and dosing ranges between 50–135mg daily.19 Due to its high lipophilicity, minocycline crosses the blood-brain barrier and achieves high concentrations in the CNS, and this may explain the higher rates of vestibular side effects (such as nausea, vomiting, dizziness, and vertigo), when compared to other tetracycline-class drugs.20
In two similarly designed clinical trials involving 1,038 moderate-to-severe acne patients, ages 12 years old, researchers found that, at 12 weeks, those prescribed extended-release minocycline 1 mg/kg daily experienced a 45.5% reduction in inflammatory lesions versus 32.4% in the placebo group (P<0.001).21 Additionally, 16.6% of the minocycline-group achieved EGSA 0 or 1 versus 8.7% of the placebo group (P<0.001) (Table 1).21 In these pivotal trials, the severity of AE were mild or moderate and included acute vestibular events (~10%) and pruritus (4.5%) (Table 1).21
In another trial of 332 inflammatory acne patients, ages 12 years and older, researchers found that, at 3 months, those prescribed minocycline 100mg daily experienced a 66.55% reduction in inflammatory lesions as compared to a 49.84% reduction in those treated with zinc 30mg daily (P<0.01) (Table 1).22 Of those treated with minocycline, 21.3% of patients reported AE, which were predominantly gastrointestinal disorders and allergic skin reactions (Table 1).22
In one trial, Stewart (2006) reported various measures at 12 weeks, including ear and labyrinth disorders, vertigo, dizziness, and patients with ≥ one acute vestibular adverse event. Incidence of dizziness ranged from 13.6% to 22.0% in the treatment groups and was 5.5% in the placebo group.23
In an open-label study of 338 acne patients, ages 13–30 years old, 12 weeks of minocycline 50mg twice-daily resulted in a significant improvement in the mean acne severity score [62.6 to 22.6, (P<0.0001)] (Table 1).24 Six percent of patients reported AE, which included diarrhea (2%), rash (~1%), and nausea (~1%) (Table 1).24 In another trial of 649 mild-to-moderate acne patients, ages 11–42 years old, researchers found that at week 18 the mean decrease in inflammatory lesions from baseline was 22.3 for those treated with minocycline 100mg (N=130) daily (Table 1).25 At week 18, the rates of gastrointestinal and cutaneous AE were <2% for the minocycline-treated patients.25
In an open-label safety study of three different minocycline dosing regimens (100mg daily, 100mg/200mg on alternate days, and 200mg daily) involving 700 acne patients, ages 13–48 years old, 13.6% of patients reported AE.26 Minocyclineinduced pigmentation was significantly higher in those treated with 200mg daily as compared to those treated with 100mg daily or 100mg/200mg on alternate days (P<0.01) (Table 1).26 Rates of gastrointestinal symptoms were similar in all groups (1.1%–2.4%), and cutaneous AE, such as urticaria, photosensitive rash, and pruritus occurred in <1% of all groups (Table 1).26
Three large retrospective studies demonstrated associations between minocycline and lupus-like syndrome, systemic lupus erythematosus (SLE), and IBD.18, 27,28 In a retrospective casecontrol study of 27,688 acne patients, ages 15–29 years old, researchers found that those who were currently prescribed any dose of minocycline were over eight times more likely to develop a lupus-like syndrome as compared with nonuse or past use of all combined oral tetracyclines [OR 8.5; 95% CI 2.1–35.0] (Table 1).2 Similarly, a retrospective cohort study of 97,694 acne patients, ages 15–35 years old, found that SLE was over twice as likely to occur in those taking minocycline, but not other oral tetracyclines [HR 2.64; 95% CI 1.51–4.66] (Table 1).28 Additionally, a retrospective study 94,487 acne patients, ages 15–35 years old, found that those who received minocycline (N=24,085) were approximately 20% more likely to develop new-onset IBD [HR 1.19; 95% CI 0.79–1.79] (Table 1).18
Tetracycline
Tetracycline was the first member of the tetracycline class. It is composed of four six-carbon rings with a hydroxyl-group and a methyl-group attached at C-6.3 Similar to other agents, tetracycline inhibits bacterial protein synthesis by impeding the 30S ribosomal subunit. Tetracycline also displays antiinflammatory properties by inhibiting neutrophil chemotaxis and matrix metalloproteinases.2,3 It is FDA-approved in the adjunctive treatment of severe acne, and dosages range from 250–500mg daily or twice-daily.29
In a trial of 305 moderate-to-severe acne patients, ages 18–35 years old, the mean papule count was significantly lower in those treated with tetracycline 250mg twice-daily (8.3) versus placebo (11.7) at week 8 (P<0.05) (Table 1).30 AE in those treated with tetracycline were diarrhea (2.5%) and epigastric pain (1.1%) (Table 1).30 In another trial of 200 moderate-tosevere acne patients, ages 14–30 years old, those treated with tetracycline (1000mg for 4 weeks followed by 500mg for 8 weeks) and erythromycin (1000mg for 4 weeks followed by 333mg for 8 weeks) saw significant reductions in mean lesion counts from baseline (P<0.0001) at week 12 (Table 1).31 Approximately ten percent of those treated with tetracycline reported AE, the majority of which included nausea and vomiting; vaginal candidiasis (1.2%), and pseudotumor cerebri (1.2%) were also reported (Table 1).31
Two retrospective studies assessed the safety of tetracycline use. In a retrospective hematology and chemistry safety study of 312 acne patients, researchers found that long term (≥3 years) tetracycline (250mg twice daily) use was generally
In two similarly designed clinical trials involving 1,038 moderate-to-severe acne patients, ages 12 years old, researchers found that, at 12 weeks, those prescribed extended-release minocycline 1 mg/kg daily experienced a 45.5% reduction in inflammatory lesions versus 32.4% in the placebo group (P<0.001).21 Additionally, 16.6% of the minocycline-group achieved EGSA 0 or 1 versus 8.7% of the placebo group (P<0.001) (Table 1).21 In these pivotal trials, the severity of AE were mild or moderate and included acute vestibular events (~10%) and pruritus (4.5%) (Table 1).21
In another trial of 332 inflammatory acne patients, ages 12 years and older, researchers found that, at 3 months, those prescribed minocycline 100mg daily experienced a 66.55% reduction in inflammatory lesions as compared to a 49.84% reduction in those treated with zinc 30mg daily (P<0.01) (Table 1).22 Of those treated with minocycline, 21.3% of patients reported AE, which were predominantly gastrointestinal disorders and allergic skin reactions (Table 1).22
In one trial, Stewart (2006) reported various measures at 12 weeks, including ear and labyrinth disorders, vertigo, dizziness, and patients with ≥ one acute vestibular adverse event. Incidence of dizziness ranged from 13.6% to 22.0% in the treatment groups and was 5.5% in the placebo group.23
In an open-label study of 338 acne patients, ages 13–30 years old, 12 weeks of minocycline 50mg twice-daily resulted in a significant improvement in the mean acne severity score [62.6 to 22.6, (P<0.0001)] (Table 1).24 Six percent of patients reported AE, which included diarrhea (2%), rash (~1%), and nausea (~1%) (Table 1).24 In another trial of 649 mild-to-moderate acne patients, ages 11–42 years old, researchers found that at week 18 the mean decrease in inflammatory lesions from baseline was 22.3 for those treated with minocycline 100mg (N=130) daily (Table 1).25 At week 18, the rates of gastrointestinal and cutaneous AE were <2% for the minocycline-treated patients.25
In an open-label safety study of three different minocycline dosing regimens (100mg daily, 100mg/200mg on alternate days, and 200mg daily) involving 700 acne patients, ages 13–48 years old, 13.6% of patients reported AE.26 Minocyclineinduced pigmentation was significantly higher in those treated with 200mg daily as compared to those treated with 100mg daily or 100mg/200mg on alternate days (P<0.01) (Table 1).26 Rates of gastrointestinal symptoms were similar in all groups (1.1%–2.4%), and cutaneous AE, such as urticaria, photosensitive rash, and pruritus occurred in <1% of all groups (Table 1).26
Three large retrospective studies demonstrated associations between minocycline and lupus-like syndrome, systemic lupus erythematosus (SLE), and IBD.18, 27,28 In a retrospective casecontrol study of 27,688 acne patients, ages 15–29 years old, researchers found that those who were currently prescribed any dose of minocycline were over eight times more likely to develop a lupus-like syndrome as compared with nonuse or past use of all combined oral tetracyclines [OR 8.5; 95% CI 2.1–35.0] (Table 1).2 Similarly, a retrospective cohort study of 97,694 acne patients, ages 15–35 years old, found that SLE was over twice as likely to occur in those taking minocycline, but not other oral tetracyclines [HR 2.64; 95% CI 1.51–4.66] (Table 1).28 Additionally, a retrospective study 94,487 acne patients, ages 15–35 years old, found that those who received minocycline (N=24,085) were approximately 20% more likely to develop new-onset IBD [HR 1.19; 95% CI 0.79–1.79] (Table 1).18
Tetracycline
Tetracycline was the first member of the tetracycline class. It is composed of four six-carbon rings with a hydroxyl-group and a methyl-group attached at C-6.3 Similar to other agents, tetracycline inhibits bacterial protein synthesis by impeding the 30S ribosomal subunit. Tetracycline also displays antiinflammatory properties by inhibiting neutrophil chemotaxis and matrix metalloproteinases.2,3 It is FDA-approved in the adjunctive treatment of severe acne, and dosages range from 250–500mg daily or twice-daily.29
In a trial of 305 moderate-to-severe acne patients, ages 18–35 years old, the mean papule count was significantly lower in those treated with tetracycline 250mg twice-daily (8.3) versus placebo (11.7) at week 8 (P<0.05) (Table 1).30 AE in those treated with tetracycline were diarrhea (2.5%) and epigastric pain (1.1%) (Table 1).30 In another trial of 200 moderate-tosevere acne patients, ages 14–30 years old, those treated with tetracycline (1000mg for 4 weeks followed by 500mg for 8 weeks) and erythromycin (1000mg for 4 weeks followed by 333mg for 8 weeks) saw significant reductions in mean lesion counts from baseline (P<0.0001) at week 12 (Table 1).31 Approximately ten percent of those treated with tetracycline reported AE, the majority of which included nausea and vomiting; vaginal candidiasis (1.2%), and pseudotumor cerebri (1.2%) were also reported (Table 1).31
Two retrospective studies assessed the safety of tetracycline use. In a retrospective hematology and chemistry safety study of 312 acne patients, researchers found that long term (≥3 years) tetracycline (250mg twice daily) use was generally
