Pharmacokinetics in children

There are only two studies in which the pharmacokinetics of levosimendan in children have been described. The study by Turanlahti et al. (single administration of 12 µg/kg in children aged 3 months – 7 yrs, n = 13) concludes that the pharmacokinetic profiles of levosimendan in adults and in children are comparable. The following values have been found:

The pharmacokinetics of the active metabolite were not investigated in the studies.

The study by Pellicer et al. states a Cmax for neonates averaging 16.5 ng/ml, a Tmax averaging 48 hours and a Cl/F averaging 0.67 l/h/kg.

dose recommendation of formulary compared to licensed use (on-label versus off-label)

No information is present at this moment.

Available formulations

No information is present at this moment.

Dosages

Renal impaiment in children > 3 months

No data is known about dosage adjustments for renal function disorders. In adults, an improvement in the renal function was seen on the one hand, but on the other caution is needed because of a possibly elevated exposure to active metabolites.

The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects

No information is present at this moment.

The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here

Contra-indications

No information available on specific contra indications in children.

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions in children

The ECG, blood pressure, heart rate, cardiac output, filling pressure and urine production should be monitored during administration and for at least 3 days after discontinuing or in the case of hepatic or renal function disorders for at least 5 days or until the patient is stable. Any low serum potassium concentration should be corrected before administration and the potassium level should be monitored during administration. Severe hypovolaemia, ventricular tachycardia and paroxysmal tachycardia that is not the result of reperfusion or life-threatening arrhythmia should be corrected before administration.

Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

• CARDIOVASCULAR SYSTEM
• CARDIAC THERAPY

CARDIAC STIMULANTS EXCL. CARDIAC GLYCOSIDES

This pages provides a list of drugs from the same ATC class for comparison. This does not necessarily mean that these drugs are interchangeable.

References

1. Egan JR, et al., Levosimendan for low cardiac output: a pediatric experience, J Intensive Care Med, 2006, 2, 183-7
2. Lechner E, et al., Use of levosimendan, a new inodilator, for postoperative myocardial stunning in a premature neonate, Pediatr Crit Care Med, 2007, 8, 61-3
3. Namachivayam P, et al., Early experience with Levosimendan in children with ventricular dysfunction., Pediatr Crit Care Med, 2006, 7, 445-8
4. Turanlahti M, et al., Pharmacokinetics of levosimendan in pediatric patients evaluated for cardiac surgery., Pediatr Crit Care Med, 2004, 5, 457-62
5. Angadi U, et al., Is levosimendan effective in paediatric heart failure and post-cardiac surgeris?, Interact Cardiovasc Thorac Surg, 2013, 17, 710-4
6. Pellicer A, et al., Phase 1 study of two inodilators in neonates undergoing cardiovascular surgery, 2013, 73, 95-103
7. Fedele F, et al., Levosimendan improves renal function in acute decompensated heart failure: possible underlying mechanisms, Eur J Heart Fail, 2014, 16, 281-8
8. Orion Pharma bvba, SmPC Simdax 11-6-2010, www.simdax.com
9. CBG, Levosimendan containing products with a 2.5 mg/mL strength and the pharmaceutical form concentrate for solution for infusion for the proposed indication treatment of patients with acutely decompensated severe chronic heart failure (ADHF), www.cbg-meb.nl, 04-02-2016
10. Amiet V. et al, Use of Levosimendan in Postoperative Setting After Surgical Repair of Congenital Heart Disease in Children., Pediatr Cardiol., 2018, Jan;39(1), 19-25
11. Thorlacius EM, et al., Levosimendan Versus Milrinone for Inotropic Support in Pediatric Cardiac Surgery: Results From a Randomized Trial., J Cardiothorac Vasc Anesth, 2020, 34, 2072-80
12. Lechner E, et al., Use of levosimendan, a new inodilator, for postoperative myocardial stunning in a premature neonate, Pediatr Crit Care Med, 2007, 8, 61-3

Changes

Therapeutic Drug Monitoring

Overdose