Composition, form of production and packaging
The solution for intravenous administration is clear, colorless or slightly yellowish.
1 ml of 1 amp.
ibuprofen 5 mg 10 mg
Excipients: trometamol, sodium chloride, sodium hydroxide, hydrochloric acid 25%, water d / u.
2 ml - ampoules of colorless glass (4) - polymer containers (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2013.
PHARMACHOLOGIC EFFECT
NSAIDs. Ibuprofen has anti-inflammatory, analgesic and antipyretic activity. Ibuprofen is a racemic mixture of S (+) - and R (-) - enantiomers. In vivo and in vitro studies suggest that the clinical activity of ibuprofen is associated with the S (+) - enantiomer. Ibuprofen is a non-selective COX inhibitor, which causes a decrease in the synthesis of prostaglandins.
Since prostaglandins delay the closure of the arterial duct after birth, it is believed that COX suppression is the main mechanism of action of ibuprofen when used for this indication.
In preterm infants, ibuprofen significantly reduces the concentrations of prostaglandins and their metabolites in plasma, especially PGE2 and 6-keto-PGF-1-alpha. In neonates receiving 3 injections of ibuprofen, low concentrations of prostaglandins persisted for up to 72 hours, whereas 72 hours after the administration of only 1 injection of ibuprofen, a repeated increase in the concentration of prostaglandins was observed.
PHARMACOKINETICS
Distribution
C max in plasma after the appointment of the first and last maintenance dose is about 35-40 mg / l, regardless of the gestational and postnatal age of children. At 24 hours after the last dose of 5 mg / kg, the remaining concentrations are about 10-15 mg / l.
The concentrations of the S-enantiomer in plasma are significantly higher than the concentrations of the R-enantiomer, which reflects a rapid chiral inversion of the R-form into the S-form in a ratio similar to that observed in adults (approximately 60%).
The apparent V d is on the average 200 ml / kg (62-350 ml / kg according to different studies). Central V d may depend on the status of the duct and decrease as the duct closes.
Most of ibuprofen, like other NSAIDs, is associated with plasma albumin, although in neonatal plasma this binding is significantly lower (95%) than in adult plasma (99%). In the newborn serum, ibuprofen competes with bilirubin for binding to albumin, so that at a high concentration of ibuprofen, the free fraction of bilirubin may increase.
Excretion
The rate of ibuprofen elimination in newborns is significantly lower than in adults and older children; T 1/2 is about 30 hours (16-43 hours). As the gestational age increases, at least at the age of 24-28 weeks, the clearance of both enantiomers increases.
INDICATIONS
- Treatment of a hemodynamically significant open arterial duct in premature newborns with a gestational age of less than 34 weeks.
DOSING MODE
The drug is administered only IV. Treatment with Pedega В® should be performed only in the neonatal intensive care unit under the supervision of an experienced neonatologist.
The course of treatment includes 3 intravenous injections of the drug, conducted at intervals of 24 hours.
The dose of ibuprofen is selected according to body weight as follows: first injection - 10 mg / kg, second and third injections - 5 mg / kg.
The Pediaa В® preparation is administered in the form of a short 15-minute infusion, preferably undiluted. If necessary, the volume can be adjusted by 0.9% sodium chloride solution for injection or 5% glucose solution for injection. The remaining unused solution should be discarded.
When determining the total volume of the solution administered, the total daily volume of the prescribed liquid should be taken into account.
If after the first or second dose the child develops anuria or obvious oliguria, the next dose is prescribed only after the restoration of normal diuresis.
If the arterial duct remains open 24 hours after the last injection or is reopened, a second course consisting of 3 doses as described above may be assigned.
If the condition does not change after the second course of treatment, surgical treatment of the open arterial duct may be required.
SIDE EFFECT
From the coagulation system: blood clotting disorders leading to bleeding, for example, intestinal and intracranial hemorrhages.
On the part of the respiratory system: breathing disorders and pulmonary hemorrhages.
On the part of the digestive system: obstruction and perforation of the intestine.
From the urinary system: a decrease in the volume of urine formed, the presence of blood in the urine.
Currently, there are data for approximately 1,000 preterm infants found in the literature on ibuprofen and obtained in clinical studies of Pedega В® . The causes of adverse events observed in preterm infants are difficult to estimate, they can be related both to the hemodynamic consequences of the open arterial duct, and to the direct effects of ibuprofen.
The adverse events described below, classified by organ systems and by frequency, are listed below. The frequency of events was determined as follows: observed very often (> 1/10), often (> 1/100, <1/10), rarely (> 1/1000, <1/100).
On the part of the organs of hematopoiesis: very often thrombocytopenia, neutropenia.
From the nervous system: often - intraventricular hemorrhage, periventricular leukomalacia.
From the respiratory system: very often - bronchopulmonary dysplasia; often - pulmonary hemorrhage; rarely - hypoxemia (occurred within 1 h after the first infusion with normalization of the state within 30 min after inhalation with nitrogen oxide).
From the side of the digestive system: often - necrotizing enterocolitis, perforation of the intestine; rarely - gastrointestinal bleeding.
From the urinary system: often - oliguria, fluid retention, hematuria; rarely acute renal failure.
Laboratory indicators: very often - an increase in the concentration of creatinine in the blood, a decrease in the concentration of sodium in the blood.
CONTRAINDICATIONS
- life-threatening infection;
- clinically pronounced bleeding, especially intracranial or gastrointestinal hemorrhage;
- thrombocytopenia or blood clotting disorder;
- pronounced impairment of kidney function;
- congenital heart disease, in which the open arterial duct is a necessary condition for a satisfactory pulmonary or systemic blood flow (for example, pulmonary atresia, heavy tetralogy of Fallot, severe coarctation of the aorta);
- diagnosed or suspected necrotizing enterocolitis;
- hypersensitivity to ibuprofen or any auxiliary substance of the drug.
The drug should be used with caution in case of suspected infectious diseases.
PREGNANCY AND LACTATION
It is intended for use only in newborns.
APPLICATION FOR FUNCTIONS OF THE LIVER
The drug is contraindicated in marked violation of kidney function.
SPECIAL INSTRUCTIONS
The Pedega В® preparation should be administered with great care to avoid extravasation followed by possible irritation of the tissues.
Since ibuprofen can inhibit platelet aggregation, premature newborns need close monitoring aimed at detecting signs of bleeding.
Since ibuprofen can reduce the clearance of aminoglycosides, with the simultaneous administration of aminoglycosides and ibuprofen, it is recommended that the concentrations of these compounds in the serum be monitored continuously.
Since it has been shown that in vitro ibuprofen competitively displaces bilirubin from the binding site with albumin, premature neonates may increase the risk of bilirubin encephalopathy. In this regard, ibuprofen should not be given to newborns with severe unconjugated hyperbilirubinemia.
It is recommended to closely monitor the function of the kidneys and the gastrointestinal tract.
Prior to the appointment of the Pedee В® drug, an appropriate echocardiographic examination is necessary to confirm the hemodynamically significant open arterial duct and exclude pulmonary hypertension and other congenital heart defects with concomitant nephrosis of the arterial duct.
Since the prophylactic use of Pedea В® in the first three days of life (beginning in the first 6 hours of life) of premature newborns with a gestational age of less than 28 weeks was accompanied by an increase in the incidence of adverse events from the lungs and kidneys, the Pedega В® drug should not be used for prophylactic purposes.
Being an NSAID, ibuprofen can mask the symptoms of infectious diseases.
It is shown that in treatment of the recommended scheme of preterm neonates with gestational age less than 27 weeks, the frequency of closure of the arterial duct is low.
Impact on the ability to drive vehicles and manage mechanisms
Not applicable. It is intended for use only in newborns.
OVERDOSE
There is no known case of overdose associated with intravenous ibuprofen administration to premature newborns.
However, an overdose is described in children who received ibuprofen for oral administration.
Observed symptoms included CNS depression, seizures, gastrointestinal disorders, bradycardia, arterial hypotension, dyspnea, impaired renal function, and hematuria.
Cases of massive overdose (after taking doses more than 1000 mg / kg), accompanied by coma, metabolic acidosis and passing renal failure are described. After the standard treatment all patients recovered. One case of overdose with a lethal outcome was registered: after taking the drug at a dose of 469 mg / kg in a 16-month-old child due to respiratory arrest, development of convulsive syndrome and subsequent aspiration pneumonia.
Treatment: conduct symptomatic therapy.
DRUG INTERACTION
Ibuprofen may reduce the effects of diuretics; in patients with dehydration diuretics may increase the risk of nephrotoxicity of NSAIDs.
Ibuprofen can enhance the effect of anticoagulants and increase the risk of bleeding.
When used concomitantly with GCS, ibuprofen may increase the risk of developing gastrointestinal bleeding.
Since ibuprofen and nitric oxide inhibit the function of platelets, their combination theoretically increases the risk of bleeding.
Avoid concomitant use of two or more NSAIDs due to an increased risk of adverse reactions.
Since ibuprofen can reduce the clearance of aminoglycosides, the simultaneous administration of these drugs may increase the risk of nephrotoxicity and ototoxicity.
Pharmaceutical interaction
Pediaa В® should not be mixed with other drugs, except for 0.9% sodium chloride solution or 5% glucose solution.
Solution Pedega В® should not come into contact with acidic solutions, for example, solutions of certain antibiotics or diuretics. To prevent significant changes in pH caused by the presence of acidic drugs that could remain in the infusion system, before and after the appointment of Pedega В® , the 1.5-2 ml of 0.9% sodium chloride solution or 5% glucose solution should be washed with the infusion system.
It is forbidden to use chlorhexidine for disinfection of the ampoule neck, since the Pediaa В® solution is not compatible with this compound. To disinfect the ampoule, 60% ethyl alcohol is recommended before use. After disinfecting the ampoule necks with an antiseptic, the ampoule should be completely dried and only then opened to exclude the interaction of the antiseptic with the PedegaВ® solution.
TERMS OF RELEASE FROM PHARMACY
The drug is approved for use only in hospitals.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children at a temperature of no higher than 25 В° C. Shelf life - 4 years.
