Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Neuropharmacology wikipedia , lookup
Pharmacokinetics wikipedia , lookup
Adherence (medicine) wikipedia , lookup
Pharmaceutical industry wikipedia , lookup
Pharmacogenomics wikipedia , lookup
Psychedelic therapy wikipedia , lookup
Prescription costs wikipedia , lookup
Theralizumab wikipedia , lookup
PHARMACY COVERAGE GUIDELINES SECTION: DRUGS NEXT REVIEW DATE: ORIGINAL EFFECTIVE DATE: LAST REVIEW DATE: LAST CRITERIA REVISION DATE: ARCHIVE DATE: 3rd QUARTER 2017 03/17/16 07/21/16 07/13/16 ISOTRETINOIN ORAL PRODUCTS: ABSORICA® (isotretinoin) oral capsule AMNESTEEM® (isotretinoin) oral capsule CLARAVIS™ (isotretinoin) oral capsule MYORISAN™ (isotretinoin) oral capsule ZENATANE™ (isotretinoin) oral capsule Coverage for services, procedures, medical devices and drugs are dependent upon benefit eligibility as outlined in the member's specific benefit plan. This Pharmacy Coverage Guideline must be read in its entirety to determine coverage eligibility, if any. This Pharmacy Coverage Guideline provides information related to coverage determinations only and does not imply that a service or treatment is clinically appropriate or inappropriate. The provider and the member are responsible for all decisions regarding the appropriateness of care. Providers should provide BCBSAZ complete medical rationale when requesting any exceptions to these guidelines. The section identified as “Description” defines or describes a service, procedure, medical device or drug and is in no way intended as a statement of medical necessity and/or coverage. The section identified as “Criteria” defines criteria to determine whether a service, procedure, medical device or drug is considered medically necessary or experimental or investigational. State or federal mandates, e.g., FEP program, may dictate that any drug, device or biological product approved by the U.S. Food and Drug Administration (FDA) may not be considered experimental or investigational and thus the drug, device or biological product may be assessed only on the basis of medical necessity. Pharmacy Coverage Guidelines are subject to change as new information becomes available. For purposes of this Pharmacy Coverage Guideline, the terms "experimental" and "investigational" are considered to be interchangeable. BLUE CROSS®, BLUE SHIELD® and the Cross and Shield Symbols are registered service marks of the Blue Cross and Blue Shield Association, an association of independent Blue Cross and Blue Shield Plans. All other trademarks and service marks contained in this guideline are the property of their respective owners, which are not affiliated with BCBSAZ. Description: Isotretinoin is indicated for the treatment of severe recalcitrant nodular acne in individuals who are unresponsive to conventional therapy, including systemic antibiotics. The nodules are inflammatory and generally have a diameter of 5 millimeters (mm) or greater, in addition, they may become suppurative or hemorrhagic. Isotretinoin is indicated in women of child bearing age who are not pregnant or are on adequate birth control. The exact mechanism of action of isotretinoin is unknown, but it has been shown to inhibit sebaceous gland function and keratinization and is associated with a reduction in sebum secretion. Page 1 of 11 PHARMACY COVERAGE GUIDELINES SECTION: DRUGS NEXT REVIEW DATE: ORIGINAL EFFECTIVE DATE: LAST REVIEW DATE: LAST CRITERIA REVISION DATE: ARCHIVE DATE: 3rd QUARTER 2017 03/17/16 07/21/16 07/13/16 ISOTRETINOIN ORAL PRODUCTS (cont.) The pathogenesis of acne in multifactorial and includes hyperkeratinization of follicles, bacterial infectious process, production of sebum, androgens, and inflammation. Acne vulgaris is considered a chronic inflammatory dermatologic disease that is notable for open and/or closed comedones (blackheads – dark or blackish bumps; and whiteheads – tiny white bumps) and inflammatory lesions including papules (small, firm, may be painful pink bumps), pustules (small, may be painful bumps with pus), or nodules/cysts (large, hard, inflamed and painful bumps). Acne pimples occur on the face, neck, chest, shoulders, back, and upper arms caused by clogged pores due to excessive sebum (oil) production. The prevalent bacterium implicated in acne is Propionibacterium acnes (P acnes), a gram-positive anaerobe that is normally found on the skin and is implicated in the inflammatory phase of acne. P acnes promotes lesions by secreting chemotactic factors that attract leukocytes to the follicle resulting in inflammation. All anti-acne agents are effective in reducing inflammatory and non-inflammatory lesions when compared to placebo based on many years of clinical experience, multiple systematic reviews, and clinical practice guidelines. There is no evidence that confirms superiority of any one branded option over available brand or generic alternatives, including available over-the-counter (OTC) products. All anti-acne products have adequate track records of safety; most are generally well tolerated, but all cause skin irritation. Published guidelines on the treatment of acne consistently recommend the use of topical antimicrobial, topical retinoid, azeleic acid, benzoyl peroxide, dapsone, and combination topical products, oral antibiotics or oral isotretinoin. Isotretinoin is approved for the treatment of severe recalcitrant nodular acne vulgaris. Use of Isotretinoin (Absorica, Amnesteem, Claravis, Myorisan, and Zenatane) is subject to a Risk Evaluation and Mitigation Strategies (REMS) program that requires provider, patient, and dispensing pharmacy be enrolled into the program. Only providers and pharmacies enrolled into the REMS may prescribe and dispense the drug, respectively, to individuals who are also in the program. A REMS program attempts to manage known or potentially serious risks associated with a drug product and is required by the Food and Drug Administration (FDA) for some drugs to ensure that the benefits of a drug outweigh its risks. Definitions: Isotretinoin (Absorica, Amnesteem, Claravis, Myorisan, and Zenatane) REMS items Enrollment and agreement information Treatment initiation information Treatment maintenance information Pharmacy requirements and responsibilities Counseling on contraception and avoidance of pregnancy Pregnancy testing in females of childbearing potential Counseling on serious risks, warnings, and precautions and safe use Drug related events: Ineffective / failure Use of a drug employing optimal doses (FDA-recommended doses) for optimal duration; where the condition being treated has not improved or worsened Page 2 of 11 PHARMACY COVERAGE GUIDELINES SECTION: DRUGS NEXT REVIEW DATE: ORIGINAL EFFECTIVE DATE: LAST REVIEW DATE: LAST CRITERIA REVISION DATE: ARCHIVE DATE: 3rd QUARTER 2017 03/17/16 07/21/16 07/13/16 ISOTRETINOIN ORAL PRODUCTS (cont.) A request for branded agent due to generic drug failure or ineffectiveness will be assessed for potential approval with documentation of use of optimal dose / duration of the generic product and meeting other criteria within the coverage guideline. When the drug in question is a combination product, there must be documentation of failure / ineffectiveness of concurrent use (each ingredient used at the same time) of individual generic components. When the drug in question is a low dose formulation, there must be documentation of failure / ineffectiveness of low dose generic formulation. Adverse Drug Event: Allergic reaction / Hypersensitivity / Intolerance Use of a drug produced a significant reaction where continued use of the drug places the individual at risk for either lack of improvement or worsening of the condition being treated or at risk for harm and the concern is documented in medical record. A significant adverse drug event is when an individual’s outcome is death, life-threatening, hospitalization (initial or prolonged), disability resulting in a significant, persistent, or permanent change, impairment, damage or disruption in the individuals’ body function/structure, physical activities or quality of life, or requires intervention to prevent permanent impairment or damage. Allergic reaction / hypersensitivity – may or may not involve the active ingredient. When the active ingredient is involved, use of same or a chemically similar agent places the individual at risk for harm when the same or chemically similar agent is used. The subsequent reaction may be the same as the original reaction or a more exaggerated response may be seen, potentially placing the individual at even greater risk for harm. If the reaction occurred from the active/main generic ingredient; request for branded agent with same active ingredient will not be considered unless it is proven (documented) that active ingredient did not cause reaction and the request meets other criteria within the coverage guideline Intolerance – these events represent circumstance(s) where use of a drug produced a significant reaction and continued use may result in non-adherence to proposed therapy and this concern is documented in medical record Contraindication Use of a drug that is not recommended by the manufacturer or FDA labelling Use of any drug in the face of a contraindication is outside of the FDA and manufacturer’s labelled recommendation and is considered investigational or experimental Non-adherence Individual does not follow prescribe regimen that places the individual at risk for lack of improvement or worsening of the condition being treated and this concern is documented in medical record Precertification: Precertification (Prior Authorization) is required for members with a Blue Cross Blue Shield of Arizona (BCBSAZ) pharmacy benefit for medication(s) or product(s) indicated in this guideline. Page 3 of 11 PHARMACY COVERAGE GUIDELINES SECTION: DRUGS NEXT REVIEW DATE: ORIGINAL EFFECTIVE DATE: LAST REVIEW DATE: LAST CRITERIA REVISION DATE: ARCHIVE DATE: 3rd QUARTER 2017 03/17/16 07/21/16 07/13/16 ISOTRETINOIN ORAL PRODUCTS (cont.) This Pharmacy Coverage Guideline does not apply to FEP or other states’ Blues Plans. Information about medications that require precertification is available at www.azblue.com/pharmacy. Some large (100+) benefit plan groups may customize certain benefits, including adding or deleting precertification requirements. All applicable benefit plan provisions apply, e.g., waiting periods, limitations, exclusions, waivers and benefit maximums. Criteria: See “Resources” section for FDA-approved dosage. Precertification for Absorica, Amnesteem, Claravis, Myorisan, and Zenatane requires completion of the specific request form in its entirety. All requested data must be provided. Once completed the form must be signed by the prescribing provider and faxed back to BCBSAZ Pharmacy Management at (602) 864-3126 or emailed to [email protected]. Incomplete forms will be returned. FDA-approved product labeling (indication, age, dosage, testing, contraindications, exclusions, etc.) of Absorica, Amnesteem, Claravis, Myorisan, and Zenatane is considered medically necessary when ALL of the following criteria are met: 1. Individual is 12 years of age or older 2. Individual has medical record documentation of a confirmed diagnosis of ONE of the following: Severe nodular acne Moderate nodular acne that is EITHER: Unresponsive to conventional therapy that includes ALL of the following: oral antibiotic used simultaneously with a topical combination product containing a retinoid, antibiotic, benzoyl peroxide Acne that has relapsed quickly after finishing oral antibiotic Acne that produced physical scarring or resulted in significant psychosocial distress 3. Dose will be 0.25-2 mg/kg/day depending on severity with a goal of achieving 150 mg/kg cumulative amount 4. Duration of use to be 4-8 months (16-32 weeks) 5. Any retreatment course is initiated after 2 months or more off therapy 6. For Absorica: individual is unable to use ALL of the following: Amnesteem (isotretinoin) oral capsule Claravis (isotretinoin) oral capsule Myorisan (isotretinoin) oral capsule Zenatane (isotretinoin) oral capsule Page 4 of 11 PHARMACY COVERAGE GUIDELINES SECTION: DRUGS NEXT REVIEW DATE: ORIGINAL EFFECTIVE DATE: LAST REVIEW DATE: LAST CRITERIA REVISION DATE: ARCHIVE DATE: 3rd QUARTER 2017 03/17/16 07/21/16 07/13/16 ISOTRETINOIN ORAL PRODUCTS (cont.) 7. Absence of ALL of the following contraindications: Pregnancy in a woman of child bearing potential Hypersensitivity to Absorica, Amnesteem, Claravis, Myorisan, and Zenatane or any of their components 8. Absence of ALL of the following exclusions: Concomitant use with tetracyclines Concurrent use of vitamin A Concurrent use with St. John’s Wort Chronic long term use at any dose Woman who is nursing an infant or child Absorica, Amnesteem, Claravis, Myorisan, and Zenatane for all other indications not previously listed is considered experimental or investigational based upon: 1. 2. 3. 4. Lack of final approval from the Food and Drug Administration, and Insufficient scientific evidence to permit conclusions concerning the effect on health outcomes, and Insufficient evidence to support improvement of the net health outcome, and Insufficient evidence to support improvement of the net health outcome as much as, or more than, established alternatives, and 5. Insufficient evidence to support improvement outside the investigational setting. This includes but is not limited to the following: Use of any of these agents for cosmetic purpose, the contract benefit language will be applied to determine coverage Liver spots Melasma Photo-aged skin Wrinkles History: Pharmacy and Therapeutics review Director Pharmacy Mgmt. review Pharmacy and Therapeutics review Director Pharmacy Mgmt. review Date: 07-21-2016 07-13-2016 03-17-2016 03-10-2016 Activity: Approved revisions Criteria revisions Adopted guideline Development Criteria Revisions: Date: Criteria: 07-13-16 2. Individual has medical record documentation of a confirmed diagnosis of severe recalcitrant nodular acne in an individual with ALL of the following: Multiple nodules of 5 mm or greater Page 5 of 11 Revisions: 2. Individual has medical record documentation of a confirmed diagnosis of ONE of the following: Severe nodular acne Moderate nodular acne that is EITHER: PHARMACY COVERAGE GUIDELINES SECTION: DRUGS NEXT REVIEW DATE: ORIGINAL EFFECTIVE DATE: LAST REVIEW DATE: LAST CRITERIA REVISION DATE: ARCHIVE DATE: 3rd QUARTER 2017 03/17/16 07/21/16 07/13/16 ISOTRETINOIN ORAL PRODUCTS (cont.) Unresponsive to conventional therapy that includes ALL of the following: generic topical retinoids, generic topical antibiotics, generic oral antibiotics, and generic combination topical therapy Unresponsive to oral antibiotics 07-13-16 Unresponsive to conventional therapy that includes ALL of the following: oral antibiotic used simultaneously with a topical combination product containing a retinoid, antibiotic, benzoyl peroxide Acne that has relapsed quickly after finishing oral antibiotic Acne that produced physical scarring or resulted in significant psychosocial distress Added 3. Dose will be 0.25-2 mg/kg/day depending on severity with a goal of achieving 150 mg/kg cumulative amount 07-13-16 3. Duration of use to be 20 weeks per treatment course 4-8 months (16-32 weeks) AND any retreatment course is initiated after 2 months or more off therapy 07-13-16 Removed 5. ALL of the following baseline tests have been completed before initiation of treatment: Two pregnancy tests at least 19 days apart, for females of reproductive potential Negative pregnancy test for females of reproductive potential before receiving each refill Fasting lipid profile including triglycerides Liver function tests Screened for significant psychiatric disorders 07-13-16 Removed 8. For female individual of reproductive potential, at least two (2) of the following forms of effective contraception are being used simultaneously: Tubal sterilization Partner’s vasectomy Intrauterine device Page 6 of 11 4. Duration of use to be 4-8 months (16-32 weeks) PHARMACY COVERAGE GUIDELINES SECTION: DRUGS NEXT REVIEW DATE: ORIGINAL EFFECTIVE DATE: LAST REVIEW DATE: LAST CRITERIA REVISION DATE: ARCHIVE DATE: 3rd QUARTER 2017 03/17/16 07/21/16 07/13/16 ISOTRETINOIN ORAL PRODUCTS (cont.) Hormonal (combination oral contraceptives, transdermal patch, injectables, implantables, or vaginal ring) Male latex condom with or without spermicide Diaphragm with spermicide Cervical cap with spermicide Vaginal sponge (contains spermicide) Resources: Absorica. Package Insert. Revised by manufacturer 09/2015. Accessed 03/10/2016. Amnesteem. Package Insert. Revised by manufacturer 03/2015. Accessed 03/15/2016. Claravis. Package Insert. Revised by manufacturer 01/2015. Accessed 03/15/2016. Myorisan. Package Insert. Revised by manufacturer 09/2015. Accessed 03/15/2016. Zenatane. Package Insert. Revised by manufacturer 06/2015. Accessed 03/15/2016. FDA-approved indication and dosage: Indication Recommended Dose ABSORICA is a retinoid indicated for the treatment of severe recalcitrant nodular acne in patients 12 years of age and older. Recommended dosage of 0.5 to 1 mg/kg/day given in two divided doses without regards to meals for 15 to 20 weeks. Limitations of Use ABSORICA may only be administered to patients enrolled in the iPLEDGE program. Once daily dosing is not recommended. Perform pregnancy tests prior to prescribing, each month during therapy, end of therapy, and one month after discontinuation. Prior to prescribing, perform fasting lipid profile and liver function tests. ABSORICA is not substitutable with other forms of isotretinoin. AMNESTEEM is indicated for the treatment of severe recalcitrant nodular acne. Nodules are inflammatory lesions with a diameter of 5 mm or greater. The nodules may AMNESTEEM should be administered with a meal (see PRECAUTIONS: Information for Patients). Page 7 of 11 PHARMACY COVERAGE GUIDELINES SECTION: DRUGS NEXT REVIEW DATE: ORIGINAL EFFECTIVE DATE: LAST REVIEW DATE: LAST CRITERIA REVISION DATE: ARCHIVE DATE: 3rd QUARTER 2017 03/17/16 07/21/16 07/13/16 ISOTRETINOIN ORAL PRODUCTS (cont.) become suppurative or hemorrhagic. “Severe,” by definition, means “many” as opposed to “few or several” nodules. Because of significant adverse effects associated with its use, Amnesteem should be reserved for patients with severe nodular acne who are unresponsive to conventional therapy, including systemic antibiotics. In addition, Amnesteem is indicated only for those female patients who are not pregnant, because Amnesteem can cause severe birth defects (see Boxed CONTRAINDICATIONS AND WARNINGS). A single course of therapy for 15 to 20 weeks has been shown to result in complete and prolonged remission of disease in many patients. If a second course of therapy is needed, it should not be initiated until at least 8 weeks after completion of the first course, because experience has shown that patients may continue to improve while off Amnesteem. The optimal interval before retreatment has not been defined for patients who have not completed skeletal growth (see WARNINGS: Skeletal: Bone Mineral Density, Hyperostosis, and Premature Epiphyseal Closure). The recommended dosage range for Amnesteem is 0.5 to 1 mg/kg/day given in two divided doses with food for 15 to 20 weeks. In studies comparing 0.1, 0.5 and 1 mg/kg/day, it was found that all dosages provided initial clearing of disease, but there was a greater need for retreatment with the lower dosages. During treatment, the dose may be adjusted according to response of the disease and/or the appearance of clinical side effects — some of which may be dose related. Adult patients whose disease is very severe with scarring or is primarily manifested on the trunk may require dose adjustments up to 2 mg/kg/day, as tolerated. Failure to take Amnesteem with food will significantly decrease absorption. Before upward dose adjustments are made, the patients should be questioned about their compliance with food instructions. The safety of once daily dosing with Amnesteem has not been established. Once daily dosing is not recommended. If the total nodule count has been reduced by more than 70% prior to completing 15 to 20 weeks of treatment, the drug may be discontinued. After a period of 2 months or more off therapy, and if warranted by persistent or recurring severe nodular acne, a second course of therapy may be initiated. The optimal interval before retreatment has not been defined for patients who have not completed skeletal growth. Long-term use of Amnesteem, even in low doses, has not been studied, and is not recommended. It is important that Amnesteem be given at the recommended doses for no longer than the recommended duration. The effect of long-term use of Amnesteem on bone loss is unknown (see WARNINGS: Skeletal: Bone Mineral Density, Hyperostosis, and Premature Epiphyseal Closure). Contraceptive measures must be followed for any subsequent course of therapy (see PRECAUTIONS). CLARAVIS (isotretinoin capsules, USP) is indicated for the treatment of severe recalcitrant nodular acne. Nodules are inflammatory lesions with a diameter of 5 mm or greater. The nodules may become suppurative or hemorrhagic. “Severe,” by definition, means “many” as opposed to “few or several” nodules. Because of significant adverse effects associated with its use, Claravis should be reserved for patients with severe nodular acne who are unresponsive to conventional therapy, including systemic antibiotics. In addition, Claravis is indicated only for those female patients who are not pregnant, CLARAVIS should be administered with a meal (see PRECAUTIONS, Information for Patients). The recommended dosage range for Claravis is 0.5 to 1 mg/kg/day given in two divided doses with food for 15 to 20 weeks. In studies comparing 0.1, 0.5, and 1 mg/kg/day, it was found that all dosages provided initial clearing of disease, but there was a greater need for retreatment with the lower dosages. During treatment, the dose may be adjusted according to response of the disease and/or the appearance of clinical side effects – some of which may be dose related. Adult patients whose disease is very severe Page 8 of 11 PHARMACY COVERAGE GUIDELINES SECTION: DRUGS NEXT REVIEW DATE: ORIGINAL EFFECTIVE DATE: LAST REVIEW DATE: LAST CRITERIA REVISION DATE: ARCHIVE DATE: 3rd QUARTER 2017 03/17/16 07/21/16 07/13/16 ISOTRETINOIN ORAL PRODUCTS (cont.) because Claravis can cause severe birth defects (see Boxed CONTRAINDICATIONS AND WARNINGS). A single course of therapy for 15 to 20 weeks has been shown to result in complete and prolonged remission of disease in many patients. If a second course of therapy is needed, it should not be initiated until at least 8 weeks after completion of the first course, because experience has shown that patients may continue to improve while off Claravis. The optimal interval before retreatment has not been defined for patients who have not completed skeletal growth (see WARNINGS, Skeletal, Bone Mineral Density, Hyperostosis, and Premature Epiphyseal Closure). with scarring or is primarily manifested on the trunk may require dose adjustments up to 2 mg/kg/day, as tolerated. Failure to take Claravis with food will significantly decrease absorption. Before upward dose adjustments are made, the patients should be questioned about their compliance with food instructions. The safety of once daily dosing with Claravis has not been established. Once daily dosing is not recommended. If the total nodule count has been reduced by more than 70% prior to completing 15 to 20 weeks of treatment, the drug may be discontinued. After a period of 2 months or more off therapy, and if warranted by persistent or recurring severe nodular acne, a second course of therapy may be initiated. The optimal interval before retreatment has not been defined for patients who have not completed skeletal growth. Long-term use of Claravis, even in low doses, has not been studied, and is not recommended. It is important that Claravis be given at the recommended doses for no longer than the recommended duration. The effect of longterm use of Claravis on bone loss is unknown (see WARNINGS, Skeletal, Bone Mineral Density, Hyperostosis and Premature Epiphyseal Closure). Contraceptive measures must be followed for any subsequent course of therapy (see PRECAUTIONS). MYORISAN is indicated for the treatment of severe recalcitrant nodular acne. Nodules are inflammatory lesions with a diameter of 5 mm or greater. The nodules may become suppurative or hemorrhagic. “Severe,” by definition, means “many” as opposed to “few or several” nodules. Because of significant adverse effects associated with its use, Myorisan should be reserved for patients with severe nodular acne who are unresponsive to conventional therapy, including systemic antibiotics. In addition, Myorisan is indicated only for those female patients who are not pregnant, because Myorisan can cause severe birth defects (see Boxed CONTRAINDICATIONS AND WARNINGS). A single course of therapy for 15 to 20 weeks has been shown to result in complete and prolonged remission of disease in many patients. If a second course of therapy is needed, it should not be initiated until at least 8 weeks after completion of the first course, because experience has shown that patients may continue to improve while off Myorisan. The optimal interval before retreatment has not been defined for patients who have not completed skeletal MYORISAN should be administered with a meal (see PRECAUTIONS: Information for Patients). The recommended dosage range for Myorisan is 0.5 to 1 mg/kg/day given in two divided doses with food for 15 to 20 weeks. In studies comparing 0.1, 0.5, and 1 mg/kg/day, it was found that all dosages provided initial clearing of disease, but there was a greater need for retreatment with the lower dosages. During treatment, the dose may be adjusted according to response of the disease and/or the appearance of clinical side effects — some of which may be dose related. Adult patients whose disease is very severe with scarring or is primarily manifested on the trunk may require dose adjustments up to 2 mg/kg/day, as tolerated. Failure to take Myorisan with food will significantly decrease absorption. Before upward dose adjustments are made, the patients should be questioned about their compliance with food instructions. The safety of once daily dosing with Myorisan has not been established. Once daily dosing is not recommended. Page 9 of 11 PHARMACY COVERAGE GUIDELINES SECTION: DRUGS NEXT REVIEW DATE: ORIGINAL EFFECTIVE DATE: LAST REVIEW DATE: LAST CRITERIA REVISION DATE: ARCHIVE DATE: 3rd QUARTER 2017 03/17/16 07/21/16 07/13/16 ISOTRETINOIN ORAL PRODUCTS (cont.) growth (see WARNINGS: Skeletal: Bone Mineral Density, Hyperostosis , Premature Epiphyseal Closure) If the total nodule count has been reduced by more than 70% prior to completing 15 to 20 weeks of treatment, the drug may be discontinued. After a period of 2 months or more off therapy, and if warranted by persistent or recurring severe nodular acne, a second course of therapy may be initiated. The optimal interval before retreatment has not been defined for patients who have not completed skeletal growth. Long-term use of Myorisan, even in low doses, has not been studied, and is not recommended. It is important that Myorisan be given at the recommended doses for no longer than the recommended duration. The effect of longterm use of Myorisan on bone loss is unknown (see WARNINGS: Skeletal: Bone Mineral Density, Hyperostosis, and Premature Epiphyseal Closure). Contraceptive measures must be followed for any subsequent course of therapy (see PRECAUTIONS). Zenatane™ is indicated for the treatment of severe recalcitrant nodular acne. Nodules are inflammatory lesions with a diameter of 5 mm or greater. The nodules may become suppurative or hemorrhagic. “Severe,” by definition, means “many” as opposed to “few or several” nodules. Because of significant adverse effects associated with its use, Zenatane™ should be reserved for patients with severe nodular acne who are unresponsive to conventional therapy, including systemic antibiotics. In addition, Zenatane™ is indicated only for those female patients who are not pregnant, because Zenatane™ can cause severe birth defects (see Boxed CONTRAINDICATIONS AND WARNINGS). A single course of therapy for 15 to 20 weeks has been shown to result in complete and prolonged remission of disease in many patients. If a second course of therapy is needed, it should not be initiated until at least 8 weeks after completion of the first course, because experience has shown that patients may continue to improve while off Zenatane™. The optimal interval before retreatment has not been defined for patients who have not completed skeletal growth (see WARNINGS: Skeletal: Bone Mineral Density, Hyperostosis, and Premature Epiphyseal Closure). Zenatane™ should be administered with a meal (see PRECAUTIONS: Information for Patients). The recommended dosage range for Zenatane™ is 0.5 to 1.0 mg/kg/day given in two divided doses with food for 15 to 20 weeks. In studies comparing 0.1, 0.5, and 1.0 mg/kg/day, it was found that all dosages provided initial clearing of disease, but there was a greater need for retreatment with the lower dosages. During treatment, the dose may be adjusted according to response of the disease and/or the appearance of clinical side effects — some of which may be dose related. Adult patients whose disease is very severe with scarring or is primarily manifested on the trunk may require dose adjustments up to 2.0 mg/kg/day, as tolerated. Failure to take Zenatane™ with food will significantly decrease absorption. Before upward dose adjustments are made, the patients should be questioned about their compliance with food instructions. The safety of once daily dosing with Zenatane™ has not been established. Once daily dosing is not recommended. If the total nodule count has been reduced by more than 70% prior to completing 15 to 20 weeks of treatment, the drug may be discontinued. After a period of 2 months or more off therapy, and if warranted by persistent or recurring severe nodular acne, a second course of therapy may be initiated. The optimal interval before retreatment has not been defined for patients who have not completed skeletal growth. Long-term use of Zenatane™, even in low doses, has not been studied, and is not recommended. It is important that Zenatane™ be given at the recommended doses for no longer than the recommended duration. The Page 10 of 11 PHARMACY COVERAGE GUIDELINES SECTION: DRUGS NEXT REVIEW DATE: ORIGINAL EFFECTIVE DATE: LAST REVIEW DATE: LAST CRITERIA REVISION DATE: ARCHIVE DATE: 3rd QUARTER 2017 03/17/16 07/21/16 07/13/16 ISOTRETINOIN ORAL PRODUCTS (cont.) effect of long-term use of Zenatane™ on bone loss is unknown (see WARNINGS: Skeletal: Bone Mineral Density, Hyperostosis, and Premature Epiphyseal Closure). Contraceptive measures must be followed for any subsequent course of therapy (see PRECAUTIONS). Page 11 of 11