Aczone

Name: Aczone

Other uses for this medicine

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

What other information should I know?

Keep all appointments with your doctor and the laboratory.

Do not let anyone else use your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

What happens if I miss a dose?

Apply the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next dose. Do not use extra medicine to make up the missed dose.

Aczone Dosage and Administration

For topical use only. Not for oral, ophthalmic, or intravaginal use.

After the skin is gently washed and patted dry, apply approximately a pea-sized amount of Aczone Gel, 7.5%, in a thin layer to the entire face once daily. In addition, a thin layer may be applied to other affected areas once daily. Rub in Aczone Gel, 7.5%, gently and completely.

If there is no improvement after 12 weeks, treatment with Aczone Gel, 7.5% should be reassessed (2).

Adverse Reactions

Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

A total of 2161 subjects were treated with Aczone Gel, 7.5%, for 12 weeks in 2 controlled clinical trials. The population ranged in age from 12 to 63 years, was 56% female, and 58% Caucasian. Adverse drug reactions that were reported in at least 0.9% of subjects treated with Aczone Gel, 7.5% appear in Table 1 below.

Table 1 Adverse Reactions Occurring in at Least 0.9% of Subjects with Acne Vulgaris in 12-week Controlled Clinical Trials
Aczone Gel, 7.5%
(N=2161)
Vehicle
(N=2175)
Application Site Dryness 24 (1.1%) 21 (1.0%)
Application Site Pruritus 20 (0.9%) 11 (0.5%)

Experience with Oral Use of Dapsone

Although not observed in the clinical trials with topical dapsone, serious adverse reactions have been reported with oral use of dapsone, including agranulocytosis, hemolytic anemia, peripheral neuropathy (motor loss and muscle weakness), and skin reactions (toxic epidermal necrolysis, erythema multiforme, morbilliform and scarlatiniform reactions, bullous and exfoliative dermatitis, erythema nodosum, and urticaria).

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of topical dapsone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Methemoglobinemia has been identified during postmarketing use of topical dapsone [see Warnings and Precautions (5.1)].

Use in specific populations

Pregnancy

Teratogenic Effects: Pregnancy Category C

There are no adequate and well controlled studies in pregnant women. Aczone Gel, 7.5%, should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Dapsone has been shown to have an embryocidal effect in rats and rabbits when administered orally during the period of organogenesis in doses of 75 mg/kg/day and 150 mg/kg/day, respectively (approximately 1400 and 425 times, respectively, the systemic exposure that is associated with the maximum recommended human dose (MRHD) of Aczone Gel, 7.5%, based on AUC comparisons). These effects may have been secondary to maternal toxicity.

Nursing Mothers

Although systemic absorption of dapsone following topical application of Aczone Gel, 7.5%, is minimal relative to oral dapsone administration, it is known that dapsone is excreted in human milk. Because of the potential for oral dapsone to cause adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue Aczone Gel, 7.5%, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and efficacy was evaluated in 1066 subjects aged 12-17 years old treated with Aczone Gel, 7.5% in the clinical trials. The safety profile for Aczone Gel, 7.5%, was similar to the vehicle control group. Safety and effectiveness of Aczone Gel, 7.5%, have not been established in pediatric patients below the age of 12 years.

Geriatric Use

Clinical trials of Aczone Gel, 7.5% did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects.

Glucose-6-phosphate Dehydrogenase (G6PD) Deficiency

Individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency may be more prone to methemoglobinemia and hemolysis [see Warnings and Precautions (5.1)].

Aczone Gel, 5% and vehicle were evaluated in a randomized, double-blind, cross-over design clinical study of 64 subjects with G6PD deficiency and acne vulgaris. Subjects were Black (88%), Asian (6%), Hispanic (2%) or of other racial origin (5%). Blood samples were taken at Baseline, Week 2, and Week 12 during both vehicle and Aczone Gel, 5% treatment periods. Some of these subjects developed laboratory changes suggestive of hemolysis, but there was no evidence of clinically significant hemolytic anemia in this study [see Warnings and Precautions (5.1)].

Clinical Studies

The safety and efficacy of once daily use of Aczone Gel, 7.5%, was assessed in two 12-week multicenter, randomized, double-blind, vehicle-controlled studies. Efficacy was assessed in a total of 4340 subjects 12 years of age and older. The majority of the subjects had moderate acne vulgaris, 20 to 50 inflammatory and 30 to 100 non-inflammatory lesions at baseline, who were randomized to receive either Aczone Gel, 7.5% or vehicle.

Treatment response was defined at Week 12 as the proportion of subjects who were rated “none” or “minimal” with at least a two-grade improvement from baseline on the Global Acne Assessment Score (GAAS), and mean absolute change from baseline in both inflammatory and non-inflammatory lesion counts. A GAAS score of “none” corresponded to no evidence of facial acne vulgaris. A GAAS score of “minimal” corresponded to a few non-inflammatory lesions (comedones) being present and to a few inflammatory lesions (papules/pustules) that may be present.

The GAAS success rate, mean reduction, and percent reduction in acne lesion counts from baseline after 12 weeks of treatment are presented in the following table.

Table 3 Clinical Efficacy of Aczone® Gel at Week 12 in Subjects with Acne Vulgaris
Trial 1 Trial 2
Aczone® Gel, 7.5%
(N=1044)
Vehicle

(N=1058)
Aczone® Gel, 7.5%
(N=1118)
Vehicle

(N=1120)
Global Acne Assessment Score
GAAS Success (Score 0 or 1) 30% 21% 30% 21%
Inflammatory Lesions
Mean absolute reduction 16.1 14.3 15.6 14.0
Mean percent reduction 56% 49% 54% 48%
Non-inflammatory Lesions
Mean absolute reduction 20.7 18.0 20.8 18.7
Mean percent reduction 45% 39% 46% 41%

Warnings

Contraindications

None

Cautions

Cases of methemoglobinemia, with resultant hospitalization reported postmarketing in association with 5% gel formulation; patients with glucose-6-phosphate dehydrogenase deficiency or congenital or idiopathic methemoglobinemia are more susceptible to drug-induced methemoglobinemia; avoid use of 5% gel in those patients with congenital or idiopathic methemoglobinemia

No events of peripheral neuropathy observed with topical dapsone; peripheral neuropathy reported with oral dapsone

Serious skin reactions have not been observed with topical application, but are associated with oral therapy and include toxic epidermal necrolysis, erythema multiforme, morbilliform and scarlatiniform reactions, bullous and exfoliative dermatitis, erythema nodosum, and urticaria

What other drugs will affect Aczone gel?

Aczone can cause a serious condition called methemoglobinemia, especially if you use certain medicines at the same time, including sulfa drugs, acetaminophen (Tylenol), nitroglycerin or other nitrite heart medications, seizure medicine, and several other drugs. Tell your doctor about all medicines you use, and those you start or stop using during your treatment with Aczone gel.

This list is not complete. Other drugs may interact with dapsone topical, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

For the Consumer

Applies to dapsone topical: topical gel/jelly

Along with its needed effects, dapsone topical (the active ingredient contained in Aczone) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking dapsone topical:

Incidence not known
  • Bluish-colored lips, fingernails, or palms
  • dark urine
  • difficult breathing
  • dizziness or lightheadedness
  • fever
  • headache
  • pale skin
  • rapid heart rate
  • sore throat
  • unusual bleeding or bruising
  • unusual tiredness or weakness

Some side effects of dapsone topical may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Dryness, redness, oiliness, or peeling at the application site

Dapsone Levels and Effects while Breastfeeding

Summary of Use during Lactation

Dapsone can be used during breastfeeding; however, hemolytic anemia might occur, especially in newborn infants and those with G-6-PD deficiency. One source states that use of dapsone in the treatment of leprosy is advantageous because it kills the organisms in breastmilk.[1] Monitor the infant for signs of hemolysis, especially in newborn or premature breastfed infants.

Drug Levels

Maternal Levels. In one mother who was 41 days postpartum, a random milk level of dapsone was about 1.1 mg/L with a maternal dose of 50 mg daily. Monoacetyldapsone was not detectable in milk although the maternal serum level was 744 mcg/L.[2]

Three women who were 2 to 5 days postpartum were given a single dose of 100 mg of dapsone orally. Milk samples were obtained at various times up to about 220 hours after the dose. The authors calculated that the breastfed infants would receive an average of 9.6% (range 4.6 to 14.3%) of the maternal weight-adjusted dosage.[3]

Infant Levels. A mother who was 41 days postpartum was taking dapsone 50 mg daily. Her breastfed infant's serum had levels of 439 mcg/L of dapsone and 204 mcg/L of monoacetyldapsone.[2]

Effects in Breastfed Infants

A case of mild hemolytic anemia occurred in a 41-day-old breastfed infant whose mother was taking dapsone 50 mg daily. The hemolysis was probably caused by dapsone in milk.[2]

A woman with leprosy took dapsone, clofazimine and rifampin during pregnancy and breastfeeding. Her infant developed skin discoloration attributed to clofazimine which reversed 3 months after cessation of breastfeeding.[4]

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

Alternate Drugs to Consider

(Leprosy) Clofazimine, (Topical for Acne) Adapalene, Azeleic Acid, Benzoyl Peroxide, Clindamycin, Erythromycin, Tretinoin

References

1. Jopling WH. Handbook of leprosy. 3rd Ed. London: Heinemann Medical Books Ltd. 1984:86-7.

2. Sanders SW, Zone JJ, Foltz RL et al. Hemolytic anemia induced by dapsone transmitted through breast milk. Ann Intern Med. 1982;96:465-6. PMID: 7065565

3. Edstein MD, Veenendaal JR, Newman K, Hyslop R. Excretion of chloroquine, dapsone and pyrimethamine in human milk. Br J Clin Pharmacol. 1986;22:733-5. PMID: 3567020

4. Ozturk Z, Tatliparmak A. Leprosy treatment during pregnancy and breastfeeding: A case report and brief review of literature. Dermatol Ther. 2017;30:e12414. PMID: 27549245

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