Iloprost Waymade
Iloprost — Nebuliser solution for pulmonary arterial hypertension
Quick Facts About Iloprost Waymade
Key Takeaways About Iloprost Waymade
- Inhaled prostacyclin for PAH: Iloprost Waymade is a synthetic prostacyclin analogue administered via nebuliser to treat pulmonary arterial hypertension
- Selective pulmonary vasodilation: Inhaled delivery targets the lung vasculature directly, reducing systemic side effects compared with intravenous prostacyclins
- Multiple daily inhalations required: Treatment involves 6 to 9 nebulisation sessions per day, each lasting 4-10 minutes depending on device
- Must be supervised by specialists: Initiation and dose adjustment should only be performed by physicians experienced in pulmonary hypertension management
- Improves exercise capacity: Clinical trials demonstrate significant improvement in 6-minute walk distance and haemodynamic parameters in PAH patients
What Is Iloprost Waymade and What Is It Used For?
Iloprost Waymade is a nebuliser solution containing the active ingredient iloprost, a synthetic analogue of prostacyclin (PGI2). It is used to treat pulmonary arterial hypertension (PAH) in adult patients with WHO functional class III, improving exercise capacity and reducing symptoms such as breathlessness and fatigue.
Pulmonary arterial hypertension is a progressive and serious condition characterised by abnormally elevated blood pressure within the pulmonary arteries. These are the blood vessels that carry blood from the right side of the heart to the lungs. In PAH, the walls of these arteries become thickened and stiff, which increases resistance to blood flow and forces the right ventricle to work harder. Over time, this can lead to right heart failure and significantly reduced quality of life.
Iloprost belongs to a class of medications known as prostacyclin analogues. Prostacyclin is a naturally occurring substance in the body that dilates blood vessels, inhibits platelet aggregation, and has anti-inflammatory and cytoprotective properties. In patients with PAH, the prostacyclin pathway is impaired, contributing to vasoconstriction, vascular remodelling, and thrombosis within the pulmonary vasculature. Iloprost mimics the action of natural prostacyclin to counteract these processes.
When inhaled via a nebuliser, iloprost is delivered directly to the lung vasculature, where it causes selective dilation of pulmonary blood vessels. This targeted delivery offers a key advantage over intravenous prostacyclin analogues, as it reduces the degree of systemic vasodilation and associated side effects such as severe hypotension. The inhaled route allows iloprost to act preferentially on well-ventilated areas of the lungs, improving ventilation-perfusion matching.
The clinical efficacy of inhaled iloprost was established in the landmark AIR (Aerosolized Iloprost Randomized) study, a multicentre randomised controlled trial involving 203 patients with PAH and chronic thromboembolic pulmonary hypertension. The study demonstrated significant improvements in a combined endpoint of 6-minute walk distance and WHO functional class, with a responder rate of 16.8% in the iloprost group compared to 4.9% in the placebo group. Subsequent studies, including the STEP trial, confirmed additional benefits when iloprost was combined with the oral endothelin receptor antagonist bosentan.
How does Iloprost Waymade work in the body?
Iloprost exerts its pharmacological effects primarily through activation of the prostacyclin (IP) receptor on vascular smooth muscle cells and platelets. When iloprost binds to the IP receptor, it stimulates the enzyme adenylyl cyclase, which increases intracellular levels of cyclic adenosine monophosphate (cAMP). Elevated cAMP levels cause relaxation of vascular smooth muscle, leading to vasodilation, and inhibit platelet activation and aggregation.
Beyond vasodilation, iloprost has several additional biological effects that may be beneficial in PAH. These include anti-proliferative effects on vascular smooth muscle cells, which may help to slow the process of vascular remodelling. Iloprost also has cytoprotective effects on vascular endothelial cells and anti-inflammatory properties that may reduce the inflammatory component of pulmonary vascular disease.
After inhalation, iloprost reaches peak plasma concentrations within approximately 5 minutes. The drug has a short elimination half-life of approximately 20 to 30 minutes, which necessitates frequent dosing throughout the day. Iloprost is metabolised primarily via beta-oxidation of the carboxyl side chain, and the metabolites are excreted mainly in the urine. The rapid onset and short duration of action mean that the pulmonary vasodilatory effects are greatest immediately following each inhalation and diminish within 1-2 hours.
Iloprost Waymade is not a cure for pulmonary arterial hypertension. It is a symptomatic treatment that helps to reduce pulmonary vascular resistance and improve exercise capacity. Patients should continue all other prescribed PAH medications unless instructed otherwise by their specialist physician. Treatment goals include improving functional capacity, haemodynamics, and long-term outcomes.
What Should You Know Before Taking Iloprost Waymade?
Before using Iloprost Waymade, inform your doctor about all medical conditions, particularly bleeding disorders, low blood pressure, heart valve defects, and liver or kidney disease. Do not use if you are pregnant, breastfeeding, or have conditions where platelet inhibition could increase bleeding risk.
Iloprost Waymade is a potent medication with significant effects on the cardiovascular system and platelet function. Before initiating treatment, your specialist physician will perform a thorough assessment of your medical history, current medications, and overall health status. This evaluation is essential to ensure that iloprost therapy is appropriate and safe for you.
Contraindications
Iloprost Waymade should not be used in the following situations:
- Hypersensitivity: Known allergy to iloprost or any of the excipients in the formulation
- High bleeding risk: Conditions where the antiplatelet effects of iloprost could increase the risk of haemorrhage, such as active peptic ulcers, trauma, or intracranial haemorrhage
- Severe coronary heart disease or unstable angina: The vasodilatory effects may worsen myocardial ischaemia
- Myocardial infarction within the last 6 months: Haemodynamic changes could be dangerous in recent heart attack patients
- Decompensated heart failure not under close medical supervision: Severe right or left heart failure that is not adequately controlled
- Severe arrhythmias: Uncontrolled heart rhythm disturbances
- Cerebrovascular events within the last 3 months: Recent stroke or transient ischaemic attack
- Pulmonary veno-occlusive disease: Iloprost may worsen pulmonary oedema in this condition
- Congenital or acquired heart valve defects: Where myocardial function is impaired independently of pulmonary hypertension
Warnings and Precautions
Several important precautions should be considered during treatment with Iloprost Waymade:
Blood pressure monitoring: Iloprost can cause significant drops in systemic blood pressure, particularly at the start of treatment and during dose titration. Blood pressure should be monitored closely, especially in patients already taking antihypertensive medications. Patients should avoid standing up too quickly after inhalation sessions to minimise the risk of orthostatic hypotension and syncope (fainting).
Bronchospasm risk: Inhaled iloprost may provoke bronchospasm in patients with hyperreactive airways. This is particularly relevant for patients with concurrent asthma or chronic obstructive pulmonary disease (COPD). If bronchospasm occurs during treatment, the physician may need to consider adding a bronchodilator to the treatment regimen or discontinuing iloprost.
Hepatic impairment: Iloprost clearance is reduced in patients with liver disease. Dose adjustments may be necessary, and liver function should be monitored during treatment. Patients with severe hepatic impairment (Child-Pugh class C) should use iloprost with particular caution.
Renal impairment: Although iloprost is not primarily cleared by the kidneys, patients with significant renal impairment should be monitored carefully, as accumulation of metabolites may occur. Dialysis patients require careful dose titration.
Iloprost can cause a significant drop in blood pressure. Do not drive or operate heavy machinery immediately after taking a dose, particularly during the dose titration phase. If you experience dizziness, lightheadedness, or feel faint, sit or lie down immediately and contact your doctor. The risk is higher if you are also taking blood pressure-lowering medications.
Pregnancy and Breastfeeding
There is insufficient clinical data on the use of iloprost in pregnant women. Animal reproduction studies have shown adverse effects at doses several times higher than the recommended human dose, including delayed foetal development and skeletal abnormalities. Iloprost Waymade should not be used during pregnancy unless the potential benefit clearly justifies the potential risk to the foetus. Women of childbearing potential must use effective contraception during treatment.
It is not known whether iloprost or its metabolites are excreted in human breast milk. Given the potential for serious adverse effects in the nursing infant, breastfeeding is not recommended during treatment with Iloprost Waymade. If treatment is essential, the decision to discontinue breastfeeding or to discontinue the drug should take into account the importance of the drug to the mother.
How Does Iloprost Waymade Interact with Other Drugs?
Iloprost Waymade can interact with anticoagulants, antihypertensive agents, other vasodilators, and antiplatelet drugs. These interactions may increase the risk of bleeding or cause excessive blood pressure drops. Always inform your physician about all medications, supplements, and herbal products you are taking.
Drug interactions with iloprost are primarily related to its vasodilatory and antiplatelet properties. Because iloprost causes blood vessels to dilate and inhibits platelet aggregation, combining it with other drugs that have similar effects can lead to additive or synergistic interactions. Understanding these interactions is crucial for safe and effective treatment.
Major Interactions
The following drug classes have clinically significant interactions with iloprost:
| Drug / Class | Type of Interaction | Clinical Effect | Recommendation |
|---|---|---|---|
| Anticoagulants (warfarin, heparin, DOACs) | Pharmacodynamic | Increased bleeding risk due to additive antiplatelet and anticoagulant effects | Monitor INR and bleeding signs closely; dose adjustment of anticoagulant may be needed |
| Antihypertensives (ACE inhibitors, ARBs, calcium channel blockers) | Pharmacodynamic | Enhanced blood pressure lowering; risk of symptomatic hypotension and syncope | Monitor blood pressure closely; consider dose reduction of antihypertensive if needed |
| Other vasodilators (nitrates, PDE-5 inhibitors such as sildenafil, tadalafil) | Pharmacodynamic | Potentiated vasodilation; risk of severe hypotension | Use combination cautiously with close haemodynamic monitoring; PDE-5 inhibitors often used in PAH combination therapy under specialist supervision |
| Antiplatelet agents (aspirin, clopidogrel, prasugrel) | Pharmacodynamic | Additive inhibition of platelet function; increased bleeding risk | Avoid concurrent use unless clinically indicated; monitor for signs of bleeding |
| NSAIDs (ibuprofen, naproxen, diclofenac) | Pharmacodynamic | Increased gastrointestinal bleeding risk; potential reduction in iloprost efficacy | Use with caution; consider gastroprotection if concurrent use is necessary |
Minor Interactions
Some additional interactions to be aware of include the potential for iloprost to enhance the blood pressure-lowering effects of beta-blockers and diuretics. While these interactions are generally manageable, patients should be aware of symptoms of low blood pressure such as dizziness, lightheadedness, and visual disturbances. Additionally, although iloprost is not significantly metabolised by the cytochrome P450 enzyme system, patients should inform their doctor about all medications they are taking, including herbal supplements such as ginkgo biloba and garlic, which may have additional antiplatelet effects.
There are no known significant pharmacokinetic interactions with food or beverages. However, smoking may reduce the effectiveness of inhaled iloprost by causing bronchoconstriction and impairing drug delivery to the pulmonary vasculature. Patients are strongly advised to stop smoking during treatment.
What Is the Correct Dosage of Iloprost Waymade?
The recommended starting dose is 2.5 micrograms per inhalation session, which may be increased to 5 micrograms if the lower dose is well tolerated. Treatment involves 6 to 9 inhalation sessions per day during waking hours, with each session lasting approximately 4 to 10 minutes depending on the nebuliser device used.
Dosing of Iloprost Waymade must be individualised and supervised by a physician experienced in the management of pulmonary arterial hypertension. The dose is expressed as the amount of iloprost delivered at the mouthpiece of the nebuliser, not the amount placed in the nebuliser chamber. The difference is important because a proportion of the drug is lost during the nebulisation process.
Adults
Standard Adult Dosing
Starting dose: 2.5 micrograms of iloprost at the mouthpiece per inhalation session.
Maintenance dose: If the starting dose is well tolerated, the dose should be increased to 5 micrograms per inhalation session. If the 5 microgram dose causes intolerable side effects, it may be reduced back to 2.5 micrograms.
Frequency: 6 to 9 inhalation sessions per day, spread evenly throughout waking hours. Ideally, the interval between inhalations should be approximately 2 hours, but it should not be less than 2 hours.
Daily dose: Depending on the dose per session, the total daily inhaled dose ranges from 15 micrograms (6 sessions x 2.5 mcg) to 45 micrograms (9 sessions x 5 mcg).
| Patient Group | Starting Dose | Maintenance Dose | Frequency | Notes |
|---|---|---|---|---|
| Adults | 2.5 mcg per session | 5 mcg per session | 6-9 sessions/day | Increase only if 2.5 mcg is tolerated |
| Hepatic impairment | 2.5 mcg per session | Titrate cautiously | 6-9 sessions/day | Reduced clearance; monitor closely |
| Renal impairment (dialysis) | 2.5 mcg per session | Titrate cautiously | 6-9 sessions/day | No specific dose adjustment; caution advised |
Children
The safety and efficacy of iloprost in children and adolescents under 18 years of age have not been established. There are insufficient data from clinical studies in the paediatric population. Iloprost Waymade is therefore not recommended for use in children unless prescribed by a specialist in paediatric pulmonary hypertension with careful risk-benefit assessment. Some specialist centres have used inhaled iloprost off-label in children with PAH, but this practice requires individual evaluation and close monitoring.
Elderly
No specific dose adjustments are recommended for elderly patients solely on the basis of age. However, elderly patients are more likely to have impaired hepatic or renal function and to be taking concomitant medications that could interact with iloprost. Therefore, dose titration should be performed with particular caution in this population, with careful monitoring of blood pressure and side effects. The starting dose of 2.5 micrograms is recommended, with gradual dose increases as tolerated.
Missed Dose
If you miss a scheduled inhalation session, take the next dose at the usual time. Do not double the dose or take extra inhalations to compensate for a missed session. Maintain the recommended minimum interval of approximately 2 hours between inhalation sessions. If you frequently miss doses, discuss strategies for improving adherence with your healthcare team, as consistent dosing is important for optimal therapeutic effect.
Overdose
No cases of overdose with inhaled iloprost have been well documented. Based on the pharmacological properties of iloprost, an overdose would be expected to cause symptoms related to excessive vasodilation and platelet inhibition. Potential symptoms include severe hypotension, headache, flushing, nausea, vomiting, diarrhoea, and an increased risk of bleeding. In the event of a suspected overdose, treatment should be supportive and symptomatic. Stop the inhalation immediately and monitor blood pressure closely. There is no specific antidote for iloprost.
Iloprost Waymade must be used with a compatible nebuliser device. The duration of each inhalation session depends on the specific nebuliser used: approximately 4-10 minutes with an appropriate device. Always follow the manufacturer's instructions for your specific nebuliser. Do not mix iloprost solution with other medications in the nebuliser chamber. Clean the device regularly as directed to ensure consistent drug delivery.
What Are the Side Effects of Iloprost Waymade?
The most common side effects of Iloprost Waymade include vasodilation (flushing), headache, cough, jaw pain, nausea, hypotension, and dizziness. Most side effects are dose-related and often diminish over time. Serious side effects such as syncope (fainting) and severe hypotension may occur and require medical attention.
Like all medicines, Iloprost Waymade can cause side effects, although not everybody gets them. Many of the side effects are related to the vasodilatory mechanism of action of iloprost and tend to be more prominent during the dose titration phase when the body is adjusting to the medication. The following list categorises adverse effects by their frequency of occurrence based on clinical trial data and post-marketing surveillance.
Very Common
- Vasodilation (flushing, warmth, redness of skin)
- Headache
- Cough
- Hypotension (low blood pressure)
- Nausea
Common
- Jaw pain (trismus) — often described as a tightness or ache in the jaw
- Dizziness and lightheadedness
- Diarrhoea
- Vomiting
- Pharyngolaryngeal pain (throat discomfort)
- Syncope (fainting)
- Peripheral oedema (swelling of hands and feet)
- Chest discomfort
- Rash
Uncommon
- Bronchospasm (wheezing and difficulty breathing)
- Thrombocytopenia (low platelet count)
- Tachycardia (rapid heartbeat)
- Haemorrhage (bleeding) at various sites
- Dysgeusia (altered taste)
- Oral or tongue irritation
Rare
- Pulmonary oedema (especially in patients with veno-occlusive disease)
- Severe hypersensitivity or anaphylactoid reactions
- Renal failure
- Pulmonary haemorrhage
Most side effects associated with inhaled iloprost are mild to moderate in severity and are related to the drug's vasodilatory action. Flushing and headache are the most frequently reported and tend to occur shortly after each inhalation session. These effects typically diminish within 30-60 minutes as the drug's effects wear off. With continued treatment, many patients find that these side effects become less pronounced as the body develops some tolerance.
Cough is a common side effect that is related to the inhalation route of administration rather than the pharmacological action of iloprost itself. Using proper inhalation technique and taking slow, steady breaths during nebulisation can help to minimise coughing. If cough is persistent and troublesome, your doctor may consider a pre-treatment bronchodilator.
Jaw pain is a characteristic side effect of prostacyclin analogues and may be noticed particularly during eating. It is typically mild and intermittent but can be bothersome. The mechanism is believed to involve vasodilation of blood vessels in the jaw and masticatory muscles. If jaw pain is severe, reducing the dose from 5 micrograms to 2.5 micrograms per session may help.
Contact your doctor or seek emergency medical attention if you experience any of the following: severe or prolonged fainting episodes, difficulty breathing that worsens after inhalation, signs of bleeding (unusual bruising, blood in urine or stools, prolonged bleeding from cuts), severe chest pain, or signs of an allergic reaction (swelling of face, lips, tongue, or throat; difficulty breathing; severe rash).
How Should You Store Iloprost Waymade?
Store Iloprost Waymade below 25°C in the original packaging to protect from light. Do not freeze. Discard any remaining solution after opening an ampoule. Keep out of reach and sight of children. Do not use after the expiry date.
Proper storage of Iloprost Waymade is essential to maintain the stability and effectiveness of the medication. Iloprost is a sensitive compound that can degrade when exposed to excessive heat, light, or improper conditions. Following storage guidelines ensures that each dose delivers the intended amount of active medication.
The nebuliser solution should be stored at a temperature below 25 degrees Celsius (77 degrees Fahrenheit). Avoid storing ampoules near heat sources, in direct sunlight, or on window sills. Do not refrigerate or freeze the solution, as extreme cold can alter the formulation. Keep the ampoules in their original cardboard packaging until use to protect them from light exposure, which can cause chemical degradation of iloprost.
Each ampoule of Iloprost Waymade is intended for single use only. After opening an ampoule, any solution remaining in the ampoule or nebuliser chamber after the inhalation session should be discarded safely. Do not save or re-use leftover solution, as the sterility of the product cannot be guaranteed once opened. Do not transfer the solution into other containers.
Always check the expiry date printed on both the outer carton and the individual ampoule before use. Do not use Iloprost Waymade after the expiry date has passed. Expired medication may not be effective and could potentially be harmful. Return any expired or unused medication to your pharmacist for safe disposal. Do not dispose of medications via household waste or wastewater systems.
What Does Iloprost Waymade Contain?
Each millilitre of Iloprost Waymade nebuliser solution contains 20 micrograms of iloprost (as iloprost trometamol). The solution also contains trometamol, ethanol, sodium chloride, hydrochloric acid (for pH adjustment), and water for injections.
Understanding the composition of your medication can be important, particularly if you have known allergies or sensitivities to specific excipients. The following provides a detailed breakdown of the active and inactive ingredients in Iloprost Waymade:
Active ingredient: Iloprost (as iloprost trometamol) — 20 micrograms per millilitre. Iloprost is the pharmacologically active compound responsible for the therapeutic effects. It is a synthetic analogue of prostacyclin with modifications to improve chemical stability and receptor selectivity compared with natural prostacyclin, which has a very short half-life of only 2-3 minutes.
Excipients (inactive ingredients):
- Trometamol (tromethamine): A buffering agent that helps to maintain the pH of the solution within the optimal range for stability and tolerability during inhalation
- Ethanol: Present in small quantities as a co-solvent to ensure complete dissolution of iloprost in the aqueous solution
- Sodium chloride: Added to adjust the tonicity (salt concentration) of the solution, making it closer to physiological levels and reducing irritation during inhalation
- Hydrochloric acid: Used in minute amounts for pH adjustment during manufacturing
- Water for injections: The base solvent that constitutes the majority of the solution volume
The solution is clear and colourless to slightly yellow. Do not use the solution if it appears discoloured, cloudy, or contains visible particles. Each ampoule contains either 1 ml or 2 ml of solution, depending on the pack size. The solution is sterile and pyrogen-free.
Patients with known intolerance to ethanol should be aware that small amounts are present in the formulation. The ethanol content is minimal and unlikely to cause effects in most patients, but this should be discussed with the prescribing physician if there are concerns.
Frequently Asked Questions About Iloprost Waymade
Iloprost Waymade is used to treat pulmonary arterial hypertension (PAH), a condition where blood pressure in the pulmonary arteries is abnormally elevated. It is administered by inhalation using a nebuliser device and works by dilating blood vessels in the lungs, reducing pulmonary vascular resistance, and improving exercise capacity. It is typically prescribed for patients with WHO functional class III PAH who have not responded adequately to other treatments or as part of a combination therapy regimen.
Treatment with Iloprost Waymade involves 6 to 9 inhalation sessions per day during waking hours. Each session lasts approximately 4 to 10 minutes depending on the nebuliser device used. The sessions should be spread evenly throughout the day, with a minimum interval of approximately 2 hours between doses. Your doctor will determine the appropriate number of daily sessions based on your individual response and tolerability.
The most common side effects include flushing (vasodilation), headache, cough, low blood pressure, and nausea. Jaw pain, dizziness, diarrhoea, and throat discomfort are also commonly reported. Most side effects are mild to moderate, related to the vasodilatory action of the drug, and tend to diminish over time. If side effects are troublesome, the dose can be reduced from 5 micrograms to 2.5 micrograms per session.
Iloprost Waymade should not be used during pregnancy unless the potential benefit clearly justifies the potential risk to the foetus. Animal studies have shown adverse reproductive effects. Women of childbearing potential should use effective contraception during treatment. If you become pregnant while using iloprost, contact your doctor immediately. The decision to continue or discontinue treatment will depend on the severity of your PAH and available alternative therapies.
Yes, Iloprost Waymade is frequently used as part of combination therapy for PAH. The STEP trial demonstrated additional benefits when inhaled iloprost was combined with the endothelin receptor antagonist bosentan. Iloprost may also be used alongside phosphodiesterase-5 inhibitors (such as sildenafil or tadalafil). However, combination therapy should only be initiated and managed by a specialist in pulmonary hypertension, as additive vasodilatory effects require careful monitoring of blood pressure and haemodynamics.
Store Iloprost Waymade below 25 degrees Celsius in the original packaging to protect from light. Do not freeze. Each ampoule is for single use only — discard any remaining solution after your inhalation session. Do not use the medication after the expiry date. Keep out of reach and sight of children. Return unused or expired medication to your pharmacist for safe disposal.
References
All medical information on this page is based on peer-reviewed research, international guidelines, and regulatory authority data. The following sources were consulted:
- Olschewski H, Simonneau G, Galié N, et al. Inhaled iloprost for severe pulmonary hypertension. New England Journal of Medicine. 2002;347(5):322-329. doi:10.1056/NEJMoa020204
- McLaughlin VV, Oudiz RJ, Frost A, et al. Randomized study of adding inhaled iloprost to existing bosentan in pulmonary arterial hypertension (STEP). American Journal of Respiratory and Critical Care Medicine. 2006;174(11):1257-1263.
- Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. European Heart Journal. 2022;43(38):3618-3731.
- European Medicines Agency (EMA). Iloprost — Summary of Product Characteristics. Available at: www.ema.europa.eu
- Galié N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. European Heart Journal. 2016;37(1):67-119.
- World Health Organization. WHO Model List of Essential Medicines — 23rd List, 2023.
- British National Formulary (BNF). Iloprost. National Institute for Health and Care Excellence (NICE).
- Hoeper MM, Schwarze M, Ehlerding S, et al. Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue. New England Journal of Medicine. 2000;342(25):1866-1870.
Editorial Team
This article has been written, fact-checked, and medically reviewed by the iMedic Medical Editorial Team, comprising licensed physicians with specialist qualifications in pulmonary medicine, pharmacology, and internal medicine.
Licensed physicians with specialist knowledge in pulmonary medicine and pharmacology. All content is written following evidence-based medicine principles and the GRADE evidence framework.
Independent medical review board consisting of specialist physicians who verify all clinical claims against current international guidelines (ESC/ERS 2022, EMA SmPC, WHO).
Editorial standards: All content follows the iMedic editorial process, which includes systematic literature review, medical writing by qualified physicians, independent peer review, and regular updates when new evidence emerges. We declare no conflicts of interest and receive no pharmaceutical industry funding. For more details, see our editorial standards.