California compliance policy summary and declaration

COMPLIANCE POLICY SUMMARY

It is the policy of Mist Pharmaceutical, LLC (“Mist”) to comply with all applicable laws and regulations and industry standards, including the PhRMA Code on Interactions with Healthcare Professionals and the Compliance Program Guidance for Pharmaceutical Manufacturers developed by the U.S. Department of Health and Human Services Office of the Inspector General (the “OIG Guidance”). Our Comprehensive Compliance Program incorporates the following elements from the OIG Guidance:

  • Written Policies and Procedures
  • Compliance Committee
  • Effective Training and Education
  • Effective Lines of Communication
  • Internal Monitoring and Auditing
  • Enforcement Through Discipline Pursuant to Published Guidelines; and
  • Prompt Response and Corrective Action for Detected Problems

Mist sales and marketing personnel interact with healthcare professionals to provide them with information about Mist products and other relevant educational or scientific topics. Mist believes that these interactions provide educational value to healthcare professionals and help benefit patients. In connection with certain of these interactions, Mist may provide promotional materials, or educational items intended to benefit a patient or related to a healthcare professionals’ practice. Mist may also on occasion offer modest meals to healthcare professionals in connection with educational presentations. The PhRMA Code allows pharmaceutical companies to provide “items designed primarily for the education of patients or healthcare professionals if the items are not of substantial value ($100 or less) and do not have value to healthcare professionals outside of his or her professional responsibilities.” On occasion Mist may approve the distribution of an educational item to a healthcare professional in accordance with the PhRMA Code standards. Mist’s Comprehensive Compliance Program is designed to ensure that these activities are conducted in lawful manner.

California Health and Safety Code §§ 119400-119402 requires pharmaceutical companies to make available their Comprehensive Compliance Program and to set an annual aggregate limit on certain promotional expenditures provide to a healthcare professional as defined under the California law.

ANNUAL SPEND LIMIT

Subject to this California law, Mist has determined that the annual aggregate limit on covered promotional expenditures in California is set at $500.00 per covered healthcare professional for each calendar year. This limit may be revised by Mist from time to time. It is important to note that this annual dollar limit is an upper limit. It is not an accurate representation of the average value of gifts, promotional materials, items or activities that Mist may provide generally to a healthcare professional. The average could be a lower amount. In accordance with the law, certain items and payments are excluded in determining whether the annual limit has been met. The annual limit does not include the value of:

  • Drug samples provided to healthcare professionals intended for free distribution to patients;
  • Financial support for continuing medical education forums;
  • Financial support for health educational scholarships; and
  • Payments for legitimate professional services, including professional speaking, advising, consulting, training or market research services, that are based on the fair market value of the services provided.

DECLARATION OF COMPLIANCE

Mist declares, in good faith, that Mist is in substantial compliance with its Comprehensive Compliance Program and the requirements of California Health and Safety Code §§ 119400-119402. Our declaration is based upon information available during the twelve month period from January 1, 2016 through December 31, 2016. The next declaration will be based upon information captured beginning January 1, 2017.

CONCLUSION

As appropriate and consistent with applicable law, Mist will amend and make conforming changes to its Comprehensive Compliance Program. Mist is committed to assessing ongoing compliance with its Comprehensive Compliance Program. A copy of the Comprehensive Compliance Program and this written declaration can be requested by calling 973-597-6202.

Important Safety Information

Important Safety Information

INDICATION

STENDRA is a phosphodiesterase 5 (PDE5) inhibitor indicated for the treatment of erectile dysfunction.

IMPORTANT SAFETY INFORMATION ABOUT STENDRA

  • Administration of STENDRA with any form of organic nitrates, either regularly and/or intermittently, is contraindicated. STENDRA has been shown to potentiate the hypotensive effects of nitrates.
  • STENDRA is contraindicated in patients with a known hypersensitivity to any component of the tablet.
  • Do not use STENDRA in patients who are using a Guanylate Cyclase (GC) stimulator, such as riociguat. PDE 5 inhibitors, including STENDRA may potentiate the hypotensive effects of GC stimulators
  • There is a potential for cardiac risk during sexual activity in patients with preexisting cardiovascular disease. Patients should therefore not use STENDRA if sexual activity is inadvisable due to cardiovascular status or any other reason.
  • Patients with the following characteristics (recent serious cardiovascular events, resting hypotension or uncontrolled hypertension, unstable angina, angina with sexual intercourse, New York Heart Association Class 2 or greater congestive heart failure, or hereditary degenerative retinal disorders, including retinitis pigmentosa) were not included in the clinical safety and efficacy trials. STENDRA is therefore not recommended for those patients.
  • As with other PDE5 inhibitors, STENDRA has systemic vasodilatory properties and may augment the blood pressure-lowering effect of other antihypertensive medications. Physicians should carefully consider whether patients with underlying cardiovascular disease could be affected adversely by such vasodilatory effects, especially in combination with sexual activity.
  • STENDRA metabolism is principally mediated by the CYP450 isoform 3A4 (CYP3A4). Inhibitors of CYP3A4 may reduce STENDRA clearance and increase plasma concentrations of avanafil. Do not use STENDRA in patients taking concomitant strong CYP3A4 inhibitors. For patients taking concomitant moderate CYP3A4 inhibitors, the maximum recommended dose of STENDRA is 50 mg, not to exceed once every 24 hours.
  • Prolonged erections greater than 4 hours in duration and priapism (painful erections greater than 6 hours in duration) have been reported with other PDE5 inhibitors. Patients should seek emergency treatment for an erection that lasts longer than 4 hours. If not treated immediately, penile tissue damage and permanent loss of potency could result. Use with caution in patients with anatomical deformation of the penis or in patients with conditions that may predispose them to priapism.
  • Physicians should advise patients to stop use of all PDE5 inhibitors, including STENDRA, and seek medical attention in the event of a sudden loss of vision in one or both eyes. This may be a sign of nonarteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision. STENDRA should be used with caution, and only when the anticipated benefits outweigh the risks, in patients with a history of NAION.
  • Use of PDE5 inhibitors has been associated with sudden decrease or loss of hearing, which may be accompanied by tinnitus or dizziness. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors. Patients experiencing these symptoms should be advised to stop taking STENDRA and seek prompt medical attention.
  • Physicians should discuss with patients the potential for STENDRA to augment the blood pressure-lowering effect of alpha-blockers and other antihypertensive medications.
  • Caution is advised when PDE5 inhibitors are coadministered with alpha-blockers. Patients who demonstrate hemodynamic instability on alpha-blocker therapy alone are at increased risk of symptomatic hypotension with concomitant use of PDE5 inhibitors. Patients should be stable on alpha-blocker therapy prior to initiating treatment with a PDE5 inhibitor. In those patients who are stable on alpha-blocker therapy, PDE5 inhibitors should be initiated at the lowest dose (STENDRA 50 mg). In those patients already taking an optimized dose of a PDE5 inhibitor, alpha-blocker therapy should be initiated at the lowest dose. Stepwise increase in alpha-blocker dosage may be associated with further lowering of blood pressure when taking a PDE5 inhibitor.
  • Both alcohol and PDE5 inhibitors including STENDRA act as vasodilators. When vasodilators are taken in combination, blood-pressure-lowering effects of each individual compound may be increased. Physicians should therefore inform patients that substantial consumption of alcohol (ie, greater than 3 units) in combination with STENDRA may increase the potential for orthostatic signs and symptoms, including increase in heart rate, decrease in standing blood pressure, dizziness, and headache.
  • The safety and efficacy of combinations of STENDRA with other treatments for ED have not been studied. The use of such combinations is therefore not recommended.
  • The safety of STENDRA is unknown in patients with bleeding disorders and patients with active peptic ulceration. In vitro studies with human platelets indicate that STENDRA potentiates the anti-aggregatory effect of sodium nitroprusside (a nitric oxide [NO] donor).
  • The use of STENDRA offers no protection against sexually transmitted diseases. Counseling patients about the protective measures necessary to guard against sexually transmitted diseases, including Human Immunodeficiency Virus (HIV), should be considered.
  • The most common adverse reactions (greater than or equal to 2%) include headache, flushing, nasal congestion, nasopharyngitis, and back pain.
  • Drug interactions: STENDRA can potentiate the hypotensive effect of nitrates, alpha-blockers, antihypertensives, and alcohol. CYP3A4 inhibitors (eg, ketoconazole, ritonavir, erythromycin) increase STENDRA exposure.

Please see full Prescribing Information.

References: 1. STENDRA [package insert]. Mist Pharmaceuticals.; 2015. 2. Viagra® [package insert]. Pfizer Inc; 2015. 3. Levitra® [package insert]. Bayer Healthcare Pharmaceuticals Inc.; 2015. 4. Staxyn® [package insert]. Bayer Healthcare Pharmaceuticals Inc.; 2015. 5. Cialis® [package insert]. Eli Lilly and Company; 2016. 6. Goldstein I, McCullough AR, Jones LA, et al. A randomized, double-blind, placebo-controlled evaluation of the safety and efficacy of avanafil in subjects with erectile dysfunction. J Sex Med. 2012; 9(4):1122-1133. 7. Goldstein I, Jones LA, Belkoff LH, et al. Avanafil for the treatment of erectile dysfunction: a multicenter, randomized, double-blind study in men with diabetes mellitus. Mayo Clin Proc. 2012; 87(9):843-852. 8. Data on File. Clinical Study Report. Mist Pharmaceuticals.; 2014. 9. Mulhall JP, Burnett AL, Wang R, et al. A phase 3, placebo controlled study of the safety and efficacy of avanafil for the treatment of erectile dysfunction after nerve sparing radical prostatectomy. J Urol. 2013; 189(6):2229-2236. 10. Belkoff LH, McCullough A, Goldstein I, et al. An open-label, long-term evaluation of the safety, efficacy and tolerability of avanafil in male patients with mild to severe erectile dysfunction. Int J Clin Pract. 2013;67(4):333-341.