Effective Date

Date of Origin 

4/1/2023

Acticlate^®

(doxycycline hyclate)

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 (<4 months) to areas with chloroquine and/or pyrimethamine-sulfadoxine resistant strains

• In severe acne, doxycycline may be useful adjunctive therapy

Generic equivalent available

24

Doryx MPC^®

(doxycycline hyclate delayed-release)

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 (<4 months) to areas with chloroquine and/or pyrimethamine-sulfadoxine resistant strains

• In severe acne, doxycycline may be useful adjunctive therapy

1

Doryx^®

(doxycycline hyclate delayed-release)

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 equivalent available

3

Doxycycline monohydrate

(doxycycline)

Tablet

Capsule

• 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 equivalents available

2

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 (<4 months) to areas with chloroquine and/or pyrimethamine-sulfadoxine resistant strains

• In severe acne, doxycycline may be useful adjunctive therapy

Generic equivalent available

4; 7; 29

Minocin^®

(minocycline)

Capsule

• 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 equivalent 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 

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. Solodyn did not demonstrate any effect on non-inflammatory lesions

Generic equivalents are available

12,30

Minolira^®

(minocycline)

Tablet

• To treat only inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 12 years of age and older.  Minolira has not been evaluated in the treatment of infections

26

Monodox^®

(doxycycline monohydrate)

Capsule

• 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 equivalent available

5

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.

6

Seysara^®

(sarecycline)

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.  To reduce the development of drug-resistant bacteria as well as to maintain the effectiveness of other antibacterial drugs, Seysara should be used only as indicated

28

Solodyn^®

(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.  Solodyn did not demonstrate any effect on non-inflammatory lesions

12

Targadox^®

(doxycycline hyclate)

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 equivalent available

25

Vibramycin^®

(doxycycline)

Capsule

Suspension

Syrup 

• 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 equivalents available (capsule, suspension only)

8

Ximino^®

(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

• Ximino did not demonstrate any effect on non-inflammatory acne lesions. Safety of Ximino has not been established beyond 12 weeks of use

27

Acne Vulgaris

The American Academy of Dermatology suggests several options for treatment of acne vulgaris. Recommendations for topical acne therapies include benzoyl peroxide or combination of 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. Topical antibiotics are not recommended in monotherapy due to risk of bacterial resistance. 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 postinflammatory 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)

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 weeks

2. Percentage of subjects with an Evaluator’s Global Severity Assessment (EGSA) of clear or almost clear at 12 weeks.

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)

1

Doryx MPC prescribing information. Mayne Pharma. February 2020.

2

Doxycycline monohydrate tablet prescribing information. Mylan Pharmaceuticals Inc. March 2018.

3

Doryx prescribing information. Mayne Pharma. February 2020.

4

Doxycycline hyclate prescribing information. Mayne Pharma, Inc. March 2020.

5

Monodox prescribing information. Aqua Pharmaceuticals LLC. April 2017.

6

Oracea prescribing information. Galderma Laboratories, L.P. August 2017.

7

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

8

Vibramycin prescribing information. Pfizer Inc. December 2019.

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. Baush Health US, Inc. January 2019.

11

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

12

Solodyn prescribing information. Valeant Pharmaceuticals North America. September 2017.

13

Clinical Pharmacology. Monographs: Minocycline. Available at: http://www.clinicalpharmacology-ip.com/.

14

Zaenglein, Andrea 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. Available at: https://www.jaad.org/article/S0190-9622(15)02614-6/fulltext.

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. Sun Pharmaceuticals, Inc. November 2018.

28

Seysara prescribing information. Almirall, LLC. June 2020.

29

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

30

Minocycline ER prescribing information. Arminda Pharmaceuticals. December 2022

ACTICLATE*doxycycline hyclate tab  ; DOXYCYCLINE*doxycycline hyclate tab  ; LYMEPAK*doxycycline hyclate tab  ; TARGADOX*doxycycline hyclate tab

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

M ; N ; O

O ; Y

COREMINO*minocycline hcl tab er  ; MINOCYCLINE*minocycline hcl tab er  ; MINOLIRA*minocycline hcl tab er  ; 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

M ; 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

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  ; MINOCYCLINE*minocycline hcl cap

100 MG ; 50 MG ; 75 MG

M ; N ; O

O ; Y

DOXYCYCLINE HYCLATE*Doxycycline Hyclate Cap 100 MG

100 MG

M ; N ; O

O ; Y

DOXYCYCLINE*doxycycline (rosacea) cap delayed release  ; ORACEA*doxycycline (rosacea) cap delayed release

40 MG

M ; N ; O

M

SEYSARA*sarecycline hcl tab

100 MG ; 150 MG ; 60 MG

M ; N ; O

N

VIBRAMYCIN*doxycycline calcium syrup

50 MG/5ML

M ; N ; O

N

DOXYCYCLINE*doxycycline monohydrate for susp  ; VIBRAMYCIN*doxycycline monohydrate for susp

25 MG/5ML

M ; N ; O

O ; Y

MINOCYCLINE*minocycline hcl cap er  ; XIMINO*minocycline hcl cap er

135 MG ; 45 MG ; 90 MG

M ; N ; O

M

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

Morgidox 1x100mg ; Morgidox 2x100mg ; Vibramycin

Doxycycline Hyclate Cap 100 MG

100 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 calcium syrup

50 MG/5ML

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

Brand and Nonpreferred generic agents will be approved when BOTH of the following are met:

1. ONE of the following:
   1. The patient’s medication history includes use of a preferred generic doxycycline agent in the past 180 days 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 includes use of a preferred generic minocycline agent in the past 180 days 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