Quinapril Hydrochloride/Hydrochlorothiazide

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|Quinapril Hydrochloride/Hydrochlorothiazide

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Quinapril Hydrochloride/Hydrochlorothiazide

Pronouncation: (KWIN-uh-PRILL HIGH-droe-KLOR-ide/ high-droe-klor-THIGH-uh-zide)
Class: Antihypertensive combination

Trade Names:
Accuretic
- Tablets 10 mg quinapril/12.5 mg HCTZ
- Tablets 20 mg quinapril/12.5 mg HCTZ
- Tablets 20 mg quinapril/25 mg HCTZ

Mechanism of Action

Pharmacology

Quinapril

Competitively inhibits angiotensin I-converting enzyme, resulting in the prevention of angiotensin I conversion to angiotensin II, a potent vasoconstrictor that stimulates aldosterone secretion. This action results in a decrease in sodium and fluid retention, an increase in diuresis, and a decrease in BP.

Hydrochlorothiazide (HCTZ)

Increases chloride, sodium, and water excretion by interfering with transport of sodium ions across renal tubular epithelium.

Indications and Usage

Treatment of hypertension.

Contraindications

Patients with a history of angioedema related to previous treatment with an ACE inhibitor; patients with anuria; hypersensitivity to sulfonamide-derived drugs or any component of the product.

Dosage and Administration

The fixed combination is not indicated for initial therapy. The combination may be substituted for the titrated components.

Adults

PO Quinapril monotherapy is an effective treatment of hypertension over a dose range of 10 to 80 mg/day administered every day. HCTZ is effective in doses of 12.5 to 50 mg every day. Patients whose BP is not adequately controlled with quinapril monotherapy may be given quinapril/HCTZ (10/12.5 or 20/12.5). Further increases in dose of either or both components depend on the clinical response. Generally, the dose of HCTZ should not be increased until 2 to 3 wk have elapsed.

Renal Function Impairment
Adults

No adjustment required as long as Ccr is greater than 30 mL/min; in severe renal impairment, loop diuretics are preferred to thiazides.

Storage/Stability

Store tablets at controlled room temperature (68° to 77°F). Keep container tightly closed.

Drug Interactions

ACTH, corticosteroids

Electrolyte depletion may be intensified, especially hypokalemia.

Alcohol, barbiturates (eg, phenobarbital), narcotics

Orthostatic hypotension may be potentiated.

Anticoagulants (eg, warfarin)

Anticoagulant effect may be decreased.

Antidiabetic agents (eg, insulin, sulfonylureas), antigout agents (eg, probenecid)

Dosage adjustment may be necessary because of possible HCTZ-induced elevation in blood glucose levels.

Cardiac glycosides (eg, digoxin)

Possible digitalis toxicity associated with hypokalemia.

Cholestyramine, colestipol

May impair the absorption of HCTZ.

Insulin

In diabetic patients, requirements of insulin may be increased, decreased, or unchanged.

Lithium

Plasma levels of lithium may be elevated, increasing the risk of toxicity.

NSAIDs

May reduce the natriuretic and antihypertensive effect of HCTZ.

Potassium supplements, potassium-sparing diuretics (eg, spironolactone)

Increased risk of hyperkalemia.

Nondepolarizing muscle relaxants (eg, tubocurarine)

Effects may be increased.

Pressor amines (eg, norepinephrine)

Response to pressor amines may be decreased.

Tetracycline and other drugs that interact with magnesium

Because of the magnesium content in quinapril, absorption of tetracycline may be reduced, decreasing the therapeutic effect.

Laboratory Test Interactions

Hydrochlorothiazide

May decrease serum protein-bound iodine levels without signs of thyroid disturbances.

Adverse Reactions

Cardiovascular

Bradycardia; cor pulmonale; vasculitis; deep thrombosis; vasodilatation; chest pain.

Quinapril

Syncope.

Hydrochlorothiazide

Orthostatic hypotension.

CNS

Dizziness; somnolence; paralysis; hemiplegia; speech disorder; abnormal gait; meningism; amnesia; headache; fatigue; insomnia; vertigo; asthenia.

Quinapril

Depression.

Hydrochlorothiazide

Lightheadedness; paresthesia; weakness; restlessness.

Dermatologic

Urticaria; macropapular rash; petechiases.

EENT

Esophagitis; abnormal vision; rhinitis.

Quinapril

Amblyopia.

Hydrochlorothiazide

Transient blurred vision; xanthopsia.

GI

GI carcinoma; vomiting; diarrhea; nausea; abdominal pain; constipation; dyspepsia.

Hydrochlorothiazide

Pancreatitis; sialadenitis; diarrhea; cramping; gastric irritation; anorexia.

Genitourinary

Abnormal kidney function; albuminuria; pyuria; hematuria; nephrosis.

Hydrochlorothiazide

Renal failure; renal dysfunction; interstitial nephritis.

Hematologic

Anemia.

Hydrochlorothiazide

Aplastic anemia; agranulocytosis; leukopenia; thrombocytopenia; hemolytic anemia.

Hepatic

Cholestatic jaundice; hepatitis.

Hydrochlorothiazide

Jaundice (intrahepatic cholestatic).

Metabolic

Weight loss.

Hydrochlorothiazide

Hyperglycemia; glucosuria; hyperuricemia; hypokalemia; hyponatremia; hypochloremic alkalosis.

Respiratory

Coughing; pneumonia; asthma; respiratory infiltration; lung disorder; upper respiratory tract infection; bronchitis.

Miscellaneous

Shock; accidental injury; neoplasm; cellulitis; ascites; generalized edema; hernia; myopathy; myositis; arthritis; myalgia; viral infection; angioedema.

Quinapril

Back pain; anaphylactoid reactions.

Hydrochlorothiazide

Muscle spasm; hypersensitivity (including necrotizing angiitis, Stevens-Johnson syndrome, respiratory distress [including pneumonia and pulmonary edema], purpura, urticaria, rash, and photosensitivity).

Precautions

Warnings

When used in pregnancy during the second and third trimesters, ACE inhibitors can cause injury and even death to the developing fetus. When pregnancy is detected, discontinue therapy as soon as possible.


Monitor

Monitor blood sugar in diabetic patient when drug is started or dose is changed.


Pregnancy

Category D (second and third trimester); Category C (first trimester). ACE inhibitors (eg, quinapril) can cause injury or death to fetus if used during second or third trimester. When pregnancy is detected, discontinue as soon as possible.

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established.

Elderly

Select dose with caution, reflecting greater frequency of decreased hepatic, renal, or cardiac function and comorbidity.

Renal Function

Use with caution.

Hepatic Function

Use with caution.

Anaphylactoid reactions

Reported in patients with a history of angioedema, undergoing desensitizing treatment with Hymenoptera venom, and in patients dialyzed with high-flux membranes.

Angioedema

Use with extreme caution in patients with a history of angioedema. Angioedema associated with laryngeal edema may be fatal. Angioedema may occur more frequently in black patients receiving an ACE inhibitor compared with non-black patients.

Cough

Chronic cough may occur during treatment.

Electrolyte imbalance

Treatment with thiazide diuretics has been associated with hypokalemia, hyponatremia, hypochloremic alkalosis, hypercalcemia, and hypomagnesemia. Do not initiate therapy prior to correction of imbalance.

Hepatic failure

Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and death.

Hypotension

Decreases in BP may occur, especially in salt- or volume-depleted patients as a result of dialysis, prolonged diuretic therapy, dietary salt restriction, diarrhea, or vomiting. Volume and salt depletion should be corrected before initiating therapy with quinapril/HCTZ.

Metabolic disturbances

Thiazide diuretics tend to reduce glucose tolerance, raise cholesterol, triglycerides, and uric acid levels.

Neutropenia/Agranulocytosis

Has occurred with other ACE inhibitors.

Surgery/Anesthesia

In patients undergoing surgery or during anesthesia with agents that produce hypotension, angiotensin II formation, secondary to compensatory renal release, may be blocked.

Systemic Lupus Erythematosus (SLE)

HCTZ may exacerbate or activate SLE.

Overdosage

Symptoms

Dehydration, electrolyte imbalance (hypokalemia [which may accentuate cardiac arrhythmias in patients receiving digitalis], hypochloremia, hyponatremia), hypotension.

Patient Information

  • Explain name, dose, action, and potential side effects of drug.
  • Advise patient to take prescribed dose every day without regard to meals.
  • Advise patient to try to take each dose at about the same time every day.
  • Inform patient that drug controls, but does not cure, hypertension and to continue taking drug as prescribed even when BP is not elevated.
  • Caution patient not to change the dose or stop taking unless advised by health care provider.
  • Instruct patient to continue taking other BP medications as prescribed by health care provider.
  • Instruct patient in BP and pulse measurement skills.
  • Advise patient to monitor and record BP and pulse at home and to inform health care provider if abnormal measurements are noted. Also, advise patient to take record of BP and pulse to each follow-up visit.
  • Caution patient to avoid sudden position changes to prevent orthostatic hypotension.
  • Instruct patient to lie or sit down if experiencing dizziness or lightheadedness when standing.
  • Caution patient that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to excessive fall in BP resulting in lightheadedness or fainting.
  • Instruct diabetic patient to monitor blood glucose more frequently when drug is started or dose is changed and to inform health care provider of significant changes in readings.
  • Caution patient to avoid unnecessary exposure to UV light (sunlight, tanning booths) and to use sunscreen and wear protective clothing when exposed to UV light to avoid photosensitivity reaction.
  • Emphasize to hypertensive patient importance of other modalities on BP: weight control, regular exercise, smoking cessation, and moderate intake of alcohol and salt.
  • Advise women to notify health care provider if pregnant, planning to become pregnant, or breastfeeding.
  • Instruct patient to stop taking drug and immediately report any of the following symptoms to health care provider: fainting, swelling of the face, lips, eyelids or tongue, difficulty breathing.
  • Instruct patient to inform health care provider if a persistent cough develops while taking this medication.
  • Caution patient not to take any prescription or OTC medications, potassium-containing salt substitutes, potassium supplements, or dietary supplements unless advised by health care provider.
  • Advise patient that follow-up visits and lab tests may be required to monitor therapy and to keep appointments.




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