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

Logo QUINASPEN

SCHEDULING STATUS:
S3

PROPRIETARY NAME
(and dosage form):

QUINASPEN
QUINASPEN 5 mg TABLET
QUINASPEN 10 mg TABLET
QUINASPEN 20 mg TABLET
QUINASPEN 40 mg TABLET

COMPOSITION
Each tablet contains:
QUINASPEN 5 mg TABLET:
        Quinapril hydrochloride equivalent to 5 mg
quinapril.
QUINASPEN 10 mg TABLET
        Quinapril hydrochloride equivalent to 10 mg quinapril.
QUINASPEN 20 mg TABLET:
        Quinapril hydrochloride equivalent to 20 mg quinapril.
QUINASPEN 40 mg TABLET:
        Quinapril hydrochloride equivalent to 40 mg quinapril.

PHARMACOLOGICAL CLASSIFICATION
A 7.1.3 Other hypotensives.

PHARMACOLOGICAL ACTION
Quinapril 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 approximately 60%, with wide variability between patients. The plasma half-life is approximately one hour, which is increased in renal impairment. The time to achieve peak serum concentration is within one hour. Quinapril is renally eliminated and excreted 100% unchanged in the urine.

INDICATIONS
QUINASPEN tablets are indicated for the following:
Hypertension:
  QUINASPEN is indicated for the treatment of mild to moderate hypertension.
  QUINASPEN is effective as monotherapy or concomitantly with diuretics in patients with hypertension.
Congestive Heart Failure:
  QUINASPEN is indicated for the treatment of unresponsive systolic left ventricular failure of various aetiologies in which afterload reduction is advocated.

CONTRA-INDICATIONS
Sensitivity to any of the components of QUINASPEN.
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)
QUINASPEN 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 normovolumic 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 QUINASPEN 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 QUINASPEN. 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 QUINASPEN 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 QUINASPEN 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 QUINASPEN 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 100 mm/Hg or lower or cardiogenic shock. During the first 3 days following the infarction, the dose should be reduced if the systolic blood pressure is 120 mm/Hg or lower. Maintenance doses should be reduced to 5 mg or temporarily to 2,5 mg if systolic blood pressure is 100 mm/Hg or lower. If hypotension persists (systolic blood pressure less than 90 mm/Hg or more than 1 hour) then QUINASPEN 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 -QUINASPEN may cause an increase in serum potassium levels.
Renovascular disease -QUINASPEN 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 QUINASPEN 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 QUINASPEN 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 QUINASPEN, QUINASPEN 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 QUINASPEN again.
QUINASPEN 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 QUINASPEN 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 QUINASPEN. Blood pressure monitoring should be increased when any NSAID is added or discontinued in a patient treated with QUINASPEN.
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 QUINASPEN 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.
QUINASPEN 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 QUINASPEN should be closely monitored.
Peritoneal dialysis may be of some benefit in the clearance of QUINASPEN 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:
Monotherapy:
Adults: Initial dose is 10 mg once daily. The dose should be adjusted according to blood pressure response. The usual effective maintenance dose is 20 to 40 mg/day given as a single dose or divided into two doses with a maximum of 40 mg per day (although, up to 80 mg/day has been given). Generally, dosage adjustments should be made at intervals of four weeks or according to patient’s response. Long-term control is maintained in most patients with a single daily dosage regimen.
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.
Concomitant diuretics:
Adults: Initial dose is 5 mg in order to determine if excess hypotension will occur.
This may be increased at intervals of 4 weeks until the therapeutic effect is reached.
Adjustments should be based on clinical response. Maintenance dosing range is 20 to 40 mg/day given as a single dose or divided into two doses with a maximum of 40 mg per day (although, up to 80 mg/day has been given).
Congestive Heart Failure:
Adults: Initial dose is a single 5 mg dose, followed by close monitoring of the patient, for symptomatic hypotension. Patients may be titrated up to 40 mg per day given in two divided doses with concomitant diuretic and/or cardiac glycoside therapy.
Patients can, however, normally be maintained effectively on doses of 10 to 20 mg per day given in one or two doses with concomitant therapy.
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 QUINASPEN, diuretics should be discontinued 2 to 3 days before beginning therapy with QUINASPEN. In patients where diuretic therapy cannot be discontinued, treatment with QUINASPEN should be initiated with an initial dose is 5 mg, and medical supervision provided for patient’s up to two hours after the initial dose of QUINASPEN. Subsequent dosage adjustments will depend on the therapeutic response.
Renal impairment: A lower dose is required. If creatinine clearance is <40 mL/min the starting dose should be the lowest recommended daily dose. The dose may be increased as needed according to therapeutic response to a maximum of 40 mg/day.
QUINASPEN is not affected by the presence of food. QUINASPEN 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 QUINASPEN 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 QUINASPEN has been given concomitantly with a diuretic. Dosage reduction or discontinuation of QUINASPEN 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, QUINASPEN 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. QUINASPEN is removable by haemodialysis.

IDENTIFICATION
QUINASPEN
5 mg tablets:
Beige coloured , oval-shaped, film-coated tablet with breakline on one side.
QUINASPEN 10 mg tablets:
Beige coloured , oval-shaped, film-coated tablet with breakline on one side.
QUINASPEN 20 mg tablets:
Beige coloured , round, film-coated tablet with breakline on one side.
QUINASPEN 40 mg tablets:
Beige coloured , oval-shaped, film-coated tablet with breakline on one side.

PRESENTATION
Blister strips of 15 tablets with clear, colourless, blister forming PA/AL/PVC on top and silver aluminum foil printed with black ink on the bottom. Blisters strips are packed in cartons containing 30 tablet each.
Patient Ready Packs with 28 tablets enclosed in a metallised lay flat plastic bag (bank bag) sealed with a zipper mechanism (Tender purposes only).

STORAGE INSTRUCTIONS
Store in a dry place below 25°C.
Protect from light.
Keep the blister in the carton until required for use.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER
QUINASPEN
5 mg: 37/7.1.3/0599
QUINASPEN 10 mg: 37/7.1.3/0600
QUINASPEN 20 mg: 37/7.1.3/0601
QUINASPEN 40 mg: 37/7.1.3/0602

NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION
PHARMACARE LIMITED
Building 12
Healthcare Park
Woodlands Drive
Woodmead
2148
South Africa

DATE OF PUBLICATION OF PACKAGE INSERT
3 February 2005

575029/051010
UNIPRINT - POS

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

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