 4 of 14

low-density lipoprotein apheresis with dextran sulphate absorption. In these patients, consideration should be given to using a

different type of dialysis membrane or a different class of medication.

Surgery/anaesthesia: hypotension may occur in patients undergoing major surgery or during treatment with anaesthetic

agents that are known to lower blood pressure. If hypotension occurs, it may be corrected by volume expansion.

Diabetic patients: the glycaemia levels should be closely monitored in diabetic patients previously treated with oral

antidiabetic drugs or insulin, namely during the first month of treatment with an ACE inhibitor.

As with other angiotensin converting enzyme inhibitors, CAPTOR-HCT is apparently less effective in lowering blood pressure in

black people than in non-blacks, possibly because of higher prevalence of low-renin states in the black hypertensive

population.

Dual blockade of the renin-angiotensin-aldosterone system (RAAS)

There is evidence that the concomitant use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of

hypotension, hyperkalaemia and decreased renal function (including acute renal failure). Dual blockade of RAAS through the

combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is therefore not recommended (see sections 4.5

and 5.1).

If dual blockade therapy is considered absolutely necessary, this should only occur under specialist supervision and subject to

frequent close monitoring of renal function, electrolytes and blood pressure.

ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.

HYDROCHLOROTHIAZIDE

Renal impairment: in patients with renal disease, thiazides may precipitate azotaemia. Cumulative effects of the drug may

develop in patients with impaired renal function. If progressive renal impairment becomes evident, as indicated by a rising

non-protein nitrogen, careful reappraisal of therapy is necessary, with consideration given to discontinuing diuretic therapy

(see section 4.3).

Hepatic impairment: thiazides should be used with caution in patients with impaired hepatic function or progressive liver

disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma (see section 4.3).

Metabolic and endocrine effects: thiazide therapy may impair glucose tolerance. In diabetic patients dosage adjustments of

insulin or oral hypoglycaemic agents may be required. Latent diabetes mellitus may become manifest during thiazide therapy.

Increases in cholesterol and triglyceride levels have been associated with thiazide diuretic therapy.

Hyperuricaemia may occur or frank gout may be precipitated in certain patients receiving thiazide therapy.

Electrolyte imbalance: as for any patient receiving diuretic therapy, periodic determination of serum electrolytes should be

performed at appropriate intervals. Thiazides, including hydrochlorothiazide, can cause fluid or electrolyte imbalance

(hypokalaemia, hyponatraemia, and hypochloraemic alkalosis). Warning signs of fluid or electrolyte imbalance are dryness of

mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pain or cramps, muscular fatigue, hypotension, oliguria,

tachycardia, and gastrointestinal disturbances such as nausea or vomiting.

Although hypokalaemia may develop with the use of thiazide diuretics, concurrent therapy with captopril may reduce

diuretic-induced hypokalaemia. The risk of hypokalaemia is greatest in patients with cirrhosis of the liver, in patients

experiencing brisk diuresis, in patients who are receiving inadequate oral intake of electrolytes and in patients receiving

concomitant therapy with corticosteroids or ACTH (see section 4.5).

Dilutional hyponatraemia may occur in oedematous patients in hot weather. Chloride deficit is generally mild and usually does

not require treatment. Thiazides may decrease urinary calcium excretion and cause an intermittent and slight elevation of

serum calcium in the absence of known disorders of calcium metabolism. Marked hypercalcaemia may be evidence of hidden

hyperparathyroidism. Thiazides should be discontinued before carrying out tests for parathyroid function. Thiazides have been

shown to increase the urinary excretion of magnesium, which may result in hypomagnesaemia.

Acute myopia and secondary angle-closure glaucoma: Sulfonamide medicinal products or sulfonamide derivative medicinal

products can cause an idiosyncratic reaction, resulting in transient myopia and acute angle-closure glaucoma. While

hydrochlorothiazide is a sulfonamide, only isolated cases of acute angle-closure glaucoma without definite causal association

have been reported so far with hydrochlorothiazide.

Health Products Regulatory Authority

24 November 2019

CRN008X7G

Page 5 of 14

Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of medicinal

product initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss.

The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. Prompt medical or surgical treatment may

need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure

glaucoma may include a history of sulfonamides or penicillin allergy.

Anti-doping test: hydrochlorothiazide contained in this medication could produce a positive analytic result in an anti- doping

test.

Non-melanoma skin cancer

An increased risk of non-melanoma skin cancer (NMSC) [basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)] with

increasing cumulative dose of hydrochlorothiazide (HCTZ) exposure has been observed in two epidemiological studies based

on the Danish National Cancer Registry. Photosensitizing actions of HCTZ could act as a possible mechanism for NMSC.

Patients taking HCTZ should be informed of the risk of NMSC and advised to regularly check their skin for any new lesions and

promptly report any suspicious skin lesions. Possible preventive measures such as limited exposure to sunlight and UV rays and,

in case of exposure, adequate protection should be advised to the patients in order to minimize the risk of skin cancer.

Suspicious skin lesions should be promptly examined potentially including histological examinations of biopsies. The use of

HCTZ may also need to be reconsidered in patients who have experienced previous NMSC (see also section 4.8).

Other: sensitivity reactions may occur in patients with or without a history of allergy or bronchial asthma. The possibility of

exacerbation or activation of systemic lupus erythematosus has been reported.

CAPTOPRIL/HYDROCHLOROTHIAZIDE COMBINATION

Pregnancy: ACE inhibitors should not be initiated during pregnancy. Unless continued ACE inhibitor therapy is considered

essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established

safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors should be stopped

immediately, and, if appropriate, alternative therapy should be started (see section 4.3 and 4.6).

Risk of hypokalaemia: the combination of an ACE inhibitor with a thiazide diuretic does not rule out the occurrence of

hypokalaemia. Regular monitoring of kalaemia should be performed.

Combination with lithium: CAPTOR-HCT is not recommended in association with lithium due to the potentiation of lithium

toxicity (see section 4.5).

Lactose: Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose

malabsorption should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interactions

CAPTOPRIL

Potassium sparing diuretics, potassium supplements or potassium-containing salt substitutes

Although serum potassium usually remains within normal limits, hyperkalaemia may occur in some patients treated with

captopril. Potassium sparing diuretics (e.g. spironolactone, triamterene, or amiloride), potassium supplements, or

potassium-containing salt substitutes may lead to significant increases in serum potassium. Care should also be taken when

captopril is co-administered with other agents that increase serum potassium, such as trimethoprim and cotrimoxazole

(trimethoprim/sulfamethoxazole) as trimethoprim is known to act as a potassium-sparing diuretic like amiloride. Therefore, the

combination of captopril with the above-mentioned drugs is not recommended. If concomitant use is indicated, they should be

used with caution and with frequent monitoring of serum potassium.

Diuretics (thiazide or loop diuretics): prior treatment with high dose diuretics may result in volume depletion and a risk of

hypotension when initiating therapy with captopril (see section 4.4). The hypotensive effects can be reduced by discontinuation

of the diuretic, by increasing volume or salt intake or by initiating therapy with a low dose of captopril. However, no clinically

significant drug interactions have been found in specific studies with hydrochlorothiazide or furosemide.

Health Products Regulatory Authority

24 November 2019

CRN008X7G

Page 6 of 14

Other antihypertensive agents: captopril has been safely co-administered with other commonly used antihypertensive agents

(e.g. beta-blockers and long-acting calcium channel blockers). Concomitant use of these agents may increase the hypotensive

effects of captopril. Treatment with nitroglycerine and other nitrates, or other vasodilators, should be used with caution.

Alpha blocking agents: Concomitant use of alpha blocking agents may increase the antihypertensive effects of captopril and

increase the risk of orthostatic hypotension.

Treatments of acute myocardial infarction: captopril may be used concomitantly with acetylsalicylic acid (at cardiologic

doses), thrombolytics, beta-blockers and/or nitrates in patients with myocardial infarction.

Tricyclic antidepressants/antipsychotics: ACE inhibitors may enhance the hypotensive effects of certain tricyclic

antidepressants and antipsychotics (see section 4.4). Postural hypotension may occur.

Allopurinol, procainamide, cytostatic or immunosuppressive agents: concomitant administration with ACE inhibitors may

lead to an increased risk for leucopenia especially when the latter are used at higher than currently recommended doses.

Medicinesincreasing the risk of angioedema

Concomitant use of ACE inhibitors with sacubitril/valsartan is contraindicated as this increases the risk of angioedema (see

section 4.3 and 4.4).

Concomitant use of ACE inhibitors with racecadotril, mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus) and vildagliptin

may lead to an increased risk for angioedema (see section 4.4).

Sympathomimetics: may reduce the antihypertensive effects of ACE inhibitors; patients should be carefully monitored.

Sympathomimetics: may reduce the antihypertensive effects of ACE inhibitors; patients should be carefully monitored.

Antidiabetics: pharmacological studies have shown that ACE inhibitors, including captopril, can potentiate the blood

glucose-reducing effects of insulin and oral antidiabetics such as sulphonylurea in diabetics. Should this very rare interaction

occur, it may be necessary to reduce the dose of the antidiabetic during simultaneous treatment with ACE inhibitors.

Dual blockade of the renin-angiotensin-aldosterone system (RAAS) with ACE-inhibitors, angiotensin II receptor

blockers or aliskiren

Clinical trial data has shown that dual blockade of the renin-angiotensin-aldosterone-system (RAAS) through the combined use

of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher frequency of adverse events such as

hypotension, hyperkalaemia and decreased renal function (including acute renal failure) compared to the use of a single

RAAS-acting agent (see sections 4.3, 4.4 and 5.1).

Ciclosporin

Hyperkalaemia may occur during concomitant use of ACE inhibitors with ciclosporin. Monitoring of serum potassium is

recommended.

Heparin

Hyperkalaemia may occur during concomitant use of ACE inhibitors with heparin. Monitoring of serum potassium is

recommended.

HYDROCHLOROTHIAZIDE

Amphotericin B (parenteral), carbenoxolone, corticosteroids, corticotropin (ACTH) or stimulant laxatives:

hydrochlorothiazide may intensify electrolyte imbalance, particularly hypokalaemia.

Calcium salts: increased serum calcium levels due to decreased excretion may occur when administered concurrently with

thiazide diuretics.

Cardiac glycosides: enhanced possibility of digitalis toxicity associated with thiazide induced hypokalaemia.

Colestyramine resin and colestipol: may delay or decrease absorption of hydrochlorothiazide. Sulphonamide diuretics should

be taken at least one hour before or four to six hours after these medications.

Health Products Regulatory Authority

24 November 2019

CRN008X7G

Page 7 of 14

Nondepolarising muscle relaxants (e.g. tubocurarine chloride): effects of these agents may be potentiated by

hydrochlorothiazide.

Drugs associated with torsades de pointes: because of the risk of hypokalaemia, caution should be used when

hydrochlorothiazide is coadministered with drugs associated with torsades de pointes, e.g. some antiarrhythmics, some

antipsychotics and other drugs known to induce torsades de pointes.

Carbamazepine: concomitant use of carbamazepine and hydrochlorothiazide has been associated with the risk of

symptomatic hyponatraemia. Electrolytes should be monitored during concomitant use. If possible, another class of diuretics

should be used.

CAPTOPRIL/HYDROCHLOROTHIAZIDE COMBINATION

Lithium: reversible increases in serum lithium concentrations and toxicity have been reported during concomitant

administration of lithium with ACE inhibitors. Concomitant use of thiazide diuretics may increase the risk of lithium toxicity and

enhance the already increased risk of lithium toxicity with ACE inhibitors. The combination of captopril and hydrochlorothiazide

with lithium is therefore not recommended and careful monitoring of serum lithium levels should be performed if the

combination proves necessary.

Non-steroidal anti-inflammatory medicinal products: it has been described that non-steroidal anti-inflammatory medicinal

products (NSAIDs) and ACE inhibitors exert an additive effect on the increase in serum potassium, whereas renal function may

decrease.

These effects are, in principle, reversible. Rarely, acute renal failure may occur, particularly in patients with compromised renal

function such as the elderly or dehydrated. Chronic administration of NSAIDs may reduce the antihypertensive effect of an ACE

inhibitor. The administration of NSAIDs may reduce the diuretic, natriuretic and antihypertensive effects of thiazide diuretics.

Clinical Chemistry Captopril may cause a false-positive urine test for acetone. Hydrochlorothiazide may cause diagnostic

interference of the bentiromide test. Thiazides may decrease serum PBI (Protein Bound Iodine) levels without signs of thyroid

disturbance.

Co-trimoxazole (trimethoprim/sulfamethoxazole)

Patients taking concomitant co-trimoxazole (trimethoprim/sulfamethoxazole) may be at increased risk for hyperkalaemia (see

section 4.4).

4.6 Fertility, pregnancy and lactation

Pregnancy:

ACE-inhibitors:

The use of ACE inhibitors is not recommended during the first trimester of pregnancy (see section 4.4). The use of ACE

inhibitors is contraindicated during the second and third trimesters of pregnancy (see sections 4.3 and 4.4).

Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of

pregnancy has not been conclusive; however a small increase in risk cannot be excluded. Unless continued ACE inhibitor

therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments

which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors

should be stopped immediately, and, if appropriate, alternative therapy should be started.

Exposure to ACE inhibitor therapy during the second and third trimesters is known to induce human foetotoxicity (decreased

renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia).

(See section 5.3). Should exposure to ACE inhibitors have occurred from the second trimester of pregnancy, ultrasound check

of renal function and skull is recommended. Infants whose mothers have taken ACE inhibitors should be closely observed for

hypotension (see sections 4.3 and 4.4).

Health Products Regulatory Authority

24 November 2019

CRN008X7G

Page 8 of 14

Hydrochlorothiazide:

There is limited experience with hydrochlorothiazide during pregnancy, especially during the first trimester. Animal studies are

insufficient. Hydrochlorothiazide crosses the placenta. Based on the pharmacological mechanism of action of

hydrochlorothiazide its use during the second and third trimester may compromise foeto-placental perfusion and may cause

foetal and neonatal effects like icterus, disturbance of electrolyte balance and thrombocytopenia.

Hydrochlorothiazide should not be used for gestational oedema, gestational hypertension or preeclampsia due to the risk of

decreased plasma volume and placental hypoperfusion, without a beneficial effect on the course of the disease.

Hydrochlorothiazide should not be used for essential hypertension in pregnant women except in rare situations where no other

treatment could be used.

Lactation:

Captopril: Limited pharmacokinetic data demonstrate very low concentrations in breast milk (see section 5.2). Although these

concentrations seem to be clinically irrelevant, the use of Captor-HCT in breastfeeding is not recommended for preterm infants

and for the first few weeks after delivery, because of the hypothetical risk of cardiovascular and renal effects and because there

is not enough clinical experience.

In the case of an older infant, the use of Captor-HCT in a breast-feeding mother may be considered if this treatment is

necessary for the mother and the child is observed for any adverse effect.

Hydrochlorothiazide:

Hydrochlorothiazide is excreted in human milk in small amounts. Thiazides in high doses causing intense diuresis can inhibit

the milk production. The use of Captor-HCT during breastfeeding is not recommended. If Captor-HCT is used during

breastfeeding doses should be kept as low as possible.

4.7 Effects on ability to drive and use machines

As with other antihypertensives, the ability to drive and use machines may be reduced, e.g. at the start of the treatment or

when the dose is modified, and also when used in combination with alcohol, but these effects depend on the individual's

susceptibility.

4.8 Undesirable effects

Frequency is defined using the following convention:

Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare

(<1/10,000), Not known (cannot be estimated from the available data)

CAPTOPRIL Undesirable effects reported for captopril and/or ACE inhibitor therapy include:

Blood and lymphatic system disorders:

Very rare: neutropenia/agranulocytosis (see section 4.4), pancytopenia particularly in patients with renal dysfunction (see

section 4.4), anaemia (including aplastic and haemolytic), thrombocytopenia, lymphadenopathy, eosinophilia, auto-immune

diseases and/or positive ANA-titres.

Metabolism and nutrition disorders:

Uncommon: anorexia

Very rare: hyperkalaemia, hypoglycaemia (see section 4.4).

Psychiatric disorders:

Common: sleep disorders

Very rare: confusion, depression.

Nervous system disorders:

Common: taste impairment, dizziness

Uncommon: headache, paraesthesia

Rare: drowsiness

Very rare: cerebrovascular incidents, including stroke, cerebrovascular insufficiency and syncope.

Eye disorders:

Health Products Regulatory Authority

24 November 2019

CRN008X7G

Page 9 of 14

Very rare: blurred vision.

Cardiac disorders:

Uncommon: tachycardia or tachyarrhythmia, angina pectoris, palpitations

Very rare: cardiac arrest, cardiogenic shock.

Vascular disorders:

Uncommon: hypotension (see section 4.4), Raynaud syndrome, flush, pallor.

Respiratory, thoracic and mediastinal disorders:

Common: dry, irritating (non-productive) cough (see section 4.4) and dyspnoea

Very rare: bronchospasm, rhinitis, allergic alveolitis/eosinophilic pneumonia.

Gastrointestinal disorders:

Common: nausea, vomiting, gastric irritations, abdominal pain, diarrhoea, constipation, dry mouth, peptic ulcer.

Rare: stomatitis/aphthous ulcerations, intestinal angiodema (see section 4.4)

Very rare: glossitis, pancreatitis.

Hepatobiliary disorders:

Very rare: impaired hepatic function and cholestasis (including jaundice), hepatitis including necrosis, elevated liver enzymes

and bilirubin.

Skin and subcutaneous tissue disorders:

Common: pruritus, rash, alopecia

Uncommon: angioedema (see section 4.4)

Very rare: urticaria, Stevens-Johnson syndrome, erythema multiforme, photosensitivity, erythroderma, pemphigoid reactions

and exfoliative dermatitis.

Musculoskeletal and connective tissue disorders:

Very rare: myalgia, arthralgia.

Renal and urinary disorders:

Rare: renal function disorders including renal failure, polyuria, oliguria, increased urine frequency

Very rare: nephrotic syndrome.

Reproductive system and breast disorders:

Very rare: impotence, gynaecomastia.

General disorders and administration site conditions:

Uncommon: chest pain, fatigue, malaise

Very rare: fever.

Investigations:

Very rare: proteinuria, eosinophilia, increase of serum potassium, decrease of serum sodium, elevation of BUN, serum

creatinine and serum bilirubin, decreases in haemoglobin, haematocrit, leucocytes, thrombocytes, positive ANAtitre, elevated

ESR.

HYDROCHLOROTHIAZIDE

Infections and infestations: sialadenitis.

"Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Non-melanoma skin cancer* (basal cell carcinoma and squamous cell carcinoma (frequency not known))

*See description of selected adverse reactions"

Blood and lymphatic system disorders: leucopenia, neutropenia/agranulocytosis, thrombocytopenia, aplastic anaemia,

haemolytic anaemia, bone marrow depression.

Health Products Regulatory Authority

24 November 2019

CRN008X7G

Page 10 of 14

Metabolism and nutrition disorders: anorexia, hyperglycaemia, gycosuria, hyperuricaemia, electrolyte imbalance (including

hyponatraemia and hypokalaemia), increases in cholesterol and triglycerides.

Psychiatric disorders: restlessness, depression, sleep disturbances.

Nervous system disorders: loss of appetite, paraesthesia, light-headedness.

Eye disorders: xanthopsia, transient blurred vision, acute myopia, secondary acute angle-closure glaucoma.

Ear and labyrinth disorders: vertigo.

Cardiac disorders: postural hypotension, cardiac arrhythmias.

Vascular disorders: necrotising angiitis (vasculitis, cutaneous vasculitis).

Respiratory, thoracic and mediastinal disorders: respiratory distress (including pneumonitis and pulmonary oedema).

Gastrointestinal disorders: gastric irritation, diarrhoea, constipation, pancreatitis.

Hepato-biliary disorders: jaundice (intrahepatic cholestatic jaundice).

Skin and subcutaneous tissue disorders: photosensitivity reactions, rash, cutaneous lupus erythematosus-like reactions,

reactivation of cutaneous lupus erythematosus, urticaria, anaphylactic reactions, toxic epidermal necrolysis.

Musculoskeletal and connective tissue disorders: muscle spasm.

Renal and urinary disorders: renal dysfunction, interstitial nephritis.

General disorders and administration site conditions: fever, weakness.

"Description of selected adverse reactions

Non-melanoma skin cancer: Based on available data from epidemiological studies, cumulative dose-dependent association

between HCTZ and NMSC has been observed (see also sections 4.4 and 5.1)".

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 of overdosage are: increased diuresis, electrolyte imbalance, severe hypotension, depression of consciousness

(including coma), convulsions, paresis, cardiac arrhythmias, bradycardia, renal failure.

Measures to prevent absorption (e.g. gastric lavage, administration of absorbing agents and sodium sulfate within 30 minutes

after intake) and hasten elimination should be applied if ingestion is recent. If hypotension occurs, the patient should be placed

in the shock position and sodium chloride and volume supplementation should be given rapidly.

Treatment with angiotensin-II can be considered. Bradycardia or extensive vagal reactions should be treated by administering

atropine. The use of a pacemaker may be considered. Constant monitoring of water, electrolyte and acid base balance, blood

glucose is essential. In case of hypokalaemia, potassium substitution is necessary.

Captopril may be removed from circulation by haemodialysis. The degree to which hydrochlorothiazide is removed by

haemodialysis has not been established.

5 PHARMACOLOGICAL PROPERTIES

Health Products Regulatory Authority

24 November 2019

CRN008X7G

Page 11 of 14

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: ACE (Angiotensin-Converting-Enzyme) inhibitors, combinations, ATC code: C09BA01.

CAPTOR-HCT is a combination of an ACE inhibitor, captopril, and an antihypertensive diuretic, hydrochlorothiazide. The

combination of these agents has an additive antihypertensive effect, reducing blood pressure to a greater degree than either

component alone.

-Captopril is an angiotensin converting enzyme (ACE) inhibitor, i.e. it inhibits ACE, the enzyme involved in the conversion of

angiotensin I to angiotensin II -a vasoconstrictor which also stimulates aldosterone secretion by the adrenal cortex.

Such inhibition leads to: -reduced aldosterone secretion, -increased plasma renin activity, since aldosterone no longer exerts

negative feedback, -a drop in total peripheral resistance (with a preferential effect on muscles and kidneys) which is not

accompanied by water and sodium retention or reflex tachycardia during long-term treatment. Captopril also exerts its

antihypertensive effect in subjects with low or normal renin concentrations.

Captopril is effective at all stages of hypertension, i.e. mild, moderate or severe. A reduction in supine and standing systolic and

diastolic blood pressures is observed. After a single dose, the antihypertensive effect is evident fifteen minutes post-dose and

reaches a maximum between 1 h and 1.5 h after administration of the drug. Its duration of action is dose-dependent and varies

from 6 to 12 hours. Blood pressure becomes normalised (seated DBP <90 mmHg) in patients after two weeks to one month of

treatment and the drug retains its effectiveness over the course of time. Patients are also classified as responders if seated DBP

decreased by 10% or more from baseline-BP. Rebound hypertension does not occur when treatment is discontinued. The

treatment of hypertension with captopril leads to an increase in arterial compliance, a rise in renal blood flow without any

significant drop in the glomerular filtration rate, and a decrease in left ventricular hypertrophy.

Two large randomised, controlled trials (ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global

Endpoint Trial) and VA NEPHRON-D (The Veterans Affairs Nephropathy in Diabetes)) have examined the use of the

combination of an ACE-inhibitor with an angiotensin II receptor blocker.

ONTARGET was a study conducted in patients with a history of cardiovascular or cerebrovascular disease, or type 2 diabetes

mellitus accompanied by evidence of end-organ damage. VA NEPHRON-D was a study in patients with type 2 diabetes mellitus

and diabetic nephropathy.

These studies have shown no significant beneficial effect on renal and/or cardiovascular outcomes and mortality, while an

increased risk of hyperkalaemia, acute kidney injury and/or hypotension as compared to monotherapy was observed. Given

their similar pharmacodynamic properties, these results are also relevant for other ACE-inhibitors and angiotensin II receptor

blockers.

ACE-inhibitors and angiotensin II receptor blockers should therefore not be used concomitantly in patients with diabetic

nephropathy.

ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) was a study designed to test

the benefit of adding aliskiren to a standard therapy of an ACE-inhibitor or an angiotensin II receptor blocker in patients with

type 2 diabetes mellitus and chronic kidney disease, cardiovascular disease, or both. The study was terminated early because of

an increased risk of adverse outcomes. Cardiovascular death and stroke were both numerically more frequent in the aliskiren

group than in the placebo group and adverse events and serious adverse events of interest (hyperkalaemia, hypotension and

renal dysfunction) were more frequently reported in the aliskiren group than in the placebo group.

-Hydrochlorothiazide is a thiazide diuretic which acts by inhibiting the reabsorption of sodium in the cortical diluting segment

of renal tubules. It increases the excretion of sodium and chloride in urine and, to a lesser extent, the excretion of potassium

and magnesium, thereby increasing urinary output and exerting an antihypertensive effect.

The time to onset of diuretic activity is approximately 2 hours. Diuretic activity reaches a peak after 4 hours and is maintained

for 6 to 12 hours.

Above a certain dose, thiazide diuretics reach a plateau in terms of therapeutic effect whereas adverse reactions continue to

multiply. When treatment is ineffective, increasing the dose beyond recommended doses serves no useful purpose and often

gives rise to adverse reactions.

-The concomitant administration of captopril and hydrochlorothiazide in clinical trials led to greater reductions in blood

pressure than when either of the products was administered alone. The administration of captopril inhibits the renin

Health Products Regulatory Authority

24 November 2019

CRN008X7G

Page 12 of 14

angiotensin aldosterone system and tends to reduce hydrochlorothiazide-induced potassium loss. Combination of an ACE

inhibitor with a thiazide diuretic produces a synergistic effect and also lessens the risk of hypokalaemia provoked by the

diuretic alone.

Non-melanoma skin cancer: Based on available data from epidemiological studies, cumulative dose-dependent association

between HCTZ and NMSC has been observed. One study included a population comprised of 71,533 cases of BCC and of 8,629

cases of SCC matched to 1,430,833 and 172,462 population controls, respectively. High HCTZ use (≥50,000 mg cumulative) was

associated with an adjusted OR of 1.29 (95% CI: 1.23-1.35) for BCC and 3.98 (95% CI: 3.68-4.31) for SCC. A clear cumulative

dose response relationship was observed for both BCC and SCC. Another study showed a possible association between lip

cancer (SCC) and exposure to HCTZ: 633 cases of lip-cancer were matched with 63,067 population controls, using a risk-set

sampling strategy. A cumulative dose-response relationship was demonstrated with an adjusted OR 2.1 (95% CI: 1.7-2.6)

increasing to OR 3.9 (3.0-4.9) for high use (~25,000 mg) and OR 7.7 (5.7-10.5) for the highest cumulative dose (~100,000 mg)

(see also section 4.4).

5.2 Pharmacokinetic properties

Captopril is quickly absorbed after oral administration and maximum serum concentrations are obtained around one hour after

administration. Minimum mean absorption is approximately 75%. Peak plasma concentrations are reached within 60-90

minutes. The presence of food in the gastrointestinal tract reduces absorption by about 30-40%. Approximately 25-30% of the

circulating drug is bound to plasma proteins.

The apparent elimination half-life of unchanged captopril in blood is about 2 hours. Greater than 95% of the absorbed dose is

eliminated in the urine within 24 hours; 40-50% is unchanged drug and the remainder are inactive disulphide metabolites

(captopril disulphide and captopril cysteine disulphide). Impaired renal function could result in drug accumulation.

Studies in animals indicate that captopril does not cross the blood-brain barrier to any significant extent. Oral absorption of

hydrochlorothiazide is relatively rapid. The mean plasma half-life in fasted individuals has been reported to be 5 to 15 hours.

Hydrochlorothiazide is eliminated rapidly by the kidney, and excreted unchanged (>95%) in the urine.

Lactation:

In the report of twelve women taking oral captopril 100mg 3 times daily, the average peak milk level was 4.7µg/L and occurred

3.8 hours after the dose. Based on these data, the maximum daily dosage that a nursing infant would receive is less than

0.002% of the maternal daily dosage.

5.3 Preclinical safety data

Animal studies performed during organogenesis with captopril and/or hydrochlorothiazide have not shown any teratogenic

effect but captopril has produced foetal toxicity in several species, including foetal mortality during late pregnancy, growth

retardation and postnatal mortality in the rat. Non-clinical data reveal no other specific hazard for human based on

conventional studies of safety pharmacology, repeated dose toxicology, genotoxicity and carcinogenicity.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Microcrystalline Cellulose

Lactose Monohydrate

Pregelatinised Maize starch

Stearic Acid

Magnesium Stearate

6.2 Incompatibilities

Not applicable.

Health Products Regulatory Authority

24 November 2019

CRN008X7G

Page 13 of 14

6.3 Shelf life

5 years.

6.4 Special precautions for storage

Do not store above 25°C.

Health Products Regulatory Authority

24 November 2019

CRN008X7G

Page 14 of 14

6.5 Nature and contents of container

Captor-HCT tablets are packed in blisters of polypropylene and aluminium foil in packs of 30 tablets and sample packs of 10

tablets.

Not all pack sizes may be marketed.

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

Rowex Ltd

Newtown

Bantry

Co. Cork

Ireland

8 MARKETING AUTHORISATION NUMBER

PA0711/025/003

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 16

October 1998

Date of last renewal: 16

October 2008

10 DATE OF REVISION OF THE TEXT

November 2019

Similar products

Search alerts related to this product

View documents history

Share this information