Growth Hormone Therapy: A Specialty Pharmacy Overview

Growth hormone deficiency in children and adults is a disease state that utilizes growth hormone therapy. Here is what specialty pharmacists can do for these patients and what they should know about these conditions.

One of the therapeutic categories that has historically fallen into the realm of specialty management is growth hormone therapy. The 9th edition of the EMD Serono Specialty Digest reports that 96% of health plans surveyed had prior authorization strategies in place to ensure appropriate utilization of growth hormone therapy in 2012—up 13% from 2011 and leading the specialty therapeutic categories as the most commonly managed therapeutic class. Furthermore, 71% of plans surveyed have indicated that they have selected a preferred product in this category. Programs to reduce drug costs and reduce product waste are also common among those specialty pharmacies that work with health plans to manage their growth hormone population.¹

Growth hormone in the body is responsible for stimulating normal growth of skeletal, connective, muscle, and organ tissues in children and adolescents and also plays a key role in the metabolism of adults. The recombinant somatropin products available in the marketplace mimic these actions and bind to growth hormone receptors to produce a variety of direct and indirect physiologic effects.²

GROWTH HORMONE INDICATIONS

There are many different disease states in which growth hormone therapy is used (Table). Growth hormone deficiency in children and adults is among the more common indications. Childhood onset growth hormone deficiency can be secondary to congenital, genetic, acquired, or idiopathic causes. Adult onset growth hormone deficiency can be endogenous or can occur as a result of other hormone deficiencies such as hypopituitarism caused by trauma, surgery, radiation, or pituitary disease.²

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Idiopathic short stature (ISS) can also be treated with growth hormone therapy. ISS is a medical condition in which the height of the individual is more than 2 standard deviations below the mean for the patient’s age, sex, and population group, with no evidence of systemic, endocrine, nutritional, or chromosomal abnormalities. Children with ISS have a normal birth weight and adequate endogenous growth hormone levels. ISS encompasses up to 80% of all short children at or below 2 standard deviations below the mean and includes short children who have constitutional delay of growth and puberty and familial short stature.³

Prader-Willi Syndrome (PWS) results from an abnormality on the 15th chromosome and causes low muscle tone, short stature, incomplete sexual development, cognitive and motor deficits, a chronic feeling of hunger, and a metabolism that uses significantly less calories than normal. This can lead to excessive overeating and life-threatening obesity if calories and food consumption are not strictly monitored. When a patient with PWS is born, the first phase is failure to thrive due to weak muscles and difficulty with the sucking reflex. Between the age of 2 and 5 years, the second stage typically begins and includes an extreme unsatisfied drive to consume food which lasts throughout the lifetime of the patient. PWS occurs equally in females and males and occurs in approximately 1 in 15,000 children.⁴

Turner Syndrome (TS) is found exclusively in females and occurs when 1 of the 2 X chromosomes is missing or incomplete. It affects 1 in 2500 female births, and there are estimated to be 71,000 females living with TS in the United States. Short stature, incomplete sexual development, and ovarian failure and infertility are common characteristics of TS.⁵

Patients who are small for gestational age (SGA) can also benefit from growth hormone therapy. SGA is a term used for a baby who is born smaller than expected for the number of weeks of pregnancy. Typically, these babies have birth weights below the 10th percentile for babies of the same gestational age. SGA infants may be proportionately small or they may be of normal length and size but have lower weight and body mass. Most SGA is caused by fetal growth problems that occur during pregnancy, such as intrauterine growth restriction when the fetus does not receive necessary nutrients and oxygen needed for proper growth and development. Intrauterine growth restriction is often due to chromosomal abnormalities, maternal disease, severe problems with the placenta, or other problems.⁶

In patients with growth failure associated with renal failure, more than 50% of adults with childhood-onset chronic kidney disease achieve final heights that are below the third percentile. Chronic kidney disease can be associated with metabolic acidosis, endocrinopathy, anemia, and cardiac dysfunction that may also result in growth failure. There is some indication that growth hormone therapy may have a positive impact on cellular metabolism and immune regulation in addition to growth.⁷

Noonan Syndrome is caused by changes in 1 of several autosomal dominant genes. It affects approximately 1 in 2500 people and typically manifests as unusual facial characteristics, short stature, heart defects present at birth, bleeding problems, developmental delays, and problems with the development of the rib cage.⁸

Human growth hormone can also be used in patients with HIV-related wasting with high doses found to increase weight and lean body mass.⁹ In addition, patients with short bowel syndrome may benefit from utilization of growth hormone by reducing their parenteral nutrition requirements.¹⁰ Patients with deficiency in the short stature homeobox-containing gene (SHOX) due to deletion, mutation, or reduced expression may also benefit from growth hormone therapy to treat the resultant short stature.¹¹

POTENTIAL FOR ABUSE

One of the concerns for growth hormone therapy is the well-publicized potential for abuse. Healthy adults may abuse growth hormone in the hopes of stopping or reversing the aging process or in the hopes of improving athletic performance, although there have been conflicting results in clinical trials designed to measure endurance, strength, muscle mass, and fat mass in healthy patients. Abuse of growth hormone can lead to a variety of adverse events in the short term including joint and muscle pain, fluid build-up, and swelling in the joints. Growth hormone taken in high doses over a long period of time may lead to heart disease. In addition, growth hormone sold without a prescription or otherwise obtained illegally may be counterfeit or contain unknown or harmful ingredients and may not be produced in a safe manner.¹²

SPECIALTY PHARMACY CONSIDERATIONS^2,13-23

Here is what specialty pharmacists can do for growth hormone therapy patients and what they should know about the conditions associated with it:

• Counsel patients on potential side effects, therapy considerations, and potential drug—drug interactions.
• Become familiar with the various delivery devices specific to different growth hormone therapies in order to provide mixing instructions if necessary, injection training, and answer patient questions regarding dosage delivery.
• Assess barriers in adherence and persistency of growth hormone therapy.
• Provide tools to remove identified barriers to adherence and persistency such as copayment assistance resour-ces, refill management, and reminder strategies for the patient.
• Become familiar with the process and required elements for prior authorizations, if necessary. Manufacturer reimbursement resources may also be of assistance and can be found on the respective product websites.
• Monitoring parameters may include bone age determination, growth rate, an ophthalmologic exam, serum growth hormone levels, and thyroid function tests.
• Serum levels of inorganic phosphorus, alkaline phosphatase, parathyroid hormone, and insulin-like growth factor 1 may increase during somatropin therapy and should be periodically monitored.
• Patients with preexisting tumors should be monitored for progression, recurrence, or a second neoplasm.
• Glucose levels should be periodically monitored in all patients. Doses of concurrent antihyperglycemic drugs in diabetic patients may require adjustment.
• Monitor for fluid retention and communicate with prescriber about dose reduction as necessary.
• Hypothyroidism may become evident or worsened.
• Be aware that children with an onset of a limp or hip or knee pain may need to be evaluated for a slipped capital femoral epiphysis.
• Preexisting scoliosis may progress in patients who experience rapid growth.
• Consider pancreatitis in patients with persistent severe abdominal pain.
• Growth hormone therapy should be discontinued in patients with PW syndrome if signs of upper airway obstruction or sleep apnea occur.

References:

• EMD Serono Specialty Digest: Managed Care Strategies for Specialty Pharmaceuticals. 9th ed. http://specialtydigest.emdserono.com. Published 2013. Accessed June 17, 2013.
• Somatropin. Clinical Pharmacology. Elsevier/Gold Standard. Published 2013. Accessed June 17, 2013.
• Cohen P, Rogol AD, Deal CL, et al. Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop. J Clin Endocrinol Metab. 2008;93(11):4210-4217.
• What is Prader-Willi syndrome? Prader-Willi Syndrome Association. www.pwsausa.org/syndrome/index.htm . Published November 2012. Accessed June 17, 2013.
• Turner syndrome fact sheet. Turner Syndrome Society of the United States. http://turnersyndrome.org/learn-about-ts/fact-sheet . Accessed June 17, 2013.
• Small for gestational age. Lucile Packard Children’s Hospital at Stanford. www.lpch.org/DiseaseHealthInfo/HealthLibrary/hrnewborn/sga.html . Accessed June 17, 2013.
• Bamgbola OF, Kaskel FJ. Growth hormone therapy in chronic kidney disease. Growth Genetics Horm. 2005;21(1).
• Learning about Noonan syndrome. National Human Genome Research Institute.www.genome.gov/25521674. Published September 2011. Accessed June 17, 2013.
• HIV treatment directory: human growth hormone. AIDSMAP website. www.aidsmap.com/Human-growth-hormone/page/1731628. Accessed June 17, 2013.
• Short bowel syndrome: recent clinical outcomes with growth hormone. Gastroenterology. 2006; 130(2):S122-S126. www.gastrojournal.org/article/S0016-5085(05)02425-X/abstract. Accessed June 17, 2013.
• What conditions does Humatrope treat: growth failure in children with short stature homeobox-containing gene (SHOX) deficiency. www.humatrope.com/Pages/shox.aspx. Lilly; March 2013. Accessed June 17, 2013.
• Growth hormone use and abuse. The Hormone Foundation, 2009. www.google.com/url?sa=t&rct=j&q=&esrc=s&frm=1&source=web&cd=2&ved=0CDoQFjAB&url=http%3A%2F%2Fwww.researchgate.net%2Fpublication%2F26274481_Patient_information_page._Growth_hormone_use_and_abuse %2Ffile%2F79e4151228b732ada3.pdf&ei=A5PCUajpIKn84AO86oD4CQ&usg=AFQjCNGjxFZOlBAjpr6dLGDVb3udMwssXQ&sig2=Q1N1qr0fkhcO0rCJ3bwgRw. Accessed June 17, 2013.
• Genotropin [prescribing information]. Pfizer; February 2012. www.pfizer.com/files/products/uspi_genotropin.pdf. Accessed June 17, 2013.
• Humatrope [prescribing information]. Lilly USA; August 2011. http://pi.lilly.com/us/humatrope-pi.pdf. Accessed June 17, 2013.
• Norditropin [prescribing information]. Novo Nordisk; March 2009. www.novo-pi.com/norditropin.pdf. Accessed June 17, 2013.
• Nutropin AQ [prescribing information]. Genentech; April 2012. www.gene.com/download/pdf/nutropin_aq_PI.pdf. Accessed June 17, 2013.
• Omnitrope [prescribing information]. Sandoz; July 2011. www.omnitrope.com/omnitrope/prescribing-information.html. Accessed June 17, 2013.
• Saizen [prescribing information]. EMD Serono; April 2012. www.emdserono.com/cmg.emdserono_us/en/images/saizen.ce.pi_tcm115_19400.pdf?Version. Accessed June 17, 2013.
• Serostim [prescribing information]. EMD Serono; April 2012. www.serostim.com/files/pdfs/SEROSTIM_PI.pdf. Accessed June 17, 2013.
• Tev-Tropin [prescribing information]. Teva Biologics and Specialty Products; July 2011. www.tev-tropin.com/pdf/C_TT%20PI%20Rev.%20L%2007-2011.pdf. Accessed June 17, 2013.
• Zorbtive [prescribing information]. EMD Serono; January 2012. www.emdserono.com/cmg.emdserono_us/en/images/PI%20Zorbtive%208.8mg_HCP_Jan12_tcm115_105820.pdf?Version=. Accessed June 17, 2013.
• Accretropin [prescribing information]. Cangene Corporation; March 2007. www.accessdata.fda.gov/drugsatfda_docs/label/2008/021538lbl.pdf. Accessed June 17, 2013.
• US Food and Drug Administration. Drug Approval Package: Valtropin; April 2007. www.accessdata.fda.gov/drugsatfda_docs/label/2008/021538lbl.pdf. Accessed June 17, 2013.

The above information is a selective summary of publicly available information and is accurate as of the date of writing. Please consult the sources for complete reference information. The views expressed in this article are those of the author alone and not of Managed Health Care Associates, Inc.

About the Author

Stacey Ness, PharmD, RPh, MSCS, AAHIVP, has worked in both national specialty pharmacy and payer organizations and has experience in clinical management, adherence, and persistency programs, as well as chronic disease cost optimization strategies. Dr. Ness is active in the Consortium of Multiple Sclerosis Centers, Academy of Managed Care Pharmacy, National Home Infusion Association, National Association of Specialty Pharmacy, Specialty Pharmacy Certification Board, and Hematology and Oncology Pharmacy Association, and has served on the Minnesota Medicaid Drug Formulary Committee since 2008. She is a multiple sclerosis certified specialist, a credentialed HIV pharmacist, and currently serves as the director of specialty clinical services at Managed Health Care Associates, Inc, a health care services organization based in Florham Park, New Jersey.