Quinapril / Hydrochlorothiazide (Apo-Quinapril/HCTZ)

1. Health Canada Product Monograph — Quinapril / Hydrochlorothiazide

• This medication treats high blood pressure (essential hypertension) in patients who need combination therapy.
• This fixed-dose combination is not intended for starting treatment; patients should first have their quinapril and hydrochlorothiazide doses individually adjusted (titrated) before switching to the combination tablet.

Contraindicated in pregnancy. Confirm pregnancy status and discuss alternative therapy with the prescriber before dispensing.

• This medication is contraindicated in women who are pregnant, trying to become pregnant, or of childbearing potential who are not using effective contraception.
• ACE inhibitors like quinapril can cause serious injury or death to a developing fetus, particularly during the second and third trimesters.
• If pregnancy is detected, this medication should be stopped as soon as possible.
• Exposure during the first trimester has also been linked to heart and nervous system malformations.
• The thiazide component crosses the placenta and may cause fetal or newborn jaundice or low platelet counts.

• This medication is contraindicated during breastfeeding, because both the ACE inhibitor and thiazide components pass into human breast milk.

• The blood-pressure-lowering effect appears similar in older adults (over 65) and younger adults given the same doses, without an increase in side effects.
• The recommended starting dose of quinapril is still 10 mg once daily, adjusted for kidney function, followed by careful titration.

• No data are available on the use of this medication in children, so it is not approved for pediatric use.

• This combination product is not used to start treatment; the individual ACE inhibitor and diuretic doses should be established first, then switched to this fixed combination if appropriate.
• Once a patient's blood pressure is controlled on the individual components at doses matching an available combination strength, the combination tablet may be substituted for convenience.
• Patients typically do not need more than 50 mg of hydrochlorothiazide daily, particularly when combined with other blood pressure medications.
• In patients with reduced kidney function, the starting quinapril dose should be lowered based on creatinine clearance, and this fixed combination is not recommended for patients with severe kidney impairment.
• If a diuretic cannot be stopped before starting therapy, close medical supervision is needed for the first dose due to the risk of a sudden blood pressure drop.
• If a dose is missed, take it as soon as possible, but skip it if it is almost time for the next dose; do not double up.

If overdose is suspected, seek emergency medical attention immediately or contact your regional Poison Control Centre without delay.

• No specific data are available on overdose with this combination product or with quinapril alone.
• The most likely effect of an overdose is severe low blood pressure, which is typically treated with intravenous saline solution.
• Dialysis has little effect on removing quinapril from the body.
• Hydrochlorothiazide overdose typically causes symptoms of electrolyte loss (low potassium, low chloride, low sodium) and dehydration from excessive urination.
• If a patient is also taking digitalis-type heart medication, low potassium from an overdose may worsen heart rhythm problems.

• Headache may occur.
• Dizziness may occur.
• Cough, which is typically dry and persistent, may occur.
• Fatigue may occur.
• Muscle aches (myalgia) may occur.
• Nausea or vomiting may occur.
• Diarrhea may occur.
• Stomach pain may occur.
• Indigestion (dyspepsia) may occur.
• Sore throat (pharyngitis) or a stuffy/runny nose (rhinitis) may occur.
• Sleep disturbances, including insomnia or excessive sleepiness, may occur.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Angioedema (swelling of the face, lips, tongue, or throat) may occur and can be life-threatening if it affects the airway.
• A sudden, significant drop in blood pressure may occur, especially after the first dose or a dose increase.
• Kidney function may worsen, particularly in patients with pre-existing kidney disease, heart failure, or those taking diuretics.
• High potassium levels (hyperkalemia) may occur, especially with kidney problems, diabetes, or other potassium-raising medications.
• Low potassium, low sodium, or low chloride levels may occur due to the diuretic component.
• Liver problems, including hepatitis and yellowing of the skin or eyes (jaundice), have been reported rarely.
• A drop in white blood cells (agranulocytosis) has been reported rarely, more often in patients with existing kidney or connective tissue disease.
• Serious skin reactions, including exfoliative dermatitis and erythema multiforme, may occur.
• Sudden severe eye problems, including acute angle-closure glaucoma or acute nearsightedness, may occur, usually within hours to weeks of starting treatment.
• Long-term hydrochlorothiazide use has been associated with an increased risk of non-melanoma skin cancer.
• Acute respiratory distress syndrome, a severe lung reaction, has been reported very rarely with hydrochlorothiazide.
• Seek urgent medical attention for facial or throat swelling, difficulty breathing or swallowing, severe dizziness or fainting, or sudden vision changes.

• Use with caution in patients who are volume-depleted from diuretics, low-salt diets, vomiting, or diarrhea, due to a higher risk of a sudden blood pressure drop.
• Use with caution in patients with heart failure or reduced kidney function, monitoring kidney function and electrolytes closely.
• Use with caution in patients with liver disease, since fluid and electrolyte changes can trigger liver-related complications.
• Use with caution in patients with diabetes, since blood sugar control may be affected.
• Use with caution in patients with a history of allergy, asthma, or a personal or family history of psoriasis.
• Use with caution in patients with gout, since thiazides can raise uric acid levels.
• Use with caution in patients with a history of skin cancer or significant sun exposure, and advise sun protection.
• Use with caution before major surgery, as blood pressure drops can occur during anesthesia.

• Contraindicated in patients hypersensitive to this drug or any ingredient in the tablet.
• Contraindicated in patients with a history of angioedema related to previous ACE inhibitor treatment.
• Contraindicated in combination with sacubitril/valsartan, or within 36 hours of stopping it, due to increased angioedema risk.
• Contraindicated in patients hypersensitive to other sulfonamide-derived drugs because of the hydrochlorothiazide component.
• Contraindicated in patients with anuria (absence of urine production).
• Contraindicated in women who are pregnant, trying to become pregnant, or not using adequate contraception.
• Contraindicated in women who are breastfeeding.
• Contraindicated in combination with aliskiren-containing medicines in patients with diabetes, moderate-to-severe kidney impairment, high potassium, or hypotensive heart failure.
• Contraindicated in combination with angiotensin receptor blockers (ARBs) in patients with diabetes and organ damage, moderate-to-severe kidney impairment, high potassium, or hypotensive heart failure.
• Contraindicated in patients with the rare hereditary condition of galactose intolerance or glucose-galactose malabsorption, since the tablets contain lactose.

• Combining this medication with sacubitril/valsartan increases the risk of angioedema and requires a 36-hour separation between the two drugs.
• Potassium-sparing diuretics, potassium supplements, and salt substitutes containing potassium can raise blood potassium to dangerous levels when combined with this medication.
• Combining this medication with an angiotensin receptor blocker or aliskiren increases the risk of low blood pressure, high potassium, and kidney problems, and is contraindicated in several patient groups.
• NSAIDs, including selective COX-2 inhibitors, can reduce the blood-pressure-lowering effect of this medication and increase the risk of kidney problems, especially in older, dehydrated, or kidney-impaired patients.
• Lithium levels can rise to toxic levels when combined with this medication; concurrent use is generally not recommended.
• Digoxin combined with this medication requires close monitoring, since electrolyte changes can increase the risk of digoxin toxicity.
• Alcohol, barbiturates, or narcotics can worsen the blood-pressure-lowering effect and increase the risk of dizziness or fainting, especially when starting treatment.
• Cholestyramine and other bile acid sequestrants can reduce absorption of the hydrochlorothiazide component and should be taken several hours apart from this medication.
• Corticosteroids can worsen potassium loss when combined with this medication.
• Antidiabetic medications, including insulin, may need dose adjustment, since this medication can affect blood sugar control in both directions.
• Tetracycline antibiotics may be less well absorbed when taken with this medication due to its magnesium content.
• DPP-4 inhibitors, mTOR inhibitors, and neutral endopeptidase inhibitors may increase the risk of angioedema when combined with this medication.
• Trimethoprim-containing antibiotics can increase the risk of severe high potassium, especially in older or kidney-impaired patients.
• Calcium and vitamin D supplements combined with this medication can raise blood calcium levels, requiring monitoring.

• This medication can be taken with or without food; however, a high-fat meal can moderately reduce absorption of the quinapril component, so taking it with a regular, lighter meal or without food is preferred for consistent absorption.

• This medication may be taken at any time of day, with or without food, though avoiding high-fat meals around dosing helps ensure consistent absorption; try to take it at the same time each day.

• Store this medication at room temperature, between 15°C and 30°C, protected from moisture, with the container tightly closed.

• This medication combines two blood-pressure-lowering medicines in one tablet and is generally used once you are already stable on the individual components.
• Watch for facial, lip, tongue, or throat swelling, which can signal a serious allergic reaction requiring emergency care.
• Rise slowly from sitting or lying down, especially when starting treatment, to reduce dizziness from low blood pressure.
• Routine blood tests to check kidney function and electrolytes are an important part of monitoring this medication.
• Protect your skin from excess sun exposure and report any new or changing skin spots to your healthcare professional.