INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo RAMPIL 1,25 MG CAPSULE
RAMPIL 2,5 MG CAPSULE
RAMPIL 5 MG CAPSULE
RAMPIL 10 MG CAPSULE

SCHEDULING STATUS:
S3

PROPRIETARY NAME
(and dosage form):

RAMPIL 1,25 MG CAPSULE
RAMPIL 2,5 MG CAPSULE
RAMPIL 5 MG CAPSULE
RAMPIL 10 MG CAPSULE

COMPOSITION
RAMPIL
1,25 mg - Each capsule contains 1,25 mg of
ramipril.
RAMPIL 2,5 mg - Each capsule contains 2,5 mg of ramipril.
RAMPIL 5 mg - Each capsule contains 5 mg of ramipril.
RAMPIL 10 mg - Each capsule contains 10 mg of ramipril.

PHARMACOLOGICAL CLASSIFICATION
A 7.1.3 Other hypotensives

PHARMACOLOGICAL ACTION
Ramipril inhibits angiotensin I-converting enzyme (ACE) activity. It inhibits the conversion of the relatively inactive angiotensin I to the active angiotensin II.
Angiotensin II is a potent vasocontrictor and stimulates the release of aldosterone.
Decreased angiotensin II levels result in a decrease in vasopressor activity and reduction in aldosterone secretion, which may result in small increases in serum potassium.
It is also thought that ACE inhibition may inhibit degradation of bradykinin, leading to increased bradykinin levels.
Pharmacokinetics:
The extent of absorption after oral administration is 60% with wide variability between patients. The plasma half-life is increased in renal impairment. The time to achieve peak serum concentration is within 1 hour. Ramipril is renally eliminated and excreted 100% unchanged in the urine.

INDICATIONS
RAMPIL
capsules are indicated for the following:
Mild to moderate hypertension.
Cardiac failure following myocardial infarction.
To reduce proteinuria and the decline in glomerular filtration rate in patients with diabetic nephropathy and hypertension.
To reduce the risk of myocardial infarction, stroke or cardiovascular death and to reduce the need for revascularisation procedures in patients with an increased cardiovascular risk such as manifest coronary heart disease (with or without a history of myocardial infarction), a history of stroke or a history of peripheral vascular disease.
To reduce the risk of myocardial infarction, stroke or cardiovascular death in diabetic patients.

CONTRA-INDICATIONS
Sensitivity to any of the components of RAMPIL.
Patients with a history of angioedema related to previous ACE-inhibitor therapy or angiotensin receptor blocker.
Hereditary or idiopathic angioedema.
Aortic stenosis.
Hypertrophic obstructive cardiomyopathy.
Severe renal function impairment (creatinine clearance below 30 mL/min).
Renal artery stenosis in patients with a single kidney.
Concomitant therapy with potassium sparing diuretics such as spironolactone, triamterene, amiloride.
Porphyria.

WARNINGS
Should a woman become pregnant while receiving an ACE inhibitor, the treatment must be stopped promptly and changed to a different medicine. (SEE PREGNANCY AND LACTATION)
If a woman is contemplating pregnancy, a different class of medicine should be used.
(SEE PREGNANCY AND LACTATION)
RAMPIL should be used with caution in the following conditions:
Cerebrovascular disease or ischaemic heart disease - Reduction in blood pressure could aggravate these conditions and may result in myocardial infarction and cerebrovascular accidents.
Volume depleted patients (e.g. by diuretic therapy, dietary salt restriction, dialysis, diarrhoea or vomiting) - Although it may occur in normo volumic patients, hypotension is more likely in volume depleted patients. A sudden reduction in angiotensin II may result in sudden and severe hypotension. There is also an increased risk of RAMPIL induced renal failure, especially in those with congestive heart failure.
Patients at a high risk of symptomatic hypotension e.g. patients with salt or volume depletion with or without hyponatraemia should have these conditions corrected before therapy with RAMPIL. Monitoring is required after initiating therapy.
Severe autoimmune disease, especially systemic lupus erythematosus, other collagen vascular disease or scleroderma: Increase the risk for development of neutropenia or agranulocytosis.
In acute myocardial infarction, treatment with RAMPIL should not be initiated in patients with evidence of renal dysfunction (serum creatinine concentrations exceeding 177 micromol/L or proteinuria exceeding 500 mg/24 hours). If renal dysfunction develops during treatment (serum creatinine concentrations exceeding 177 micromol/L or doubling of the pre-treatment value) then RAMPIL may need to be withdrawn (see also contra-indications).
In acute myocardial infarction, patients may develop persistent hypotension and/or impaired renal function.
Hypotension in acute myocardial infarction - Treatment with RAMPIL must not be initiated in acute myocardial infarction patients who are at risk of further serious haemodynamic deterioration after treatment with a vasodilator. These include patients with systolic blood pressure of 99,98 mmHg or lower or cardiogenic shock. During the first 3 days following the infarction, the dose should be reduced if the systolic blood pressure is 119,93 mmHg or lower. Maintenance doses should be reduced to 5 mg or temporarily to 2,5 mg if systolic blood pressure is 99,98 mmHg or lower. If hypotension persists (systolic blood pressure less than 89,93 mmHg or more than 1 hour) then RAMPIL should be withdrawn.
Bone marrow depression - Increased risk of agranulocytosis and neutropenia.
Diabetes mellitus - Increased risk of hyperkalaemia, as well as hypoglycaemia may occur.
Hyperkalaemia -RAMPIL may cause an increase in serum potassium levels.
Renovascular disease -RAMPIL should not be used in patients with renovascular disease or suspected renovascular disease but it may be used cautiously in severe resistant hypertension in such patients. In this instance RAMPIL should only be used under specialist supervision. The elderly, patients with peripheral vascular diseases or generalised atherosclerosis may have asymptomatic renovascular disease. (SEE DOSAGE AND DIRECTIONS FOR USE)
Renal artery stenosis, bilateral or in one kidney or renal transplant - Increased risk of renal function impairment may increase blood urea and serum creatinine concentrations, which may be reversible upon discontinuation of therapy. There is also an increased risk of agranulocytosis and neutropenia when immunosuppressants are concurrently administered.
Renal function impairment - Decreased elimination of RAMPIL resulting in an increased risk of hyperkalaemia. These patients may require lower doses.
Anaphylactoid reactions have occurred in patients using ACE inhibitors during desensitising protocols involving for example, hymenoptera venom.
Anaphylactoid reactions have been reported in patients exposed to either high-flux membrane dialysis or low-density lipoprotein apheresis with dextran sulfate absorption.
Hypersensitivity/Angioedema - If Angioedema of the face, extremities, lips, tongue, glottis and/or larynx is observed in patients treated with RAMPIL, RAMPIL should be discontinued promptly. These patients should be monitored to ensure complete resolution of symptoms.
Angioedema associated with laryngeal oedema may be fatal. Where there is involvement of the tongue, glottis or larynx, likely to cause airway obstruction, appropriate emergency therapy should be administered. This may include the administration of adrenaline and/or the maintenance of a patent airway. The patient should be under close medical supervision until complete and sustained resolution of symptoms has occurred. These patients should never receive any RAMPIL again.
RAMPIL causes a higher rate of angioedema in black patients than in non-black patients.
Safety and efficacy in children have not been established.
Concomitant therapy with potassium sparing diuretics such as spironolactone, triamterene, amiloride may lead to hyperkalaemia, which may be severe and lead to cardiac conduction abnormalities, dysarrythmias and cardiac arrest.

INTERACTIONS
Concomitant use of RAMPIL with:
Diuretics, alcohol and hypotension-producing medications - The antihypertensive effect is additive. Dosage adjustments may be necessary during concurrent use or when one medicine is discontinued.
Loop thiazide or related diuretics - “First dose hypotension”may occur (SEE DOSAGE AND DIRECTIONS FOR USE).
Indomethacin and nonsteroidal anti-inflammatory medicines (NSAIDs) - reduce the antihypertensive effects of RAMPIL. Blood pressure monitoring should be increased when any NSAID is added or discontinued in a patient treated with RAMPIL.
Potassium supplements or potassium sparing diuretics such as spironolactone, triamterene or amiloride - Concurrent administration may result in hyperkalaemia.
Lithium - Increases in lithium concentrations have been reported. Frequent monitoring of serum lithium concentrations is recommended.

PREGNANCY AND LACTATION
Use of RAMPIL limited to the first trimester does not appear to present a significant risk to the foetus, but foetal exposure after this time has been associated with teratogenicity and severe toxicity in the foetus and newborn, including death. RAMPIL crosses the placenta. Foetal exposure to ACE inhibitors during the second and third trimester can cause hypotension, renal failure, anuria, skull hypoplasia, hyperkalaemia and oliguria. Oligohydramnios may occur resulting in pulmonary hypoplasia, limb contractures and craniofacial deformation.
Infants who have been exposed in utero to RAMPIL should be closely monitored.
Peritoneal dialysis may be of some benefit in the clearance of RAMPIL from the neonatal circulation. Safety in lactation has not been established.

DOSAGE AND DIRECTIONS FOR USE
May be taken with/without meals preferably at the same time every day.
Hypertension
Adults: Initial dose is 2,5 mg RAMPIL once daily (for patients not on diuretics). The dose should be adjusted according to blood pressure response. Dosage should be increased to 5 mg RAMPIL and up to a maximum of 10 mg once daily at intervals of 1 to 2 weeks. The dose range is 2,5 - 10 mg.
The full therapeutic effect may take several weeks. Therefore, if the desired effect has not been achieved within 2 to 4 weeks the dose may be increased.
To reduce the risk of myocardial infarction, stroke or cardiovascular death
Adults: Initial dose is 2,5 mg RAMPIL once daily. This may be increased at intervals of 4 weeks until the therapeutic effect is reached. Adjustments should be based on clinical response. The increase should be implemented by doubling the dose after one week of treatment. Three weeks later, it should be doubled again to the normal maintenance dose of 10 mg once daily.
Non-diabetic and diabetic nephropathy
Adults: Initial dose is 1,25 mg RAMPIL once daily. Adjustments should be based on clinical response. The dose, if increased, should be implemented by doubling the dose at intervals of two to three weeks. The maximum permitted daily dose is 10 mg.
Post-myocardial infarction
Treatment with RAMPIL should be initiated in hospital three to ten days after acute myocardial infarction if the patient manifests with evidence of heart failure and is haemodynamically stable.
Adults: 2,5 mg twice daily for two days. If well tolerated the dose may be increased to 5 mg RAMPIL twice daily.
If patients are unable to tolerate 2,5 mg initially, 1,25 mg RAMPIL twice daily may be given initially and later increased to 2,5 mg twice daily.

Dosing in high-risk individuals:
Diuretic-treated patients: In order to minimise the possibility of sudden and severe hypotension which may occur within the first 1 to 5 hours after the initial dose of RAMPIL, diuretics should be discontinued 2 to 3 days before beginning therapy with RAMPIL. In patients where diuretic therapy cannot be discontinued, treatment with RAMPIL should be initiated with a 1,25 mg dose. Subsequent dosage adjustments will depend on the therapeutic response.
Renovascular hypertension - Dose should be lowered and the patient should be monitored.
RAMPIL is not affected by the presence of food. RAMPIL should be administered as a single daily dose at approximately the same time every day.

SIDE EFFECTS AND SPECIAL PRECAUTIONS
Side Effects:
Haematological:
Less frequent: Decreases in white blood cell count, haemoglobin and haematocrit, bone marrow depression, anaemia, thrombocytopenia, agranulocytosis, haemolytic anaemia.
Cardiovascular:
Less frequent: Orthostatic effects (including hypotension, myocardial infarction, cerebrovascular accident, palpitations, tachycardia. Neurolgical:
Frequent: Dizziness, headache, fatigue.
Less frequent: Mood alterations, mental confusion, paraesthesia, vertigo, sleep disturbances.
Endocrine/Metabolic:
Less frequent: Hyperkalaemia, hyponatraemia, increases in blood urea, increases in serum creatinine.
Gastrointestinal:
Frequent: Diarrhoea, nausea.
Less frequent: Abdominal pain, indigestion, dry mouth, pancreatitis, vomiting, taste disturbances.
Kidney/Genitourinary:
Less frequent: Uraemia, oligouria, anuria, renal dysfunction, acute renal failure, impotence.
Liver/hepatic:
Less frequent: Hepatitis (hepatocellular or cholestatic) jaundice, increases in liver enzymes, increases in serum bilirubin.
Musculoskeletal:
Less frequent: Asthaenia.
Respiratory:
Frequent: Cough.
Less frequent: Bronchospasm, rhinitis, sinusitis.
Skin:
Less frequent: Rash, urticaria, diaphoresis, alopecia, pruritus, psoriasis, severe skin disorders including pemphigus, toxic epidermal necrolysis, Stevens-Johnson Syndrome and erythema multiforme.
Other:
Less frequent: Hypersensitivity/angioedema reactions: angioedema of the face, which may be fatal, extremities, lips, tongue, glottis and/or larynx, and intestinal angioedema. A symptom complex has been reported which may include: fever, vasculitis, myalgia, arthritis/arthralgia, a positive antinuclear antibodies (ANA), elevated erythrocyte sedimentation rate, eosinophilia and leucocytosis. Rash, photosensitivity or other dermatological manifestations may occur.
Special precautions:
Myocardial infarction and cerebrovascular accidents may be due to severe falls in blood pressure in high-risk patients e.g. those with ischaemic heart disease or cerebrovascular disease.
In volume depleted patients or patients with ischaemic heart disease or cerebrovascular disease, therapy should be monitored especially when the dose of RAMPIL or diuretic is adjusted.
If hypotension occurs, the patient should be placed in the supine position and if necessary receive an intravenous infusion of 0,9% saline.
Increases in blood urea and serum creatinine have been seen in patients with no apparent pre-existing vascular disease, especially when RAMPIL has been given concomitantly with a diuretic. Dosage reduction or discontinuation of RAMPIL or the diuretic may be required.
Signs of facial or extremity swelling or difficulty in swallowing or breathing, requires immediate medical attention, because of the risk of angioedema.
Caution when driving or performing tasks requiring alertness because of possible dizziness.
In patients undergoing major surgery or during anaesthesia with agents that produce hypotension, RAMPIL may block angiotension II formation secondary to complementary rennin release. If hypotension occurs and is considered to be due to this mechanism, it can be corrected by volume expansion.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
(See SIDE EFFECTS AND SPECIAL PRECAUTIONS)
Symptoms of overdose:
Severe hypotension, electrolyte disturbances and renal failure.
Treatment of overdose:
Treatment is symptomatic and supportive. Activated charcoal may be given in severe overdosage if the patient presents within 1 hour of ingestion. Treatment consists of volume expansion to correct hypotension and treating dehydration and electrolyte imbalances. RAMPIL is removable by haemodialysis.

IDENTIFICATION
RAMPIL
1,25 mg: Hard gelatin #4 capsule with yellow opaque body and yellow opaque cap. The cap has radially imprinted “RM 1,25”
Capsules contain a white to off-white powder.
RAMPIL 2,5 mg: Hard gelatin size #4 capsule with orange opaque body and orange opaque cap. The cap has radially imprinted “RM 2,5”
Capsules contain a white to off-white powder.
RAMPIL 5 mg: Hard gelatin size #4 capsule with Swedish orange opaque body and Swedish orange opaque cap. The cap has radially imprinted “RM 5”
Capsules contain a white to off-white powder.
RAMPIL 10 mg: Hard gelatin size #4 capsule with blue opaque body and blue opaque cap. The cap has radially imprinted “RM 10”
Capsules contain a white to off-white powder.

PRESENTATION
SECURITAINERS:
White, round, rigid, polypropylene (plastic) container with a Jayfilla and sealed with a white snap-on (LDPE) plastic cap containing 30 or 60 capsules.
PVC/PVDC BLISTER (Strip of 10 capsules)
Blister strip composed of PVC/PVDC 250/40 micron & 155 mm wide with an aluminium foil backing. The blister strips are packed in cartons of either 30 or 60 capsules.
PVC/ACLAR BLISTER (Strip of 10 capsules) Blister strip composed of PVC/ACLAR 200/7 7.5 mil/2 mil & 155 mm wide with an aluminium foil backing. The blister strips are packed in cartons of either 30 or 60 capsules.
PA/ALU/PVC BLISTER (Strip of 10 capsules)
Blister strip composed of polyamide/aluminium/PVC with an aluminium foil backing.
The blister strips are packed in cartons of either 30 or 60 capsules.

STORAGE INSTRUCTIONS
Store below 25°C in tightly closed containers. Protect from light.
Keep the blisters in the carton until required for use.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER
RAMPIL
1,25 mg : A39/7.1.3/0141
RAMPIL 2,5 mg : A39/7.1.3/0142
RAMPIL 5 mg : A39/7.1.3/0143
RAMPIL 10 mg : A39/7.1.3/0144

NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION
PHARMACARE LIMITED
Healthcare Park
Woodlands Drive
Woodmead

DATE OF PUBLICATION OF PACKAGE INSERT
19 August 2005

575003/050721
UNIPRINT - POS

New addition to this site: January 2006
Source: Pharmaceutical Industry

SAEPI HOME PAGE      TRADE NAME INDEX      GENERIC NAME INDEX      FEEDBACK
Information presented by Malahyde Information Systems © Copyright 1996-2005