ACCUZIDE 20
ACCUZIDE 20
Composition
Active ingredients: 1 film-coated tablet contains 21.7 mg quinapril hydrochloride (corresponding to 20 mg quinapril) and 12.5 mg hydrochlorothiazide. Excipients: candelilla wax, crospovidone, hydroxypropylcellulose, lactose 1 H2O, macrogol 400, heavy basic magnesium carbonate, magnesium stearate, methylhydroxypropylcellulose, polyvidone, colouring agents E 171, E 172. Indication Essential hypertension (non-organic high blood pressure), when treatment with a combination preparation is indicated. Combination therapy is always recommended if monotherapy intended for initial control of hypertension is not adequately effective. A fixed combination is not appropriate for dose adjustments but serves as a substitute when the maintenance doses of the individual components correspond to those of the fixed combination.
Contraindications
Contraindications
are illnesses or conditions under which certain medications should not be used or used only after the physician has carefully assessed the need, since in these conditions the expected benefits do not outweigh the possible risks. For the physician to decide whether contraindications exist, he must be informed of prior illnesses, concurrent diseases, any concomitant medication as well as patient's particular lifestyle habits. Sometimes contraindications may only become apparent or known after treatment has started with this medication. In such cases you should inform your physician Accuzide 20 should not be used in the following conditions: Hypersensitivity to quinapril hydrochloride, thiazide or sulfonamides (watch for possible cross-reaction); tendency to tissue swelling (angioneurotic edema e.g. as a result of previous ACE inhibitor therapy); severe impairment of renal function (serum creatinine more than 1.8 mg/dl or creatinine clearance less than 30 ml/min; dialysis; renal artery stenosis (bilateral or unilateral); after kidney transplantation; aortic or mitral valve stenosis or other obstructive outflow conditions of the heart (hypertrophic cardiomyopathy); untreated weakness of the cardiac muscle (decompensated heart failure); primary elevated aldosterone concentration in the blood (primary hyperaldosteronism); severe impairment of hepatic function (hepatic pre-coma/coma) or primary liver disease; severe electrolyte imbalance (hypercalcemia, hyponatremia, hypokalemia); children (due to lack of clinical experience). Prior to administration of an ACE inhibitor like Accuzide 20, pregnancy must be ruled out in women of childbearing age and, during treatment with Accuzide 20, reliable contraceptive measures must be taken. However, if pregnancy occurs during Accuzide 20 treatment, the physician should be consulted and a switch made to a different therapy with lower risk to the fetus, since Accuzide 20, especially during the last 6 months of pregnancy, may be harmful to the fetus. If treatment of a nursing mother becomes necessary, the infant should be weaned. Accuzide 20 should only be used after very precise risk/benefit assessment and under regular monitoring of certain clinical and laboratory-chemical parameters in: Increased secretion of protein in urine (more than 1 g/day) (proteinuria); impaired immunoreaction or collagen diseases (e.g. lupus erythematosus, scleroderma); concurrent therapy with drugs which suppress the defense reactions (immunosuppressants, e.g. corticosteroids, cytostatics, antimetabolites), allopurinol, procainamide or lithium; gout; hypovolemia (reduced blood volume); cerebral sclerosis (sclerosis of blood vessels in the brain); coronary sclerosis (sclerosis of blood vessels in the heart); manifest or latent diabetes mellitus (known or suspected blood sugar elevation); impaired liver function. NOTE: see also on Dosage and Administration Kidney function must be checked and salt/fluid deficiency balanced prior to administration of Accuzide 20 Especially at the start of therapy, Accuzide 20 should be administered with precaution along with continuous monitoring of blood pressure and/or certain laboratory values in: patients with impaired renal function (serum creatinine up to 1.8 mg/dl or creatinine clearance 30-60 ml/min; patients with severe hypertension; elderly patients (over 65 years). During treatment with Accuzide 20, dialysis or hemofiltration (blood cleansing) should not be made with polyacrylnitril- methallylsulfonate high-flux membranes (such as AN 69), since the danger exists during dialysis or hemofiltration that hypersensitivity reactions (anaphylactoid reactions) leading to and including lifethreatening shock, may occur. In the case of emergency dialysis or hemofiltration, a switch must first be made to a different antihypertensive medication (not an ACE inhibitor) or a different dialysis membrane used. Please inform your physician that you are being treated with Accuzide 20 or that you require dialysis so that he can make allowances for this during treatment.
Side Effects
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Precaution
s Medications, whilst having a desirable effect can also produce undesirable side effects. Side effects which have been observed in patients taking Accuzide 20 as well as other ACE inhibitors or hydrochlorothiazide are listed below. These may not necessarily occur in every patient Cardiovascular At the initiation of Accuzide 20 therapy, and in patients with salt and/or fluid deficiency (e g. as a result of vomiting/diar- rhea or previous diuretic treatment), severe hypertension and if the dosage of Accuzide 20 has been increased, occasional excessive reduction of the blood pressure may occur along with symptoms such as blurred vision, feeling of weakness and dizziness up to syncope (loss of consciousness). During treatment with hydrochloro-thiazide, changes in the ECG and cardiac arrhythmias may occur frequently due to potassium deficiency In individual cases, excessive reduction of blood pressure has been reported in connection with: tachycardia (increased head rate), palpitations, cardiac arrhythmia, angina pectoris, myocardial infarction, transient deficiency of blood supply to the brain (Transient Ischemic Attack - TIA), stroke (cerebral insult) Kidneys Occasionally, in isolated cases, renal impairment may occur or become more pronounced progressing to acute renal failure. Increased protein excretion in urine (proteinuria), sometimes accompanied by deterioration of renal function, has been rarely observed. Isolated cases of renal inflammation (non- bacterial interstitial nephritis) resulting in acute kidney failure, have been reported whilst taking hydrochlorothiazide. Respiratory Tract Occasionally, dry irritative cough and bronchitis, rarely shortness of breath, inflammation of the sinuses (sinusitis), runny nose (rhinitis), isolated cramp-like narrowing of the bronhci resulting in shortness of breath (bronchospasms), inflammatory changes in the mucosa of the tongue (glossitis) and dry mouth may occur. In isolated cases, sudden onset of fluid accumulation in the lungs (pulmonary edema) with symptoms of shock has been described, presumably caused by an allergic reaction to hydrochlorothiazide. In isolated cases, tissue swelling (angioneurotic edema), progressing to involvement of the larynx, pharynx and/or tongue were reported with ACE inhibitor use. Should such a condition arise, immediate subcutaneous administration of 5. 913 0.3-0.5 mg epinephrine or slow intravenous administration of 0.1 mg epinephrine under ECG and blood pressure monitoring, followed by systemic glucocorticoid administration is required. Intravenous administration of antihistamines and H2 receptor antagonists is also recommended. In addition to epinephrine, administration of C, inactivator may be considered in cases of known C, inactivator deficiency. Gastrointestinal Tract Occasionally, nausea, upper abdominal pain, and indigestion may occur, rarely vomiting, diarrhea, constipation and loss of appetite Individual cases of jaundice due to bile retention (cholestatic icterus), liver dysfunction, inflammation of the liver (hepatitis), and intestinal occlusion (sub-ileus, ileus) have been described under ACE inhibitor therapy. Skin, Blood Vessels Occasionally, allergic skin reactions such as rash (exanthema), rarely irritating rash (urticaria), itching (pruritus) and skin reactions like erythema multiforme, Stevens- Johnson syndrome, lupus erythematosus (isolated cases after treatment with hydrochlorothiazide), or angioneurotic edema involving the lips, face and/or extremities, may occur. In individual cases, the skin changes may be accompanied by fever, muscle and joint pain (myalgia, arthralgia, arthritis), vascular inflammation (vasculitis) and certain changes in laboratory values (eosinophilia, leukocytosis, elevated EST and/or elevated ANA titer). If serious skin reactions are suspected, the physician must be consulted at once and therapy with Accuzide 20 terminated. Anaphylactoid reactions, psoriasis-like skin changes, sensitivity to light (photosensitivity), reddening of the face (flushes), sweating (diaphoresis), loss of hair (alopecia), loss of fingernails/toenails (onycholysis) and potentiation of vascular cramps in Raynaud's disease have been observed in isolated cases. With high doses of hydrochlorothiazide, blood clots and occlusion of blood vessels (thromboses and embolisms) have occurred as a result of fluid loss, especially in elderly patients with vascular diseases. Reduction in the secretion of tears has rarely been observed during treatment with hydrochlorothiazide. Nervous System Occasionally, headache, fatigue, somnolence, weakness, apathy, rarely depression, giddiness, insomnia, impotence, tingling, feeling of numbness or cold extremities (parasthesias), impaired equilibrium, disorientation, mood swings, tinnitus, blurred vision and change in the sense of taste or transient loss of the sense of taste may occur, partly due to imbalance of the fluid and electrolytes. Musculoskeletal System Rarely, muscle cramps, weakness of the skeletal muscles, muscle pain and, as a result of potassium deficiency, signs of lameness (paresis), may occur. Laboratory Parameters Occasionally, there may be a decrease in hemoglobin concentration, hematocrit, white blood cells or platelets. Rarely, especially in patients with impaired kidney function, collagen diseases or concurrent therapy with allopurinol, procainamide or certain drugs which suppress the defense mechanisms, a pathological reduction or change in the blood count (anemia, thrombocytopenia, neutropenia, eosinophilia) may also occur. In isolated cases, hemolysis/hemolytic anemia, with or without G-6-PDH deficiency, has been reported, although no causal relationship to ACE inhibitors could be demonstrated. The component hydrochlorothiazide may occasionally elicit potassium, chloride and magnesium deficiencies in the blood and calcium excess in the blood, glucosuria and metabolic-related alkalosis. Elevation in blood sugar, cholesterol, triglycerides, uric acid and serum amylase have been observed. Occasionally, in patients with impaired renal function, the serum concentrations of urea, creatinine and potassium may increase and the sodium concentration may decrease. Increased protein elimination (proteinuria) in urine may occur. In isolated cases, serum bilirubin and liver enzyme concentrations may become elevated. NOTES The above laboratory parameters should be monitored regularly prior to and during Accuzide 20 therapy. At the start of therapy and in high risk patients (patients with impaired renal function, collagen diseases, treatment with immunosuppressants, allopurinol, procainamide, digitalis glycosides, glucocorticoids, laxatives, elderly patients), control of serum electrolytes, creatinine, blood sugar and blood count are required at short intervals. If symptoms arise such as fever, lymph node swelling and/or inflammed throat during therapy, the white blood count should be immediately checked. Effects on Ability to Drive and Operate Machinery Treatment of high blood pressure with this drug requires regular medical supervision. Due to individual variations, the capability of operating machinery, including motor vehicles, may be impaired. This applies especially at the beginning of treatment, switching from other medications and when alcohol is consumed. The medication should not be used after the expiry date printed on the pack. Keep medicine safe and out of the reach of children.
Drug Interactions
The effects of many drugs can be influenced by use of other drugs at the same time. Therefore, inform your physician if you are currently taking drugs, or may need to use other drugs with this medication. Your physician can tell you whether reactions can be anticipated or whether special measures, like dose adjustments, may be necessary if you use these medications. The following interactions have been described when Accuzide 20, other ACE inhibitors or hydrochlorothiazide are used concurrently with: - Table salt: reduction in the antihypertensive effect of Accuzide 20; antihypertensive drugs (such as other diuretics, beta-blockers), nitrates, vasodilators, barbiturates, phenothiazines, tricyclic antidepressants, alcohol: potentiation of the antihypertensive effect of Accuzide 20; - Pain relievers and drugs to reduce inflammation (such as salicylic acid, indomethacin): possible decrease in antihypertensive effect of Accuzide 20. Acute kidney failure may be elicited, especially in cases of low blood volume; - High dose salicylate administration: potentiation of the damaging effect of salicylates on the central nervous system due to hydrochlorothiazide; - Potassium, potassium-sparing diuretics (such as spironolactone, amiloride, triamterene): greater increase in serum potassium concentration due to quinapril. - Lithium: elevation of serum lithium concentration (regular checkups), thus potentiation of the cardiac and nerve-damaging effects of lithium; - Alcohol: potentiation of alcohol effects. Digitalis glycosides: effects and side effects of digitalis glycosides may be potentiated by presence of potassium and/or magnesium deficiency; - Oral anti-diabetic drugs, insulin: weakening of the effect due to hydrochlorothiazide. - Catecholamines (such as epinephrine): weakening of the effect due to hydrochlorothiazide; - Potassium-eliminating diuretics (such as furosemide), glucocorticoids, ACTH, carbenoxolone, amphotericin B, penicillin G, salicylates or laxative abuse: elevated potassium and/or magnesium loss due to hydrochlorothiazide. - Cholestyramine or Colestipol: reduced absorption of hydrochlorothiazide. Allopurinol, procainamide, drugs suppressing immune reactions (cytostatics, immunosuppressants, systemic corticosteroids): decrease in white blood cell count (leukopenia); - Drugs which inhibit cell division (cytostatics such as cyclophosphamide, fluorouracil, methotrexate: increased damaging effect to the bone marrow (especially granulocy-topenia), due to 5. 914 sec t io n r PFIZER hydrochlorothiazide; sedatives, narcotics: potentiated decrease in blood pressure (if receiving Accuzide 20 therapy, the anesthetist should be informed); - Methyldopa: isolated cases of hemolysis due to formation of antibodies to hydrochlorothiazide; - Neuroleptic drugs, imipramine: potentiation of the antihypertensive effect of Accuzide 20; - Tetracyclines: reduced absorption of tetracyclines. NOTE Accuzide 20 should not be used in conjunction with polyacrylnitril-methallylsul- fonate high-flux membranes (such as AN 69) (see
Contraindications
).
Dosage and Administration
Basically, treatment of hypertension should be initiated with low doses of a single substance. The fixed combination Accuzide 20 (consisting of 20 mg quinapril and 12.5 mg hydrochlorothiazide) should be used only after prior therapy with the free combination of quinapril hydrochloride and hydrochlorothiazide resulting in normalization of blood pressure. The maintenance dose of the free combination should correspond to that of the fixed combination. If the blood pressure does not respond adequately to the combination of 20 mg quinapril and 12.5 mg hydrochlorothiazide (corresponding to 1 film-coated tablet Accuzide 20), the dosage of Accuzide 20 may not be increased Your physician will determine the appropriate dose. Dosing should be adjusted to suit the needs of the individual patient. Unless otherwise prescribed, the dose for patients in whom the combination therapy is indicated is 1 film-coated Accuzide 20 tablet in the morning. This dose should not be exceeded. Dosing in moderately impaired renal function (creatinine clearance 30-60 ml/min or serum creatinine concentration 1.2-1.8 mg/dl) and elderly patients (over 65 years). Dose adjustment must be made with special care (titration of the individual components). The initial dose for patients with mild impairment of renal function (creatinine clearance 30-60 ml/min) should be 5 mg quinapril as monotherapy, which may be titrated up to the appropriate dose level of not more than 20 mg quinapril. The dose for patients who also require a diuretic can subsequently be titrated for hydrochlorothiazide. Control of blood pressure can then be continued with Accuzide 20. Patients with severe kidney failure (creatinine clearance less than 30 ml/min) should be excluded from treatment with quinapril hydrochloride or Accuzide 20. Nature and Duration of Treatment Accuzide 20 may be taken irrespective of meals. The daily dose should be swallowed whole with plenty of liquid and taken as a single dose in the morning. The physician will decide on the duration of treatment.
Packaging
t: 30 (blister packs, film-coated).