PEDEA
Active material: Ibuprofen
When ATH: C01EB16
CCF: NSAIDs for the treatment of heart disease in preterm infants
ICD-10 codes (testimony): Q25.0
When CSF: 05.01.01.06
Manufacturer: NYCOMED AUSTRIA GmbH (Austria)
Pharmaceutical form, composition and packaging
The solution for the on / in the clear, colorless or slightly yellow.
| 1 ml | 1 amp. | |
| Ibuprofen | 5 mg | 10 mg |
Excipients: trometamol, sodium chloride, Sodium hydroxide, hydrochloric acid 25%, water d / and.
2 ml – colorless glass vials (4) – plastic containers (1) – packs cardboard.
Pharmacological action
NSAIDs. Ibuprofen obladaet protivovospalitelynoy, analgesic and antipyretic activity. Ibuprofen is a racemic mixture of S(+)- and R(-)-enantiomers. Исследования in vivo и in vitro indicates, that the clinical activity of ibuprofen is associated with S(+)-enantiomer. Ibuprofen is a non-selective inhibitor of cyclooxygenases, causes a decrease in prostaglandin synthesis.
Since prostaglandins delayed closure of the ductus arteriosus after birth, believe, COX inhibition that is the major mechanism of action of ibuprofen in the application for this indication.
Premature newborns ibuprofen significantly reduced concentrations of prostaglandins and their metabolites in the plasma, especially PGE2 and 6-keto- PGF-1-альфа. Newborns, received 3 ibuprofen injection, low concentrations of prostaglandin remained pending 72 no, whereas through 72 Only hours after his appointment 1 re-injection of ibuprofen was observed increase in the concentration of prostaglandins.
Pharmacokinetics
Distribution
Cmax in plasma after administration of the first and last maintenance doses are about 35-40 mg / l, regardless of the gestational and postnatal age of children. Through 24 h after administration of the last dose 5 mg / kg the residual concentration of about 10-15 mg / l.
Concentrations of S-enantiomer in the plasma much higher concentrations of R-enantiomer, reflecting rapid chiral inversion of R-form to the S-form in a ratio of, similar to that observed in adults (about 60%).
In Кажущийсяd averages 200 ml / kg (62-350 ml / kg, according to various studies). Central Vd It may depend on the status of the ductus and decrease as ductal closure.
Most of ibuprofen, as well as other NSAIDs, It related to plasma albumin, Although plasma newborns is significantly less pronounced binding (95%), adults than in plasma (99%). In the serum of newborns ibuprofen competes with bilirubin for binding to albumin, resulting in high concentrations of ibuprofen free fraction of bilirubin may increase.
Deduction
The rate of elimination in newborns ibuprofen significantly lower, than in adults and older children; T1/2 is about 30 no (16-43 no). With increasing gestational age, at least, aged 24-28 weeks, clearance of both enantiomers increases.
Testimony
- Treatment of hemodynamically significant patent ductus arteriosus in preterm newborn infants with gestational age less 34 weeks.
Dosage regimen
The drug is administered only in /. Treatment with Pede® It should be carried out only in the neonatal intensive care unit under the supervision of an experienced neonatologist.
The treatment involves 3 I / injections, conducted with an interval of 24 no.
Ibuprofen dose is adjusted depending on the body weight as follows:: the first injection – 10 mg / kg, second and third injection – 5 mg / kg.
The drug Pede® administered in the form of a short 15-minute infusion, preferably, undiluted. If necessary, the volume administered may be adjusted 0.9 % sodium chloride solution for injection or 5% glucose solution for injection. The remaining unused solution should be discarded.
In determining the total volume of solution injected should take into account the total daily fluid volume designated.
If, after the first or second dose, the child develops anuria or manifest oliguria, next dose is prescribed only after the restoration of normal urine output.
If the ductus arteriosus remains open through 24 hours after the last injection and reopen, It can be assigned to a second course, consisting of 3 doses, as described above.
If, after the second treatment condition is not changed, It may require surgical treatment of patent ductus arteriosus.
Side effect
From the blood coagulation system: blood coagulation disorders, leading to bleeding, eg, intestinal and intracranial bleeding.
The respiratory system: respiratory failure and pulmonary hemorrhage.
From the digestive system: obstruction and perforation of the intestine.
From the urinary system: decrease in the volume of urine produced, the presence of blood in urine.
Currently, there are some data regarding 1000 preterm infants, found in the literature about ibuprofen and obtained in clinical trials of the drug Pede®. The reasons for adverse events, observed in preterm infants, It is difficult to assess, tk. They may be associated with hemodynamic consequences of patent ductus arteriosus, and direct effects of ibuprofen.
Below are described adverse events, classified by organ system and frequency. The frequency of events was determined as follows: observed very often (>1/10), often (>1/100, <1/10), rarely (>1/1000, <1/100).
From the hematopoietic system: Often – thrombocytopenia, neutropenia.
From the nervous system: often – intraventricular hemorrhage, periventricular leukomalacia.
The respiratory system: Often – bronholegochnaya dysplasia; often – pneumorrhagia; rarely – anoxemia (occurred within 1 hours after the first infusion with the normalization condition for 30 min after the inhalation of nitric oxide).
From the digestive system: often – necrotizing enterocolitis, intestinal perforation; rarely – gastrointestinal bleeding.
From the urinary system: often – oligurija, fluid retention, hematuria; rarely – acute renal failure.
From the laboratory parameters: Often – increasing the concentration of creatinine in the blood, reducing the concentration of sodium in the blood.
Contraindications
- Life-threatening infection;
- Clinically significant bleeding, especially intracranial or gastrointestinal haemorrhage;
- Thrombocytopenia or clotting disorder;
- Severe renal impairment;
- Congenital heart disease, where the ductus arteriosus is a prerequisite for satisfactory pulmonary or systemic blood flow (eg, pulmonary atresia, severe tetralogy of Fallot, severe coarctation of the aorta);
- Confirmed or suspected necrotising enterocolitis;
- Hypersensitivity to ibuprofen or any subsidiary of the drug substance.
The drug should be used with caution with suspected infectious diseases.
Pregnancy and lactation
Designed for use in newborns.
Cautions
The drug Pede® should be administered with caution, to avoid extravasation with consequent possible tissue irritation.
As ibuprofen may inhibit platelet aggregation, preterm infants require close monitoring, aimed at identifying signs of bleeding.
As ibuprofen may decrease the clearance of aminoglycosides, with a joint appointment of aminoglycosides and ibuprofen it is recommended to continuously monitor the concentrations of these compounds in serum.
As shown, Chto in vitro ibuprofen competitive vыtesnyaet bilirubin in places with svyazыvaniya alybuminom, in premature infants may increase the risk of bilirubin encephalopathy. Therefore, ibuprofen should not be given to newborns with severe unconjugated hyperbilirubinemia.
It is recommended to closely monitor kidney function and gastrointestinal tract.
Before the appointment of the drug Pede® necessary to carry out the corresponding echocardiography, for, to confirm hemodynamically significant patent ductus arteriosus and to exclude pulmonary hypertension and other congenital heart defects with a concomitant patent ductus arteriosus.
Since prophylactic use Pede® in the first three days of life (commencing on the first 6 hours of life) preterm infants with a gestational age of less than 28 weeks was accompanied by an increase in the frequency of adverse events in the lungs and kidneys, drug Pede® should not be used prophylactically.
As NSAIDs, Ibuprofen may mask the symptoms of infectious diseases.
Displaying, that the treatment on the recommended scheme of premature infants with gestational age less 27 weeks of the closing rate of the ductus arteriosus is low.
Effects on ability to drive vehicles and management mechanisms
Not applicable. Designed for use in newborns.
Overdose
It is not known a single case of overdose, associated with on / in the ibuprofen in preterm neonates.
However described overdose in children, the ibuprofen oral.
Observed symptoms included CNS depression, convulsions, gastrointestinal disorders, ʙradikardiju, hypotension, shortness of breath, renal failure and hematuria.
There are cases of massive overdose (after receiving the dose more 1000 mg / kg), accompanied by coma, metabolic acidosis and passing kidney failure. After the standard treatment, all patients recovered. Registered one case of fatal overdose: after administration at a dose 469 mg / kg in 16-month-old child in connection with the cessation of breathing, development of seizures and subsequent aspiration pneumonia.
Treatment: symptomatic therapy.
Drug Interactions
Ibuprofen may attenuate the effects of diuretics; in patients with dehydration diuretics may increase the risk of nephrotoxicity of NSAIDs.
Ibuprofen may increase the effect of anticoagulants and enhance the risk of bleeding.
At simultaneous application with Valium ibuprofen may increase the risk of gastrointestinal bleeding.
As ibuprofen and nitric oxide inhibit platelet function, combination theoretically increase the risk of bleeding.
Avoid concomitant use of two or more NSAIDs due to the increased risk of adverse reactions.
As ibuprofen may decrease the clearance of aminoglycosides, while the appointment of these drugs may increase the risk of nephrotoxicity and ototoxicity.
Pharmaceutical interaction
The drug Pede® should not be mixed with other drugs, Besides 0.9% sodium chloride or 5% glucose solution.
The solution Pede® not be in contact with acidic solutions, eg, solutions of certain antibiotics or diuretics. To avoid significant changes in pH, caused by the presence of acidic drugs, which could remain in the infusion system, before and after the appointment of Pede® should be rinsed infusion system 1.5-2 ml 0.9% sodium chloride or 5% glucose solution.
Do not use chlorhexidine to disinfect the neck of the ampoule, because the solution Pede® not compatible with the compound. To disinfect the vial before use is recommended 60% ethanol. After disinfecting the neck of the ampoule with an antiseptic ampoule must be completely dry and only then open, to eliminate interference with an antiseptic solution Pede®.
Conditions of supply of pharmacies
The drug is approved for use only in hospitals.
Conditions and terms
The drug should be stored out of reach of children at or above 25 ° C. Shelf life – 4 year.
