Angilock® Plus
Losartan Potassium USP + Hydrochlorothiazide BP
PRESENTATION antihypertensive agents. Angilock® Plus may be
Angilock® Plus 50/12.5 tablet: Each film-coated tablet administered with or without food. Patients with Renal
contains Losartan Potassium USP 50 mg and Impairment: The usual regimens of therapy with
Hydrochlorothiazide BP 12.5 mg. Angilock® Plus may be followed as long as the patient's
creatinine clearance is greater than 30 mL/min. In patients
PHARMACOLOGY with more severe renal impairment, loop diuretics are
Angiotensin II (formed from angiotensin I in a reaction preferred to thiazides, so Angilock® Plus is not
catalyzed by angiotensin converting enzyme) is a potent recommended. Patients with Hepatic Impairment:
vasoconstrictor, the primary vasoactive hormone of the Angilock® Plus is not recommended for titration in
renin-angiotensin system and an important component in patients with hepatic impairment because the appropriate
the pathophysiology of hypertension. It also stimulates 25 mg starting dose of Losartan cannot be given.
aldosterone secretion by the adrenal cortex. Losartan and
its principle active metabolite block the vasoconstrictor CONTRAINDICATION
and aldosterone secreting effects of angiotensin II by This combination is contraindicated in patients who are
selectively blocking the binding of angiotensin II to the AT1 hypersensitive to any component of this product. Because
receptor found in many tissues, (e.g. vascular smooth of the hydrochlorothiazide component, this product is
muscle, adrenal gland). There is also an AT2 receptor found contraindicated in patients with anuria or hypersensitivity
in many tissues but it is not known to be associated with to other sulfonamide-derived drugs. Do not co-administer
cardiovascularhomeostasis. Both Losartan and its principal aliskiren with this combination in patients with diabetes.
active metabolite do not exhibit any partial agonist activity
at the AT1 receptor and have much greater affinity (about PRECAUTION
1000-fold) for the AT1 receptor than for the AT2 receptor. In Periodic determination of serum electrolytes to detect
vitro binding studies indicate that Losartan is a reversible, possible electrolyte imbalance should be performed at
competitive inhibitor of the AT1 receptor. Neither Losartan appropriate intervals. All patients receiving thiazide
nor its active metabolite inhibits ACE; nor do they bind to or therapy should be observed for clinical signs of fluid or
block other hormone receptors or ionchannels known to electrolyte imbalance. Serum and urine electrolyte
be important in cardiovascular regulation. determinations are particularly important when the
Hydrochlorothiazide is a thiazide diuretic. Thiazides affect patient is vomiting excessively or receiving parenteral
the renal tubular mechanisms of electrolyte reabsorption, fluids. Hyperuricemia may occur or frank gout may be
directly increasing excretion of sodium and chloride in precipitated in certain patients receiving thiazide therapy.
approximately equivalent amounts. Indirectly, the diuretic Because losartan decreases uric acid, losartan in
action of hydrochlorothiazide reduces plasma volume, with combination with hydrochlorothiazide attenuates the
consequent increase in plasma renin activity, in aldosterone diuretic-induced hyperuricemia. In diabetic patients,
secretion, in urinary potassium loss and decreases in serum dosage adjustments of insulin or oral hypoglycemic agents
potassium. The renin-aldosterone link is mediated by may be required. Hyperglycemia may occur with thiazide
angiotensin II, so coadministration of an angiotensin II diuretics. Thus latent diabetes mellitus may become
receptor antagonist tends to reverse the potassium loss manifest during thiazide therapy.
associated with these diuretics.
SIDE EFFECTS
PHARMACOKINETICS Abdominal pain, Edema/swelling, Palpitation, Back pain,
Absorption: Following oral administration, Losartan is well Dizziness, Cough, Sinusitis, Upper respiratory tract
absorbed, with systemic bioavailability of losartan infection, rash etc.
approximately 33%. Mean peak concentrations of Losartan
occur at about one hour, and that of its active metabolite at OVERDOSE
about 3-4 hours. Hydrochlorothiazide is rapidly absorbed Losartan Potassium: Limited data are available in regard to
from the gastrointestinal tract with an oral bioavailability of overdosage in humans. The most likely manifestation of
about 65% to 75%. Peak concentrations of overdosage would be hypotension and tachycardia;
Hydrochlorothiazide were reached approximately 2 hours bradycardia could occur from parasympathetic (vagal)
after dosing. Distribution: Both Losartan and its active stimulation. If symptomatic hypotension occur, supportive
metabolite are highly bound to plasma proteins, primarily treatment should be instituted. Neither Losartan nor its
albumin, with plasma free fractions of 1.3% and 0.2% active metabolite can be removed by hemodialysis.
respectively. The volume ofL./distribution of Losartan is Hydrochlorothiazide: The most common signs and
about 34 liters, and that of the active metabolite is about 12 symptoms observed are those caused by electrolyte
liters. Hydrochlorothiazide crosses the placental but not the depletion (hypokalemia, hypochloremia, hyponatremia)
blood-brain barrier and is excreted in breast milk. and dehydration resulting from excessive diuresis. If
Metabolism: Losartan is an orally active agent that digitalis has also been administered, hypokalemia may
undergoes substantial first-pass metabolism by accentuate cardiac arrhythmias. The degree to which
cytochrome P450 enzymes. It is converted, in part, to an Hydrochlorothiazide is removed by hemodialysis has not
active carboxylic acid metabolite, that is responsible for been established.
most of the angiotensin II receptor antagonism that follows
oral losartan administration. Various losartan metabolites DRUG INTERACTION
have been identified in human plasma and urine. In Losartan Potassium: There is no pharmacokinetic
addition to the active carboxylic acid metabolite, several interaction between Losartan and hydrochlorothiazide. As
inactive metabolites are formed. Hydrochlorothiazide is not with other drugs that block angiotensin II or its effects,
metabolized. Excretion: The terminal half-life of Losartan concomitant use of potassium-sparing diuretics (e.g.,
itself is about 2 hours, and that of the active spironolactone, triamterene, amiloride), potassium
metabolite, about 6-9 hours. Both biliary and urinary supplements or salt substitutes containing potassium may
excretion contribute substantially to elimination of lead to increases in serum potassium. Serum lithium level
Losartan and its metabolites. Hydrochlorothiazide is should be monitored during concomitant use with
eliminated rapidly by the kidney. The plasma half-life is Losartan. Renal function should be monitored periodically
5.6–14.8 hours. At least 61% of the oral dose is eliminated in patients receiving Losartan and NSAID therapy. The
unchanged within 24 hours. antihypertensive effect of angiotensin II receptor
antagonists, including losartan, may be attenuated by
INDICATIONS NSAIDs, including selective COX-2 inhibitors. Dual
Hypertension: Angilock® Plus is indicated for the blockade of the RAS with angiotensin receptor blockers,
treatment of hypertension. This fixed dose combination is ACE inhibitors, or aliskiren is associated with increased risks
not indicated for initial therapy of hypertension, except of hypotension, syncope, hyperkalemia, and changes in
when the hypertension is severe enough that the value of renal function (including acute renal failure) compared to
Losartan Potassium USP + Hydrochlorothiazide BP
PRESENTATION antihypertensive agents. Angilock® Plus may be
Angilock® Plus 50/12.5 tablet: Each film-coated tablet administered with or without food. Patients with Renal
contains Losartan Potassium USP 50 mg and Impairment: The usual regimens of therapy with
Hydrochlorothiazide BP 12.5 mg. Angilock® Plus may be followed as long as the patient's
creatinine clearance is greater than 30 mL/min. In patients
PHARMACOLOGY with more severe renal impairment, loop diuretics are
Angiotensin II (formed from angiotensin I in a reaction preferred to thiazides, so Angilock® Plus is not
catalyzed by angiotensin converting enzyme) is a potent recommended. Patients with Hepatic Impairment:
vasoconstrictor, the primary vasoactive hormone of the Angilock® Plus is not recommended for titration in
renin-angiotensin system and an important component in patients with hepatic impairment because the appropriate
the pathophysiology of hypertension. It also stimulates 25 mg starting dose of Losartan cannot be given.
aldosterone secretion by the adrenal cortex. Losartan and
its principle active metabolite block the vasoconstrictor CONTRAINDICATION
and aldosterone secreting effects of angiotensin II by This combination is contraindicated in patients who are
selectively blocking the binding of angiotensin II to the AT1 hypersensitive to any component of this product. Because
receptor found in many tissues, (e.g. vascular smooth of the hydrochlorothiazide component, this product is
muscle, adrenal gland). There is also an AT2 receptor found contraindicated in patients with anuria or hypersensitivity
in many tissues but it is not known to be associated with to other sulfonamide-derived drugs. Do not co-administer
cardiovascularhomeostasis. Both Losartan and its principal aliskiren with this combination in patients with diabetes.
active metabolite do not exhibit any partial agonist activity
at the AT1 receptor and have much greater affinity (about PRECAUTION
1000-fold) for the AT1 receptor than for the AT2 receptor. In Periodic determination of serum electrolytes to detect
vitro binding studies indicate that Losartan is a reversible, possible electrolyte imbalance should be performed at
competitive inhibitor of the AT1 receptor. Neither Losartan appropriate intervals. All patients receiving thiazide
nor its active metabolite inhibits ACE; nor do they bind to or therapy should be observed for clinical signs of fluid or
block other hormone receptors or ionchannels known to electrolyte imbalance. Serum and urine electrolyte
be important in cardiovascular regulation. determinations are particularly important when the
Hydrochlorothiazide is a thiazide diuretic. Thiazides affect patient is vomiting excessively or receiving parenteral
the renal tubular mechanisms of electrolyte reabsorption, fluids. Hyperuricemia may occur or frank gout may be
directly increasing excretion of sodium and chloride in precipitated in certain patients receiving thiazide therapy.
approximately equivalent amounts. Indirectly, the diuretic Because losartan decreases uric acid, losartan in
action of hydrochlorothiazide reduces plasma volume, with combination with hydrochlorothiazide attenuates the
consequent increase in plasma renin activity, in aldosterone diuretic-induced hyperuricemia. In diabetic patients,
secretion, in urinary potassium loss and decreases in serum dosage adjustments of insulin or oral hypoglycemic agents
potassium. The renin-aldosterone link is mediated by may be required. Hyperglycemia may occur with thiazide
angiotensin II, so coadministration of an angiotensin II diuretics. Thus latent diabetes mellitus may become
receptor antagonist tends to reverse the potassium loss manifest during thiazide therapy.
associated with these diuretics.
SIDE EFFECTS
PHARMACOKINETICS Abdominal pain, Edema/swelling, Palpitation, Back pain,
Absorption: Following oral administration, Losartan is well Dizziness, Cough, Sinusitis, Upper respiratory tract
absorbed, with systemic bioavailability of losartan infection, rash etc.
approximately 33%. Mean peak concentrations of Losartan
occur at about one hour, and that of its active metabolite at OVERDOSE
about 3-4 hours. Hydrochlorothiazide is rapidly absorbed Losartan Potassium: Limited data are available in regard to
from the gastrointestinal tract with an oral bioavailability of overdosage in humans. The most likely manifestation of
about 65% to 75%. Peak concentrations of overdosage would be hypotension and tachycardia;
Hydrochlorothiazide were reached approximately 2 hours bradycardia could occur from parasympathetic (vagal)
after dosing. Distribution: Both Losartan and its active stimulation. If symptomatic hypotension occur, supportive
metabolite are highly bound to plasma proteins, primarily treatment should be instituted. Neither Losartan nor its
albumin, with plasma free fractions of 1.3% and 0.2% active metabolite can be removed by hemodialysis.
respectively. The volume ofL./distribution of Losartan is Hydrochlorothiazide: The most common signs and
about 34 liters, and that of the active metabolite is about 12 symptoms observed are those caused by electrolyte
liters. Hydrochlorothiazide crosses the placental but not the depletion (hypokalemia, hypochloremia, hyponatremia)
blood-brain barrier and is excreted in breast milk. and dehydration resulting from excessive diuresis. If
Metabolism: Losartan is an orally active agent that digitalis has also been administered, hypokalemia may
undergoes substantial first-pass metabolism by accentuate cardiac arrhythmias. The degree to which
cytochrome P450 enzymes. It is converted, in part, to an Hydrochlorothiazide is removed by hemodialysis has not
active carboxylic acid metabolite, that is responsible for been established.
most of the angiotensin II receptor antagonism that follows
oral losartan administration. Various losartan metabolites DRUG INTERACTION
have been identified in human plasma and urine. In Losartan Potassium: There is no pharmacokinetic
addition to the active carboxylic acid metabolite, several interaction between Losartan and hydrochlorothiazide. As
inactive metabolites are formed. Hydrochlorothiazide is not with other drugs that block angiotensin II or its effects,
metabolized. Excretion: The terminal half-life of Losartan concomitant use of potassium-sparing diuretics (e.g.,
itself is about 2 hours, and that of the active spironolactone, triamterene, amiloride), potassium
metabolite, about 6-9 hours. Both biliary and urinary supplements or salt substitutes containing potassium may
excretion contribute substantially to elimination of lead to increases in serum potassium. Serum lithium level
Losartan and its metabolites. Hydrochlorothiazide is should be monitored during concomitant use with
eliminated rapidly by the kidney. The plasma half-life is Losartan. Renal function should be monitored periodically
5.6–14.8 hours. At least 61% of the oral dose is eliminated in patients receiving Losartan and NSAID therapy. The
unchanged within 24 hours. antihypertensive effect of angiotensin II receptor
antagonists, including losartan, may be attenuated by
INDICATIONS NSAIDs, including selective COX-2 inhibitors. Dual
Hypertension: Angilock® Plus is indicated for the blockade of the RAS with angiotensin receptor blockers,
treatment of hypertension. This fixed dose combination is ACE inhibitors, or aliskiren is associated with increased risks
not indicated for initial therapy of hypertension, except of hypotension, syncope, hyperkalemia, and changes in
when the hypertension is severe enough that the value of renal function (including acute renal failure) compared to
