Product Overview
[Drug Name]
Generic Name: Telmisartan and Hydrochlorothiazide Tablets
Trade Name: Mikasu
English Name: Telmisartan and Hydrochlorothiazide Tablets
Chinese Pinyin: TiMiShaTanQingLvSaiQinPian
[Ingredients]
Telmisartan, hydrochlorothiazide
[Appearance]
White tablets.
[Indications]
For the treatment of essential hypertension. Mikasu fixed-dose combination (telmisartan 80 mg/hydrochlorothiazide 12.5 mg) is indicated for the treatment of patients whose blood pressure is inadequately controlled with telmisartan alone.
[Dosage and Administration]
Adults: For adult patients whose blood pressure is inadequately controlled with telmisartan alone, Mikasu should be administered once daily with water, either before or after meals. It is recommended that the doses of both components of the combination be titrated before switching to a combination formulation. If appropriate, switching from telmisartan monotherapy to a combination formulation may be considered. For patients whose blood pressure cannot be adequately controlled with telmisartan 80 mg, Mikasartan 80/12.5 mg can be administered.
Renal Impairment: Regular renal function monitoring is recommended. Hepatic Impairment: For patients with mild to moderate hepatic impairment, the dose should not exceed Mikasartan 40/12.5 mg once daily. Mikasartan should not be used in patients with severe hepatic impairment. Thiazide diuretics should be used with caution in patients with hepatic impairment.
Geriatric Use: No dose adjustment is required.
Pediatric and Adolescent Use: The safety and efficacy of Mikasartan in children and adolescents up to 18 years of age have not been established.
[Adverse Reactions]
1. Side effects due to fluid and electrolyte imbalances are common.
2. Hyperglycemia.
3. Hyperuricemia.
4. Allergic reactions, such as rash and urticaria, are rare.
5. Leukopenia or leukopenia, thrombocytopenic purpura, are also rare.
6. Other rare events include cholecystitis, pancreatitis, sexual dysfunction, photosensitivity, and color vision impairment.
7. Diarrhea and angioedema. These are mostly mild and transient, generally not requiring discontinuation of treatment. Their occurrence is not dose-related.
[Contraindications]
Hypersensitivity to the active ingredient or any excipients of Mikasol; 1. Hypersensitivity to other sulfonamide derivatives (because hydrochlorothiazide is a sulfonamide derivative); 2. Pregnancy during the second and third trimesters, and during breastfeeding (see Section 4.6, Pregnancy and Breastfeeding); 3. Cholestatic and biliary obstructive diseases; 4. Severe hepatic impairment; 5. Severe renal impairment (creatinine clearance <30 ml/min); 6. Refractory hypokalemia and hypercalcemia; 7. Second and third trimesters of pregnancy and breastfeeding; 8. Patients with biliary obstructive diseases; 9. Patients with severe hepatic insufficiency; 10. Patients with severe renal impairment (creatinine clearance <30 ml/min).
[Precautions]
1. If symptomatic hypotension occurs with an overdose of this drug, supportive treatment should be initiated. This drug cannot be removed by hemodialysis. 2. This drug may enhance the antihypertensive effect of antihypertensive drugs. 3. Serum lithium levels should be monitored when used concomitantly with certain medications. 4. No dose adjustment is required for patients with mild to moderate renal impairment. The dose for patients with mild to moderate hepatic impairment should not exceed 40 mg daily. 5. This drug is contraindicated in pregnant and breastfeeding women. 6. The safety of this drug in pediatric patients has not been established; use with caution in children. 7. Cross-allergy: Cross-reactivity with sulfonamides, furosemide, bumetanide, and carbonic anhydrase inhibitors. 8. Interference with diagnosis: May cause impaired glucose tolerance, increased blood glucose, urine glucose, blood bilirubin, blood calcium, blood uric acid, blood cholesterol, triglycerides, and low-density lipoprotein cholesterol, and decreased blood magnesium, potassium, sodium, and urine calcium. 9. Use with caution in the following conditions: ① Patients with anuria or severe renal impairment, as this class of drugs is less effective and high doses can lead to drug accumulation and increased toxicity; ② Diabetes; ③ Hyperuricemia or a history of gout; ④ Severe liver damage, as fluid and electrolyte imbalances can induce hepatic coma; ⑤ Hypercalcemia; ⑥ Hyponatremia; ⑦ Lupus erythematosus, which may aggravate the condition or induce activity; ⑧ Pancreatitis; ⑨ Sympathectomy (enhanced antihypertensive effect); ⑩ Infants with jaundice. 10. Follow-up tests: ① Serum electrolytes; ② Blood glucose; ③ Serum uric acid; ④ Serum creatinine and urea nitrogen; ⑤ Blood pressure. 11. Start with the minimum effective dose to minimize side effects and reduce reflex renin and aldosterone secretion. 12. Patients prone to hypokalemia should receive potassium supplements or use the drug in combination with a potassium-sparing diuretic, as appropriate.
[Use in Special Populations]
Precautions for Pregnancy and Lactation:
Contraindicated for use during pregnancy. Use with caution in lactating women.
[Drug Interactions]
Store tightly closed in a cool, dry place.
[Pharmacological Actions]
Telmisartan is an orally active, specific angiotensin II receptor (AT1) antagonist. It binds to the AT1 subtype of the angiotensin II receptor (the known site of angiotensin II action) with high affinity and long-lasting binding, but lacks any partial agonist effects. The potential for receptor overstimulation due to increased angiotensin II levels caused by telmisartan is unknown. Telmisartan may decrease blood aldosterone levels. Telmisartan does not inhibit plasma renin or block ion channels. Angiotensin-converting enzyme (ACE) kinase II also degrades bradykinin. Since telmisartan does not inhibit ACE, adverse reactions due to enhanced bradykinin activity are unlikely. Telmisartan has no affinity for other receptors, including AT2 and other less well-characterized AT receptors whose functions are still unclear. In humans, administration of 80 mg of telmisartan almost completely inhibits the angiotensin II-induced increase in blood pressure, with the inhibitory effect persisting for 24 hours and still measurable after 48 hours. The antihypertensive effect becomes increasingly evident within 3 hours after the first dose of telmisartan. Maximum antihypertensive effect is achieved 4 weeks after the start of treatment and is maintained with long-term treatment. Ambulatory blood pressure monitoring shows that the antihypertensive effect persists for more than 24 hours after dosing, including the 4 hours before the next dose. This finding was confirmed in placebo-controlled clinical trials: the trough-to-peak ratio remained consistently above 80% after dosing with 40 mg and 80 mg of telmisartan. There is a clear dose-time dependence for return to baseline SBP. Data regarding DBP are conflicting. In patients with hypertension, telmisartan reduces both systolic and diastolic blood pressure without affecting heart rate. The antihypertensive efficacy of telmisartan is comparable to that of other leading antihypertensive drugs. (Clinical studies have compared telmisartan with amlodipine, atenolol, enalapril, hydrochlorothiazide, losartan, and lisinopril.) If telmisartan treatment is abruptly discontinued, blood pressure gradually returns to pre-treatment levels over several days, without rebound hypertension. In clinical trials directly comparing two antihypertensive drugs, the incidence of dry cough was significantly lower in patients treated with telmisartan than in those treated with angiotensin-converting enzyme inhibitors. The effect of telmisartan on mortality and cardiovascular morbidity is currently unknown. Toxicology: At doses used in preclinical safety studies, which are comparable to clinically effective doses, telmisartan can cause decreases in red blood cell indices (erythrocytes, hemoglobin, and hematocrit), altered renal hemodynamics (increased blood urea nitrogen and creatinine), and elevated serum potassium in normotensive animals. Renal tubular dilation and atrophy have been observed in dogs. Digestive mucosal damage (erosions, ulcers, or inflammation) has also been observed in rats and dogs. Preclinical studies have shown that these adverse pharmacological reactions are common to both angiotensin-converting enzyme inhibitors and angiotensin II antagonists and can be prevented with oral salt supplementation. Increased plasma renin activity and juxtaglomerular cell hypertrophy/proliferation have been observed in both species. These changes are also common to angiotensin-converting enzyme inhibitors and other angiotensin II antagonists and are not clinically specific. Animal studies have shown potential adverse effects of telmisartan on postnatal fetal development, including weight loss, delayed eye opening, and increased mortality. In vitro studies have not demonstrated mutagenicity or related mutagenic activity. No carcinogenicity has been observed in studies in mice and rats. Hydrochlorothiazide: 1. Effects on water and electrolyte excretion. ① Diuretic effect: Increased urinary excretion of sodium, potassium, chloride, phosphorus, and magnesium, while decreased urinary calcium excretion. The mechanism of action of this class of drugs is primarily to inhibit sodium chloride reabsorption in the distal tubule proximal and, to a lesser extent, the proximal tubule, thereby increasing Na-K exchange in the distal tubule and collecting duct and enhancing K+ secretion. Their mechanism of action is not yet fully understood. All drugs in this class inhibit carbonic anhydrase activity to varying degrees, which may explain their effects on the proximal tubule. They also inhibit phosphodiesterase activity, reducing tubular fatty acid uptake and mitochondrial oxygen consumption, thereby inhibiting active tubular reabsorption of Na and Cl-. (2) Antihypertensive effect. In addition to diuretic and natriuretic effects, extrarenal mechanisms may also contribute to blood pressure reduction, possibly by increasing gastrointestinal sodium excretion. (2) Effects on renal hemodynamics and glomerular filtration function. Due to decreased renal tubular reabsorption of water and sodium, increased intratubular pressure and increased water and sodium flow through the distal convoluted tubule stimulate the macula densa through the tubuloglomerular reflex, increasing renal secretion of renin and angiotensin. This leads to renal vasoconstriction, decreased renal blood flow, constriction of the afferent and efferent glomerular arterioles, and a decrease in glomerular filtration rate. This decrease in renal blood flow and glomerular filtration rate, as well as the lack of effect on the loop of Henle, are the main reasons why this class of drugs has a far inferior diuretic effect compared to loop diuretics.
[Approval Number]
National Medicine Standard No. J20140014
[Manufacturer]
Company Name: Shanghai Boehringer Ingelheim Pharmaceuticals Co., Ltd.
