2 Cardiovascular system
2.14 Drugs affecting the ductus arteriosus
thrombocytopenia, increased platelet count, alo-pecia, Stevens-Johnson syndrome, and toxic epidermal necrolysis
Licensed use not licensed for use in children Indication and dose
Hyperlipidaemia including familial hyper-cholesterolaemia(on specialist advice only) . By mouth
Child 10–18 years200 mg once daily adjusted according to response to max. 200 mg 3 times daily
Bezafibrate(Non-proprietary)A
Tablets, bezafibrate 200 mg, net price 100-tab pack
= £11.23. Label: 21 Bezalipc(Roche)A
Tablets, f/c, bezafibrate 200 mg, net price 100-tab pack = £9.15. Label: 21
FENOFIBRATE
Cautions see under Bezafibrate; liver function tests recommended every 3 months for first year (discontinue treatment if significantly raised) Hepatic impairment avoid in severe impairment Renal impairment reduce dose if estimated glomerular filtration rate less than 60 mL/minute/
1.73 m2; avoid if estimated glomerular filtration rate less than 15 mL/minute/1.73 m2
Contra-indications gall bladder disease; photo-sensitivity to ketoprofen
Pregnancy embryotoxicity in animal studies—
manufacturer advises avoid
Breast-feeding manufacturer advises avoid—no information available
Side-effects see under Bezafibrate; also very rarely hepatitis, pancreatitis, and interstitial pneumopathies
Licensed use LipantilcMicro 67 is licensed for use in children with hypercholesterolaemia Indication and dose
Hyperlipidaemias including familial hyper-cholesterolaemia(on specialist advice only) . By mouth
Child 4–15 years1 capsule/20 kg body-weight daily
Child 15–18 yearsinitially 3 capsules daily in divided doses; usual range 2-4 capsules daily
Lipantilc(Solvay)A
LipantilcMicro 67 capsules, yellow, fenofibrate (micronised) 67 mg, net price 90-cap pack = £23.30.
Label: 21
ing to renal failure; avoid if possible in severe impairment
Contra-indications life-threatening infection;
active bleeding especially intracranial or gastro-intestinal; thrombocytopenia or coagulation defects; marked unconjugated hyperbilirubinae-mia; known or suspected necrotising enterocoli-tis; pulmonary hypertension
Side-effects intestinal perforation; intraventricu-lar haemorrhage; ischaemic brain injury;
bronchopulmonary dysplasia, pulmonary haemorrhage; thrombocytopenia, neutropenia, oliguria, haematuria, fluid retention, hyponatr-aemia; less commonly gastro-intestinal haemorr-hage; hypoxaemia
Licensed use Orphan licence for the injection for closure of ductus arteriosus in premature neo-nates less than 34 weeks gestational age
Indication and dose Closure of ductus arteriosus . By slow intravenous injection
Neonateinitially 10 mg/kg as a single dose followed at 24-hour intervals by 2 doses of 5 mg/kg; course may be repeated after 48 hours if necessary
Mild to moderate pain, pain and inflammation of soft tissue injuries and rheumatic disease, pyrexiasection 10.1.1
Administration By slow intravenous injection over 15 minutes, preferably undiluted. May be diluted, with Glucose 5% or Sodium Chloride 0.9%
Pedeac(Orphan Europe)A
Intravenous solution, ibuprofen 5 mg/mL, net price 4 2-mL vials = £263.00
INDOMETACIN
Cautions see notes above; also may mask symp-toms of infection; may reduce urine output by 50% or more (monitor carefully—see also under Anuria or Oliguria, below) and precipitate renal impairment especially if extracellular volume depleted, heart failure, sepsis, or concomitant use of nephrotoxic drugs; may induce hyponatr-aemia; inhibition of platelet aggregation (monitor for bleeding);interactions: Appendix 1 (NSAIDs) Anuria or oliguriaIf anuria or marked oliguria (urinary output less than 0.6 mL/kg/hour), delay further doses until renal function returns to normal
Hepatic impairment can cause fluid retention;
avoid in severe hepatic impairment
Renal impairment use lowest effective dose and monitor renal function; sodium and water reten-tion; deterioration in renal function possibly lead-ing to renal failure; avoid if possible in severe impairment
Contra-indications untreated infection, bleeding (especially with active intracranial haemorrhage or gastro-intestinal bleeding); thrombocytopenia, coagulation defects, necrotising enterocolitis Side-effects haemorrhagic, renal,
gastro-intes-tinal, metabolic, and coagulation disorders;
pulmonary hypertension, intracranial bleeding, fluid retention, and exacerbation of infection Indication and dose
Closure of ductus arteriosus
. By intravenous infusion over 20–30 minutes Neonate under 48 hoursinitially 200 micr-ograms/kg as a single dose followed by (if urine
output adequate) 2 doses of 100 micrograms/kg at intervals of 12–24 hours; course may be repeated after 48 hours if necessary Neonate 2–7 daysinitially 200 micrograms/kg as a single dose followed by (if urine output adequate) 2 doses of 200 micrograms/kg at intervals of 12–24 hours; course may be repeated after 48 hours if necessary Neonate over 7 daysinitially 200 micrograms/
kg as a single dose followed by (if urine output adequate) 2 doses of 250 micrograms/kg at intervals of 12–24 hours; course may be repeated after 48 hours if necessary NoteIn some units by intravenous infusion initially 100 micrograms/kg (200 micrograms/kg if sympto-matic) then 100 micrograms/kg every 24 hours for 5 further doses
Pain and inflammation in rheumatic disease section 10.1.1
Administration For intravenous infusion dilute each vial with 1–2 mL Sodium Chloride 0.9% or Water for Injections
Indocid PDAc(IDIS)A
Injection, powder for reconstitution, indometacin (as sodium trihydrate), net price 3 1-mg vials =
£43.50 (hosp. only)
Maintenance of patency
In the newborn with duct-dependent congenital heart disease it is often necessary to maintain the patency of the ductus arteriosus whilst awaiting surgery.
Alprostadil (prostaglandin E1) and dinoprostone (prostaglandin E2) are potent vasodilators that are effective for maintaining the patency of the ductus arter-iosus. They are usually given by continuous intravenous infusion, but oral dosing of dinoprostone is still used in some centres.
IBUPROFEN (continued)
BNFC 2009 2.14 Drugs affecting the ductus arteriosus
165
2Cardiovascularsystem
During the infusion of a prostaglandin, the newborn requires careful monitoring of heart rate, blood pressure, respiratory rate, and core body temperature. In the event of complications such as apnoea, profound bradycardia, or severe hypo-tension, the infusion should be temporarily stopped and the complication dealt with; the infusion should be restarted at a lower dose. Recurrent or prolonged apnoea may require ventilatory support in order for the prostaglandin infusion to continue.
ALPROSTADIL
Cautions see notes above; also history of haemorrhage; avoid in hyaline membrane dis-ease; monitor arterial pressure, respiratory rate, heart rate, temperature, and venous blood pres-sure in arm and leg; facilities for intubation and ventilation must be immediately available; inter-actions: Appendix 1 (alprostadil)
Side-effects apnoea (particularly in neonates under 2 kg), flushing, bradycardia, hypotension, tachycardia, cardiac arrest, oedema, diarrhoea, fever, convulsions, disseminated intravascular coagulation, hypokalaemia; cortical proliferation of long bones; weakening of the wall of the ductus arteriosus and pulmonary artery may follow prolonged use; gastric-outlet obstruction reported
Indication and dose
Maintaining patency of the ductus arteriosus . By continuous intravenous infusion
Neonateinitially 5–10 nanograms/kg/minute, adjusted according to response in steps of 5–
10 nanograms/kg/minute; max. 100 nan-ograms/kg/minute (but associated with increased side-effects)
NoteAlprostadil doses in BNFC may differ from those in product literature
Administration dilute 150 micrograms/kg body-weight to a final volume of 50 mL with Glucose 5% or Sodium Chloride 0.9%; an intravenous infusion rate of 0.1 mL/hour provides a dose of 5 nanograms/kg/minute. Undiluted solution must not come into contact with the barrel of the plastic syringe; add the required volume of alprostadil to a volume of infusion fluid in the syringe and then make up to final volume Prostin VRc(Pharmacia)A
Intravenous solution, alprostadil 500 micrograms/
mL in alcohol. For dilution and use as an infusion.
Net price 1–mL amp = £75.19 (hosp.only)
DINOPROSTONE
Cautions see notes above; also history of haemorrhage; avoid in hyaline membrane dis-ease; monitor arterial oxygenation, heart rate, temperature, and blood pressure in arm and leg;
facilities for intubation and ventilation must be immediately available;interactions: Appendix 1 (prostaglandins)
Contra-indications
Hepatic impairment manufacturer advises avoid in hepatic impairment
Renal impairment manufacturer advises avoid in renal impairment
Side-effects nausea, vomiting, diarrhoea; flush-ing, bradycardia, hypotension, cardiac arrest;
respiratory depression and apnoea, particularly with high doses and in low birth-weight neonates, bronchospasm; pyrexia and raised white blood cell count, shivering; local reactions, erythema; if used for longer than 5 days, gastric outlet obstruction; cortical hyperostosis (prolonged use) Licensed use not licensed for use in children
Indication and dose
Maintaining patency of the ductus arteriosus . By continuous intravenous infusion
Neonateinitially 5–10 nanograms/kg/minute, increased as necessary in 5 nanogram/kg/min-ute increments to 20 nanograms/kg/minnanogram/kg/min-ute NoteDoses up to 100 nanograms/kg/minute have been used but are associated with increased side-effects
. By mouth
Neonate20–25 micrograms/kg every 1–2 hours doubled if necessary; if treatment continues for more than 1 week gradually reduce the dose Administration for continuous intravenous infusion,
dilute to a concentration of 1 microgram/mL with Glucose 5% or Sodium Chloride 0.9%.
For administration by mouth, injection solution can be given orally; dilute with water ProstincE2(Pharmacia)A
Intravenous solution, for dilution and use as an infusion, dinoprostone 1 mg/mL, net price 0.75-mL amp = £8.52; 10 mg/mL, 0.5-mL amp = £18.40 (both hosp. only)
Extemporaneous formulations available see Extemporaneous Preparations, p. 8
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2.14 Drugs affecting the ductus arteriosus BNFC 20092Cardiovascularsystem