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Showing content with the highest reputation since 08/10/2019 in Tutorials

  1. 2 points
    Dose & administration Three doses at 24-hour intervals, as intravenous injections over 15 minutes, or by oro-gastric administration: 1st dose: 10 mg/kg 2nd and 3rd dose: 5 mg/kg Indications Closure of the patent ductus arteriosus. Contraindications and special considerations (incl incompatibilities) Contraindications include: duct-dependent cardiovascular malformation active bleeding, including intracranial, gastrointestinal or lung bleeding necrotizing enterocolitis (confirmed or suspected) significant thrombocytopenia or coagulation defects significantly reduced renal function significant hyperbilirubinemia Pulmonary hypertension has been reported when ibuprofen was given within 6 hours after birth. Concomitant use the following pharmaceuticals products is not recommended: diuretics: ibuprofen may reduce the effect of diuretics, and diuretics may increase the risk of renal insufficiency in dehydrated patients. anticoagulants: ibuprofen may inhibit platelet function and concomitant use with anticoagulants may increase the risk of bleeding corticosteroids: concomitant use with ibuprofen may increase the risk of gastrointestinal bleeding nitric oxide: since both nitric oxide and ibuprofen inhibit platelet function, concomitant use may in theory increase the risk of bleeding other NSAIDs: concomitant use of more than one NSAID should be avoided because of the increased risk of adverse reactions aminoglycosides: ibuprofen may reduce clearance of aminoglycosides, concomitant use may increase the risk of nephrotoxicity and ototoxicity, and surveillance of serum levels of aminoglycides should be performed Ibuprofen should not be administrated with any acidic solution. Adverse effects Oligura and transient renal insufficiency. Ibuprofen has less renal side-effects than indomethacin. Pharmacological aspects Ibuprofen is an anti-inflammatory drug (NSAID) that reduces the synthesis of prostaglandins through a non-selective inhibition of cyclo-oxygenase. Prostaglandins are involved in the persistence of the ductus arteriosus after birth, through relaxation of the muscle layer of the ductus arteriosus. The reduction of prostaglandins by ibuprofen is believed to be the main mechanism of action. The estimated T1/2 is 30 (16-43) hours. References Summary of product characteristics. Pedea -EMEA/H/C/000549 -IG/392. (URL) Ibuprofen for the treatment of patent ductus arteriosus in preterm or low birth weight infants. Cochrane Database of Systematic Reviews 2015, Issue 2. Art. No.: CD003481. 
PMID: 25692606 Pulmonary hypertension after ibuprofen prophylaxis in very preterm infants. Lancet 2002; 359: 1486–88. PMID: 11988250 Document version history 2017-02-10 / Stefan Johansson
  2. 1 point
    Dose & administration Closure of Ductus Arteriosus: Dose is dependent on age of infant at time of therapy and course includes three doses given IV with 12 to 24 hour intervals between doses (ref 1). Post-natal age at first dose: Less than 48 hours: 1st dose 0.2 mg/kg, followed by 2nd and 3rd doses of 0.1 mg/kg/dose 2-7 days: 0.2 mg/kg/dose >7 days: 1st dose: 0.2 mg/kg, followed by 2nd and 3rd doses of 0.25 mg/kg/dose If the ductus arteriosus closes or is significantly reduced in size after an interval of 48 hours or more from completion of the first course, no further doses are necessary. If the ductus arteriosus re-opens, a second course of 1 to 3 doses may be given, each dose separated by a 12 to 24 hour interval as described above. Prevention of intraventricular hemorrhage: Although dosing regimes of 0.1-0.2 mg/kg/dose have been studied, the largest RCT (ref 2) used the following schedule: 0.1mg/kg/dose IV over 20 minutes and every 24 hours, beginning the first day of life and for a total of 3 doses. Indications To close a hemodynamically significant patent ductus arteriosus in preterm infants. To prevent intraventricular hemorrhage in preterm infants, weighing less than 1250g. Contraindications and special considerations (incl incompatibilities) Contraindications include active bleeding, significant thrombocytopenia or coagulation defects, necrotizing enterocolitis, untreated proven or suspected infection, and significantly impaired renal function. Incompatibilities: Solution: 7.5% dextrose in water and 10% dextrose in water Injection site: calcium gluconate, cimetidine, dobutamine, dopamine, gentamicin, and tobramycin Adverse effects Bleeding problems, higher incidence of transient oliguria and elevations of serum creatinine, decreased platelet aggregation, and hypoglycemia. Further, gastrointestinal perforations may occur if used concurrently with corticosteroids. For this reason, concomitant administration of indomethacin and glucocorticoids should be avoided. If anuria or marked oliguria (urinary output <0.6 mL/kg/hr) is evident at the scheduled time of the second or third dose of, do not give additional doses until laboratory studies indicate that renal function has returned to normal. Pharmacological aspects The exact mechanism of action through which indomethacin causes closure of a patent ductus arteriosus is not known, but inhibition of prostaglandin synthesis is the suggested mechanism of action. The plasma half-life of indomethacin is variable among premature infants and has shown to vary inversely with postnatal age and weight: Postnatal age less than 7 days old averaged 20 hours Postnatal age more than 7 days old averaged 12 hours Weighing less than 1000 g averaged 21 hours Weighing more than 1000 g averaged 15 hours Monitor urine output, serum electrolytes, glucose, creatinine and blood urea nitrogen levels, platelet counts, and signs of bleeding should be monitored during treatment. References Product Information: indomethacin IV injection. APP Pharmaceuticals, LLC (per Manufacturer), Schaumburg, IL, Mar, 2010. (URL) Long-Term Effects of Indomethacin Prophylaxis in Extremely-Low-Birth-Weight Infants. N Engl J Med 2001; 344:1966-1972. PMID: 11430325 Indomethacin Prophylaxis to Prevent Intraventricular Hemorrhage: Association between Incidence and Timing of Drug Administration. The Journal of pediatrics. 2013;163(3):706-10.e1. PMID: 23522865 Effects of Indomethacin Prophylaxis Timing on IVH and PDA in Extremely Low Birth Weight (ELBW) Infants. Archives of disease in childhood Fetal and neonatal edition. 2016;101(5):F418-F422. PMID: 18661761 Managing the patent ductus arteriosus in the premature neonate: a new look at what we thought we knew. Semin Perinatol Apr, 2012; 36(2): 130-138. PMID: 22414884 Prophylactic intravenous indomethacin for preventing mortality and morbidity in preterm infants. Cochrane Database Syst Rev 2010, Issue 7. Art. No.: CD000174. PMID: 20614421
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