……………For Your Drug Information ………….

2. Emend® (aprepitant) – a neurokinin-1 (NK-1) receptor antagonist indicated for the prevention of acute and delayed nausea and vomiting caused by chemotherapy. The drug, due to its extensive metabolism via the CYP450-3A4, will have several significant drug interactions to monitor. It is available in 80 mg and 125 mg capsules with dosing as follows: 125 mg 1 hour before receiving chemotherapy and then 80 mg daily in the morning for 2 days following chemotherapy. Manufactured by Merck & Co. Inc., a 3 day course of therapy will cost approximately $250.00.

3. Aralast® (human alpha-1 proteinase inhibitor) – indicated for augmentation therapy in patients with congenital deficiency of the alpha-1 proteinase inhibitor with clinical emphysema. This product will not cure nor will it reverse existing lung damage, but will prevent further complications associated with this disorder. The drug will be manufactured by Alpha and distributed by Baxter, and will most likely be handled via special registry.

4. Oxytrol® (oxybutinin transdermal patch) – for the treatment of overactive bladder. The patch is manufactured by Watson Pharmaceuticals. Each 39 mg/cm² system contains 36 mg oxybutinin for delivery of 3.9 mg/day. The patch will be applied twice weekly (or every 3-4 days).

3. A gluten restricted diet is necessary for patients with a history of primary intestinal malabsorption (celiac disease and sprue), gluten-induced enteropathy and dermatitis herpetiformis. Starches, binders, fillers, and excipients found in various pharmaceuticals can be problematic in this patient population. Contacting the pharmaceutical manufacturer would be necessary to clarify if a product if gluten-free.

( See Micromedex 2003-Drug Consults, Topic: Gluten-free Pharmaceuticals for additional information sources. Additional resources could be found in the internet about drug listings.)

A: Linezolid is a weak and reversible MAO-I. The drug company (Pharmacia) does not warrant them serious enough to cause labeling changes / contraindications.²

The following is a list of agents that have been observed to cause significant effects when given concomitantly with linezolid and some agents which have no observed effects.

Recommend to avoid or use alternate agent if using with Linezolid:

Tyramine foods (tyramine content exceeding 100mg) – cause increase in BP

Phenylpropanolamine (PPA) and Pseudoephedrine (PSE) – cause increase in BP

Proceed with caution (weigh risk vs. benefit): ^{1, 2, and 3}

Dopamine and Epinephrine – cause increase in BP

SSRI – could potentially cause Serotonin Syndrome (confusion, delirium, restlessness,

Tremors, blushing, diaphoresis, hyperpyrexia)

No reported interaction: ^{1, 2, 3}

Meperidine (Demerol) – no effects seen if given with Linezolid during and post-

marketing studies.

Dextromethorphan – no Serotonin syndrome reported with Linezolid during marketing trials

Suggested course of action:

Patient receiving linezolid and Dopamine, Epinephrine - educational approach only – send an FYI note or verbally talk to the caregivers (whichever is appropriate). They need to watch for BP spikes (especially for patients with labile BP’s), during and immediately after linezolid infusions.

Patient receiving SSRI and Linezolid – educational approach only – the caregivers/ prescribers need to watch for symptoms of serotonin syndrome while they are on both.

Patients on PPA or PSE and linezolid – avoid PPA or PSE or high Tyramine foods while on linezolid.

1. Drugdex 2003 – Linezolid – Drug interaction

2. Personal Communication – Pharmacia Upjohn

3. Zyvox PPI - 2001

Reference: #9;

1. Prevacid PPI – 2002

2. Personal Communication – TAP Pharmaceuticals

A: Yes. Neither bacterial nor any viral infection is a contraindication for administering Synagis. Although the drug is indicated for prevention of RSV infection, it is still recommended to continue giving Synagis, in the presence of an RSV infection, because there are different strains of RSV and Synagis will be used as a prevention for other future RSV infection. Doses should not be skipped if RSV infection is present as it depletes the level of the drug in the body, interrupting its rise to steady state.

A: There have been no official stability studies with Ferrlecit, hence the package insert states that it should be used immediately after compounding. However, there is nothing unstable about the molecule – and there is experiential use with making the drug in the morning and using it in dialysis shifts throughout the day. There were no reported problems, so one could infer that the drug is stable in solution for at least 12 hours. Ferrlecit can also be given IVP ² (125mg over 10min), hence eliminating the need for compounding.

Reference:

1. Personal Communication – Watson Pharmaceuticals

2. Drugdex- Ferrlecit (2003)

A: Acetazolamide sustained release capsule (Diamox Sequels®) is the oral dosage form most commonly utilized for the treatment of chronic open-angle glaucoma with the normal dose being 500 mg BID. When acetazolamide is used for the short term treatment of metabolic alkalosis, the 250 mg tablet (non-susutained release form) would be the preferred product. The tablet has a quicker onset of action and a shorter duration of action. This pharmacokinetic profile would be preferable in patients who require only 2-3 doses of oral acetazolamide. If the patient require chronic therapy a switch to the sustained release form would be reasonable for patient convenience and to insure compliance. After 4 weeks of therapy with Diamox Sequels® 500 mg BID versus acetazolamide 250mg tablets QID, steady state serum concentrations were essentially the same.

Reference:

1. Drugdex 2003 – Acetazolamide – Therapeutic Uses
2. Diamox PPI- Wyeth Ayerst Laboratories

1. There are several differences between lean body mass (LBM), ideal body weight

(IBW), and adjusted body weight, even though they are often used interchangeably.

LBM: Accounts for >99% of the body’s metabolic activity and is comprised of non-fat-cell mass and intercellular connective tissue. One of the most accurate ways to measure this is via whole body densitometry measurements by underwater immersion; however, this measurement is not portable and patient cooperation is difficult to obtain. Other measurements such as anthropometric or bioelectric impedance are easier to use but less accurate.

IBW: This is often used as an easy alternative to LBM; however, the equations used are rough estimates. The most common equation for this parameter is the one developed by Devine:

IBW (males) = 50 kg + 2.3 kg/in for ht over 5 ft

IBW (females) = 45.5 kg + 2.3 kg/in for ht over 5 ft

Adjusted Body Weight: This is used as a "happy medium" when total body weight

may overestimate and IBW may underestimate drug distribution.

Adjusted weight = 0.4 (TBW-IBW) + IBW

When considering which of these weights to use, you would want to consider the

lipophilicity and the Volume of distribution (Vd) of the drug in question. For example, drugs with a small Vd that are known to be hydrophilic, such as rocuronium, you could use a conservative approach and dose based on IBW, since you would expect little if any drug to distribute to adipose tissues. However, when dosing drugs of moderate volumes of distribution, such as aminoglycosides and phenytoin, an adjusted dosing weight is recommended. Lipophilic drug distribution is often difficult to predict and the question of whether or not to use a conservative approach is determined by assessing the need for rapid response as well as the safety and toxicity of the drug. For example, digoxin is highly lipophilic and has a large Vd. However, when loading doses are given, they are generally based on IBW instead of TBW, and the total loading dose is divided into smaller doses spread out over a period of time.

Reference:

1. Erstad, BL. AJHP. 59(1): 2105-2110.

Symptoms associated with hypophosphatemia include muscle weakness, rhabdomyolysis, respiratory failure, difficulty in weaning from ventilators, altered mental status, altered myocardial performance, and hemolytic anemia. This consult is designed to help guide your recommendations but each patient must be assessed on an individual basis.

*These lab values will be helpful with other issues that are associated with hypophosphatemia.

a). Patient has recently been started on parenteral or enteral nutrition support. Patients who have been NPO for 3-5 days and have recently begun parenteral or enteral nutrition support often develop "refeeding syndrome" which manifests as hypophosphatemia, hypomagnesemia, etc. during the early days of nutrition support. Hypophosphatemia can also develop in patients who are being feed >35 kcal/kg/day. PLEASE REFER QUESTIONS ABOUT THESE TYPES OF PATIENTS TO NUTRITION SUPPORT SERVICE AT 655-3834.

b). Patients receiving phosphate binding antacids, or sucralfate may develop hypophosphatemia. These drugs should be discontinued if possible.

c). Patients with hypercalcemia should be treated very cautiously to avoid metastatic calcification of tissues. If the product of the serum calcium and phosphate exceeds 60 mg²/dl² then very cautious replacement therapy should be instituted by a physician familiar with phosphate replacement therapy. Ionized calcium levels provide the most accurate picture of patient’s calcium status. If a ionized calcium is not available then serum albumin levels must also be assessed. Serum calcium levels may be falsely low in patients with hypoalbuminemia. For every 1 gm/dl fall in serum albumin below 4, serum calcium will fall about 0.8 mg/dl.

Example: NS has a serum calcium value of 7.6 mg/dl and a serum albumin of 1.5 gm/dl. What is her adjusted serum calcium level?

Take 4 – 1.5 = 2.5 then 2.5 x 0.8 = 2 then 7.6 + 2 = 9.6 mg/dl adjusted calcium values.

d). Patients with renal dysfunction (creatinine clearance < 30 ml/min) should be given about one half or less of the normal dose recommendations.

e). Assess patient’s serum sodium and potassium values. Unless the patient’s potassium is greater than 4 mmol/dl, potassium phosphate is often the preferred form of salt supplement as these patients often have a concomitant hypokalemia. Sodium phosphate would be the preferred supplement in patients with renal dysfunction or serum potassium greater than 4 mmol/dl.

Note: Patients that are critically ill may require more aggressive therapy and more frequent monitoring of therapy.

This table can serve as a guideline for phosphate replacement therapy:

#Maximum rates of 7.5 – 8 mmol of phophorus/hr have been used but rapid infusion of phosphorus has been associated with hypotension, hypocalcemia, and development or renal failure.

*Use actual body weight unless >130% of ideal body weight. If > 130% of ideal body weight then use adjusted weight (Calculation is Adjusted weight = 0.25[actual body weight – ideal body weight] + ideal body weight). Note: This Adjusted weight does not utilize the same formula we use for other drugs!!!

Suggest that the oral route may be used for patients with mild to moderate hypophosphatemia (who are currently tolerating other PO therapy) and use the IV route for patients with severe depletions. Oral dose replacements should be divided into 2-3 doses to avoid problems with GI intolerance.

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

+These items are formulary of OSF Saint Francis Medical Center

When suggesting either PO or IV replacement therapy one should always keep in mind the amount of sodium or potassium that is provided in a particular product.

Phosphate for IV replacement therapy is available as a sodium or potassium salt. The potassium salt provides 3 mmoles of phosphate and 4.4 meq of potassium per ml. The sodium salt provides 3 mmoles of phosphate and 4 meq of sodium per ml.

To prevent confusion, the drug should be ordered in millimoles of phosphorus. Phosphate salts are compatible in either dextrose or sodium containing solutions. Generally, dilute desired IV dose in 250 ml of D5W or Normal Saline. [Note: A minimum of 100 ml of solution should be used for every 10 meq of potassium given (or 50 ml of solution for every 10 meq of potassium if a central line is being used)]. If a patient requires larger doses, repletion may occur over shorter time periods when venous access or compatibility with other maintenance infusions becomes problematic (see maximum rates of infusion listed above).

Recheck a serum phosphorus level 4-6 hours after the PO dose or start of IV replacement therapy (or with AM labs). Patients who have severe hypophosphatemia and are critically ill may require multiple doses of replacement therapy before normalization of serum phosphorus levels occur. Levels should be monitored daily for at least 2-3 days after a severely low level has been treated. Calcium levels, and if appropriate sodium and potassium levels, should also be monitored.

References:

1. Micromedex 2003 Drug Consult on hypophosphatemia. Drug Evaluations: K-Phos Neutral, Neutra-Phos (and K), Fleets Phospho-soda, and Uro-KP-Neutral.

2. Applied Therapeutics: The Clinical Use of Drugs. 6^th Edition

3. Drug Information Handbook, 8^th Edition, 2001-2002.

4. Wilson: Williams Textbook of Endocrinology, 9^th Edition Copyright 1998; pg: 1193-95.

5. Dickerson RN. Guidelines for the Intravenous Management of Hypophosphatemia, Hypomagnesemia, Hypokalemia, and Hypocalcemia. Hospital Pharmacy, Vol.36 (11)1201-1208.

6. Clark CL. Sacks GS, et al. Treatment of hypophophatemia in patients receiving specialized nutrition support using a graduated dosing scheme: Results from a prospective clinical trial. Critical Care Medicine, Vol.23 (9)1504-1511.

7. Perreault MM. Ostrop NJ, Tierney MG. Efficacy and Safety of Intravenous Phosphate Replacement in Critically Ill Patients. The Annals of Pharmacotherapy, Vol.31:683-687.

Note: The article by Dickerson in Hospital Pharmacy provides practical information that is easy to read, copies of the article can be found in the Drug Information files: Diseases: Hypophosphatemia. Please make a copy for yourself and return the original to the DI files.

Atomoxetine is the first selective norepinephrine reuptake inhibitor to be approved by the FDA for the treatment of Attention Deficit - Hyperactivity Disorder (ADHD). The drug is manufactured and distributed by Eli Lilly and Company. Atomoxetine is approved for use in children, as well as adults. Stattera® is available in 10, 18, 25, 40, and 60 mg capsules.

Atomoxetine is well absorbed after oral administration and may be given without regard to food. The drug is primarily metabolized via cytochrome P450 (Cyp2D6) with an estimated half-life of approximately 5 hours. Drug interactions primarily occur with other drugs that are cleared through the Cyp2D6 isoenzyme of P450. The metabolism of this drug is subject to genetic variations in the Cyp2D6 isoenzyme with subjects either being poor or extensive metabolizers. Atomoxetine does not inhibit or induce the Cyp2D6 pathway. Atomoxetine is extensively metabolized, with less than 3% of the drug being excreted unchanged in the urine. Pharmacokinetics have been studied in adults and children 6 years and older. The kinetics in children and adolescents are similar to those in adults.

Atomoxetine Drug Interactions: In patients who are considered extensive metabolizers of the atomoxetine, inhibitors of Cyp2D6 (eg. paroxetine, fluoxetine, and quinidine) may require dosage adjustments. Stattera® can increase blood pressure, and heart rate and can additive cardiovascular effects with albuterol and pressor agents. Use of Strattera® and MAOI’s is contraindicated. A two week wash-out period should be allowed after discontinuing either drug or before starting either drug, in patients who have been exposed to both drug classes.

Atomoxetine is generally well tolerated with the most common side effects being listed in pediatric patients as: dyspepsia, nausea, vomiting, fatigue, appetite suppression, dizziness, and mood swings (incidence of 5% or greater or at least twice as common when compared to placebo). The most common side effects listed in adult patients were: constipation, dry mouth, nausea, appetite suppression, dizziness, insomnia, sexual dysfunction, urinary dysfunction (hesitation or retention), and dysmenorrhea.

Comparative Studies: The effectiveness of Strattera® was established in 6 randomized, double-blind, placebo controlled studies. Four of these trials compared atomoxetine with placebo, 2 of these trials compared atomoxetine with methylphenidate. Atomoxetine was shown to have comparable efficacy to methylphenidate with possibly fewer side effects seen in the atomoxetine group in one trial. ²

Atomoxetine Dosing:

Children and adolescents </= 70 kg: Start with 0.5mg/kg/day and can be increased every 3 days, to a maximum of 1.2 mg/kg given once daily or divided and given twice daily.

Adolescents and adults > 70 kg: Start with 40 mg daily with increases made at a minimum of 3 day intervals, to a target dose of 80 mg daily (or 40 mg BID). The dose may be further increased to a maximum of 100 mg after a 2 – 4 week period with the 80 mg dosing if optimal responses have not been obtained.

Reference: Package insert, Eli Lilly and Co. Atomoxetine, Strattera®

² Kratochil CJ, et al. Atomoxetine and methylphenidate treatment in children with ADHD: A prospective, randomized open-label trial. J. Am. Acad. Child Adolesc. Psychiatry, July 2002, 41(7):776-784.

Acetaminophen Study Medication will be taken from Suremeds

ANGIOMAX Study Medication will be stored in Main Pharmacy

AT-3 ECMO Study Medication will be stored in Gerlach Pharmacy

CAPS Study Medication will be stored in Gerlach Pharmacy

Ketorolac Study Medication will be stored in Gerlach Pharmacy

RESOLVE Study Medication will be stored in Gerlach Pharmacy
 

RSV Thickened Formula Study
Randomization list will be in Gerlach
Pharmacy ID Binder ( no drug involved)

ADDRESS Study Medication will be stored in Gerlach Pharmacy

APOLLO Study Medication will be stored in Main Pharmacy

BAXTER rAHF-PFM Study Medication will be stored in Main Pharmacy

CORLOPAM Study Medication will be stored in Gerlach Pharmacy

DEDAS Study Medication will be stored in Gerlach Pharmacy

EXCLAIM Study Medication will be stored in Main Pharmacy

ONO Stroke Study Medication will be stored in Gerlach Pharmacy

PREVENT Study Medication will be stored in Main Pharmacy

SYNERGY Study Medication will be stored in Gerlach Pharmacy