Last Updated on eMC 05-06-2017 View medicine  | E. R. Squibb & Sons Limited Contact details

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

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:29-05-2017

Legal Category:POM

Black Triangle (CHM): NO

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).

 

 

Reasons for adding or updating:

  • 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 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:23-09-2015

Legal Category:POM

Black Triangle (CHM): NO

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

Reasons for adding or updating:

  • Change to section 4.4 - Special warnings and precautions for use

Date of revision of text on the SPC:03-03-2014

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 4.4 has been revised to include safety information on glaucoma or myopia with the use of HCTZ.

Sections 2, 3, 4.2, 4.3 and 4.8 have also been revised in line with the QRD template.

Reasons for adding or updating:

  • Change to section 4.6 - Fertility, pregnancy and lactation
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:20-09-2012

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



4.6     Pregnancy and lactation

Pregnancy:

ACE-inhibitors:

The use of ACE inhibitorsGiven 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


May 2011
September 2012

Reasons for adding or updating:

  • Change to section 6. 5 - Nature and Contents of Container

Date of revision of text on the SPC:01-05-2011

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

30 pack size added.

Reasons for adding or updating:

  • Correction of spelling/typing errors

Date of revision of text on the SPC:01-05-2011

Legal Category:POM

Black Triangle (CHM): NO

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:01-05-2011

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

The content of lactose has been corrected in Section 2.

Reasons for adding or updating:

  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 4.6 - Pregnancy and Lactation
  • Change to section 5.2 - Pharmacokinetic Properties

Date of revision of text on the SPC:23-04-2010

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Summary

 

4.3     Contraindications

 

Hypersensitivity to the active substances or to any of the excipients or to any other ACE inhibitor or to any other sulphonamide-derived drug.

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 trimesters of pregnancy (see sections 4.4 and 4.6).

Lactation (see section 4.6).

 

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.

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 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).

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: elevations in serum potassium have been observed in some patients treated with ACE inhibitors, including captopril. Patients at risk for the development of hyperkalaemia include those with renal insufficiency, diabetes mellitus, or those using concomitant potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes; or those patients taking other drugs associated with increases in serum potassium (e.g. heparin). If concomitant use of the above mentioned agents is deemed appropriate, regular monitoring of serum potassium is recommended.

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 hemodynamically 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/mm3) 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 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, <Capozide> 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.

 

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.

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

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: <Capozide> is not recommended during the first trimester of pregnancy (see section 4.6). If treatment is discontinued due to pregnancy the prescriber should decide whether treatment of hypertension should be continued.

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 sections 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: Capozide 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, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

 

4.6     Pregnancy and lactation

 

Pregnancy:

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 <Capozide> is contra-indicated during the 2nd and 3rd trimester of pregnancy (see section 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).

 

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:

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.

 

<Capozide> is not recommended during the first trimester of pregnancy (see section 4.4.). When a pregnancy is planned or confirmed, an alternative treatment should be initiated as soon as possible. Controlled studies with ACE inhibitors have not been done in humans, but limited number of cases of first trimester exposures have not shown malformations.

 

<Capozide> is contraindicated (see section 4.3) during the second and third trimesters of pregnancy. Prolonged captopril exposure during the second and third trimesters is known to induce toxicity in foetuses (decreased renal function, oligohydramnios, skull ossification retardation) and in neonates (neonatal renal failure, hypotension, hyperkalaemia) (see also section 5.3).

 

Hydrochlorothiazide in case of prolonged exposure during the third trimester of pregnancy may cause a foeto-placental ischaemia and risk of growth retardation. Moreover, rare cases of hypoglycaemia and thrombocytopenia in neonates have been reported in case of exposure near the term.

 

Hydrochlorothiazide can reduce plasma volume as well as the uteroplacental blood flow.

 

Should exposure to <Capozide> have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended.

 

<Capozide> is contraindicated during breast-feeding (see section 4.3).

Both captopril and hydrochlorothiazide are excreted in human breast milk. Thiazides during breast feeding by lactating mothers have been associated with a decrease or even suppression of the milk lactation. Hypersensitivity to sulfonamide-derived drugs, hypokalaemia and nuclear icterus might occur.

 

Because of the potential for serious adverse reactions in nursing infants from both drugs, a decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with <Capozide> should be made taking into account the benefit of breast-feeding to the child and the benefit of <Capozide> therapy to the woman.

 

 

 

 

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 100 mg 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.

 

 

 

10.     DATE OF REVISION OF THE TEXT

 

8th October 2009April 2010

 

 

 

 

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 6. 5 - Nature and Contents of Container

Date of revision of text on the SPC:23-07-2008

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 4.2 Adults: Removal of statement about tablet strenghts that are not avaliable in UK
Section 4.4 Angioedema: Additional information
Section 6.2: Information regarding nature and contents of container section revised and updated

Reasons for adding or updating:

  • Change to section 7 - Marketing Authorisation Holder

Reasons for adding or updating:

  • Correction of spelling/typing errors

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 - Contra-indications
  • Change to section 4.4 - Special Warnings and Precautions for Use
  • Change to section 4.5 - Interactions with other Medicaments 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

Reasons for adding or updating:

  • Transferred from eMC version 1

Reasons for adding or updating:

  • Transferred from eMC version 1

Reasons for adding or updating:

  • No reasons supplied