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Tyrvaya (varenicline) Prior Authorization with Quantity Limit Program Summary

Policy Number: PH-91164

This program applies to Blue Partner, Commercial, GenPlus, SourceRx series and Health Insurance Marketplace formularies.        

POLICY REVIEW CYCLE

Effective Date

Date of Origin   

07-01-2024           

FDA LABELED INDICATIONS AND DOSAGE

Agent(s)

FDA Indication(s)

Notes

Ref#

Acticlate®

(doxycycline hyclate)*

Tablet

Treatment of infections due to susceptible strains of microorganisms (refer to labeling for additional details)

Adjunctive therapy for acute intestinal amebiasis adjunct to amebicides

Prophylaxis of malaria due to Plasmodium falciparum in short-term travelers (less than 4 months) to areas with chloroquine and/or pyrimethamine-sulfadoxine resistant strains

Adjunctive therapy for severe acne

*generic available

24

Doryx® MPC

(doxycycline hyclate delayed-release)

Tablet

Treatment of infections due to susceptible strains of microorganisms (refer to labeling for additional details)

Adjunctive therapy for acute intestinal amebiasis adjunct to amebicides

Prophylaxis of malaria due to Plasmodium falciparum in short-term travelers (less than 4 months) to areas with chloroquine and/or pyrimethamine-sulfadoxine resistant strains

Adjunctive therapy for severe acne

1

Doryx®

(doxycycline hyclate delayed-release)*

Tablet

Treatment of infections due to susceptible strains of microorganisms (refer to labeling for additional details)

Adjunctive therapy for acute intestinal amebiasis adjunct to amebicides

Prophylaxis of malaria due to Plasmodium falciparum in short-term travelers (less than 4 months) to areas with chloroquine and/or pyrimethamine-sulfadoxine resistant strains

Adjunctive therapy for severe acne

*generic available

3

doxycycline hyclate

Delayed-release capsule*

Delayed-release tablet*

Tablet*

For the treatment of infections due to susceptible strains of microorganisms (refer to labeling for additional details)

In acute intestinal amebiasis, doxycycline may be a useful adjunct to amebicides

For the prophylaxis of malaria due to Plasmodium falciparum in short-term travelers (less than 4 months) to areas with chloroquine and/or pyrimethamine-sulfadoxine resistant strains

In severe acne, doxycycline may be useful adjunctive therapy

*generic available

4; 7; 29

doxycycline monohydrate

Capsule

Treatment of infections due to susceptible strains of microorganisms (refer to labeling for additional details)

Adjunctive therapy for acute intestinal amebiasis adjunct to amebicides

Adjunctive therapy for severe acne

5

Doxycycline 

(doxycycline monohydrate)*

Tablet

Treatment of infections due to susceptible strains of microorganisms (refer to labeling for additional details)

Adjunctive therapy for acute intestinal amebiasis adjunct to amebicides

Adjunctive therapy for severe acne

*generic available

2

Minocin®

(minocycline hydrochloride)*

Capsule

Treatment of infections due to susceptible strains of microorganisms (refer to labeling for additional details)

Adjunctive therapy for acute intestinal amebiasis adjunct to amebicides

Adjunctive therapy for severe acne

*generic available

10

Minocycline extended-release

Capsule

 

To treat only inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 12 years of age and older

27

minocycline

Tablet*

For the treatment of infections due to susceptible strains of microorganisms (see labeling for details)

In acute intestinal amebiasis, minocycline may be a useful adjunct to amebicides

For the treatment of asymptomatic carriers of Neisseria meningitidis to eliminate meningococci from the nasopharynx

In severe acne, minocycline may be useful adjunctive therapy 

*generic available

11

Minocycline 

Extended-Release Tablet*

To treat only inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 12 years of age and older

*generic available

30

Minolira™

(minocycline hydrochloride extended-release)

Tablet

To treat only inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 12 years of age and older

Limitations of Use: Minolira has not been evaluated in the treatment of infections.

26

Oracea®

(doxycycline delayed-release)

Capsule*

For the treatment of only inflammatory lesions (papules and pustules) of rosacea in adult patients. No meaningful effect was demonstrated for generalized erythema (redness) of rosacea.

Limitations of use:

  • This formulation of doxycycline has not been evaluated in the treatment or prevention of infections.
  • Oracea has not been evaluated for the treatment of erythematous, telangiectatic, or ocular components of rosacea. 

*generic available

6

Seysara®

(sarecycline hydrochloride)

Tablet

To treat inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 9 years of age or older

Limitations of Use:

  • Efficacy of Seysara beyond 12 weeks and safety beyond 12 months have not been established.
  • Seysara has not been evaluated in the treatment of infections.

28

Solodyn®

(minocycline hydrochloride film coated extended-release)*

Tablet

To treat only inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 12 years of age and older 

Limitations of use:

  • Solodyn did not demonstrate any effect on non-inflammatory lesions. 
  • Safety of Solodyn has not been established beyond 12 weeks of use. 
  • This formulation of minocycline has not been evaluated in the treatment of infections. 

*generic available

12

Targadox®

(doxycycline hyclate)*

Tablet

Treatment of infections due to susceptible strains of microorganisms (refer to labeling for additional details)

Adjunctive therapy for acute intestinal amebiasis adjunct to amebicides

Prophylaxis of malaria due to Plasmodium falciparum in short-term travelers (less than 4 months) to areas with chloroquine and/or pyrimethamine-sulfadoxine resistant strains

Adjunctive therapy for severe acne

*generic available

25

Tetracycline

Tablets

Treatment of infections due to susceptible strains of microorganisms (refer to labeling for additional details)

Adjunctive therapy for acute intestinal amebiasis adjunct to amebicides

Adjunctive therapy for severe acne

32

Vibramycin®

Capsule (doxycycline hyclate)*

Suspension (doxycycline monohydrate)*

Treatment of infections due to susceptible strains of microorganisms (refer to labeling for additional details)

Adjunctive therapy for acute intestinal amebiasis adjunct to amebicides

Prophylaxis of malaria due to Plasmodium falciparum in short-term travelers (less than 4 months) to areas with chloroquine and/or pyrimethamine-sulfadoxine resistant strains

Adjunctive therapy for severe acne

*generic available

8

Ximino®

(minocycline hydrochloride extended-release)

Capsule

To treat only inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 12 years of age and older

Limitations of Use: Ximino did not demonstrate any effect on non-inflammatory acne lesions. Safety of Ximino has not been established beyond 12 weeks of use. This formulation of minocycline has not been evaluated in the treatment of infections. 

27

See package insert for FDA prescribing information:  https://dailymed.nlm.nih.gov/dailymed/index.cfm

CLINICAL RATIONALE

Acne Vulgaris

The American Academy of Dermatology suggests several options for treatment of acne vulgaris in adolescents and young adults. Recommendations for topical acne therapies include benzoyl peroxide or combination with topical antibiotics (e.g., erythromycin or clindamycin) as monotherapy for mild acne, or in conjunction with topical retinoid, or systemic antibiotic therapy for moderate to severe acne. Clindamycin 1% solution or gel is currently the preferred topical antibiotic for acne therapy. Erythromycin 2% is available in multiple formulations but has reduced efficacy compared to clindamycin due to resistance of cutaneous Staphylococci and P acnes.(14)

Topical adapalene, tretinoin, and benzoyl peroxide can be safely used in the management of preadolescent acne in children. Azelaic acid is useful as an adjunctive acne treatment and is recommended in the treatment of post-inflammatory dyspigmentation. Topical dapsone 5% gel is recommended for inflammatory acne, particularly in adult females with acne. There is limited data to support sulfur, nicotinamide, resorcinol, sodium sulfacetamide, aluminum chloride, and zinc in the treatment of acne.(14) If topical antibiotic treatment is to be prolonged for more than a few weeks, topical benzoyl peroxide should be added, or used in combination products.(31)

Systemic antibiotics have been a mainstay for acne treatment for years.(14) They are indicated for use in moderate to severe inflammatory acne and should be used in combination with a topical retinoid and benzoyl peroxide. Tetracyclines are considered first-line therapy in moderate to severe acne, except when contraindicated. Doxycycline and minocycline are more effective than tetracycline, but neither is superior to each other. Oral erythromycin and azithromycin should be reserved for those who cannot use tetracyclines. The use of other systemic antibiotics is discouraged due to limited data for use in acne. Trimethoprim-sulfamethoxazole and trimethoprim use should be restricted to patients who are unable to tolerate tetracycline or in treatment-resistant patients.(14) Concomitant topical therapy with benzoyl peroxide or a retinoid should be used with systemic antibiotics and for maintenance after completion of systemic antibiotic therapy.(14)

Reviews of tetracycline agents used in the treatment of acne(15,16) have found tetracycline, minocycline, and doxycycline all to be effective in the treatment of acne, particularly during the inflammatory stage. One review of seven randomized trials which were set up to compare the efficacy of tetracyclines found no evidence of superiority of one tetracycline over another in reducing acne lesion counts.(15) Evidence-based recommendations for treatment of pediatric acne from the American Academy of Pediatrics consider oral antibiotics appropriate for moderate to severe inflammatory acne. Tetracycline derivatives, including tetracycline, doxycycline and minocycline are not to be used in children younger than 8 years of age.(23)

There are several other treatment options for acne. Hormonal therapy or oral contraceptives and isotretinoin are suggested; however, caution is needed for both therapies for adverse events and monitoring. There is limited evidence for the use and benefit of physical modalities for the routine treatment of acne, including pulsed dye laser, glycolic acid peels, and salicylic acid peels. Intralesional corticosteroid injections are effective in the treatment of individual acne nodules. Furthermore, no current data supports any specific dietary changes to manage acne. However, data suggests that high glycemic index diets maybe associated with acne and limited evidence suggests that some dairy products, particularly skim milk, may influence acne.(14)

Rosacea

Although there is no cure for rosacea, its features may be reduced or controlled with a range of topical and oral therapies as well as appropriate skin care and lifestyle management. Combination therapy to target the specific features of each patient with rosacea is often necessary for effective treatment. Patients and features of the disease may respond well or less well to various agents, and when treatments are effective, the mechanism(s) of action may be unclear. First-line therapies include topical agents, such as azelaic acid and metronidazole. When first-line treatments for inflammation are inadequate or when rosacea is more severe, oral antibiotics or retinoids are sometimes used, although data is sparse. Oral antibiotics often used include tetracycline, doxycycline, and minocycline.(9)

Minocycline

The safety and efficacy of Solodyn in the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris was assessed in two 12-week, multi-center, randomized, double-blind, placebo-controlled, studies in subjects greater than 12 years. The mean age of subjects was 20 years and subjects were from the following racial groups: white (73%), Hispanic (13%), black (11%), Asian/Pacific islander (2%), and other (2%). In the two efficacy and safety trials, a total of 924 subjects with non-nodular moderate to severe acne vulgaris received 1 mg/kg of Solodyn or placebo for a total of 12 weeks. The two primary efficacy endpoints were:

  1. Mean percent change in inflammatory lesion counts from baseline to 12 weeksPercentage of subjects with an Evaluator’s Global Severity Assessment (EGSA) of clear or almost clear at 12 weeks.
  2. Patients on Solodyn had a greater mean percent improvement in inflammatory lesions (43.1% and 45.8% in studies one and two respectively) compared to placebo (31.7% and 30.8%) (p<0.05). Solodyn did not demonstrate any effect on non-inflammatory lesions.(13)

There are no clinical studies comparing extended-release minocycline with older immediate-release formulations. A Medical Letter review of Solodyn concluded “Solodyn is an expensive new formulation of minocycline labeled for once-daily use. Whether Solodyn is as effective as immediate-release minocycline and less likely to cause vertigo remains to be established.(17)

Doxycycline

Oracea, indicated for the treatment of inflammatory lesions (papules and pustules) of rosacea in adult patients, is comprised of 30 mg immediate release and 10 mg delayed release doxycycline. While the mechanism of action is not fully understood, it is thought to be due to an anti-inflammatory effect.(6)

The safety and efficacy of Oracea was evaluated in two double-blind, randomized, placebo controlled trials involving 537 patients for the treatment of rosacea. Both phase III trials were 16 weeks in duration. Oracea therapy resulted in a mean decrease in lesion count from baseline of 11.8 and 9.5 in study one and two respectively compared to 5.9 and 4.3 for placebo respectively (p<0.05). Patients on Oracea did not demonstrate improvement in erythema compared to placebo.(6)

The FDA noted that the magnitude of efficacy shown is clinically somewhat limited and modest for an oral medication. The manufacturer has stated that at the systemic concentration provided by Oracea, doxycycline is not effective as an antimicrobial agent and appears to exert its action independent of antibacterial activity. The sponsor has not submitted data supporting this mechanism of action. Furthermore, there are some possible indicators of antibacterial action in the form of an increase in diarrhea in the active treatment arms of the pivotal trials.(18)

A double-blind randomized trial compared Oracea 40 mg once daily to doxycycline 100 mg once daily in the treatment of moderate to severe rosacea for 16 weeks. There was no statistically significant difference in the primary efficacy endpoint of the change in total lesion count. There was a higher incidence of GI adverse events related to doxycycline 100 mg versus Oracea (26% vs 5%); however, the discontinuation rate was 50% higher with Oracea versus doxycycline 100 mg.(19)

Safety

Doxycycline and minocycline are contraindicated in persons who have shown hypersensitivity to any of the tetracyclines.(1-4,6-8,11-12,24-30)

Minocin is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines or to any of the components of the product formulation.(10) 

Doxycycline capsules are contraindicated in persons who have shown hypersensitivity to any of the tetracyclines or to any of the components of the product formulation.(5)

Tetracycline tablets are contraindicated in persons who have shown hypersensitivity to any of the tetracyclines.(32)

REFERENCES

Number

Reference

1

Doryx MPC prescribing information. Mayne Pharma Commercial LLC. May 2023.

2

Doxycycline monohydrate tablet prescribing information. Zydus Pharmaceuticals USA Inc. September 2022.

3

Doryx prescribing information. Mayne Pharma. July 2022.

4

Doxycycline hyclate prescribing information. Mayne Pharma, Inc. October 2022.

5

Doxycycline capsules prescribing information. Chartwell RX, LLC. February 2023.

6

Oracea prescribing information. Galderma Laboratories, L.P. January 2023.

7

Doxycycline hyclate prescribing information (20 mg). Lannett Company, Inc. July 2020.

8

Vibramycin prescribing information. Pfizer Inc. December 2022.

9

Thiboutot D, Anderson R, Cook-Bolden F, et. al. Standard management options for rosacea: The 2019 update by the National Rosacea Society Expert Committee. J Am Acad Dermatol. 2020;82:1501-10.

10

Minocin prescribing information. Melinta Therapeutics, LLC. February 2021.

11

Minocycline tablet prescribing information. Sun Pharmaceutical Industries, Inc. June 2018.

12

Solodyn prescribing information. Bausch Health US LLC. September 2017.

13

Clinical Pharmacology. Monographs: Minocycline.

14

Zaenglein, Andrew L, MD, et al. American Academy of Dermatology. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74:945-73. 

15

Simonart T, Dramaix M, De Maertelaer V. Efficacy of tetracyclines in the treatment of acne vulgaris: a review. Br J Dermatol. 2007;158:208-16.

16

Sapadin AN, Fleischmajer R. Tetracyclines: nonantibiotic properties and their clinical implications. J Am Acad Dermatol. 2006;54:258-65.

17

Anon. Extended-release minocycline (Solodyn) for acne. Med Lett Drugs Ther. 2006;48(1248): 95-96.

18

Center for Drug Evaluation and Research. FDA Medical Review: Oracea. Application Number 50-805. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/050805s000_MedR.pdf.

19

Del Rosso JQ, Schlessinger J, Werschler P. Comparison of anti-inflammatory dose doxycycline versus doxycycline 100 mg in the treatment of rosacea. J Drugs Dermatology. 2008;7(6): 573-576.

20

May D, Kelsberg G, Safrenek S. What is the most effective treatment for acne rosacea? J Fam Pract. February 2011:60(2):108a-108c.

21

Goldgar C, Keahey D, Houchins J. Treatment options for acne rosacea. Am Fam Physician. 2009;80(5):461-468.

22

Treatment guidelines from the Medical Letter: Drugs for acne, rosacea, and psoriasis. Medical Letter. 2013;11(125):1-8.

23

Eichenfield L, Krakowski A, Piggott C, et al. Evidence-based recommendations for the diagnosis and treatment of pediatric acne. Pediatrics. 2013;131;S163-S186.

24

Acticlate prescribing information. Almirall, LLC. March 2020.

25

Targadox prescribing information. Journey Medical Corporation. March 2020.

26

Minolira prescribing information. EPI Health, Inc. June 2018.

27

Ximino prescribing information. Journey Medical Corporation. January 2021.

28

Seysara prescribing information. Almirall, LLC. March 2023. 

29

Doxycycline hyclate delayed release tablet prescribing information. Basiem, LLC. April 2019.

30

Minocycline ER prescribing information. Arminda Pharmaceuticals. December 2022

31

Kaiane A, Habeshian, Bernard A. Cohen; Current Issues in the Treatment of Acne Vulgaris. Pediatrics. 2020; 145(2);S225-S230.

32

Tetracycline prescribing information. Pharmaka Generics Inc. January 2024.

POLICY AGENT SUMMARY STEP THERAPY

Target Brand Agent Name(s)

Target Generic Agent Name(s)

Strength

Targeted MSC

Available MSC

Final Age Limit

Preferred Status

M ; N ; O

tetracycline hcl tab

250 MG ; 500 MG

M ; N ; O ; Y

N

Acticlate ; Lymepak ; Targadox

doxycycline hyclate tab

100 MG ; 150 MG ; 20 MG ; 50 MG ; 75 MG

M ; N ; O

O ; Y

Coremino ; Minolira ; Solodyn

minocycline hcl tab er

105 MG ; 115 MG ; 135 MG ; 45 MG ; 55 MG ; 65 MG ; 80 MG ; 90 MG

M ; N ; O ; Y

N ; O ; Y

Doryx

Doxycycline Hyclate Tab Delayed Release 200 MG

200 MG

M ; N ; O ; Y

O ; Y

Doryx

Doxycycline Hyclate Tab Delayed Release 50 MG

50 MG

M ; N ; O ; Y

O ; Y

Doryx

Doxycycline Hyclate Tab Delayed Release 80 MG

80 MG

M ; N ; O ; Y

N

Doryx mpc

Doxycycline Hyclate Tab Delayed Release

60 MG

M ; N ; O ; Y

N

Doryx mpc

Doxycycline Hyclate Tab Delayed Release 120 MG

120 MG

M ; N ; O ; Y

N

Minocin

minocycline hcl cap

100 MG ; 50 MG ; 75 MG

M ; N ; O

O ; Y

Oracea

doxycycline (rosacea) cap delayed release

40 MG

M ; N ; O

O ; Y

Seysara

sarecycline hcl tab

100 MG ; 150 MG ; 60 MG

M ; N ; O

N

Vibramycin

Doxycycline Hyclate Cap 100 MG

100 MG

M ; N ; O

O ; Y

Vibramycin

doxycycline monohydrate for susp

25 MG/5ML

M ; N ; O

O ; Y

Ximino

minocycline hcl cap er

135 MG ; 45 MG ; 90 MG

M ; N ; O

M

CLIENT SUMMARY – STEP THERAPY

Target Brand Agent Name(s)

Target Generic Agent Name(s)

Strength

Client Formulary

tetracycline hcl tab

250 MG ; 500 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Acticlate ; Lymepak ; Targadox

doxycycline hyclate tab

100 MG ; 150 MG ; 20 MG ; 50 MG ; 75 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Coremino ; Minolira ; Solodyn

minocycline hcl tab er

105 MG ; 115 MG ; 135 MG ; 45 MG ; 55 MG ; 65 MG ; 80 MG ; 90 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Doryx

Doxycycline Hyclate Tab Delayed Release 200 MG

200 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Doryx

Doxycycline Hyclate Tab Delayed Release 50 MG

50 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Doryx

Doxycycline Hyclate Tab Delayed Release 80 MG

80 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Doryx mpc

Doxycycline Hyclate Tab Delayed Release

60 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Doryx mpc

Doxycycline Hyclate Tab Delayed Release 120 MG

120 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Minocin

minocycline hcl cap

100 MG ; 50 MG ; 75 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Oracea

doxycycline (rosacea) cap delayed release

40 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Seysara

sarecycline hcl tab

100 MG ; 150 MG ; 60 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Vibramycin

Doxycycline Hyclate Cap 100 MG

100 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Vibramycin

doxycycline monohydrate for susp

25 MG/5ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Ximino

minocycline hcl cap er

135 MG ; 45 MG ; 90 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

STEP THERAPY CLINICAL CRITERIA FOR APPROVAL

Module

Clinical Criteria for Approval

Brand and Nonpreferred generic agent(s) will be approved when BOTH of the following are met

  1. ONE of the following:
    1. The patient’s medication history of use in the past 180 days includes a preferred generic doxycycline agent OR
    2. The patient has an intolerance or hypersensitivity to a preferred generic doxycycline agent OR
    3. The patient has an FDA labeled contraindication to ALL preferred generic doxycycline agents AND
  2. ONE of the following:
    1. The patient’s medication history of use in the past 180 days includes a preferred generic minocycline agent OR
    2. The patient has an intolerance or hypersensitivity to a preferred generic minocycline agent OR
    3. The patient has an FDA labeled contraindication to ALL preferred generic minocycline agents

Length of Approval:  12 months

*Step therapy requirement may not apply if a prior health plan paid for the medication - documentation of a paid claim may be required.

This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.
The purpose of Blue Cross and Blue Shield of Alabama’s pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.
Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.

ALBP _  Commercial _ CSReg _ Oral_Tetracycline_Derivatives_ST _ProgSum_ 07-01-2024  _  © Copyright Prime Therapeutics LLC. May 2024 All Rights Reserved