Appeal type: Experimental/Investigational
Decision: Upheld

Diagnosis: Abdominal Pain
Treatment: Amitiza 8 micrograms (MCG) Capsule, 60 for 30 days
The insurer denied the Amitiza 8 micrograms (MCG) Capsule, 60 for 30 days.
The denial is upheld. 

The patient is a female. The request in this case is for prescription Amitiza for chronic refractory constipation. 

According to the adverse determination, the drug is off label and does not meet the plans criteria for off table use in a child of this age. Denial criteria were the following: "Amitiza is not FDA [Food and Drug Administration]-approved for your diagnosis of abdominal pain in a young child. Therefore, this is an off-label request. According to our off-label policy, use of a drug for a condition for which the drug was not approved by the FDA [Food and Drug Administration] may be considered medically appropriate when the request meets the following criteria. For non-cancer related therapy, the use must be listed in DrugDex (a drug information resource) as recommendation class IIa or higher. If the use is listed as IIb or is not listed, then there must be one published article or two published abstracts (article summaries) with enough subjects demonstrating that the use of the drug is generally safe and effective. Treatment with Amitiza for abdominal pain in a young child does not meet all of the above criteria for off label use of an FDA [Food and Drug Administration] approved drug. Therefore, this request for your treatment with Amitiza has been deemed experimental/investigational and we cannot authorize coverage under your benefit." 

Two peer-reviewed articles were presented in which patients of this age were treated for constipation. 

The patient is a former premature infant. She has had constipation since shortly after birth and has not responded to conventional therapies approved and administered. This included Miralax, lactulose, senna, bisacodyl and multiple clean outs at home and inpatient. She also has abdominal pain felt to be due to chronic constipation, encopresis and GERD (gastroesophageal reflux disease). Her work up included abdominal x-ray and lab assessment. She is in the process of being referred to a motility specialist in Boston. She has PMH (past medical history) significant for Henoch-Schonlein Purpura.

No, the health plan should not cover the treatment with Amitiza 8 microgram (MCG) Capsule 60 for 30 days.

Based on lack of significant literature support, including Clinicaltrials.gov study, the denial of the proposed treatment is upheld. As stated previously by a prior reviewer, "As constipation in children is not a rare disease, and the primary lit was from several years ago for children but has not led to approval for Amitiza in children or further studies to evaluate Amitiza in children, would not consider this sufficient primary literature for approval. This study was also limited by lack of placebo, which study authors noted is important since strong placebo effect was seen in study with PEG [polyethylene-glycol] 3350 for functional constipation. Primary lit for review from several years ago was provided and the primary lit that was found does not meet off label criteria, would recommend that the decision to deny coverage of Amitiza (manufactured by Takeda) be upheld on appeal." This reviewer supports this conclusion and recommendation as well.

The patient's work up for abdominal pain and chronic constipation included endoscopy and colonoscopy, barium enema, upper gastrointestinal (UGI) study, lab assessment, ultrasound (US), laboratory results, and physical office visits.

No, the requested health service is not likely to be more beneficial than and standard treatment(s) for the insured's condition or disease based on two studies, one of which included patients under seven but there were limited numbers in this age group. In addition, there is lack efficacy in the clinical trials for patients six and above.

Per the reference below:
The primary purpose of this study is to evaluate the safety and efficacy of lubiprostone in a pediatric population with constipation, including the pharmacokinetics of lubiprostone, in a subset of patients.

Safety and effectiveness have not been established in pediatric patients less than six years of age.

Effectiveness has not been established in pediatric patients six years and older. Efficacy was not demonstrated for the treatment of Pediatric Functional Constipation (PFC) in a 12 week, randomized, double-blind, placebo controlled trial conducted in 606 patients six to 17 years with Pediatric Functional Constipation (PFC) comparing Amitiza to placebo. The primary efficacy endpoint was an overall response based on spontaneous bowel movement frequency over the duration of the trial; the treatment difference from placebo was not statistically significant. In this age group, adverse reactions to Amitiza were similar to those reported in adults. In a 36-week, long-term safety extension trial after approximately nine months of treatment with Amitiza, a single case of reversible elevation of alanine aminotransferase (ALT) (17-times upper limit of normal [ULN]), aspartate aminotransferase (AST) (13-times upper limit of normal [ULN]), and gamma-glutamyl transferase (GGT) (9-times upper limit of normal [ULN]) was observed in a child with baseline elevated values (less than or equal to 2.5-times upper limit of normal [ULN]).