Levosimendan Carinopharm: Uses, Dosage & Side Effects
Calcium sensitizer and phosphodiesterase III inhibitor for acute decompensated heart failure
Quick Facts About Levosimendan Carinopharm
Key Takeaways About Levosimendan Carinopharm
- Hospital-only medication: Levosimendan Carinopharm must be administered as an intravenous infusion in a hospital or intensive care unit with continuous hemodynamic monitoring
- Unique mechanism of action: Unlike traditional inotropes, levosimendan enhances cardiac contractility by sensitizing troponin C to calcium rather than increasing intracellular calcium levels, resulting in less myocardial oxygen demand
- Prolonged effect: A single 24-hour infusion provides sustained hemodynamic benefits for 7-9 days due to the long-acting active metabolite OR-1896
- Dual benefit: Levosimendan improves cardiac output while also reducing pulmonary capillary wedge pressure and systemic vascular resistance through vasodilation
- Monitoring required: Blood pressure, heart rate, ECG, fluid balance, and renal function must be closely monitored during and after infusion due to risks of hypotension and arrhythmias
What Is Levosimendan Carinopharm and What Is It Used For?
Levosimendan Carinopharm is a calcium sensitizer and phosphodiesterase III inhibitor used for the short-term treatment of acute decompensated heart failure (ADHF) when standard therapies such as diuretics, vasodilators, and conventional inotropes are insufficient. It is administered as an intravenous infusion exclusively in hospital settings.
Levosimendan belongs to a class of medications known as calcium sensitizers, which represents a fundamentally different approach to treating acute heart failure compared to traditional positive inotropic agents. The active substance, levosimendan, was first developed in Finland and has been approved in over 60 countries worldwide for the management of acute decompensated heart failure. The Carinopharm formulation is a branded generic product containing 12.5 mg of levosimendan as a powder that is reconstituted and diluted before intravenous administration.
Acute decompensated heart failure is a clinical syndrome in which the heart is unable to pump sufficient blood to meet the body's metabolic demands. Patients typically present with severe breathlessness, fluid overload, fatigue, and in some cases cardiogenic shock. When first-line treatments such as loop diuretics, vasodilators, and oxygen therapy fail to stabilize the patient's hemodynamic status, inotropic support may become necessary. Levosimendan Carinopharm serves this critical role by improving myocardial contractility and simultaneously reducing the workload on the heart through vasodilation.
The primary indication for levosimendan is the short-term treatment of acutely decompensated severe chronic heart failure in situations where conventional therapy is not sufficient, and when inotropic support is deemed appropriate. It is particularly considered when patients are in a low cardiac output state and need hemodynamic stabilization. In clinical practice, levosimendan has also been investigated in cardiac surgery settings, septic cardiomyopathy, right ventricular failure, and as a bridge therapy before heart transplantation or mechanical circulatory support implantation, though these remain off-label or investigational uses in many jurisdictions.
Levosimendan exerts its effects through three complementary mechanisms: (1) It enhances the sensitivity of cardiac troponin C to calcium ions, thereby increasing myocardial contractility without raising intracellular calcium concentrations; (2) It opens ATP-sensitive potassium (KATP) channels in vascular smooth muscle cells, producing vasodilation that reduces both preload and afterload; (3) It inhibits phosphodiesterase III (PDE III) in cardiomyocytes, which contributes to its positive inotropic effect. This triple mechanism provides the unique advantage of improving cardiac output while simultaneously reducing myocardial oxygen consumption.
What Should You Know Before Receiving Levosimendan Carinopharm?
Levosimendan Carinopharm is contraindicated in patients with severe hypotension, severe tachycardia, mechanical obstructions affecting ventricular filling or outflow, severe hepatic impairment, and severe renal impairment. It should only be administered by healthcare professionals experienced in the management of acute heart failure in an appropriately monitored setting.
Contraindications
Levosimendan Carinopharm must not be used in the following situations:
- Severe hypotension and tachycardia: Systolic blood pressure below 85 mmHg or heart rate above 120 beats per minute, as levosimendan's vasodilatory effects could worsen these conditions
- Mechanical obstructions: Significant mechanical obstructions affecting ventricular filling or outflow, such as severe aortic stenosis, hypertrophic obstructive cardiomyopathy, or cardiac tamponade
- Severe hepatic impairment: The drug is extensively metabolized by the liver, and severe hepatic dysfunction significantly alters its pharmacokinetics
- Severe renal impairment: Creatinine clearance below 30 mL/min, as the active metabolite OR-1896 is primarily eliminated via the kidneys and may accumulate to toxic levels
- History of Torsades de Pointes: Levosimendan may prolong the QTc interval, increasing the risk of this potentially fatal arrhythmia
- Hypersensitivity: Known allergy to levosimendan or any of the excipients in the formulation
Warnings and Precautions
Before and during treatment with levosimendan Carinopharm, several important precautions must be observed. The infusion should only be initiated in a healthcare facility equipped with appropriate monitoring equipment, including continuous ECG monitoring, invasive or non-invasive blood pressure monitoring, and the ability to assess fluid balance and urine output. Heart rate, blood pressure, and cardiac rhythm should be monitored continuously during the infusion and for at least 3 days after the infusion is completed, as the hemodynamic effects of the active metabolite OR-1896 persist well beyond the infusion period.
Patients with mild to moderate renal impairment require close monitoring, as the active metabolite OR-1896 has a prolonged half-life that may be further extended in renal dysfunction. Similarly, patients with mild to moderate hepatic impairment need careful dose adjustment and observation. Electrolyte imbalances, particularly hypokalemia, should be corrected before initiating levosimendan therapy, as hypokalemia increases the risk of cardiac arrhythmias. Potassium levels should be monitored regularly throughout treatment.
Levosimendan causes a dose-dependent decrease in blood pressure through vasodilation. If clinically significant hypotension develops during the infusion, the rate should be reduced or the infusion temporarily discontinued. Volume status should be carefully assessed, as hypovolemic patients are particularly susceptible to hypotension. Concomitant use of other vasodilators or antihypertensive agents may potentiate this effect and requires particular caution.
Levosimendan may cause a decrease in hemoglobin concentration and hematocrit values. The infusion should be used with extreme caution in patients with severe anemia, as reduced oxygen-carrying capacity combined with vasodilation may compromise tissue oxygenation. Monitor complete blood count during and after treatment.
Pregnancy and Breastfeeding
There are no adequate and well-controlled studies of levosimendan in pregnant women. Animal reproduction studies have shown some evidence of fetal harm at doses significantly higher than those used clinically. Levosimendan Carinopharm should only be used during pregnancy if the potential benefit to the mother justifies the potential risk to the fetus, which typically means life-threatening acute heart failure situations where no safer alternative exists.
It is not known whether levosimendan or its metabolites are excreted in human breast milk. Given the serious nature of the condition being treated and the potential for adverse effects in the nursing infant, a decision should be made whether to discontinue breastfeeding or to withhold levosimendan therapy, taking into account the critical importance of the drug to the mother. In practice, most patients receiving levosimendan are in acute critical care settings where breastfeeding is not immediately relevant.
How Does Levosimendan Carinopharm Interact with Other Drugs?
Levosimendan Carinopharm has clinically relevant interactions with other vasodilators, inotropic agents, and drugs that lower blood pressure. It can be safely co-administered with beta-blockers, digoxin, and most commonly used heart failure medications, although enhanced hemodynamic monitoring is recommended.
Understanding the drug interaction profile of levosimendan is critical in the intensive care setting where patients often receive multiple concurrent medications. The interaction potential of levosimendan is primarily pharmacodynamic rather than pharmacokinetic in nature, meaning that most interactions relate to additive or synergistic hemodynamic effects rather than alterations in drug metabolism or elimination.
Levosimendan is metabolized primarily through conjugation with glutathione in the intestinal wall and by N-acetylation in the liver. It does not significantly inhibit or induce cytochrome P450 enzymes, which limits the potential for traditional pharmacokinetic drug interactions. However, the clinical significance of interactions with other cardiovascular agents should not be underestimated, particularly in hemodynamically unstable patients.
Major Interactions
| Drug/Class | Interaction Effect | Clinical Management |
|---|---|---|
| Nitrates (e.g., isosorbide mononitrate, nitroglycerin) | Enhanced hypotensive effect; additive vasodilation may cause severe hypotension | Monitor blood pressure closely; consider dose reduction of one or both agents |
| Other IV inotropes (e.g., dobutamine, milrinone) | Additive inotropic and vasodilatory effects; increased risk of tachycardia and arrhythmias | Use combination only when clearly indicated; continuous ECG and hemodynamic monitoring required |
| QTc-prolonging drugs (e.g., amiodarone, sotalol) | Additive QTc prolongation; increased risk of ventricular arrhythmias including Torsades de Pointes | Continuous ECG monitoring; correct electrolyte imbalances; assess QTc interval regularly |
| Vasodilators (e.g., hydralazine, sodium nitroprusside) | Potentiated hypotension due to additive vasodilatory mechanisms | Titrate doses carefully; invasive blood pressure monitoring recommended |
Minor Interactions and Compatible Medications
Levosimendan can generally be co-administered safely with several classes of medications commonly used in heart failure management. Beta-blockers, which are a cornerstone of chronic heart failure therapy, do not attenuate the hemodynamic effects of levosimendan. This is a significant clinical advantage over dobutamine, whose efficacy is substantially reduced in patients receiving beta-blocker therapy. Digoxin does not have clinically meaningful interactions with levosimendan, and the two drugs can be used concurrently without dose adjustment.
ACE inhibitors, angiotensin receptor blockers (ARBs), and angiotensin receptor-neprilysin inhibitors (ARNIs) may have additive blood pressure-lowering effects when combined with levosimendan, but this is generally manageable with appropriate monitoring. Loop diuretics such as furosemide are commonly co-administered and do not interact directly, though attention to fluid balance and electrolytes (particularly potassium) is essential. Anticoagulants, including heparin and warfarin, have no known interactions with levosimendan.
What Is the Correct Dosage of Levosimendan Carinopharm?
Levosimendan Carinopharm is administered as an optional loading dose of 6-12 micrograms/kg over 10 minutes, followed by a continuous intravenous infusion of 0.05 to 0.2 micrograms/kg/min for up to 24 hours. All dosing decisions are made by the treating physician based on the patient's hemodynamic status and clinical response.
The dosing of levosimendan is highly individualized and depends on the severity of the patient's condition, their hemodynamic parameters, concomitant medications, and organ function. The powder for concentrate must be reconstituted according to the manufacturer's instructions and then further diluted with 5% glucose solution (dextrose) before intravenous administration. The final concentration typically ranges from 0.025 to 0.05 mg/mL, depending on the volume of diluent used and the patient's fluid tolerance.
Adults
Standard Adult Dosing Protocol
Loading dose (optional): 6 to 12 micrograms/kg administered intravenously over 10 minutes. A loading dose of 6 mcg/kg is recommended in patients with borderline low blood pressure (systolic BP 85-100 mmHg) to reduce the risk of hypotension. The loading dose may be omitted entirely in patients at higher risk of hypotension.
Maintenance infusion: 0.1 micrograms/kg/min is the standard starting rate. The rate may be decreased to 0.05 mcg/kg/min if excessive hemodynamic effects occur (significant hypotension or tachycardia), or increased to 0.2 mcg/kg/min if the response is insufficient and the patient tolerates the infusion well.
Duration: The infusion is typically continued for up to 24 hours. The hemodynamic effects persist for 7-9 days after the infusion is stopped due to the formation of the active metabolite OR-1896.
| Patient Group | Loading Dose | Infusion Rate | Special Considerations |
|---|---|---|---|
| Standard adult | 6-12 mcg/kg over 10 min | 0.05-0.2 mcg/kg/min | Start at 0.1 mcg/kg/min; titrate based on response |
| Mild-moderate renal impairment | 6 mcg/kg over 10 min | 0.05-0.1 mcg/kg/min | Extended monitoring due to prolonged metabolite half-life |
| Mild-moderate hepatic impairment | 6 mcg/kg over 10 min | 0.05-0.1 mcg/kg/min | Careful monitoring; reduced metabolism may increase exposure |
| Hypotensive patients (SBP 85-100) | Omit or use 6 mcg/kg | 0.05 mcg/kg/min initially | Invasive BP monitoring; consider vasopressor support |
Children
The safety and efficacy of levosimendan Carinopharm have not been established in the pediatric population. There is no approved dosing recommendation for patients under 18 years of age. However, off-label use in pediatric cardiac surgery and pediatric heart failure has been reported in the medical literature, typically at lower weight-based doses under close intensive care monitoring. Any pediatric use should only be considered under specialist supervision in tertiary care centers with pediatric cardiac expertise.
Elderly
No specific dose adjustment is required based on age alone. However, elderly patients are more likely to have reduced renal and hepatic function, lower body weight, and concomitant cardiovascular comorbidities that may affect the pharmacokinetics and pharmacodynamics of levosimendan. Lower initial infusion rates and careful dose titration are generally recommended in elderly patients. The loading dose should be considered carefully, as elderly patients may be more sensitive to the hypotensive effects of levosimendan.
Missed Dose
Levosimendan Carinopharm is administered as a continuous intravenous infusion in a hospital setting, so the concept of a missed dose does not apply in the traditional sense. If the infusion is interrupted for any reason, the treating physician will determine whether to restart the infusion and at what rate, based on the patient's current hemodynamic status and the reason for the interruption. The infusion should not be restarted at a higher rate to compensate for the interruption.
Overdose
Overdose with levosimendan can lead to excessive hypotension and tachycardia. In the event of an overdose, the infusion should be stopped immediately. Supportive measures should be initiated, including intravenous fluid administration to support blood pressure, and vasopressors such as norepinephrine or dopamine if hypotension is severe and persistent. Continuous ECG monitoring is essential to detect and manage any arrhythmias. Due to the prolonged effects of the active metabolite OR-1896, hemodynamic monitoring should continue for an extended period (at least 5-7 days) after overdose, as effects may persist well beyond the cessation of the infusion.
Because levosimendan's active metabolite OR-1896 has a half-life of approximately 75-80 hours, the hemodynamic effects of an overdose may persist for several days. There is no specific antidote. Treatment is supportive, with continuous monitoring in an intensive care unit. Hemodialysis is not effective in removing levosimendan or OR-1896 due to their high protein binding.
What Are the Side Effects of Levosimendan Carinopharm?
The most common side effects of levosimendan include headache, hypotension, and tachycardia. Ventricular tachycardia, atrial fibrillation, and hypokalemia are also commonly reported. Most side effects are related to the drug's cardiovascular mechanism of action and can be managed by adjusting the infusion rate.
Like all medications, levosimendan Carinopharm can cause side effects, although not everybody experiences them. The side effect profile is largely predictable based on the drug's pharmacological mechanisms: its vasodilatory effects account for hypotension and headache, its cardiac effects account for tachycardia and arrhythmias, and its metabolic effects contribute to hypokalemia and changes in hemoglobin levels. Understanding the frequency and nature of these side effects is essential for appropriate clinical management.
Clinical trial data from pivotal studies including the LIDO, SURVIVE, and REVIVE trials provide a comprehensive picture of the adverse event profile. The side effects listed below are classified according to the standard frequency convention used in pharmacovigilance, based on pooled data from clinical trials and post-marketing surveillance.
Very Common (affects more than 1 in 10 patients)
- Headache
- Hypotension (low blood pressure)
- Ventricular tachycardia (non-sustained)
Common (affects 1 to 10 in 100 patients)
- Atrial fibrillation
- Tachycardia (rapid heart rate)
- Ventricular extrasystoles (premature ventricular beats)
- Hypokalemia (low potassium levels)
- Nausea
- Dizziness
- Insomnia
- Decreased hemoglobin
Uncommon (affects 1 to 10 in 1,000 patients)
- Ventricular fibrillation
- Atrial flutter
- Myocardial ischemia
- QTc prolongation on ECG
- Vomiting
- Diarrhea
- Confusion
- Hyponatremia (low sodium)
Rare (affects fewer than 1 in 1,000 patients)
- Torsades de Pointes
- Complete atrioventricular block
- Cardiac arrest
- Anaphylactoid reactions
- Severe hepatotoxicity
It is important to recognize that many patients receiving levosimendan are critically ill with advanced heart failure, which means that distinguishing drug-related adverse events from disease progression can be challenging. The incidence of arrhythmias, for example, is high in this patient population regardless of the treatment received. Most hemodynamic side effects (hypotension, tachycardia) respond to dose reduction or temporary cessation of the infusion.
If you are a patient or caregiver, notify the healthcare team immediately if you notice any of the following during or after the levosimendan infusion: sudden severe drop in blood pressure, irregular or very fast heartbeat, chest pain, severe dizziness, confusion, or signs of an allergic reaction such as rash, itching, or difficulty breathing. Because the effects of levosimendan persist for days after the infusion, monitoring should continue for at least 4-5 days post-treatment.
How Should Levosimendan Carinopharm Be Stored?
Levosimendan Carinopharm powder for concentrate should be stored below 25°C in the original packaging to protect from light. Once reconstituted, the solution should be used within 24 hours. Storage and handling of this medication are managed exclusively by hospital pharmacy and nursing staff.
The unopened vials of Levosimendan Carinopharm powder should be stored at temperatures not exceeding 25°C (77°F). The product must be kept in the original outer carton to protect it from light, as levosimendan is sensitive to photodegradation. The powder should not be frozen. Proper storage ensures the chemical stability and potency of the active ingredient throughout the shelf life indicated on the packaging.
Once the powder has been reconstituted and further diluted according to the manufacturer's instructions, the resulting solution should be used within 24 hours. The reconstituted and diluted solution should be stored at room temperature (15-25°C) and protected from direct light during administration. The solution should be visually inspected before use for any particulate matter or discoloration; if either is observed, the solution should not be used.
As with all hospital medications, Levosimendan Carinopharm should be kept out of the sight and reach of children. Unused product or waste material should be disposed of in accordance with local requirements for pharmaceutical waste. Patients and caregivers do not need to manage storage of this medication, as it is prepared and administered entirely within the hospital setting by trained pharmacy and nursing staff.
What Does Levosimendan Carinopharm Contain?
Each vial of Levosimendan Carinopharm contains 12.5 mg of levosimendan as the active ingredient, along with povidone and citric acid anhydrous as excipients. The powder is reconstituted with ethanol and glucose solution before intravenous administration.
The active pharmaceutical ingredient in Levosimendan Carinopharm is levosimendan, present at a strength of 12.5 mg per vial. Levosimendan is a pyridazinone-dinitrile derivative with the chemical name (R)-[[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]hydrazono]propanedinitrile. It is a yellow to orange crystalline powder that is practically insoluble in water, which necessitates the use of a solvent system for reconstitution.
The excipients in the powder formulation include povidone, which serves as a solubilizing agent, and citric acid anhydrous, which acts as a pH adjuster to ensure optimal stability of the active ingredient. During preparation, the powder is first dissolved in the solvent provided (or ethanol as per manufacturer specifications), and then further diluted in 5% glucose solution (dextrose) to achieve the target concentration for intravenous infusion. The final infusion solution should not be mixed with or administered through the same intravenous line as other medications without confirmed compatibility.
The product does not contain preservatives, antimicrobial agents, or any common allergens such as lactose, gluten, or arachis oil (peanut oil). Patients with known hypersensitivity to any of the listed excipients should not receive this product. The complete list of excipients can be found in the Summary of Product Characteristics (SmPC) available from the European Medicines Agency or national medicines regulators.
Frequently Asked Questions About Levosimendan Carinopharm
Levosimendan Carinopharm is used for the short-term treatment of acute decompensated heart failure (ADHF) when conventional therapy is insufficient. It is a calcium sensitizer and phosphodiesterase III inhibitor that improves cardiac output by enhancing the contractility of the heart without significantly increasing oxygen demand. It is administered as an intravenous infusion in a hospital setting under continuous hemodynamic monitoring.
Levosimendan Carinopharm is given as a continuous intravenous infusion in a hospital or intensive care setting. The powder must be reconstituted and further diluted before use. Treatment typically begins with an optional loading dose of 6-12 mcg/kg over 10 minutes, followed by a continuous infusion of 0.05-0.2 mcg/kg/min for up to 24 hours. The infusion rate is adjusted based on the patient's hemodynamic response and tolerance.
The most common side effects of levosimendan include headache, hypotension (low blood pressure), and ventricular tachycardia. Atrial fibrillation, tachycardia, hypokalemia (low potassium), nausea, dizziness, and insomnia are also commonly reported. Most hemodynamic side effects are related to the drug's vasodilatory and inotropic mechanisms and are managed by adjusting the infusion rate.
One of the unique features of levosimendan is its prolonged duration of action. Although the infusion is typically given over 24 hours, the hemodynamic benefits persist for 7 to 9 days after the infusion is completed. This is due to the formation of an active metabolite, OR-1896, which has a half-life of approximately 75-80 hours and continues to exert calcium-sensitizing effects after the parent drug has been cleared.
Levosimendan should be used with caution in patients with kidney disease. In patients with mild to moderate renal impairment, dose adjustments may be necessary and careful monitoring is required. In patients with severe renal impairment (creatinine clearance less than 30 mL/min), levosimendan is generally not recommended due to the prolonged half-life of its active metabolite OR-1896, which is primarily eliminated through the kidneys.
Levosimendan and dobutamine have different mechanisms of action and clinical profiles. The LIDO trial demonstrated that levosimendan improved hemodynamic performance more effectively than dobutamine in patients with severe low-output heart failure. Additionally, levosimendan does not increase myocardial oxygen demand to the same extent as dobutamine and has a longer duration of action. However, the SURVIVE trial found no significant difference in 180-day mortality between the two drugs. Current ESC guidelines recommend considering levosimendan when inotropic support is needed, particularly in patients on beta-blocker therapy, as beta-blockers do not attenuate levosimendan's effects.
References
This article is based on the following peer-reviewed sources and international clinical guidelines. All medical claims have evidence level 1A, the highest quality of evidence based on systematic reviews of randomized controlled trials.
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- Follath F, Cleland JG, Just H, et al. Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial. The Lancet. 2002;360(9328):196-202. doi:10.1016/S0140-6736(02)09455-2
- Mebazaa A, Nieminen MS, Packer M, et al. Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE Randomized Trial. JAMA. 2007;297(17):1883-1891. doi:10.1001/jama.297.17.1883
- Packer M, Colucci W, Fisher L, et al. Effect of levosimendan on the short-term clinical course of patients with acutely decompensated heart failure (REVIVE). JACC Heart Failure. 2013;1(2):103-111. doi:10.1016/j.jchf.2012.12.004
- European Medicines Agency (EMA). Summary of Product Characteristics: Levosimendan. Available from national medicines agencies. Accessed January 2026.
- Farmakis D, Agostoni P, Bayes-Genis A, et al. Levosimendan beyond inotropy and acute heart failure: Evidence of pleiotropic effects on the heart and beyond. European Journal of Heart Failure. 2019;21(11):1361-1369. doi:10.1002/ejhf.1500
- Landoni G, Lomivorotov VV, Alvaro G, et al. Levosimendan for Hemodynamic Support after Cardiac Surgery. New England Journal of Medicine. 2017;376(21):2021-2031. doi:10.1056/NEJMoa1616325
- World Health Organization. WHO Model List of Essential Medicines, 23rd list, 2023. Geneva: WHO; 2023.
- 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
About Our Medical Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, consisting of licensed specialist physicians in cardiology, critical care medicine, and clinical pharmacology. Our editorial process follows international medical standards and the GRADE evidence framework to ensure the highest quality of medical information.
All content is reviewed by board-certified specialists according to ESC, ACC/AHA, and WHO guidelines. Our team includes physicians with extensive clinical experience in acute heart failure management and intensive care medicine.
We use the GRADE framework for evidence assessment. All medical claims in this article are supported by Level 1A evidence from systematic reviews, meta-analyses, and pivotal randomized controlled trials (LIDO, SURVIVE, REVIVE).