Lostad HCT

Lostad HCT

losartan + hydrochlorothiazide

Manufacturer:

Stellapharm

Marketer:

Stadpharm
Full Prescribing Info
Contents
Losartan potassium, hydrochlorothiazide.
Description
One Lostad HCT 50/12.5 film-coated tablet contains 50 mg of losartan potassium and 12.5 mg of hydrochlorothiazide.
Action
Pharmacology: Pharmacodynamics: Losartan and its principal active metabolite block the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor found in many tissues, (e.g., vascular smooth muscle, adrenal gland). The active metabolite is 10 to 40 times more potent by weight than losartan and appears to be a reversible, non-competitive inhibitor of the AT1 receptor. Neither losartan nor its active metabolite inhibits ACE (kininase II, the enzyme that converts angiotensin I to angiotensin II and degrades bradykinin); nor do they bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.
Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts. Indirectly, the diuretic action of hydrochlorothiazide reduces plasma volume, with aldosterone secretion, increases in urinary potassium. The renin-aldosterone link is mediated by angiotesin II, so coadministration of an angiotensin II receptor antagonist tends to reverse the potassium loss associated with these diuretics. The mechanism of the antihypertensive effect of thiazides is unknown.
Non-melanoma skin cancer: Based on available data from epidemiological studies, cumulative dose-dependent association between HCTZ and NMSC has been observed. One study included a population comprised of 71,533 cases of BCC and of 8,629 cases of SCC matched to 1,430,833 and 172,462 population controls, respectively. High HCTZ use (≥ 50,000 mg cumulative) was associated with an adjusted OR of 1.29 (95% CI: 1.23-1.35) for BCC and 3.98 (95% Cl: 3.68-4.31) for SCC. A clear cumulative dose response relationship was observed for both BCC and SCC. Another study showed a possible association between lip cancer (SCC) and exposure to HCTZ: 633 cases of lip-cancer were matched with 63,067 population controls, using a risk-set sampling strategy. A cumulative dose-response relationship was demonstrated with an adjusted OR 2.1 (95% Cl: 1.7-2.6) increasing to OR 3.9 (3.0-4.9) for high use (~25,000 mg) and OR 7.7 (5.7-10.5) for the highest cumulative dose (~100,000 mg).
Pharmacokinetics: Losartan is readily absorbed from the gastrointestinal tract following oral administration, but undergoes substantial first-pass metabolism resulting in a systemic bioavailability of about 33%. It is metabolised to an active carboxylic acid metabolite E-3174 (EXP-3174), which has greater pharmacological activity than losartan; some inactive metabolites are also formed. Metabolism is primarily by cytochrome P450 isoenzymes CYP2C9 and CYP3A4. Peak plasma concentrations of losartan and E-3174 occur about 1 hour and 3 to 4 hours, respectively, after an oral dose. Both losartan and E-3174 are more than 98% bound to plasma proteins. Losartan is excreted in the urine, and in the faeces via bile, as unchanged drug and metabolites. Following oral dosing about 4% of the dose is excreted unchanged in urine and about 6% is excreted in urine as the active metabolite. The terminal elimination half-lives of losartan and E-3174 are about 1.5 to 2.5 hours and 3 to 9 hours, respectively.
Hydrochlorothiazide is fairly rapidly absorbed from the gastrointestinal tract. It is reported to have a bioavaibility of about 65 to 70%. It has been estimated to have a plasma half-life of between about 5 and 15 hours and appears to be preferentially bound to red blood cells. It is excreted mainly unchanged in the urine. Hydrochlorothiazide crosses the placental barrier and is distributed into breast milk.
Indications/Uses
Lostad HCT 50/12.5 is indicated for the treatment of hypertension. This fixed dose combination is not indicated for initial therapy of hypertension, except when the hypertension is severe enough that the value of achieving prompt blood pressure control exceeds the risk of initiating therapy in these patients. Lostad HCT 50/12.5 is indicated to reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy, but there is evidence that this benefit does not apply to Black patients.
Dosage/Direction for Use
Dosage: Hypertension: Dose titration by clinical effect: A patient whose blood pressure is not adequately controlled with losartan monotherapy or hydrochlorothiazide alone, may be switched to 1 tablet once daily. If blood pressure remains uncontrolled after about 3 weeks of therapy, the dose may be increased to 2 tablets once daily.
The usual dose is 1 tablet once daily. More than 2 tablets once daily is not recommended. The maximal antihypertensive effect is attained about 3 weeks after initiation of therapy.
Severe hypertension: The starting dose is 1 tablet once daily. For patients who do not respond adequately to 1 tablet after 2 to 4 weeks of therapy, the dosage may be increased to 2 tablets once daily. The maximum dose is 2 tablets once daily.
Hypertensive patients with left Ventricular Hypertrophy: Treatment should be initiated with Losartan 50 mg once daily. 1 tablet may be substituted if the blood pressure reduction is unadequate.
Administration: Lostad HCT 50/12.5 is administered orally as a single dose at any time of day, with or without food.
Overdosage
Losartan potassium: Limited data are available in regard to overdosage in humans. The most likely manifestation of overdosage would be hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted. Neither losartan nor its active metabolite can be removed by hemodialysis.
Hydrochlorothiazide: The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias. The degree to which hydrochlorothiazide is removed by hemodialysis has not been established.
Contraindications
Lostad HCT 50/12.5 is contraindicated in patients who are hypersensitive to any component of this product. Because of the hydrochlorothiazide component, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.
Special Precautions
Losartan should be used with caution in patients with renal artery stenosis.
Losartan is excreted in urine and in bile and reduced doses may therefore be required in patients with renal impairment and should be considered in patients with hepatic impairment.
Patients with volume depletion (for example those who have received high-dose diuretic therapy) may experience hypotension; volume depletion should be corrected before starting therapy, or a low initial dose should be used.
Since hyperkalaemia may occur, serum-potassium concentrations should be monitored, especially in the elderly and patients with renal impairment, and the concomitant use of potassium-sparing diuretics should generally be avoided.
Lostad HCT 50/12.5 is not recommended for patients with hepatic impairment who require titration with losartan.
Periodic determination of serum electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals. All patients receiving thiazide therapy should be observed for clinical signs of fluid or electrolyte imbalance: hyponatremia, hypochloremic alkalosis, and hypokalemia.
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.
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.
Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus.
Thiazide therapy may impair glucose tolerance. Dosage adjustment of antidiabetic agents, including insulin, may be required.
Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving thiazide therapy. Because losartan decreases uric acid, losartan in combination with hydrochlorothiazide attenuates the diuretic-induced hyperuricemia.
In diabetic patients, dosage adjustments of insulin or oral hypoglycemic agents may be required. Hyperglycemia may occur with thiazide diuretics. Thus latent diabetes mellitus may become manifest during thiazide therapy.
The antihypertensive effects of the drug may be enhanced in the postsympathectomy patient.
Thiazides have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia.
Increases in cholesterol and triglyceride levels may be associated with thiazide diuretic therapy.
Non-melanoma skin cancer: An increased risk of non-melanoma skin cancer (NMSC) [basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)] with increasing cumulative dose of hydrochlorothiazide (HCTZ) exposure has been observed in two epidemiological studies based on the Danish National Cancer Registry. Photosensitizing actions of HCTZ could act as a possible mechanism for NMSC.
Patients taking HCTZ should be informed of the risk of NMSC and advised to regularly check their skin for any new lesions and promptly report any suspicious skin lesions. Possible preventive measures such as limited exposure to sunlight and UV rays and, in case of exposure, adequate protection should be advised to the patients in order to minimize the risk of skin cancer. Suspicious skin lesions should be promptly examined potentially including histological examinations of biopsies. The use of HCTZ may also need to be reconsidered in patients who have experienced previous NMSC.
Effects on Ability to Drive and Use Machines: There are no data to suggest that Lostad HCT 50/12.5 affects the ability to drive and use machines. However, patients who experience dizziness while taking Lostad HCT 50/12.5 should refrain from driving or operating machinery.
Use In Pregnancy & Lactation
Pregnancy: When used in pregnancy during the second and third trimesters, drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus. When pregnancy is detected, losartan should be discontinued as soon as possible.
Lactation: It is not known whether losartan is excreted in human milk, but significant levels of losartan and its active metabolite were 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.
Adverse Reactions
Losartan potassium: Adverse effects of losartan have been reported to be usually mild and transient, and include dizziness, headache, and dose-related orthostatic hypotension.
Hypotension may occur particularly in patients with volume depletion (for example those who have received high-dose diuretics).
Impaired renal function and, rarely, rash, urticaria, pruritus, angioedema, and raised liver enzyme values may occur.
Hyperkalaemia, myalgia, and arthralgia have been reported.
Losartan appears less likely than ACE inhibitors to cause cough.
Other adverse effects that have been reported with angiotensin II receptor antagonists include respiratory-tract disorders, back pain, gastrointestinal disturbances, fatigue, and neutropenia.
Rhabdomyolysis has been reported rarely.
Hydrochlorothiazide: Body as a whole: Weakness, chest pain.
Digestive: Pancreatitis, jaundice (intrahepatic cholestatic jaundice), sialadenitis, cramping, gastric irritation.
Hematologic: Aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia.
Hypersensitivity: Purpura, photosensitivity, urticaria, necrotizing angiitis (vasculitis and cutaneous vasculitis), fever, respiratory distress including pneumonitis and pulmonary edema.
Metabolic: Hyperglycemia, glycosuria, hyperuricemia.
Musculoskeletal: Muscle spasm.
Nervous system/psychiatric: Restlessness.
Renal: Renal failure, renal dysfunction, interstitial nephritis.
Skin: Erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis.
Special senses: Transient blurred vision, xanthopsia.
Neoplasms benign, malignant and unspecified (incl cysts and polyps): Non-melanoma skin cancer (Basal cell carcinoma and Squamous cell carcinoma). Based on available data from epidemiological studies, cumulative dose-dependent association between HCTZ and NMSC has been observed.
Drug Interactions
Losartan potassium: No significant drug-drug pharmacokinetic interactions have been found in interaction studies with hydrochlorothiazide, digoxin, warfarin, cimetidine and phenobarbital.
Rifampicin, an inducer of drug metabolism, decreased the concentrations of losartan and its active metabolite.
Fluconazole, an inhibitor of P450 2C9, decreased active metabolite concentration and increased losartan concentration.
As with other drugs that block angiotensin II or its effects, concomitant use of potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium may lead to increases in serum potassium.
As with other antihypertensive agents, the antihypertensive effect of losartan may be blunted by the non-steroidal anti-inflammatory drug indomethacin.
Hydrochlorothiazide: 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.
Non-steroidal anti-inflammatory drugs including selective cyclooxygenase-2 inhibitors: In some patients, the administration of a non-steroidal anti-inflammatory agent including a selective cyclooxygenase-2 inhibitor can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing and thiazide diuretics.
Storage
Protect from light. Do not store above 30°C.
MIMS Class
Angiotensin II Antagonists / Diuretics
ATC Classification
C09DA01 - losartan and diuretics ; Belongs to the class of angiotensin II receptor blockers (ARBs) in combination with diuretics. Used in the treatment of cardiovascular disease.
Presentation/Packing
FC tab (white, round-shaped, biconvex, plain on both sides) 30's.
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