National Medical Policy

National Medical Policy Subject: Policy Number: Histamine Desensitization Therapy NMP351 Effective Date*: June 2007 Updated: June 2015 This National Medical Policy is subject to the terms in the IMPORTANT NOTICE at the end of this document For Medicaid Plans: Please refer to the appropriate Medicaid Manuals for coverage guidelines prior to applying Health Net Medical Policies The Centers for Medicare & Medicaid Services (CMS) For Medicare Advantage members please refer to the following for coverage guidelines first: Use Source Reference/Website Link X National Coverage Determination (NCD) Intravenous Histamine Therapy (30.6): http://www.cms.gov/medicare-coveragedatabase/search/advanced-search.aspx National Coverage Manual Citation Local Coverage Determination (LCD)* Article (Local)* Other None Use Health Net Policy Instructions Medicare NCDs and National Coverage Manuals apply to ALL Medicare members in ALL regions. Medicare LCDs and Articles apply to members in specific regions. To access your specific region, select the link provided under Reference/Website and follow the search instructions. Enter the topic and your specific state to find the coverage determinations for your region. *Note: Health Net must follow local coverage determinations (LCDs) of Medicare Administration Contractors (MACs) located outside their service area when those MACs have exclusive coverage of an item or service. (CMS Manual Chapter 4 Section 90.2) Histamine Desensitization Therapy Jun 15 1

If more than one source is checked, you need to access all sources as, on occasion, an LCD or article contains additional coverage information than contained in the NCD or National Coverage Manual. If there is no NCD, National Coverage Manual or region specific LCD/Article, follow the Health Net Hierarchy of Medical Resources for guidance. Current Policy Statement Health Net Inc. considers histamine desensitization therapy (e.g., intravenous histamine infusion or subcutaneous injection of histamine) for the treatment of intractable headaches (e.g., chronic cluster headaches and migraines) not medically necessary, due to a lack of evidence in the peer review published literature validating the safety and efficacy for this indication. Codes Related To This Policy NOTE: The codes listed in this policy are for reference purposes only. Listing of a code in this policy does not imply that the service described by this code is a covered or noncovered health service. Coverage is determined by the benefit documents and medical necessity criteria. This list of codes may not be all inclusive. On October 1, 2015, the ICD-9 code sets used to report medical diagnoses and inpatient procedures will be replaced by ICD-10 code sets. Health Net National Medical Policies will now include the preliminary ICD-10 codes in preparation for this transition. Please note that these may not be the final versions of the codes and that will not be accepted for billing or payment purposes until the October 1, 2015 implementation date. ICD-9 Codes 346.00-346.91 Variants of migraine (cluster headache) 784.0 Headache ICD-10 Codes G43.00-G43.119 G44.1-G44.89 Migraine Headache CPT Codes 95199 Unlisted allergy/clinical immunologic service or procedure HCPCS Codes N/A Scientific Rationale Update June 2010 Millán-Guerrero et al (2008) evaluated the therapeutic potential of subcutaneous administration of histamine in migraine prophylaxis, compared with oral administration of topiramate. Ninety patients with migraine were selected in a 12- week double-blind controlled clinical trial to evaluate the efficacy of subcutaneous administration of histamine (1-10 ng twice a week) compared with oral administration of topiramate (100 mg daily dose). The variables studied were: headache intensity, frequency, duration, analgesic intake and Migraine Disability Assessment. The data collected during the 12 weeks of treatment revealed that Histamine Desensitization Therapy Jun 15 2

headache symptoms improved in both the histamine and topiramate groups, which was evident within the first month after the initiation of treatment, with statistically significant (p < 0.001) reductions in headache frequency (50%), Migraine Disability Assessment score (75%), intensity of pain (51%), duration of migraine attacks (45%), as well as in the use of rescue medication (52%). The authors concluded this study provides evidence of the efficacy of subcutaneously applied histamine and orally administered topiramate in migraine prophylaxis. They suggest subcutaneously applied histamine may represent a novel and effective therapeutic alternative in resistant migraine patients. Millán-Guerrero et al (2009) also compared the efficacy and tolerability of the subcutaneous administration of histamine and botulinum toxin type A (BoNTA) in migraine prophylaxis. One hundred patients with migraine were selected in a 12- week double-blind controlled clinical trial to evaluate the efficacy of subcutaneous administration of histamine (1-10 ng twice a week) n = 50, compared with administration of 50 U of BoNTA (one injection cycle) n = 50. The data collected during the 4th week of treatment revealed a significant decrease in all parameters studied, in histamine and BoNTA (P < 0.001). After 4 weeks of treatment, but one injection cycle of 50 U BoNTA had only a 40-day period of efficacy. The author concluded both histamine and BoNTA are similarly effective and well tolerated in reducing or eliminating headache in migraine prophylaxis. Low doses of histamine applied subcutaneously may represent a novel and effective therapeutic alternative in migraine patients and lay the clinical and pharmacological groundwork for the use of H3 agonist in migraine prophylaxis. In summary, there is a lack of long term evidence in the peer review published literature addressing the safety and efficacy of subcutaneous or intravenous histamine desensitization therapy as a treatment or prevention of intractable headaches. Scientific Rationale Migraine is second most common type of headache, found more commonly in women, characterized by episodic attacks of unilateral or bilateral head pain and associated symptoms. The International Headache Society (IHS) redefined and classified headaches to formulate the current categorization. The headache previously described as classic migraine is now known as migraine with aura, and that described as common migraine is now termed migraine without aura. Migraines without aura are the most common, accounting for more than 80% of all migraines. Migraine aura is the complex of neurologic symptoms that accompanies migraine headache. Auras typically occur before the onset of migraine headache, and the headache usually begins simultaneously with or just after the end of the aura phase. Typical auras may involve visual disturbances, sensory symptoms, motor weakness or speech disturbances. Migraines occur at any time but most often begin early in the morning. The pain is usually gradual in onset, following a crescendo pattern with gradual but complete resolution. The headaches are often worsened by rapid head motion, sneezing, straining, constant motion, or physical exertion. Nonpharmacologic treatment of migraine headache include relaxation training, biofeedback, stimulant reduction, behavior therapy and trigger avoidance (e.g. certain foods, hormonal changes, physical exertion, fatigue, certain medications and stress.) The abortive (acute, symptomatic) therapy of migraine should be given early Histamine Desensitization Therapy Jun 15 3

in the course of the headache and may include nonsteroidal antiinflammatory drugs (NSAIDs), triptans (e.g. Imitrex), dihydroergotamine (DHE), acetaminophen and antiemetics. Prophylactic headache treatment is indicated if the headaches are frequent, long lasting, or account for a significant amount of total disability. The American Academy of Neurology practice parameter states the goals of preventive therapy are to reduce attack frequency, severity and duration; improve responsiveness to treatment of acute attacks and improve function and reduce disability. Beta blockers, antidepressants, anticonvulsants (now commonly called neurostabilizers) calcium antagonists, nonsteroidal agents, and serotonin receptor antagonists are effective for migraine prevention. Botulinum toxin A (Botox) may be beneficial in select patients with intractable migraine headaches that fail to respond to conventional preventive medication. Cluster headaches, unlike migraine, are relatively uncommon, affecting men more often than women. The cause of cluster headache is unknown. This form of neurovascular headache are intense, repetitive headaches that occur for weeks to months at a time, followed by periods of remission. The pain is of short duration, lasting a few moments to 2 hours. The pain associated with cluster headache is sudden, intense unilateral pain that is typically located at the temple and periorbital region. The pain is typically associated with ipsilateral lacrimation, nasal congestion, conjunctival injection, miosis, ptosis, lid edema and a sense of restlessness or agitation. Cluster headaches are classified as episodic or chronic. Episodic cluster headaches are the most common and occur in periods lasting from 7 days to 1 year separated by pain-free periods lasting 1 month or longer. Chronic cluster headaches occur for more than 1 year without remission or with remissions lasting less than 1 month. Most patients with cluster headaches will require both prophylactic and abortive treatment for the duration of the cluster, however, abortive therapy can be difficult because of the short duration of each episode. Oxygen inhalation is the standard recommended therapy for cluster headaches. Subcutaneous or intranasal sumatriptan (Imitrex) is an effective acute treatment for episodic and chronic cluster headaches. Other treatment options include dihydroergotamine (DHE) administered by nasal spray or injection, nasal lidocaine 4% topical solution, and capsaicin. Prophylactic therapy should be started as soon as possible at the onset of a cluster episode and continued until the patient is headache-free for at least 14 days. The goal of preventive treatment is to suppress individual attacks and to maintain that remission throughout the patient's typical cluster period. Verapamil is the first-line prophylactic drug for both episodic and chronic clusters. Some other medications that have been found to be useful include prednisone, dexamethasone, ergotamine derivatives, lithium carbonate, and topiramate. Prophylactic medications can be tapered after the expected duration of the cluster has passed. The drugs can be restarted if symptoms recur at the lowest effective dose. Patients with chronic cluster headaches that are refractive to medical therapy or have medical conditions that preclude medical options, surgical treatment may be considered. Surgical techniques are based on ablation of components of the sensory trigeminal nerve and the cranial parasympathetic system or nervus intermedius. Methods include radiofrequency trigeminal rhizolysis, glycerol injection into the trigeminal cistern, and gamma knife radiosurgery. Histamine Desensitization Therapy Jun 15 4

Histamine desensitization was introduced in the 1940s and 1950s, according to Sargeant and Blanda (2005.) Patients were treated with subcutaneous and intravenous injection of histamine as a means of treating cluster headaches. This treatment was based on the contention that metabolic derangement of histamine played an important role in producing cluster headaches. However, at that time, the episodic nature of clusters was not recognized fully, therefore, spontaneous improvements were attributed to treatment. Results were inconsistent with minimal hard data on recurrence rates and follow-up duration. Histamine is thought to play a role in the modulation of pain and has been shown to induce migraine, prompting investigation of histamine desensitization for prophylaxis against intractable migraine. Usually, patients are treated as inpatient and receive increasing doses of histamine or N-methyl-histamine via intravenous (IV) infusion, repetitively over a course of approximately ten days. This therapy is intended for patients with moderate or severe recurrent migraine that is unresponsive to other forms of therapy, or for patients with chronic cluster headache refractory to other treatments. According to Centers for Medicare and Medicaid Services National Coverage Decision policy on Intravenous Histamine Therapy, The only accepted and scientifically valid medical use of histamine is diagnostic, including tests to assess the ability of the stomach to secrete acid, the integrity of peripheral sensory nerves (e.g., in leprosy), the circulatory competency in limb extremities and the presence of a pheochromocytoma. However, there is no scientifically valid clinical evidence that histamine therapy is effective for any condition regardless of the method of administration, nor is it accepted or widely used by the medical profession. Therefore, histamine therapy cannot be considered reasonable and necessary, and program payment for such therapy is not made. It is unclear whether desensitization plays a role in any improvement in headaches. There is limited data on the efficacy of histamine desensitization in the treatment of intractable migraine or cluster headaches. Most of the evidence on histamine desensitization for migraines has been reported by the same authors. Histamine desensitization may be effective in some patients with severe, recurrent migraine headaches that are unresponsive to other medications or treatment, however, the role for this therapy in the migraine or cluster headache treatment regimen is unclear. In a controlled, double-blind, clinical trial, Millan-Guerrero R et al. (1999) examined the efficacy of the subcutaneous administration (twice a week) of consecutively increasing doses of histamine (0.1 to 1 ng) in the prophylaxis of migraine, compared to placebo, for 12 weeks in sixty patients with a history of migraines for more than 1 year and one to six headache attacks per month. The patients had no additional neurological or cardiovascular pathologies. Comparison between the groups treated with placebo (n = 30) and histamine (n = 30), on data collected for the 4th, 8th, and 12th weeks of treatment, revealed that histamine exerted a significantly (P <.0001) greater reduction (compared to placebo) in the frequency, intensity, and duration of migraine attacks, as well as on the use of rescue medication. No significant adverse experiences or side effects were noted in either group. Histamine Desensitization Therapy Jun 15 5

In 2003, Millán-Guerrero et al. published the results of a phase I and phase II trial in the same paper. The phase I clinical trial, studied the effects of the subcutaneous administration of Nalpha-methylhistamine and placebo in thirty healthy volunteers, to assess undesirable symptomatic effects. The investigator reported that none of the variables studied showed significant differences (P>.05), and no secondary effects were observed at doses below 10 ng. The efficacy of Nalpha-methylhistamine in reducing headache intensity, frequency, and duration and in decreasing analgesic intake was also investigated in the phase II trial of eighteen patients with migraine headache. The investigator reported that Nalpha-methylhistamine, at doses of 1 to 3 ng, significantly reduced (P<.0001) the frequency, intensity, and duration of migraine attacks, as well as the need for rescue analgesics. However, at doses greater than 3 ng, patients experienced intense headache. The investigator concluded that the studies provide evidence of the safety and efficacy of Nalphamethylhistamine applied subcutaneously at doses of 1 to 3 ng twice a week. In a Phase III clinical trial, Millan-Guerrero R et al. (2006) evaluated the efficacy of subcutaneous administration of Nalpha-methylhistamine 1 to 3 ng twice a week against placebo in 60 patients with migraine, as defined by the International Headache Society. The outcome of headache intensity, frequency, duration, and analgesic intake were evaluated. Comparison between the groups treated with placebo (n=30) and Nalpha-methylhistamine (n=30), on data collected for the 4th, 8th and 12th weeks of treatment revealed that Nalpha-methylhistamine exerted a significant (p<0.0001) reduction (compared to placebo) in intensity, frequency, and duration of migraine attacks, as well as on the use of analgesic intake. No significant (p>0.05) adverse experiences or side effects developed in either group. The investigator again concluded that the study provides evidence of the efficacy of Nalpha-methylhistamine, given subcutaneously at doses of 1 to 3 ng twice a week, offering a new therapeutic alternative for the use of histaminergic H3-agonists in migraine prophylaxis. In summary, there is a lack of evidence in the peer review published literature addressing the safety and efficacy of subcutaneous or intravenous histamine desensitization therapy as a treatment for intractable headaches (or any other condition.) There lacks comparative studies to other established treatments. Large, long-term, well-designed randomized clinical trials are needed to address the safety and effectiveness of this treatment. Review History June 2007 Medical Advisory Council June 2009 Update no revisions June 2010 Update June 2010 June 2011 Update. Added Medicare Table. No revisions. June 2012 Update no revisions June 2013 Update no revisions. Codes updated June 2014 Update no revisions June 2015 Update no revisions This policy is based on the following evidence-based guidelines: Histamine Desensitization Therapy Jun 15 6

1. Biondi D, Mendes P. Treatment of primary headache: cluster headache. In: Standards of care for headache diagnosis and treatment. Chicago (IL): National Headache Foundation; 2004. p. 59-72. 2. Landy S, Smith T. Treatment of primary headache: acute migraine treatment. In: Standards of care for headache diagnosis and treatment. Chicago (IL): National Headache Foundation; 2004. p. 27-39. Kaniecki R, Lucas S. Treatment of primary headache: preventive treatment of migraine. In: Standards of care for headache diagnosis and treatment. Chicago (IL): National Headache Foundation; 2004. p. 40-52. 3. Headache Classification Committee of the International Headache Society. The International Classification of Headache Disorders. Cephalalgia 2004; 24:1. 4. Silberstein, SD. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000; 55:754. Available at: http://www.neurology.org/cgi/reprint/55/6/754.pdf 5. Snow V, Weiss K, Wall EM, Mottur-Pilson C. Pharmacologic management of acute attacks of migraine and prevention of migraine headache. Ann Intern Med 2002 Nov 19;137(10):840-52. 6. Hayes Health Technology Brief. Histamine Desensitization Therapy for Prophylaxis Against Intractable Migraine or Chronic Cluster Headaches. Feb 2007. Updated February 2009. Archived in 2010. References Update June 2015 1. Kacperski J. Prophylaxis of Migraine in Children and Adolescents. Paediatr Drugs. 2015 Mar 20 2. Serrano D, Buse DC, Manack Adams A, et al. Acute Treatment Optimization in Episodic and Chronic Migraine: Results of the American Migraine Prevalence and Prevention (AMPP) Study. Headache. 2015 Apr;55(4):502-18. References Update June 2014 1. Carod-Artal FJ. Tackling chronic migraine: current perspectives. J Pain Res. 2014 Apr 8;7:185-194. 2. Proietti Cecchini A, Grazzi L. Emerging therapies for chronic migraine. Curr Pain Headache Rep. 2014 Apr;18(4):408 3. Rosario D, Pinto G. Role of Gender and Serum Immunoglobulin E (IGE) levels on Severity of Migraine. J Clin Diagn Res. 2014 Feb;8(2):57-8. 4. Schwedt TJ. Chronic migraine. BMJ. 2014 Mar 24;348:g1416. References Update June 2011 1. U.S. Food and Drug Administration (FDA). Allergenics. Updated November 11, 2009. Available at: http://www.fda.gov/cber/allergenics.htm. 2. U.S. Food and Drug Administration (FDA). National Drug Code Directory. Histamine. April 19, 2010. Available at: http://www.fda.gov/cder/ndc/database/default.htm. References Update June 2010 1. Millán-Guerrero RO, Isais-Millán R, Barreto-Vizcaíno S, et al. Subcutaneous histamine versus topiramate in migraine prophylaxis: a double-blind study. 2. Millán-Guerrero RO, Isais-Millán S, Barreto-Vizcaíno S, et al. Subcutaneous histamine versus botulinum toxin type A in migraine prophylaxis: a randomized, double-blind study. Eur J Neurol. 2009 Jan;16(1):88-94. Histamine Desensitization Therapy Jun 15 7

3. Millán-Guerrero RO, Isais-Millán R. New therapeutic alternatives in migraine prophylaxis using histamine H3 receptor agonists. Gac Med Mex. 2008 Jul- Aug;144(4):291-5 References 1. Beck E, Sieber W, Trejo R. Management of Cluster Headache. American Family Physician. 2005 Feb, Vol. 71. No. 4 2. Sargeant L, Blanda M. Cluster headache. emedicine. Last updated March 2005. Available at: http://www.emedicine.com/emerg/topic229.htm 3. May, A. Cluster headache: pathogenesis, diagnosis, and management. Lancet 2005; 366:843 4. Van Vliet, JA, Bahra, A, Martin, V, et al. Intranasal sumatriptan in cluster headache: Randomized placebo-controlled double-blind study. Neurology 2003; 60:630 5. Cittadini, E, May, A, Straube, A, et al. Effectiveness of intranasal zolmitriptan in acute cluster headache: a randomized, placebo-controlled, double-blind crossover study. Arch Neurol 2006; 63:1537 6. Matharu, MS, Levy, MJ, Meeran, K, Goadsby, PJ. Subcutaneous octreotide in cluster headache: randomized placebo-controlled double-blind crossover study. Ann Neurol 2004; 56:488 7. Leone, M, D'Amico, D, Frediani, F, et al. Verapamil in the prophylaxis of episodic cluster headache: A double-blind study versus placebo. Neurology 2000; 54:1382. 8. Linde, K, Rossnagel, K. Propranolol for migraine prophylaxis. Cochrane Database Syst Rev 2004 9. Silberstein, SD, Goadsby, PJ. Migraine: preventive treatment. Cephalalgia 2002; 22:491. 10. Chronicle, E, Mulleners, W. Anticonvulsant drugs for migraine prophylaxis. Cochrane Database Syst Rev 2004 11. Blanda M, Wright J. Headache, Migraine. emedicine. Last updated July 2006. Available at: http://www.emedicine.com/emerg/topic230.htm 12. Millan-Guerrero RO, Isais-Millan R, Benjamin TH, Tene CE. Nalpha-methyl histamine safety and efficacy in migraine prophylaxis: phase III study. Can J Neurol Sci. 2006 May;33(2):195-9. 13. Freitag FG. Cluster headache. Prim Care. 2004 Jun;31(2):313-29, vi. 14. Millan-Guerrero RO, Pineda-Lucatero AG, Hernandez-Benjamin T, et al. Nalphamethylhistamine safety and efficacy in migraine prophylaxis: phase I and phase II studies. Headache. 2003 Apr;43(4):389-94. 15. Guerrero RO, Cardenas MA, Ocampo AA, Pacheco MF. Histamine as a therapeutic alternative in migraine prophylaxis: a randomized, placebo-controlled, doubleblind study. Headache. 1999 Sep;39(8):576-80. 16. Mansfield LE. The role of antihistamine therapy in vascular headaches. J Allergy Clin Immunol. 1990 Oct;86(4 Pt 2):673-6. 17. Ryan RE Jr, Ryan RE Sr. Cluster headaches. Otolaryngol Clin North Am. 1989 Dec;22(6):1131-44. 18. Sahai-Srivastava S, Cowan R. Pathophysiology and Treatment of Migraine and Related Headache. emedicine. Last updated Apr. 2007. Available at: http://www.emedicine.com/neuro/topic517.htm 19. Anselmi B, Tarquini R, Panconesi A, et al. Serum beta-endorphin increase after intravenous histamine treatment of chronic daily headache. Recenti Prog Med. 1997 Jul-Aug;88(7-8):321-4. 20. Thomsen LL, Olesen J. Nitric oxide in primary headaches. Curr Opin Neurol. 2001 Jun;14(3):315-21. Histamine Desensitization Therapy Jun 15 8

21. Krabbe AA, Olesen J. Headache provocation by continuous intravenous infusion of histamine. Clinical results and receptor mechanisms. Pain. 1980 Apr;8(2):253-9. 22. Centers for Medicare and Medicaid Services. NCD for Intravenous Histamine Therapy. Available at: http://www.cms.hhs.gov/mcd/viewncd.asp?ncd_id=30.6&ncd_version=1&basket =ncd%3a30%2e6%3a1%3aintravenous+histamine+therapy Important Notice General Purpose. Health Net's National Medical Policies (the "Policies") are developed to assist Health Net in administering plan benefits and determining whether a particular procedure, drug, service or supply is medically necessary. The Policies are based upon a review of the available clinical information including clinical outcome studies in the peer-reviewed published medical literature, regulatory status of the drug or device, evidence-based guidelines of governmental bodies, and evidence-based guidelines and positions of select national health professional organizations. Coverage determinations are made on a case-by-case basis and are subject to all of the terms, conditions, limitations, and exclusions of the member's contract, including medical necessity requirements. Health Net may use the Policies to determine whether under the facts and circumstances of a particular case, the proposed procedure, drug, service or supply is medically necessary. The conclusion that a procedure, drug, service or supply is medically necessary does not constitute coverage. The member's contract defines which procedure, drug, service or supply is covered, excluded, limited, or subject to dollar caps. The policy provides for clearly written, reasonable and current criteria that have been approved by Health Net s National Medical Advisory Council (MAC). The clinical criteria and medical policies provide guidelines for determining the medical necessity criteria for specific procedures, equipment, and services. In order to be eligible, all services must be medically necessary and otherwise defined in the member's benefits contract as described this "Important Notice" disclaimer. In all cases, final benefit determinations are based on the applicable contract language. To the extent there are any conflicts between medical policy guidelines and applicable contract language, the contract language prevails. Medical policy is not intended to override the policy that defines the member s benefits, nor is it intended to dictate to providers how to practice medicine. Policy Effective Date and Defined Terms. The date of posting is not the effective date of the Policy. The Policy is effective as of the date determined by Health Net. All policies are subject to applicable legal and regulatory mandates and requirements for prior notification. If there is a discrepancy between the policy effective date and legal mandates and regulatory requirements, the requirements of law and regulation shall govern. * In some states, prior notice or posting on the website is required before a policy is deemed effective. For information regarding the effective dates of Policies, contact your provider representative. The Policies do not include definitions. All terms are defined by Health Net. For information regarding the definitions of terms used in the Policies, contact your provider representative. Policy Amendment without Notice. Health Net reserves the right to amend the Policies without notice to providers or Members. In some states, prior notice or website posting is required before an amendment is deemed effective. No Medical Advice. The Policies do not constitute medical advice. Health Net does not provide or recommend treatment to members. Members should consult with their treating physician in connection with diagnosis and treatment decisions. No Authorization or Guarantee of Coverage. The Policies do not constitute authorization or guarantee of coverage of particular procedure, drug, service or supply. Members and providers should refer to the Member contract to determine if exclusions, limitations, and dollar caps apply to a particular procedure, drug, service or supply. Policy Limitation: Member s Contract Controls Coverage Determinations. Statutory Notice to Members: The materials provided to you are guidelines used by this plan to authorize, modify, or deny care for persons with similar illnesses or conditions. Specific care and treatment may vary depending on individual need and the benefits covered under your contract. The determination of coverage for a particular procedure, drug, service or supply is not based upon the Policies, but rather is subject to the facts of the individual clinical case, terms and conditions of the member s contract, and requirements of applicable laws and regulations. The contract language contains specific terms and conditions, including pre-existing conditions, limitations, exclusions, benefit maximums, eligibility, and other relevant terms and conditions of coverage. In the event the Member s contract (also known as the Histamine Desensitization Therapy Jun 15 9

benefit contract, coverage document, or evidence of coverage) conflicts with the Policies, the Member s contract shall govern. The Policies do not replace or amend the Member s contract. Policy Limitation: Legal and Regulatory Mandates and Requirements The determinations of coverage for a particular procedure, drug, service or supply is subject to applicable legal and regulatory mandates and requirements. If there is a discrepancy between the Policies and legal mandates and regulatory requirements, the requirements of law and regulation shall govern. Reconstructive Surgery CA Health and Safety Code 1367.63 requires health care service plans to cover reconstructive surgery. Reconstructive surgery means surgery performed to correct or repair abnormal structures of the body caused by congenital defects, developmental abnormalities, trauma, infection, tumors, or disease to do either of the following: (1) To improve function or (2) To create a normal appearance, to the extent possible. Reconstructive surgery does not mean cosmetic surgery," which is surgery performed to alter or reshape normal structures of the body in order to improve appearance. Requests for reconstructive surgery may be denied, if the proposed procedure offers only a minimal improvement in the appearance of the enrollee, in accordance with the standard of care as practiced by physicians specializing in reconstructive surgery. Reconstructive Surgery after Mastectomy California Health and Safety Code 1367.6 requires treatment for breast cancer to cover prosthetic devices or reconstructive surgery to restore and achieve symmetry for the patient incident to a mastectomy. Coverage for prosthetic devices and reconstructive surgery shall be subject to the co-payment, or deductible and coinsurance conditions, that are applicable to the mastectomy and all other terms and conditions applicable to other benefits. "Mastectomy" means the removal of all or part of the breast for medically necessary reasons, as determined by a licensed physician and surgeon. Policy Limitations: Medicare and Medicaid Policies specifically developed to assist Health Net in administering Medicare or Medicaid plan benefits and determining coverage for a particular procedure, drug, service or supply for Medicare or Medicaid members shall not be construed to apply to any other Health Net plans and members. The Policies shall not be interpreted to limit the benefits afforded Medicare and Medicaid members by law and regulation. Histamine Desensitization Therapy Jun 15 10