Appeal type: Formulary Exception
Decision: Upheld

Diagnosis: Metastatic oropharyngeal cancer (CA). 
Treatment: Tramadol HCL (hydrochloride) 5 mg (milligrams) /ml (milliliter) Solution. 

The insurer denied coverage for Tramadol HCL (hydrochloride) 5 mg (milligrams) /ml (milliliter) Solution. 
 
The denial is upheld. 

According to the clinical documentation provided for review, the patient has the medical diagnosis of metastatic oropharyngeal cancer (CA). The patient is on a feeding tube and has a tracheostomy (trach). The patient has biopsy proven cancer. At a follow-up visit with the patient's Oncologist it was noted that the patient was having back pain just below the scapulae, which she rates a 4 or 5 on a pain scale of 0 to 10. The patient is currently using Tylenol and gabapentin. Her doctor recommended Tramadol for the pain. 

The insurer has denied coverage for Tramadol HCL (hydrochloride) 5 mg (milligrams) /ml (milliliter) Solution. The denial was because the patient must show that she has had serious side effects or drug failure with all formulary alternatives within this drug class. Formulary alternatives include oxycodone/APAP (Tylenol) solution, oxycodone concentrate, morphine sulfate solution, meperidine solution, hydromorphone liquid, hydrocodone bitartrate/acetaminophen solution, or acetaminophen with codeine phosphate solution. 

It is noted the patient does not want to take opioids. 

The formulary alternatives are roughly equivalent to tramadol, in equivalent doses. Tramadol is also an opioid analgesic and opioid activity is the overriding contributor to its pharmacological effects. Both an immediate release and extended-release oral formulation are available in the US (United States). In 2014, the drug was reclassified as Schedule IV; a nod to its abuse potential although still not in the Schedule II category occupied by most opioid analgesics. As a result, tramadol is included today in all state prescription drug monitoring programs (PDMPs) nationwide. Tramadol is approved for the treatment of moderate to moderately severe pain in adults. 

As per Up to Date, "Tramadol and tapentadol are centrally acting analgesics whose mode of action is based both on the mu receptor binding and monoamine (serotonin and norepinephrine) reuptake blockade. Tramadol is widely used in some countries for moderate to severe cancer pain as an alternative to other opioids [52,53], but it is not used as commonly in the United States. Evidence is limited comparing either drug with other opioids in terms of either efficacy or tolerability in patients with cancer-related pain:...A Cochrane review of 10 studies comparing tramadol with either placebo or an active control in 958 adults with moderate to severe cancer pain concluded that there was limited, very low-quality evidence from randomized trials that tramadol produces pain relief in some adults with pain due to cancer, and very low-quality evidence that it is not as effective as morphine [55]. 

Based on this limited evidence and clinical experience, it is reasonable to conclude that either tramadol or tapentadol could be used to treat cancer pain, but there is no known advantage in selecting one or the other over the pure mu agonist opioids that are conventionally used for this indication. 

Note that the reference to mu receptor binding includes the commonly used opiates oxycodone, hydrocodone, codeine, etc. as detailed in Up to Date. 

The formulary drugs were not tried, and the patient did not have an adverse reaction or contraindication. The formulary drugs are not expected to cause adverse effects. The formulary drugs are not expected to be ineffective. The non-formulary drug is not expected to be more effective that the formulary alternatives. 

The carrier's denial of Request for Formulary Exception for Tramadol HCL 5 mg/ml Solution is upheld.