Blopress Plus Warnings

Fetal/Neonatal Morbidity and Mortality: Drugs that act directly on the renin-angiotensin system can cause fetal and neonatal morbidity and death when administered to pregnant women. Several dozen cases have been reported in the world literature in patients who were taking angiotensin-converting enzyme inhibitors. Post-marketing experience has identified reports of fetal and neonatal toxicity in babies born to women treated with candesartan cilexetil during pregnancy.
Because candesartan cilexetil is a component of Blopress Plus, Blopress Plus should be discontinued as soon as possible when pregnancy is detected.
The use of drugs that act directly on the renin-angiotensin system during the 2nd and 3rd trimesters of pregnancy has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure and death.
Oligohydramnios in this setting has been associated with fetal limb contractures, craniofacial deformation and hypoplastic lung development.
Prematurity, intrauterine growth retardation and patent ductus arteriosus have also been reported, although it is not clear whether these occurrences were due to exposure to the drug.
These adverse effects do not appear to have resulted from intrauterine drug exposure that has been limited to the 1st trimester. Mothers whose embryos and foetuses are exposed to an angiotensin II receptor antagonist only during the 1st trimester should be so informed. Nonetheless, when patients become pregnant, physicians should have the patient discontinue the use of Blopress Plus as soon as possible.
Rarely (probably less often than once in every thousand pregnancies), no alternative to a drug acting on the renin-angiotensin system will be found. In these rare cases, the mothers should be apprised of the potential hazards to their foetuses, and serial ultrasound examinations should be performed to assess the intra-amniotic environment.
If oligohydramnios is observed, Blopress Plus should be discontinued unless it is considered life saving for the mother.
Contraction stress testing (CST), a nonstress 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 foetus has sustained irreversible injury.
Infants with histories of in utero exposure to an angiotensin II receptor antagonist 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.
Candesartan Cilexetil-Hydrochlorothiazide: There was no evidence of teratogenicity or other adverse effects on embryo-fetal development when pregnant mice, rats or rabbits were treated orally with candesartan cilexetil alone or in combination with hydrochlorothiazide.
For mice, the maximum dose of candesartan cilexetil was 1000 mg/kg/day [about 150 times the maximum recommended daily human dose (MRHD)].
For rats, the maximum dose of candesartan cilexetil was 100 mg/kg/day (about 31 times the MRHD).
For rabbits, the maximum dose of candesartan cilexetil was 1 mg/kg/day (a maternally toxic dose that is about half the MRHD).
In each of these studies, hydrochlorothiazide was tested at the same dose level (10 mg/kg/day, about 4, 8 and 15 times the MRHD in mice, rats and rabbits, respectively). There was no evidence of harm to the rat or mouse foetus, or embryo in studies in which hydrochlorothiazide was administered alone to the pregnant rat or mouse at doses of up to 1000 and 3000 mg/kg/day, respectively.
Thiazides cross the placental barrier and appear in cord blood. There is risk of fetal or neonatal jaundice, thrombocytopenia and possibly other adverse reactions that have occurred in adults.
Hypotension in Volume- and Salt-Depleted Patients: Based on adverse events reported from all clinical trials of Blopress Plus, excessive reduction of blood pressure was rarely seen in patients with uncomplicated hypertension treated with candesartan cilexetil and hydrochlorothiazide (0.4%). Initiation of antihypertensive therapy may cause symptomatic hypotension in patients with intravascular volume or sodium depletion eg, in patients treated vigorously with diuretics or in patients on dialysis. These conditions should be corrected prior to administration of Blopress Plus, or the treatment should start under close medical supervision.
If hypotension occurs, the patient should be placed in the supine position and, if necessary, given an IV infusion of normal saline. A transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized.
Hydrochlorothiazide: Impaired Hepatic Function: Thiazide diuretics 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.
Hypersensitivity Reaction: Hypersensitivity reactions to hydrochlorothiazide may occur in patients with or without a history of allergy or bronchial asthma, but are more likely in patients with such a history.
Systemic Lupus Erythematosus: Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus.
Lithium Interaction: Lithium generally should not be given with thiazides.
Use in lactation: It is not known whether candesartan is secreted in human milk, but candesartan has been shown to be present in rat milk. Thiazides appear in human milk. Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.