Pedee - instructions for use, dose, side effects, contraindications

Ibuprofen has anti-inflammatory, analgesic and antipyretic activity. Ibuprofen is a racemic mixture of S (+) and R (-) enantiomers. Research in vivo and in vitro suggest that the clinical activity of ibuprofen is associated with the S (+) enantiomer. Ibuprofen is a nonselective inhibitor of cyclooxygenases, which causes a decrease in the synthesis of prostaglandins.

Since prostaglandins delay the closure of the arterial duct after birth, it is believed that suppression of cyclooxygenase is the main mechanism of action of ibuprofen when used for this indication.

Pharmacokinetics:

The maximum plasma concentrations after the appointment of the first and last maintenance dose are about 35-40 mg / l, regardless of the gestational and postnatal age of children. After 24 hours after the last dose of 5 mg / kg, the residual concentrations are about 10-15 mg / l.

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 the ratio,similar to that observed in adults (approximately 60%). The apparent volume of distribution is on average 200 ml / kg (62-350 ml / kg according to different studies). The central volume of distribution may depend on the status of the duct and decrease as the duct closes.

The rate of ibuprofen elimination in newborns is significantly lower than in adults and older children; the half-life 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. Most of ibuprofen, like other NSAIDs, is associated with plasma albumin, although in neonatal plasma this binding is significantly less (95%) than in adult plasma (99%). In the serum of newborns ibuprofen competes with bilirubin for binding to albumin, as a result of which, at high concentrations of ibuprofen, the free fraction of bilirubin may increase.

In premature newborns ibuprofen significantly reduces the concentration of prostaglandins and their metabolites in plasma, especially PGE2 and b-keto-PGF-l-alpha. In newborns who received 3 doses of ibuprofen,low concentrations of prostaglandins persisted for up to 72 hours, whereas 72 hours after the administration of only 1 dose of ibuprofen, a repeated increase in the concentration of prostaglandins was observed.

Indications:Treatment of a hemodynamically significant open arterial duct in premature newborns with a gestational age of less than 34 weeks.

Contraindications:

Pediaa® is contraindicated in the following cases:

- life-threatening infection;

- clinically pronounced bleeding, especially intracranial or gastrointestinal hemorrhage;

- thrombocytopenia or blood clotting disorder;

- Significant 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.

Carefully:

The drug should be used with caution in case of suspected infectious diseases.

The Pedega® preparation should be administered with great care to avoid extravasation followed by possible irritation of the tissues. Because the ibuprofen can suppress platelet aggregation, premature newborns need close monitoring aimed at detecting signs of bleeding.

Because the ibuprofen can reduce the clearance of aminoglycosides, with the joint appointment of aminoglycosides and ibuprofen it is recommended to constantly monitor the concentrations of these compounds in the serum.

Since it is shown that in vitro ibuprofen competitively displaces bilirubin from the binding site with albumin, in preterm infants, the risk of bilirubin encephalopathy may increase. Concerning ibuprofen should not be prescribed to newborns with severe unconjugated hyperbilirubinemia. It is recommended to closely monitor the function of the kidneys and gastrointestinal tract.

Pregnancy and lactation:It is intended for use only in newborns.

Dosing and Administration:

The drug is administered only intravenously.

Treatment with Pedega® should only be performed in the neonatal intensive care unit under the supervision of an experienced neonatologist.The course of treatment includes three intravenous doses of Pedega®, given at intervals of 24 hours.

The dose of ibuprofen is selected depending on the body weight as follows:

- 1st injection: 10 mg / kg

- 2nd and 3rd injections: 5 mg / kg.

The Pediaa® preparation is administered in the form of a short 15-minute infusion, preferably undiluted. If necessary, the volume can be adjusted with a solution of sodium chloride 9 mg / ml (0.9%) for injection or a solution of glucose 50 mg / ml (5%) 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 effects:

- Violations of blood clotting leading to bleeding, for example, intestinal and intracranial hemorrhages; breathing disorders and pulmonary hemorrhage;

- disorders of the digestive system, for example, obstruction and perforation of the intestine;

- a violation of the kidneys, for example, 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 received at clinical trials of Pedega®. The causes of adverse events observed in premature newborns 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).

Infringements from	Often: thrombocytopenia, neutropenia
circulatory and
lymphatic system
Infringements from	Often: intraventricular hemorrhage,
nervous system	periventricular leukomalacia
Infringements from	Often: bronchopulmonary dysplasia
respiratory system,	Often: pulmonary hemorrhage
organs of the chest and	Rarely: hypoxemia (occurred within 1 hour after
the mediastinum	first infusion with normalization of the condition for 30
	minutes after inhalation with nitric oxide).
Gastrointestinal	Often: necrotizing enterocolitis, perforation
disorders	intestines
	Rarely: gastrointestinal bleeding
Infringements from	Often: oliguria, fluid retention, hematuria
kidney and urinary tract	Rarely: acute renal failure
Deviations from the norm	Often: increase in creatinine concentration in
laboratory data	blood, a decrease in the concentration of sodium in the blood
research

Overdose:

There is no known case of an overdose associated with the intravenous administration of ibuprofen to premature newborn children.

However, an overdose is described in children who received ibuprofen for oral administration: the symptoms observed included CNS depression, seizures, gastrointestinal disorders, bradycardia, 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 fatal outcome was registered: after taking a dose of 469 mg / kg in a 16-month-old child due to respiratory arrest, and development of convulsive syndrome and subsequent aspiration pneumonia. In case of an overdose of ibuprofen, symptomatic therapy is necessary.

Interaction:

Ibuprofen, like other NSAIDs, can interact with the following medicines:

- diuretics: ibuprofen can reduce the effects of diuretics; in patients with dehydration diuretics may increase the risk of nephrotoxicity of NSAIDs;

- anticoagulants: ibuprofen can enhance the effect of anticoagulants and increase the risk of bleeding;

- glucocorticosteroids: ibuprofen may increase the risk of gastrointestinal bleeding;

- Nitric oxide: since both drugs suppress the function of platelets, their combination theoretically increases the risk of bleeding;

- other NSAIDs: concomitant use of two or more NSAIDs should be avoided due to an increased risk of adverse reactions;

aminoglycosides: since ibuprofen can reduce the clearance of aminoglycosides, while the prescription of these drugs may increase the risk of nephrotoxicity and ototoxicity.

Incompatibility

This drug should not be mixed with other drugs.

A solution of Pedega® should not come into contact with acidic solutions, for example, solutions of certain antibiotics or diuretics. Between infusions of various medicines it is necessary to wash the infusion system.

It is forbidden to use chlorhexidine for disinfecting the neck of the ampoule, since the Pedia® 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 Pedega® solution.

This drug should not be mixed with other drugs, except 0.9% (9 mg / ml) of sodium chloride solution for injection or 5% (50 mg / ml) of glucose solution.

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®, it is necessary to rinse the infusion system of 1.5-2 ml with a 0.9% (9 mg / ml) solution of sodium chloride or 5% (50 mg / ml) of the glucose solution for injection.

Special instructions:

Prior to the appointment of the Pedega® preparation, an appropriate echocardiographic examination should be performed 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® 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, Pedega® should not be used for preventive purposes.

Being a non-steroidal anti-inflammatory drug (NSAID), ibuprofen can mask the symptoms of infectious diseases.

It is shown that in treatment of the recommended scheme of premature newborns with gestational age less than 27 weeks, the frequency of closure of the arterial duct is low.

Effect on the ability to drive transp. cf. and fur:Not applicable. It is intended for use only in newborns.

Form release / dosage:

Solution for intravenous administration 5 mg / ml.

Packaging:2 ml of solution in ampoules of colorless hydrolytic glass type I. The ampoule is marked with a break point and a marking strip.

Four ampoules are placed in a detachable container of foamed polymer, the container is placed in a cardboard box along with the instructions for use.

Storage conditions:Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.

Shelf life:4 years. Do not use after the expiration date.

Terms of leave from pharmacies:For hospitals

Registration number:LSR-008162/08

Date of registration:16.10.2008

The owner of the registration certificate:Orphan EuropeOrphan Europe France

Manufacturer: & nbsp

ORPHAN EUROPE France

Representation: & nbspRUSFIK LLC RUSFIK LLC Russia

Information update date: & nbsp22.12.2014

Illustrated instructions

Instructions

Pedee® (Pedea)