Fimasartan Tablets 60 mg
COMPOSITION :
Fimasartan Potassium Trihydrate
equivalent to Fimasartan 60 mg
DOSAGE FORM/S:
Film coated tablet
It is used for the treatment of hypertension and heart failure
DOSE AND METHOD OF ADMINIsTRATION:
Oral dosage
Adults: The recommended starting dose is 60 mg once a day with or without food. If blood pressure is not adequately
controlled with 60 mg, suggested adding a second antihypertensive drug. Whenever possible, it is recommended that Fimasartan be administered at the same time every day.
The reducing effect of blood pressure Fimasartan is evident from 2 weeks of starting treatment and usually a maximum reduction is obtained after 8-12 weeks of treatment.
No dose adjustment is required in patients with mild to moderate renal impairment (creatinine clearance 30-80 ml/min) The Fimasartan is contraindicated in patients with
severe renal impairment (creatinine clearance 30 ml/ min). No dose adjustment is required in patients with mild hepatic impairment. Fimasartan use in patients with moderate hepatic impairment is not recommended to severe. No dose adjustment is required in patients> 65 years.
USE IN SPECIAL POPULATIONS:
Pregnancy and Lactation:
The fimasartan should not be administered during the second or third trimester of pregnancy unless the potential benefits to the mother outweigh the possible risks. The
Fimasartan is classitied in category D pregnancy risk. Therefore, as soon as pregnancy Is detected, should take all
possible measures to try to discontinue the drug. Drugs acting On the renin-angiotensin system have been associated with fetal and neonatal injury when administered to pregnant women. Some of these injuries were hypotension, fetal skull hypoplasia, anuria, ologohidramnios, renal insufficiency and fetal death It is unknown whether Fimasartan is excreted in human milk. Breastfeeding is not recommended.
CONTRA-INDICATIONS:
Hypersensitivity to the active substance or to any of the excipients.
The Fimasartan be used with caution in patients whose renal function depends on the activity of the renin- angiotensin-aldosterone system RAS (eg patients with heart failure). ACE inhibitors and antagonists of angiotensin l receptors, affect the RAS system and cause
an increase in serum creatinine in susceptible individuals. Although generaly serum creatinine returns to normal with continued treatment, in some cases there has been oliguria, progressive azotemia and renal failure. In
addition, ACE inhibitors are associated with azotemia in patients with unilateral or bilateral renal artery stenosis. The. Fimasartan is not recommended in patients with severe renal impairment or end (creatinine clearance 30 mi/ min) or in patients on hemodialysis (no experience in this patient population.
The Fimasartan not been studied in patients with hepatic impairment or moderate to severe in patients with
hepatobiliary obstruction. Not to be used in these patient.
DRUG INTERACTIONS:
The Fimasartan may increase the hypotensive effect of other antihypertensive or diuretic drugs when administered Concomitantly. Ihis property can be beneficial, but requires adjustments in dose to avoId episodes of hypotension.
Do not co-administer Fimasartan with renin inhibitors such as aliskiren. No significant interactions between Warfarin and Fimasartan.
UNDESIRABLE EFFECTS:
Adverse reactions caused by the Fimasartan has been deduced from studies in 852 patients. Fimasartan in these patients received doses ranging from 60 to 120 mg for 4 to 12 weeks. Of these, 85 patients received the drug for 6 months or more.
Most adverse events reported were mild to moderate, transient and frequency rate was independent of dose. The adverse events most frequently reported were headache and dizziness. Other adverse events reported during clinical trials (adverse events considered definitely related, probably related or possibly related to Fimasartan) were:
Central nervous system:
common: headache, dizziness Uncommon: syncope, sedation, migraine.
Common:
Gastrointestinal disorders dyspepsia, vomiting, nausea, upper abdominal pain.
Strange asthenia, body feeling:
General Disorders and
Administration Site: uncommon
Clinical laboratory abnormalities: Uncommon: increased ALI, increased AST, thrombocytopenia, increased CPK blood
Respiratory, thoracic and mediastinal disorders:
Uncommon: cough
Disorders musculoskeletal and connective tissue
disorders: Uncommon: muscle cramps, stiffness musculo-skeletal
Skin and subcutaneous tissue disorders: Uncommon: pruritus, urticaria localized
Vascular disorders.: Uncommon: flushing
Disorders of the reproductive system and mammary
glands: Uncommon: Erectile Dysfunction
In an observational, open-label clinical study, the safety and efficacy of Fimasartan in patients With hypetension,
at doses of 60 and 120 mg per day given at least two months was determined. A total of 14,151 patients, 450 (3.31%) reported an adverse event following
administration of the drug; but only in 333 patients (2.35%) was suspected adverse reaction that was related to it. The most common adverse events were dizziness (1.55%) and headache (0.52%) Other less common symptoms
were tatigue, itching, abdominal pain, nausea, cough, sleep disturbances, tachycardia, acroparesthesias, chest
pain, diarrhea and back pain. Ihere were 168 caseS (1.19%) in which patients discontinued treatment; only 135 of these discontinuities (0.95% of all patients) were related to administration of Fimasartan.
Most adverse events resolved spontaneously (76.2%) and no events resulted in death or life-threatening. There were no significant differences (p= 0.66) in the frequency of adverse events between doses of 60 mg (n = 10,5433 .19 %) compared with the dose of 120 mg (n 3,608;3.02%)
TO report adverse events, call toll free on: 1800220408 or Contact us at drugsafety@ajantapharma.com
The most likely effect of over dosage is hypotension. In the event of over dosage, the patient should be carefully monitored and treatment should be symptomatic and Supportive.
PHARMACODYNAMIC AND PHARMACOKINETIC PROPERTIES:
Pharmacodynamic Properties
Angiotensin ll receptor blocker
Fimasartan antagonizes angiotensin AT1 receptor subtype. Have identified two subtypes of angiotensin 1 receptor, called AIT and AI2, of which the Al2 is not involved in cardiOvascular homeostasis. Ihe Fimasartan has a much greater affinity for the AT1 receptor than to the AT2 and join the first blocks the effects of angiotensin.
Angiotensin is a vasoactive hormone of renin-angiotensin system plays an important role in regulating the pressure and arteral pathophysiology of hypertension and congestive heart failure. In addition to being a potent
vasoconstrictor, angiotensin I stimulates aldosterone secretion by the adrenal glands. Thus, blocking the effects of angiotensin ll, the Fimasartan resistenca decreases systemic vascular without causing a significant change in heart rate. In response to blockade of AT1 receptors will increase plasma levels of renin and angiotensin il
Low doses of Fimasartan not seem to affect the plasma levels of aldosterone, although higher doses produced a
decrease in aldosterone levels, without affecting or affected very little serum potassium. As Fimasartan not
inhibit the converting enzyme inhibitor, did not inhibit the degradation of bradykinin. Nor significantiy affect serum
trigiycerides, totalcholesterol, giucose or uric acid.
Pharmacokinetic Properties
Absorption:
Time to peak plasma concentration (Tmax) following single oral administration of fimasartan at dOses of 20-480 mg in healthy subjects ranged 0.5 3 hours with the terminal half-life (t1/2) being 5 16 hours. Similar results
were obtained in patients with hypertension, i.e., Tmax ranged 0.5-1.3 hours andt1/2 were 7 10 hours following
Timasartan administration at doses 20 180 mg. Several Subjects showed a second peak, and the total systemic
exposure as assessed by the area under the Concentration-time curve was linear (i.e., dose independent).
Accumulation index was 1.20 1.26 and 1.02- 1.08 for healthy subjects and patients, respectively. Ihe absolute
bioavailability of fimasartan in healthy subjects following 60 mg oral administration compared to 30 mg intravenous infusion was estimated to be 19%. These results support the notion that oral fimasartan is rapidly absorbed, have linear pharmacokinetic profiles over 20 480 mg doses, and accumulation is minimal when dosed once daily. Therefore, the total systemic exposure can be easily predicted for each dose, which helps increase certainty about the safe and effective use of fimasartan in a clinical setting.
Distribution and Protein Binding:
In vitro protein binding in human plasma ranged 95.6 97.2% at fimasartan concentrations of 0.01-100 HgimL,
which was not dose-dependent. These results were similar to those obtained in the dog and rat using the in vitro and ex vivo methods.
Metabolism:
In vitro study showed CYP3A4 would be mainly involved in fimasartan metabolism. Fimasartan has not been shown to inhibit or induce other CYP enzymes. The parent drug was 2 85% of the fimasartan moieties found in human plasma with a few metabolites identified, which supports the hotion that the pharmacological action of fimasartan is mainly driven by the parent drug. The most abundant Circulating metabolites of fimasartan in plasma in healthy male subjects were idenified as desulfo-fimasartan and fimasartan-S-oxide. These metabolites accounted for approximately 14% (each 7%) of the total drug related exposure. No parent or metabolite has been assayed in human faeces; however, in vivo metabolism of fimasartan is most likely to be minimal given the systemic exposure level of fimasartan was weakly increased by specific CYP3A4 inhibitors. These favorable pharmacokinetic properties of fimasartan enable its safe use in a clinical setting.
Elimination:
Approximately 3- 5% of fimasartan dose was recovered in urine by 24 or 144 hours post-dose following oral administration in healthy male subjects and patients With hypertension. Therefore, the kidney is very less likely
involved in the elimination of fimasartan.
INCOMPATIBILITIES : Not applicable
SHELF-LIFE : 2 years
PACKAGING INFORMATION : Alu Alu Blister pack
STORAGEAND HANDLING INSTRUCTIONS:
Store below 30°C. Protect from light and moisture.
Keep out of the reach of children.
PRESENTATION : Available in a blister pack of 10 tablets.
Manufactured in India by : Ajatta pharma limited.