Acne medications

Acne lesions can be classified as:

a) Non-inflammatory –
i) Open comedones (black heads)
ii) Closed comedones (white heads)

b) Inflammatory –
i) Superficial: Papules, pustules (< 5mm)
ii) Deep: small nodules (> 5mm, painful, indurated), large nodules (> 1 cm) and
cysts

Severity of acne follows the criteria:

Severity Criteria
Mild <20 comedones, or <15 inflammatory lesions, or total lesion count <30
Moderate 20-100 comedones, or 15-50 inflammatory lesions, or total lesion count 30-125
Severe >5 cysts, or total comedone count > 100, or total inflammatory count >50, or
total lesion count >125

o List drugs that are used for acne

Topical preparations

1. Benzoyl peroxide (BPO)

It has anti-inflammatory, antibacterial, and comedolytic activity. BPO has the advantage
of not inducing bacterial resistance.

Lower concentrations of BPO (2.5% or 5%) are preferred as there is increased irritation
with increasing concentrations (10%) of benzoyl peroxide. It is applied once or twice daily.

Avoid simultaneous BPO application with topical tretinoin as it can lead to oxidation of the
tretinoin.

BPO can bleach hair and clothes and has the potential to cause allergic contact
dermatitis in 1 - 2.5% of patients.

2. Antibiotic

Topical antibiotics, clindamycin 1% and erythromycin 2%, are effective against

inflammatory lesions. They are applied once or twice daily.

Avoid using antibiotics as monotherapy to prevent increasing bacterial resistance.

Co-prescribe BPO as it reduces the likelihood of antibiotic-resistant bacteria emerging.

They can cause mild skin irritation and on rare occasions cause sensitisation.

3. Retinoids

The topical retinoids - tretinoin, isotretinoin, and the retinoid-like drug, adapalene - are
useful in treating inflammatory and non-inflammatory lesions in mild to moderate acne.
 Topical retinoid therapy acts on follicular keratinocytes to prevent excessive cornification
and follicular blockage. It may also reduce the release of pro-inflammatory cytokines.

Tretinoin and isotretinoin is applied once at night; adapalene once daily, either in the
morning or at night. Bedtime application has been preferred with tretinoin as it is light
sensitive.

The most common side effect is irritation with erythema and scaling. Patients should be
instructed to apply very small amounts initially, or on alternate days.

Patients using tretinoin are more susceptible to the effect of ultraviolet irradiation,
especially at the start of the therapy.

4. Combination products

a) Epiduo (adapalene 0.1% and BPO 2.5%)

It has comparable-to-superior efficacy compared with single agent monotherapy of

adapalene or BPO

b) Clindoxyl (clindamycin 1% and BPO 2.5%)

It was reported to significantly reduce inflammatory and non-inflammatory lesions

compared to either BPO or clindamycin alone

Combination products may be more convenient for patients to use as they reduce the
numbers of products and applications required and thus may increase compliance.

5. Azelaic acid

Azelaic acid has similar properties to benzoyl peroxide. It also may cause irritation, which
can be helped by reducing the frequency of application or temporarily discontinuing
treatment.

Available as a 20% cream, it is applied twice daily. It is fairly well tolerated, with a small
group of patients complaining of transient cutaneous irritation and erythema.

6. Salicylic acid

Salicylic acid is available at a concentration of 0.5 – 2% in a number of creams and

lotions. It inhibits comedogenesis by promoting the desquamation of follicular epithelium.
It is well tolerated and applied once or twice daily.

Oral preparations

1. Oral antibiotics

Tetracycline, doxycycline, minocycline, erythromycin and cotrimoxazole are commonly

used. These drugs penetrate the follicle and sebaceous gland well and decrease
colonization by P. acnes. They also have an anti-inflammatory effect independent of their
antimicrobial properties.
 There is no conclusive evidence to suggest that any antibiotic is more efficacious than the
other. Choice of antibiotic should be determined by the side effect and tolerability profile.

It is recommended to start with the higher dose for 6 - 8 weeks initially, and when better
reduce to the lower dose till inflamed lesions are cleared. The antibiotic should be
changed if the acne is not significantly better after 6 - 8 weeks of the higher dose of
antibiotic.

Average duration of antibiotic therapy for responsive patients ranges from 2 - 4 months,
up to 6 months. Antibiotics should be used for the shortest possible time and discontinued
when further improvement is unlikely

Simultaneous use of topical and oral antibiotics should be avoided to prevent

development of resistance. However, concomitant BPO can reduce bacterial resistance

2. Oral contraceptives

Sebum production is controlled by androgens, and oral contraceptives are known to

reduce androgen levels by increasing sex hormone–binding globulin levels, thus reducing
the availability of biologically active free testosterone.

Estelle-35 which consists of Ethinylestradiol 35mg with Cyproterone acetate 2mg

Side effects:
Breakthrough bleeding or spotting is particularly common during the first 1-2 months of
taking oral contraceptives. This almost always resolves without any treatment within two
to three months. Forgetting a pill can also cause breakthrough bleeding

Other common side effects include:

• nausea and vomiting
• bloating and abdominal cramps
• breast tenderness
• headache or migraine
• intolerance to contact lenses
• weight changes
• mood swings
• pigmentation of the skin

o Know their indications

Topical treatment Oral drugs

Type of acne Azelaic Salicylic Oral
Retinoids Antibiotic Antibiotic Isotretinoin
acid acid contraceptive
Comedonal




acne
Mild
papulopustular


acne
Moderate


papulopustular


(for females)
acne
Moderate to




severe
nodular acne

o Appreciate use of oral antibiotics in treatment of moderate to severe acne vulgaris

Guide to antibiotic therapy

Drug Dosage Adverse effects Contraindications Comments

Tetracycline 500 – 1000 mg/d GI side effects, Contraindicated in Taken on empty
Stains forming teeth, children less than stomach
Hypersensitivity / 12 years old and Decreased
Fixed drug eruption, pregnancy (FDA absorption if taken
Vaginal candidiasis Cat D) with iron, calcium
and dairy products
Avoid in renal &
hepatic disease
Doxycycline 100 – 200 mg/d GI side effects, Taken after meals
Oesophagitis, Take with large
Photosensitivity, glass of water to
Pseudotumour cerebri decrease dyspepsia
Decreased
absorption if taken
with iron, calcium
and other dairy
products

Safe in renal
impairment
Minocycline 100 – 200 mg/d Vestibular toxicity – Taken after meals
vertigo, dizziness, Expensive
Blue-grey cutaneous Some authorities
pigmentation, suggest screening
** ***
Lupus-like syndrome, ANA and LFT in
Hepatitis young women on
long-term treatment
Erythromycin 500 – 1000 mg/d GI side effects, Safe in pregnancy Taken after meals
Rashes (FDA Cat B) (unless enteric
coated)
Potential drug
interactions with
carbamazepine,
theophylline,
cyclosporine due to
CYP-450 inhibition
Cotrimoxazole 2-4 tablets daily GI side effects, Contraindicated in Screen G6PD
Rashes, 3rd trimester of Useful for gram-
*
sulphamethoxazole SJS / TEN , pregnancy negative folliculitis
800-1600 mg Bone marrow (newborn Counsel the patient
*
+trimethoprim 160- suppression, kernicterus) the risk of SJS/TEN
320 mg Headache, fatigue,
nausea
SJS – Stevens-Johnson syndrome
TEN – Toxic Epidermal Necrolysis
ANA - Antinuclear antibody test
LFT – Liver function test

o Know the indications for use of isotretinoin in severe cystic acne and acne that has not
responded to other treatment

Indications:
1) Severe nodulocystic acne
2) Severe persistent acne that has failed to respond to at least 2 adequate courses of
different systemic antibiotic treatment despite compliance
3) Patients with severe scarring, psychological and/or physical as a result of acne
4) Severe gram-negative folliculitis which has failed antibiotic therapy

Dosing:
Standard dose regimen (0.5 - 1.0 mg/kg); Low dose regimen (0.25 - 0.5 mg/kg)

Aim for a cumulative dose of 120 mg/kg. The cumulative dose can be increased up to
150mg/kg in severe recalcitrant nodulocystic acne.

Start at 0.25 mg/kg/day initially, gradually increasing to a dose of 1 mg/kg/day if the patient
can tolerate

Absorption of isotretinoin is improved when taken with food (especially high-fat meals); thus,
administration during meals is recommended.

o List side effects of oral isotretinoin and appreciate risks of teratogenicity

Teratogenecity
Mucocutaneous – dry skin and mucous membranes, photosensitivity
Myalgia & arthralgia
Skeletal changes – hyperostosis, periostosis, demineralization, premature closure of
epiphyses
Hepatotoxicity
Hyperlipidaemia or hypertriglycerideamia
Pancreatitis
Depression & suicide - The link between isotretinoin and depression is still controversial. It is
unclear whether patients with pre-treatment history of depression are more at risk with
isotretinoin. There have been reports implicating isotretinoin with mood change, but no
definitive studies have been published to date.
Pseudotumour cerebri

o Know and appreciate the importance of blood tests for monitoring

Laboratory Monitoring

• Baseline liver function tests (LFT) & fasting serum lipids & triglycerides

• Baseline urine pregnancy test for females

• Repeat LFT & fasting lipids and triglycerides 6 to 8 weeks after commencement of
treatment, or earlier if pre-treatment values necessitate closer monitoring. If these tests
are normal, there may not be a need for frequent repeat blood tests, unless the dose of
medication is raised

Normal values Suggested values to Suggested values

necessitate close above which one
monitoring (monthly) should consider
 discontinuation
Triglycerides < 160 mg/dl > 300 mg/dl > 400 mg/dl
< 2.3 mmol/l > 3.39 mmol/l > 4.52 mmol/l
ALT 1 – 40 U/l > 60 U/l > 2x upper limit
AST 6 – 40 U/l > 60 U/l > 2x upper limit
ALT – Alanine Aminotransferase
AST – Aspartate Aminotransferase

A suggested approach for markedly elevated triglycerides > 4.5mmol/L is to

• stop the drug
• repeat the test in 4 weeks
• advise a low fat diet
• consider restarting at 50% the dose

Hematologic monitoring -
Current evidence does not support routine monitoring of hematologic parameters during
therapy due to a low incidence of significant hematologic abnormalities

Miscellaneous -
Patients should avoid elective procedures to skin (wax epilation, dermabrasion, laser
treatments) during treatment and for at least 6 months after cessation of therapy with
isotretinoin

Concurrent treatment with tetracyclines should be avoided due to risk of pseudotumour

cerebri

o Appreciate drug safety issues and the use of these drugs during pregnancy and
lactation

1. Isotretinoin

Pregnancy

Major fetal abnormalities (up to 28%), spontaneous abortion, premature births, and low IQ
scores have been reported. Hence, pregnancy is an absolute contraindication for females of
childbearing potential.

Pre-treatment urine pregnancy test should be done, as well as noting the date of the last
menstrual period.

Female patients should have practiced contraception 1 month prior and 1 month after
stopping isotretinoin therapy.

Contraindicated in females of childbearing potential unless on 2 forms of contraception or

abstinence at least 1 month prior, during and 1 month after discontinuation.

Lactation

Excretion in breast milk unknown, hence it is not recommended in lactating women.

 2. Other drugs

Drug Pregnancy (FDA category) Lactation

Topical drugs
Azelaic acid B Moderately safe
Benzoyl peroxide C Compatible
Clindamycin B Compatible
Erythromycin B Compatible
Retinoids C Moderately safe
Salicylic acid C Compatible
Oral drugs
Usually compatible with
breastfeeding; avoid in G6PD-
Cotrimoxazole C
deficient infants due to risk of
haemolysis
Erythromycin B Compatible
May reduce bone growth with
Tetracyclines D
prolonged exposure
Oral contraceptive X Avoid
Isotretinoin X Avoid