Usage
- Fimasartan is prescribed for the treatment of essential hypertension (high blood pressure).
- Pharmacological classification: Angiotensin II Receptor Blocker (ARB).
- Mechanism of Action: Fimasartan blocks the action of angiotensin II, a hormone that causes blood vessels to constrict, by selectively blocking the angiotensin II type 1 (AT1) receptor. This blockage leads to vasodilation (widening of blood vessels), which lowers blood pressure.
Alternate Names
- No widely used alternate names exist.
- Brand Names: Kanarb, Dukarb (combination with amlodipine).
How It Works
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Pharmacodynamics: Fimasartan lowers blood pressure by blocking the AT1 receptor, preventing angiotensin II from binding and causing vasoconstriction. This results in vasodilation and a reduction in blood pressure. It does not show any agonistic activity at the AT2 receptor.
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Pharmacokinetics:
- Absorption: Fimasartan is absorbed orally, reaching peak plasma concentration within 0.5-3 hours in healthy individuals and 0.5–1.3 hours in hypertensive patients. Some individuals exhibit a second absorption peak. The total systemic exposure (AUC) is linear and dose-independent.
- Metabolism: Primarily metabolized by CYP3A4. Over 90% of the drug is metabolized into stable metabolites.
- Elimination: Predominantly eliminated through fecal and biliary excretion. Less than 3% is excreted in the urine within 24 hours of administration. The terminal half-life is 5-16 hours in healthy subjects and 7-10 hours in hypertensive patients.
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Mode of Action: Fimasartan competitively binds to the AT1 receptor, preventing angiotensin II from binding. This inhibition prevents the vasoconstricting effects of angiotensin II, resulting in vasodilation and a decrease in blood pressure.
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Receptor binding, enzyme inhibition, or neurotransmitter modulation: Fimasartan selectively and competitively binds to the AT1 receptor. No significant interaction or inhibition of other receptors, enzymes, or neurotransmitters has been reported.
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Elimination pathways: Primarily fecal and biliary excretion, with minimal renal excretion.
Dosage
Standard Dosage
Adults:
- Initial dose: 60 mg once daily, with or without food.
- Maintenance dose: Can be increased to 120 mg once daily if blood pressure is not adequately controlled. It is recommended to take the medication at the same time each day.
Children:
- No established dosage guidelines for children. Safety and efficacy have not been established.
Special Cases:
- Elderly Patients: No initial dosage adjustment is required. Titration based on blood pressure response is recommended.
- Patients with Renal Impairment:
- Mild to moderate impairment (creatinine clearance 30-80 mL/min): No dosage adjustment necessary.
- Severe impairment (creatinine clearance <30 mL/min): Initial dose 30 mg once daily, not to exceed 60 mg.
- Patients with Hepatic Dysfunction:
- Mild impairment: No dosage adjustment.
- Moderate to severe impairment: Not recommended.
- Patients with Comorbid Conditions: Dosage adjustments may be needed based on individual patient response and the presence of other medical conditions. Careful monitoring is recommended.
Clinical Use Cases
- Intubation, Surgical Procedures, Mechanical Ventilation, Intensive Care Unit (ICU) Use, Emergency Situations: No specific dosage recommendations exist for these clinical scenarios. Dosage adjustments should be determined by the treating physician based on patient-specific factors and clinical needs.
Dosage Adjustments:
- Dosage adjustments may be required in patients with renal or hepatic dysfunction, as outlined above.
- Dose titration based on therapeutic response and blood pressure control is recommended.
Side Effects
Common Side Effects:
Rare but Serious Side Effects:
- Hypotension
- Angioedema (swelling of the face, lips, tongue, or throat)
- Hyperkalemia
Long-Term Effects:
- Limited data are available on the long-term effects of Fimasartan. However, like other ARBs, long-term use may be associated with a potential risk of renal impairment.
Adverse Drug Reactions (ADR):
- As with any medication, serious adverse drug reactions can occur. Patients should report any unusual symptoms promptly to their healthcare provider.
Contraindications
- Hypersensitivity to fimasartan.
- Pregnancy (especially second and third trimesters).
- Concurrent use with aliskiren in patients with diabetes.
- Anuria.
Drug Interactions
- Other antihypertensive medications: Additive hypotensive effects may occur.
- Potassium-sparing diuretics or potassium supplements: Increased risk of hyperkalemia.
- NSAIDs (Nonsteroidal anti-inflammatory drugs): May reduce the antihypertensive effect of fimasartan and increase the risk of renal impairment.
- Lithium: Fimasartan may increase lithium levels.
- CYP3A4 inhibitors: May increase fimasartan plasma concentrations.
- CYP3A4 inducers: May decrease fimasartan plasma concentrations.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: D (FDA classification). Fimasartan is contraindicated during pregnancy, especially in the second and third trimesters, due to the risk of fetal harm.
- Breastfeeding: It is not known whether fimasartan is excreted in human milk. The use of fimasartan during breastfeeding is not recommended.
Drug Profile Summary
- Mechanism of Action: Angiotensin II receptor blocker (ARB).
- Side Effects: Dizziness, headache, hypotension, hyperkalemia, angioedema.
- Contraindications: Hypersensitivity, pregnancy, concurrent use with aliskiren in patients with diabetes, anuria.
- Drug Interactions: Other antihypertensives, potassium-sparing diuretics, NSAIDs, lithium, CYP3A4 inhibitors/inducers.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy, not recommended during breastfeeding.
- Dosage: Adults: 60-120 mg once daily. Renal impairment: dose adjustment required for severe impairment. Hepatic dysfunction: avoid in moderate/severe cases.
- Monitoring Parameters: Blood pressure, renal function (serum creatinine, potassium), signs of angioedema.
Popular Combinations
- Fimasartan/Hydrochlorothiazide: This combination is used to enhance the antihypertensive effect in patients whose blood pressure is not adequately controlled by fimasartan alone. The diuretic hydrochlorothiazide promotes sodium and water excretion, further lowering blood pressure.
- Fimasartan/Amlodipine: This combination provides synergistic blood pressure lowering through different mechanisms of action. Amlodipine is a calcium channel blocker that relaxes blood vessels.
Precautions
- General Precautions: Monitor blood pressure and renal function regularly. Assess for signs of angioedema.
- Specific Populations: Use with caution in patients with renal or hepatic impairment, heart failure, or those on a salt-restricted diet.
- Lifestyle Considerations: Encourage lifestyle modifications, including diet, exercise, and weight management.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Fimasartan?
A: The recommended initial dose is 60 mg once daily for adults. This can be increased to 120 mg daily if blood pressure is not adequately controlled. Dose adjustments are necessary for patients with severe renal impairment.
Q2: What is the mechanism of action of Fimasartan?
A: Fimasartan blocks the AT1 receptor, preventing angiotensin II from binding and causing vasoconstriction. This results in vasodilation and a decrease in blood pressure.
Q3: What are the common side effects of Fimasartan?
A: The most common side effects are dizziness and headache.
Q4: Is Fimasartan safe in pregnancy?
A: No, Fimasartan is contraindicated during pregnancy, particularly in the second and third trimesters, due to the risk of fetal harm.
Q5: What are the major drug interactions with Fimasartan?
A: Fimasartan may interact with other antihypertensives, potassium-sparing diuretics, NSAIDs, lithium, and CYP3A4 inhibitors/inducers.
Q6: How should Fimasartan be administered?
A: Fimasartan is administered orally, once daily, with or without food. It’s best taken at the same time each day.
Q7: What should I monitor in a patient taking Fimasartan?
A: Monitor blood pressure, renal function (serum creatinine, potassium), and for any signs and symptoms of angioedema.
Q8: Can Fimasartan be used in patients with hepatic impairment?
A: Fimasartan is not recommended in patients with moderate to severe hepatic impairment.
Q9: What is the difference between Fimasartan and other ARBs?
A: While its mechanism of action is similar to other ARBs, Fimasartan has a longer half-life, allowing for once-daily dosing. It also has a higher potency compared to some earlier ARBs like losartan.
Q10: How effective is Fimasartan in lowering blood pressure?
A: Fimasartan has been shown to effectively lower both systolic and diastolic blood pressure in clinical trials. The degree of reduction varies depending on the individual and dosage.
