Prior Authorization Guideline
Guideline: MPD PHC - Marinol
Therapeutic Class: Anti-Emetic Agents
Therapeutic Sub-Class: Cannabinoid
Client: 2007 MPD PHC
Approval Date: 10/3/2006
Revision Date: 12/5/2006
**THIS GUIDELINE IS USED TO DETERMINE PART B VS PART D COVERAGE**
I.
BENEFIT COVERAGE
A. Background
Section 4557 of the Balanced Budget Act of amends §1861(s)(2) by extending the
coverage of oral anti-emetic drugs under the following conditions:1
•
•
•
•
Coverage is provided only for oral drugs approved by the FDA for use as antiemetics;
The oral anti-emetic(s) must either be administered by the treating physician or in
accordance with a written order from the physician as part of a cancer chemotherapy
regimen;
Oral anti-emetic drug(s) administered with a particular chemotherapy treatment must
be initiated within 2 hours of the administration of the chemotherapeutic agent and
may be continued for a period not to exceed 48 hours from that time; and
The oral anti-emetic drug(s) provided must be used as a full therapeutic replacement
for the intravenous anti-emetic drugs that would have otherwise been administered at
the time of the chemotherapy treatment
B. Formulary Status
Table 1. Formulary status
Non-Formulary Products
Formulary Products
Tier 4
Marinol® (dronabinol)*
* Subject to Prior Authorization
II.
INDICATIONS
A. FDA Approved Indications2
1. Anorexia in Patients with AIDS
Marinol is indicated for the treatment of anorexia associated with weight loss in patients
with AIDS
2. Nausea and Vomiting
Marinol is indicated for the treatment of nausea and vomiting associated with cancer
chemotherapy in patients who have failed to respond adequately to conventional
antiemetic treatments.
III.
GUIDELINE
A. Part B
1. Marinol will be covered under Part B based on both of the following criteria:1
a. Oral anti-emetic drug administered with chemotherapy treatment that is initiated
within 2 hours of the administration of chemotherapy and continued for a period
not to exceed 48 hours from that time
-ANDb. Oral anti-emetic drug is used as a full therapeutic replacement for IV anti-emetic
drugs that would have been administered at the time of the chemotherapy
treatment
B. Part D – Nausea and Vomiting Associated with Cancer Chemotherapy
1. Marinol will be covered under Part D based on the following criteria:
a. All of the following:
(1) Patient does not meet criteria for Part B above
-AND(2) History of failure or contraindication to a 5HT-3 Receptor Antagonist (e.g.,
Anzemet, Kytril or Zofran)2,a
-AND(3) History of failure or contraindication to one agent from at least one of the
following drug classes:2,a
i.
Antihistamines (Prochlorperazine, Promethazine)
ii. Corticosteroids (Dexamethasone)
iii. Prokinetic Agents (Metoclopramide)
iv. Antipsychotic Agents (Haloperidol)
- OR b. As continuation of therapy for treatment covered under Part B
Authorization will be issued for length of therapy.
C. Part D – Anorexia in Patients with AIDS
1. Marinol will be covered under Part D based on all of the following criteria:
a. Diagnosis of anorexia with weight loss in patients with AIDS.2
IV.
CONTRAINDICATIONS AND WARNINGS
A. Contraindications
1. Hypersensitivity
Marinol is contraindicated in any patient who has a known sensitivity to Marinol or any
of its ingredients. It contains cannabinoid and sesame oil and should never be used by
patients allergic to these substances.
B. Warnings
1. Hazardous Activities
Patients receiving treatment with Marinol should be specifically warned not to drive,
operate machinery, or engage in any hazardous activity until it is established that they are
able to tolerate the drug and to perform such tasks safely.
V.
DOSING
Appetite Stimulation:
2.5 mg twice daily before lunch and dinner.
For patients unable to tolerate this 5 mg/day dosage, the
dosage can be reduced to 2.5 mg/day, administered as a
single dose in the evening or at bedtime.
If clinically indicated, the dosage may be gradually
increased to a maximum of 20 mg/day , administered in
divided oral doses. Caution should be exercised in
escalating the dosage because of the increased frequency
of dose-related adverse experiences at higher dosages.
Antiemetic:
5 mg/m2, given 1 to 3 hours prior to the administration
of chemotherapy, then every 2 to 4 hours after
chemotherapy is given, for a total of 4 to 6 doses/day.
Should the 5 mg/m2 dose prove to be ineffective, and in
the absence of significant side effects, the dose may be
escalated by 2.5 mg/m2 increments to a maximum of 15
mg/m2 per dose. Caution should be exercised in dose
escalation, however, as the incidence of disturbing
psychiatric symptoms increases significantly at
maximum dose.
VI.
AVAILABILITY
Marinol: 2.5 mg, 5 mg, and 10 mg capsules
Marinol is a Schedule III (CIII) controlled substance.
VII.
BACKGROUND
A. Description
Dronabinol is an orally active cannabinoid which, like other cannabinoids, has complex
effects on the central nervous system (CNS), including central sympathomimetic activity.
Cannabinoid receptors have been discovered in neural tissues. These receptors may play a
role in mediating the effects of dronabinol and other cannabinoids.
B. Clinical Studies
1. Anorexia in Patients with AIDS
Dronabinol was shown to increase appetite in patients with AIDS-related anorexia in a
multicenter, double-blind, randomized controlled trial (n=221).3 Patients randomized to
receive dronabinol 2.5 mg twice daily reported significantly improved appetite, as
measured by visual analog scale, compared to those receiving placebo (p=0.05 for all
patients, p=0.015 for evaluable patients. Mean increase in appetite from baseline to end
point was 37% and 17% in the dronabinol and placebo groups, respectively (p=0.05).
In a long-term (12 months), open label evaluation of dronabinol 2.5 mg once or twice
daily, patients treated with dronabinol maintained improvements in hunger (measured by
VAS) compared to baseline.4
A head-to-head trial between dronabinol and megestrol acetate (n=469) showed that a
greater percentage of megestrol acetate-treated patients reported appetite improvement
compared to those receiving dronabinol (75% vs. 49%, p=0.001).5 More patients
receiving megestrol acetate reported weight gain than those receiving dronabinol (11%
vs. 3%, p=0.02). Combination treatment did not result in significant improvements
compared to megestrol acetate alone.
2. Nausea and Vomiting
The use of dronabinol for chemotherapy induced nausea and vomiting was evaluated in a
randomized controlled trial comparing the combination of dronabinol and
prochlorperazine with either agent along (n=62).6 The use of combination therapy was
associated with significantly shorter duration of nausea or vomiting compared to either
agent alone (p<0.001 vs. either single agent). Differences in the number of patients who
experienced nausea or vomiting were not significant, but consistently favored groups
receiving dronabinol. Patients receiving dronabinol were more likely to experience side
effects than those receiving prochlorperazine alone (p<0.01). Neuropsychiatric side
effects occurred in 62% of patients in the dronabinol group vs. 29% in the
prochlorperazine group.
C. National Guidelines
1. National Comprehensive Cancer Network (2006)7
Breakthrough emesis presents a difficult situation, because refractory ongoing nausea and
vomiting is often challenging to reverse. Generally, it is much easier to prevent nausea
and vomiting than to treat it. The general principle of breakthrough treatment is to give an
additional agent from a different drug class. Multiple concurrent agents, perhaps in
alternating schedules or by alternating routes, may be necessary. Dopamine antagonists,
metoclopramide, butyrophenones (e.g., haloperidol), corticosteroids, and agents such as
lorazepam may be required. Routine around-the-clock administration of antiemetics
should be strongly considered, rather than PRN (as required) dosing. Adequate hydration
or fluid repletion should be ensured, and any possible electrolyte abnormalities should be
assessed and corrected.
VIII. REFERENCES
1. Centers for Medicaid & Medicare Services. Medicare Intermediary Manual Part 3 - Claims
Process (Transmittal 1848). Available at:
http://www.cms.hhs.gov/transmittals/downloads/R1848A3.pdf Accessed September 22,
2006.
2. Marinol® Prescribing Information. Solvay Pharmaceuticals, Inc., July 2006.
3. Beal JE, Olson R, Laubenstein L, et al. Dronabinol as a treatment for anorexia associated
with weight loss in patients with AIDS. J Pain Symptom Manage. 1995;10:89-97.
4. Beal JE, Olson R, Lefkowitz L, et al. Long-term efficacy and safety of dronabinol for
acquired immunodeficiency syndrome-associated anorexia. J Pain Symptom Manage.
1997;14:7-14.
5. Jatoi A, Windschitl HE, Loprinzi CL, et al. Dronabinol versus megestrol acetate versus
combination therapy for cancer-associated anorexia: a North Central Cancer Treatment
Group study. J Clin Oncol. 200220:567-573.
6. Lane M, Vogel CL, Ferguson J, et al. Dronabinol and prochlorperazine in combination for
treatment of cancer chemotherapy-induced nausea and vomiting. J Pain Symptom Manage.
1991;6:352-359.
7. National Comprehensive Cancer Network. Practice Guidelines in Oncology – v.2.2006.
Antiemesis. Available at:
http://www.nccn.org/professionals/physician_gls/PDF/antiemesis.pdf. Accessed September
22, 2006.
X.
ENDNOTES
a. Marinol is indicated for the treatment of nausea and vomiting associated with cancer
chemotherapy only in patients who have failed to respond adequately to conventional
antiemetic treatments.
This Prior Authorization Guideline represents the recommendation of Prescription Solutions’ Pharmacy and Therapeutics (P&T) Committee.
It is based upon the P&T Committee’s review of the available evidence as of the date of drafting or revision of this Prior Authorization
Guideline. It is subject to updating from time to time, based upon changes in scientific knowledge and information.
This Prior Authorization Guideline is intended as a resource for making coverage decisions for Health Plan members, but it does not replace
an individualized case-by-case review and medical necessity determination for each Health Plan member.
Copyright © 2006 by Prescription Solutions. All rights reserved. This Prior Authorization Guideline is intended for use by Prescription
Solutions and Health Plan employees and applicable contracted providers and practitioners only. The information contained in this Prior
Authorization Guideline is confidential and proprietary to Prescription Solutions and shall not be used, reproduced, or transferred in whole or
in part without Prescription Solutions’ prior written consent.