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Medication Update: January 2007

Medication Update is a bi-monthly newsletter of the Pharmacy and Therapeutics Committee for physicians, pharmacists and nurses.

New Formulary Drugs

Ciprofloxacin/dexamethasone (Ciprodex®) ear drops

This combination product is now available for use only in patients with a tympanostomy tube or perforated eardrum. Use of tobramycin/dexamethasone (Tobradex) ear drops should be avoided in these patients.

Subcutaneous Immune Globulin injection (Vivaglobin®)

Vivaglobin is a subcutaneous option for immune globulin therapy in patients with primary immunodeficiency who need or desire an alternative form of therapy to IV or IM immunoglobulin. It has been approved for addition to the formulary for use only as a first dose when converting patients to a subcutaneous immune globulin regimen. Approval by Immunology Service is required. See article in this issue for more details.

Human papillomavirus vaccine (Gardasil®)

Human Papillomavirus vaccine prevents cervical cancer, genital warts and cervical, vulvar or vaginal dysplasias. It is given as three 0.5mL injections at 2-month intervals. It has been added to the formulary with use restricted to female patients nine years of age and older awaiting transplant or who use the CHRMC system as their medical home. Length of protection is unknown and minimum protective antibody level has not been established.

Levetiracetam (Keppra®) injection

Levetiracetam injection has been added to the formulary for use only in patients where oral administration is not feasible. When switching from oral therapy, the initial IV dose and frequency remain unchanged. Loading dose is not indicated and use for treatment of patients in status epilepticus is not recommended. For administration, intravenous levetiracetam vial is further diluted and given over 15 minutes. No infusion related adverse reactions have been reported.

Source CF vitamins

Specialty multivitamins (Source CF) softgels and 60mL pediatric drops are available as alternatives to ADEKs. The pediatric drops are more expensive, but may be more palatable than ADEKs drops. Source CF softgels can be swallowed whole and do not stain teeth like ADEKs chewables.

Pegfilgrastim (Neulasta®)

When compared to filgrastim, pegfilgrastim has an added polyethylene glycol molecule which reduces renal clearance and prolongs persistence in vivo (half life range: 46-62 hours). The effects of one dose of pegfilgrastim last fourteen days. The use of pegfilgrastim may result in increased compliance (fewer missed doses) and less wastage of unused drug at home. Pegfilgrastim injection (6mg/0.6mL prefilled syringes) has been approved for addition to the formulary for patients receiving myelosuppressive chemotherapy with at least 14 days between chemotherapy doses. It can only be given subcutaneously and not intravenously (filgrastim can be given by either route).

Lidocaine patch 5% (Lidoderm®)

It is indicated for relief of pain associated with post-herpetic neuralgia, although it has also been used successfully by pain service at CHRMC to treat neuropathic pain caused by drugs such as calcineurin-inhibitors (cyclosporine, tacrolimus) and vinca alkaloids (vinblastine, vincristine, vinorelbine). Since it is used topically, it has the advantage of minimizing systemic adverse effects and drug-drug interactions associated with oral or IV analgesics. The patch can be cut to the size of the affected area, and therefore reducing unnecessary drug absorption. Up to 3 patches can be applied for up to 12 hours at a time within a 24-hr period, but pediatric dosing guidance is very limited. Since at least 95% (655 mg) of lidocaine remains in a used patch, extra caution should be exercised when disposing used patches to avoid accidental ingestion by children and pets. Applying heat to the patch should be avoided as it can increase amount absorbed and also reduce adhesion of patch to the skin.

Mirtazapine (Remeron)

Mirtazapine is a tetracyclic antidepressant that is a third line agent in youth with sleeping problems and/or weight loss. It increases appetite and weight gain in patients with eating disorders. This medication should not be used in patients less than 12 years old.

Other Formulary Issues

Generic cyclosporine The committee approved a proposal that unless the prescriber specifically notes otherwise, pharmacy will automatically substitute an FDA-rated “AB” generic cyclosporine for Neoral ordered for all non-BMT inpatients upon initiation of cyclosporine therapy AND all non-BMT outpatients previously stabilized on generic cyclosporine.

Hydrocortisone dosing

The following will be added to the formulary:

  • when converting from IV to oral routes, a 1:1 conversion is recommended for all patients.
  • for severe neonatal hypotension or suspected adrenal insufficiency, the hydrocortisone dose is 1 mg/kg one time; repeat 1 mg/kg every 6 hours for persistent or severe hypotension.

Formulary deletions

  • Potassium iodide 325mg/5mL oral solution (PIMA); Coal tar lotion (Neutrogena T/Derm Oil); Mivacurium; Gonadarelin (Factrel) - manufacturer discontinued.

Thyroid Hormone Brand Interchangeability

By Christopher Schaffner, Pharm.D. Candidate 2007

The bioequivalence and interchangeability of brand/generic thyroid hormone preparations is still a hotly debated topic. While some medical specialty practice guidelines caution against the substitution of one thyroid preparation with another, the FDA has approved the generic forms as bioequivalent. Some opponents of therapeutic substitution argue that the FDA’s criteria for bioequivalence (AUC and Cmax of generic products within 80-125% of reference (brand) products with a 90% confidence interval) is not stringent enough. However, proponents of substitution have argued that as long as a generic product falls within the FDA’s range, any variability from the reference product can be considered insignificant because issues such as patient compliance and inconsistency of administration (with/without food) can lead to substantial variability in exogenous thyroid hormone levels.

Since dose titration can be time consuming, it seems counterproductive to potentially introduce more variability by switching thyroid products during titration and after steady state maintenance doses have been reached. However, temporarily (during hospital admission) placing a patient on a different brand of thyroid supplementation will rarely make a clinical difference. It is possible that long term steady state plasma concentrations may be slightly different if brands are interchanged during therapy. For this reason laboratory values (TSH and T4) should be checked two weeks after any product change. Dose adjustments, if at all necessary, can then be made based on lab result.

Subcutaneous use of Immune Globulin for Primary Immune Deficiency Disorder

By Jill Mack, pharmacy intern

Patients who are diagnosed with Primary Immune Deficiency Disorder (PIDD) face a lifetime of monthly intravenous infusions of immune globulin therapy to keep their immune defense somewhat normal. For most patients, the monthly intravenous infusions must be done in a clinic by a trained health care provider, which is time consuming and takes them from their normal schedule at school or work. Subcutaneous immune globulin infusion, commonly administered with a pump, is a promising alternative route of administration that would allow patients the freedom to self-infuse at home. Subcutaneous administration has also been successfully used in patients who have conditions or side effects that hinder their normal intravenous infusion, such as poor venous access, anaphylactic reactions to intravenous use, and rapid clearance following intravenous administration.

Published studies have looked at the efficacy and change in the quality of life in patients who are switched from once monthly intravenous infusions of immune globulin to about once weekly subcutaneous infusions at home. Some studies used the readily available 10% IV immune globulin products for subcutaneous administration while some used 16-16.5% products that were FDA approved for intramuscular use. For subcutaneous administration, patients are limited to 15mL of immune globulin per infusion site, which makes a product with a higher concentration preferable. If multiple injection sites are needed, a pump is usually attached to all the sites and infused simultaneously at a maximum rate of 20mL per hour. According to the studies, many patients were found to have a greatly improved quality of life after switching from IV infusions to subcutaneous use at home. The subcutaneous route of administration was effective in achieving normal serum IgG levels and had less variation in peak and trough levels in comparison to previous intravenous infusions.

Vivaglobin® was approved by FDA in January 2006. It is a 16% protein solution that is intended for subcutaneous use. The bioavailability of Vivaglobin® is about 73% in comparison to IV administration. It is recommended that the patient start treatment with Vivaglobin® one week after receiving a regularly scheduled IVIg infusion. The initial weekly Vivaglobin® dose can be calculated by multiplying the previous IVIg dose by 1.37, then dividing this dose into weekly doses based on the patient’s previous IVIg treatment interval.

With the increasing availability of alternate immune globulin products, patients will have many more options for therapy which will give them more flexibility and better control over their disease.

References

  1. E. Richard Stiehm, et al. Immunodeficiency and other clinical immunology: Slow subcutaneous human intravenous immunoglobulin in the treatment of antibody immunodeficiency: Use of an old method with a new product. J Allergy Clin Immunol 1998 June; 101(6): 848-9.
  2. UWE Nicolay, et al. Health-related quality of life and treatment satisfaction in North American patients with primary immunodeficiency diseases receiving subcutaneous IgG selfinfusions at home. Journal of Clinical Immunology 2006 Jan; 26(1):65-72.
  3. Vivaglobin Dossier information, ZLB Behring, August, 2006.

Credits

Editors

  • Anny Chan, PharmD
  • Eric Harvey, PharmD, MBA, BCPS

P&T Chairs

  • Janet Englund, MD
  • Eric Harvey, PharmD, MBA, BCPS

Address

Children's Hospital and Regional Medical Center P&T Committee, R-3409
4800 Sand Point Way NE
PO Box 5371/R-3409
Seattle, WA 98105