Trimethoprim (Idotrim)
Antibiotic for the treatment and prevention of urinary tract infections
Trimethoprim is a prescription antibiotic used to treat and prevent urinary tract infections (UTIs). It belongs to the dihydrofolate reductase inhibitor class of antibiotics and works by blocking bacterial folate synthesis, which is essential for DNA replication and bacterial growth. Trimethoprim is one of the most commonly prescribed antibiotics for uncomplicated lower UTIs worldwide and is listed on the WHO Model List of Essential Medicines. It is effective against most common urinary pathogens, particularly Escherichia coli, and is generally well tolerated with a short treatment course.
Quick Facts
Key Takeaways
- Trimethoprim is a first-line antibiotic for uncomplicated lower urinary tract infections (cystitis) and is also used for long-term UTI prophylaxis.
- The typical adult dose is 150–200 mg twice daily or 300 mg at bedtime for acute UTIs, usually for 3–7 days.
- Do not use trimethoprim if you have severe liver impairment, blood dyscrasias, or megaloblastic anaemia due to folate or vitamin B12 deficiency.
- Trimethoprim can cause hyperkalaemia (high potassium), especially when combined with spironolactone, ACE inhibitors, or angiotensin receptor blockers — monitor electrolytes.
- Seek immediate medical attention if you develop a sore throat with fever, unusual bleeding or bruising, or a severe skin rash — these may indicate serious blood or skin disorders.
What Is Trimethoprim and What Is It Used For?
Trimethoprim is a synthetic antibacterial agent belonging to the dihydrofolate reductase (DHFR) inhibitor class of antimicrobials. First introduced into clinical practice in the 1960s, trimethoprim has become one of the most widely prescribed antibiotics for uncomplicated urinary tract infections across the globe. The World Health Organization includes trimethoprim on its Model List of Essential Medicines, recognising it as one of the most important medications needed in a basic health system.
The drug exerts its antibacterial effect through a highly selective mechanism. Trimethoprim inhibits bacterial dihydrofolate reductase (DHFR), the enzyme responsible for converting dihydrofolic acid into tetrahydrofolic acid — a critical cofactor in the biosynthesis of thymidine, purines, and certain amino acids. Without tetrahydrofolic acid, bacteria cannot synthesise DNA and cannot replicate. Crucially, trimethoprim has approximately 100,000 times greater affinity for bacterial DHFR than for the human enzyme, which explains its selective toxicity against bacteria while sparing human cells.
After oral administration, trimethoprim is rapidly and almost completely absorbed from the gastrointestinal tract, with an oral bioavailability exceeding 90%. It is widely distributed throughout body tissues and fluids, achieving particularly high concentrations in the kidneys, lungs, and prostate gland. Approximately 50–60% of the administered dose is excreted unchanged in the urine, resulting in urinary concentrations that greatly exceed the minimum inhibitory concentrations (MIC) required to kill most common urinary tract pathogens.
Trimethoprim is effective against a broad spectrum of Gram-positive and Gram-negative bacteria commonly responsible for urinary tract infections, including Escherichia coli (the causative organism in approximately 80% of uncomplicated UTIs), Staphylococcus saprophyticus, Proteus mirabilis, and many strains of Klebsiella species. However, resistance patterns vary geographically, and local antibiogram data should guide prescribing decisions. In regions where E. coli resistance to trimethoprim exceeds 20%, alternative empirical antibiotics should be considered.
Primary Uses
Trimethoprim has two principal clinical applications in the management of urinary tract infections:
- Acute treatment of uncomplicated lower UTIs (cystitis) – A standard 3–7 day course effectively clears most bladder infections. International guidelines from the European Association of Urology (EAU), the Infectious Diseases Society of America (IDSA), and the National Institute for Health and Care Excellence (NICE) recommend trimethoprim as a first-line empirical agent for uncomplicated cystitis in settings where local resistance rates are below 20%.
- Long-term prophylaxis of recurrent UTIs – For patients who experience frequent recurrences (typically defined as two or more infections in six months, or three or more in twelve months), a low dose of trimethoprim (100 mg at bedtime) can significantly reduce the frequency of UTI episodes. Prophylactic courses may extend for several months under medical supervision, and several randomised controlled trials have demonstrated significant reductions in UTI recurrence rates with this approach.
Trimethoprim is frequently used as a single-agent antibiotic, but it is also available in combination with sulfamethoxazole (as co-trimoxazole or TMP-SMX). The combination provides a synergistic dual blockade of the bacterial folate synthesis pathway. However, trimethoprim alone is often preferred for uncomplicated UTIs because it has a more favourable side effect profile — avoiding the sulfonamide-related risks of Stevens-Johnson syndrome, toxic epidermal necrolysis, and haematological toxicity that are more common with co-trimoxazole.
What Should You Know Before Taking Trimethoprim?
Before starting trimethoprim, it is essential to discuss your complete medical history with your prescribing physician. Certain conditions can increase the risk of serious side effects or render the medication less effective. Your doctor needs a clear picture of your health to determine whether trimethoprim is the safest and most appropriate antibiotic for your infection.
Contraindications
Trimethoprim must not be used in the following situations:
- Known allergy to trimethoprim – Do not take this medication if you have previously experienced a hypersensitivity reaction to trimethoprim or any of the excipients in the formulation, including lactose monohydrate, maize starch, povidone, polysorbate 80, crospovidone, microcrystalline cellulose, magnesium stearate, hypromellose, or propylene glycol.
- Severe hepatic impairment – Patients with severely reduced liver function must not take trimethoprim due to the risk of drug accumulation and increased hepatotoxicity. The liver plays a role in trimethoprim metabolism, and impaired hepatic function can lead to dangerously elevated drug levels.
- Blood dyscrasias – Patients with existing blood disorders characterised by abnormal production or function of blood cells should avoid trimethoprim, as it can further suppress bone marrow function and worsen cytopenias.
- Megaloblastic anaemia – If you have anaemia caused by vitamin B12 or folate deficiency (megaloblastic anaemia), trimethoprim is contraindicated because its mechanism of action involves inhibition of folate metabolism, which could exacerbate this condition.
Warnings and Precautions
Inform your doctor before starting trimethoprim if you have any of the following conditions, as they may require closer monitoring, dosage adjustments, or selection of an alternative antibiotic:
- Kidney disease or impaired renal function – Trimethoprim is primarily excreted by the kidneys. Patients with reduced renal function may require dose adjustments to prevent drug accumulation and toxicity. Your doctor will assess your kidney function (typically by measuring serum creatinine and estimated glomerular filtration rate) before prescribing trimethoprim. It is also important to note that trimethoprim itself can raise serum creatinine levels by competitively inhibiting creatinine secretion in the renal tubules — this is a pharmacological effect, not a sign of kidney damage, but it can complicate the interpretation of kidney function tests.
- Porphyria – Trimethoprim should be used with caution in patients with porphyria, a rare group of inherited metabolic disorders affecting haem biosynthesis. The drug may potentially precipitate acute porphyric attacks in susceptible individuals.
- Elderly patients or children on long-term therapy – Prolonged or high-dose treatment with trimethoprim requires regular monitoring of blood counts (full blood count, including platelet count) to detect early signs of bone marrow suppression, particularly megaloblastic changes due to folate depletion.
- Suspected or confirmed folate deficiency – Because trimethoprim acts as a folate antagonist, patients with pre-existing folate deficiency are at increased risk of developing haematological complications. Supplemental folic acid may be prescribed alongside trimethoprim in these cases.
Stop taking trimethoprim and contact your doctor or nearest emergency department immediately if you experience any of the following: swelling of the face, tongue, or throat; difficulty swallowing; hives combined with breathing difficulties (angioedema — may affect up to 1 in 1,000 users). Also seek urgent medical care for prolonged or severe diarrhoea (which may indicate pseudomembranous colitis) or a severe skin rash with blistering or sores in the mouth, eyes, or genital area (which may indicate Stevens-Johnson syndrome or toxic epidermal necrolysis).
Trimethoprim can rarely affect white blood cells, reducing the body's ability to fight infection. If you develop a sore throat, fever, unusual paleness, or red spots on the skin during treatment (particularly with prolonged courses or high doses), contact your doctor promptly so that a blood test can be performed to rule out agranulocytosis or other blood count abnormalities.
Pregnancy and Breastfeeding
Trimethoprim requires careful consideration during pregnancy and breastfeeding. The risks and benefits must be weighed individually by a healthcare professional:
- Pregnancy – Trimethoprim is generally not recommended during pregnancy, particularly during the first trimester, unless the doctor has specifically determined that the benefits outweigh the risks. As a folate antagonist, trimethoprim theoretically poses a risk to fetal development because folate is critical for neural tube formation and rapid cell division in early pregnancy. If trimethoprim is deemed necessary during pregnancy, supplemental folic acid is usually co-prescribed to mitigate this risk. Women of childbearing age taking trimethoprim should ensure adequate folate intake.
- Breastfeeding – Trimethoprim passes into breast milk in small quantities, but it is unlikely to affect a breastfed infant at standard therapeutic doses. However, your doctor should be consulted before using trimethoprim during breastfeeding, especially if the course extends beyond a few days or if the infant has any known health conditions.
Always consult your doctor or midwife before taking any medication during pregnancy or while breastfeeding.
Driving and Operating Machinery
Trimethoprim has no known clinically significant effects on the ability to drive or operate machinery. You are personally responsible for assessing whether you are fit to drive a motor vehicle or perform tasks requiring heightened alertness. Although side effects affecting driving ability are not expected with trimethoprim, rare adverse effects such as dizziness or headache may occur. If you experience these symptoms, avoid driving until they resolve.
Lactose Content
Trimethoprim 100 mg film-coated tablets contain 52.3 mg lactose (as monohydrate) per tablet. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should consult their doctor before taking these tablets. The oral suspension formulation may be an alternative for lactose-intolerant patients.
How Does Trimethoprim Interact with Other Drugs?
Drug interactions can reduce the effectiveness of trimethoprim, increase the risk of adverse effects, or alter the activity of co-administered medications. It is critical to inform your prescribing physician and pharmacist about all medications you currently take, including prescription drugs, over-the-counter products, vitamins, and herbal supplements. Trimethoprim is known to interact with several commonly used medications, and these interactions require careful clinical management.
Major Interactions
| Interacting Drug | Effect | Clinical Significance |
|---|---|---|
| Warfarin | Trimethoprim inhibits the hepatic metabolism of warfarin, increasing its anticoagulant effect and INR | Significantly increased bleeding risk; INR should be monitored more frequently and warfarin dose adjusted |
| Methotrexate | Both drugs inhibit folate metabolism; combined use causes synergistic folate depletion and enhanced bone marrow suppression | Potentially severe pancytopenia; avoid combination or use with extreme caution under specialist supervision with folate rescue |
| Phenytoin | Trimethoprim inhibits the hepatic metabolism of phenytoin, leading to elevated phenytoin serum concentrations | Risk of phenytoin toxicity (nystagmus, ataxia, drowsiness); monitor phenytoin levels and adjust dose |
| Spironolactone / Potassium-sparing diuretics | Combined potassium-retaining effects can lead to severe hyperkalaemia | Life-threatening arrhythmias possible; monitor serum potassium closely, especially in elderly or renal-impaired patients |
| ACE inhibitors / ARBs | Additive hyperkalaemic effect; trimethoprim blocks sodium channels in the distal nephron (similar mechanism to amiloride) | Elevated potassium risk; check electrolytes within 3–5 days of starting the combination |
| Ciclosporin | Increased risk of nephrotoxicity when combined with trimethoprim | Monitor renal function closely; consider alternative antibiotic in transplant patients |
Minor Interactions
| Interacting Drug | Effect | Clinical Significance |
|---|---|---|
| Glibenclamide (glyburide) | Trimethoprim may enhance the hypoglycaemic effect of sulfonylureas | Monitor blood glucose more frequently; dose adjustment may be needed |
| Digoxin | Trimethoprim may increase serum digoxin concentrations by reducing renal clearance | Monitor digoxin levels; watch for signs of toxicity (nausea, visual disturbances, arrhythmia) |
| Rifampicin | Rifampicin is a potent CYP enzyme inducer that may reduce trimethoprim plasma concentrations | Potentially reduced trimethoprim efficacy; clinical monitoring advised |
| Dapsone | Both drugs may increase the serum concentrations of each other | Increased risk of side effects from both drugs; monitor closely |
| Zidovudine | Trimethoprim may increase zidovudine exposure by inhibiting its renal elimination | Monitor for zidovudine-related haematological toxicity |
| Pyrimethamine | Both drugs are folate antagonists; combined use potentiates antifolate effects | Increased risk of megaloblastic anaemia; supplement with folinic acid (leucovorin) if combination is necessary |
Trimethoprim can interfere with the Jaffé reaction used to measure serum creatinine, causing a falsely elevated creatinine reading. This occurs because trimethoprim competitively inhibits creatinine secretion in the renal proximal tubule, not because of actual kidney damage. This effect is reversible and resolves after the drug is discontinued. If your kidney function is being assessed during trimethoprim treatment, inform your doctor so that results can be interpreted correctly, or an alternative measurement (such as cystatin C) can be used.
What Is the Correct Dosage of Trimethoprim?
Always take trimethoprim exactly as your doctor or pharmacist has instructed. Do not alter your dose or stop the medication early without consulting your healthcare provider. Completing the full prescribed course is essential to ensure the infection is fully eradicated and to minimise the risk of antimicrobial resistance.
The dose of trimethoprim is determined by your doctor based on the type and severity of infection, your age, body weight, kidney function, and other individual factors. The following are general dosing guidelines based on international pharmacological references:
Adults
Acute Uncomplicated UTI (Cystitis)
150–200 mg twice daily (morning and evening), or 300 mg once daily at bedtime. The typical duration of treatment is 3 days for uncomplicated cystitis in women (as recommended by NICE and EAU guidelines), though some physicians may prescribe 5–7 days depending on clinical circumstances and local guidelines.
Long-term UTI Prophylaxis
100 mg once daily at bedtime. Prophylactic treatment is typically continued for 3–6 months, after which the need for ongoing prophylaxis should be reassessed. Clinical trials have demonstrated that this regimen significantly reduces the rate of UTI recurrence in women with frequent infections.
Children
Children Over 3 Months of Age
The dose is calculated individually by the prescribing physician based on the child's body weight and age. The oral suspension formulation (10 mg/ml) is typically used for children who cannot swallow tablets. A commonly used guideline dose is approximately 4 mg/kg twice daily, but this must be confirmed by the treating doctor.
Children Over 12 Years
The dosage for children over 12 years is the same as for adults: 150–200 mg twice daily or 300 mg at bedtime for acute UTI, and 100 mg at bedtime for long-term prophylaxis.
Patients with Kidney Impairment
Trimethoprim is primarily eliminated by the kidneys, so dose reduction is necessary in patients with impaired renal function. Your doctor will determine the appropriate dose based on your estimated glomerular filtration rate (eGFR) or creatinine clearance. In general, doses should be reduced or the dosing interval extended in patients with significant renal impairment to prevent drug accumulation and increased risk of side effects.
Missed Dose
If you forget to take a dose, take it as soon as you remember — unless it is nearly time for your next scheduled dose. In that case, skip the missed dose and continue with your normal dosing schedule. Do not take a double dose to make up for a forgotten one.
Overdose
If you take more trimethoprim than prescribed, or if a child accidentally ingests the medication, contact your doctor, hospital, or poison control centre immediately for a risk assessment and advice. Symptoms of overdose may include nausea, vomiting, dizziness, headache, confusion, and bone marrow depression. Treatment is supportive and may include gastric lavage (if the ingestion was recent) and folinic acid (leucovorin) administration to counteract the antifolate effects.
The score line on trimethoprim tablets is not intended for breaking the tablet in half. The tablet should be swallowed whole with water. If you have difficulty swallowing tablets, ask your doctor about the oral suspension formulation (10 mg/ml), which is available for both adults and children.
What Are the Side Effects of Trimethoprim?
Like all medicines, trimethoprim can cause side effects, although not everybody gets them. Most side effects are mild and transient, resolving after the completion of the treatment course. However, some rare adverse reactions can be serious and require prompt medical attention.
Swelling of the face, tongue, or throat; difficulty swallowing; hives with breathing difficulties (angioedema). Prolonged or severe diarrhoea (may indicate pseudomembranous colitis). An extremely severe allergic skin reaction with blisters or sores in the mouth, eyes, or genital area (Stevens-Johnson syndrome). Severe widespread skin damage with skin peeling (toxic epidermal necrolysis).
Common
May affect up to 1 in 10 people
- Nausea and vomiting
- Inflammation of the tongue (glossitis)
- Itching (pruritus)
- Skin rash
Uncommon
May affect up to 1 in 100 people
- Urticaria (hives)
- Changes in blood cell counts (increased or decreased numbers of certain blood cells)
Rare
May affect up to 1 in 1,000 people
- Aseptic meningitis (inflammation of the brain membranes)
- Hypersensitivity reactions (fever, allergic shock)
- Diarrhoea
- Photosensitivity (increased sensitivity to sunlight)
- Skin changes (sometimes severe, including erythema multiforme)
- Conjunctivitis (inflammation of the eye)
- Blood count changes (including agranulocytosis, thrombocytopenia)
- Angioedema (swelling of face, tongue, throat)
- Pseudomembranous colitis (severe intestinal inflammation)
- Stevens-Johnson syndrome (severe blistering skin reaction)
Very Rare
May affect up to 1 in 10,000 people
- Serum sickness-like reaction (skin rash, joint pain, swollen lymph nodes)
- Uveitis (inflammation inside the eye)
- Hyperkalaemia (elevated potassium levels in the blood)
- Toxic epidermal necrolysis (severe skin peeling)
Frequency Not Known
Cannot be estimated from available data
- Low levels of certain white blood cells (neutropenia, leucopenia)
- Methaemoglobinaemia (disorder affecting oxygen transport in the blood)
- Changes in liver enzyme values (seen on blood tests)
- Cholestasis (reduced bile flow from the liver)
- Cholestatic jaundice (yellowing of skin and eyes)
- Oral and genital thrush (fungal overgrowth)
The risk of haematological side effects (blood disorders) is increased with prolonged treatment courses, high doses, pre-existing folate deficiency, and in elderly patients. If your doctor prescribes trimethoprim for an extended period, they should arrange for regular blood count monitoring to detect any early signs of bone marrow suppression.
If you experience any side effects, including those not listed above, talk to your doctor or pharmacist. You can also report side effects directly to your national pharmacovigilance agency (for example, the FDA MedWatch programme in the United States, the Yellow Card Scheme in the United Kingdom, or the EMA EudraVigilance system in the European Union). By reporting side effects, you help improve the safety information available for this medication.
How Should You Store Trimethoprim?
Proper storage of trimethoprim is essential to maintain the medication's potency and safety throughout its shelf life. Follow these storage guidelines:
- Temperature: No special temperature requirements — store at standard room temperature (typically below 25°C / 77°F). Avoid exposure to excessive heat or freezing conditions.
- Light protection: Trimethoprim is light-sensitive. Store the tablets or suspension in the original packaging to protect them from light degradation.
- Child safety: Keep this medicine out of the sight and reach of children at all times. Consider using a child-resistant container if available.
- Expiry date: Do not use trimethoprim after the expiry date stated on the label and carton. The expiry date refers to the last day of the stated month.
- Disposal: Do not dispose of medicines via household waste or down the drain. Return unused or expired medications to your local pharmacy for safe disposal. These measures help protect the environment from pharmaceutical contamination.
If you are using the oral suspension formulation, check the manufacturer's instructions for any specific storage conditions after opening, such as refrigeration requirements or a reduced shelf life once opened.
What Does Trimethoprim Contain?
Active Ingredient
The active substance is trimethoprim. Each film-coated tablet contains 100 mg of trimethoprim. The oral suspension contains 10 mg/ml of trimethoprim.
Inactive Ingredients (Excipients)
The film-coated tablets contain the following excipients: lactose monohydrate, maize starch, pregelatinised starch, povidone, polysorbate 80, crospovidone, microcrystalline cellulose, magnesium stearate, hypromellose, and propylene glycol. These ingredients serve as binders, fillers, disintegrants, and coating agents to ensure consistent tablet quality, stability, and dissolution.
Appearance and Pack Sizes
Trimethoprim 100 mg tablets are white, film-coated, round, convex tablets with a score line, approximately 9 mm in diameter. The score line is not intended for splitting the tablet. Tablets are available in plastic containers of 30 or 100 tablets, depending on the formulation and market.
Frequently Asked Questions About Trimethoprim
Trimethoprim is a prescription antibiotic used primarily to treat uncomplicated lower urinary tract infections (UTIs), such as cystitis (bladder infections). It is also used for long-term prophylaxis in patients with recurrent UTIs. Trimethoprim works by inhibiting bacterial folate synthesis, which is essential for DNA replication and bacterial growth. It is effective against most common urinary pathogens, particularly Escherichia coli, which causes approximately 80% of uncomplicated UTIs.
Most patients begin to notice improvement in UTI symptoms within 24 to 48 hours of starting trimethoprim. However, it is crucial to complete the full prescribed course of treatment (typically 3 to 7 days) even if symptoms improve earlier. Stopping the antibiotic prematurely increases the risk of treatment failure, recurrent infection, and the development of antimicrobial resistance.
Trimethoprim is generally not recommended during pregnancy, especially during the first trimester, because it is a folate antagonist and may theoretically interfere with fetal neural tube development. If your doctor determines that the benefits outweigh the risks, trimethoprim may be prescribed alongside supplemental folic acid. Alternative antibiotics that are considered safer in pregnancy (such as nitrofurantoin in the second trimester or cefalexin) are usually preferred. Always consult your healthcare provider before taking any medication during pregnancy.
Yes, trimethoprim can significantly enhance the anticoagulant effect of warfarin by inhibiting its hepatic metabolism. This interaction raises the International Normalised Ratio (INR) and increases the risk of bleeding. If you are taking warfarin and are prescribed trimethoprim, your doctor should monitor your INR more frequently (typically within 3–5 days of starting the antibiotic) and may need to reduce your warfarin dose temporarily. Inform your doctor immediately if you notice any signs of unusual bleeding or bruising.
Yes, trimethoprim can cause hyperkalaemia (elevated blood potassium levels). This occurs because trimethoprim blocks epithelial sodium channels in the distal nephron of the kidney, reducing potassium excretion — a mechanism similar to the potassium-sparing diuretic amiloride. The risk is significantly increased when trimethoprim is taken with other potassium-raising medications such as spironolactone, ACE inhibitors, or angiotensin receptor blockers, and in patients with kidney impairment or diabetes. Symptoms of severe hyperkalaemia include muscle cramps, irregular heartbeat, weakness, nausea, and dizziness. Your doctor may check your potassium levels if you are at higher risk.
Trimethoprim is a single-agent antibiotic, while co-trimoxazole (also known as TMP-SMX) is a combination of trimethoprim and sulfamethoxazole. Both target the bacterial folate synthesis pathway, but at different steps, creating a synergistic antibacterial effect. For uncomplicated UTIs, trimethoprim alone is often preferred because it has a better side effect profile — co-trimoxazole carries additional risks of severe skin reactions (Stevens-Johnson syndrome), blood disorders, and hypersensitivity reactions related to the sulfonamide component. Co-trimoxazole may be preferred for certain other infections, such as Pneumocystis jirovecii pneumonia, where the synergistic combination is particularly effective.
References
- World Health Organization. WHO Model List of Essential Medicines – 23rd List. Geneva: WHO; 2023. Available from: who.int
- European Association of Urology (EAU). Guidelines on Urological Infections. EAU Guidelines; 2024. Available from: uroweb.org
- Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011;52(5):e103–e120. doi:10.1093/cid/ciq257
- National Institute for Health and Care Excellence (NICE). Urinary tract infection (lower): antimicrobial prescribing. NICE guideline [NG109]. 2018 (updated 2023). Available from: nice.org.uk
- British National Formulary (BNF). Trimethoprim. NICE/BNF; 2025. Available from: bnf.nice.org.uk
- European Medicines Agency (EMA). Trimethoprim – Summary of Product Characteristics. EMA; 2024.
- Antoniou T, Gomes T, Juurlink DN, et al. Trimethoprim-sulfamethoxazole–induced hyperkalemia in patients receiving inhibitors of the renin-angiotensin system: a population-based study. Arch Intern Med. 2010;170(12):1045–1049. doi:10.1001/archinternmed.2010.142
- Fralick M, Macdonald EM, Gomes T, et al. Co-trimoxazole and sudden death in patients receiving inhibitors of renin-angiotensin system: population based study. BMJ. 2014;349:g6196. doi:10.1136/bmj.g6196
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