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Medication Safety Issues
Sound-alike/look-alike issues:
Indapamide may be confused with Iopidine®
International issues:
Pretanix® [Hungary] may be confused with Protonix® which is a brand name for pantoprazole in the U.S.
Pronunciation
(in DAP a mide)
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Management of mild-to-moderate hypertension; treatment of edema in heart failure and nephrotic syndrome
Pregnancy Risk Factor
B (manufacturer); D (expert analysis)
Lactation
Excretion in breast milk unknown
Contraindications
Hypersensitivity to indapamide or any component of the formulation, thiazides, or sulfonamide-derived drugs; anuria; renal decompensation; pregnancy (based on expert analysis)
Warnings/Precautions
Concerns related to adverse effects:
• Electrolyte disturbances: Hypokalemia, hypochloremic alkalosis, and hyponatremia can occur.
• Photosensitivity: Photosensitization may occur.
• Sulfa allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with thiazide or sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe. Discontinue if signs of hypersensitivity are noted.
Disease-related concerns:
• Diabetes: Use with caution in patients with prediabetes or diabetes mellitus; may see a change in glucose control.
• Gout: In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated.
• Hepatic impairment: Use with caution in patients with severe hepatic dysfunction; in cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy.
• Hypercholesterolemia: Use with caution in patients with moderate or high cholesterol concentrations.
• Hypokalemia: Use with caution in patients with hypokalemia; correct before initiating therapy.
• Renal impairment: Avoid in severe renal disease (ineffective).
• Systemic lupus erythematosus (SLE): Can cause SLE exacerbation or activation.
Adverse Reactions
1% to 10%:
Cardiovascular: Palpitation (<5%), flushing, orthostatic hypotension
Central nervous system: Headache (?5%), nervousness (?5%), dizziness (<5%), drowsiness (<5%), lightheadedness (<5%), restlessness (<5%), vertigo (<5%), agitation, anxiety, depression, fatigue, lassitude, lethargy, malaise
Dermatologic: Hives (<5%), pruritus (<5%), rash (<5%)
Endocrine & metabolic: Hyperglycemia (<5%), hyperuricemia (<5%)
Gastrointestinal: Abdominal pain, anorexia, bloating, constipation, cramping, diarrhea, dry mouth, gastric irritation, nausea, vomiting, weight loss
Genitourinary: Glycosuria (<5%), impotence (<5%), libido reduced (<5%), nocturia, polyuria, urinary frequency
Neuromuscular & skeletal: Weakness (?5%), muscle cramps, spasm
Ocular: Blurred vision (<5%)
Renal: Cutaneous vasculitis (<5%), necrotizing angiitis, vasculitis
Respiratory: Rhinorrhea (<5%)
<1%, postmarketing, and/or case reports (limited to important or life-threatening): Hepatitis, hypercalcemia, jaundice, liver function test abnormality, pancreatitis, purpura
Drug Interactions
ACE Inhibitors: Thiazide Diuretics may enhance the hypotensive effect of ACE Inhibitors. Specifically, postural hypotension which can accompany ACE Inhibitor initiation. Thiazide Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. Risk C: Monitor therapy
Alcohol (Ethyl): May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Alfuzosin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Allopurinol: Thiazide Diuretics may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Analgesics (Opioid): May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Antidiabetic Agents: Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Artemether: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Barbiturates: May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Thiazide Diuretics. The diuretic response is likewise decreased. Risk D: Consider therapy modification
Calcitriol: Thiazide Diuretics may enhance the hypercalcemic effect of Calcitriol. Risk C: Monitor therapy
Calcium Salts: Thiazide Diuretics may decrease the excretion of Calcium Salts. Continued concomitant use can also result in metabolic alkalosis. Risk C: Monitor therapy
Chloroquine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Ciprofloxacin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy
Dofetilide: Thiazide Diuretics may enhance the QTc-prolonging effect of Dofetilide. Thiazide Diuretics may increase the serum concentration of Dofetilide. Risk X: Avoid combination
Dronedarone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Dronedarone. Risk X: Avoid combination
Gadobutrol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk D: Consider therapy modification
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents. Risk C: Monitor therapy
Lithium: Thiazide Diuretics may decrease the excretion of Lithium. Risk D: Consider therapy modification
Lumefantrine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Nilotinib: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Nonsteroidal Anti-Inflammatory Agents: May diminish the therapeutic effect of Thiazide Diuretics. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Pimozide: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Pimozide. Risk X: Avoid combination
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
QTc-Prolonging Agents: May enhance the adverse/toxic effect of other QTc-Prolonging Agents. Their effects can be additive, causing life-threatening ventricular arrhythmias. Risk D: Consider therapy modification
QuiNINE: QTc-Prolonging Agents may enhance the QTc-prolonging effect of QuiNINE. QuiNINE may enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Tetrabenazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Tetrabenazine. Risk X: Avoid combination
Thioridazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Ziprasidone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Ziprasidone. The risk of a severe arrhythmia may be increased. Risk X: Avoid combination
Ethanol/Nutrition/Herb Interactions
Herb/Nutraceutical: Avoid herbs with hypertensive properties (bayberry, blue cohosh, cayenne, ephedra, ginger, ginseng [American], kola, licorice); may diminish the antihypertensive effect of indapamide. Avoid herbs with hypotensive properties (black cohosh, California poppy, coleus, golden seal, hawthorn, mistletoe, periwinkle, quinine, shepherd's purse); may enhance the hypotensive effect of indapamide.
Mechanism of Action
Diuretic effect is localized at the proximal segment of the distal tubule of the nephron; it does not appear to have significant effect on glomerular filtration rate nor renal blood flow; like other diuretics, it enhances sodium, chloride, and water excretion by interfering with the transport of sodium ions across the renal tubular epithelium
Pharmacodynamics/Kinetics
Onset of action: 1-2 hours
Duration: ?36 hours
Absorption: Complete
Protein binding, plasma: 71% to 79%
Metabolism: Extensively hepatic
Half-life elimination: 14-18 hours
Time to peak: 2-2.5 hours
Excretion: Urine (~60%) within 48 hours; feces (~16% to 23%)
Dosage
Adults: Oral:
Edema: 2.5-5 mg/day. Note: There is little therapeutic benefit to increasing the dose >5 mg/day; there is, however, an increased risk of electrolyte disturbances
Hypertension: 1.25 mg in the morning, may increase to 5 mg/day by increments of 1.25-2.5 mg; consider adding another antihypertensive and decreasing the dose if response is not adequate
Administration: Oral
May be taken with food or milk. Take early in day to avoid nocturia. Take the last dose of multiple doses no later than 6 PM unless instructed otherwise.
Monitoring Parameters
Blood pressure (both standing and sitting/supine), serum electrolytes, renal function, assess weight, I & O reports daily to determine fluid loss
Dietary Considerations
May be taken with food or milk to decrease GI adverse effects.
Patient Education
Do not take any new medication during therapy unless approved by prescriber. Take as directed, early in the day. Do not exceed recommended dosage. This medication does not replace other antihypertensive interventions; follow prescriber's instructions for diet and lifestyle changes. If you have diabetes, monitor serum glucose closely (medication may decrease effect of oral hypoglycemics). Monitor weight on a regular basis. Report sudden or excessive weight gain (>5 lb/week), swelling of ankles or hands, or respiratory difficulty. You may experience dizziness, weakness, or drowsiness (use caution when rising from sitting or lying position, when climbing stairs and when driving or engaging in tasks that require alertness until response to drug is known); sensitivity to sunlight (use sunblock, wear protective clothing or sunglasses); impotence (reversible); or dry mouth or thirst (frequent mouth care, chewing gum, or sucking lozenges may help). Report any changes in visual acuity; unusual bleeding; chest pain or palpitations; or numbness, tingling, cramping of muscles. Pregnancy/breast-feeding precaution: Inform prescriber if you are pregnant. Consult prescriber if breast-feeding.
Geriatric Considerations
Thiazide diuretics lose efficacy when Clcr is <30-35 mL/minute. Many elderly may have Clcr below this limit. Calculate Clcr for elderly before initiating therapy. Indapamide has the advantage over thiazide diuretics in that it is effective when Clcr is <30 mL/minute.
Cardiovascular Considerations
Indapamide may be used to treat hypertension but offers no compelling advantages over thiazide diuretics in this setting.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Orthostatic hypotension, palpitations, flushing, xerostomia (normal salivary flow resumes upon discontinuation), and rhinorrhea.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
Indapamide is one of the drugs confirmed to prolong the QT interval and is accepted as having a risk of causing torsade de pointes. The risk of drug-induced torsade de pointes is extremely low when a single QT interval prolonging drug is prescribed. In terms of epinephrine, it is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval. Until more information is obtained, it is suggested that the clinician consult with the physician prior to the use of a vasoconstrictor in suspected patients, and that the vasoconstrictor (epinephrine, mepivacaine and levonordefrin [Carbocaine® 2% with Neo-Cobefrin®]) be used with caution.
Dental Comment
Indapamide is known to prolong the QT interval. The QT interval is measured as the time and distance between the Q point of the QRS complex and the end of the T wave in the ECG tracing. After adjustment for heart rate, the QT interval is defined as prolonged if it is more than 450 msec in men and 460 msec in women. A long QT syndrome was first described in the 1950s and 60s as a congenital syndrome involving QT interval prolongation and syncope and sudden death. Some of the congenital long QT syndromes were characterized by a peculiar electrocardiographic appearance of the QRS complex involving a premature atria beat followed by a pause, then a subsequent sinus beat showing marked QT prolongation and deformity. This type of cardiac arrhythmia was originally termed “torsade de pointes” (translated from the French as “twisting of the points”). Indapamide is considered as having a risk of causing torsade de pointes. Since it is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval, a medical consult is suggested.
Mental Health: Effects on Mental Status
May rarely cause mood changes
Mental Health: Effects on Psychiatric Treatment
May decrease lithium clearance resulting in an increase in serum lithium levels and potential lithium toxicity; monitor serum lithium levels
Nursing: Physical Assessment/Monitoring
Assess allergy history prior to beginning therapy (sulfonamides, thiazides). Assess potential for interactions with other pharmacological agents or herbal products patient may be taking (eg, altered effect of oral hypoglycemics, increased risk of hypotension or toxicity). Assess results of laboratory tests, therapeutic effectiveness (according to purpose for use), and adverse response (hypotension, hypokalemia, confusion) at regular intervals during therapy. Instruct patients with diabetes to monitor glucose levels closely; may interfere with oral hypoglycemic medications. Teach patient proper use, possible side effects (eg, orthostatic hypotension, photosensitivity) and appropriate interventions, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: 1.25 mg, 2.5 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Indapamide)
1.25 mg (90): $15.00
2.5 mg (30): $13.99
International Brand Names
Lexi-Comp.com
Last full review/revision November 2009
Content last modified November 2009
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