Accuretic (antihypertensives_diuretics)

Accuretic 10/12.5 mg film-coated tablets.

Overdose

No data are available for Accuretic with respect to overdosage in humans.

The most likely clinical manifestation would be symptoms attributable to quinapril monotherapy overdosage such as severe hypotension, which would usually be treated by infusion of intravenous normal saline.

The most common signs and symptoms observed for HCTZ monotherapy overdosage are those caused by electrolyte depletion (hypokalaemia, hypochloraemia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalaemia may accentuate cardiac arrhythmias.

No specific information is available on the treatment of overdosage with quinapril/HCTZ.

Haemodialysis and peritoneal dialysis have little effect on the elimination of quinapril and quinaprilat. Treatment is symptomatic and supportive consistent with established medical care.

Shelf life

3 years.

Incompatibilities

Not applicable.

List of excipients

Magnesium carbonate

Lactose

Povidone

Crospovidone

Magnesium stearate

Candelilla wax

Colourings: Opadry pink OY-S-6937 (contains iron dioxide (E172), titanium dioxide (E171), hydroxypropylmethyl cellulose, hydroxypropyl cellulose and polyethylene glycol).

Undesirable effects

The following undesirable effects have been observed and reported during treatment with quinapril/HCTZ with the following frequencies: very common (>1/10); common (>1/100 to <1/10); uncommon (>1/1,000 to ≤1/100); rare (>1/10,000 to ≤1/1,000); very rare (≤1/10,000), not known (cannot be estimated from the available data).

* Such increases are more likely to occur in patients receiving concomitant diuretic therapy than those on monotherapy with quinapril. These observed increases will often reverse on continued therapy.

# Adverse reactions associated with quinapril component, frequencies observed when taking quinapril/HCTZ.

## Adverse reactions associated with quinapril component, frequencies observed in quinapril, adverse reactions not associated with quinapril/HCTZ component.

∞ In patients with a congenital G-6-PDH deficiency, individual cases of haemolytic anaemia# have been reported.

Clinical Laboratory Test Findings:

Serum electrolytes

Serum uric acid

Glucose

Changes in magnesium, PBI (protein bound iodine), parathyroid function tests and calcium

Haematology test

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Preclinical safety data

The results of the preclinical tests do not add anything of further significance to the prescriber.

Pharmacotherapeutic group

Pharmacodynamic properties

Pharmacotherapeutic group: quinapril and diuretics, ATC code: C09BA06.

Quinapril is rapidly de-esterified to quinaprilat (quinapril diacid, the principal metabolite), which is a potent angiotensin-converting enzyme (ACE) inhibitor.

Quinapril and HCTZ lower blood pressure by different, though complementary mechanisms. With diuretic treatment, blood pressure and blood volume fall, resulting in a rise in angiotensin II levels which tend to blunt the hypotensive effect. Quinapril blocks this rise in angiotensin II. The antihypertensive effects of quinapril and HCTZ are additive.

It should be noted that in controlled clinical trials, ACE inhibitors have an effect on blood pressure that is less in black patients than in non-black patients, although this difference is reported to disappear when a diuretic is added.

Two large randomised, controlled trials (ONTARGET (On-going Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) and VA NEPHRON-D (The Veterans Affairs Nephropathy in Diabetes)) have examined the use of the combination of an ACE inhibitor with an angiotensin II receptor blocker.

ONTARGET was a study conducted in patients with a history of cardiovascular or cerebrovascular disease, or type 2 diabetes mellitus accompanied by evidence of end-organ damage. VA NEPHRON-D was a study in patients with type 2 diabetes mellitus and diabetic nephropathy.

These studies have shown no significant beneficial effect on renal and/or cardiovascular outcomes and mortality, while an increased risk of hyperkalaemia, acute kidney injury and/or hypotension as compared to monotherapy was observed. Given their similar pharmacodynamic properties, these results are also relevant for other ACE inhibitors and angiotensin II receptor blockers.

ACE inhibitors and angiotensin II receptor blockers should therefore not be used concomitantly in patients with diabetic nephropathy.

ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) was a study designed to test the benefit of adding aliskiren to a standard therapy of an ACE inhibitor or an angiotensin II receptor blocker in patients with type 2 diabetes mellitus and chronic kidney disease, cardiovascular disease, or both. The study was terminated early because of an increased risk of adverse outcomes. Cardiovascular death and stroke were both numerically more frequent in the aliskiren group than in the placebo group and adverse events and serious adverse events of interest (hyperkalaemia, hypotension and renal dysfunction) were more frequently reported in the aliskiren group than in the placebo group.

Pharmacokinetic properties

Quinapril

Peak plasma quinapril concentrations are observed within 1 hour of oral administration. The extent of absorption is approximately 60%, and is not influenced by food. Following absorption, quinapril is deesterified to its major active metabolite, quinaprilat, and to minor inactive metabolites. Quinapril has an apparent half-life of approximately 1 hour. Peak plasma quinaprilat concentrations are observed approximately 2 hours following an oral dose of quinapril. Quinaprilat is eliminated primarily by renal excretion and has an effective accumulation half-life of 7 hours. In patients with renal insufficiency and creatinine clearance of ≤40 mL/min, peak and trough quinaprilat concentrations increase, time to peak concentration increases, apparent half-life increases, and time to steady state may be delayed. The elimination of quinaprilat is also reduced in elderly patients (>65 years) and correlates well with the impaired renal function which frequently occurs in the elderly. Studies in rats indicate that Accuretic and its metabolites do not cross the blood-brain barrier.

Hydrochlorothiazide

After oral administration of HCTZ, diuresis begins within 2 hours, peaks in about 4 hours, and lasts about 6 to 12 hours. HCTZ is excreted unchanged by the kidney. When plasma levels have been followed for at least 24 hours, the plasma half-life has been observed to vary between 4 to 15 hours. At least 61% of the oral dose is eliminated unchanged within 24 hours. HCTZ crosses the placenta but not the blood-brain barrier.

Lactation

After a single oral dose of 20 mg of quinapril in six breast-feeding women, the M/P (milk to plasma ratio) for quinapril was 0.12. Quinapril was not detected in milk after 4 hours after the dose. Quinalaprilat milk levels were undetectable (<5 μg/L) at all time points. It is estimated that a breastfed infant would receive about 1.6% of the maternal weight-adjusted dosage of quinapril.

Date of revision of the text

02/2018

Marketing authorisation holder

Pfizer Limited

Ramsgate Road

Sandwich

Kent

CT13 9NJ

United Kingdom

Special precautions for storage

Do not store above 25°C.

Store in the original package in order to protect from moisture.

Nature and contents of container

Double sided aluminium foil blister enclosed in printed carton. Available in pack sizes of 7, 28, 30, 100 and 156.

Not all pack sizes may be marketed.

Marketing authorisation number(s)

PL 00057/0518

Special precautions for disposal and other handling

No special requirements for disposal.

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

Date of first authorisation/renewal of the authorisation

Date of first authorisation: 1 May 2003

Date of latest renewal: 1 May 2003