Prior Auth Protocol

FDA Approved Indications:

For women with severe diarrhea-predominant irritable bowel syndrome (IBS) who have:

chronic IBS symptoms (generally lasting 6 months or longer)
had anatomic or biochemical abnormalities of the gastrointestinal tract excluded, and
not responded adequately to conventional therapy

Severe IBS includes diarrhea and 1 or more of the following:

frequent and severe abdominal pain/discomfort
frequent bowel urgency or fecal incontinence
disability or restriction of daily activities due to IBS

Health Net Approved Indications and Usage Guidelines:

Physician is enrolled in the Prescribing Program for Lotronex

AND

Patient has read and signed the Patient Acknowledgement Form for Lotronex

AND

IBS symptoms are chronic and recurrent (lasting 6 months or longer)

AND

Physician has ruled-out anatomic or biochemical abnormalities of the gastrointestinal tract. Documentation may be required on any of the following: GI consult notes including reports from diagnostic procedures (e.g. colonoscopy or sigmoidoscopy), CBC, and TSH to rule out other causes.

AND

Failure or clinically significant adverse effects to conventional therapy e.g. psyllium (Metamucil) for the last 1-2 months and
- Anti-diarrhea agent
- Antispasmodic agent

AND

Patient has confirmed diagnosis of severe diarrhea-predominant IBS (Must have 1, 2 and 3)
1. Frequent and severe abdominal pain/discomfort ( at least 6 months)
2. Frequent bowel urgency or fecal incontinence (> 3 times per day)
3. Disability or restriction of daily activities due to IBS

Coverage is Not Authorized For:

IBS if patient has history of chronic or severe constipation, or sequelae from constipation: intestinal obstruction, stricture, toxic megacolon, GI perforations/adhesions; ischemic colitis: impaired intestinal circulation, thrombophlebitis, hypercoagulable state, Crohn's disease or ulcerative colitis, diverticulitis: severe hepatic impairment
Do not initiate in patients with constiation
Concomitant use of fluvoxamine
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:

Lotronex should be discontinued immediately in patients who develop constipation or symptoms of ischemic colitis. Patients should immediately report constipation or symptoms of ischemic colitis to their physician. Lotronex should not be resumed in patients who develop ischemic colitis. Patients who have constipation should immediately contact their physician if the constipation does not resolve after Lotronex is discontinued. Patients with resolved constipation should resume Lotronex only on the advice of their treating physician.
Concomitant administration of Lotronex with fluvoxamine is contraindicated. Fluvoxamine, a known strong inhibitor of CYP1A2, has been shown to increase mean Lotronex plasma concentrations (AUC) approximately 6-fold and prolong the half-life by approximately 3-fold.
Infrequent but serious GI adverse events have been reported with the use of Lotronex. These events, including ischemic colitis and serious complications of constipation, have resulted in hospitalization, and rarely, blood transfusion, surgery, and death.
One study of 662 men with diarrhea-predominant IBS showed Lotronex 1 mg twice daily provided a significantly higher average rate of adequate relief of IBS pain and discomfort during weeks 5-12 of the treatment phase (primary endpoint) compared to placebo.
Commercially available Lotronex is prescribed and distributed under a restricted distribution program, which is intended to control its access and to educate program participants (clinicians, pharmacists, patients) about the risks and benefits of the drug. Prescribers must enroll in the Prometheus Prescribing Program for Lotronex by calling 1-888-423-5227 or visiting http://www.lotronexppl.com to complete the Prescriber Enrollment Form.
The Prescribing Program for Lotronex was implemented to help reduce the risk of serious GI adverse events. Only physicians who have enrolled in the Prescribing Program for Lotronex, based on their understanding of the benefits and risks, can prescribe Lotronex.
Before receiving the initial prescription for Lotronex, the patient must read and sign the Patient Acknowledgement Form for Lotronex. Lotronex should not be used by patients who are unable to understand or comply with the Patient Acknowledgement Form for Lotronex.

Therapeutic Alternatives:

Drug	Dosing Regimen	Dose Limit/ Maximum Dose
Anti-diarrhea agents diphenoxylate/atropine (Lomotil^R)	Initial dose 5 mg PO QID Individualize dose.	If no clinical improvement after treatment with 20 mg/day for at least 10 days, symptoms are unlikely to be controlled by further use.
loperamide (Imodium^R)	Adults: 4 mg PO followed by 2 mg after each unformed stool until diarrhea is resolved; then individualize dose. Administer optimal daily dose (4-8 mg) as single or divided doses.	If no clinical improvement after treatment with 16 mg/day for at least 10 days, symptoms are unlikely to be controlled by further use.
Antispasmodic/anticholineric agents dicyclomine (Bentyl^R)	Adults: 80mg/day PO divided QID then increase to 160 mg/day	160 mg/day
hyoscyamine (Levsin^R, Levbid^R)	Adults: Levsin: 0.125 - 0.25 mg PO Q 4h Levbid: 0.375 - 0.75 mg PO Q 12h	1.5 mg/day
hyoscyamine, atropine, scopolamine, phenobarbital (Donnatal^R, Donnatal Extentabs^R)	Adults: Donnatal: 1-2 tablets or 5-10 mL of elixir PO TID-QID Donnatal Extentabs: 1 tablet PO Q 12h; may increase to 1 tablet PO Q 8h if needed	Donnatal: 8 tablets (40 mL)/day Donnatal Extentabs: 3 tablets/day

* Requires Prior Authorization

Recommended Dosing Regimen and Authorization Limit:

Drug	Dosing Regimen	Authorization Limit
Lotronex^TM (alosetron)	Starting dose should be 0.5 mg PO BID Dosage can be increased to 1 mg PO BID, after 4 weeks if well tolerated but symptoms not controlled Therapy to be stopped if symptoms are not controlled after 4 weeks of 1 mg PO BID therapy	Length of Benefit

Product Availability:

Tablets: 0.5 mg, 1 mg

References:

Lotronex [Prescribing Information] San Diego, CA: Prometheus Laboratories, Inc; March 2014.
Irritable Bowel Syndrome Self Help and Support Group. Diagnostic Criteria. Available at: http://www.ibsgroup.org/diagnosis. Accessed June 06, 2015.
Rome Foundation. Rome III Criteria for IBS. Available at: http://www.romecriteria.org/assets/pdf/20_RomeIII_apB_899-916.pdf. Accessed June 30, 2014.
Chey WD, Chey WY, Heath AT, et al. Long-term safety and efficacy of alosetron in women with severe diarrhea-predominant irritable bowel syndrome. Am J Gastroenterol 2004;99(11):2195-203.
Chang L, Amen VZ, Dukes GE, et al. A dose-ranging, phase II study of the efficacy and safety of alosetron in men with diarrhea-predominant IBS. Am J Gastroentrol. 2005;100(1):115-23.
Micromedex^R Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed June 06, 2015.
Lotronex. American Hospital Formulary Service Drug Information. Available at: http://medicinescomplete/com/mc/ahsf/current/. Accessed June 30, 2014.