Index of drugs

Treatment of haemodynamically significant persistent ductus arteriosus in newborns born before 34 weeks of gestation.

1 ml of solution contains 5 mg of Ibuprofen (and 7.5 mg of sodium).

A non-steroidal anti-inflammatory drug that, in addition to anti-inflammatory activity, also has analgesic and antipyretic properties; a non-selective cyclooxygenase inhibitor that causes reduced prostaglandin synthesis. Racemic mixture of S (+) and R (-) enantiomers: the S (+) isomer is responsible for the therapeutic activity of the drug. Prostaglandins contribute to the maintenance of patent ductus arteriosis after birth, which is why it is assumed that this is the main mechanism of action of ibuprofen in this indication. In preterm newborns, ibuprofen significantly reduces plasma concentrations of prostaglandins and their metabolites, especially PGE2 and 6-keto-PGF-1-α. In newborns who received 3 doses of Ibuprofen, low concentrations of prostaglandins were maintained up to 72 hours, while after only one dose of ibuprofen, their re-growth was observed after 72 hours. C_max drug in the blood plasma was in the range of 35-40 mg / l after the initial loading dose of 10 mg / kg and after the last maintenance dose, regardless of gestational or postnatal age. The residual concentrations are about 10-15 mg / L 24 hours after the last dose of 5 mg / kg. Ibuprofen is highly bound to plasma albumin, although the amount of bound drug appears to be significantly lower (95%) compared to adult plasma (99%). The elimination half-life is estimated at approximately 30 hours (16-43).

Hypersensitivity to the active substance or any of the excipients. Life threatening infection. Active bleeding (especially intracranial or gastrointestinal haemorrhage). Thrombocytopenia or blood coagulation disorders. Significant impairment of renal function. Congenital heart defect in which the ductus arteriosus persists is necessary to ensure a sufficient blood flow in the pulmonary and systemic circulation (eg, pulmonary valve obstruction, severe Fallot tetralogy, major aortic stenosis). Confirmed or suspected necrotizing enterocolitis.

Before administration of the preparation, appropriate echocardiography should be performed to detect persistent haemodynamically significant arterial ductus and exclude pulmonary hypertension as well as congenital heart disease. Because prophylactic use of the drug in the first 3 days of life (from 6 hours after birth) in premature babies before 28 weeks of pregnancy led to the occurrence of adverse effects on lung and kidney function, the drug should not be used prophylactically at any time during pregnancy. In particular, severe hypoxia with pulmonary hypertension was observed in 3 neonates within the first hour after the first infusion, with symptoms disappearing within 30 min after initiation of inhaled nitric oxide therapy. If hypoxia develops during or after the infusion, special attention should be paid to pulmonary pressure. Because it was shown that under conditionsin vitro ibuprofen displaces bilirubin from its binding site with albumin, the risk of bilirubin encephalopathy in preterm newborns may increase. Therefore, ibuprofen should not be used in infants with markedly elevated bilirubin levels. Ibuprofen may mask the typical symptoms of infection - in the presence of an infection, care must be taken when using the preparation. The preparation should be administered with caution to avoid blood extravasation and associated tissue irritation. Because ibuprofen may inhibit platelet aggregation, premature babies should be monitored for signs of bleeding. Ibuprofen may reduce the clearance of aminoglycosides, therefore it is recommended to closely monitor their serum levels when used with ibuprofen. As with other NSAIDs, careful monitoring of renal and gastrointestinal function is recommended.In preterm newborns before 27 weeks of gestation, the closing rate of persistent ductus arteriosus (33 to 50%) was small with the recommended dosing schedule. The preparation contains less than 1 mmol sodium (15 mg) in 2 ml, i.e. it can be considered as sodium-free.

Not applicable.

Very common: thrombocytopenia, neutropenia, broncho-pulmonary dysplasia, increased creatinine and decreased sodium in the blood. Common: intraventricular hemorrhage, periventricular leukomalacia, pulmonary haemorrhage, necrotizing enterocolitis, intestinal perforation, oliguria, fluid retention, hematuria. Uncommon: hypoxemia, gastrointestinal haemorrhage, acute renal failure. In clinical trials during which the formulation was administered prophylactically during the first 6 hours of life, 3 hypoxic patients born prematurely up to 28 weeks of gestation experienced severe hypoxia with pulmonary hypertension (this reaction occurred within the first hour after the first infusion, with symptoms resolved within 30 minutes after starting inhalation therapy with nitric oxide). There are also post-marketing reports on pulmonary hypertension in premature newborns who received the preparation in a healthcare unit.

Intravenously, only in neonatal intensive care centers under the supervision of an experienced neonatologist. The treatment cycle includes a 3-fold intravenous injection of the preparation at 24-hour intervals. The first injection should occur within the first 6 hours of life. The ibuprofen dose should be adjusted according to the child's body weight as follows: 1. injection: 10 mg / kg; 2nd and 3rd injection: 5 mg / kg If anuria or manifest oliguria occurs after the first or second dose, the Next dose should be withheld until urine output is reached in normal amounts. Ifductus arteriosus it will not be closed within 48 hours after the last injection or if it is re-opened, a second course of 3 injections may be used as described above. If flow conditions do not change after the second course of therapy, surgical treatment of persistent ductus arteriosus may be necessary.Way of giving. The drug should be administered as a short intravenous infusion over 15 minutes, preferably undiluted. If necessary, the volume of solution for injection can be topped up with a NaCl solution for injection of 9 mg / ml (0.9%) or a Glucose solution for injection 50 mg / ml (5%). Any unused volume of solution should be discarded. The total volume of the injected solution should be adjusted to the total daily intake of fluids.