Prozart Plus

Each film-coated tablet contains: Losartan Potassium 50 mg, Hydrochlorothiazide 12.5 mg.

Pharmacology: Pharmacokinetics: Bioavailability of Losartan potassium is about 33% and is not altered by presence of food. About 14% of administered drug is metabolized into E-3174 in most cases. T-max for the drug is 1 hour and 3-4 hours for its metabolite. Terminal of the half-life of the drug could be 4 hours to 6 hours depending upon the population type. Losartan Potassium is converted in the liver, to its active metabolite E-3174, which is more potent antagonist of the At1 receptor. E-3174 is responsible for the most pharmacological effects of Losartan Potassium. Its half-life contributes to the extended duration of action of the drug. 30% of patients with severe hypertension get their conditions managed with Losartan Potassium plus Hydrochlorothiazide 12.5 mg in 12 weeks period. Clinical studies show that compared to Losartan potassium monotherapy the combination therapy is found to reduce diastolic BP additionally by 4 to 6 months of Hg in patients.

Treatment of hypertension for patients in whom combination therapy is appropriate.

For patients whose blood pressure are adequately controlled with Losartan monotherapy, initial dose is one tablet once daily. If blood pressure remains uncontrolled after about 3 weeks of therapy, the dose may be increased to two tablets once daily. Or as prescribed by the physician.

The most likely manifestation of overdosage would be hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. Electrolyte depletion and dehydration occurs with overdose of Hydrochlorothiazide. In the event of overdosage, symptomatic and supportive measures should be employed. Neither Losartan nor its active metabolite can be removed from hemodialysis.

Hypersensitivity to Losartan Potassium and or Hydrochlorothiazide or other Sulphonamide derived drugs.

Should be used with caution in patients with impaired hepatic function or progressive liver disease. Since, drug acting directly on Angiotensin II receptors are known to cause mortality of fetus, therapy should be discontinued as soon as possible, whenever pregnancy is reported in patients on this therapy.

Hypersensitivity: Angioedema.
Hepatic Renal Impairment: Losartan and Hydrochlorothiazide is not recommended for patients with hepatic impairment or severe renal impairment (creatinine clearance <30 mL/minute).
Losartan: Renal Function Impairment: As a consequence of inhibiting the renin-angiotensin system, changes in renal function including renal failure have been reported in susceptible individuals; these changes in renal function may be reversible upon discontinuation of therapy.
Hydrochlorothiazide: Hypotension and electrolyte/fluid imbalance: As with all antihypertensive therapy, symptomatic hypotension may occur in some patients. Patients should be observed for clinical signs of fluid and electrolyte imbalance (e.g., Volume depletion, hyponatremia, hypochloremic alkalosis, hypomagnesemia or hypokalemia) which may occur during inter current diarrhea or vomiting.
Periodic determination of serum electrolytes should be performed at appropriate intervals in such patients.
Metabolic and endocrine effects: Thiazide therapy may impair glucose tolerance. Dosage adjustment of antidiabetic agents, including insulin, may be required.
Thiazides may decrease urinary calcium excretion and may cause intermittent and slight elevation of serum calcium. Marked hypercalcemia may be evidence of hidden hyperparathyroidism. Thiazides should be discontinued before carrying out test for parathyroid function.
Increases in cholesterol and triglyceride levels may be associated with thiazide diuretic therapy.
Thiazide therapy may precipitate hyperuricemia and/or gout in certain patients. Because Losartan decreases uric acid, Losartan in combination with Hydrochlorothiazide attenuates the diuretic-induced hyperuricemia.
Impaired hepatic function: Based on pharmacokinetic data which demonstrates significantly increased plasma concentrations of Losartan in cirrhotic patients, a lower dose should be considered for patients with impaired liver function.
Use in Pregnancy: When used in pregnancy during the 2nd and 3rd 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 and Hydrochlorothiazide should be discontinued as soon as possible.
Although there is no experience with the use of Losartan and Hydrochlorothiazide in pregnant women, animal studies with Losartan Potassium have demonstrated fetal and neonatal injury and death, the mechanism of which is believed to be pharmacologically mediated through effects on the renal perfusion, which is dependent upon the development of the renin-angiotensin system, begins in the 2nd trimester; thus, risk to the fetus increases if losartan and hydrochlorothiazide is administered during 2nd or 3rd trimesters of pregnancy.
Thiazides cross the placental barrier and appear in cord blood. The routine use of diuretics in otherwise healthy pregnant women is not recommended and exposes mother and fetus to unnecessary hazard including fetal and neonatal jaundice, thrombocytopenia and possibly other adverse reactions which have occurred in the adult. Diuretics do not prevent development of toxemia of pregnancy and there is no satisfactory evidence that they are useful in the treatment of toxemia.
Use in Lactation: It is not known whether Losartan is excreted in the milk, but significant levels of Losartan and its active metabolite were shown to be present in rat 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.
Use in Children: Safety and effectiveness in the children have not been established.
Use in Elderly: In clinical studies, there were no clinically significant differences in the efficacy and safety profiles of Losartan and Hydrochlorothiazide in older (>65 years) and younger patients (<65 years).
Of the total number of patients receiving Losartan Potassium in controlled clinical studies, 391 patients (19%) were 65 years and over, whole 37 patients 92%) were 75 years and over. No overall differences in effectiveness or safety were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

The adverse effect of profile of the Losartan potassium - Hydrochlorothiazide combination resembles those for Losartan Potassium monotherapy. Such as facial edema, fever, orthostatic effects, syncope; Cardiovascular: angina pectoris, second degree AV block, CVA, hypotension, myocardial infarction, arrhythmias including atrial fibrillation; palpitation, sinus bradycardia, tachycardia, ventricular tachycardia, ventricular fibrillation; Digestive: anorexia, constipation, dental pain, dry mouth, flatulence, gastritis, vomiting; Hematologic: anemia; Metabolic: gout; Musculoskeletal: arm pain, hip pain, joint swelling, knee pain, musculoskeletal pain, shoulder pain, stiffness, arthralgia, arthritis, fibromyalgia, muscle weakness; Nervous System/Psychiatric: anxiety disorder, ataxia, confusion, depression, dream abnormality, hypesthesia, decreased libido, memory impairment, migraine, nervousness, paresthesia, peripheral neuropathy, panic disorder, sleep disorder, somnolence, tremor, vertigo; Respiratory: dyspnea, bronchitis, pharyngeal discomfort, epistaxis, rhinitis, respiratory congestion; Skin: alopecia, dermatitis, dry skin, ecchymosis, erythema, flushing, photosensitivity, pruritus, rash, sweating, urticaria; Special senses: blurred vision, burning/stinging in the eye, conjunctivitis, taste perversion, tinnitus, decrease in visual acuity; Urogenital: impotence, nocturia, urinary frequency, urinary tract infection.

Losartan: In clinical pharmacokinetic trials, no drug interactions of clinical significance have been identified with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin.
Rifampicin and fluconazole have been reported to reduce levels of active metabolite. The clinical consequences of these interactions have not been evaluated. As with other hypertensive agents the antihypertensive effect of losartan may be attenuated by the non-steroidal anti-inflammatory drug indomethacin.
Hydrochlorothiazide: When given concurrently, the following drugs may interact with thiazide diuretics: 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.
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 58% and 43% respectively.
Corticosteroid, ACTH: Intensified electrolyte depletion, particularly hypokalemia.
Pressor Amines (eg. Adrenaline): 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: Diuretic agents reduce the renal clearance of lithium and a high risk of lithium toxicity; concomitant use is not recommended.
Nonsteroidal Anti-Inflammatory Drugs: In some patients, the administration of a nonsteroidal anti-inflammatory agent can reduce the diuretic, natriuretic and antihypertensive effects of diuretics.
Drug/Laboratory Test Interactions: Because of their effects on calcium metabolism, thiazides may interfere with test for parathyroid function.

Store at temperatures not exceeding 30°C.

Angiotensin II Antagonists / Diuretics

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.

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