Ramipril Tablets BP 5mg (Taj Pharma)

  1. Name of the medicinal product

Ramipril Tablets BP 5mg (Taj Pharma)
Ramipril Tablets BP 10mg (Taj Pharma)

  1. Qualitative and quantitative composition

a) Each uncoated tablet contains:
Ramipril BP                                 5mg
Excipients:                                   q.s.

b) Each uncoated tablet contains:
Ramipril BP                                 10mg
Excipients:                                   q.s.

For the full list of excipients, see 6.1

  1. Pharmaceutical form

Uncoated Tablet

  1. Clinical particulars

4.1 Therapeutic indications

– Treatment of hypertension.

– Cardiovascular prevention: reduction of cardiovascular morbidity and mortality in patients with:

  • manifest atherothrombotic cardiovascular disease (history of coronary heart disease or stroke, or peripheral vascular disease) or
  • diabetes with at least one cardiovascular risk factor (see section 5.1).

– Treatment of renal disease:

  • Incipient glomerular diabetic nephropathy as defined by the presence of microalbuminuria,
  • Manifest glomerular diabetic nephropathy as defined by macroproteinuria in patients with at least one cardiovascular risk factor (see section 5.1),
  • Manifest glomerular non diabetic nephropathy as defined by macroproteinuria ≥ 3 g/day (see section 5.1).

– Treatment of symptomatic heart failure.

– Secondary prevention after acute myocardial infarction: reduction of mortality from the acute phase of myocardial infarction in patients with clinical signs of heart failure when started > 48 hours following acute myocardial infarction.

4.2 Posology and method of administration

Posology

It is recommended that Ramipril Taj Pharma is taken each day at the same time of the day.

Ramipril Taj Pharma can be taken before, with or after meals, because food intake does not modify its bioavailability (see section 5.2). Ramipril Taj Pharma has to be swallowed with liquid. It must not be chewed or crushed.

Adults

Diuretic-Treated patients

Hypotension may occur following initiation of therapy with Ramipril Taj Pharma; this is more likely in patients who are being treated concurrently with diuretics. Caution is therefore recommended since these patients may be volume and/or salt depleted.

If possible, the diuretic should be discontinued 2 to 3 days before beginning therapy with Ramipril Taj Pharma (see section 4.4).

In hypertensive patients in whom the diuretic is not discontinued, therapy with Ramipril Taj Pharma should be initiated with a 1.25 mg dose. Renal function and serum potassium should be monitored. The subsequent dose of Ramipril Taj Pharma should be adjusted according to blood pressure target.

Hypertension

The dose should be individualised according to the patient profile (see section 4.4) and blood pressure control.

Ramipril Taj Pharma may be used in monotherapy or in combination with other classes of antihypertensive medicinal products (see sections 4.3, 4.4, 4.5 and 5.1).

Starting dose

Ramipril Taj Pharma should be started gradually with an initial recommended dose of 2.5 mg daily.

Patients with a strongly activated renin-angiotensin-aldosterone system may experience an excessive drop in blood pressure following the initial dose. A starting dose of 1.25 mg is recommended in such patients and the initiation of treatment should take place under medical supervision (see section 4.4).

Titration and maintenance dose

The dose can be doubled at interval of two to four weeks to progressively achieve target blood pressure; the maximum permitted dose of Ramipril Taj Pharma is 10 mg daily. Usually the dose is administered once daily.

Cardiovascular prevention

Starting dose

The recommended initial dose is 2.5 mg of Ramipril Taj Pharma once daily.

Titration and maintenance dose

Depending on the patient’s tolerability to the active substance, the dose should be gradually increased. It is recommended to double the dose after one or two weeks of treatment and – after another two to three weeks – to increase it up to the target maintenance dose of 10 mg Ramipril Taj Pharma once daily.

See also posology on diuretic treated patients above.

Treatment of renal disease

In patients with diabetes and microalbuminuria:

Starting dose:

The recommended initial dose is 1.25 mg of Ramipril Taj Pharma once daily.

Titration and maintenance dose

Depending on the patient’s tolerability to the active substance, the dose is subsequently increased. Doubling the once daily dose to 2.5 mg after two weeks and then to 5 mg after a further two weeks is recommended.

In patients with diabetes and at least one cardiovascular risk

Starting dose:

The recommended initial dose is 2.5 mg of Ramipril Taj Pharma once daily.

Titration and maintenance dose

Depending on the patient’s tolerability to the active substance, the dose is subsequently increased. Doubling the daily dose to 5 mg Ramipril Taj Pharma after one or two weeks and then to 10 mg Ramipril Taj Pharma after a further two or three weeks is recommended. The target daily dose is 10 mg.

In patients with non- diabetic nephropathy as defined by macroproteinuria ≥ 3 g/day.

Starting dose:

The recommended initial dose is 1.25 mg of Ramipril Taj Pharma once daily.

Titration and maintenance dose

Depending on the patient’s tolerability to the active substance, the dose is subsequently increased. Doubling the once daily dose to 2.5 mg after two weeks and then to 5 mg after a further two weeks is recommended.

Symptomatic heart failure

Starting dose

In patients stabilized on diuretic therapy, the recommended initial dose is 1.25 mg daily.

Titration and maintenance dose

Ramipril Taj Pharma should be titrated by doubling the dose every one to two weeks up to a maximum daily dose of 10 mg. Two administrations per day are preferable.

Secondary prevention after acute myocardial infarction and with heart failure

Starting dose

After 48 hours, following myocardial infarction in a clinically and haemodynamically stable patient, the starting dose is 2.5 mg twice daily for three days. If the initial 2.5 mg dose is not tolerated a dose of 1.25 mg twice a day should be given for two days before increasing to 2.5 mg and 5 mg twice a day. If the dose cannot be increased to 2.5 mg twice a day the treatment should be withdrawn.

See also posology on diuretic treated patients above.

Titration and maintenance dose

The daily dose is subsequently increased by doubling the dose at intervals of one to three days up to the target maintenance dose of 5 mg twice daily.

The maintenance dose is divided in 2 administrations per day where possible.

If the dose cannot be increased to 2.5 mg twice a day treatment should be withdrawn. Sufficient experience is still lacking in the treatment of patients with severe (NYHA IV) heart failure immediately after myocardial infarction. Should the decision be taken to treat these patients, it is recommended that therapy be started at 1.25 mg once daily and that particular caution be exercised in any dose increase.

Special populations

Patients with renal impairment

Daily dose in patients with renal impairment should be based on creatinine clearance (see section 5.2):

– if creatinine clearance is ≥ 60 ml/min, it is not necessary to adjust the initial dose (2.5 mg/day); the maximal daily dose is 10 mg;

– if creatinine clearance is between 30-60 ml/min, it is not necessary to adjust the initial dose (2.5 mg/day); the maximal daily dose is 5 mg;

– if creatinine clearance is between 10-30 ml/min, the initial dose is 1.25 mg/day and the maximal daily dose is 5 mg;

– in haemodialysed hypertensive patients: Ramipril Taj Pharma is slightly dialysable; the initial dose is 1.25 mg/day and the maximal daily dose is 5 mg; the medicinal product should be administered few hours after haemodialysis is performed.

Patients with hepatic impairment (see section 5.2)

In patients with hepatic impairment, treatment with Ramipril Taj Pharma must be initiated only under close medical supervision and the maximum daily dose is 2.5 mg Ramipril Taj Pharma.

Elderly

Initial doses should be lower and subsequent dose titration should be more gradual because of greater chance of undesirable effects especially in very old and frail patients. A reduced initial dose of 1.25 mg Ramipril Taj Pharma should be considered.

Paediatric population

The safety and efficacy of Ramipril Taj Pharma in children has not yet been established.

Currently available data for Ramipril Taj Pharma are described in sections 4.8, 5.1, 5.2 and 5.3 but no specific recommendation on posology can be made.

Method of administration

Oral use.

4.3 Contraindications

  • Hypersensitivity to the active substance, to any of the excipients listed in section 6.1 or any other ACE (Angiotensin Converting Enzyme) inhibitors (see section 6.1)
  • History of angioedema (hereditary, idiopathic or due to previous angioedema with ACE inhibitors or AIIRAs)
  • Extracorporeal treatments leading to contact of blood with negatively charged surfaces (see section 4.5)
  • Significant bilateral renal artery stenosis or renal artery stenosis in a single functioning kidney
  • 2ndand 3rdtrimesters of pregnancy (see sections 4.4 and 4.6)
  • Ramipril Taj Pharma must not be used in patients with hypotensive or haemodynamically unstable states.
  • The concomitant use of Ramipril Taj Pharma 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).
  • Concomitant use with sacubitril/valsartan therapy. Ramapril must not be initiated earlier than 36 hours after the last dose of sacubitril/varsartan (see also sections 4.4 and 4.5).

4.4 Special warnings and precautions for use

Special populations

Pregnancy:

  • ACE inhibitors such as Ramipril Taj Pharma, or Angiotensin II Receptor Antagonists (AIIRAs) should not be initiated during pregnancy. Unless continued ACE inhibitor/ AIIRAs therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors/ AIIRAs should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.6).
  • Patients at particular risk of hypotension

– Patients with strongly activated renin-angiotensin-aldosterone system

Patients with strongly activated renin-angiotensin-aldosterone system are at risk of an acute pronounced fall in blood pressure and deterioration of renal function due to ACE inhibition, especially when an ACE inhibitor or a concomitant diuretic is given for the first time or at first dose increase.

Significant activation of renin-angiotensin-aldosterone system is to be anticipated and medical supervision including blood pressure monitoring is necessary, for example in:

– patients with severe hypertension

– patients with decompensated congestive heart failure

– patients with haemodynamically relevant left ventricular inflow or outflow impediment (e.g. stenosis of the aortic or mitral valve)

– patients with unilateral renal artery stenosis with a second functional kidney

– patients in whom fluid or salt depletion exists or may develop (including patients with diuretics)

– patients with liver cirrhosis and/or ascites

– patients undergoing major surgery or during anaesthesia with agents that produce hypotension.

Generally, it is recommended to correct dehydration, hypovolaemia or salt depletion before initiating treatment (in patients with heart failure, however, such corrective action must be carefully weighed out against the risk of volume overload).

– 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.

– Transient or persistent heart failure post MI

– Patients at risk of cardiac or cerebral ischemia in case of acute hypotension

The initial phase of treatment requires special medical supervision.

  • Elderly

See section 4.2.

Surgery

It is recommended that treatment with angiotensin converting enzyme inhibitors such as Ramipril Taj Pharma should be discontinued where possible one day before surgery.

Monitoring of renal function

Renal function should be assessed before and during treatment and dosage adjusted especially in the initial weeks of treatment. Particularly careful monitoring is required in patients with renal impairment (see section 4.2). There is a risk of impairment of renal function, particularly in patients with congestive heart failure or after a renal transplant.

Angioedema

Angioedema has been reported in patients treated with ACE inhibitors including Ramipril Taj Pharma (see section 4.8).

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 Ramipril Taj Pharma. Treatment with Ramipril Taj Pharma 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.

Intestinal angioedema has been reported in patients treated with ACE inhibitors including Ramipril Taj Pharma (see section 4.8). These patients presented with abdominal pain (with or without nausea or vomiting).

In case of angioedema, Ramipril Taj Pharma must be discontinued.

Emergency therapy should be instituted promptly. Patient should be kept under observation for at least 12 to 24 hours and discharged after complete resolution of the symptoms.

Anaphylactic reactions during desensitization

The likelihood and severity of anaphylactic and anaphylactoid reactions to insect venom and other allergens are increased under ACE inhibition. A temporary discontinuation of Ramipril Taj Pharma should be considered prior to desensitization.

Electrolyte monitoring: hyperkalaemia

Hyperkalaemia has been observed in some patients treated with ACE inhibitors including Ramipril Taj Pharma. ACE inhibitors can cause hyperkalaemia because the inhibit the release of aldosterone. The effect is usually not significant in patients with normal renal function. However, in patients with impaired renal function, age (> 70 years), uncontrolled diabetes mellitus, conditions such as dehydration, acute cardiac decompensation, metabolic acidosis 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, hyperkalaemia 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).

Electrolyte monitoring: hyponatremia

Syndrome of Inappropriate Anti-diuretic Hormone (SIADH) and subsequent hyponatremia has been observed in some patients treated with Ramipril Taj Pharma. It is recommended that serum sodium levels be monitored regularly in the elderly and in other patients at risk of hyponatremia.

Neutropenia/agranulocytosis

Neutropenia/agranulocytosis, as well as thrombocytopenia and anaemia, have been rarely seen and bone marrow depression has also been reported. It is recommended to monitor the white blood cell count to permit detection of a possible leucopoenia. More frequent monitoring is advised in the initial phase of treatment and in patients with impaired renal function, those with concomitant collagen disease (e.g. lupus erythematosus or scleroderma), and all those treated with other medicinal products that can cause changes in the blood picture (see sections 4.5 and 4.8).

Ethnic differences

ACE inhibitors cause higher rate of angioedema in black patients than in non black patients.

As with other ACE inhibitors, Ramipril Taj Pharma may be less effective in lowering blood pressure in black people than in non black patients, possibly because of a higher prevalence of hypertension with low renin level in the black hypertensive population.

Cough

Cough has been reported with the use of ACE inhibitors. Characteristically, the cough is non-productive, persistent and resolves after discontinuation of therapy. ACE inhibitor-induced cough should be considered as part of the differential diagnosis of cough.

4.5 Interaction with other medicinal products and other forms of interaction

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).

Contra-indicated combinations

Extracorporeal treatments leading to contact of blood with negatively charged surfaces such as dialysis or haemofiltration with certain high-flux membranes (e.g. polyacrylonitril membranes) and low density lipoprotein apheresis with dextran sulphate due to increased risk of severe anaphylactoid reactions (see section 4.3). If such treatment is required, consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive agent.

Medicinal products increasing 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).

Precautions for use

Medicinal products increasing the risk of angioedema: 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).

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 Ramipril Taj Pharma. 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 Ramipril Taj Pharma is co-administered with other agents that increase serum potassium, such as trimethoprim and co-trimoxazole (trimethoprim/sulfamethoxazole) as trimethoprim is known to act as a potassium-sparing diuretic like amiloride. Therefore, the combination of Ramipril Taj Pharma with the above-mentioned medicinal products is not recommended. If concomitant use is indicated, they should be used with caution and with frequent monitoring of serum potassium.

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.

Antihypertensive agents (e.g. diuretics) and other substances that may decrease blood pressure (e.g. nitrates, tricyclic antidepressants, anaesthetics, acute alcohol intake, baclofen, alfuzosin, doxazosin, prazosin, tamsulosin, terazosin): Potentiation of the risk of hypotension is to be anticipated (see section 4.2 for diuretics).

Vasopressor sympathomimetics and other substances (e.g. isoproterenol, dobutamine, dopamine, epinephrine) that may reduce the antihypertensive effect of Ramipril Taj Pharma: Blood pressure monitoring is recommended.

Allopurinol, immunosuppressants, corticosteroids, procainamide, cytostatics and other substances that may change the blood cell count: Increased likelihood of haematological reactions (see section 4.4).

Lithium salts: Excretion of lithium may be reduced by ACE inhibitors and therefore lithium toxicity may be increased. Lithium level must be monitored.

Antidiabetic agents including insulin: Hypoglycaemic reactions may occur. Blood glucose monitoring is recommended.

Non-steroidal anti-inflammatory medicinal products and acetylsalicylic acid: Reduction of the antihypertensive effect of Ramipril Taj Pharma is to be anticipated. Furthermore, concomitant treatment of ACE inhibitors and NSAIDs may lead to an increased risk of worsening of renal function and to an increase in kalaemia.

4.6 Fertility, pregnancy and lactation

Pregnancy

Ramipril Taj Pharma is not recommended during the first trimester of pregnancy (see section 4.4) and is contraindicated during the second and third trimesters of pregnancy (see section 4.3).

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 anti-hypertensive 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.

ACE inhibitor/ Angiotensin II Receptor Antagonist (AIIRA) therapy exposure 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 also 5.3 ‘Preclinical safety data’). Should exposure to ACE inhibitor have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended. Newborns whose mothers have taken ACE inhibitors should be closely observed for hypotension, oliguria and hyperkalaemia (see also sections 4.3 and 4.4).

Breast-feeding

Because insufficient information is available regarding the use of Ramipril Taj Pharma during breastfeeding (see section 5.2), Ramipril Taj Pharma is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.

4.7 Effects on ability to drive and use machines

Some adverse reactions (e.g. symptoms of a reduction in blood pressure such as dizziness) may impair the patient’s ability to concentrate and react and, therefore, constitute a risk in situations where these abilities are of particular importance (e.g. operating a vehicle or machinery).

This can happen especially at the start of treatment, or when changing over from other preparations. After the first dose or subsequent increases in dose it is not advisable to drive or operate machinery for several hours.

4.8 Undesirable effects

Summary of safety profile

The safety profile of Ramipril Taj Pharma includes persistent dry cough and reactions due to hypotension. Serious adverse reactions include angioedema, hyperkalaemia, renal or hepatic impairment, pancreatitis, severe skin reactions and neutropenia/agranulocytosis.

Tabulated list of adverse reactions

Adverse reactions 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).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Frequency / System Organ Class Common Uncommon Rare Very rare Not known
Blood and lymphatic system disorders Eosinophilia White blood cell count decreased (including neutropenia or agranulocytosis), red blood cell count decreased, haemoglobin decreased, platelet count decreased Bone marrow failure, pancytopenia, haemolytic anaemia
Immune system disorders Anaphylactic or anaphylactoid reactions, antinuclear antibody increased
Endocrine disorders Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Metabolism and nutrition disorders Blood potassium increased Anorexia, decreased appetite Blood sodium decreased
Psychiatric disorders Depressed mood, anxiety, nervousness, restlessness, sleep disorder including somnolence Confusional state Disturbance in attention
Nervous system disorders Headache, dizziness Vertigo, paraesthesia, ageusia, dysgeusia Tremor, balance disorder Cerebral ischaemia including ischaemic stroke and transient ischaemic attack, psychomotor skills impaired, burning sensation, parosmia
Eye disorders Visual disturbance including blurred vision Conjunctivitis
Ear and labyrinth disorders Hearing impaired, tinnitus
Cardiac disorders Myocardial ischaemia including angina pectoris or myocardial infarction, tachycardia, arrhythmia, palpitations, oedema peripheral
Vascular disorders Hypotension, orthostatic blood pressure decreased, syncope Flushing Vascular stenosis, hypoperfusion, vasculitis Raynaud’s phenomenon
Respiratory, thoracic and mediastinal disorders Non-productive tickling cough, bronchitis, sinusitis, dyspnoea Bronchospasm including asthma aggravated, nasal congestion
Gastrointestinal disorders Gastrointestinal inflammation, digestive disturbances, abdominal discomfort, dyspepsia, diarrhoea, nausea, vomiting Pancreatitis (cases of fatal outcome have been very exceptionally reported with ACE inhibitors), pancreatic enzymes increased, small bowel angioedema, abdominal pain upper including gastritis, constipation, dry mouth Glossitis Aphtous stomatitis
Hepato-biliary disorders Hepatic enzymes and/or bilirubin conjugated increased Jaundice cholestatic, hepatocellular damage Acute hepatic failure, cholestatic or cytolytic hepatitis (fatal outcome has been very exceptional).
Skin and subcutaneous tissue disorders Rash in particular maculo-papular Angioedema; very exceptionally, the airway obstruction resulting from angioedema may have a fatal outcome; pruritus, hyperhidrosis Exfoliative dermatitis, urticaria, onycholysis, Photosensitivity reaction Toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, psoriasis aggravated, dermatitis psoriasiform, pemphigoid or lichenoid exanthema or enanthema, alopecia
Musculoskeletal, connective tissue and bone disorders Muscle spasms, myalgia Arthralgia
Renal and urinary disorders Renal impairment including renal failure acute, urine output increased, worsening of a pre-existing proteinuria, blood urea increased, blood creatinine increased
Reproductive system and breast disorders Transient erectile impotence, libido decreased Gynaecomastia
General disorders and administration site conditions Chest pain, fatigue Pyrexia Asthenia

Paediatric population

The safety of Ramipril Taj Pharma was monitored in 325 children and adolescents, aged 2-16 years old during 2 clinical trials. Whilst the nature and severity of the adverse events are similar to that of the adults, the frequency of the following is higher in the children:

  • Tachycardia, nasal congestion and rhinitis, “common” (i.e. ≥ 1/100 to < 1/10) in paediatric, and “uncommon” (i.e. ≥ 1/1,000 to < 1/100) in adult population.
  • Conjunctivitis “common” (i.e. ≥ 1/100 to < 1/10) in paediatric and “rare” (i.e. ≥ 1/10,000 to < 1/1,000) in adult population.
  • Tremor and urticaria “uncommon” (i.e. ≥ 1/1,000 to < 1/100) in paediatric population and “rare” (i.e. ≥ 1/10,000 to < 1/1,000) in adult population.

The overall safety profile for Ramipril Taj Pharma in paediatric patients does not differ significantly from the safety profile in adults.

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.

4.9 Overdose

Symptoms

Symptoms associated with overdose of ACE inhibitors may include excessive peripheral vasodilatation (with marked hypotension, shock), bradycardia, electrolyte disturbances, and renal failure.

Management

The patient should be closely monitored and the treatment should be symptomatic and supportive. Suggested measures include primary detoxification (gastric lavage, administration of adsorbents) and measures to restore haemodynamic stability, including, administration of alpha 1 adrenergic agonists or angiotensin II (angiotensinamide) administration. Ramipril Taj Pharmaat, the active metabolite of Ramipril Taj Pharma is poorly removed from the general circulation by haemodialysis.

  1. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Agents acting on the renin-angiotensin system, ACE inhibitors, plain. Mechanism of action

Ramipril Taj Pharmaat, the active metabolite of the prodrug Ramipril Taj Pharma, inhibits the enzyme dipeptidylcarboxypeptidase I (synonyms: angiotensin-converting enzyme; kininase II). In plasma and tissue this enzyme catalyses the conversion of angiotensin I to the active vasoconstrictor substance angiotensin II, as well as the breakdown of the active vasodilator bradykinin. Reduced angiotensin II formation and inhibition of bradykinin breakdown lead to vasodilatation.

Since angiotensin II also stimulates the release of aldosterone, Ramipril Taj Pharmaat causes a reduction in aldosterone secretion. The average response to ACE inhibitor monotherapy was lower in black (Afro-Caribbean) hypertensive patients (usually a low-renin hypertensive population) than in non-black patients.

Pharmacodynamic effects

Antihypertensive properties:

Administration of Ramipril Taj Pharma causes a marked reduction in peripheral arterial resistance. Generally, there are no major changes in renal plasma flow and glomerular filtration rate. Administration of Ramipril Taj Pharma to patients with hypertension leads to a reduction in supine and standing blood pressure without a compensatory rise in heart rate.

In most patients the onset of the antihypertensive effect of a single dose becomes apparent 1 to 2 hours after oral administration. The peak effect of a single dose is usually reached 3 to 6 hours after oral administration. The antihypertensive effect of a single dose usually lasts for 24 hours.

The maximum antihypertensive effect of continued treatment with Ramipril Taj Pharma is generally apparent after 3 to 4 weeks. It has been shown that the antihypertensive effect is sustained under long term therapy lasting 2 years.

Abrupt discontinuation of Ramipril Taj Pharma does not produce a rapid and excessive rebound increase in blood pressure.

Heart failure:

In addition to conventional therapy with diuretics and optional cardiac glycosides, Ramipril Taj Pharma has been shown to be effective in patients with functional classes II-IV of the New-York Heart Association. The medicinal product had beneficial effects on cardiac haemodynamics (decreased left and right ventricular filling pressures, reduced total peripheral vascular resistance, increased cardiac output and improved cardiac index). It also reduced neuroendocrine activation.

Clinical efficacy and safety

Cardiovascular prevention/Nephroprotection

A preventive placebo-controlled study (the HOPE-study), was carried out in which Ramipril Taj Pharma was added to standard therapy in more than 9,200 patients. Patients with increased risk of cardiovascular disease following either atherothrombotic cardiovascular disease (history of coronary heart disease, stroke or peripheral vascular disease) or diabetes mellitus with at least one additional risk factor (documented microalbuminuria, hypertension, elevated total cholesterol level, low high-density lipoprotein cholesterol level or cigarette smoking) were included in the study.

The study showed that Ramipril Taj Pharma statistically significantly decreases the incidence of myocardial infarction, death from cardiovascular causes and stroke, alone and combined (primary combined events).

The HOPE study: Main results

Ramipril Taj Pharma Placebo relative risk

(95% confidence interval)

p-value
% %
All patients n = 4,645 n = 4,652
Primary combined events 14.0 17.8 0.78 (0.70-0.86) < 0.001
Myocardial infarction 9.9 12.3 0.80 (0.70-0.90) < 0.001
Death from cardiovascular causes 6.1 8.1 0.74 (0.64-0.87) < 0.001
Stroke 3.4 4.9 0.68 (0.56-0.84) < 0.001
Secondary endpoints
Death from any cause 10.4 12.2 0.84 (0.75-0.95) 0.005
Need for Revascularisation 16.0 18.3 0.85 (0.77-0.94) 0.002
Hospitalisation for unstable angina 12.1 12.3 0.98 (0.87-1.10) NS
Hospitalisation for heart failure 3.2 3.5 0.88 (0.70-1.10) 0.25
Complications related to diabetes 6.4 7.6 0.84 (0.72-0.98) 0.03

The MICRO-HOPE study, a predefined substudy from HOPE, investigated the effect of the addition of Ramipril Taj Pharma 10 mg to the current medical regimen versus placebo in 3,577 patients at least ≥ 55 years old (with no upper limit of age), with a majority of type 2 diabetes (and at least another CV risk factor), normotensive or hypertensive.

The primary analysis showed that 117 (6.5 %) participants on Ramipril Taj Pharma and 149 (8.4 %) on placebo developed overt nephropathy, which corresponds to a RRR 24 %; 95 % CI [3-40], p = 0.027.

The REIN study, a multicenter randomized, double-blind parallel group, placebo-controlled study aimed at assessing the effect of treatment with Ramipril Taj Pharma on the rate of decline of glomerular function rate (GFR) in 352 normotensive or hypertensive patients (18-70 years old) suffering from mild (i.e. mean urinary protein excretion > 1 and < 3 g/24 h) or severe proteinuria (≥ 3 g/24 h) due to chronic non-diabetic nephropathy. Both subpopulations were prospectively stratified.

The main analysis of patients with the most severe proteinuria (stratum prematurely disrupted due to benefit in Ramipril Taj Pharma group) showed that the mean rate of GFR decline per month was lower with Ramipril Taj Pharma than with placebo; -0.54 (0.66) vs. -0.88 (1.03) ml/min/month, p = 0.038. The intergroup difference was thus 0.34 [0.03-0.65] per month, and around 4 ml/min/year; 23.1 % of the patients in the Ramipril Taj Pharma group reached the combined secondary endpoint of doubling of baseline serum creatinine concentration and/or end-stage renal disease (ESRD) (need for dialysis or renal transplantation) vs. 45.5 % in the placebo group (p = 0.02).

Dual blockade of the renin-angiotensin-aldosterone system (RAAS) Two large randomised, controlled trials (ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Taj Pharma 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.

Secondary prevention after acute myocardial infarction

The AIRE study included more than 2,000 patients with transient/persistent clinical signs of heart failure after documented myocardial infarction. The Ramipril Taj Pharma treatment was started 3 to 10 days after the acute myocardial infarction. The study showed that after an average follow-up time of 15 months the mortality in Ramipril Taj Pharma-treated patients was 16.9 % and in the placebo treated patients was 22.6 %. This means an absolute mortality reduction of 5.7 % and a relative risk reduction of 27 % (95 % CI [11-40 %]).

Paediatric Population

In a randomized, double-blind, placebo-controlled clinical study involving 244 paediatric patients with hypertension (73% primary hypertension), aged 6-16 years, patients received either low dose, medium dose or high dose of Ramipril Taj Pharma to achieve plasma concentrations of Ramipril Taj Pharmaat corresponding to the adult dose range of 1.25 mg, 5 mg and 20 mg on the basis of body weight. At the end of 4 weeks, Ramipril Taj Pharma was ineffective in the endpoint of lowering systolic blood pressure but lowered diastolic blood pressure at the highest dose. Both medium and high doses of Ramipril Taj Pharma showed significant reduction of both systolic and diastolic blood pressure in children with confirmed hypertension.

This effect was not seen in a 4 weeks dose-escalation, randomized, double-blind withdrawal study in 218 paediatric patients aged 6-16 years (75% primary hypertension), where both diastolic and systolic blood pressures demonstrated a modest rebound but not a statistically significant return to the baseline, in all three dose levels tested [low dose (0.625 mg – 2.5 mg), medium dose (2.5 mg – 10 mg) or high dose (5mg – 20 mg)] Ramipril Taj Pharma based on weight. Ramipril Taj Pharma did not have a linear dose response in the paediatric population studied.

5.2 Pharmacokinetic properties

Absorption

Following oral administration Ramipril Taj Pharma is rapidly absorbed from the gastrointestinal tract: peak plasma concentrations of Ramipril Taj Pharma are reached within one hour. Based on urinary recovery, the extent of absorption is at least 56 % and is not significantly influenced by the presence of food in the gastrointestinal tract. The bioavailability of the active metabolite Ramipril Taj Pharmaat after oral administration of 2.5 mg and 5 mg Ramipril Taj Pharma is 45 %.

Peak plasma concentrations of Ramipril Taj Pharmaat, the sole active metabolite of Ramipril Taj Pharma are reached 2-4 hours after Ramipril Taj Pharma intake. Steady state plasma concentrations of Ramipril Taj Pharmaat after once daily dosing with the usual doses of Ramipril Taj Pharma are reached by about the fourth day of treatment.

Distribution

The serum protein binding of Ramipril Taj Pharma is about 73 % and that of Ramipril Taj Pharmaat about 56 %.

Biotransformation

Ramipril Taj Pharma is almost completely metabolised to Ramipril Taj Pharmaat, and to the diketopiperazine ester, the diketopiperazine acid, and the glucuronides of Ramipril Taj Pharma and Ramipril Taj Pharmaat.

Elimination

Excretion of the metabolites is primarily renal.

Plasma concentrations of Ramipril Taj Pharmaat decline in a polyphasic manner. Because of its potent, saturable binding to ACE and slow dissociation from the enzyme, Ramipril Taj Pharmaat shows a prolonged terminal elimination phase at very low plasma concentrations.

After multiple once-daily doses of Ramipril Taj Pharma, the effective half-life of Ramipril Taj Pharmaat concentrations was 13-17 hours for the 5-10 mg doses and longer for the lower 1.25-2.5 mg doses. This difference is related to the saturable capacity of the enzyme to bind Ramipril Taj Pharmaat.

Lactation

A single oral dose of Ramipril Taj Pharma produced an undetectable level of Ramipril Taj Pharma and its metabolite in breast milk. However the effect of multiple doses is not known.

Patients with renal impairment (see section 4.2)

Renal excretion of Ramipril Taj Pharmaat is reduced in patients with impaired renal function, and renal Ramipril Taj Pharmaat clearance is proportionally related to creatinine clearance. This results in elevated plasma concentrations of Ramipril Taj Pharmaat, which decrease more slowly than in subjects with normal renal function.

Patients with hepatic impairment (see section 4.2)

In patients with impaired liver function, the metabolism of Ramipril Taj Pharma to Ramipril Taj Pharmaat was delayed, due to diminished activity of hepatic esterases, and plasma Ramipril Taj Pharma levels in these patients were increased. Peak concentrations of Ramipril Taj Pharmaat in these patients, however, are not different from those seen in subjects with normal hepatic function.

Paediatric population

The pharmacokinetic profile of Ramipril Taj Pharma was studied in 30 paediatric hypertensive patients, aged 2-16 years, weighing >10 kg. After doses of 0.05 to 0.2 mg/kg, Ramipril Taj Pharma was rapidly and extensively metabolized to Ramipril Taj Pharmaat. Peak plasma concentrations of Ramipril Taj Pharmaat occurred within 2-3 hours. Ramipril Taj Pharmaat clearance highly correlated with the log of body weight (p<0.01) as well as dose (p<0.001). Clearance and volume of distribution increased with increasing children age for each dose group.

The dose of 0.05 mg /kg in children achieved exposure levels comparable to those in adults treated with Ramipril Taj Pharma 5mg. The dose of 0.2 mg/kg in children resulted in exposure levels higher than the maximum recommended dose of 10 mg per day in adults.

5.3 Preclinical safety data

Oral administration of Ramipril Taj Pharma has been found to be devoid of acute toxicity in rodents and dogs. Studies involving chronic oral administration have been conducted in rats, dogs and monkeys. Indications of plasma electrolyte shifts and changes in blood picture have been found in the 3 species. As an expression of the pharmacodynamic activity of Ramipril Taj Pharma, pronounced enlargement of the juxtaglomerular apparatus has been noted in the dog and monkey from daily doses of 250 mg/kg/d. Rats, dogs and monkeys tolerated daily doses of 2, 2.5 and 8 mg/kg/d respectively without harmful effects. . Irreversible kidney damage has been observed in very young rats given a single dose of Ramipril Taj Pharma.

Reproduction toxicology studies in the rat, rabbit and monkey did not disclose any teratogenic properties.

Fertility was not impaired either in male or in female rats.

The administration of Ramipril Taj Pharma to female rats during the foetal period and lactation produced irreversible renal damage (dilatation of the renal pelvis) in the offspring at daily doses of 50 mg/kg body weight or higher.

Extensive mutagenicity testing using several test systems has yielded no indication that Ramipril Taj Pharma possesses mutagenic or genotoxic properties.

  1. Pharmaceutical particulars

6.1 List of excipients

Microcrystalline cellulose, Pregelatinised starch, Silicium dioxide precipitated, Glycine hydrochloride, Glycerol dibehenate, Red iron oxide as colorant

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

Aluminium/aluminium strips

3 years

Polypropylene container and aluminium/aluminium blister

2 years

6.4 Special precautions for storage

Do not store above 25°C. Store in the original package in order to protect from moisture.

6.5 Nature and contents of container

The tablets are packed in aluminium/aluminium strips, aluminium/aluminium blisters or PP container with HDPE closure.

Pack sizes

Al/Al strips: 14, 28, 56 and 98 tablets

Al/Al blister: 14, 28, 56 and 98 tablets

PP container: 20, 28, 30, 50, 100, 250 tablets

Not all pack sizes may be marketed

6.6 Special precautions for disposal and other handling

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

  1. Manufactured By:
    Taj Pharmaceuticals Ltd.
    Mumbai, India Unit No. 214, Old Bake House,
    Maharashtra Chambers of commerce Lane, Fort,
    Mumbai-400001 at: Ahmedabad- Gujarat, INDIA.

Ramipril Tablets BP 5mg (Taj Pharma)
Ramipril Tablets BP 10mg (Taj Pharma)

Package leaflet: Information for the user

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 Ramipril Taj Pharma is and what it is used for.
    2. What you need to know before you take Ramipril Taj Pharma.
    3. How to take Ramipril Taj Pharma.
    4. Possible side effects.
    5. How to store Ramipril Taj Pharma.
    6. Contents of the pack and other information.
  2. What Ramipril Taj Pharma is and what it is used for

The name of your medicine is Ramipril Taj Pharma 1.25mg, 2.5mg, 5mg or 10mg Tablets (called Ramipril Taj Pharma throughout this leaflet). It belongs to a group of medicines called ACE inhibitors (Angiotensin Converting Enzyme Inhibitors).

Ramipril Taj Pharma works by:

  • Decreasing your body’s production of substances that could raise your blood pressure
  • Making your blood vessels relax and widen
  • Making it easier for your heart to pump blood around your body.

Ramipril Taj Pharma can be used:

  • To treat high blood pressure (hypertension)
  • To reduce the risk of you having a heart attack or stroke
  • To reduce the risk or delay the worsening of kidney problems (whether or not you have diabetes)
  • To treat your heart when it cannot pump enough blood to the rest of your body (heart failure)
  • As treatment following heart attack (myocardial infarction) complicated with heart failure.
  1. What you need to know before you take Ramipril Taj Pharma

Do not take and tell your doctor before taking this medicine if:

  • If you are allergic to Ramipril Taj Pharma, any other ACE inhibitor medicine or any of the other ingredients of this medicine listed in section 6.
    Signs of an allergic reaction may include a rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue.
  • If you have ever had a serious allergic reaction called “angioedema”. The signs include itching, hives (urticaria) red marks on the hands, feet and throat, swelling of the throat and tongue, swelling around the eyes and lips, difficulty breathing and swallowing.
  • 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.
  • If you are having dialysis or any other type of blood filtration. Depending on the machine that is used, Ramipril Taj Pharma may not be suitable for you.
  • If you have kidney problems where the blood supply to your kidney is reduced (renal artery stenosis)
  • During the last 6 months of pregnancy (see section below on “Pregnancy and breast-feeding”).
  • If your blood pressure is abnormally low or unstable. Your doctor will need to make this assessment.
  • If you have diabetes or impaired kidney function and you are treated with a blood pressure lowering medicine containing aliskiren.

Do not take Ramipril Taj Pharma if any of the above apply to you. If you are not sure, talk to your doctor before taking Ramipril Taj Pharma.

Warnings and precautions

Talk to your doctor or pharmacist before taking Ramipril Taj Pharma:

  • If you have heart, liver or kidney problems
  • If you have lost a lot of body salts or fluids (through being sick (vomiting), having diarrhoea, sweating more than usual, being on a low salt diet, taking diuretics (water tablets) for a long time or having had dialysis)
  • If you are going to have treatment to reduce your allergy to bee or wasp stings (desensitization)
  • If you are going to receive an anaesthetic. This may be given for an operation or any dental work. You may need to stop your Ramipril Taj Pharma treatment one day beforehand; ask your doctor for advice
  • If you have high amounts of potassium in your blood (shown in blood test results)
  • If you are taking medicines or have conditions which may decrease sodium levels in your blood. Your doctor may carry out regular blood tests, particularly for checking the levels of sodium in your blood especially if you are elderly.
  • If you are taking medicines that may increase the risk of angioedema, a serious allergic reaction, such as mTOR inhibitors (e.g. temsirolimus, everolimus, sirolimus), vildagliptin, neprilysin (NEP) inhbitors (such as racecadotril) or sacubitril/valsartan. For sacubitril/valsartan, see section 2 ‘Do not take Ramipril Taj Pharma’.
  • If you have a collagen vascular disease such as scleroderma or systemic lupus erythematosus
  • You must tell your doctor if you think that you are (or might become) pregnant. Ramipril Taj Pharma is not recommended in the first 3 months of pregnancy and may cause serious harm to your baby after 3 months of pregnancy (see section below on “Pregnancy and breast-feeding”).
  • If you are taking any of the following medicines used to treat high blood pressure:
    • an angiotensin II receptor blocker (ARBs) (also known as sartans-for example valsartan, telmisartan, irbesartan), in particular if you have diabetes-related kidney problems.
    • aliskiren

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 Ramipril Taj Pharma”.

Children and adolescents

Ramipril Taj Pharma is not recommended for use in children and adolescents below 18 years of age because the safety and efficacy of Ramipril Taj Pharma in children has not yet been established.

If any of the above apply to you (or you are not sure), talk to your doctor before taking Ramipril Taj Pharma.

Other medicines and Ramipril Taj Pharma

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This is because Ramipril Taj Pharma can affect the way some other medicines work. Also some medicines can affect the way Ramipril Taj Pharma works.

Tell your doctor if you are taking any of the following medicines. They can make Ramipril Taj Pharma work less well:

  • Medicines used to relieve pain and inflammation (e.g. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) such as ibuprofen or indometacin and aspirin)
  • Medicines used for the treatment of low blood pressure, shock, cardiac failure, asthma or allergies such as ephedrine, noradrenaline or adrenaline. Your doctor will need to check your blood pressure.

Tell your doctor if you are taking any of the following medicines. They can increase the chance of getting side effects if you take them with Ramipril Taj Pharma:

  • Sacubitril/valsartan – used for treating a type of long term (chronic) heart failure in adults (see section 2 ‘Do not take Ramipril Taj Pharma’)
  • Medicines used to relieve pain and inflammation (e.g. Non-Steroidal Anti- Inflammatory Drugs (NSAIDs) such as ibuprofen or indometacin and aspirin)
  • Medicines for cancer (chemotherapy)
  • Medicines to stop the rejection of organs after a transplant such as ciclosporin
  • Diuretics (water tablets) such as furosemide
  • Medicines which can increase the amount of potassium in your blood such as spironolactone, triamterene, amiloride, potassium salts, trimethoprim alone or in combination with sulfamethoxazole (for infections) and heparin (for thinning blood)
  • Steroid medicines for inflammation such as prednisolone
  • Allopurinol (used to lower the uric acid in your blood)
  • Procainamide (for heart rhythm problems)
  • Temsirolimus (for cancer)
  • Sirolimus, everolimus (for prevention of graft rejection)
  • Vildagliptin (used for treating type 2 diabetes)
  • Racecadotril (used against diarrhoea)
  • 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 Ramipril Taj Pharma” and “Warnings and precautions”).

Tell your doctor if you are taking any of the following medicines. They may be affected by Ramipril Taj Pharma:

  • Medicines for diabetes such as oral glucose lowering medicines and insulin. Ramipril Taj Pharma may lower your blood sugar. Check your blood sugar closely while taking Ramipril Taj Pharma.
  • Lithium (for mental health problems). Ramipril Taj Pharma may increase the amount of lithium in your blood. Your lithium levels will need to be closely checked by your doctor.

If any of the above apply to you (or you are not sure), talk to your doctor before taking Ramipril Taj Pharma.

Ramipril Taj Pharma with food and alcohol

  • Drinking alcohol with Ramipril Taj Pharma may make you feel dizzy or light-headed. If you are concerned about how much you can drink while you are taking Ramipril Taj Pharma, discuss this with your doctor as medicines used to reduce blood pressure and alcohol can have additive effects.
  • Ramipril Taj Pharma may be taken with or without food.

Pregnancy and breast-feeding

Pregnancy

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

You should not take Ramipril Taj Pharma in the first 12 weeks of pregnancy and you must not take them at all from the 13th week as their use during pregnancy may possibly be harmful to the baby. If you become pregnant while on Ramipril Taj Pharma, tell your doctor immediately. A switch to a suitable alternative treatment should be carried out in advance of a planned pregnancy.

Breastfeeding

You should not take Ramipril Taj Pharma if you are breast-feeding.

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

Driving and using machines

You may feel dizzy, while taking Ramipril Taj Pharma.

This is more likely to happen when you start taking Ramipril Taj Pharma or start taking a higher dose. If this happens, do not drive or use any tools or machines.

  1. How to take Ramipril Taj Pharma

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

How much to take

Treatment of high blood pressure

  • The usual starting dose is 1.25 mg or 2.5 mg once daily.
  • Your doctor will adjust the amount you take until your blood pressure is controlled.
  • The maximum dose is 10 mg once daily.
  • If you are already taking diuretics (water tablets), your doctor may stop or reduce the amount of the diuretic you take before beginning treatment with Ramipril Taj Pharma.

To reduce the risk of you having a heart attack or stroke

  • The usual starting dose is 2.5 mg once daily.
  • Your doctor may then decide to increase the amount you take.
  • The usual dose is 10 mg once daily.

Treatment to reduce or delay the worsening of kidney problems

  • You may be started on a dose of 1.25 mg or 2.5 mg once daily.
  • Your doctor will adjust the amount you are taking.
  • The usual dose is 5 mg or 10 mg once daily.

Treatment of heart failure

  • The usual starting dose is 1.25 mg once daily.
  • Your doctor will adjust the amount you take.
  • The maximum dose is 10 mg daily. Two administrations per day are preferable.

Treatment after you have had a heart attack

  • The usual starting dose is 1.25 mg once daily to 2.5 mg twice daily.
  • Your doctor will adjust the amount you take.
  • The usual dose is 10 mg daily. Two administrations per day are preferable.

Elderly

Your doctor will reduce the initial dose and adjust your treatment more slowly.

Taking this medicine

  • Take this medicine by mouth at the same time of the day each day.
  • Swallow the tablets whole with liquid.
  • Do not crush or chew the tablets.

If you take more Ramipril Taj Pharma than you should

Tell a doctor or go to the nearest hospital casualty department straight away. Do not drive to the hospital, get somebody else to take you or call for an ambulance. Take the medicine pack with you. This is so the doctor knows what you have taken.

If you forget to take Ramipril Taj Pharma

  • If you miss a dose, take your normal dose when it is next due.
  • Do not take a double dose to make up for a forgotten tablet.

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

  1. Possible side effects

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

Stop taking Ramipril Taj Pharma and see a doctor straight away, if you notice any of the following serious side effects – you may need urgent medical treatment:

  • Swelling of the face, lips or throat which make it difficult to swallow or breathe, as well as itching and rashes. This could be a sign of a severe allergic reaction to Ramipril Taj Pharma tablets.
  • Severe skin reactions including rash, ulcers in your mouth, worsening of a pre-existing skin disease, reddening, blistering or detachment of skin (such as Stevens-Johnson syndrome, toxic epidermal necrolysis or erythema multiform).

Tell your doctor immediately if you experience:

  • Faster heart rate, uneven or forceful heartbeat (palpitations), chest pain, tightness in your chest or more serious problems including heart attack and stroke
  • Shortness of breath or a cough. These could be signs of lung problems
  • Bruising more easily, bleeding for longer than normal, any sign of bleeding (e.g. bleeding from the gums), purple spots, blotching on the skin or getting infections more easily than usual, sore throat and fever, feeling tired, faint, dizzy or having pale skin. These can be signs of blood or bone marrow problems
  • Severe stomach pain which may reach through to your back. This could be a sign of pancreatitis (inflammation of the pancreas).
  • Fever, chills, tiredness, loss of appetite, stomach pain, feeling sick, yellowing of your skin or eyes (jaundice). These can be signs of liver problems such as hepatitis (inflammation of the liver) or liver damage.

Other side effects include:

Tell your doctor if any of the following gets serious or lasts longer than a few days.

Common (may affect up to 1 in 10 people)

  • Headache or feeling tired
  • Feeling dizzy. This is more likely to happen when you start taking Ramipril Taj Pharma or start taking a higher dose
  • Fainting, hypotension (abnormally low blood pressure), especially when you stand or sit up quickly
  • Dry tickly cough, inflammation of your sinuses (sinusitis) or bronchitis, shortness of breath
  • Stomach or gut pain, diarrhoea, indigestion, feeling or being sick
  • Skin rash with or without raised area
  • Chest pain
  • Cramps or pain in your muscles
  • Blood tests showing more potassium than usual in your blood.

Uncommon (may affect up to 1 in 100 people)

  • Balance problems (vertigo)
  • Itching and unusual skin sensations such as numbness, tingling, pricking, burning or creeping on your skin (paraesthesia)
  • Loss or change in the way things taste
  • Sleep problems
  • Feeling depressed, anxious, more nervous than usual or restless
  • Blocked nose, difficulty breathing or worsening of asthma
  • A swelling in your gut called “intestinal angioedema” presenting with symptoms like abdominal pain, vomiting and diarrhoea
  • Heartburn, constipation or dry mouth
  • Passing more water (urine) than usual over the day
  • Sweating more than usual
  • Loss or decrease of appetite (anorexia)
  • Increased or irregular heartbeat
  • Swollen arms and legs. This may be a sign of your body holding onto more water than usual
  • Flushing
  • Blurred vision
  • Pain in your joints
  • Fever
  • Sexual inability in men, reduced sexual desire in men or women
  • An increased number of certain white blood cells (eosinophilia) found during a blood test
  • Blood tests showing changes in the way your liver, pancreas or kidneys are working.

Rare (may affect up to 1 in 1,000 people)

  • Feeling shaky or confused
  • Red and swollen tongue
  • Severe flaking or peeling of the skin, itchy, lumpy rash
  • Nail problems (e.g. loosening or separation of a nail from its bed)
  • Skin rash or bruising
  • Blotches on your skin and cold extremities
  • Red, itchy, swollen or watery eyes
  • Disturbed hearing and ringing in your ears
  • Feeling weak
  • Blood tests showing a decrease in the number of red blood cells, white blood cells or platelets or in the amount of haemoglobin.

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

  • Being more sensitive to the sun than usual.

Other side effects reported:

Tell your doctor if any of the following gets serious or lasts longer than a few days.

  • Difficulty concentrating
  • Swollen mouth
  • Blood tests showing too few blood cells in your blood
  • Blood tests showing less sodium than usual in your blood
  • Concentrated urine (dark in colour), feel or are sick, have muscle cramps, confusion and fits which may be due to inappropriate ADH (anti-diuretic hormone) secretion. If you have these symptoms contact your doctor as soon as possible.
  • Fingers and toes changing colour when you are cold and then tingling or feeling painful when you warm up (Raynaud’s phenomenon)
  • Breast enlargement in men
  • Slowed or impaired reactions
  • Burning sensation
  • Change in the way things smell
  • Hair loss.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. By reporting side effects you can help provide more information on the safety of this medicine.

  1. How to store Ramipril Taj Pharma

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 cartons and blister packs after EXP. The expiry date refers to the last day of that month. This medicine does not require any special storage conditions.

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

  1. Contents of the pack and other information

What Ramipril Taj Pharma Tablets contain.

  • The active substance is Ramipril .
  • Tablets: The other ingredients are hypromellose, pregelatinised maize starch, microcrystalline cellulose, sodium stearyl fumarate.
  • The 2.5mg tablets also contain yellow ferric oxide.
  • The 5mg tablets also contain red ferric oxide.

What Ramipril Taj Pharma Tablets look like and contents of the pack

  • Ramipril Taj Pharma 1.25mg Tablets are white to almost white oblong tablets with score-line. The upper face is marked with 1.25 and a logo ( ) and the lower face is marked with HMN and 1.25. The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.
  • Ramipril Taj Pharma 2.5mg Tablets are yellowish to yellow oblong tablets with a score-line. The upper face is marked with 2.5 and a logo ( ) and the lower face is marked with HMR and 2.5. The tablet can be divided into equal halves.
  • Ramipril Taj Pharma 5mg Tablets are pale red oblong tablets with a score-line. The upper face is marked with 5 and a logo ( ) and the lower face is marked with HMP and 5. The tablet can be divided into equal halves.
  • Ramipril Taj Pharma 10mg Tablets are white to almost white oblong tablets with a score-line. The upper face is marked with HMO/HMO and the lower face is unmarked. The tablet can be divided into equal halves.

All strengths are supplied in PVC aluminium blisters in packs of 28 or 30 tablets. Not all pack sizes may be marketed.

  1. Manufactured By:
    Taj Pharmaceuticals Ltd.
    Mumbai, India Unit No. 214, Old Bake House,
    Maharashtra Chambers of commerce Lane, Fort,
    Mumbai-400001 at: Ahmedabad- Gujarat, INDIA.

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