Indapamide + Olmesartan Medoxomil

Usage

• Medical Conditions: This fixed-dose combination medication is primarily prescribed for the management of essential hypertension (high blood pressure) in patients whose blood pressure is not adequately controlled by olmesartan medoxomil or indapamide alone. It can also be used as initial therapy in patients likely to require multiple drugs to achieve blood pressure goals. It’s especially beneficial in patients with type 2 diabetes to prevent microalbuminuria and proteinuria or offer end-organ protection.
• Pharmacological Classification: Antihypertensive (Angiotensin II Receptor Blocker [ARB] + Thiazide-like Diuretic).
• Mechanism of Action: Olmesartan medoxomil blocks the action of angiotensin II, a hormone that causes blood vessels to constrict, leading to vasodilation and lowered blood pressure. Indapamide, a thiazide-like diuretic, increases the excretion of sodium and water by the kidneys, further reducing blood volume and blood pressure. The combination provides synergistic antihypertensive effects.

Alternate Names

• There are no widely recognized alternate names for this combination itself. However, the individual components have various names (e.g., for olmesartan medoxomil: Benicar, Olmetec).
• Brand Names: Brand names vary regionally; examples include Olmesar-ID and Olmecip-ID in India. There are also numerous generic versions containing the same active ingredients.

How It Works

• Pharmacodynamics: Olmesartan medoxomil is a prodrug rapidly hydrolyzed to olmesartan, which selectively blocks the angiotensin II type 1 (AT1) receptor. This inhibits the vasoconstricting and aldosterone-secreting effects of angiotensin II, resulting in vasodilation, decreased peripheral resistance, and reduced blood volume. Indapamide inhibits sodium reabsorption in the distal convoluted tubule, increasing sodium and water excretion. The combined effect reduces blood volume, decreases peripheral resistance, and lowers blood pressure.

• Pharmacokinetics: Absorption: Olmesartan medoxomil is rapidly absorbed after oral administration, with peak plasma concentrations reached in 1-2 hours. Indapamide is well-absorbed from the gastrointestinal tract, achieving peak plasma levels in 1-2 hours as well. Metabolism: Olmesartan medoxomil undergoes rapid and complete hydrolysis to olmesartan, the active metabolite. Olmesartan is not further metabolized. Indapamide is partially metabolized in the liver. Elimination: Olmesartan is primarily eliminated in feces and urine with a half-life of 13 hours. Indapamide is excreted mainly by the kidneys with a half-life of approximately 18 hours.

• Mode of Action: Olmesartan exerts its effect by competitively binding to the AT1 receptor, preventing angiotensin II from binding and triggering vasoconstriction. Indapamide acts by inhibiting the sodium-chloride cotransporter in the distal convoluted tubule, thus impeding sodium reabsorption. Neither drug significantly affects CYP enzymes.

Dosage

Standard Dosage

Adults:

The usual recommended starting dose is one tablet containing 20 mg olmesartan medoxomil and 1.25 mg indapamide once daily. After 1-2 weeks, the dose may be increased to one tablet containing 40 mg olmesartan medoxomil and 1.25 mg indapamide once daily as needed.

Children:

Olmesartan medoxomil monotherapy is approved for pediatric use, but the combination with indapamide is not typically recommended for children.

Special Cases:

• Elderly Patients: No initial dosage adjustment is generally required. Close monitoring is advised, especially in those with volume depletion or concurrent illnesses.
• Patients with Renal Impairment: Use cautiously. Closely monitor renal function and serum electrolytes. Dosage adjustment may be necessary based on creatinine clearance. In severe renal impairment, consider a lower initial dose and a maximum dose not exceeding 20 mg of olmesartan medoxomil with 1.25 mg indapamide.
• Patients with Hepatic Dysfunction: Use cautiously. Closely monitor liver function tests and serum electrolytes. No initial dosage adjustment is generally required, but reduce dosage in severe hepatic impairment.
• Patients with Comorbid Conditions: In patients with conditions like diabetes, heart failure, and other cardiovascular diseases, dose adjustments should be made based on individual needs and under careful medical supervision.

Clinical Use Cases

The provided sources do not specify dosage recommendations for intubation, surgical procedures, mechanical ventilation, ICU use, or specific emergency situations with the use of indapamide combined with olmesartan medoxomil.

Dosage Adjustments

Dose adjustments should be individualized based on patient response, blood pressure control, and tolerance. Consider renal function, hepatic function, and the presence of other medical conditions when modifying dosage.

Side Effects

Common Side Effects

Dizziness, lightheadedness, headache, back pain, diarrhea, bronchitis, flu-like symptoms, and upper respiratory tract infections.

Rare but Serious Side Effects

Angioedema (swelling of the face, lips, tongue, or throat), hypotension, syncope, acute renal failure, hyperkalemia, hyponatremia, severe skin rashes, and hepatotoxicity.

Long-Term Effects

Electrolyte imbalances (hypokalemia, hyponatremia), worsening of renal function, and the development of gout.

Adverse Drug Reactions (ADR)

Anaphylaxis, Stevens-Johnson Syndrome, and other severe hypersensitivity reactions.

Contraindications

Hypersensitivity to olmesartan medoxomil, indapamide, or other sulfonamides, pregnancy (especially second and third trimesters), anuria, and bilateral renal artery stenosis.

Drug Interactions

• Other antihypertensives (additive hypotensive effect).
• Nonsteroidal anti-inflammatory drugs (NSAIDs) (may reduce the antihypertensive effect and increase the risk of renal impairment).
• Potassium supplements or salt substitutes containing potassium (increased risk of hyperkalemia).
• Lithium (increased plasma lithium levels).
• Certain antibiotics, antifungals, anti-HIV drugs, and anti-epileptic medications (may alter metabolism and serum levels of either drug).
• Alcohol, grapefruit juice, and St. John’s wort (may interact with indapamide, altering its metabolism and effectiveness).

Pregnancy and Breastfeeding

• Pregnancy Safety Category: D (olmesartan medoxomil) and C (indapamide). Contraindicated during pregnancy, especially in the second and third trimesters. May cause fetal harm or death.

• Breastfeeding: Not recommended. Olmesartan may pass into breast milk, and potential effects on nursing infants are unknown. Indapamide can reduce breast milk production. Safer alternatives should be considered.

Drug Profile Summary

• Mechanism of Action: Olmesartan blocks angiotensin II receptors, causing vasodilation. Indapamide increases sodium and water excretion.
• Side Effects: Dizziness, headache, back pain, diarrhea, hyperkalemia, hyponatremia.
• Contraindications: Pregnancy, anuria, bilateral renal artery stenosis, hypersensitivity to sulfonamides.
• Drug Interactions: Other antihypertensives, NSAIDs, potassium supplements, lithium.
• Pregnancy & Breastfeeding: Contraindicated in pregnancy, not recommended while breastfeeding.
• Dosage: Starting dose 20mg/1.25mg once daily, max 40mg/1.25mg once daily.
• Monitoring Parameters: Blood pressure, renal function, electrolytes (potassium, sodium).

Popular Combinations

While this medication itself combines two drugs, further combinations are possible. Additional antihypertensive medications might be added (e.g., calcium channel blockers, beta-blockers) if blood pressure control remains suboptimal. However, each added medication increases the risk of side effects and interactions, requiring careful consideration.

Precautions

• General Precautions: Assess renal and hepatic function, electrolyte levels, and blood pressure before and during treatment. Monitor for signs of hypotension, hyperkalemia, and hyponatremia. Screen for sulfonamide allergy.

• Specific Populations:

  • Pregnant Women: Contraindicated.
  • Breastfeeding Mothers: Not recommended.
  • Children & Elderly: Use cautiously. Dose adjustments may be necessary.
  • Menstruating Individuals: No specific precautions related to menstruation have been noted.

• Lifestyle Considerations: Encourage lifestyle modifications such as a healthy diet, regular exercise, smoking cessation, and limiting alcohol intake. Avoid excessive salt restriction with indapamide. Caution patients about possible dizziness, especially with the initial dose, and advise against driving or operating machinery until the effects are known.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Indapamide + Olmesartan Medoxomil?

A: The recommended starting dose is 20 mg olmesartan medoxomil/1.25 mg indapamide once daily. This may be increased to a maximum of 40 mg olmesartan medoxomil/1.25 mg indapamide once daily after 1-2 weeks if needed.

Q2: How does this combination medication lower blood pressure?

A: It works through two mechanisms. Olmesartan blocks angiotensin II receptors, causing vasodilation. Indapamide increases sodium and water excretion, reducing blood volume.

Q3: Can I take this medication if I have kidney disease?

A: Use with caution in patients with renal impairment. Closely monitor renal function and electrolytes. Dosage adjustments may be necessary.

Q4: What are the most common side effects?

A: Dizziness, headache, back pain, and gastrointestinal issues like diarrhea are common.

Q5: Are there any serious side effects I should be aware of?

A: Angioedema, hypotension, hyperkalemia, hyponatremia, and acute renal failure are rare but potentially serious side effects. Seek immediate medical attention if these occur.

Q6: Can I take this medication if I am pregnant or breastfeeding?

A: No. This medication is contraindicated during pregnancy, particularly in the second and third trimesters, due to the risk of fetal harm. It is also not recommended during breastfeeding.

Q7: What other medications should I avoid while taking this medication?

A: Avoid other antihypertensives without careful dose adjustment. Caution should be used with NSAIDs, potassium supplements, and lithium. Inform your doctor about all other medications and supplements you are taking.

Q8: What should I do if I miss a dose?

A: Take the missed dose as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and continue with your regular dosing schedule. Do not double the dose to catch up.

Q9: Can I drink alcohol while taking this medication?

A: Alcohol can exacerbate the hypotensive effects of this medication and should be consumed in moderation.

Q10: Can this medication be used in children?

A: The combination is not typically recommended for children. While olmesartan medoxomil is approved for pediatric use as monotherapy, the combination with indapamide requires further study. Consult a pediatrician for appropriate pediatric hypertension management.