MICARDROXI-PLUS 40
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Chemical Name:
Telmisartan+Hydrochlorothiazide -
Therapeutic Category:
Cardiovascular drugs -
Pharmacologic Category:
Angiotensin II Receptor Blocker - Diuretic, Thiazide -
Pharmaceutical Form:
Tablets -
Composition:
Telmisartan 40mg+Hydrochlorothiazide 12.5mg
MICARD ROXI-Plus
Tablets
Telmisartan & Hydrochlorothiazide
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WARNING:
FETAL TOXICITY:
When pregnancy is detected, discontinue Telmisartan/Hydrochlorothiazide as soon as possible.
Drugs that act directly on the renin-angiotens in system can cause injury and death to the developing fetus.
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1-COMPOSITION:
MICARD ROXI Plus 40–Tablets: Each tablet contains Telmisartan 40mg+ Hydrochlorothiazide 12.5mg.
MICARD ROXI Plus 80–Tablets: Each tablet contains Telmisartan 80mg+ Hydrochlorothiazide 12.5mg.
EXCIPIENTS:
MICARD ROXI Plus 40:
Magnesium Stearate, Sodium starch glycolate, Sodium hydroxide, Microcrystalline Cellulose, Povidone, Croscarmellose sodium, Lactose monohydrate, Ethanol, Sunset yellow, Maize starch.
MICARD ROXI Plus 80:
Magnesium Stearate, Sodium starch glycolate, Sodium hydroxide, Microcrystalline Cellulose, Povidone, Croscarmellose sodium, Lactose monohydrate, Lactose anhydrous, Ethanol, Red Iron Oxide, Maize starch.
2-MECHANISM OF ACTION:
This product is a combination of two drugs with antihypertensive properties: a thiazide diuretic, hydrochlorothiazide, and an angiotensin II receptor blocker (ARB), Telmisartan.
Telmisartan:
Telmisartan blocks the vasoconstrictor and aldosterone secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Its action is therefore independent of the pathways for angiotensin II synthesis.
Telmisartan has much greater affinity (>3,000-fold) for the AT1 receptor than for the AT2 receptor.
Hydrochlorothiazide:
Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium salt and chloride in approximately equivalent amounts. Indirectly, the diuretic action of hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases in serum potassium. The renin-aldosterone link is mediated by angiotensin II, so coadministration of an ARB tends to reverse the potassium loss associated with these diuretics. The mechanism of the antihypertensive effect of thiazides is not fully understood.
3-PHARMACOKINETICS:
Telmisartan
Absorption: Following oral administration, peak concentrations (Cmax) of telmisartan are reached in 0.5 to 1 hour after dosing. Food slightly reduces the bioavailability of telmisartan, TELMISARTAN / HYDROCHLOROTHIAZIDE can be administered with or without food. The absolute bioavailability of telmisartan is dose dependent.
Distribution: Telmisartan is highly bound to plasma proteins ( > 99.5%)
Metabolism: Telmisartan is metabolized by conjugation to form a pharmacologically inactive acyl glucuronide.
Elimination: Following either intravenous or oral administration, most of the administered dose (> 97%) was eliminated unchanged in feces via biliary excretion; only minute amounts were found in the urine.
Total plasma clearance of telmisartan is > 800 mL/min. Terminal half-life and total clearance appear to be independent of dose.
Hydrochlorothiazide
After oral administration of hydrochlorothiazide, diuresis begins within 2 hours, peaks in about 4 hours, and lasts approximately 6 to 12 hours.
Hydrochlorothiazide is not metabolized but is eliminated rapidly by the kidney. The plasma half-life has been observed to vary between 5.6 and 14.8 hours. At least 61% of the oral dose is eliminated unchanged within 24 hours.
Hydrochlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk.
4-INDICATIONS:
Telmisartan and hydrochlorothiazide is indicated for the treatment of hypertension, to lower blood pressure.
Telmisartan and hydrochlorothiazide is not indicated for initial therapy for the treatment of hypertension.
may be used alone or in combination with other antihypertensive agents.
5-CONTRAINDICATIONS:
In patients who are hypersensitive to any component of this product.
In patients with anuria.
For co-administration with aliskiren in patients with diabetes
6-WARNINS AND PERCAUTIONS:
Hypotension in Volume- Or Salt-Depleted Patients:
In patients with an activated renin-angiotensin system, such as volume- or salt-depleted patients (e.g., those being treated with high doses of diuretics), symptomatic hypotension may occur after initialization of treatment with Telmisartan /Hydrochlorothiazide. Correct volume or salt depletion prior to administration of Telmisartan /Hydrochlorothiazide.
Impaired Renal Function:
Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing oliguria, progressive azotemia, or acute renal failure on Telmisartan /Hydrochlorothiazide. Monitor renal function periodically in these patients. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on Telmisartan /Hydrochlorothiazide.
Electrolytes and Metabolic Disorders:
Drugs, including telmisartan, that inhibit the renin-angiotensin system can cause hyperkalemia, particularly in patients with renal insufficiency, diabetes, or combination use with other angiotensin receptor blockers or ACE inhibitors and the concomitant use of other drugs that raise serum potassium levels.
Hydrochlorothiazide can cause hypokalemia and hyponatremia. Thiazides have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia. Hypomagnesemia can result in hypokalemia which may be difficult to treat despite potassium repletion. Monitor serum electrolytes periodically.
Hydrochlorothiazide decreases urinary calcium excretion and may cause elevations of serum calcium.
Hydrochlorothiazide may alter glucose tolerance and raise serum levels of cholesterol and triglycerides. Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving thiazide therapy. Because telmisartan decreases uric acid, telmisartan in combination with hydrochlorothiazide attenuates the diuretic-induced hyperuricemia.
Hypersensitivity Reaction:
hydrochlorothiazide
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.
Acute Myopia and Secondary Angle-Closure Glaucoma
Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angleclosure glaucoma may include a history of sulfonamide or penicillin allergy.
Systemic Lupus Erythematosus
Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus.
Postsympathectomy Patients
The antihypertensive effects of hydrochlorothiazide may be enhanced in the postsympathectomy patient.
7-PregnancyCategory D
Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death.
When pregnancy is detected, discontinue Telmisartan /Hydrochlorothiazide as soon as possible.
8-NURSING MOTHERS:
It is not known whether telmisartan is excreted in human milk, but telmisartan was shown to be present in the milk of lactating rats. Thiazides appear in human milk. Because of the potential for adverse effects on the nursing infant, decide whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
9-PEDIATRIC USE:
Safety and effectiveness of Telmisartan /Hydrochlorothiazide in pediatric patients have not been established.
10-GERIATRIC USE:
No overall differences in effectiveness and safety of telmisartan /hydrochlorothiazide were observed in these patients compared to younger patients
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range.
11-USE IN PATIENTS WITH HEPATIC IMPAIRMENT:
Patients with biliary obstructive disorders or hepatic insufficiency should initiate treatment under close medical supervision using the 40 mg/12.5 mg combination.
12-USE IN PATIENTS WITH RENAL IMPAIRMENT:
Safety and effectiveness of Telmisartan/Hydrochlorothiazide in patients with severe renal impairment (CrCl ≤ 30 mL/min) have not been established. In patients with severe renal impairment, Telmisartan/Hydrochlorothiazide tablets are not recommended. No dose adjustment is required in patients with mild (CrCl 60 to 90 mL/min) or moderate (CrCl 30 to 60 mL/min) renal impairment.
13-DRUG INTERACTIONS:
Agents Increasing Serum Potassium:
Co-administration of telmisartan with other drugs that raise serum potassium levels may result hyperkalemia. Monitor serum potassium in such patients.
Lithium:
Increases in serum lithium concentrations and lithium toxicity have been reported with concomitant use of thiazide diuretics or angiotensin II receptor antagonists, including telmisartan. Monitor lithium levels in patients receiving Telmisartan /Hydrochlorothiazide and lithium.
Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors:
Telmisartan:
Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors): In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with ARBs, including telmisartan, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. The antihypertensive effect of ARBs may be attenuated by NSAIDs. Therefore, monitor renal function and blood pressure periodically in patients receiving Telmisartan / Hydrochlorothiazide and NSAIDs.
Hydrochlorothiazide:
Administration of a non-steroidal anti-inflammatory agent, including a selective COX2 inhibitor, can reduce the diuretic, natriuretic, and antihypertensive effects of diuretics. Therefore, when Telmisartan/Hydrochlorothiazide and non-steroidal anti-inflammatory agents including selective COX2 inhibitors are used concomitantly, observe closely to determine if the desired effect of the diuretic is obtained.
Dual Blockade of the Renin-Angiotensin-Aldosterone System and Changes in Renal Function:
Dual blockade of the renin-angiotensin-aldosterone system with angiotensin blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and renal impairment.
In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on Telmisartan /Hydrochlorothiazide and other agents that affect the RAS (e.g., concomitant use of an ACE inhibitor with an ARB).
Do not co-administer aliskiren with Telmisartan /Hydrochlorothiazide in patients with diabetes. Avoid concomitant use of aliskiren with Telmisartan/Hydrochlorothiazide in patients with renal impairment (GFR < 60 mL/min/1.73 m²).
Digoxin :
When telmisartan was co-administered with digoxin, median increases in digoxin peak plasma concentration and in trough concentration were observed. Monitor digoxin levels in patients taking concomitant Telmisartan /Hydrochlorothiazide and digoxin.
Antidiabetic Drugs (Oral Agents and Insulin):
Dosage adjustment of antidiabetic drugs may be required when coadministered with hydrochlorothiazide.
Cholestyramine and Colestipol Resins:
Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Stagger the dosage of hydrochlorothiazide and the resin such that hydrochlorothiazide is administered at least 4 hours before or 4 to 6 hours after the administration of the resin.
14-ADVERSE REACTIONS:
Telmisartan:
Impotence, increased sweating, fushing, allergy, fever, leg pain, chest pain, palpitation, angina pectoris, abnormal ECG, hypertension, peripheral edema, insomnia, somnolence, migraine, paresthesia, involuntary muscle contractions, hypoesthesia, flatulence, constipation, gastritis, dry mouth, hemorrhoids, gastroesophageal refux, toothache, elevations of liver enzymes or serum bilirubin, gout, hypercholesterolemia, diabetes mellitus, arthritis, arthralgia, leg cramps, myalgia, anxiety, depression, nervousness, infection, abscess, otitis media, asthma, rhinitis, dyspnea, epistaxis, dermatitis, eczema, pruritus, micturition frequency, cystitis, cerebrovascular disorder, abnormal vision, conjunctivitis, tinnitus, earache.
Hydrochlorothiazide:
Weakness, pancreatitis, jaundice (intrahepatic cholestatic jaundice), sialadenitis, cramping, gastric Irritation, aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia purpura, photosensitivity, urticaria, necrotizing angiitis (vasculitis and cutaneous vasculitis), fever, respiratory distress including pneumonitis and pulmonary edema, anaphylactic reactions, hyperglycemia, glycosuria, muscle spasm, restlessness, interstitial nephritis, erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including, toxic epidermal necrolysis, transient blurred vision, xanthopsia.
15-DOSAGE AND ADMINISTRATION:
Initiate a patient whose blood pressure is not adequately controlled with telmisartan monotherapy 80 mg on Telmisartan /Hydrochlorothiazide, 80 mg/12.5 mg once daily. Dose can be titrated up to 160 mg/25 mg after 2 to 4 weeks, if necessary.
Initiate a patient whose blood pressure is not adequately controlled by 25 mg once daily of hydrochlorothiazide, or is controlled but who experiences hypokalemia with this regimen on
Telmisartan /Hydrochlorothiazide 80 mg / 12.5 mg once daily. Dose can be titrated up to 160 mg/25 mg after 2 to 4 weeks, if necessary.
Patients titrated to the individual components (telmisartan and hydrochlorothiazide) may instead receive the corresponding dose of Telmisartan /Hydrochlorothiazide.
Telmisartan /Hydrochlorothiazide may be administered with other antihypertensive drugs.
Dose Adjustment for Hepatic Impairment:
Initiate patients with biliary obstructive disorders or hepatic insufficiency under close medical supervision using the 40mg/12.5mg combination. TELMISARTAN/ HYDROCHLOROTHIAZIDE tablets are not recommended for patients with severe hepatic impairment
16-OVERDOSE:
Telmisartan
Limited data are available with regard to overdosage of telmisartan in humans. The most likely manifestations of overdosage with telmisartan are hypotension, dizziness, and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted. Telmisartan is not removed by hemodialysis.
Hydrochlorothiazide
The most common signs and symptoms observed in patients with a hydrochlorothiazide overdose 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.
17-PACKAGING:
MICARD ROXI Plus 40- Tablets: Carton package of 20 tablets in blisters
MICARD ROXI Plus 80- Tablets: Carton package of 10 or 20 tablets in blisters.
18-STORAGE CONDITIONS:
Store MICARD ROXI- Plus- Tablets at a temperature between (15-30)°C.
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