Levosimendan Amdipharm

Name: Levosimendan Amdipharm: Uses, Dosage & Side Effects
Creator: iMedic Medical Editorial Team
Published: 2025-07-14T08:00:00+00:00

Calcium Sensitizer (Inodilator) for Acute Decompensated Heart Failure

Rx – Prescription Only ATC: C01CX08 Calcium Sensitizer

Active Ingredient: Levosimendan
Available Form: Concentrate for IV infusion
Strength: 2.5 mg/ml
Common Brands: Simdax, Levosimendan Tillomed, Kalceks

✓ Medically reviewed | Last reviewed: January 29, 2026 | Evidence level: 1A

Levosimendan Amdipharm is an intravenous calcium sensitizer used for the short-term treatment of acute decompensated severe chronic heart failure when conventional therapy is insufficient. It works through a dual mechanism: enhancing cardiac contractility by sensitizing troponin C to calcium and producing vasodilation through ATP-sensitive potassium channel opening. Administered only in hospital settings under close hemodynamic monitoring, levosimendan improves cardiac output, reduces pulmonary congestion, and relieves dyspnea. Its hemodynamic effects persist for up to 7–9 days after the infusion ends.

Published: July 14, 2025

Reading time: 14 minutes

Reviewed: January 29, 2026

Quick Facts About Levosimendan Amdipharm

Active Ingredient

Levosimendan

Calcium sensitizer

Drug Class

Inodilator

Calcium sensitizer

ATC Code

C01CX08

Other cardiac stimulants

Common Use

Heart Failure

Acute decompensated

Available Form

IV Infusion

2.5 mg/ml concentrate

Prescription Status

Rx Only

Hospital use only

Key Takeaways About Levosimendan Amdipharm

Dual mechanism: Levosimendan enhances cardiac contractility through calcium sensitization and reduces cardiac workload through vasodilation, improving both pump function and hemodynamics.
Hospital-only medicine: It is administered exclusively as an intravenous infusion in hospital intensive care or cardiac care units under continuous hemodynamic monitoring.
Prolonged effect: Hemodynamic benefits persist for 7 to 9 days after a single 24-hour infusion due to the long-acting active metabolite OR-1896.
Key monitoring: Blood pressure, heart rate, ECG, and clinical status are continuously monitored during and for 4–5 days after infusion to detect hypotension or arrhythmias.
Contains ethanol: Each 5 ml vial contains approximately 3,925 mg of ethanol (anhydrous), which may be relevant for patients with liver disease, epilepsy, or alcohol dependence.

What Is Levosimendan Amdipharm and What Is It Used For?

Levosimendan Amdipharm is a calcium sensitizer and potassium channel opener (inodilator) given as an intravenous infusion to treat acute decompensated severe chronic heart failure when standard treatments alone are insufficient.

Levosimendan Amdipharm contains the active substance levosimendan at a concentration of 2.5 mg/ml. It is supplied as a concentrated solution that must be diluted before administration. The diluted solution is given as an intravenous infusion (drip) in a hospital setting where your heart function and vital signs can be closely monitored by medical professionals.

Heart failure occurs when the heart muscle is unable to pump blood efficiently enough to meet the body's needs. In acute decompensated heart failure, the condition worsens suddenly, leading to fluid accumulation in the lungs (pulmonary congestion), severe shortness of breath, and reduced blood flow to vital organs. When standard treatments such as diuretics (water pills), ACE inhibitors, and other conventional heart failure medications fail to provide adequate relief, levosimendan may be considered as an additional short-term therapy.

Levosimendan works through two complementary mechanisms. First, it sensitizes the cardiac contractile protein troponin C to calcium, which means the heart muscle contracts more effectively without requiring higher levels of intracellular calcium. This is fundamentally different from traditional inotropes like dobutamine or milrinone, which increase calcium levels inside heart cells and can be associated with higher oxygen consumption and arrhythmia risk. Second, levosimendan opens ATP-sensitive potassium channels in vascular smooth muscle cells, leading to relaxation of blood vessels. This vasodilation reduces the resistance the heart has to pump against (afterload) and decreases the volume of blood returning to the heart (preload), thereby relieving pulmonary congestion.

The combined effect is improved cardiac output, decreased pulmonary wedge pressure, relief from breathlessness, and enhanced oxygen delivery to vital organs. The clinical improvement typically becomes apparent within the first few hours of infusion and continues for several days after the infusion is stopped, owing to the formation of the long-acting active metabolite OR-1896, which has a half-life of approximately 75–80 hours.

Approved Indication

Levosimendan Amdipharm is approved for the short-term treatment of acutely decompensated severe chronic heart failure (ADHF) in adults, specifically in situations where conventional therapy is considered insufficient and when inotropic support is deemed appropriate. It is not intended for long-term or repeated routine use, although repeat treatment may be considered by the treating physician in selected cases.

What Should You Know Before Receiving Levosimendan Amdipharm?

Levosimendan Amdipharm must not be used in patients with severe hypotension, severe tachycardia, severe hepatic or renal impairment, mechanical cardiac obstruction, or a history of Torsades de Pointes. Special caution is needed if you have kidney disease, liver disease, anemia, or cardiac arrhythmias.

Contraindications

You must not receive Levosimendan Amdipharm if any of the following apply:

Allergy: Known hypersensitivity to levosimendan or any of the excipients (povidone, citric acid, anhydrous ethanol).
Severe hypotension: Very low blood pressure that could be dangerously worsened by the vasodilatory effects of levosimendan.
Severe tachycardia: Abnormally rapid heart rate, as levosimendan may further increase heart rate.
Severe renal impairment: Severely reduced kidney function, because active metabolites accumulate and clearance is impaired.
Severe hepatic impairment: Severely reduced liver function, which affects drug metabolism and can lead to unpredictable drug levels.
Mechanical obstruction: Cardiac conditions that obstruct the filling or emptying of the ventricles (such as severe aortic stenosis or hypertrophic obstructive cardiomyopathy).
History of Torsades de Pointes: A specific type of ventricular arrhythmia that could be triggered or worsened.

Warnings and Precautions

Speak with your doctor or nurse before receiving Levosimendan Amdipharm if you have:

Mild to moderate kidney disease: Extra caution and monitoring is required, as reduced renal clearance may prolong the duration of drug effects.
Mild to moderate liver disease: Although dose adjustment may not be necessary, careful monitoring is advised since levosimendan is metabolized by the liver.
Anemia with chest pain: Low hemoglobin combined with ischemic symptoms requires special consideration, as any further reduction in blood pressure or increase in heart rate could exacerbate myocardial ischemia.
Rapid heart rate or irregular heart rhythm: Including atrial fibrillation. Your doctor will exercise additional caution, as levosimendan can cause tachycardia and other arrhythmias.
Low potassium levels (hypokalemia): This electrolyte imbalance should be corrected before starting treatment, as it increases the risk of arrhythmias.

Important monitoring: Your medical team will continuously monitor your blood pressure, heart rate, ECG (heart rhythm), and clinical status during the infusion and for up to 4–5 days afterward. The hemodynamic effects of levosimendan persist well beyond the infusion period due to the active metabolite OR-1896.

Pregnancy and Breastfeeding

If you are pregnant, think you may be pregnant, plan to become pregnant, or are breastfeeding, inform your doctor before receiving this medicine.

Pregnancy: The safety of levosimendan during pregnancy has not been established in humans. Animal studies have shown insufficient data regarding reproductive toxicity. Your doctor will carefully weigh the potential benefit to you against any possible risk to your unborn child before deciding to use this medicine.

Breastfeeding: Evidence suggests that levosimendan and its metabolites pass into breast milk. To avoid potential cardiovascular effects in the nursing infant, breastfeeding should be discontinued during and after treatment with Levosimendan Amdipharm. Your doctor will advise on when it is safe to resume breastfeeding.

Children and Adolescents

Levosimendan Amdipharm should not be given to children or adolescents under 18 years of age, as the safety and efficacy in this population have not been established.

Ethanol Content

This medicine contains 3,925 mg of alcohol (anhydrous ethanol) per 5 ml vial, equivalent to approximately 98% v/v. The amount in one 5 ml vial corresponds to approximately 99 ml of beer or 41 ml of wine. This may be relevant for:

Patients with liver disease or epilepsy
Pregnant or breastfeeding women
Patients with current or previous alcohol dependence
The effect of other medicines (alcohol may alter their efficacy)

However, the effects of the ethanol content are generally reduced because levosimendan is typically administered slowly over 24 hours.

How Does Levosimendan Amdipharm Interact with Other Drugs?

Levosimendan may enhance the blood-pressure-lowering effects of other cardiovascular medications. Notable interactions include combined hypotension with IV inotropes and nitrates, and increased orthostatic hypotension with isosorbide mononitrate.

Inform your doctor about all medicines you are currently taking, have recently taken, or might take. Because levosimendan lowers blood pressure and causes vasodilation, combining it with other cardiovascular medications that also lower blood pressure can result in additive hypotensive effects that may require dose adjustments or enhanced monitoring.

Notable Drug Interactions

Interacting Drug	Type	Effect	Clinical Action
Isosorbide mononitrate	Major	Enhanced orthostatic hypotension (drop in blood pressure when standing up)	Close blood pressure monitoring; avoid concurrent use if possible
IV inotropes (dobutamine, milrinone)	Moderate	Additive blood pressure lowering; enhanced inotropic effect	Monitor hemodynamics closely; adjust infusion rates as needed
Nitroglycerin (glyceryl trinitrate)	Moderate	Additive vasodilation and hypotension	Monitor blood pressure; reduce nitrate dose if necessary
ACE inhibitors / ARBs	Moderate	Additive blood pressure reduction	Continue standard heart failure therapy; monitor BP closely
Beta-blockers	Minor	No clinically significant pharmacokinetic interaction; beta-blockers do not reduce levosimendan efficacy	Continue beta-blocker therapy; no dose adjustment needed
Digoxin	Minor	No clinically relevant pharmacokinetic interaction reported	No dose adjustment; standard monitoring

Note for healthcare professionals: Levosimendan does not inhibit cytochrome P450 enzymes (CYP1A2, CYP2A6, CYP2C19, CYP2D6, CYP2E1, CYP3A4) at therapeutic concentrations, which minimizes the potential for pharmacokinetic drug-drug interactions. However, pharmacodynamic interactions with other vasodilators and inotropic agents should always be anticipated.

What Is the Correct Dosage of Levosimendan Amdipharm?

Levosimendan Amdipharm is administered as an intravenous infusion in hospital. Treatment typically starts with an optional loading dose over 10 minutes, followed by a continuous infusion for up to 24 hours. The dose is individually titrated based on the patient's hemodynamic response.

Levosimendan Amdipharm is only for use in hospitals with adequate monitoring facilities and expertise in using inotropic agents. The concentrate must be diluted before administration and is given through either a peripheral or central intravenous line. Your doctor will determine the most appropriate dose for you based on your clinical condition and response to treatment.

Administration Protocol

Optional Loading Dose

An initial loading dose of 6–12 mcg/kg may be given as an intravenous infusion over 10 minutes. This provides a rapid onset of hemodynamic effect. However, the loading dose may be omitted in patients who are hypotensive or at risk of excessive blood pressure reduction, as it can cause a significant drop in blood pressure.

Continuous Infusion

Following the optional loading dose, a continuous infusion is administered at a rate of 0.05–0.2 mcg/kg/min for up to 24 hours. The recommended starting rate is typically 0.1 mcg/kg/min. Based on the patient's hemodynamic response, the rate may be:

Decreased to 0.05 mcg/kg/min if there is excessive hypotension or tachycardia
Increased to 0.2 mcg/kg/min if the response is insufficient and the patient is tolerating the medication well

Dilution Instructions

Target Concentration	Volume of Concentrate	Diluent (5% Glucose)	Total Volume
0.025 mg/ml	5 ml (12.5 mg)	500 ml	505 ml
0.05 mg/ml	10 ml (25 mg)	500 ml	510 ml

Important: Do not dilute levosimendan to a concentration higher than 0.05 mg/ml, as opalescence and precipitation may occur. The diluted solution must be used within 24 hours. Always inspect the diluted solution visually for particles and discoloration before administration.

Renal Impairment

Levosimendan should be used with caution in patients with mild to moderate renal impairment. The active metabolite OR-1896 is partially cleared by the kidneys, and reduced renal function may lead to prolonged hemodynamic effects. Levosimendan must not be used in patients with severe renal impairment.

Hepatic Impairment

In patients with mild to moderate hepatic impairment, levosimendan should be used with caution, although no specific dose adjustment appears necessary based on available data. The drug is metabolized in the liver, and patients with liver dysfunction should be monitored more closely. Levosimendan must not be used in patients with severe hepatic impairment.

Overdose

If too much levosimendan is administered, the most likely effects are an excessive drop in blood pressure (hypotension) and an increase in heart rate (tachycardia). Treatment of overdose is supportive and symptomatic, based on the patient's clinical status. There is no specific antidote. Due to the long duration of action of the active metabolite, observation may be required for an extended period. In cases of severe hypotension, intravenous fluids and vasopressors may be necessary.

What Are the Side Effects of Levosimendan Amdipharm?

The most common side effects of levosimendan are tachycardia (rapid heart rate), hypotension (low blood pressure), and headache. Common effects include atrial fibrillation, extrasystoles, hypokalemia, dizziness, and gastrointestinal disturbances. Tell your doctor immediately if you experience any side effects.

Like all medicines, Levosimendan Amdipharm can cause side effects, although not everybody gets them. Because levosimendan is given in a hospital intensive care setting, side effects are closely monitored and managed by the medical team. The severity of side effects often reflects the underlying severity of heart failure rather than the drug itself.

Seek immediate medical attention if you experience severe dizziness or fainting (signs of excessive blood pressure drop), rapid or irregular heartbeat, difficulty breathing, or signs of an allergic reaction (rash, itching, swelling). In the hospital setting, your care team will be monitoring for these continuously.

Very Common

May affect more than 1 in 10 people

Tachycardia (abnormally rapid heart rate)
Hypotension (low blood pressure)
Headache

Common

May affect up to 1 in 10 people

Hypokalemia (low potassium levels in the blood)
Insomnia (difficulty sleeping)
Dizziness
Atrial fibrillation (irregular heart rhythm)
Extrasystoles (extra heartbeats)
Heart failure worsening
Myocardial ischemia (reduced blood and oxygen supply to the heart)
Nausea
Constipation
Diarrhea
Vomiting
Anemia (low red blood cell count)

Frequency Not Known

Cannot be estimated from available data

Hypersensitivity reactions (may include rash and itching)
Ventricular fibrillation (a serious type of irregular heartbeat where the ventricles quiver instead of pumping properly)

Your medical team will monitor you continuously during the infusion and can slow down the infusion rate or stop it entirely if side effects occur. Many of these side effects are related to the pharmacological action of the drug (lowering blood pressure, increasing heart rate) and can be managed by adjusting the infusion rate.

It is important to understand that patients receiving levosimendan typically have severe heart failure with multiple comorbidities and are on several other medications. Therefore, some of the symptoms listed above may be related to the underlying condition rather than the medication itself. Your treating physician will carefully evaluate any new symptoms in context.

Reporting side effects: If you experience any side effects, whether listed above or not, talk to your doctor, pharmacist, or nurse. You can also report suspected side effects to your national medicines regulatory authority (e.g., the EMA in Europe, the FDA in the United States, or the MHRA in the United Kingdom).

How Should Levosimendan Amdipharm Be Stored?

Levosimendan Amdipharm must be stored in a refrigerator at 2°C–8°C. Do not freeze. Once diluted, the solution must be used within 24 hours.

Proper storage of Levosimendan Amdipharm is essential to maintain its potency and safety. The following storage requirements apply:

Temperature: Store in a refrigerator at 2°C to 8°C (36°F to 46°F).
Do not freeze: Freezing can damage the formulation and render it unsuitable for use.
After dilution: The diluted solution should be used within 24 hours. Any unused solution after this time must be discarded.
Expiry date: Do not use this medicine after the expiry date stated on the carton and vial label after "EXP." The expiry date refers to the last day of that month.
Keep out of sight and reach of children.
Disposal: Do not throw away medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures help to protect the environment.

In the hospital setting, the pharmacy and nursing staff are responsible for proper storage and preparation. The concentrated solution is a clear yellow to orange liquid. Before administration, healthcare professionals will visually inspect the diluted solution for particles and discoloration. Cloudy or discolored solutions must not be used.

What Does Levosimendan Amdipharm Contain?

Each milliliter of Levosimendan Amdipharm concentrate contains 2.5 mg of levosimendan as the active substance. Excipients include povidone, citric acid, and anhydrous ethanol.

Active Substance

The active ingredient is levosimendan 2.5 mg/ml. Levosimendan is the (R)-enantiomer of simendan, a pyridazinone-dinitrile derivative. It acts as a calcium sensitizer by binding to the N-terminal domain of cardiac troponin C in a calcium-dependent manner, thereby stabilizing the calcium-bound conformation and enhancing cardiac contractility.

Excipients (Inactive Ingredients)

Povidone: A pharmaceutical excipient used as a solubilizing and stabilizing agent.
Citric acid: Used to maintain the appropriate pH of the solution.
Ethanol (anhydrous): Used as a co-solvent. Each 5 ml vial contains approximately 3,925 mg of ethanol (equivalent to about 98% v/v).

Appearance and Pack Sizes

Levosimendan Amdipharm is a clear yellow to orange concentrated solution supplied in Type I glass vials containing 5 ml. Each vial delivers 12.5 mg of levosimendan. Available pack sizes are 1, 4, or 10 vials. Not all pack sizes may be marketed in all countries.

Marketing Authorization Holder

Amdipharm Limited, Dublin 9, Ireland.

Frequently Asked Questions About Levosimendan Amdipharm

What is Levosimendan Amdipharm used for?

Levosimendan Amdipharm is used for the short-term treatment of acute decompensated severe chronic heart failure. It is prescribed when standard heart failure medications (such as diuretics, ACE inhibitors, and beta-blockers) are not providing sufficient relief. The drug is administered as an intravenous infusion in a hospital setting, typically in an intensive care or cardiac care unit, where patients can be closely monitored.

It works by improving the heart's ability to pump blood while simultaneously relaxing blood vessels, which reduces the workload on the heart and relieves symptoms like severe breathlessness and fluid buildup in the lungs.

How long does a levosimendan infusion take?

A typical levosimendan infusion consists of two phases: an optional loading dose given over 10 minutes, followed by a continuous infusion that usually lasts up to 24 hours. However, the total duration is determined by the treating physician based on the patient's clinical response and hemodynamic status.

One of the unique features of levosimendan is that its beneficial effects on the heart continue for 7 to 9 days after the infusion is stopped. This prolonged effect is due to the formation of an active metabolite called OR-1896, which has a long half-life. Your medical team may continue to monitor you for 4 to 5 days after the infusion ends.

What are the most common side effects of levosimendan?

The most common side effects (affecting more than 1 in 10 patients) are tachycardia (rapid heart rate), hypotension (low blood pressure), and headache. These effects are directly related to the drug's mechanism of action — it increases heart rate as a reflex response to vasodilation and blood pressure lowering.

Common side effects (up to 1 in 10) include atrial fibrillation, extrasystoles, dizziness, insomnia, nausea, constipation, diarrhea, vomiting, low potassium levels, and anemia. All side effects are closely monitored during hospitalization, and the infusion rate can be adjusted or stopped if needed.

How does levosimendan differ from dobutamine and milrinone?

Levosimendan works through a fundamentally different mechanism compared to dobutamine and milrinone. Dobutamine is a beta-adrenergic agonist that increases intracellular calcium levels to improve contractility, while milrinone is a phosphodiesterase-3 inhibitor that prevents the breakdown of cyclic AMP, also raising intracellular calcium.

Levosimendan, by contrast, sensitizes cardiac myofilaments to existing calcium without significantly increasing intracellular calcium levels. This means it enhances contractility without proportionally increasing myocardial oxygen consumption, which is a significant advantage in patients with ischemic heart disease. Additionally, levosimendan's vasodilatory properties reduce both preload and afterload, and its effects last 7–9 days after a single infusion due to active metabolites, whereas dobutamine and milrinone effects cease shortly after stopping the infusion.

Can levosimendan be given more than once?

Repeat administration of levosimendan may be considered in patients who have previously responded well to treatment and who experience a subsequent episode of acute decompensation. Some clinical studies and real-world experience have explored intermittent or repeated levosimendan infusions, particularly in patients with advanced heart failure.

However, the decision to repeat treatment must be made by the treating physician on an individual basis, taking into account the patient's overall clinical status, response to previous treatment, and current hemodynamic parameters. There should be an adequate interval between infusions to allow the effects of the previous dose and its metabolites to diminish.

Is levosimendan safe during pregnancy and breastfeeding?

The safety of levosimendan during pregnancy has not been established. Animal studies have provided insufficient data regarding potential reproductive toxicity. Levosimendan should only be used during pregnancy when the potential benefit to the mother clearly justifies the potential risk to the fetus. This is a clinical decision made by the treating physician in emergency situations.

Regarding breastfeeding, there is evidence that levosimendan and its metabolites can pass into breast milk. To avoid possible cardiovascular side effects in the nursing infant, breastfeeding should be stopped during treatment and for a period after the infusion ends (your doctor will advise on the appropriate duration given the long-acting metabolite).

References

This article is based on the approved Summary of Product Characteristics (SmPC) for Levosimendan Amdipharm, international clinical guidelines, and peer-reviewed medical literature. All information has been independently reviewed by our medical editorial team.

European Medicines Agency (EMA). Levosimendan Amdipharm – Summary of Product Characteristics. Last updated December 2025. Available from: www.ema.europa.eu
McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42(36):3599–3726. doi:10.1093/eurheartj/ehab368
Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. Circulation. 2022;145(18):e895–e1032. doi:10.1161/CIR.0000000000001063
Packer M, Colucci W, Fisher L, et al. Effect of levosimendan on the short-term clinical course of patients with acutely decompensated heart failure. JACC Heart Fail. 2013;1(2):103–111. doi:10.1016/j.jchf.2012.12.004
Mebazaa A, Nieminen MS, Filippatos GS, et al. Levosimendan vs. dobutamine: outcomes for acute heart failure patients on beta-blockers in SURVIVE. Eur J Heart Fail. 2009;11(3):304–311. doi:10.1093/eurjhf/hfn045
Pollesello P, Parissis J, Kivikko M, Harjola VP. Levosimendan meta-analyses: Is there a pattern in the effect on mortality? Int J Cardiol. 2016;209:77–83. doi:10.1016/j.ijcard.2016.02.014
Farmakis D, Agostoni P, Baholli L, et al. A pragmatic multicenter randomized controlled trial with levosimendan in acute heart failure: the LEVO-D trial. Eur Heart J. 2023;44(suppl 2):ehad655.2283.
World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd list (2023). Available from: www.who.int
British National Formulary (BNF). Levosimendan monograph. National Institute for Health and Care Excellence (NICE). Available from: bnf.nice.org.uk
Toller W, Heringlake M, Guba F, Groesdonk HV. Levosimendan, a new inotropic and vasodilator agent. Anesthesiology. 2006;104(3):556–569. doi:10.1097/00000542-200603000-00024

Editorial Team

This article was written by the iMedic Medical Editorial Team, comprising licensed specialist physicians in cardiology, clinical pharmacology, and intensive care medicine. Our team adheres to strict editorial standards based on evidence-based medicine principles.

Medical review process: All content undergoes a rigorous review process including initial drafting by clinical pharmacists, medical accuracy review by board-certified cardiologists, and final editorial review for clarity and accessibility. We follow the GRADE framework for evaluating evidence quality and adhere to guidelines from the ESC, ACC/AHA, and WHO.

Conflict of interest statement: The iMedic editorial team has no financial relationships with pharmaceutical companies. All content is produced independently without commercial sponsorship or advertising influence.

Content update policy: This article is reviewed at least annually and updated whenever significant new clinical evidence, regulatory changes, or safety information becomes available.

Class	See drug class above
Form	See dosage section
Take with food?	See dosing instructions
Prescription required	Yes (in most regions)