Prior Auth Protocol

FDA Approved Indications:

Revatio: Treatment of pulmonary arterial hypertension (World Health Organization (WHO) Group 1) in adults to improve exercise ability and delay clinical worsening.
Adcirca: Treatment of pulmonary arterial hypertension (WHO Group 1) to improve exercise ability.

Health Net Approved Indications and Usage Guidelines:

Diagnosis of pulmonary arterial hypertension (PAH) (WHO Group 1)

AND

Revatio requests: For patients less than 18 years of age, failure or clinically significant adverse effects to two other PAH therapies

Coverage is Not Authorized For:

Patients taking nitrates (e.g., Nitrodur^R, Nitrobid^R, Nitrostat^R, Isordil^R, Ismo^R)
Patients taking gunylate cyclase (GC) stimulators (e.g., Adempas^R)
Patients taking phosphodiesterase type 5 (PDE-5) inhibitors
Non-FDA approved indications, which are not listed in the Health Net Approved Indications and Usage Guidelines section, unless there is sufficient documentation of efficacy and safety in the published literature.

General Information:

Revatio is not recommended to be used in pediatric patients. An increase in mortality was observed with increasing Revatio doses. The hazard ratio for high dose compared to low dose was 3.5 (p=0.015). Causes of death were typical of patients with PAH. Use of Revatio, particularly chronic use, is not recommended in children. The FDA advised against the off-label use of Revatio in children aged 1 through 17 years, but clarified that there may be situations in which the benefit-risk profile of Revatio may be acceptable in individual children, for example, when other treatment options are limited and Revatio can be used with close monitoring.
Safety and efficacy of Adcirca have not established in pediatric patients younger than 18 years.
Adding Revatio to bosentan therapy does not result in any beneficial effect on exercise capacity.
Studies establishing effectiveness of Revatio were short-term (12 to 16 weeks), and included predominately patients with New York Heart Association (NYHA) Functional Class II-III symptoms. Etiologies were idiopathic (71%) or associated with connective tissue disease (25%).
Studies establishing effectiveness of Adcirca included predominately patients with NYHA Functional Class II - III symptoms and etiologies of idiopathic or heritable PAH (61%) or PAH associated with connective tissue diseases (23%).
Use of Adcirca should be avoided in patients with severe renal impairment (Creatinine clearance <30 mL/min and on hemodialysis) or severe hepatic impairment (Child Pugh Class C). Use of Adcirca should be avoided in patients taking potent inhibitors of CYP3A (ketoconazole or itraconazole) or potent inducers of CYP3A (rifampin).
WHO classifies patients into 5 groups based on etiologies of pulmonary hypertension

Group 1 PAH: sporadic idiopathic pulmonary arterial hypertension (IPAH), heritable IPAH, PAH caused by diseases of the pulmonary arterioles and drug and toxin-induced PAH
Group 2 Pulmonary Hypertension (PH): due to cardiac origin
Group 3 PH: due to severe lung diseases or hypoxemia
Group 4 PH: Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
Group 5 PH: miscellaneous, unclear causes

Adcirca potentiates the hypotensive effect of nitrates. This potentiation is thought to result from the combined effects of nitrates and Adcirca on the nitric oxide/cGMP pathay.
Greater risk of hypotenstion when Revatio is concomitantly used with nitrates either regularly or intermittently. Adcirca and Revatio should not be used with other phosphodiesterase-5 inhibitors due to additive adverse effects, including hypotension.
Adcirca and Revatio may potentiate the hypotensive effects of GC stimulators.

Therapeutic Alternatives:

Drug	Dosing Regimen	Dose Limit/ Maximum Dose
Flolan^R, Veletri^R(epoprostenol)*	Initiate chronic infusion rate at 2 ng/kg/min continuous IV infusion via central catheter and increase in increments of 2 ng/kg/min every 15 min until dose-limiting pharmacological effects are elicited or until a tolerance limit is established or further increases are not clinically warranted.	Titrate as needed and tolerated, avoid abrupt withdrawal. Should dose-limiting effects occur, reduce infusion rate by 2 ng/kg/min every 15 minutes.
Letairis^TM(ambrisentan)	5 to 10 mg PO QD	10 mg PO QD
Remodulin^R (treprostinil)*	Initiate at 1.25 ng/kg/min SC continuous infusion (undiluted) or IV continuous infusion (diluted). The infusion rate should be increased in increments of 1.25 ng/kg/min per week for the first four weeks then 2.5 ng/kg/min per week for the remaining duration of infusion depending on clinical response. Avoid abrupt discontinuation. Transition from Flolan: Initial Remodulin dose is 10% of the current Flolan dose. Dose should be increased as Flolan dose is decreased.	40 ng/kg/min. Titrate as tolerated. Avoid abrupt withdrawal.
Tracleer^R (bosentan)	Initiate: 62.5 mg PO BID for 4 weeks Maintenance: Up to 125 mg PO BID (if body wt.< 40 kg and age > 12 y/o initial and maintenance is 62.5 mg PO BID)	125 mg PO BID
Ventavis^R (iloprost)*	2.5 - 5 mcg inhaled PO 6 to 9 times per day (no more than every two hours) Do not initiate therapy in patients with systolic blood pressure (SBP) below 85 mmHg	45 mcg (5 mcg nine times per day)
Tyvaso^R(treprostinil)*	Initial dosage: Inhale 3 breaths PO (18 mcg) per treatment session. If 3 breaths are not tolerated, reduce to 1 or 2 breaths. Administer in 4 separate treatment sessions each day approximately four hours apart, during waking hours. Dosage should be increased by an additional 3 breaths at approximately 1-2 week intervals, if tolerated. Titrate to target maintenance dosage of 9 breaths (54 mcg) per treatment session.	9 breaths (54 mcg) QID
Opsumit^R (macitentan)*	10 mg PO QD	10 mg PO QD
Orenitram^TM(treprostinil)*	Initial dosage: 0.25 mg PO BID or 0.125 mg PO TID Increase by 0.25 or 0.5 mg BID or 0.125 mg TID every 3 to 4 days to achieve optimal clinical response.	21 mg PO BID
Adempas^R(riociquat)*	1 mg PO TID If hypotension is a problem, may initiate at 0.5 mg PO TID; Increase by 0.5 mg every 2 weeks as tolerated up to a max dose of 2.5 mg PO TID.	2.5 mg PO TID

* Requires Prior Authorization

Recommended Dosing Regimen and Authorization Limit:

Drug	Dosing Regimen	Authorization Limit
Revatio	Tablets and Oral Suspension: 5 mg or 20 mg PO TID taken approximately 4 to 6 hours apart Injection: 2.5 mg or 10 mg IV bolus TID	Length of benefit
Adcirca	40 mg PO QD	Length of Benefit

Product Availability:

Revatio: 20 mg tablets; 10 mg (12.5 mL) single use vial; 10 mg/mL powder for oral suspension

Adcirca: 20 mg tablets

References:

1. Revatio [Prescribing Information] New York, NY: Pfizer; April 2015.
2. Adcirca [Prescribing Information] Indianapolis, IN: Eli Lilly; April 2015.
3. Sildenafil. American Hospital Formulary Service Drug Information. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed January 12, 2016.
4. Tadalafil. American Hospital Formulary Service Drug Information. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed January 12, 2016.
5. Micromedex^R Healthcare Series [Internet database]. Greenwood Village, CO: Thomson Healthcare. Updated periodically. Accessed January 12, 2016.
6. Clinical Pharmacology Web site. Available at: http://clinicalpharmacology-ip.com/default.aspx. Accessed January 15, 2016.
7. Medscape Web site. The Classification of Pulmonary Arterial Hypertension. Updated 2006. Available at: http://www.medscape.org/viewarticle/544175. Accessed January 12, 2016.