WARNINGS AND PRECAUTIONS
Fetal Toxicity
Pregnancy Category D
Use of drugs that act
on the renin-angiotensin system during the second and third trimesters
of pregnancy reduces fetal renal function and increases fetal and
neonatal morbidity and death. Resulting oligohydramnios can be associated
with fetal lung hypoplasia and skeletal deformations. Potential neonatal
adverse effects include skull hypoplasia, anuria, hypotension, renal
failure, and death. When pregnancy is detected, discontinue MICARDIS
as soon as possible
[see Use in Specific Populations ]
.
Hypotension
In patients with an activated renin-angiotensin
system, such as volume- or salt-depleted patients (e.g., those being
treated with high doses of diuretics), symptomatic hypotension may
occur after initiation of therapy with MICARDIS. Either correct this
condition prior to administration of MICARDIS, or start treatment
under close medical supervision with a reduced dose.
If hypotension does occur, the patient should be placed
in the supine position and, if necessary, given an intravenous 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.
Hyperkalemia
Hyperkalemia may occur in patients on ARBs,
particularly in patients with advanced renal impairment, heart failure,
on renal replacement therapy, or on potassium supplements, potassium-sparing
diuretics, potassium-containing salt substitutes or other drugs that
increase potassium levels. Consider periodic determinations of serum
electrolytes to detect possible electrolyte imbalances, particularly
in patients at risk.
Impaired HepaticFunction
As the majority
of telmisartan is eliminated by biliary excretion, patients with biliary
obstructive disorders or hepatic insufficiency can be expected to
have reduced clearance. Initiate telmisartan at low doses and titrate
slowly in these patients
[see Use in Specific Populations and Clinical Pharmacology ]
.
Impaired RenalFunction
As a consequence
of inhibiting the renin-angiotensin-aldosterone system, anticipate
changes in renal function in susceptible individuals. In patients
whose renal function may depend on the activity of the renin-angiotensin-aldosterone
system (e.g., patients with severe congestive heart failure or renal
dysfunction), treatment with angiotensin-converting enzyme (ACE) inhibitors
and angiotensin receptor antagonists has been associated with oliguria
and/or progressive azotemia and (rarely) with acute renal failure
and/or death. Similar results have been reported with MICARDIS
[see Clinical Pharmacology ]
.
In studies
of ACE inhibitors in patients with unilateral or bilateral renal artery
stenosis, increases in serum creatinine or blood urea nitrogen were
observed. There has been no long term use of MICARDIS in patients
with unilateral or bilateral renal artery stenosis, but anticipate
an effect similar to that seen with ACE inhibitors.
Dual Blockade ofthe Renin-Angiotensin-Aldosterone System
Dual blockade of the RAS with angiotensin-receptor
blockers, ACE inhibitors, or aliskiren is associated with increased
risks of hypotension, hyperkalemia, and changes in renal function
(including acute renal failure) compared to monotherapy.
The ONTARGET
trial enrolled 25,620 patients ≥55 years old with atherosclerotic
disease or diabetes with end-organ damage, randomizing them to telmisartan
only, ramipril only, or the combination, and followed them for a median
of 56 months. Patients receiving the combination of MICARDIS and ramipril
did not obtain any additional benefit compared to monotherapy, but
experienced an increased incidence of renal dysfunction (e.g., acute
renal failure) compared with groups receiving telmisartan alone or
ramipril alone.
In most patients no benefit
has been associated with using two RAS inhibitors concomitantly. In
general, avoid combined use of RAS inhibitors. Closely monitor blood
pressure, renal function, and electrolytes in patients on MICARDIS
and other agents that affect the RAS.
Do not co-administer
aliskiren with MICARDIS in patients with diabetes. Avoid concomitant
use of aliskiren with MICARDIS in patients with renal impairment (GFR
<60 mL/min/1.73 m2).
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy Category D. [See Warnings and Precautions ]
.
Use of drugs that act on the renin-angiotensin system
during the second and third trimesters of pregnancy reduces fetal
renal function and increases fetal and neonatal morbidity and death.
Resulting oligohydramnios can be associated with fetal lung hypoplasia
and skeletal deformations. Potential neonatal adverse effects include
skull hypoplasia, anuria, hypotension, renal failure, and death. When
pregnancy is detected, discontinue MICARDIS as soon as possible. These
adverse outcomes are usually associated with use of these drugs in
the second and third trimester of pregnancy. Most epidemiologic studies
examining fetal abnormalities after exposure to antihypertensive use
in the first trimester have not distinguished drugs affecting the
renin-angiotensin system from other antihypertensive agents. Appropriate
management of maternal hypertension during pregnancy is important
to optimize outcomes for both mother and fetus.
In the unusual case that there is no appropriate alternative
to therapy with drugs affecting the renin-angiotensin system for a
particular patient, apprise the mother of the potential risk to the
fetus. Perform serial ultrasound examinations to assess the intra-amniotic
environment. If oligohydramnios is observed, discontinue MICARDIS,
unless it is considered lifesaving for the mother. Fetal testing may
be appropriate, based on the week of pregnancy. Patients and physicians
should be aware, however, that oligohydramnios may not appear until
after the fetus has sustained irreversible injury. Closely observe
infants with histories of in utero exposure to MICARDIS for hypotension,
oliguria, and hyperkalemia
[see Use in Specific
Populations ]
.
Nursing Mothers
It is not known whether telmisartan is excreted in human milk, but
telmisartan was shown to be present in the milk of lactating rats.
Because of the potential for adverse effects on the nursing infant,
decide whether to discontinue nursing or discontinue the drug, taking
into account the importance of the drug to the mother.
Pediatric Use
Neonates with a history of in utero exposure to MICARDIS:
If oliguria or hypotension occurs, direct attention toward
support of blood pressure and renal perfusion. Exchange transfusions
or dialysis may be required as a means of reversing hypotension and/or
substituting for disordered renal function.
Safety and effectiveness in pediatric patients have
not been established
[see Clinical Pharmacology ]
.
Geriatric Use
Of
the total number of patients receiving MICARDIS in hypertension clinical
studies, 551 (19%) were 65 to 74 years of age and 130 (4%) were 75
years or older. No overall differences in effectiveness and safety
were observed in these patients compared to younger patients and other
reported clinical experience has not identified differences in responses
between the elderly and younger patients, but greater sensitivity
of some older individuals cannot be ruled out.
Of the total number of patients receiving MICARDIS in
the cardiovascular risk reduction study (ONTARGET), the percentage
of patients ≥65 to <75 years of age was 42%; 15% of patients were
≥75 years old. No overall differences in effectiveness and safety
were observed in these patients compared to younger patients and other
reported clinical experience has not identified differences in responses
between the elderly and younger patients, but greater sensitivity
of some older individuals cannot be ruled out.
Hepatic Insufficiency
Monitor carefully and uptitrate slowly in
patients with biliary obstructive disorders or hepatic insufficiency
[see Warnings and Precautions ]
.
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