Tritace 1.25 mg Tablets

Tritace 2.5 mg Tablets

Tritace 5 mg Tablets

Tritace 10 mg Tablets

1.25 mg ramipril.

2.5 mg ramipril.

5 mg ramipril

10 mg ramipril.

For excipients, see 6.1.

Tablet

1.25mg: White to almost white oblong tablets with score-line.

Upper stamp: 1.25 & logo ()

Lower stamp: HMN & 1.25

2.5mg: Yellowish to yellow oblong tablets with score-line.

Upper stamp: 2.5 & logo ()

Lower stamp: HMR & 2.5

5mg: Pale red oblong tablets with score-line.

Upper stamp: 5 & logo ()

Lower stamp: HMP & 5.

10mg: White to almost white, oblong tablets with a score-line

Upper stamp: HMO/HMO

For reducing the risk of myocardial infarction, stroke, cardiovascular death or need for revascularisation procedures in patients of 55 years or more who have clinical evidence of cardiovascular disease (previous MI, unstable angina or multivessel CABG or multivessel PTCA), stroke or peripheral vascular disease.

Also for reducing the risk of myocardial infarction, stroke, cardiovascular death or need for revascularisation procedures in diabetic patients of 55 years or more who have one or more of the following clinical findings: hypertension (systolic blood pressure > 160mmHg or diastolic blood pressure > 90mmHg); high total cholesterol (>5.2 mmol/L); low HDL (<0.9 mmol/L); current smoker; known microalbuminuria; clinical evidence of previous vascular disease.

Tritace is indicated for the treatment of mild to moderate hypertension.

Congestive heart failure as adjunctive therapy to diuretics with or without cardiac glycosides.

Tritace has been shown to reduce mortality when given to patients surviving acute myocardial infarction with clinical evidence of heart failure.

Oral administration.

Dosage and Administration:

Reducing the risk of myocardial infarction, stroke or cardiovascular death and/or the need for revascularisation procedures: The recommended initial dose is 2.5mg Tritace once a day. Depending on the tolerability, the dose should be gradually increased. It is therefore recommended that this dose is doubled after about one week of treatment then, after a further 3 weeks, it should be finally increased to 10mg. The usual maintenance dose is 10mg Tritace once a day. Patients already stabilised on lower doses of Tritace for other indications where possible should be titrated to 10mg Tritace once daily.

Hypertension: The recommended initial dosage in patients not on diuretics and without congestive heart failure is 1.25 mg Tritace once a day. Dosage should be increased incrementally at intervals of 1 - 2 weeks, based on patient response, up to a maximum of 10 mg once a day.

A 1.25 mg dose will only achieve a therapeutic response in a minority of patients. The usual maintenance dose is 2.5 - 5 mg as a single daily dose. If the patient response is still unsatisfactory at a dose of 10 mg Tritace, combination treatment is recommended.

In hypertensive patients who also have congestive heart failure, with or without associated renal insufficiency, symptomatic hypotension has been observed after treatment with ACE inhibitors. In these patients therapy should be started at a dose of 1.25 mg under close medical supervision in hospital.

Congestive heart failure: Recommended initial dose: In patients stabilised on diuretic therapy the initial dose is 1.25 mg once daily. Depending on the patient's response, the dose may be increased. It is recommended that the dose, if increased, be doubled at intervals of 1 to 2 weeks. If a daily dose of 2.5 mg or more is required, this may be taken as a single dose or as two divided doses. Maximum permitted daily dose: 10 mg.

Post myocardial infarction: Initiation of therapy: Treatment must be started in hospital between day 3 and day 10 following AMI. The starting dose is 2.5 mg twice a day with one taken in the morning and one in the evening. The dose can then be increased to 5 mg twice a day after 2 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 5.0 mg twice a day at intervals of 1 to 3 days.

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 1.25mg once daily and that particular caution be exercised in any dose increase.

Maintenance dose: 2.5 to 5.0 mg twice a day.

Maximum daily dose: 10mg.

Patients on diuretics/Patients with salt depletion: In diuretic treated patients, the diuretic should be discontinued for 2-3 days (or longer depending on the duration of action of the diuretic), or at least the dose reduced, to reduce the likelihood of symptomatic hypotension. It may be resumed later if required. The initial daily dose in patients previously treated with a diuretic is generally 1.25mg Tritace.

In patients with incompletely corrected fluid or salt depletion, in patients with severe hypertension, as well as in patients in whom a hypotensive reaction would constitute a particular risk, (e.g., with relevant stenoses of the coronary or cerebral vessels), a reduced initial dose of 1.25mg Tritace should be considered.

Dosage adjustment in renal impairment: The usual dose of Tritace is recommended for patients with a creatinine clearance > 30 ml/min (serum creatinine < 165 μmol/l). For patients with a creatinine clearance < 30 ml/min (serum creatinine >165 μmol/l) the initial dose is 1.25 mg Tritace once daily and the maximum dose 5 mg Tritace once daily.

In patients with severe renal impairment (creatinine clearance < 10 ml/min and serum creatinine of 400-650 μmol/l), the recommended initial dose is also 1.25 mg Tritace once a day, but the maintenance dose should not exceed 2.5 mg Tritace once a day.

Dosage in hepatic impairment: In patients with impaired liver function the metabolism of the parent compound ramipril, and therefore the formation of the bioactive metabolite ramiprilat, is delayed due to a diminished activity of esterases in the liver, resulting in elevated plasma ramipril levels. Treatment with ramipril should therefore be initiated at a dose of 1.25 mg under close medical supervision in patients with impaired liver function.

Higher doses should be used with caution.

Elderly: Caution in all elderly patients especially those with concomitant use of diuretics, congestive heart failure or renal or hepatic insufficiency. A reduced initial dose of 1.25mg Tritace should be considered. The dose should then be titrated accordingly

Children: Tritace has not been studied in children, and therefore use in this age group is not recommended.

Tritace should be swallowed whole with a glass of water. The tablets must not be chewed or crushed. The absorption of ramipril is not affected by food and Tritace may therefore be taken before, during or after a meal.

Hypersensitivity to ramipril, any of the excipients of Tritace, or to any other ACE inhibitor.

History of angioedema.

Haemodynamically relevant bilateral renal artery stenosis or unilateral in the single kidney.

Hypotensive or haemodynamically unstable patients.

Pregnancy.

Breast-feeding women.

Concomitant use of ACE inhibitors and extracorporeal treatments leading to contact of blood with negatively charged surfaces must be avoided, since such use may lead to severe anaphylactoid reactions. Such extracorporeal treatments include dialysis or haemofiltration with certain high-flux (e.g. polyacrylonitril) membranes and low-density lipoprotein apheresis with dextran sulfate. This combination should therefore be avoided, either by use of alternative antihypertensive drugs or alternative membranes for dialysis.

Warnings:

Angioedema - Head, Neck or Extremities

Angioedema occurring during treatment with an ACE inhibitor necessitates immediate discontinuation of the drug. Angioedema of the face, extremities, lips, tongue, glottis or larynx has been reported in patients treated with ACE inhibitors and hospitalisation of the patient is advisable.

Angioedema –Intestinal

Intestinal angioedema has been reported in patients treated with ACE inhibitors.

These patients presented with abdominal pain (with or without nausea or vomiting); in some cases facial angioedema also occurred. The intestinal angioedema symptoms resolved after stopping the ACE inhibitor.

Tritace should not be used in patients with aortic or mitral valve stenosis or outflow obstruction (see Precautions section below).

Precautions:

Assessment of renal function: Evaluation of the patient should include assessment of renal function prior to initiation of therapy and during treatment.

Impaired renal function: Patients with renal insufficiency may require reduced or less frequent doses of Tritace; their renal function should be closely monitored. In the majority, renal function will not alter. There is a risk of impairment of renal function, particularly in patients with congestive heart failure or after a renal transplant, renal insufficiency and bilateral renal artery stenosis and unilateral renal artery stenosis in the single kidney. In the latter patient group, even a small increase in serum creatinine may be indicative of unilateral loss of renal function. If recognised early, such impairment of renal function is reversible upon discontinuation of therapy.

Patients haemodialysed using high flux polyacrylonitrile ('AN69') membranes are highly likely to experience anaphylactoid reactions if they are treated with ACE inhibitors. This combination should therefore be avoided, either by use of alternative antihypertensive drugs or alternative membranes for dialysis.

Similar reactions have been observed during low-density lipoprotein apheresis with dextran sulphate. This method should, therefore, not be used in patients treated with ACE inhibitors.

Some hypertensive patients with no apparent pre-existing renal disease may develop minor and usually transient increases in blood urea nitrogen and serum creatinine when Tritace is given, in particular concomitantly with a diuretic. Dosage reduction of Tritace and/or discontinuation of the diuretic may be required.

Impaired liver function: As ramipril is a prodrug metabolised to its active moiety in the liver, particular caution and close monitoring should be applied to patients with impaired liver function. The metabolism of the parent compound, and therefore the formation of the bioactive metabolite ramiprilat, may be diminished resulting in markedly elevated plasma levels of the parent compound (due to the reduced activity of esterases in the liver).

In patients in whom severe liver cirrhosis with oedema and/or ascites is present, the renin angiotensin system may be significantly activated; therefore, particular caution must be exercised in treating these patients (see also above and under “4.2 Posology and Method of Administration”).

Symptomatic hypotension: In patients with uncomplicated hypertension, symptomatic hypotension has been observed rarely after the initial dose of Tritace as well as after increasing the dose of Tritace. It is more likely to occur in patients who have been volume- and salt-depleted by prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhoea, vomiting or patients with severe heart failure. Therefore, in these patients, diuretic therapy should be discontinued and volume and/or salt depletion should be corrected before initiating therapy with Tritace.

Agranulocytosis and bone marrow depression: In patients on angiotensin converting enzyme inhibitors agranulocytosis and bone marrow depression have been seen rarely, as well as a reduction in red cell count, haemoglobin content and platelet count. These are more frequent in patients with renal impairment, especially if they have a collagen vascular disease. Regular monitoring of white blood cell counts (to permit detection of a possible leucopenia) and protein levels in urine should be considered in patients with collagen vascular disease (e.g. lupus erythematosus and scleroderma), especially associated with impaired renal function and concomitant therapy particularly with corticosteroids and anti metabolites. Patients on allopurinol, immunosuppressants and other substances that may change the blood picture also have increased likelihood of other blood picture changes.

Hyperkalaemia: Elevated serum potassium has been observed very rarely in hypertensive patients. Risk factors for the development of hyperkalaemia include renal insufficiency, potassium sparing diuretics and the concomitant use of agents to treat hypokalaemia. It is recommended that serum potassium be monitored regularly. More frequent monitoring of serum potassium is necessary in patients with impaired renal function.

Patients with hyper-stimulated renin angiotensin system: In the treatment of patients with a hyper-stimulated renin angiotensin system, particular caution must be exercised (see also under “4.2 Posology and Method of Administration”). Such patients 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 for the first time at an increased dose. Initial doses or initial dose increases must be accompanied by close blood pressure monitoring until such time as no further acute reduction in blood pressure is to be anticipated.

Significant activation of the renin angiotensin system is to be anticipated, for example:

• in patients with severe and/or malignant hypertension.

• in patients with heart failure, particularly if severe or if treated with other substances having antihypertensive potential.

• in patients with haemodynamically relevant left-ventricular inflow or outflow obstruction (e.g., aortic or mitral valve stenosis).

• in patients pre-treated with diuretics.

• in patients with fluid or salt depletion, or in those whom it may develop (as a result of insufficient fluid or salt intake, or as a result of, e.g., dialysis, diarrhoea, vomiting or excessive sweating in cases where salt and fluid replacement is inadequate).

Generally, it is recommended that dehydration, hypovolaemia or salt depletion be corrected before initiating treatment (in patients with heart failure, however, such corrective action must be carefully weighed against other risks of volume overload). When these conditions have become clinically relevant, treatment with Tritace must only be started or continued if appropriate steps are taken concurrently to prevent an excessive fall in blood pressure and deterioration of renal function.

For all of the above, the initial phase of treatment requires close medical supervision.

Patients at particular risk from a pronounced reduction in blood pressure: If symptomatic hypotension occurs, the patient should be placed in a supine position and, if necessary, receive an intravenous infusion of physiological saline. Intravenous atropine may be necessary if there is associated bradycardia. Treatment with Tritace may usually be continued following restoration of effective blood volume and blood pressure.

Surgery/anaesthesia: In patients undergoing surgery or during anaesthesia with agents producing hypotension, Tritace may block angiotensin II formation secondary to compensatory renin release. If hypotension occurs and is considered to be due to this mechanism, it can be corrected by appropriate treatment.

Vasopressor sympathomimetics: These may reduce the antihypertensive effect of Tritace. Particularly close blood pressure monitoring is recommended.

Allopurinol, immunosuppressants, corticosteroids, procainamide, cytostatics and other substances that may change the blood picture: Increased likelihood of haematological reactions (see also under “4.4 Special Warnings and Special Precautions for use”).

Lithium Salts: Excretion of lithium may be reduced by ACE inhibitors. Such reduction may lead to increased serum lithium levels and increased lithium toxicity. Lithium levels must, therefore, be monitored.

Diuretics and other antihypertensive agents: Combination with diuretics or other antihypertensive agents may potentiate the antihypertensive response to Tritace. Potassium sparing diuretics (spironolactone, amiloride, triamterene) or potassium supplements may increase the risk of hyperkalaemia. Tritace may attenuate the potassium loss caused by thiazide-type diuretics. Regular monitoring of serum sodium and potassium is recommended in patients undergoing concurrent diuretic therapy. Adrenergic-blocking drugs should only be combined with ramipril under careful supervision.

Combination with antidiabetics: When antidiabetic agents (insulin and sulphonylurea derivatives) are used concurrently, the possibility of increased blood-sugar reduction must be considered. Particularly close blood glucose monitoring is therefore recommended in the initial phase of co-administration.

Combination with NSAIDS: When ACE inhibitors are administered simultaneously with non-steroidal anti-inflammatory drugs (e.g. acetylsalicylic acid and indomethacin), attenuation of the antihypertensive effect may occur. Furthermore, concomitant use of ACE inhibitors and NSAIDs may lead to an increased risk of worsening of renal function and an increase in serum potassium.

Heparin: Rise in serum potassium concentration possible.

Desensitisation therapy: The likelihood and severity of anaphylactic and anaphylactoid reactions to insect venoma is increased under ACE inhibition. It is assumed that this effect may also occur in connection with other allergens.

The protein binding of ramipril is about 73% and of ramiprilat about 56%.

Tritace must not be taken during pregnancy. Therefore, pregnancy must be excluded before starting treatment. If the patient intends to become or becomes pregnant, treatment with ACE inhibitors must be discontinued, i.e. replaced by another form of treatment. Pregnancy must be avoided in cases where treatment with ACE inhibitors is indispensable.

It is not known if exposure limited to the first trimester only can harm the fetus. Exposure of the mother to ACE inhibitors in mid or late pregnancy has been associated with oligohydramnios and neonatal hypotension with anuria or renal failure.

From animal experiments it is known that use of ramipril may cause a decreased utero-placental perfusion. There is also a potential risk of fetal or post-natal effect as ACE inhibitors also influence the local renin-angiotensin system. In peri-post natal studies increased renal pelvic dilation was observed in the first generation offspring. However, ramipril was not fetotoxic in our studies although ACE inhibitors have shown fetotoxicity in some species.

If treatment with Tritace is necessary during lactation, the patient must not breast feed in order to prevent the infant from ingesting small quantities of ramipril with breast milk.

In individual cases, as a result of a reduction in blood pressure, treatment with Tritace may affect the ability to drive and operate machinery. This occurs especially at the start of treatment, when changing over from other preparations and during concomitant use of alcohol. After the first dose or subsequent increases in dose it is not advisable to drive or operate machinery for several hours.

Generally, adverse reactions have been mild and transient, and do not require discontinuation of therapy. The most frequently reported adverse reactions are nausea, dizziness and headache. Uncommonly drowsiness, light-headedness or impaired reactions may occur.

Reactions such as peripheral oedema, tinnitus, fatigue, visual disturbances, sweating, disturbed hearing, disturbed orthostatic regulation are rare.

Cardiovascular: Symptomatic hypotension accompanied by dizziness, weakness and nausea may occur after the initial dose of Tritace and after an increase in the dose of Tritace. It has been rarely observed, but may occur in severely salt/volume-depleted patients such as those treated with diuretics, patients on dialysis and in patients with severe congestive heart failure. Syncope has also been observed rarely.

Myocardial infarction or cerebrovascular accident possibly secondary to severe hypotension in high risk patients, chest pain, palpitations, rhythm disturbances, angina pectoris may occur.

Renal: Treatment with Tritace may impair renal function and in isolated cases progression to acute renal failure may occur.

Gastrointestinal: Treatment with Tritace may be associated with symptoms in the digestive tract, e.g. rarely dryness of the mouth, glossitis, irritation or inflammation of the oral mucosa, digestive disturbances, constipation, diarrhoea, nausea, and vomiting, (gastritis-like) stomach pain, abdominal discomfort (sometimes with increased levels of pancreatic enzymes). Uncommonly increases in hepatic enzymes and/or serum bilirubin, jaundice due to impaired excretion of bile pigment (cholestatic jaundice), acute hepatitis, potentially leading to liver failure.

Pancreatitis has been reported rarely in patients treated with ACE inhibitors; in some cases this has proved fatal.

Allergic: Hypersensitivity reactions accompanied by pruritus, rash, shortness of breath and sometimes fever may occur, but usually resolve spontaneously after withdrawal of Tritace.

In addition, the following cutaneous and mucosal reactions may occur: reddening of skin areas with accompanying heat sensation, conjunctivitis, itching, urticaria, other skin or mucosal eruptions (maculo-papular and lichenoid exanthema and enanthema, erythema multiforme), sometimes pronounced hair loss, exacerbation of perfusion disturbances due to vascular stenoses and precipitation or intensification of Raynaud's phenomenon. In isolated cases, pemphigus, exacerbation of psoriasis, psoriasiform and pemphigoid exanthema and enanthema, Stevens-Johnson syndrome, toxic epidermal necrolysis, hypersensitivity of the skin to light, and onycholysis have been observed.

See Section 4.5 (Interactions) for advice on reactions to insect venoma.

Haematological reactions: Rarely, a mild - in isolated cases severe – reduction in the red blood cell count and haemoglobin content, white blood cell or blood platelet count may develop. In isolated cases, agranulocytosis, pancytopenia and bone marrow depression may occur.

In isolated cases haemolytic anaemia may develop.

Vasculitis, muscle and joint pains, fever, or eosinophilia may occur. Raised titres of antinuclear antibodies have been seen with other ACE inhibitors.

Angioedema: See Section 4.4 (Special Warnings and Special Precautions for use). Uncommonly, pharmacologically mediated mild angioedema may occur (the incidence of ACE inhibitor angioedema seems to be increased in black, i.e. Afro-Caribbean, patients as compared with non-black patients). Serious reactions of this type and other, non-pharmacologically mediated anaphylactic or anaphylactoid reactions to ramipril or any of the other ingredients are rare.

Respiratory tract: A dry tickling cough may occur. This is possibly due to the desired ACE inhibition as are the following adverse effects: rhinitis, sinusitis, bronchitis and, especially in patients with tickling cough, bronchospasm.

Other adverse reactions: Disturbances of balance, headache, nervousness, restlessness, tremor, sleep disorders, confusion, loss of appetite, depressed mood, feeling of anxiety, paraesthesiae, uncommonly, disturbances of smell and taste or partial, sometimes complete loss of taste, muscle cramps, erectile impotence and reduced sexual desire may occur.

Laboratory test findings: Increases in blood urea nitrogen and serum creatinine may occur, in particular with renal insufficiency or in patients pre-treated with a diuretic. Pre-existing proteinuria may deteriorate (though ACE inhibitors usually reduce proteinuria), or there may be an increase in urinary output.

Sodium/Potassium serum levels - See Section 4.5 (Special warnings and special precautions for use).

Symptoms

Overdosage may cause excessive peripheral vasodilation (with marked hypotension, shock), bradycardia, electrolyte disturbances, and renal failure.

Management

General measures to ensure adequate ventilation and circulation should be taken.

Despite the benefits of gastric decontamination being uncertain, it is recommended to consider activated charcoal (50g for adults, 1g/kg for children) if the patient presents within 1 hour of ingestion of a potentially toxic amount (0.5mg/kg).

If severe hypotension occurs, the patient should be placed in the shock position and salt and volume supplementations should be given rapidly. In the event of prolonged hypotension that persists in spite of the above measures, administration of inotropes (e.g. dopamine, norepinephrine) or angiotensin II (angiotensinamide) must be considered in addition to volume and salt substitution.

Pharmacotherapeutic group: Converting Enzyme Blockers, ATC code CO2E A05.

Ramipril is a prodrug, which after absorption from the gastrointestinal tract, is hydrolysed in the liver to form the active angiotensin converting enzyme (ACE) inhibitor, ramiprilat, which is a potent and long acting ACE inhibitor. Administration of ramipril causes an increase in plasma renin activity and a decrease in plasma concentrations of angiotensin II and aldosterone. The beneficial haemodynamic effects resulting from ACE inhibition are a consequence of the reduction in angiotensin II causing dilation of peripheral vessels and reduction in vascular resistance. There is evidence suggesting that tissue ACE particularly in the vasculature, rather than circulating ACE, is the primary factor determining the haemodynamic effects.

Angiotensin converting enzyme is identical with kininase II, one of the enzymes responsible for the degradation of bradykinin. There is evidence that ACE inhibition by ramiprilat appears to have some effects on the kallikrein-kinin-prostaglandin systems. It is assumed that effects on these systems contribute to the hypotensive action of ramipril.

Administration of Tritace to hypertensive patients results in reduction of both supine and standing blood pressure. The antihypertensive effect is evident within one to two hours after the drug intake; peak effect occurs 3 - 6 hours after drug intake and has been shown to be maintained for at least 24 hours after usual therapeutic doses.

In a large endpoint study – HOPE - ramipril significantly reduced the incidence of stroke, myocardial infarction and/or cardiovascular death when compared with placebo. These benefits occurred largely in normotensive patients and were shown, using standard regression analysis techniques, to be only partially due to the relatively modest reductions in blood pressure demonstrated in the study. The 10mg dose, currently the highest safe dose level approved, was selected by the HOPE investigators from previous dose-ranging studies (SECURE, HEART) and was considered to be the most likely dose to effect full blockade of the renin-angiotensin-aldosterone system. This and other studies suggest that ACE inhibitors like ramipril are likely to have other direct effects on the cardiovascular system. These may include the antagonism of angiotensin II mediated vasoconstriction, the inhibition of proliferating vascular smooth muscle and plaque rupture, the enhancement of endothelial function, the reduction of LV hypertrophy and positive effects on fibrinolysis. Additional effects in diabetic patients may also contribute e.g. effects on insulin clearance and pancreatic blood flow.

Following oral administration ramipril is rapidly absorbed from the gastrointestinal tract; peak plasma concentrations of ramipril are reached within one hour. Peak plasma concentrations of the active metabolite, ramiprilat, are reached within 2 – 4 hours.

Plasma concentrations of ramiprilat decline in a polyphasic manner. The effective half-life of ramiprilat after multiple once daily administration of ramipril is 13 – 17 hours for 5 – 10 mg ramipril and markedly longer for lower doses, 1.25 – 2.5 mg ramipril. This difference is related to the long terminal phase of the ramiprilat concentration time curve observed at very low plasma concentrations. This terminal phase is independent of the dose, indicating a saturable capacity of the enzyme to bind ramiprilat. Steady-state plasma concentrations of ramiprilat after once daily dosing with the usual doses of ramipril are reached by about the fourth day of treatment.

Ramipril is almost completely metabolised and the metabolites are excreted mainly via the kidneys. In addition to the bioactive metabolite, ramiprilat, other, inactive metabolites have been identified, including diketopiperazine ester, diketopiperazine acid and conjugates.

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 to female rats during the fetal period and lactation produced irreversible renal damage (dilation of the renal pelvis) in the offspring at daily doses of 50 mg/kg body weight and higher.

1.25mg and 10mg: Methylhydroxypropylcellulose, pregelatinised starch, microcrystalline cellulose, sodium stearyl fumarate.

2.5mg: Methylhydroxypropylcellulose, pregelatinised starch, microcrystalline cellulose, sodium stearyl fumarate, yellow ferric oxide.

5mg: Methylhydroxypropylcellulose, pregelatinised starch, microcrystalline cellulose, sodium stearyl fumarate, red ferric oxide.

None known.

5 years (1.25mg, 2.5mg and 5mg tablets)

4 years (10mg tablets)

Store below 25°C

PVC aluminium blisters containing tablets. Available in packs of 28 tablets

None

Sanofi-aventis

One Onslow Street

Guildford

Surrey GU1 4YS

UK

1.25mg: PL 04425/0356

2.5mg: PL 04425/0357

5mg: PL 04425/0358

10mg: PL 04425/0359

30^th September 2003

10 April 2007

Legal category: POM