Dr Sharon Rees @reesprescribe
Day 1: Labelled a ‘thiazide-like’ diuretic (as it acts in the distal convoluted tubule), #indapamide is actually a non-thiazide sulfonamide. Derived in the late 1960s from benzamide (found in plants eg autumn crocus), it was designed to retain blood pressure lowering effect, as distinct from diuresis.
Dr Sharon Rees @reesprescribe
Day 2: Oral formation only for #indapamide. In the UK, licensed use for essential hypertension at 2.5 mg once daily, or modified release 1.5 mg once daily.
Dr Sharon Rees @reesprescribe
Day 3: Kinetics #indapamide; good oral absorption, cmax 1–2 hours. Binds to red blood cells and plasma proteins, and is then taken up through vascular walls where it acts. Liver metabolism via CYP3A4 with one active metabolite. Renal excretion (avoid in severe impairment), but ~ 23% gastrointestinal excretion. T½ 15–18 hours.
Dr Sharon Rees @reesprescribe
Day 4: MOA; #indapamide lowers blood pressure mainly via vascular action (as opposed to diuresis) by reducing calcium uptake in vascular smooth muscle, leading to impaired vasoconstriction. Also more vasodilation via increased prostaglandin levels (PGE2 and prostacyclin) and increased bradykinin levels (also all relevant to reduced platelet aggregation). #indapamide also reduces left ventricular hypertrophy.
Dr Sharon Rees @reesprescribe
Day 4 (cont): A major advantage for #indapamide is that as a result of its mechanism of action there is no relevant change to glucose or lipid metabolism, so does not worsen/cause type 2 diabetes (unlike some thiazide diuretics). Can use in combination with other antihypertensives.
Dr Sharon Rees @reesprescribe
Day 5: #indapamide ADEs: common include hypersensitivity reactions, rash and clinically significant electrolyte disturbances eg hypokalaemia; needs pre-therapy and regular monitoring. Rare/serious incl angioedema, renal failure, SCARs, aplastic anaemia, vision disorders (NOT exhaustive).
Dr Sharon Rees @reesprescribe
Day 5 (cont): Up to 8% population have ‘sulfa’ allergy, hence contraindication in SPC/BNF for #indapamide. Relevance re cross-sensitivity to #indapamide is unknown; individual history important.
Dr Sharon Rees @reesprescribe
Day 6: #indapamide DDIs. All NSAIDs re renal failure; multiple interactions can cause electrolyte issues eg NSAIDs, gabapentin, lithium, sertraline. Increased risk arrhythmias eg quinine. All antihypertensives potentiate hypotension. Can increase risk of allergy to allopurinol (NOT exhaustive). Metformin is in the SPC (but not BNF) as a drug–drug interaction for #indapamide re lactic acidosis risk enhanced in renal failure.
Dr Sharon Rees @reesprescribe
Day 7: As a diuretic, #indapamide is a banned substance in arena of sports doping (unless TUE); abuse possible via rapid weight loss and/or dilution of other banned agents from the increased urine volume/changes in urine content, allowing use as a ‘masking agent’.
EARN YOUR CPD CERTIFICATE
With the help of Prescribing and Therapeutics Training Ltd and the Journal of Prescribing Practice, you can earn your 1-hour CPD certificate
In addition to the tweets, read the BNF treatment summaries on diuretics and hypertension, as well as the monograph on indapamide. Another useful source is the Summary of Product Characteristics for indapamide – see links below. Please submit the answers to reesprescribe@gmail.com as a numbered list with TRUE/FALSE or the correct A,B,C,D option. If you achieve 8 or more out of 10 on the questions, a CPD certificate will be emailed to you.
Further reading on #indapamide
- Diuretics: https://bnf.nice.org.uk/treatment-summary/diuretics.html
- Hypertension: https://bnf.nice.org.uk/treatment-summary/hypertension.html
- Indapamide: https://bnf.nice.org.uk/drug/indapamide.html
- Indapamide 2.5 mg Tablets: https://www.medicines.org.uk/emc/medicine/26709#gref
There are lots of formulations for indapamide
TRUE or FALSE?
Indapamide is a loop diuretic
TRUE or FALSE?
Which is TRUE?
- Indapamide acts in the distal convoluted tubule (DCT), but its main action lowering blood pressure occurs on the blood vessels
- Indapamide acts in the Loop of Henle and effects powerful diuresis
- Indapamide dilate veins and increases afterload
- Indapamide acts at multiple sites in the nephron to exert diuresis
Indapamide is ineffective if the CrCl is below 30 mL/min
TRUE or FALSE?
Indapamide is one of the first line diuretics for the management of hypertension
TRUE or FALSE?
Which of the following is considered to be an advantage of indapamide?
- Electrolyte disturbances help to give better diuresis
- Some of the drug is excreted via the gut
- There is no relevant effect on glucose regulation
- The drug binds to red blood cells in the systemic circulation
Which of the following is a common adverse drug effect?
- Vomiting
- Vertigo
- Vision disorders
- Electrolyte disturbances
Indapamide has a ‘severe’ drug-drug interaction with allopurinol
TRUE or FALSE?
Indapamide is the only diuretic which is banned in sports doping testing
TRUE or FALSE?
It is possible to be allergic to indapamide
TRUE or FALSE?