……………For Your Drug Information ………….

1). Avinza® - a new extended release version of morphine sulfate produced by Elan. Available in 30mg, 60 mg, 90 mg, 120 mg capsules for use in moderate to severe pain in patients who need continuous analgesia.
2). Curosurf® - a new porcine lung surfactant (Poractant alpha) by Dey. Used for respiratory distress syndrome in infants. Available as 80 mg/ml for endotracheal use. Dosed as 2.5ml/kg in 2 divided doses, may repeat at 1.25 ml/kg at 12 hour intervals up to a maximum cumulative dose of 5 ml/kg.
3). Alora® - a new estradiol patch used as hormone replacement therapy in post-menopausal women. The patch is available in 0.05 mg, 0.75 mg, and
0.1 mg patch sizes from Watson Laboratories.
4). Secreflo® - a synthetic porcine secretin for use in secretin stimulation testing, causes stimulation of pancreatic secretion, including bicarbonate. Used to aid in the diagnosis of pancreatic exocrine dysfunction. Also stimulates gastrin and can aid in the diagnosis of gastrinoma.
5). Orfadin® - nitisinone is an orphan drug approved for treatment of hereditary tyrosemia type I, a rare pediatric disease causing progressive liver failure and liver cancer in young children. Available as 2, 5, and 10 mg capsules the starting dose is 1 mg/kg in 2 divided doses.
6). Benicar® - olmesartan is a new angiotensin II receptor blocker from Forest Laboratories Inc. and Sankyo Pharma Inc. The drug is approved for treatment of hypertension and is available in 5, 20, and 40 mg tablets.
7). Faslodex® - fulvestrant injection , a selective estrogen receptor antagonist for second-line treatment of metastatic breast cancer in hormone receptor positive, post-menopausal women. Dose is 250 mg once monthly.

1). Watch those peds dosing -

-Double check the dosing from 2 references if possible: common mistakes involve a mg/kg/day dose and it is written as a mg/kg/dose ...
- Double check the weight - with the nurse
- Double check the math - just because there is a mg/kg written as a dose -does not mean that they did the math correctly

Always double check to make sure that the dose conversions are appropriate. Many drugs require reduction of dose / change in frequency etc..
Oral synthroid to IV synthroid
Oral metoprolol to IV metoprolol
Oral digoxin to IV digoxin
Oral diltiazem to IV diltiazem (not appropriate unless for afib control)
Oral enalapril to IV enalapril

Any changes of drugs from oral to IV - please check carefully.

3). Modifications in the WARNINGS, PRECAUTIONS, and ADVERSE REACTIONS sections of the labels for Actos® and Avandia®. Patients who were using either of these drugs as monotherapy or in combination with insulin had problems with fluid retention. The fluid retention may cause, or worsen songestive heart failure. Recommend that the patients be observed for signs and symptoms of heart failure. Patients with rapid weight gain, edema or who develop shortness of breath ( or other symptoms of worsening CHF) should notify their doctor. Patients with NYHA Class III and IV status were not studied in clinical trials with Actos® or Avandia® and not recommended in these patients.

Fondaparinux is synthetic pentasaccharide low molecular weight heparin. The drug’s action on antithrombin III results in a reduction in thrombin (factor IIa) generation and thrombus development without inhibiting thrombin itself. Arixtra® does not interact with platelet factor 4 or platelets and may find future application for HIT (heparin induced thrombocytopenia). Fondaparinux has no significant effect on aPTT, bleeding time, or PT. Monitoring of Factor Xa levels may be necessary in selected patients.

This is the first of a new class of agents intended to selectively inhibit activated Factor X (factor Xa) by binding exclusively to antithrombin III. It is FDA approved for prophylaxis of DVT for patients undergoing hip fracture surgery, hip replacement surgery, or knee replacement surgery.

Fondaparinux is not currently formulary at OSF Saint Francis but the review is offered as this drug is being used in an investigational drug study.

Fondaparinux should be started 6 – 8 hours following surgical closure at a dose of 2.5mg SQ daily, there is one dose for ALL indications. The drug has about 50% renal clearance and is excreted as the parent compound. The manufacturer (Sanofi-Synthelabo) suggests that empiric dose reductions should occur in patients with decreased renal function.

Fondaparinux is contraindicated in patients weighing less than 50 kg and those with severe renal function. As with enoxaparin, Arixtra® should never be used in situations when spinal anesthesia or a spinal puncture was employed (e.g. epidural anesthesia).

Fondaparinux has been compared to enoxaparin for prophylaxis of DVT in total hip replacement and results of the study showed similar or slightly superior effect of fondaparinux over enoxaparin. Studies comparing fondaparinux to either heparin or dalteparin showed similar efficacy but the studies looked at indications for which fondaparinux is not currently FDA approved.

References:
Fragmin® package insert
Lovenox® package insert
Micromedex 1974 – 2002 Drug Consult on Arixtra®
Eriksson BI, Bauer KA, et al. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip-fracture surgery. NEJM November 1, 2001 Vol. 345(18): 1298 – 1310.

Ergotamine
SL: 1-3 tabs / attack (max of 3tabs ) ; 6mg/24hrs ; max limit: 2d/wk* or 10mg/wk
Oral:1 to 6 tabs /attack (max of 6tabs); 6mg/24hrs; max limit: 2d/wk* or 10mg/wk
Supp:1/2 to 2 supp /attack (max of 2 supp = 4mg) ;max limit: 2d/wk*or 10mg/wk

DHE
IM/IV 0.25 - 1mg/ attack (max 3mg/day) Max limit: 20mg/week
( repeated IV DHE, given over 3 - 7 days in an inpatient setting is effective and safe for the treatment of intractable headache in adults)
( * Can relax limits in menstrual migraine and cluster HA. From Silberstein and Young)

Clinical comparisons: (from Lipton)

Ergotamine (ET) vs DHE
DHE less arterial vasoconstriction than ET therefore less ischemic effects and higher doses tolerable
Same potency -effect for venoconstriction
DHE more potent alpha -adrenergic blocker activity
DHE less nausea/vomiting , uterotonic effects , rebound HA

Contraindications for DHE and ET : (from Lipton)
Pregnancy, renal or hepatic failure, coronary, cerebral and peripheral vascular disease; allergies, sepsis, uncontrolled hypertension

Co-administration with erythromycin (? Other macrolides - decreased metabolism of DHE or ET.

Special precautions if concomitant administration of DHE or ET with methylsergide or sumatriptan - increased risk of arteriospasms. Avoid concomitant administration ( < 24hrs within each other) with b-blockers - increase alpha adrenergic vasoconstrictive properties of DHE or ET.

IV DHE Protocols used: ( From Raskin's repetitive IV DHE protocol - modified) (detailed timing and dose chart in article )

* 0.33 - 0.5mg IV test dose (over 1-2min) and if no ADE detected , give remaining dose . Give 0.5mg IV DHE q8hrs thereafter if HA improves and no detected ADE after test dose (observe dose limits above)
* Premedicate with Reglan 10mg prior to each DHE doses x 6 doses
* Lomotil prn for diarrhea
* Benztropin (or an anticholinergic agent) prn for dystonia, akithisia, agitation
 

Continuous IV infusion: (from Ford and Ford; more details in article)
* Premedicate with Reglan 10mg in 50ml NS over 30min then 10mg in 50ml NS q8hr x 6 doses
* DHE 3mg in 1000ml NS at 42ml/hr ( will give 3mg/24hrs) - usually start at lower infusion rate and titrate to 42ml/hr.
* Lomotil prn for diarrhea, benztropin ( or an anticholinergic agent ) prn for dystonic/EPS reactions due to Reglan
* Reduce DHE infusion rate if significant nausea occurs at anytime.

IV stability:

1mg / 250ml of NS = no precipitation
Stored at room temp and exposed to fluorescent light = potency did not change after 96 hours at above condition ( Sandoz Pharmaceuticals)
3mg/1000ml NS = no ppt and lose of potency ( Ford and Ford) at above condition.

The likely mechanism by which magnesium sulfate causes bronchodilation is smooth muscle relaxation secondary to inhibition of calcium uptake. This allows bronchial smooth muscle to relax and dilate. In patients with severe asthma, magnesium sulfate 25-50mg/kg, (max 2gm) given IV over 20-30 minutes has been shown to improve peak expiratory flow rate, oxygen saturation, and respiratory rate compared to baseline. Magnesium sulfate has a short half-life and duration of action, and Dib et al1 found that a repeat bolus and start of an infusion of 20mg/kg/hr improved control. Ciarallo et al2 conducted a randomized, double-blind, placebo-controlled trial in 31 pediatric patients, giving saline vs 25mg/kg (2gm max) magnesium sulfate IV over 20 minutes. 4/15 in magnesium group went home from the emergency department, while none in the placebo group were discharged to home from ED. No adverse drug events were noted in either group.

What you need to know: PICU has adopted a 50mg/kg magnesium sulfate bolus (max 2gm) followed by a 25mg/kg/hr infusion. Serum level goals 4-6mg/dL. Patient may experience nausea, vomiting and facial paresthesia at this level. Signs of toxicity with higher magnesium levels (6-10mg/dL) include: sedation, flushing, hypoventilation, decreased deep tendon reflexes, and muscle weakness.

Diprivan® (propofol) is a medication that is often used for maintenance of ICU sedation. Rates for maintenance of intubated, mechanically ventilated patients vary from 5-50 mcg/kg/min or higher. A 10% fat emulsion is used as a vehicle to create the propofol emulsion. The addition of propofol to a patient's drug regimen adds 10 grams of fat/100ml of propofol. Problems can arise when large amounts of propofol are delivered to patients because large amounts of fat are also delivered. The A.S.P.E.N. (American Society of Parenteral and Enteral Nutrition) standards and guidelines for safe practices in parenteral nutrition suggest that 15-30 % of caloric requirements (for adults) be provided as fat. This amount can be adjusted based on patient tolerance but studies have shown limited benefit when fat amounts exceed 30%. The Nutrition Support Service generally follows a 1 gm/kg/day dosing guideline for adult patients on total parenteral nutrition (TPN). This guideline is provided to the pharmacist to remind that high doses of propofol, such as those sometimes required in obese patients, may put patients at risk for fat overload.

High doses of fat emulsion have several associated problems. Large amounts of fat can cause hypertriglyceridemia and precipitate acute pancreatitis. Large amounts of fat have been associated with immune suppression (affects lymphocye activity). Additionally, Diprivan® does not contain any preservatives and fat emulsions serve as an excellent growth media for fungus and other microorganisms.

The bottom line: When reviewing orders for Diprivan® calculate a gm/kg/day dose of the fat content (utilize dosing weight) to assess if patient is receiving > 1 gm/kg/day fat. Check to see if the patient is on TPN and notify the PEN lab (655-3834). TPN fat content is adjusted by PEN lab daily for patients receiving large doses of Diprivan®. If doses of fat exceed 1gm/kg/day suggest that MD obtain a baseline triglyceride level and that should be repeated q48-72 hours. When triglyceride levels start to approach 300 mg/dl, alternate sedative therapy may be necessary. Keep in mind that once Diprivan® reaches steady state (after very long infusions) about half the initial rate will maintain the same plasma levels.

4). IV phosphate replacement therapy, what are the dosing guidelines for administering IV phosphate replacement therapy? By: Ann Corkery

IV phosphate therapy is available as sodium or potassium form of phosphate. The potassium salt provides 3 mM of phosphate and 4.4 meq of potassium per ml. The sodium salt provides 3 mM of phosphate and 4 meq of sodium per ml. The salt chosen for replacement therapy depends on the amount of sodium or potassium that will be delivered to the patient, in relation to lab values for these two ions as listed in the patient's BMP or CMP. To prevent confusion, the drug should be ordered in millimoles of phosphorus.

Normal daily phosphate requirements:

Neonates 1-2 mMol/kg
Infants/Children 0.5-1 mMol/kg
Adolescents 10-40 mMol/day
Adults 20-50 mMol/day

Normal laboratory values for phosphorus:

Newborns 4.2 - 9 mg/dl
6 wk to 19 mos 3.8 - 6.7 mg/dl
19 mos to 3 yr 2.9 - 5.9 mg/dl
3-15 yr 3.6 - 5.6 mg/dl
> 15 yr 2.5 - 5 mg/dl

Adult patients can be classified as having mild (2.29 - 3 mg/dl), moderate (1.61 - 2.2 mg/dl) or severe (< 1.49 mg/dl) hypophosphatemia. Replacement therapy depends on the degree of hypophosphatemia. Patients with mild to moderately low phosphate levels (>2 – 2.5 mg/dl) may have the phosphate repleted by the oral route. Phosphorus can be replaced orally in doses of 30 – 60 mmoles using the products listed below. (See table below for P.O. phosphorus replacement products).

Patients with severe hypophosphatemia (<1 – 1.5 mg/dl) will require IV repletion. Generally, replace as 0.16 - 0.32 mMol/kg and give doses over 6 - 24 hours. Patients may require repeat doses until phosphorus level rises above 2 - 2.5 mg/dl. Remember to look at the amount of sodium or potassium the patient would receive and determine which salt would be better choice for repletion. (This applies to both PO and IV repletion). Patients with hypercalemia are at risk for metastatic calcification and may require less aggressive repletion. Serum calcium levels should also be monitored closely. Patients with renal failure require lower doses due to decrease ability to clear phosphorus. The following table was found in Wilson: Williams Textbook of Endocrinology, 9th Edition. (Copywright 1998 W.B. Saunders Company):

Consider: Severity of hypophosphatemia, likelihood of underlying phosphate depletion, clinical condition of the patient, renal function, serum calcium, and concurrent parenteral therapy (glucose, hyperalimentation):

Rates shown are for a 70-kg person. Most formulations available in the United States provide 3 mmol/mL of sodium or potassium phosphate. **Larger doses of phosphate should be given over 12 – 24 hour period.

Finally, a reminder that calcium salts and phosphate salts have a very limited scope of compatibility and admixture in the same IV solution is best avoided. Infusion of the phosphorus replacement dose should not be done in the same line where calcium salts are being infused.

¨ Neutra-Phos or Neutra-Phos-K caps or powder should be opened and dissolved in 75 ml of water.

Reference:
Applied Therapeutics: The Clinical Use of Drugs. 6^th Edition
Pediatric Dosage Handbook, 8th Edition, 2001-2002.
Drug Information Handbook, 9th edition, 2001-2002.
Micromedex 1974-2002, Drug consult on hypophosphatemia

5). How is Sucrose used for prevention and treatment of pain in the NICU?

Sweet-tasting substances have been shown to have a calming and analgesic effect in neonates. Premature infants have difficulty metabolizing and excreting pain medications that are routinely used in other patient populations

(e.g. acetmainophen can cause methemoglobinemia in preemies). Sucrose appears to be a safer alternative for treating minor procedural pain, such as from heelsticks or blood draws in these infants.

The NICU is using a 24% Sucrose product, Sweet-Ease®, in doses of 0.05 ml (12 mg) about 2 minutes before the painful procedure. The sucrose is being used in infants 27 weeks PCA (post-conceptual age) and greater and the maximum number of doses the infant receives depends on the PCA. The sucrose is given orally by syringe to the tongue, buccally, or is placed onto a pacifier, which is then placed in the infant’s mouth. The sucrose is used in conjunction with containment, rocking, or swaddling. The nurse will be documenting pain scores before, during, and after the painful procedure. The protocol also breaks out the number of doses a patient can receive in a 24 hour period based on the PCA. Accuchecks are done twice daily with labs or the glucose on the BMP is used. The NICU is also monitoring the infants for adverse effects such as hyperglycemia, and necrotizing enterocolitis (NEC).

Reference:
NICU protocol 2001
Franck, LS. The Use of Sucrose Analgesia to Relieve Procedural Pain in Neonates.  HYPERLINK http://www.childmed.com
www.childmed.com (c) 2000, Vol(1),Issue 1
Stevens, B. Taddio, A., et al. The efficacy of sucrose for relieving procedural pain in neonates - a systematic review and meta-analysis. Acta Paediatr 1997;86:837-42.