Lisinopril And Hydrochlorthiazide Recall
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Questions & Answers
Side Effects & Adverse Reactions
Anaphylactoid and Possibly Related Reactions
Presumably because angiotensin-converting enzyme inhibitors affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin, patients receiving ACE inhibitors (including lisinopril and hydrochlorothiazide tablets) may be subject to a variety of adverse reactions, some of them serious.
Head and Neck Angioedema
Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported rarely in patients treated with angiotensin-converting enzyme inhibitors, including lisinopril. This may occur at any time during treatment. ACE inhibitors have been associated with a higher rate of angioedema in Black than in non-Black patients. In such cases lisinopril and hydrochlorothiazide tablets should be promptly discontinued and appropriate therapy and monitoring should be provided until complete and sustained resolution of signs and symptoms has occurred. Even in those instances where swelling of only the tongue is involved, without respiratory distress, patients may require prolonged observation since treatment with antihistamines and corticosteroids may not be sufficient. Very rarely, fatalities have been reported due to angioedema associated with laryngeal edema or tongue edema. Patients with involvement of the tongue, glottis or larynx are likely to experience airway obstruction, especially those with a history of airway surgery. Where there is involvement of the tongue, glottis or larynx, likely to cause airway obstruction, subcutaneous epinephrine solution 1:1000 (0.3 mL to 0.5 mL) and/or measures necessary to ensure a patent airway, should be promptly provided. (SeeADVERSE REACTIONS.)
Patients with a history of angioedema unrelated to ACE-inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor (see also INDICATIONS AND USAGE and CONTRAINDICATIONS).
Anaphylactoid Reactions During Desensitization
Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions. In the same patients, these reactions were avoided when ACE inhibitors were temporarily withheld, but they reappeared upon inadvertent rechallenge.
Anaphylactoid Reactions During Membrane Exposure
Anaphylactoid reactions have been reported in patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption.
Hypotension and Related Effects
Excessive hypotension was rarely seen in uncomplicated hypertensive patients but is a possible consequence of lisinopril use in salt/volume-depleted persons, such as those treated vigorously with diuretics or patients on dialysis. (See PRECAUTIONS,Drug Interactions and ADVERSE REACTIONS).
Syncope has been reported in 0.8% of patients receiving lisinopril and hydrochlorothiazide tablets. In patients with hypertension receiving lisinopril alone, the incidence of syncope was 0.1%. The overall incidence of syncope may be reduced by proper titration of the individual components. (See PRECAUTIONS,DrugInteractions,ADVERSE REACTIONS and DOSAGE AND ADMINISTRATION).
In patients with severe congestive heart failure, with or without associated renal insufficiency, excessive hypotension has been observed and may be associated with oliguria and/or progressive azotemia, and rarely with acute renal failure and/or death. Because of the potential fall in blood pressure in these patients, therapy should be started under very close medical supervision. Such patients should be followed closely for the first 2 weeks of treatment and whenever the dose of lisinopril and/or diuretic is increased. Similar considerations apply to patients with ischemic heart or cerebrovascular disease in whom an excessive fall in blood pressure could result in a myocardial infarction or cerebrovascular accident.
If hypotension occurs, the patient should be placed in supine position and, if necessary, receive an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further doses which usually can be given without difficulty once the blood pressure has increased after volume expansion.
Another angiotensin converting enzyme inhibitor, captopril, has been shown to cause agranulocytosis and bone marrow depression, rarely in uncomplicated patients but more frequently in patients with renal impairment, especially if they also have a collagen vascular disease. Available data from clinical trials of lisinopril are insufficient to show that lisinopril does not cause agranulocytosis at similar rates. Marketing experience has revealed rare cases of neutropenia and bone marrow depression in which a causal relationship to lisinopril cannot be excluded. Periodic monitoring of white blood cell counts in patients with collagen vascular disease and renal disease should be considered.
Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice or hepatitis and progresses to fulminant hepatic necrosis, and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up.
Thiazides should be used with caution in severe renal disease. In patients with renal disease, thiazides may precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function.
Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.
Sensitivity reactions may occur in patients with or without a history of allergy or bronchial asthma.
The possibility of exacerbation or activation of systemic lupus erythematosus has been reported.
Lithium generally should not be given with thiazides (see PRECAUTIONS,Drug Interactions,Lisinopril and Hydrochlorothiazide).
Lisinopril and Hydrochlorothiazide
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, lisinopril and hydrochlorothiazide tablets should be discontinued as soon as possible. (See Lisinopril, Fetal/Neonatal Morbidity and Mortality, below).
Fetal/Neonatal Morbidity and Mortality
ACE inhibitors can cause fetal and neonatal morbidity and death when administered to pregnant women. Several dozen cases have been reported in the world literature. When pregnancy is detected, ACE inhibitors should be discontinued as soon as possible.
In a published retrospective epidemiological study, infants whose mothers had taken an ACE inhibitor drug during the first trimester of pregnancy appeared to have an increased risk of major congenital malformations compared with infants whose mothers had not undergone first trimester exposure to ACE inhibitor drugs. The number of cases of birth defects is small and the findings of this study have not yet been repeated.
These adverse effects do not appear to have resulted from intrauterine ACE-inhibitor exposure that has been limited to the first trimester. Mothers whose embryos and fetuses are exposed to ACE inhibitors only during the first trimester should be so informed. Nonetheless, when patients become pregnant, physicians should make every effort to discontinue the use of lisinopril and hydrochlorothiazide tablets as soon as possible.
Rarely (probably less often than once in every thousand pregnancies), no alternative to ACE inhibitors will be found. In these rare cases, the mothers should be apprised of the potential hazards to their fetuses, and serial ultrasound examinations should be performed to assess the intraamniotic environment.
If oligohydramnios is observed, lisinopril and hydrochlorothiazide tablets should be discontinued unless it is considered lifesaving for the mother. Contraction stress testing (CST), a non-stress test (NST), or biophysical profiling (BPP) may be appropriate, depending upon the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury.
Infants with histories of in utero exposure to ACE inhibitors should be closely observed for hypotension, oliguria, and hyperkalemia. If oliguria occurs, attention should be directed toward support of blood pressure and renal perfusion. Exchange transfusion or dialysis may be required as means of reversing hypotension and/or substituting for disordered renal function. Lisinopril, which crosses the placenta, has been removed from neonatal circulation by peritoneal dialysis with some clinical benefit, and theoretically may be removed by exchange transfusion, although there is no experience with the latter procedure.
No teratogenic effects of lisinopril were seen in studies of pregnant mice, rats, and rabbits. On a body surface area basis, the doses used were up to 55 times, 33 times, and 0.15 times, respectively, the MRHDD.
Studies in which hydrochlorothiazide was orally administered to pregnant mice and rats during their respective periods of major organogenesis at doses up to 3000 and 1000 mg/kg/day, respectively, provided no evidence of harm to the fetus. These doses are more than 150 times the MRHDD on a body surface area basis. Thiazides cross the placental barrier and appear in cord blood. There is a risk of fetal or neonatal jaundice, thrombocytopenia and possibly other adverse reactions that have occurred in adults.
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FDA Safety Alerts
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There is currently no manufacturer warning information available for this drug.
FDA Labeling Changes
There are currently no FDA labeling changes available for this drug.
Lisinopril and hydrochlorothiazide tablets are indicated for the treatment of hypertension.
These fixed-dose combinations are not indicated for initial therapy (see DOSAGE AND ADMINISTRATION).
In using lisinopril and hydrochlorothiazide tablets, consideration should be given to the fact that an angiotensin-converting enzyme inhibitor, captopril, has caused agranulocytosis, particularly in patients with renal impairment or collagen vascular disease, and that available data are insufficient to show that lisinopril does not have a similar risk. (See WARNINGS.)
In considering use of lisinopril and hydrochlorothiazide tablets, it should be noted that Black patients receiving ACE inhibitors have been reported to have a higher incidence of angioedema compared to non-Blacks. (See WARNINGS, Head and Neck Angioedema.)
There is currently no drug history available for this drug.
Lisinopril and hydrochlorothiazide combines an angiotensin-converting enzyme inhibitor, lisinopril, and a diuretic, hydrochlorothiazide. Lisinopril, a synthetic peptide derivative, is an oral long-acting angiotensin-converting enzyme inhibitor. It is chemically described as (S)-1-[N2-(1-carboxy-3-phenylpropyl)-L-lysyl]-L-proline dihydrate. Its molecular formula is C21H31N3O5and its structural formula is:
Lisinopril is a white, crystalline powder, with a molecular weight of 441.52. It is soluble in water, sparingly soluble in methanol, and practically insoluble in ethanol.
Hydrochlorothiazide is 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine- 7-sulfonamide 1,1-dioxide. Its molecular formula is C7H8ClN3O4S2 and its structural formula is:
Hydrochlorothiazide is a white, or practically white, crystalline powder with a molecular weight of 297.73, which is slightly soluble in water, but freely soluble in sodium hydroxide solution.
Lisinopril and hydrochlorothiazide tablets are available for oral use in three tablet combinations of lisinopril with hydrochlorothiazide: lisinopril and hydrochlorothiazide tablets 10/12.5 mg, containing 10 mg lisinopril and 12.5 mg hydrochlorothiazide, lisinopril and hydrochlorothiazide tablets 20/12.5 mg, containing 20 mg lisinopril and 12.5 mg hydrochlorothiazide and lisinopril and hydrochlorothiazide tablets 20/25 mg, containing 20 mg lisinopril and 25 mg hydrochlorothiazide.
In addition, each tablet contains the following inactive ingredients: anhydrous lactose, croscarmellose sodium and magnesium stearate. Lisinopril and hydrochlorothiazide tablets 10/12.5 mg and 20/25 mg also contain red and yellow ferric oxides.