Anti-Anginal Drugs Calcium Antagonists Cardiac Drugs: MIMS Class

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Adalat® [GITS tab]

Bayer [ Zuellig ] 
MIMS Class : Anti-Anginal Drugs, Calcium Antagonists, Cardiac Drugs 
       

See related Adalat GITS tab information


Contents Nifedipine
Indications Treatment of coronary heart disease: Chronic stable angina
pectoris (angina of effort).

Treatment of hypertension.
Dosage As much as possible, the treatment must be tailored to the
needs of the individual.

Depending on the clinical picture in each case, the basic dose


must be introduced gradually. In patients with impaired liver
function, careful monitoring and, in severe cases, a dose
reduction may be necessary.

Unless otherwise prescribed, the following dosage guidelines


are recommended for adults.

Coronary Heart Disease: Chronic Stable Angina


Pectoris (angina of effort): 1 Adalat GITS 20/30/60 tab once
daily (1 x 20 mg/day, 1 x 30 mg/day or 1 x 60 mg/day).

Hypertension: 1 Adalat GITS 20/30/60 tab once daily (1 x 20


mg/day, 1 x 30 mg/day or 1 x 60 mg/day).

A starting dose of 20 mg once daily may be considered when


medically indicated. In general, therapy should be initiated with
30 mg once daily. Interim doses ie, 40 mg, 50 mg, etc, can be
applied by combinations of, ie 20-mg + 20-mg or 20-mg + 30-
mg tabs.

Depending on the severity of the disease and the patient's


response, the dose can be increased in stages to 120 mg once
daily.

As a rule, the tablets are swallowed whole with a little liquid,


independently of meals. The tablets must not be chewed or
broken up. The attending doctor will determine the duration of
use.
Overdosage Symptoms: The following symptoms are observed in cases of
severe nifedipine intoxication: Disturbances of consciousness
to the point of coma, a drop in blood pressure,
tachycardiac/bradycardiac heart rhythm disturbances,
hyperglycemia, metabolic acidosis, hypoxia, cardiogenic shock
with pulmonary edema.

Treatment: As far as treatment is concerned, elimination of


the active substance and the restoration of stable
cardiovascular conditions have priority.

After oral ingestion, thorough gastric lavage is indicated, if


necessary, in combination with irrigation of the small intestine.
Particularly, in cases of intoxication with slow-release products
eg, Adalat GITS 20/30/60, elimination must be as complete as
possible, including the small intestine to prevent the otherwise
inevitable subsequent absorption of the active substance.

Hemodialysis serves no purpose as nifedipine is not


dialyzable, but plasmapheresis is advisable (high plasma
protein-binding, relatively low volume of distribution).

Bradycardiac heart rhythm disturbances may be treated


symptomatically with β-sympathomimetics, and in life-
threatening bradycardiac disturbances of heart rhythm,
temporary pacemaker therapy can be advisable.

Hypotension as a result of cardiogenic shock and arterial


vasodilation can be treated with calcium (10-20 mL of a 10%
calcium gluconate solution administered slowly IV and
repeated if necessary). As a result, the serum calcium can
reach the upper normal range to slightly elevated levels. If an
insufficient increase in blood pressure is achieved with
calcium, vasoconstricting sympathomimetics eg, dopamine or
noradrenaline are additionally administered. The dosage of
these drugs is determined solely by the effect obtained.

Additional liquid or volume must be administered with caution


because of the danger of overloading the heart.
Administration May be taken with or without food (Avoid grapefruit juice.
Swallow whole, do not chew/crush.).
Contraindications Known hypersensitivity to nifedipine. Cardiovascular shock.
Patients with Kock pouch (ileostomy after proctocolectomy).

Nifedipine must not be used in combination with rifampicin


because no efficient plasma levels of nifedipine may be
obtained due to enzyme induction.

Use in pregnancy & lactation: Nifedipine is contraindicated


throughout pregnancy as administration in animals was
associated with embryotoxic, fetotoxic and teratogenic effects.
All of the doses associated with the teratogenic, embryotoxic
or fetotoxic effects in animals were maternally toxic and
several times the recommended maximum dose for humans.
There are no adequate and well-controlled studies in pregnant
women.
Care must be exercised in pregnant women when
administering nifedipine in combination with IV magnesium
sulfate.

Nifedipine passes into the breast milk. As there is no


experience of possible effects on infants, breastfeeding should
first be stopped if nifedipine treatment becomes necessary
during breastfeeding period.
Special Precautions Care must be exercised in patients with very low blood
pressure (severe hypotension with systolic pressure <90 mm
Hg), in cases of manifest heart failure and in the case of
severe aortic stenosis.

As with other nondeformable material, care should be used


when administering Adalat GITS 20/30/60 in patients with
preexisting severe gastrointestinal narrowing because
obstructive symptoms may occur. In single case, obstructive
symptoms have been described without known history of
gastrointestinal disorders.

When doing barium contrast x-ray, Adalat GITS 20/30/60 may


cause false-positive effects (eg, filling defects interpreted as
polyp).

In patients with impaired liver function, careful monitoring and,


in severe cases, a dose reduction may be necessary.

Effects on the Ability to Drive or Operate Machinery: Reactions


to nifedipine, which vary in intensity from individual to
individual, can impair the ability to drive or to operate
machinery. This applies particularly at the start of treatment,
on changing the medication and in combination with alcohol.

Impairment of Fertility: In single cases of in vitro fertilization,


calcium antagonists eg, nifedipine, have been associated with
reversible biochemical changes in the spermatozoa's head
section that may result in impaired sperm function. In those
men who are repeatedly unsuccessful in fathering a child by in
vitro fertilization, and where no other explanation can be found,
calcium antagonists eg, nifedipine should be considered as
possible causes.
Adverse Drug Adalat GITS 20/30: The most common adverse reaction
Reactions based on clinical studies with Adalat GITS 20 sorted by
frequency and body system (n=5132 patients):
Incidence of Frequency ≥1% to <10%:

Body as a Whole: Asthenia (tiredness).

Cardiovascular System: Vasodilation (flushing, heat


sensation), palpitation.

Digestive System: Constipation.

Metabolic and Nutritional Disorder: Peripheral edema.

Nervous System: Dizziness, headache.

Incidence of Frequency ≥0.1% to <1%:

Body as a Whole: Pain in extremities.

Cardiovascular System: Angina pectoris-like symptoms, chest


pain, hypotension, tachycardia, syncope.

Digestive System: Diarrhea, abnormal liver function test


(increase in transaminases, intrahepatic cholestasis), nausea.

Musculoskeletal System: Myalgia.

Nervous System: Insomnia, nervousness, paresthesia, vertigo.

Respiratory System: Dyspnea.

Skin and Appendages: Pruritus, rash (exanthema, erythema).

Special Senses: Abnormal vision.

Urogenital System: Increase in daily urine excretion.

Incidence of Frequency ≥0.01% to <0.1%:

Body as a Whole: Allergic reaction (anaphylactic reaction).

Digestive System: Gastrointestinal disorder (gastrointestinal


repletion), gum hyperplasia.

Musculoskeletal System: Arthralgia.


Nervous System: Tremor.

Skin and Appendages: Urticaria.

The most common adverse reactions based on spontaneous


reports sorted by frequency and body system calculated on
patient exposure (n=1058 patients):

Incidence of Frequency <0.01%:

Hemic and Lymphatic System: Purpura.

Metabolic and Nutritional Disorder: Hyperglycemia.

Skin and Appendages: Gynecomastia, photosensitivity


dermatitis.

Other Nifedipine Formulations: Agranulocytosis, exfoliative


dermatitis, erythromelalgia.

In dialysis patients with malignant hypertension and


hypovolemia, a distinct fall in blood pressure can occur as a
result of vasodilation.

Adalat GITS 60: Frequently: At the start of treatment


especially, headaches and facial and skin reddening with a
feeling of warmth (erythema, erythromelalgia) may occur;
these effects are usually transient.

Occasionally: Dizziness, fatigue, palpitations, constipation,


lower leg edema (fluid retention in the lower leg) due to dilation
of the blood vessels. Particularly at the start of treatment,
angina pectoris attacks may occasionally occur and patients
who already have angina pectoris may experience an increase
in the frequency, duration and severity of attacks. Myocardial
infarctions have been described in isolated cases.

Rarely: Nausea, a sensation of fullness, diarrhea, tingling of


the arms and legs, elevated heart rate (tachycardia),
decreased blood pressure below the norm, skin
hypersensitivity reactions eg, pruritus, urticaria and rashes,
changes in the blood count eg, reduction in the number of red
or white blood cells or platelets (anemia, leucopenia,
thrombopenia) and bleeding in the skin and mucous
membranes with decreased numbers of blood platelets
(thrombocytopenic purpura).

In rare cases, especially in older male patients receiving long-


term therapy, enlargement of the mammary glands
(gynecomastia) has been observed; however, so far, this has
been reversible in all cases after discontinuing medication.

In extremely rare cases, long-term treatment can result in gum


changes (gingival hyperplasia) which are completely reversible
after discontinuation of Adalat GITS 60 therapy.

Isolated Cases: Liver function disorders (intrahepatic


cholestasis, increase in transaminases), a marked reduction in
certain blood cells (agranulocytosis), small red spots on the
skin and mucous membranes (purpura), scaly inflammation of
the skin (exfoliative dermatitis), inflammation of the skin after
exposure to sun or UV rays (photodermatitis), muscular pain,
trembling in the fingers, impaired vision, temporary loss of
consciousness due to an excessive fall in blood pressure and
acute generalized allergic reactions (anaphylactoid reactions)
eg, swelling of the skin and mucous membranes, swelling of
the larynx (edema of the glottis) and spasms in the bronchial
muscles which can cause shortness of breath to a potentially
fatal degree.

In isolated cases, a rise in the blood glucose level has been


observed. This is an especially important consideration in
patients with diabetes mellitus.

In isolated cases, intestinal evacuation can be impaired with


symptoms of intestinal occlusion (eg, flatulence, colic-like
pain).

Patients with impaired kidney function may experience a


temporary deterioration of kidney function.

In the early weeks of treatment, there may also be an increase


in the volume of urine passed each day.

Most of the adverse reactions mentioned previously occur at


the start of treatment, are usually temporary and do not require
any particular treatment. However, the doctor must still be
informed so that he can decide what steps to take.
Click to view ADR Monitoring Website
Drug Interactions The blood pressure-lowering effect of nifedipine may be
potentiated upon co-administration of other antihypertensive
drugs.

When nifedipine is administered simultaneously with β-


receptor blockers, the patient should be carefully monitored
since fairly severe hypotension can occur. Deterioration of
heart failure is also known to develop in isolated cases.

Nifedipine is metabolized via the cytochrome P-450 3A4


system, located both in the intestinal mucosa and in liver.
Drugs that are known to either inhibit or induce this enzyme
system may therefore alter the first-pass (after oral
administration) or the clearance of nifedipine.

Digoxin: The simultaneous administration of nifedipine and


digoxin may lead to reduced digoxin clearance and hence, an
increase in plasma concentrations of digoxin. The patient
should therefore be checked for symptoms of digoxin
overdosage as a precaution and, if necessary, the glycoside
dose should be reduced, taking account of the plasma
concentration of digoxin.

Phenytoin: Induces the cytochrome P-450 3A4 system. Upon


co-administration with phenytoin, the bioavailability
ofnifedipine is reduced and thus its efficacy weakened. When
both drugs are concomitantly administered, the clinical
response to nifedipine should be monitored and, if necessary,
an increase of the nifedipine dose considered. If the dose
of nifedipine is increased during co-administration of both
drugs, a reduction of the nifedipine dose should be considered
when the treatment with phenytoin is discontinued.

Quinidine: When nifedipine and quinidine have been


administered simultaneously, lowered quinidine levels or, after
discontinuance of nifedipine, a distinct increase in plasma
concentrations of quinidine have been observed in individual
cases. For this reason, when nifedipine is either additionally
administered or discontinued, monitoring of the quinidine
plasma concentration and, if necessary, adjustment of the
quinidine dose are recommended.

Some authors reported increased plasma concentrations


of nifedipine upon co-administration of both drugs, while others
did not observe an alteration in the pharmacokinetics
of nifedipine. Therefore, the blood pressure should be carefully
monitored if quinidine is added to an existing therapy
with nifedipine. If necessary, the dose of nifedipineshould be
decreased.

Quinupristin/Dalfopristin: Simultaneous administration of


quinupristin/dalfopristin and nifedipine may lead to increased
plasma concentrations of nifedipine. Upon co-administration of
both drugs, the blood pressure should be monitored and, if
necessary, a reduction of the nifedipine dose is considered.

Cimetidine: Due to its inhibition of cytochrome P-450 3A4,


cimetidine elevates the plasma concentrations ofnifedipine and
may potentiate the antihypertensive effect.

Rifampicin: Strongly induces the cytochrome P-450 3A4


system. Upon co-administration with rifampicin, the
bioavailability of nifedipine is distinctly reduced and thus its
efficacy is weakened. The use of nifedipine in combination with
rifampicin is therefore contraindicated.

Diltiazem: Decreases the clearance of nifedipine. The


combination of both drugs should be administered with caution
and a reduction of the nifedipine dose may be considered.

Grapefruit Juice: Inhibits the cytochrome P-450 3A4 system.


Administration of nifedipine together with grapefruit juice thus
results in elevated plasma concentrations of nifedipine due to
an increase in drug bioavailability. As a consequence, the
blood pressure-lowering effect may be increased.

Cisapride: Simultaneous administration of cisapride


and nifedipine may lead to increased plasma concentrations
ofnifedipine. Upon co-administration of both drugs, the blood
pressure should be monitored and, if necessary, a reduction of
the nifedipine dose is considered.

Theoretical Potential Interactions: Erythromycin: No interaction


studies have been carried out between nifedipineand
erythromycin. Erythromycin is known to inhibit the cytochrome
P-450 3A4-mediated metabolism of other drugs. Therefore, the
potential for an increase of nifedipine plasma concentrations
upon co-administration of both drugs cannot be excluded.

Ketoconazole, Itraconazole, Fluconazole: A formal interaction


study investigating the potential of a drug interaction
between nifedipine and ketoconazole, itraconazole or
fluconazole has not yet been performed. Drugs of this class
are known to inhibit the cytochrome P-450 3A4 system. When
administered orally together with nifedipine, a substantial
increase in systemic bioavailability of nifedipine due to an
increased absorption cannot be excluded. Upon co-
administration, the blood pressure should be monitored and, if
necessary, a reduction in the nifedipinedose is considered.

Tacrolimus: It has been shown to be metabolized via the


cytochrome P-450 3A4 system. Data recently published
indicate that the dose of nifedipine administered
simultaneously with tacrolimus may be reduced in individual
cases. Upon co-administration of both drugs, the tacrolimus
plasma concentration should be monitored and, if necessary, a
reduction in the tacrolimus dose is considered.

Carbamazepine: No formal studies have been performed to


investigate the potential interaction between nifedipineand
carbamazepine. As carbamazepine has been shown to reduce
the plasma concentrations of the structurally similar calcium-
channel blocker nimodipine due to enzyme induction, a
decrease in nifedipine plasma concentrations and hence a
decrease in efficacy cannot be excluded.

Phenobarbitone: No formal studies have been performed to


investigate the potential interaction between nifedipineand
phenobarbitone. As phenobarbitone has been shown to
reduce the plasma concentrations of the structurally similar
calcium-channel blocker nimodipine due to enzyme induction,
a decrease in nifedipine plasma concentrations and hence a
decrease in efficacy cannot be excluded.

Valproic Acid: No formal studies have been performed to


investigate the potential interaction between nifedipine and
valproic acid. As valproic acid has been shown to increase the
plasma concentrations of the structurally similar calcium-
channel blocker nimodipine due to enzyme inhibition, an
increase in nifedipine plasma concentrations and hence an
increase in efficacy cannot be excluded.

Interactions Shown Not to Exist: Concomitant administration


of nifedipine with ajmalin, benazepril, debrisoquine,doxazosin,
omeprazole, orlistat, pantoprazole, ranitidine, rosiglitazone,
talinolol, triamterene, hydrochlorothiazide has no effect on the
pharmacokinetics of nifedipine.

Concomitant administration of nifedipine and candesartan


cilexetil or cerivastatin has no effect on the pharmacokinetics
of either drug.

Aspirin: Concomitant administration of nifedipine and aspirin


100 mg has no effect on the pharmacokinetics ofnifedipine.
Co-administration of nifedipine does not alter the effect of
aspirin 100 mg on the platelet aggregation and bleeding time.

Irbesartan: Concomitant administration of nifedipine and


irbesartan has no effect on the pharmacokinetics of irbesartan.

Other Forms of Interaction: Nifedipine may cause falsely


increased spectrophotometric values of urinary vanillyl-
mandelic acid. However, measurement with HPLC is
unaffected. Antagonists eg, nifedipine, should be considered
as possible causes.

Incompatibilities: None.
View more drug interactions for Adalat
Pregnancy Category
(US FDA)
Category C: Either studies in animals have revealed adverse
effects on the foetus (teratogenic or embryocidal or other) and
there are no controlled studies in women or studies in women
and animals are not available. Drugs should be given only if
the potential benefit justifies the potential risk to the foetus.
Cautions For Usage In Adalat GITS 20/30/60, nifedipine is contained within a
nonabsorbable shell that slowly releases the drug for the body
to absorb. When this process is completed, the empty tablet is
eliminated from the body and may be noticed in the stool.

The light-sensitive active substance contained in Adalat GITS


20/30/60 is protected from light inside and outside its
packaging. The tablets must be protected from humidity and
must therefore only be removed from the foil immediately
before use.
Storage Store at temperatures not exceeding 30°C.
Description Adalat GITS 20-mg tablet also contains the following inactive
ingredients: Hydroxypropylmethyl cellulose, polyethylene
oxide, magnesium stearate, sodium chloride, red iron oxide
(E172/CI 77491), cellulose acetate, polyethylene glycol 3360,
hydroxypropyl cellulose, propylene glycol, titanium dioxide
(E171/CI 77891).

Adalat GITS 60-mg tablet also contains the following inactive


ingredients: Polyethylene glycol 3350, hydroxypropyl cellulose,
propylene glycol and titanium dioxide (E171/CI 77891).
Mechanism of Action Antianginal/Antihypertensive.

Nifedipine is a calcium antagonist of the 1,4-dihydropyridine


type. Calcium antagonists reduce the transmembrane influx of
calcium ions through the slow calcium channel into the
cell. Nifedipine acts particularly on the cells of the myocardium
and the smooth muscle cells of the coronary arteries and the
peripheral resistance vessels.

In the heart, nifedipine dilates the coronary arteries, especially


the large conductance vessels, even in the free wall segment
of partially stenosed areas. Further, nifedipine reduces the
vascular smooth muscle tone in the coronary arteries and
prevents vasospasm. The end-result is an increased post-
stenotic blood flow and an increased oxygen supply. Parallel to
this, nifedipine reduces the oxygen requirement by lowering
peripheral resistance (afterload). With long-term
use, nifedipine can also prevent the development of new
atherosclerotic lesions in the coronary arteries.

Nifedipine reduces the smooth muscle tone of the arterioles,


thus lowering the increased peripheral resistance and
consequently, the blood pressure. At the beginning of
the nifedipine treatment, there may be a transient reflex
increase in heart rate, and thus in the cardiac output. However,
this increase is not enough to compensate for the vasodilation.
In addition, nifedipine increases sodium and water excretion
both in the short- and long-term use. The blood pressure-
lowering effect of nifedipine is particularly pronounced in
hypertensive patients.

Adalat GITS 20/30/60 tablets are formulated to


provide nifedipine at an approximately constant rate over 24
hrs.Nifedipine is released from the tablet at a zero-order rate
by a membrane-controlled, osmotic push-pull process. The
delivery rate is independent of gastrointestinal pH or motility.
Upon swallowing, the biologically inert components of the
tablet remain intact during gastrointestinal transit and are
eliminated in the feces as an insoluble shell.
MIMS Class Anti-Anginal Drugs / Calcium Antagonists / Cardiac Drugs
ATC Classification C08CA05 - Nifedipine ; Belongs to the class of dihydropyridine
derivative selective calcium-channel blockers with mainly
vascular effects. Used in the treatment of cardiovascular
diseases.
Poison Schedule Rx
Presentation/Packing Tab (extended-release) 20 mg x 30's. 30 mg x 30's. 60 mg x
30's.
Manufacturer: Bayer
Distributor: Zuellig

Accupril® [film-coated tab]

Pfizer [ Zuellig ] 
MIMS Class : ACE Inhibitors 

See related Accupril film-coated tab information


Contents Quinapril HCl
Indications Treatment of hypertension. Quinapril is effective as
monotherapy or concomitantly with thiazide diuretics and β-
blockers in patients with hypertension.

Treatment of congestive heart failure when given


concomitantly with a diuretic and/or cardiac glycoside.
Dosage Hypertension: Monotherapy: The recommended initial
dosage of quinapril in patients not on diuretics is 10 or 20 mg
once daily. Depending upon clinical response, the patient's
dosage may be titrated (by doubling the dose) to a
maintenance dosage of 20 or 40 mg/day usually given as a
single dose or may be divided in 2 doses. Generally, dosage
adjustments should be made at intervals of 4 weeks. Long-
term control is maintained in most patients with a single daily
dosage regimen. Patients have been treated with dosages of
quinapril up to 80 mg/day.
Concomitant Diuretics: In patients who must continue
treatment with a diuretic, the initial recommended dosage of
quinapril is 5 mg which should subsequently be titrated (as
described previously) to the optimal response. (See
Interactions.)

Renal Impairment: Kinetic data indicate that the apparent


elimination half-life of quinaprilat increases as creatinine
clearance decreases and that elimination is dependent on the
level of renal function. Recommended starting dosages based
on clinical and pharmacokinetic data from patients with renal
impairment are as follows: Creatinine clearance >60 mL/min:
Maximum recommended initial dosage 10 mg; 30-60 mL/min:
5 mg; 10-30 mL/min: 2.5 mg; <10 mL/min: There is insufficient
experience at this time, to allow for specific dosage
recommendations in these patients.

Age alone does not appear to affect the efficacy or safety


profile of quinapril. Therefore, the recommended initial dosage
of quinapril in elderly patients is 10 mg given once daily
followed by titration to the optimal response. If the initial dose
is well tolerated, quinapril may be administered the following
day as a twice-daily regimen. In the absence of
excessive hypotension or significant deterioration of renal
function, the dose may be increased at weekly intervals based
on clinical and hemodynamic response. Congestive Heart
Failure: Quinapril is indicated as adjunctive therapy with
diuretics and/or cardiac glycosides. The recommended initial
dosage in patients with congestive heart failure is 5 mg once
or twice daily, following which the patient should be monitored
closely for symptomatic hypotension. If the initial dose of
quinapril is well tolerated, patients may be titrated up to an
effective dose, usually 10-40 mg/day given in 2 equally divided
doses with concomitant therapy.
Overdosage The oral LD50 of quinapril in mice and rats ranges from 1440-
4280 mg/kg.

No specific information is available on the treatment of


overdosage with quinapril. The most likely clinical
manifestation would be symptoms attributable to severe
hypotension, which should normally be treated by IV volume
expansion. Treatment is symptomatic and supportive
consistent with established medical care.
Hemodialysis and peritoneal dialysis have little effect on the
elimination of quinapril and quinaprilat.
Administration Should be taken on an empty stomach (Take before meals at
about the same time of day.).
Contraindications Patients who are hypersensitive to Accupril and in patients
with a history of angioedema related to previous treatment with
an ACE inhibitor. Cross-sensitivity to other ACE inhibitors has
not been evaluated.
Warnings Angioedema: Angioedema has been reported in patients
treated with angiotensin-converting enzyme inhibitors,
including in 0.1% of patients receiving quinapril. If laryngeal
stridor or angioedema of the face, tongue or glottis occur,
treatment with quinapril should be discontinued immediately;
the patient should be treated appropriately in accordance with
accepted medical care, and carefully observed until the
swelling disappears. In instances where swelling is confined to
the face and lips, the condition generally resolves without
treatment; antihistamines may be useful in relieving symptoms.
Angioedema associated with laryngeal involvement may be
fatal. Where there is involvement of the tongue, glottis or
larynx likely to cause airway obstruction, appropriate
emergency therapy, including but not limited to SC adrenaline
(epinephrine) solution 1:1000 (0.3-0.5 mL), should be promptly
administered. (See Adverse Reactions.)

Black patients receiving ACE inhibitor therapy have been


reported to have a higher incidence of angioedema compared
to non-black patients. It should also be noted that in controlled
clinical trials, ACE inhibitors have an effect on blood pressure
that is less in black patients than in non-blacks. The incidence
of angioedema in black and non-black patients during quinapril
therapy has been calculated in 2 large open-label clinical trials
evaluating the effectiveness of quinapril in the management of
hypertension. In 1 study wherein 1656 black and 10,583 non-
black patients were evaluated, the incidence of angioedema,
regardless of association to quinapril treatment was 0.3% in
blacks and 0.39% in non-blacks. In the other study (1443 black
and 9300 non-black patients), the incidence of angioedema
was 0.55% in blacks and 0.17% in non-black patients.

Patients with a history of angioedema unrelated to ACE


inhibitor therapy may be at increased risk of angioedema while
receiving an ACE inhibitor.
Anaphylactoid Reactions: Desensitization: Patients receiving
ACE inhibitors during desensitizing treatment with
hymenoptera venom have sustained life-threatening
anaphylactoid reactions. In the same patients, these reactions
have been avoided when ACE inhibitors were temporarily
withheld, but they have reappeared upon inadvertent
rechallenge.

LDL Apheresis: Patients undergoing low-density lipoprotein


apheresis with dextran-sulfate absorption when treated
concomitantly with an ACE inhibitor, have reported
anaphylactoid reactions.

Hemodialysis: Clinical evidence has shown that patients


hemodialysed using certain high-flux membranes (eg,
polyacrylonitrile membranes) are likely to experience
anaphylactoid reactions with concomitant ACE inhibitor
treatment. This combination should be avoided, either by use
of alternative antihypertensive drugs, or alternative
membranes for hemodialysis.

Hypotension: Symptomatic hypotension was rarely seen in


uncomplicated hypertensive patients treated with quinapril but
it is a possible consequence of ACE inhibition therapy in
salt-/volume-depleted patients eg, those previously treated
with diuretics, who have a dietary salt restriction, or who are on
dialysis. (See Precautions, Interactions and Adverse
Reactions.)

In patients with congestive heart failure, who are at risk of


excessive hypotension, quinapril therapy should be started at
the recommended dose under close medical supervision;
these patients should be followed closely for the first 2 weeks
of treatment and whenever the dosage of quinapril is
increased.

If symptomatic hypotension occurs, the patients should be


placed in the supine position and, if necessary, receive an IV
infusion of normal saline. A transient hypotensive response is
not a contraindication to further doses; however, lower doses
of quinapril or any concomitant diuretic therapy should be
considered if this event occurs.

Patients already receiving a diuretic when quinapril is initiated


can develop symptomatic hypotension. In patients receiving a
diuretic, it is important, if possible, to stop the diuretic for 2-3
days before starting quinapril. If blood pressure is not
controlled with quinapril alone, diuretic therapy should be
resumed. If it is not possible to withdraw diuretic therapy, begin
quinapril at a low initial dose.

Neutropenia/Agranulocytosis: ACE inhibitors have been rarely


associated with agranulocytosis and bone marrow depression
in patients with uncomplicated hypertension but more
frequently in patients with renal impairment, especially if they
also have collagen vascular disease. Agranulocytosis has
been rarely reported during treatment with quinapril. As with
other ACE inhibitors, monitoring of white blood cell counts in
patients with collagen vascular disease and/or renal disease
should be considered.

Fetal/Neonatal Morbidity and Mortality: ACE inhibitors can


cause fetal and neonatal morbidity and mortality when
administered to pregnant women. Before quinapril is used
during pregnancy, the possible adverse effects on the fetus
must be considered. Should a woman become pregnant while
receiving quinapril, the drug should be discontinued.

When ACE inhibitors have been used during the 2nd and 3rd
trimesters of pregnancy, there have been reports of
hypotension, renal failure, skull hypoplasia, and/or death in the
newborn. Oligohydramnios has also been reported,
presumably representing decreased renal function in the fetus;
limb contractures, craniofacial deformities, hypoplastic lung
development and intrauterine growth retardation have been
reported in association with oligohydramnios. While these
adverse effects do not appear to have been the result of
exposure limited to the 1st trimester, mothers whose embryos
and fetuses have been exposed only during the 1st trimester,
must be so informed. Nonetheless, should a woman become
pregnant while receiving ACE inhibitors, the drug should be
discontinued as soon as possible.

Patients who do require ACE inhibitors during the 2nd and 3rd
trimesters of pregnancy should be apprised of the potential
hazards to the fetus; frequent ultrasound examinations should
be performed to detect oligohydramnios. Patients and
physicians should be aware, however that oligohydramnios
may not appear until after the fetus has sustained irreversible
injury. If oligohydramnios is observed, quinapril should be
discontinued unless it is considered life-saving for the mother.

Other potential risks to the fetus/neonate exposed to ACE


inhibitors include intrauterine growth retardation, prematurity
and patent ductus arteriosus; fetal death also has been
reported. It is not clear, however whether these reported
events are related to ACE inhibition or the underlying maternal
disease. It is not known whether exposure limited to the 1st
trimester can adversely affect fetal outcome.

Infants exposed in utero to ACE inhibitors should be closely


observed for hypotension, oliguria and hyperkalemia. If oliguria
occurs, attention should be directed toward support of blood
pressure and renal perfusion.
Special Precautions General: Impaired Renal Function: As a consequence of
inhibiting the renin-angiotensin-aldosterone system, changes
in renal function may be anticipated in susceptible individuals.
In patients with severe heart failure whose renal function may
depend on the activity of the renin-angiotensin-aldosterone
system, treatment with ACE inhibitors including quinapril, may
be associated with oliguria and/or progressive azotemia and
rarely acute renal failure and/or death.

The half-life of quinaprilat is prolonged as creatinine clearance


falls. Patients with a creatinine clearance of <60 mL/min
require a lower initial dosage of quinapril. (See Dosage &
Administration.) These patients' dosage should be titrated
upwards based upon therapeutic response and renal function
should be closely monitored although initial studies do not
indicate that quinapril produces further deterioration in renal
function.

In clinical studies in hypertensive patients with unilateral or


bilateral renal artery stenosis, increases in blood urea nitrogen
and serum creatinine have been observed in some patients
following ACE inhibitor therapy. These increases were almost
always reversible upon discontinuation of the ACE inhibitor
and/or diuretic therapy. In such patients, renal function should
be monitored during the first few weeks of therapy.

Some patients with hypertension or heart failure with no


apparent preexisting renal vascular disease have developed
increases in blood urea and serum creatinine, usually minor
and transient, especially when quinapril has been given
concomitantly with a diuretic. This is more likely to occur in
patients with preexisting renal impairment. Dosage reduction
and/or discontinuation of a diuretic and/or quinapril may be
required.

ACE inhibitors have been associated with hypoglycemia in


diabetic patients on insulin or oral hypoglycemic agents; closer
monitoring of diabetic patients may be required.

Hyperkalemia and Potassium-Sparing Diuretics: As with other


ACE inhibitors, patients on quinapril alone may have increased
serum potassium levels. When administered concomitantly,
quinapril may reduce the hypokalemia induced by thiazide
diuretics. Quinapril has not been studied as concomitant
therapy with potassium-sparing diuretics. Because of the risk
of further potentiating increases in serum potassium, it is
advised that combination therapy with potassium-sparing
diuretics be initiated with caution and the patient's serum
potassium levels be closely monitored. (See Precautions and
Interactions.)

Surgery/Anesthesia: Caution should be exercised when


patients undergo major surgery or anesthesia since
angiotensin-converting enzyme inhibitors have been shown to
block angiotensin II formation secondary to compensatory
renin release. This may lead to hypotension which can be
corrected by volume expansion.

Information for Patients: Pregnancy: Female patients of


childbearing age should be told about the consequences of
2nd- and 3rd-trimester exposure to ACE inhibitors. These
patients should be asked to report pregnancies to their
physicians immediately.

Angioedema: Angioedema, including laryngeal edema, may


occur especially following the 1st dose of quinapril. Patients
should be advised that if any sign or symptom suggesting
angioedema occurs (ie, swelling of face, extremities, eyes,
lips, tongue; difficulty in swallowing or breathing), they should
immediately stop taking quinapril and consult with their
physician. (See Warnings.)

Hypotension: Patients should be cautioned to report


lightheadedness, especially during the first few days of
quinapril therapy. If syncope occurs, the patients should be
told not to take the drug until they have consulted with their
physician. (See Warnings.)

All patients should be cautioned that inadequate fluid intake,


excessive perspiration or dehydration may lead to an
excessive fall in blood pressure because of reduction in fluid
volume. Other causes of volume depletion eg , vomiting or
diarrhea may also lead to a fall in blood pressure; patients
should be advised to consult with their physician.

Hyperkalemia: Patients should be told not to use potassium


supplements or salt substitutes containing potassium without
consulting their physician. (See Precautions.)

Neutropenia: Patients should be told to report promptly any


indication of infection (eg, sore throat, fever), as this could be a
sign of neutropenia.

Patients planning to undergo surgery and/or anesthesia should


be told to inform their physician that they are taking an ACE
inhibitor.

Note: As with many other drugs, certain advice to patients


being treated with quinapril is warranted. This information is
intended to aid in the safe and effective use of this medication.
It is not a disclosure of all possible adverse or intended effects.

Carcinogenicity, Mutagenicity & Impairment of


Fertility: Quinapril HCl was not carcinogenic in mice or rats
when given in doses up to 75 or 100 mg/kg/day (50-60 times
the maximum human daily dose, respectively) for 104 weeks.
Neither quinapril nor quinaprilat were mutagenic in the Ames
bacterial assay with or without metabolic activation. Quinapril
was also negative in the following genetic toxicology
studies: In vitro mammalian cell point mutation, sister-
chromatid exchange in cultured mammalian cells,
micronucleus test with mice, in vitrochromosome aberration
with V79 cultured lung cells, and an in vivo cytogenetic study
with rat bone marrow. There were no adverse effects on
fertility or reproduction in rats at dose levels up to 100
mg/kg/day (60 times the maximum daily human dose). No
fetotoxic or teratogenic effects were observed in rats at
quinapril doses as high as 300 mg/kg/day (180 times the
maximum daily human dose), despite maternal toxicity at 150
mg/kg/day. Offspring body weights were reduced in rats
treated late in gestation and during lactation with doses of 25
mg/kg/day. Quinapril was not teratogenic in the rabbit;
however, as noted with other ACE inhibitors, maternal toxicity
and embryotoxicity were seen in some rabbits at doses as low
as 0.5 and 1 mg/kg/day, respectively.

Use in pregnancy: See Fetal/Neonatal Morbidity and Mortality


under Warnings.

Use in lactation: ACE inhibitors, including quinapril, are


secreted in human milk to a limited extent. Because of this,
caution should be exercised when quinapril is given to a
nursing mother.

Use in children: Safety and effectiveness of quinapril in


pediatric patients have not been established.

Use in the elderly: Elderly patients exhibited increased AUC


and peak levels for quinaprilat compared to values in younger
patients; this appeared to be related to decreased renal
function rather than age itself. In controlled and uncontrolled
studies where 21% of patients were ≥65 years, no overall
differences in effectiveness or safety were observed between
older and younger patients. However, greater sensitivity of
some older individuals cannot be ruled out.
Adverse Drug Quinapril has been evaluated for safety in 4960 subjects and
Reactions patients and was well-tolerated. Of these, 3203 patients
including 655 elderly patients, participated in controlled clinical
trials. Quinapril has been evaluated for long-term safety in
>1400 patients treated for greater than or equal to 1 year.
Adverse experiences were usually mild and transient in nature.
The most frequent clinical adverse reactions in controlled trials
were headache (7.2%), dizziness (5.5%), cough (3.9%),
fatigue (3.5%), rhinitis (3.2%), nausea and/or vomiting (2.8%)
and myalgia (2.2%). It should be noted that characteristically,
the cough is nonproductive, persistent and resolves after
discontinuation of therapy.
Discontinuation of therapy because of adverse events was
required in 5.2% of the patients treated with quinapril in
controlled clinical trials.
Adverse experiences occurring in greater than or equal to 1%
of the 3203 patients in controlled clinical trials who were
treated with quinapril with or without a concomitant diuretic are
shown in the following table. Incidence of adverse experiences
in the subset of 655 patients greater than or equal to 65 years
is given for comparison. A subset of the 2005 patients in
controlled clinical trials who were treated with quinapril
monotherapy for hypertension is also presented. (See table.)

Click on icon to see table/diagram


Clinical adverse experiences probably, possibly or definitely
related, or of uncertain relationship to therapy occurring in 0.5-
1% (except as noted) of the patients treated with quinapril
(with or without concomitant diuretic) in controlled or
uncontrolled trials and less frequent events seen in clinical
trials or post-marketing experience included:
Cardiovascular: Palpitations, vasodilatation, angina pectoris,
tachycardia.
Gastrointestinal: Flatulence, dry mouth or throat, pancreatitis.
Nervous/Psychiatric: Vertigo, nervousness, depression,
somnolence.
Integumentary: Pruritus, increased perspiration, rash, alopecia,
pemphigus, exfoliative dermatitis.
Urogenital: Urinary tract infection, impotence.
Others: Edema, arthralgia, amblyopia, hemolytic anemia.
Rare Events: Angioedema was reported in patients receiving
quinapril (0.1%). (See Warnings and Contraindications.) While
rarely seen with quinapril, eosinophilic pneumonitis, hepatitis
or hepatic failure have been reported with other ACE inhibitors.
Clinical Laboratory Test Findings: Agranulocytosis and
neutropenia have been rarely reported and the causal
relationship to quinapril is unclear. (See Warnings.)
Hyperkalemia: (See Precautions.)
Creatinine and Blood Urea Nitrogen: Increases (>1.25 times
the upper limit of normal) in serum creatinine and blood urea
nitrogen were observed in 2% and 2%, respectively, of the
patients treated with quinapril alone. Increases are more likely
to occur in patients receiving concomitant diuretic therapy than
in those on quinapril alone. These increases often reversed on
continued therapy.
Click to view ADR Monitoring Website
Drug Interactions Tetracycline: Administration of tetracycline with quinapril
reduced the absorption of tetracycline by approximately 28-
37% in subjects. Decreased absorption is due to the presence
of magnesium carbonate as an excipient in the quinapril
formulation. This interaction should be considered if co-
prescribing quinapril and tetracycline.

Lithium: Increased serum lithium levels and symptoms of


lithium toxicity have been reported in patients receiving
concomitant lithium and ACE inhibitor therapy due to the
sodium-losing effect of these agents. These drugs should be
co-administered with caution and frequent monitoring of serum
lithium levels is recommended. If a diuretic is also used, it may
increase the risk of lithium toxicity.

Other Agents: No clinically important pharmacokinetic


interactions occurred when quinapril was used concomitantly
with propranolol, hydrochlorothiazide, digoxin or cimetidine.
The anticoagulant effect of a single dose of warfarin
(measured by prothrombin time) was not significantly changed
by quinapril co-administration twice daily.

Concomitant Diuretic Therapy: As with other ACE inhibitors,


patients on diuretics, especially those on recently instituted
diuretic therapy, may occasionally experience an excessive
reduction of blood pressure after initiation of therapy with
quinapril. Hypotensive effects after the 1st dose of quinapril
may be minimized by discontinuing the diuretic a few days
prior to initiation of therapy. If it is not possible to discontinue
the diuretic, the starting dose of quinapril should be reduced.
In patients in whom a diuretic is continued, medical
supervision should be provided for up to 2 hrs after the initial
dosage of quinapril. (See Warnings and Dosage &
Administration.)

Agents Increasing Serum Potassium: If concomitant therapy of


quinapril with potassium-sparing diuretics
(eg,spironolactone, triamterene or amiloride), potassium
supplements or potassium-containing salt substitutes is
indicated, they should be used with caution and with
appropriate monitoring of serum potassium.
View more drug interactions for Accupril
Pregnancy Category
(US FDA)
Category C: Either studies in animals have revealed adverse
effects on the foetus (teratogenic or embryocidal or other) and
there are no controlled studies in women or studies in women
and animals are not available. Drugs should be given only if
the potential benefit justifies the potential risk to the foetus.
in 2nd & 3rd trimesters.
Category D: There is positive evidence of human foetal risk,
but the benefits from use in pregnant women may be
acceptable despite the risk (e.g., if the drug is needed in a
life-threatening situation or for a serious disease for which
safer drugs cannot be used or are ineffective).
Storage Store at temperature not exceeding 30°C. It should be
protected from freezing.
Description Each tablet also contains magnesium carbonate, magnesium
stearate, lactose and gelatin as inactive ingredients.

Quinapril HCl is the salt of quinapril, the ethyl ester of a


nonsulfhydryl, angiotensin-converting enzyme (ACE) inhibitor,
quinaprilat.

Quinapril HCl is [3S-[2[R*(R*)], 3R*]]-2-[2-[[1-(ethoxycarbonyl)-


3-phenylpropyl]amino]-1-oxopropyl]-1,2,3,4-tetrahydro-3-
isoquinolinecarboxylic acid, monohydrochloride.

Molecular formula: C25H30N2O5·HCl.

Molecular weight: 474.98.

Quinapril HCl is a white to off-white amorphous powder, freely


soluble in aqueous solvents with a melting point of 108-115°C.
Mechanism of Action Pharmacology: Mechanism of Action: Quinapril is rapidly
deesterified to quinaprilat (quinapril diacid, the principal
metabolite) which, in human and animal studies, is a potent
angiotensin-converting enzyme inhibitor. ACE is a peptidyl
dipeptidase that catalyzes the conversion of angiotensin I to
the vasoconstrictor angiotensin II which is involved in vascular
control and function through many different mechanisms,
including stimulation of aldosterone secretion by the adrenal
cortex. The mode of action of quinapril in humans and animals
is to inhibit circulating and tissue ACE activity, thereby
decreasing vasopressor activity and aldosterone secretion.
Removal of angiotensin II negative feedback on renin
secretion leads to increased plasma renin activity (PRA).

While the principal mechanism of antihypertensive effect is


thought to be through the renin-angiotensin-aldosterone
system, quinapril exerts antihypertensive actions even in
patients with low renin hypertension. Quinapril monotherapy
was an effective antihypertensive in all races studied, although
it was somewhat less effective in blacks (usually a
predominantly low renin group) than in non-blacks. ACE is
identical to kininase II, an enzyme that degrades bradykinin, a
potent peptide vasodilator, whether increased levels of
bradykinin play a role in the therapeutic effect of quinapril
remains to be elucidated.

In animal studies, the antihypertensive effect of quinapril


outlasts its inhibitory effect on circulating ACE, whereas tissue
ACE inhibition more closely correlates with the duration of its
antihypertensive effects.

ACE inhibitors, including quinapril, may enhance insulin


sensitivity.

Pharmacodynamics: Administration of 10-40 mg of quinapril to


patients with mild to severe hypertension results in a reduction
of both sitting and standing blood pressure with minimal effect
on heart rate. Antihypertensive activity commences within 1 hr
with peak effects usually achieved by 2-4 hrs after dosing.
Achievement of maximum blood pressure-lowering effects may
require 2 weeks of therapy in some patients. At the
recommended doses, antihypertensive effects are maintained
in most patients throughout the 24-hr dosing interval and
continued during long-term therapy.

Hemodynamic assessments in patients with hypertension have


indicated that blood pressure reduction produced by quinapril
is accompanied by a reduction in total peripheral resistance
and renal vascular resistance with little or no change in heart
rate, cardiac index, renal blood flow, glomerular filtration rate
or filtration fraction.

Concomitant therapy with thiazide-type diuretics and/or the


addition of β-blocker therapy enhances the antihypertensive
effects of quinapril, giving a blood pressure-lowering effect
greater than that seen with either agent alone.

Therapeutic effects appear to be the same for elderly (≥65


years) and younger adult patients given the same daily
dosages, with no increase in adverse events in elderly
patients.

Quinapril administration to patients with congestive heart


failure reduces peripheral vascular resistance, mean arterial
pressure, systolic and diastolic blood pressure, pulmonary
capillary wedge pressure and increases cardiac output.

In 149 patients undergoing elective coronary bypass surgery,


treatment with quinapril 40 mg reduced the incidence of
postoperative ischemic events compared to placebo during a
1-year follow-up.

In patients with documented coronary artery disease but


without manifested hypertension or heart failure, quinapril
improves abnormal endothelial function measured in coronary
and brachial arteries.

Quinapril enhances endothelial function by mechanisms


leading to increased availability of nitric oxide. Endothelial
dysfunction is considered an important underlying
pathophysiological mechanism in CAD. The clinical
significance of improving endothelial function has not been
established.

Pharmacokinetics: Following oral administration, peak


plasma quinapril concentrations are observed within 1 hr.
Based on recovery of quinapril and its metabolites in urine, the
extent of absorption is approximately 60%. Thirty-eight percent
of orally administered quinapril is systemically available as
quinaprilat. Quinapril has an apparent half-life in plasma of
approximately 1 hr. Peak plasma quinaprilat concentrations
are observed approximately 2 hrs following an oral dose of
quinapril.

Quinaprilat is eliminated primarily by renal excretion and has


an effective accumulation half-life of approximately 3 hrs.
Approximately 97% of either quinapril or quinaprilat circulating
in plasma is bound to proteins. In patients with renal
insufficiency, the apparent elimination half-life of quinaprilat
increases as creatinine clearance decreases. Pharmacokinetic
studies in patients with end-stage renal disease on chronic
hemodialysis or continuous ambulatory peritoneal dialysis
indicate that dialysis has little effect on the elimination of
quinapril and quinaprilat. There is a linear correlation between
plasma quinaprilat clearance and creatinine clearance. The
elimination of quinaprilat is also reduced in elderly patients
(≥65 years) and correlates well with their level of renal
function. (See Dosage & Administration.) Quinapril
concentrations are reduced in patients with alcoholic cirrhosis
due to impaired deesterification of quinapril. Studies in rats
indicate that quinapril and its metabolites do not cross the
blood-brain barrier.
MIMS Class ACE Inhibitors
ATC Classification C09AA06 - Quinapril ; Belongs to the class of ACE inhibitors.
Used in the treatment of cardiovascular disease.
Poison Schedule Rx
Presentation/Packing Tab (film-coated, scored) 5 mg x 56's. 10 mg x 56's. 20 mg x
56's.
Manufacturer: Pfizer
Distributor: Zuellig

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