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Bristol-Myers Squibb Pharmaceutical Limited

Watery Lane, Swords, Co. Dublin,
Telephone: 1 800 749 749
Medical Information Direct Line: Freephone: 1 800 749 749
Medical Information e-mail: Medical.information@bms.com
Summary of Product Characteristics last updated on medicines.ie: 07/06/2017
SPC Capozide (Captopril 50mg/Hydrochlorothiazide 25mg) Tablets

When a pharmaceutical company changes an SPC or PIL, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 07/06/2017 and displayed until Current
Reasons for adding or updating:
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 10 - Date of revision of the text
Date of revision of text on the SPC:   01-Jun-2017
Legal Category:   Product subject to medical prescription which may be renewed (B)

Free-text change information supplied by the pharmaceutical company



Sect 4.2

Cross reference to other sections of the SmPC added

Sect 4.3

Added the below

·          The concomitant use of Capozide with aliskiren-containing products is contraindicated in patients with diabetes mellitus or renal impairment (GFR <60 ml/min/1.73 m²) (see sections 4.5 and 5.1).

 

Sect 4.4

Added the below

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).

 

Updated section on hyperkalaemia

 

Hyperkalaemia: Hyperkalaemia may occur during treatment with an ACE inhibitor. Patients at risk for the development of hyperkalaemia include those with renal insufficiency, diabetes mellitus, hypoaldosteronism or those using concomitant potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes; or those patients taking other active substances associated with increases in serum potassium (e.g. heparin, co-trimoxazole also known as trimethoprim/sulfamethoxazole). If concomitant use of the above mentioned agents is deemed appropriate, regular monitoring of serum potassium is recommended (see section 4.5).

 

Sect 4.5

Added the below

mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus): patients taking concomitant mTOR inhibitors therapy may be at increased risk for angioedema (see section 4.4).

 

Co-trimoxazole (trimethoprim/sulfamethoxazole): patients taking concomitant co-trimoxazole (trimethoprim/sulfamethoxazole) may be at increased risk for hyperkalaemia (see section 4.4).

Updated on 11/11/2015 and displayed until 07/06/2017
Reasons for adding or updating:
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text
  • Change to section 4.3 - Contraindications
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.4 - Special warnings and precautions for use
Date of revision of text on the SPC:   05-Nov-2015
Legal Category:   Product subject to medical prescription which may be renewed (B)

Free-text change information supplied by the pharmaceutical company

section 4.3 - New bullet point added - Concomitant use ofCapozide with aliskiren-containing products in patients with diabetes mellitusor with renal impairment (glomerular filtration rate (GFR) <60 ml/min/1.73m²) (see sections 4.4, 4.5 and 5.1).$0sections 4.4 New text added - Dualblockade of the renin-angiotensin-aldosterone system (RAAS): There is evidence thatthe concomitant use of ACE-inhibitors, angiotensin II receptor blockers oraliskiren increases the risk of hypotension, hyperkalaemia and decreased renalfunction (including acute renal failure).Dualblockade of RAAS through the combined use of ACE-inhibitors, angiotensin IIreceptor blockers or aliskiren is therefore not recommended (see sections 4.5and 5.1). If dual blockade therapy is considered absolutely necessary, thisshould only occur under specialist supervision and subject to frequent closemonitoring of renal function, electrolytes and blood pressure. ACE-inhibitorsand angiotensin II receptor blockers should not be used concomitantly inpatients with diabetic nephropathy. $0$0sections 4.5 New text added - Angiotensin II receptorblockers or aliskiren: clinical trial data has shown that dual blockadeof the renin-angiotensin-aldosterone-system (RAAS) through the combined use ofACE-inhibitors, angiotensin II receptor blockers or aliskiren is associatedwith a higher frequency of adverse events such as hypotension, hyperkalaemiaand decreased renal function (including acute renal failure) compared to theuse of a single RAAS-acting agent (see sections 4.3, 4.4 and 5.1).$0$0sections 4.8 New ADR "cerebrovascularinsufficiency" added; ADR frequency updated$0$0section 5.1 New text added - Dual blockade of therenin-angiotensin-aldosterone system (RAAS):Two large randomised, controlled trials (ONTARGET(ONgoing Telmisartan Alone and in com­bi­nation with Ramipril Global EndpointTrial) and VA NEPHRON-D (The Veterans Affairs Nephro­pathy in Diabetes)) haveexamined the use of the combination of an ACE-inhibitor with an angiotensin IIreceptor blocker. ONTARGET was a study conducted in patients with ahistory of cardiovascular or cerebrovascular disease, or type 2 diabetesmellitus accompanied by evidence of end-organ damage. VA NEPHRON-D was a studyin patients with type 2 diabetes mellitus and diabetic nephropathy. These studies have shown no significant beneficialeffect on renal and/or cardiovascular outcomes and mortality, while anincreased risk of hyperkalaemia, acute kidney injury and/or hypotension ascompared to monotherapy was observed. Given their similar pharmacodynamicproperties, these results are also relevant for other ACE-inhibitors andangiotensin II receptor blockers.ACE-inhibitors and angiotensin II receptor blockersshould therefore not be used concomitantly in patients with diabeticnephropathy.ALTITUDE (Aliskiren Trial in Type 2 Diabetes UsingCardiovascular and Renal Disease Endpoints) was a study designed to test thebenefit of adding aliskiren to a standard therapy of an ACE-inhibitor or anangiotensin II receptor blocker in patients with type 2 diabetes mellitus andchronic kidney disease, cardiovascular disease, or both. The study wasterminated early because of an increased risk of adverse outcomes.Cardiovascular death and stroke were both numerically more frequent in the aliskirengroup than in the placebo group and adverse events and serious adverse eventsof interest (hyperkalaemia, hypotension and renal dysfunction) were morefrequently reported in the aliskiren group than in the placebo group.$0
Updated on 19/12/2014 and displayed until 11/11/2015
Reasons for adding or updating:
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
Date of revision of text on the SPC:   01-Apr-2014
Legal Category:   Product subject to medical prescription which may be renewed (B)

Free-text change information supplied by the pharmaceutical company

Update to include safety information on myopia and glaucoma.
Updated on 12/02/2013 and displayed until 19/12/2014
Reasons for adding or updating:
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 10 - Date of revision of the text
Date of revision of text on the SPC:   24-Sep-2012
Legal Category:   Product subject to medical prescription which may be renewed (B)

Free-text change information supplied by the pharmaceutical company



4.6     Pregnancy and lactation


Pregnancy:

ACE-inhibitors:

The use of ACE inhibitors Given the effects of the individual components in this combination product on pregnancy, the use of Capozide is not recommended during the first trimester of pregnancy (see section 4.4). The use of ACE inhibitorsCapozide is contra-indicated during the second2nd and third3rd trimester of pregnancy (see sections 4.3 and 4.4).

 

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 Capozide 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 Capozide 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 <Capozide> during breast feeding is not recommended. If <Capozide> is used during breast feeding, doses should be kept as low as possible.


10.     DATE OF REVISION OF THE TEXT

 

June 2011September 2012

Updated on 17/09/2012 and displayed until 12/02/2013
Reasons for adding or updating:
  • Change to section 6.5 - Nature and contents of container
Date of revision of text on the SPC:   20-Jun-2011
Legal Category:   Product subject to medical prescription which may be renewed (B)

Free-text change information supplied by the pharmaceutical company

30 pack size added
Updated on 12/04/2012 and displayed until 17/09/2012
Reasons for adding or updating:
  • Change to section 2 - Qualitative and quantitative composition
  • Improved electronic presentation
Date of revision of text on the SPC:   20-Jun-2011
Legal Category:   Product subject to medical prescription which may be renewed (B)

Free-text change information supplied by the pharmaceutical company

Lactose content updated and presentation of the document improved.
Updated on 08/07/2011 and displayed until 12/04/2012
Reasons for adding or updating:
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
Date of revision of text on the SPC:   20-Jun-2011
Legal Category:   Product subject to medical prescription which may be renewed (B)

Free-text change information supplied by the pharmaceutical company

The content of lactose has been amended in Section 2.
Updated on 09/11/2010 and displayed until 08/07/2011
Reasons for adding or updating:
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.6 - Pregnancy and lactation
Date of revision of text on the SPC:   01-Sep-2010
Legal Category:   Product subject to medical prescription which may be renewed (B)

Free-text change information supplied by the pharmaceutical company

In section 4.4 and 4.6, information has been added on the use of ACE inhibitors during pregnancy.
Updated on 14/07/2010 and displayed until 09/11/2010
Reasons for adding or updating:
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.6 - Pregnancy and lactation
  • Improved electronic presentation
  • Introduction of new pack/pack size
Date of revision of text on the SPC:   30-Mar-2010
Legal Category:   Product subject to medical prescription which may be renewed (B)

Free-text change information supplied by the pharmaceutical company

The SPC has beenupdated in line with QRD template.

Other minor changes have also ben made.

2.       QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Each tablet contains 50 mg of Captopril and 25 mg of Hydrochlorothiazide.

 

Excipients: Each tablet contains 70.20 mg lactose monohydrate.

 

For a full list of excipients, see section 6.1.

 

 

 

3.       PHARMACEUTICAL FORMform

 

Tablet.

A

White to off-white oval, biconvex talet with possible slight mottling.

One side of the tablet is engraved 'SQUIBB 390'tablets, with a bisect breakbar on one side and engraved "CH" on the oppositeother side.

The tablet can be divided into equal halves.

 

4.2     Posology and method of administration

 

Capozide 50mg/25mg Tablets 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 10050 mg captopril/3025 mg hydrochlorothiazide should not be exceeded.   If satisfactory reduction of blood pressure has not been achieved, additional antihypertensive medication may be added (see section 4.5).

Adults:   The 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 mg/25 25 mg, once a day, in the morning.   When clinically appropriate a direct change from monotherapy to the fixed combination may be considered.

The 25/25mg* strength may be used once a day for patients whose blood pressure is not adequately controlled by hydrochlorothiazide 25 mg monotherapy and before titration of the captopril component.   The 50/25mg and 25/25mg strengths are intended to be used once daily, as two tablets would result in an inappropriately high dose of hydrochlorothiazide (50mg/day).   The 50/15* mg strength may be administered to start the fixed combination in patients whose blood pressure is not adequately controlled by 50 mg captopril monotherapy, and/or when a lower dose of hydrochlorothiazide is preferred.

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

The combination captopril/hydrochlorothiazide is contraindicated in patients with severe renal impairment (creatinine clearance < 30 < 30 ml/min).

Special populations:   In in salt/volume depleted patients, elderly patients, and diabetic patients, the usual starting dose is 25 mg/12.5 mg once a day.

Children:   The safety and efficacyThere is no relevant indication for use of Capozide 50mg/25mg Tablets in children has not been established.


4.4 Warnings and Precuations 

Angioedema:   Angiangioneurotic oedema of the face, extremities, face, lips, mucous membranes, tongue, glottis and/or larynx may occur has been reported in patients treated with ACEangiotensin converting enzyme inhibitors, particularlyincluding Captopril. This may occur at any time during the first weeks of treatment.   However, in rare In such cases, severe angioedema may develop after long-term treatment with an ACE inhibitor.   Treatment Captopril should be discontinued promptly.   Angioedema involving the tongue, glottis or larynx may be fatal.   Emergency therapy  and appropriate monitoring should be instituted.   The patient should be hospitalised and observed for at least 12 to 24 hours and should not be discharged untilensure complete resolution of symptoms prior to dismissing the patient. In those instances where swelling has occurredbeen confined to the face and lips the condition generally resolved without treatment, although antihistamines have been useful in relieving symptoms.

Cough:   Cough

Angioneurotic oedema associated with laryngeal edema 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 (0.3 ml to 0.5 ml) 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 angioedema compared to non-blacks.

 

Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor (see section 4.3).

 

Intestinal angioedema 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 angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain (see section 4.8).

4.5 Drug interactions 

Alpha blocking agents: concomitant use of alpha blocking agents may increase the antihypertensive effects of captopril and increase the risk of orthostatic hypotension.

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.

4.6 Pregnancy 


Because of the potential for serious adverse reactions in nursing infants from both drugs, a decision should be made on whether to continue/discontinue nursingbreast-feeding or to continue/discontinue therapy,  with Capozide 50mg/25mg Tablets should be made taking into account the importancebenefit of thisbreast-feeding to the child and the benefit of Capozide 50mg/25mg Tablets therapy to the motherwoman.

 

6.3     Shelf life

 

36 months.

 

3 years.

 

6.4     Special precautions for storage

 

Do not store above 25°C.   Store in the original package.

 

 

6.5     Nature and contents of container

 

The tablets are packaged in foil strips or PVC/PVDC blisters in packs of 28 tablets.

 

 

PVC/PVDC/Aluminium foil blisters, containing 10, 12, 20, 28, 30, 42, 60, 84, 90, 98, 100 tablets.

 

Not all pack sizes may be marketed.

 

Updated on 01/09/2006 and displayed until 14/07/2010
Reasons for adding or updating:
  • Change to section 1 - Name of medicinal product
  • Change to section 3 - Pharmaceutical form
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 9 - Date of renewal of authorisation
  • Change to section 10 - Date of revision of the text
Date of revision of text on the SPC:   01/2006
Legal Category:   prescription only

Free-text change information supplied by the pharmaceutical company

Section 1: Add 50mg/25mg
Section 3: Add  

A white oval biconvex tablet with possible slight mottling.

One side of the tablet is engraved 'SQUIBB 390' with a bisect bar on the opposite side.

 

Section 4.4: Replace Therefore, it should not be used in cases of congenital galactosaemia, glucose and galactose malabsorption or lactase deficiency syndromes (rare metabolic diseases).
with  

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Section 4.8: Add to GI disorders, very rare  

Intestinal angioedema has also been reported very rarely in patients treated with ACE inhibitors and should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.

Section 6.6: Change instructions to requirements
Section 9: Change 2001 to 2006
Section 10: Replace November 2003 with April 2006
 
Updated on 16/05/2005 and displayed until 01/09/2006
Reasons for adding or updating:
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 5 - Pharmacological properties
Updated on 20/08/2003 and displayed until 16/05/2005
Reasons for adding or updating:
  • New SPC for medicines.ie
Updated on 25/06/2003 and displayed until 20/08/2003
Reasons for adding or updating:
  • Correction of spelling/typing errors
Updated on 17/06/2003 and displayed until 25/06/2003
Reasons for adding or updating:
  • New SPC for medicines.ie

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Active Ingredients

 
   Hydrochlorothiazide
   Captopril