Presentation and Status in Health Basket
This product may be administered with other antihypertensive agents. It may be administered with or without food.
Hypertension: The usual starting and maintenance dose is one tablet 50-12.5 (losartan 50 mg/hydrochlorothiazide 12.5 mg) once daily. For patients who do not respond adequately to this product 50-12.5, the dosage may be increased to two tablets of 50-12.5 once daily. The maximum dose is two tablets of this product 50-12.5 once daily. In general, the antihypertensive effect is attained within three weeks after initiation of therapy.
This product should not be initiated in patients who are intravascularly volume-depleted (e.g., those treated with high-dose diuretics).
This product is not recommended for patients with severe renal impairment (creatinine clearance ≤30 mL/min) or for patients with hepatic impairment. No initial dosage adjustment 50-12.5 is necessary for elderly patients. The maximum dose of two tablets 50-12.5 should not be used as initial therapy in elderly patients.
Reduction in the Risk of Cardiovascular Morbidity and Mortality in Hypertensive Patients with Left Ventricular Hypertrophy The usual starting dose is 50 mg of losartan once daily. If goal blood pressure is not reached with losartan 50 mg, therapy should be titrated using a combination of losartan and a low dose of hydrochlorothiazide (12.5 mg) and, if needed, the dose should then be increased to losartan 100 mg and hydrochlorothiazide 12.5 mg once daily. If necessary, the dose should be increased to losartan 100 mg and hydrochlorothiazide 25 mg once daily. Overdose No specific information is available on the treatment of overdose with Ocsaar Plus. Treatment is symptomatic and supportive. Therapy with Ocsaar Plus should be discontinued and the patient observed closely. Suggested measures include induction of emesis if ingestion is recent, and correction of dehydration, electrolyte imbalance, hepatic coma and hypotension by established procedures.
Losartan: Limited data are available in regard to overdose in humans. The most likely manifestation of overdose 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 the 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.
Hypertension when combination therapy is appropriate.
Ocsaar Plus is contraindicated in:
– patients who are hypersensitive to any component of this product.
– patients who are hypersensitive to sulfonamide-derived drugs.
– patients with anuria.
Losartan: Although there is no experience with the use of Ocsaar Plus 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 renin-angiotensin system. In humans, fetal renal perfusion, which is dependent upon the development of the renin-angiotensin system, begins in the second trimester, thus, risk to the fetus increases if losartan is administered during the second or third trimesters of pregnancy.
Hydrochlorothiazide: 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 or 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. 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 in the developing fetus. When pregnancy is detected, this product should be discontinued as soon as possible.
Losartan-Hydrochlorothiazide: Losartan potassium-hydrochlorothiazide was negative in the Ames microbial mutagenesis assay and the V-79 Chinese hamster lung cell mutagenesis assay. In addition, there was no evidence of direct genotoxicity in the in vitro alkaline elution assay in rat hepatocytes and in vitro chromosomal aberration assay in Chinese hamster ovary cells at noncytotoxic concentrations.
Losartan: Losartan potassium was negative in the microbial mutagenesis and V-79 mammalian cell mutagenesis assays. In addition, there was no evidence of direct genotoxicity in the in vitro alkaline elution and in vitro chromosomal aberration assays at concentrations that were approximately 1700 times greater than the maximum plasma level achieved in man at the recommended therapeutic dosage level. Similarly, there was no induction of chromosomal aberrations in bone marrow cells of male or female mice after the administration of toxic oral doses of up to 1500 mg/kg (4500 mg/m2 ) (750 times the maximum recommended daily human dose). In addition, the active metabolite showed no evidence of genotoxicity in the microbial mutagenesis, in vitro alkaline elution, and in vitro chromosomal aberration assays. Hydrochlorothiazide: Hydrochlorothiazide was not genotoxic in vitro in the Ames mutagenicity assay of Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 and in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations, or in vivo in assays using mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene. Positive test results were obtained only in the in vitro CHO Sister Chromatid Exchange (clastogenicity) and in the Mouse Lymphoma Cell (mutagenicity) assays, using concentrations of hydrochlorothiazide 5 from 43 to 1300 μg/ml, and in the Aspergillus nidulans non- disjunction assay at an unspecified concentration.
For the most part, adverse experiences have been mild and transient in nature and have not required discontinuation of therapy: Abdominal pain, asthenia/fatigue, chest pain, edema/swelling, palpitation, tachycardia, diarrhea, dyspepsia, nausea, back pain, muscle cramps, dizziness, headache, insomnia, cough, nasal congestion, pharyngitis, upper respiratory infection. Anaphylactoid reactions, vasculitis, hepatitis, anemia, myalgia, migraine, cough, urticaria, pruritis, heart failure.
For full details see prescribing information.
Losartan: In clinical pharmacokinetic trials, no drug interactions of clinical significance have been identified with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital (see Hydrochlorothiazide, Alcohol, barbiturates, or narcotics below), ketoconazole and erythromycin. Rifampin and fluconazole have been reported to reduce levels of active metabolite. The clinical consequences of these interactions have not been evaluated. 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 attenuated by the non- steroidal anti- inflammatory drug indomethacin. Non-steroidal anti-inflammatory drugs (NSAIDs) including selective cyclooxygenase-2 inhibitors (COX-2 inhibitors) may reduce the effect of diuretics and other antihypertensive drugs. Therefore, the antihypertensive effect of angiotensin II receptor antagonists may be attenuated by NSAIDs including selective COX-2 inhibitors. In some patients with compromised renal function who are being treated with non-steroidal antiinflammatory drugs, including selective cyclooxygenase-2 inhibitors, the co-administration of angiotensin II receptor antagonists may result in a further deterioration of renal function including possible acute failure which is usually reversible.
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 85 and 43 percent, respectively. Corticosteroids, ACTH – intensified electrolyte depletion, particularly hypokalemia. Pressor amines (e.g., 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 add a high risk of lithium toxicity; concomitant use is not recommended. Refer to the package inserts for lithium preparations before use of such preparations. Non-Steroidal Anti-Inflammatory Drugs – In some patients, the administration of a non-steroidal antiinflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium and thiazide diuretics.
Pregnancy and 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 in the developing fetus. When pregnancy is detected, this product should be discontinued as soon as possible.
Use in Breastfeeding: Losartan It is not known whether losartan is excreted in human milk. However, significant levels of losartan and the active metabolite were shown to be present in rat milk. Hydrochlorothiazide 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 Ocsaar Plus, taking into account the importance of the drug to the mother.
No specific information is available on the treatment of overdose with Ocsaar Plus. Treatment is symptomatic and supportive. Therapy with Ocsaar Plus should be discontinued and the patient observed closely. Suggested measures include induction of emesis if ingestion is recent, and correction of dehydration, electrolyte imbalance, hepatic coma and hypotension by established procedures.