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Ibuprofen


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

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Thanks @Stephan . How about the use of ranitidine meanwhile the ibuprofen is used, especially the PO administration. Is there any evidence that it decreases the side effect of ibuprofen in regard to gastric irritation !? Does it interfere with the effectivity of the ibuprofen. In my unit after a day 1-2 if any deterioration of the RFT we do switch to paracetamol course. And the deterioration we detected it in case of extreme preterms 24-26 weekers .  Our observation - personal experience- that paracetamol has closed the PDA, in couple of cases where ibuprofen was started but then stopped, and switched to use of paracetamol . 

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@Rola alzir thanks for your comment. I am not aware of any data supporting the use of ranitidin (or other anti-acid drugs) with ibuprogen.

In general, the use of anti-acids seems to have few (if any) positive effects, but side-effects. Read the blog post below by Keith Barrington (from 2013 but still relevant) and when it comes to GERD, check out the document by ESPGHAN

https://neonatalresearch.org/2013/12/06/acid-suppression-doesnt-work-and-its-not-safe-phunny-how-we-got-here/ 

https://www.ncbi.nlm.nih.gov/pubmed/29470322

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On 9/7/2019 at 8:24 AM, Rola alzir said:

Thanks @Stephan . How about the use of ranitidine meanwhile the ibuprofen is used, especially the PO administration. Is there any evidence that it decreases the side effect of ibuprofen in regard to gastric irritation !? Does it interfere with the effectivity of the ibuprofen. In my unit after a day 1-2 if any deterioration of the RFT we do switch to paracetamol course. And the deterioration we detected it in case of extreme preterms 24-26 weekers .  Our observation - personal experience- that paracetamol has closed the PDA, in couple of cases where ibuprofen was started but then stopped, and switched to use of paracetamol . 

 

Thanks @Stefan Johansson

This explains the issue of antacids with suspected  GERD . 

What I was wondering about is the combination of the ranitidine with the use of ibuprofen in cases where PDA was hemodynamically significant , mandating medical closure . 

If this topic is been touched or investigated or the combination is been practiced . To hear from those who have any input about it .  

i will share  these provided links with my colleagues as the use of Esomeprazole is practiced here for neonatal GERD cases. 

 

Thanks a lot for the the rich input 

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10 minutes ago, Rola alzir said:

 

Thanks @Stefan Johansson

This explains the issue of antacids with suspected  GERD . 

What I was wondering about is the combination of the ranitidine with the use of ibuprofen in cases where PDA was hemodynamically significant , mandating medical closure . 

If this topic is been touched or investigated or the combination is been practiced . To hear from those who have any input about it .  

i will share  these provided links with my colleagues as the use of Esomeprazole is practiced here for neonatal GERD cases. 

 

Thanks a lot for the the rich input 

As Stefen Said there is no role of antacid while giving Ibuprofen. For first instance why you want to give antacids for Ibuprofen? if it is to prevent gastric irritation then answer is No. As far as RFT are concerned , all these side effects are transient and will resolve with time. all you need to do is to reduce fluids management and reduce if oliguria during therapy with ibuprofen. 

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@Stefan Johansson I have been through the link attached . It’s interesting reading. Still I would like to know more about acetaminophen which we used to use sin my unit , as in extreme preterm where RFT is of concern we do go with acetaminophen with ECHo repeat on D4 of treatment . We do give total 7 days , providing that initial baseline LFT is reassuring. 

Q please : you do start ibuprofen even if baby is not yet fully fed ? As you have mentioned it’s been given early in first 14-21 days . Means at 7DOL it can still be initiated. 

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