Prinzide Side Effects

Please note - some side effects for Prinzide may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).

Side Effects of Prinzide - for the Consumer

Prinzide

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Prinzide:

Dizziness; headache; lightheadedness; nausea; persistent nonproductive cough; tiredness; vomiting.

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); chest pain or discomfort; confusion; dark urine; fainting; fast, slow, or irregular heartbeat; increased thirst; joint pain, stiffness, or swelling; muscle cramps or weakness; numbness or tingling of hands or feet; persistent and unusual stomach pain; persistent sore throat or fever; red, swollen, or blistered skin; severe dizziness or lightheadedness; shortness of breath; sudden unusual weight loss or gain; trouble swallowing; unusual bruising or bleeding; unusual or severe weakness or tiredness; vision changes; yellowing of the skin or eyes.

Prinzide Side Effects - for the Professional

Prinzide

Prinzide has been evaluated for safety in 930 patients, including 100 patients treated for 50 weeks or more.

In clinical trials with Prinzide no adverse experiences peculiar to this combination drug have been observed. Adverse experiences that have occurred have been limited to those that have been previously reported with lisinopril or hydrochlorothiazide.

The most frequent clinical adverse experiences in controlled trials (including open label extensions) with any combination of lisinopril and hydrochlorothiazide were: dizziness (7.5 percent), headache (5.2 percent), cough (3.9 percent), fatigue (3.7 percent) and orthostatic effects (3.2 percent), all of which were more common than in placebo-treated patients. Generally, adverse experiences were mild and transient in nature; but see WARNINGS regarding angioedema and excessive hypotension or syncope. Discontinuation of therapy due to adverse effects was required in 4.4 percent of patients, principally because of dizziness, cough, fatigue and muscle cramps.

Adverse experiences occurring in greater than one percent of patients treated with lisinopril plus hydrochlorothiazide in controlled clinical trials are shown below.

Clinical adverse experiences occurring in 0.3 to 1.0 percent of patients in controlled trials included: Body as a Whole: Chest pain, abdominal pain, syncope, chest discomfort, fever, trauma, virus infection. Cardiovascular: Palpitation, orthostatic hypotension. Digestive: Gastrointestinal cramps, dry mouth, constipation, heartburn. Musculoskeletal: Back pain, shoulder pain, knee pain, back strain, myalgia, foot pain. Nervous/Psychiatric: Decreased libido, vertigo, depression, somnolence. Respiratory: Common cold, nasal congestion, influenza, bronchitis, pharyngeal pain, dyspnea, pulmonary congestion, chronic sinusitis, allergic rhinitis, pharyngeal discomfort. Skin: Flushing, pruritus, skin inflammation, diaphoresis. Special Senses: Blurred vision, tinnitus, otalgia. Urogenital: Urinary tract infection.

Angioedema: Angioedema has been reported in patients receiving Prinzide, with an incidence higher in Black than in non-Black patients. Angioedema associated with laryngeal edema may be fatal. If angioedema of the face, extremities, lips, tongue, glottis and/or larynx occurs, treatment with Prinzide should be discontinued and appropriate therapy instituted immediately. In rare cases, intestinal angioedema has been reported with angiotensin converting enzyme inhibitors including lisinopril.

Hypotension: In clinical trials, adverse effects relating to hypotension occurred as follows: hypotension (1.4), orthostatic hypotension (0.5), other orthostatic effects (3.2). In addition syncope occurred in 0.8 percent of patients.

Cough: See PRECAUTIONS, Cough.

Clinical Laboratory Test Findings

Serum Electrolytes: See PRECAUTIONS.

Creatinine, Blood Urea Nitrogen: Minor reversible increases in blood urea nitrogen and serum creatinine were observed in patients with essential hypertension treated with Prinzide. More marked increases have also been reported and were more likely to occur in patients with renal artery stenosis.

Serum Uric Acid, Glucose, Magnesium, Cholesterol, Triglycerides and Calcium: See PRECAUTIONS.

Hemoglobin and Hematocrit: Small decreases in hemoglobin and hematocrit (mean decreases of approximately 0.5 g percent and 1.5 vol percent, respectively) occurred frequently in hypertensive patients treated with Prinzide but were rarely of clinical importance unless another cause of anemia coexisted. In clinical trials, 0.4 percent of patients discontinued therapy due to anemia.

Liver Function Tests: Rarely, elevations of liver enzymes and/or serum bilirubin have occurred.

Other adverse reactions that have been reported with the individual components are listed below:

Lisinopril

In clinical trials adverse reactions which occurred with lisinopril were also seen with Prinzide. In addition, and since lisinopril has been marketed, the following adverse reactions have been reported with lisinopril and should be considered potential adverse reactions for Prinzide: Body as a Whole: Anaphylactoid reactions, malaise, edema, facial edema, pain, pelvic pain, flank pain, chills; Cardiovascular: Cardiac arrest, myocardial infarction or cerebrovascular accident, possibly secondary to excessive hypotension in high- risk patients, pulmonary embolism and infarction, worsening of heart failure, arrhythmias (including tachycardia, ventricular tachycardia, atrial tachycardia, atrial fibrillation, bradycardia, and premature ventricular contractions), angina pectoris, transient ischemic attacks, paroxysmal nocturnal dyspnea, decreased blood pressure, peripheral edema, vasculitis; Digestive: Pancreatitis, hepatitis (hepatocellular or cholestatic jaundice), gastritis, anorexia, flatulence, increased salivation; Endocrine: Diabetes mellitus, syndrome of inappropriate antidiuretic hormone secretion (SIADH); Hematologic: Rare cases of neutropenia, thrombocytopenia, and bone marrow depression have been reported. Hemolytic anemia has been reported; a causal relationship to lisinopril cannot be excluded; Metabolic: Gout, weight loss, dehydration, fluid overload, weight gain; Musculoskeletal: Arthritis, arthralgia, neck pain, hip pain, joint pain, leg pain, arm pain, lumbago; Nervous System/Psychiatric: Ataxia, memory impairment, tremor, insomnia, stroke, nervousness, confusion, peripheral neuropathy (e.g., paresthesia, dysesthesia), spasm, hypersomnia, irritability; Respiratory: Malignant lung neoplasms, hemoptysis, pulmonary edema, pulmonary infiltrates, eosinophilic pneumonitis, bronchospasm, asthma, pleural effusion, pneumonia, wheezing, orthopnea, painful respiration, epistaxis, laryngitis, sinusitis, pharyngitis, rhinitis, rhinorrhea, chest sound abnormalities; Skin: Urticaria, alopecia, herpes zoster, photosensitivity, skin lesions, skin infections, pemphigus, erythema. Other severe skin reactions (including toxic epidermal necrolysis, Stevens-Johnson syndrome and cutaneous pseudolymphoma) have been reported rarely; causal relationship has not been established; Special Senses: Visual loss, diplopia, photophobia, taste disturbances; Urogenital: Acute renal failure, oliguria, anuria, uremia, progressive azotemia, renal dysfunction, pyelonephritis, dysuria, breast pain.

Miscellaneous: A symptom complex has been reported which may include a positive ANA, an elevated erythrocyte sedimentation rate, arthralgia/arthritis, myalgia, fever, vasculitis, leukocytosis, eosinophilia, photosensitivity, rash, and other dermatological manifestations.

Fetal/Neonatal Morbidity and Mortality: See WARNINGS, Pregnancy, Lisinopril, Fetal/Neonatal Morbidity and Mortality.

Hydrochlorothiazide

Body as a Whole: Weakness; Digestive: Anorexia, gastric irritation, cramping, jaundice (intrahepatic cholestatic jaundice), pancreatitis, sialadenitis, constipation; Hematologic: Leukopenia, agranulocytosis, thrombocytopenia, aplastic anemia, hemolytic anemia; Musculoskeletal: Muscle spasm; Nervous System/Psychiatric: Restlessness; Renal: Renal failure, renal dysfunction, interstitial nephritis; Skin: Erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis, alopecia; Special Senses: Xanthopsia; Hypersensitivity: Purpura, photosensitivity, urticaria, necrotizing angiitis (vasculitis and cutaneous vasculitis), respiratory distress including pneumonitis and pulmonary edema, anaphylactic reactions.

Side Effects by Body System

Cardiovascular

Cardiovascular side effects are relatively common. Hypotension and orthostasis have been associated with lisinopril and hydrochlorothiazide (HCTZ) in approximately 1.4% and 3.2% of patients, respectively. In one study, the incidence of hypotension-related undesirable side effects was 4% in patients with congestive heart failure (CHF), compared to 0.6% in patients without CHF. Angina pectoris or palpitations have been reported in approximately 1% of patients. HCTZ-induced hypokalemia can predispose some patients to various cardiac arrhythmias, such as ventricular ectopy and complete AV heart block. Hypokalemia is much less likely with the addition of lisinopril, since ACE inhibitors may decrease serum aldosterone. Angioneurotic edema (0.2% of patients) has been associated with lisinopril therapy.

Hypotension is most likely in patients who are sodium and intravascular volume depleted.

A possible relationship between lisinopril use and a case of penile angioedema has been published. After six days of lisinopril therapy, a 74-year-old patient complained of penile "swelling". Lisinopril was suspected as the cause of the angioedema and was discontinued. The localized angioedema resolved within a few days following discontinuation.

Renal

Patients with renal artery stenosis maintain glomerular filtration by efferent arteriolar vasoconstriction, which is blocked by lisinopril.

Although lisinopril may be associated with a rise in serum creatinine and BUN, GFR has been shown to remain unchanged or improve in most patients.

HCTZ has been used to treat nephrogenic diabetes insipidus. However, a case in which the drug was believed to have caused this condition has been reported.

Renal side effects including new or worsened renal insufficiency may develop in up to 10% of patients. This problem may be more likely in patients with preexisting renal insufficiency or who are angiotensin-dependent, such as patients with CHF. Patients with renal artery stenosis should not receive lisinopril or any other ACE inhibitor since it may precipitate acute renal failure. While there is a growing body of literature describing decreased proteinuria in some patients, new onset proteinuria may develop during ACE inhibition. Rare cases of interstitial nephritis have been associated with hydrochlorothiazide.

Nervous system

Nervous system side effects have included dizziness in 8% and headache in 5% of patients. Paresthesias are reported in 2% of patients. Rare cases of cerebrovascular insufficiency have been associated with hydrochlorothiazide-induced plasma volume contraction.

Respiratory

A retrospective study has revealed a significantly higher incidence of discontinuation of ACE inhibitor therapy due to cough among black patients compared to non-black patients (9.6% vs. 2.4%).

Respiratory side effects, including reversible dry cough, have been reported in up to 4% of patients. Cough appears to be as common in women as men, but in some reviews, women have reported cough more often than men. Rare respiratory system side effects include stridor associated with lisinopril and acute noncardiogenic pulmonary edema associated with hydrochlorothiazide.

Hypersensitivity

In at least two cases of lisinopril-associated angioedema of the face and neck, the affected patients did not have a history of reactive airways disease. Patients with intestinal angioedema generally present with abdominal pain (with or without nausea or vomiting) and in some cases there was no prior history of facial angioedema, and C-1 esterase levels were normal. These symptoms resolve after stopping the ACE inhibitor.

A 68-year-old man with a history of hypertension, diabetes mellitus, stroke, and myocardial infarction developed dyspnea, chest tightness, and increased oxygen requirements one week after beginning lisinopril. Associated findings included a truncal rash, arterial acidosis, and vocal cord edema and erythema per bronchoscopy. The patient required artificial airway management and corticosteroid therapy. Lisinopril was not at first suspected, and due to improvement, the patient was extubated. While still receiving lisinopril, stridor and dyspnea persisted, requiring reintubation of the patient. Once suspected, lisinopril was discontinued, and the patient improved without recurrent respiratory complaints.

A 68-year-old man with a history of myocardial infarction (MI) developed dyspnea, chest tightness, a low grade fever, dizziness, sweating, and vomiting associated with cyanosis, a mild leukocytosis, radiographic evidence of pulmonary edema, clinical evidence of hypovolemia, and respiratory acidosis. MI and infection were ruled out. The patient recovered after restoration of his intravascular volume with saline and albumin. The only precipitating factor per history was the ingestion of HCTZ, which the patient had taken without incident for two years. Rechallenge resulted in recurrent acute pulmonary edema. Other signs of hypersensitivity, such as rash and eosinophilia, were absent.

Hypersensitivity reactions to either drug are rare but may be life-threatening. Rash is reported in less than 2% of patients. ACE inhibitor-induced angioedema occurs in approximately 0.2% of patients. Angioedema of the face, extremities, lips, tongue, glottis and/or pharynx have been reported rarely in patients receiving ACE inhibitors. Obstructive laryngeal and glossal angioedema due to lisinopril is a rare, but potentially fatal reaction. In addition, intestinal angioedema has been reported in patients treated with ACE inhibitors. It is recommended that any patient with dyspnea, dysphagia, or significant facial angioedema stop therapy immediately and avoid ACE inhibitor therapy in general.

Hypersensitivity reactions to hydrochlorothiazide may present as nausea, vomiting, diarrhea, or rash. Case reports of acute pulmonary edema, interstitial cystitis, interstitial nephritis, and anaphylaxis have been associated with hydrochlorothiazide.

Metabolic

HCTZ may increase total serum cholesterol by 11%, LDL lipoprotein cholesterol by 12%, and VLDL lipoprotein cholesterol levels by 50%, as well as reduce insulin secretion. It should be used with caution in patients with diabetes or hypercholesterolemia.

Hyperuricemia may be an important consideration in patients with a history of gout. Hypophosphatemia and low serum magnesium concentrations may also occur, but are usually clinically insignificant except in malnourished patients.

Metabolic side effects including hypokalemia associated with hydrochlorothiazide is much less likely with the addition of lisinopril because ACE inhibitors may decrease serum aldosterone levels. By the same token, the mild hyperkalemia, although clinically insignificant, that often accompanies the use of lisinopril, is much less likely due to hydrochlorothiazide-induced kaliuresis. Hydrochlorothiazide can induce metabolic alkalosis, hyponatremia, hypomagnesemia, hypercalcemia, hyperglycemia, and elevated serum uric acid levels. It may also increase serum cholesterol. Lisinopril and other ACE inhibitors appear to have a beneficial effect on plasma insulin levels. Cases of hypoglycemia have been reported in diabetic patients receiving ACE inhibitors when concurrently treated with oral antidiabetic agents or insulin.

Dermatologic

A 67-year-old white woman with hypothyroidism, hypercalcemia, depression, and hypertension developed facial erythema, headaches, tremors, confusion, and personality changes associated with a new positive ANA and anti-nRNP, and skin biopsy consistent with lupus erythematosus while taking HCTZ, levothyroxine, and amitriptyline. The eruption resolved upon discontinuation of HCTZ, but she later developed a higher ANA titer associated with symptomatic diffuse interstitial pulmonary infiltrates. She was successfully treated with corticosteroids.

Dermatologic reactions associated with hydrochlorothiazide have included erythema annular centrifugum, acute eczematous dermatitis, and morbilliform or leukocytoclastic vasculitis. Thiazides may induce phototoxic dermatitis. In addition, a rare, distinct entity with clinical and laboratory features indistinguishable from those of subacute cutaneous lupus erythematosus has been associated with hydrochlorothiazide. Rare instances of alopecia, erythema, and pruritus have been reported in 1% or less of patients taking lisinopril alone. In addition, cutaneous pseudolymphoma has been reported in patients taking lisinopril.

Gastrointestinal

Gastrointestinal disturbances have included diarrhea (3%), nausea (2%), and vomiting (1%) in patients treated with lisinopril. Taste disturbances and constipation are reported in less than 1% of patients taking lisinopril alone. Rare cases of pancreatitis have been associated with lisinopril and HCTZ. In addition, rare cases of acute cholecystitis have been associated with HCTZ.

Thiazide diuretics may increase serum cholesterol and triglycerides, resulting in an increased risk of cholesterol gallstone formation. Cases of bowel strictures associated with thiazide ingestion have been reported in the 1960's, although these patients were on a combination HCTZ-potassium product.

Endocrine

Endocrinologic problems associated with thiazide diuretics have included glucose intolerance and a potentially deleterious effect on the lipid profile, either of which may be important in some patients with or who are at risk for diabetes or coronary artery disease.

Case reports have suggested that lisinopril may rarely result in the development of the syndrome of inappropriate secretion of antidiuretic hormone.

A prospective study of 34 patients who received oral thiazide diuretics for 14 years without interruption revealed an increased mean fasting blood glucose level after treatment. Withdrawal of thiazide therapy for seven months in 10 of the patients resulted in mean reductions of 10% in fasting blood glucose and 25% in the 2-hour glucose tolerance test value. A control group was not reported.

Hematologic

A case of a 52-year-old man who developed noninfectious hematuria, proteinuria, and IgA leukocytoclastic vasculitis has been reported. Lisinopril alone was discontinued, and the patient recovered within three months.

There are rare case reports of HCTZ-induced immune hemolytic anemia. The following illustrates a fatal case:

A 53-year-old man with hypertension developed nausea, vomiting, diarrhea, and progressive anorexia and weakness associated with scleral icterus, anemia with spherocytosis, dark red urine with proteinuria, bilirubinuria, hemoglobinuria, and elevated lactic dehydrogenase levels 18 months after beginning HCTZ and methyldopa. Haptoglobin was less than 50 mg/dL. Direct and indirect Coombs tests were positive. The patient died suddenly. Autopsy revealed no obvious cause of death, left ventricular hypertrophy, and mild coronary atherosclerosis.

Hematologic side effects are rare. Neutropenia and bone marrow depression have rarely been associated with lisinopril and other ACE inhibitors. Isolated cases of immune-complex hemolytic anemia, aplastic anemia, and thrombocytopenia have been associated with hydrochlorothiazide. A case of Henoch-Schonlein purpura complicated by polyarthritis has been associated with lisinopril.

Musculoskeletal

Musculoskeletal cramps have been reported in 2% of patients.

Genitourinary

Genitourinary complaints are limited to impotence in approximately 1% of male patients treated with hydrochlorothiazide.

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