A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Zestoretic Side Effects, and Drug Interactions - Lisinopril-hydrochlorothiazide
Zestoretic Side Effects, and Drug Interactions - Lisinopril-hydrochlorothiazide
SIDE EFFECTS
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.
|
|
Percent of Patients in Controlled Studies
|
|
|
Lisinopril-Hydrochlorothiazide (n=930) Incidence (discontinuation)
|
Placebo (n=207) Incidence
|
|
Dizziness
|
7.5 (0.8)
|
1.9
|
|
Headache
|
5.2 (0.3)
|
1.9
|
|
Cough
|
3.9 (0.6)
|
1.0
|
|
Fatigue
|
3.7 (0.4)
|
1.0
|
|
Orthostatic Effects
|
3.2 (0.1)
|
1.0
|
|
Diarrhea
|
2.5 (0.2)
|
2.4
|
|
Nausea
|
2.2 (0.1)
|
2.4
|
|
Upper Respiratory Infection
|
2.2 (0.0)
|
0.0
|
|
Muscle Cramps
|
2.0 (0.4)
|
0.5
|
|
Asthenia
|
1.8 (0.2)
|
1.0
|
|
Paresthesia
|
1.5 (0.1)
|
0.0
|
|
Hypotension
|
1.4 (0.3)
|
0.5
|
|
Vomiting
|
1.4 (0.1)
|
0.5
|
|
Dyspepsia
|
1.3 (0.0)
|
0.0
|
|
Rash
|
1.2 (0.1)
|
0.5
|
|
Impotence
|
1.2 (0.3)
|
0.0
|
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. (See WARNINGS.)
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. (See WARNINGS.)
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. (See PRECAUTIONS.)
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 (see WARNINGS,
Hepatic Failure).
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 (see WARNINGS,
Anaphylactoid and Possibly Related 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 (see WARNINGS,
Hypotension), 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) (see WARNINGS,
Hepatic Failure), gastritis, anorexia, flatulence, increased salivation;
Endocrine: Diabetes mellitus; 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 and Stevens-Johnson
syndrome) 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 (see PRECAUTIONS
and DOSAGE AND ADMINISTRATION), 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 (see WARNINGS);
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.
DRUG INTERACTIONS
Lisinopril
Hypotension — Patients on Diuretic Therapy: Patients
on diuretics, and especially those in whom diuretic therapy was recently instituted,
may occasionally experience an excessive reduction of blood pressure after initiation
of therapy with lisinopril. The possibility of hypotensive effects with lisinopril
can be minimized by either discontinuing the diuretic or increasing the salt
intake prior to initiation of treatment with lisinopril. If it is necessary
to continue the diuretic, initiate therapy with lisinopril at a dose of 5 mg
daily, and provide close medical supervision after the initial dose for at least
two hours and until blood pressure has stabilized for at least an additional
hour. (See WARNINGS and DOSAGE
AND ADMINISTRATION.) When a diuretic is added to the therapy of
a patient receiving lisinopril, an additional antihypertensive effect is usually
observed. (See DOSAGE AND ADMINISTRATION.)
Non-steroidal Anti-inflammatory Agents: In some patients
with compromised renal function who are being treated with non-steroidal anti-inflammatory
drugs, the co-administration of lisinopril may result in a further deterioration
of renal function. These effects are usually reversible.
Reports suggest that NSAIDs may diminish the antihypertensive
effect of ACE-inhibitors, including lisinopril. The interaction should be given
consideration in patients taking NSAIDs concomitantly with ACE-inhibitors.
Other Agents: Lisinopril has been used concomitantly
with nitrates and/or digoxin without evidence of clinically significant adverse
interactions. No meaningful clinically important pharmacokinetic interactions
occurred when lisinopril was used concomitantly with propranolol, digoxin, or
hydrochlorothiazide. The presence of food in the stomach does not alter the
bioavailability of lisinopril.
Agents Increasing Serum Potassium: Lisinopril attenuates
potassium loss caused by thiazide-type diuretics. Use of lisinopril with potassium-sparing
diuretics (e.g., spironolactone, triamterene, or amiloride), potassium supplements,
or potassium-containing salt substitutes may lead to significant increases in
serum potassium. Therefore, if concomitant use of these agents is indicated,
because of demonstrated hypokalemia, they should be used with caution and with
frequent monitoring of serum potassium.
Lithium: Lithium toxicity has been reported in patients
receiving lithium concomitantly with drugs which cause elimination of sodium,
including ACE inhibitors. Lithium toxicity was usually reversible upon discontinuation
of lithium and the ACE inhibitor. It is recommended that serum lithium levels
be monitored frequently if lisinopril is administered concomitantly with lithium.
Hydrochlorothiazide
When administered concurrently the following drugs may interact
with thiazide diuretics.
Alcohol, barbiturates, or narcotics — potentiation
of orthostatic hypotension may occur.
Antidiabetic drugs (oral agents and insulin) —
dosage adjustment of the antidiabetic drug may be required.
Other antihypertensive drugs — additive effect
or potentiation.
Cholestyramine and colestipol resins — Absorption
of hydrochlorothiazide is impaired in the presence of anionic exchange resins.
Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide
and reduce its absorption from the gastrointestinal tract by up to 85 and 43
percent, respectively.
Corticosteroids, ACTH — intensified electrolyte
depletion, particularly hypokalemia.
Pressor amines (e.g., norepinephrine) — possible
decreased response to pressor amines but not sufficient to preclude their use.
Skeletal muscle relaxants, nondepolarizing (e.g., tubocurarine)
— possible increased responsiveness to the muscle relaxant.
Lithium — should not generally be given with
diuretics. Diuretic agents reduce the renal clearance of lithium and add a high
risk of lithium toxicity. Refer to the package insert for lithium preparations
before use of such preparations with PRINZIDE.
Non-steroidal Anti-inflammatory Drugs — In some
patients, the administration of a non-steroidal antiinflammatory agent can reduce
the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing
and thiazide diuretics. Therefore, when PRINZIDE and non-steroidal anti-inflammatory
agents are used concomitantly, the patient should be observed closely to determine
if the desired effect of PRINZIDE is obtained.
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