Acne vulgaris, or simply acne, is the most common skin disease in the world. It affects approximately 40 to 50 million adults in the United States alone. Although, neither contagious nor malignant, acne can make you lose self-confidence and feel depressed. Sometimes pimples can be so stubborn, all efforts to mask and treat them go in vain. You end up being a recluse who avoids socializing in order to avert awkward queries regarding your skin condition. Acne treatment is tediously long and requires perseverance. This article will discuss acne remedies and acne medications in detail.

Does Acne Vulgaris Affect Everyone?

Acne vulgaris commonly assaults when you enter the golden period of life – the adolescence or teen years.  It is the time period when you undergo a lot of physical, emotional and hormonal changes.

Although for some, the time period may bring perks of glowing and flawless skin, a large number of individuals have to bear the distressing hormonal acne. Being an adolescent afflicted with acne, you become quite sensitive, irritable and sometimes embarrassed.

The most depressing part is the obstinate and intractable nature of the condition since, it tests the patience of the affected. The treatment requires strong adherence and compliance to the acne treatment which most people fail to cope with.

An estimated once in a life outbreak of acne is faced by every individual during the course of their life.

The disease reaches its peak at a mean age of 18 years but in many cases in U.S., the disease progression continues in the later stages (20-40 years) of adulthood as well.  This is called adult acne.

There are many reasons why acne vulgaris should not be taken lightly and waiting for it to diminish itself is not the solution for acne in all the cases. Scientific researchers, clinical studies and literature reviews of a plethora of publications on acne vulgaris tell a very grave tale of this menace.

What Causes Acne Vulgaris?

The insight into the pathogenesis or causes of acne reveals that multiple factors are involved in the development of this dermatological condition. Also, the condition manifests itself in varied forms depending on the race, sex, ethnicity, pubertal status and age.

The primary cause of acne is the plugging of the skin pores with dead skin and excessive sebum or oil infected by bacterium Propionibacterium acnes.

Your pores bear hair follicles underneath the skin that are connected to the sebaceous or oil glands. The oily or sebaceous glands are responsible for the secretion and production of oil, or sebum, under the skin. This oil prevents your skin from being over dried by keeping it lubricated and protected.

However, in case of acne vulgaris, the sebaceous glands become overactive producing copious amounts of oil under the skin which then clogs the skin pores bearing hair follicle. Dead skin cells are then also trapped in the clogged hair follicle as skin sheds approximately 30,000 dead cells every hour inside the hair follicle.

Prolonged plugging of the hair follicle results in the invasion of special bacteria that lives in the oily areas of the skin- the P. acnes. This bacterium is the component of normal flora on your skin.

P.acnes flourishes in sebum which provides growth medium in the form of triglycerides. The bacteria invade the lining of the skin and the skin pore, hydrolyze triglycerides into fatty acids and glycerol and multiply in large amounts resulting in the acne.

What Are The Signs & Symptoms Of Acne Vulgaris?

Acne vulgaris manifests itself in multiple forms such as:

  • Pimples
  • Pustules
  • White Or Black Heads – White heads are formed when the skin pore is clogged with excess sebum and dead skin whereas black heads are formed when the skin pore is clogged the same as in white head but the pore at the surface of the skin remains open resulting in oxidation of melanin – a skin pigment in the dead skin cells – changing the characteristic brown color to black.
  • Cysts
  • Pus – Another symptom of acne vulgaris is pus. Pus is formed when white blood cells reach the acne site to fight off this bacterium. If the white blood cells die fighting off the bacterium, they accumulate along with the dead skin at the acne site resulting in the formation of white liquid called pus.

Psychological Trauma Caused By Acne

Apart from having apparent lesions – in some severe cases even scars- on the face and other visible body parts, the disease plays a major role in modulating the social life of the person affecting mental health at the crucial developing stages of social interactions. Other than the presence of acne, patients suffer from:

  • Low self-confidence
  • A tendency to isolate themselves from the society because of the fear of being shamed in the public based on their appearance and anxiety leading to depression at large.

Am I At Risk Of Acne?

A number of factors play role in the manifestation of acne:

  • Hormonal Imbalance

Is The Number #1 Cause Of Acne In Teens: During adolescence, the hormonal imbalance is the pivotal factor. The androgen hormone testosterone is believed to be the main culprit behind hormonal acne. There is excess production of this hormone in individuals suffering from acne.

  • Genetic Predisposition & Poor Hygiene Are Sometimes To Be Blamed

Thriving on junk food and lifestyle pattern, particularly night eating syndrome that involves munching on late night fat- and sugar-rich meals and colas, are also a reason for pimple outbreak.

  • Family History

If one of your family members has (a history of) acne vulgaris, you are three times more like to suffer as well.

  • Stress

plays a major role in aggravating the pimple flare ups, although it rarely provokes acne outbreak. Exactly how stress aggravates acne is little understood but it is believed that cells that produce sebum have receptors for stress hormones. When the stress hormone – cortisol – is released, it binds with the receptors increasing sebum production. The sebum mixes with dead cells and bacteria and clogs up the hair follicles.

  • Insulin Resistance

Can also increase your risk of acne. Insulin resistance is a condition in which the body is unable to utilize insulin properly. Insulin resistance, along with insulin-like growth factor –I (IGF-1) and growth hormone, can cause acne by activating androgen glands. When androgen glands, i.e., ovaries, testes and adrenal glands, are activated the male hormones are released which trigger sebum production and acne.

  • Body Mass Index (BMI)

The more the BMI, the more your risk of acne. Increased BMI leads to insulin resistance and androgen-excess which, as we have learned by now, are a direct and indirect cause of acne.

  • Other Factors

Such as smoking, unhygienic lifestyle, and overuse of cosmetics can also cause or worsen acne. You can find more about these in Acne e-Book.

Acne Treatment

How to cure acne is one question that keeps haunting the victims. They try several acne remedies but the stubborn pimples keep coming back.

Is there any best acne treatment that stops acne once and for all?

There are many treatments available for the effective management of acne at different grades of outbreak such as:

  • Topical and oral medicines
  • Dermatological products such as acne cream, acne cleanser, acne facewash

However, no matter which forms of acne is manifested, one thing is for sure – you need patience to manage it.

Acne treatment is classified as:

  1. Complementary and Alternative Medications (CAM)
  2. Over The Counter (OTC) Medicines
  3. Prescribed Medications

Complementary and Alternative Medications (CAM) For Acne Treatment

A number of alternative or miscellaneous acne remedies exist such as:

  • Chemical peels composed of glycolic acid and salicylic acid
  • Intralesional corticosteroid injections
  • Novel modalities such as pulsed dye laser or photodynamic therapy
  • Herbal therapies comprising tea tree oil or berberry extract

The role of diet has also been studied in the development of acne and foods bearing high glycemic index have been rendered to play a subsidiary role in this regard.

American Academy of Dermatology explains the alternative therapies for acne to be divided into some classes;

  • Herbal treatments
  • Homeopathic interventions
  • Psychological therapies and latest hypnosis therapies.

These alternative therapies are in use since long and the data so far coincides with the word of mouth that these therapies, in fact, are useful. But, scientifically speaking, these therapies lack credibility in terms of reliable data from studies.

That is why the American Academy of Dermatology as of 2016 recommends the alternative therapies (complementary therapies as well) with ‘B’ strength based on level 2 evidence from the studies conducted on these therapies.

Some of the important Complementary and Alternative Medications have been highlighted in detail in terms of the research based facts and figures regarding their effectiveness towards acne in the e-book on acne. These include:

  • Tea Tree Oil
  • Coconut Oil
  • Linoleic Acid
  • Pyridoxine
  • Ayurvedic Medications
  • Acupuncture and Biofeedback

Learn more about how these therapies in the e-book on acne.

Over The Counter (OTC) Drugs For Acne Vulgaris Treatment

Over the counter drugs or as they go by the name ‘OTC’ are widely available commercially as treatments for mild acne in the long term or even for the repeated breakout of acne which occurs from time to time.

The nature of the OTCs for acne cure varies in the form in which they are made available ranging from different constituents in the form lotions, gels, and even the products which are directed to be left on the skin for a while.

Acne treatment in the form of OTC often contains one or a combination of anti-acne agents and are made to work in different ways in terms of reduction of acne.

The Journal of American Academy of Dermatology (JAAD) has recommends following OTC products for the management of acne vulgaris.

·         Retinoids and retinoid-like medications

·         Keratolytics

·         Antibiotics

·         Benzoyl peroxide

·         Salicylic acid

·         Azelaic acid

·         Sulfur and resorcinol

·         Zinc

·         Corticosteroids

·         Anti-androgens

These medications should be used according to clinical practice guidelines established by clinical experts.

The U.S. Food and Drug Administration has repeatedly warned the users of OTCs to observe caution while using them since in some cases, they have caused serious reactions leading to an inflammation/swelling of the facials parts (cheeks, tongue, and lips) as well as the throat. This kind of a reaction has ample chances of turning out into a life-threatening condition. But at the same time, it is very easy to confuse the irritation and itching as a result of the application of any such product with the adverse reaction mentioned before.

Let us look at some of OTC Topical Therapies For Acne Vulgaris

First-Line Acne Treatment

Benzoyl peroxide, oral antibiotics (oral erythromycin, azithromycin) and retinoids serve as the first-line treatment for mild, moderate and severe acne treatment.

For mild acne, benzoyl peroxide and topical antibiotics (clindamycin or erythromycin) are given as combination or monotherapy whereas for moderate to severe acne, both agents are used in conjunction with topical retinoids or systemic antibiotics which include:

  • Tetracyclines (doxycycline, minocycline)
  • Macrolides (erythromycin, azithromycin)
  • Clindamycin
  • Trimethoprim with or without sulfamethoxazole
  • Ampicillin or amoxicillin

Benzoyl peroxide (BP) is an anti-bacterial that has an ability to release free oxygen and act as a free radical scavenger. It is effective in killing P.acnes bacterium and is the best acne treatment.

BP also acts as comedolytic – implying that it prevents blockage of skin pores and blemish formation due to entrapment of oil and dead skin cells.

BP can also prevent acne flare ups and is most commonly used as supplementary agent to other topical or systemic antibiotics for acne.

It is available in multiple preparations as acne facewash, acne creams, gels, and foams.

The most frequently experienced side effects of benzoyl peroxide are usually mild in nature such as:

  • Skin irritation
  • Dryness
  • Peeling or flakiness
  • Stinging or burning sensation at the application site.

Patients having past history of hypersensitivity to benzoyl peroxide should not use it. The side effects can be curtailed by following the FDA safety measures.

One way to determine whether you have hypersensitivity to BP is to apply the cream on affected areas only for the first few days. If rash or irritation occurs, it means you are allergic.

Topical Antibiotics For Acne Vulgaris Treatment

The best acne treatment is 1% clindamycin gel or solution for acne treatment.

Erythromycin is also available as topical medication in the form of pledgets, lotions or gels but its efficacy is less in comparison to clindamycin due to development of resistance by Staphylococcus residing in the skin and P.acnes.

However, topical antibiotics and benzoyl peroxide are also available that are more effective in improving the compliance against these medications.

Wash and dry the skin prior to medication application and apply the lotion or solution as a thin film. Avoid rubbing into the skin.

Improvement should begin to appear within six weeks of acne medication and pimples should begin to subside. You should continue therapy for 12 weeks. Topical erythromycin requires strict adherence and must be continued as a maintenance therapy even after achieving beneficial effects. If no positive response appears, seek specialist opinion.

Serious side effects such as shortness of breath, severe allergic reaction or watery or bloody diarrhea should be reported immediately and the product be discontinued immediately. Diarrhea may be a sign of new infection acquired during the treatment.

Clindamycin for topical application is available as Clindamycin phosphate solution or pledget or clindamycin gel. The solution / gel and pledget should be applied twice daily as a thin film or pad, respectively.

Side effects are same as localized skin irritation manifested as dryness, burning or stinging sensation, peeling or flaking of the skin. Clindamycin topical preparations must not be used concurrently with erythromycin or non-depolarizing neuromuscular agents due to drug interactions between these medicines. The prescriber must be informed of the past medication of any medicine that may interact with these topical antibiotics.

Topical Retinoids For Pimples

Retinoids are derivatives of vitamin A. These are comedylytic in nature and the best acne medication available.

The three most important active derivates of retinoic acid are: Tretinoin, Adapalene and Tazarotene.

Since retinoids are also associated with skin irritation, burning, hypersensitivity, stinging and peeling effects, you must undergo a patch test before continuing with the product. Retinoids, like tetracyclines, are also prone to photosensitivity and must not be worn during day time unless inevitable.

Moreover, if it is compulsion than a sunscreen or sunblock must be applied on the skin prior to application of retinoid medication.

Like all topical medications, skin must be cleansed and patted dry before applying the preparation and it must be applied twice daily. Be careful to avoid the sensitive parts, the eyes and the mouth. The preparation must be applied in minimal amounts in order to avoid skin irritation. However, if burning or stinging sensation becomes unbearable then discontinue and consult your dermatologist. Abrasive and astringent products must be avoided while on topical medications.

Azelaic Acid, Dapsone, Salicylic Acid

all three serve as comedolytic agents and prevent blockage of skin pores.

Azelaic acid (Azelex) also possesses additional properties as an antibacterial and anti-inflammatory agent and is prescribed in patients with sensitive skin, manifesting redness, inflammation or pimples on their facial skin.

The acne cream is applied twice a day and it takes at least four weeks to observe full benefits.

Dapsone Gel : has recently emerged as a new treatment option in acne vulgaris.

The drug shares the similar properties of antimicrobial and anti-inflammatory agent as Azelaic acid and is effective against both inflammatory and non-inflammatory acne vulgaris.

Studies have shown dapsone gel to counteract inflammatory, non-inflammatory and total lesion count when applied for a period of 12 weeks. It is pregnancy category C.

Salicylic acid For Pimples: is available in several dosage forms such as acne cream, lotions, foams, soap and pads. Salicylic acid works as a comedolytic The frequency application is three times a day but it tends to produce dryness on the skin so frequency of application might be reduced in that case or can be applied on alternate days.

Topical Nicotinamide (Nicam, Freederm) For Acne: is a vitamin B3 preparation that has anti-inflammatory properties. It keeps skin hydrated and reduces pigmentation and soreness. It is quite effective in reducing acne flare-ups.

Nicotinamide is applied directly on the affected area. Care should be to taken to avoid a direct contact with eyes.

Wash your face before you apply the gel. The gel can cause dryness, flakiness and stingy feeling; you can use moisturizer before the gel application but avoid oily creams or cosmetics because they can clog pores.

Nicotinamide clears up the skin within six weeks of use but can be continued for longer if acne re-appears.

Topical Sulfacetamide (Klaron) – Another Acne Cure: is a sulfonamide antibiotic that inhibits folic acid synthesis in the bacteria. It is available in the form of suspension that is applied as a thin film on the skin.

Sulfacetamide is mild and well-tolerated but may cause itching, stinging or redness. Discontinue the product and speak with the doctor if side-effects cause distress.

If you have a history of asthma or hypersensitivity to sulfa-drugs, avoid sulfacetamide altogether.

Prescription Medications For Acne Treatment

Before we comment on the prescription drugs it is necessary to know when to switch over to the prescription drugs from OTC and what kind of treatment to follow.

According to Medline Plus, self-care and acne remedies at home can help a person take care of the acne vulgaris outbreak for a variable time frame. But there are many conditions which are a clear-cut indication of consulting a professional dermatologist in order to initiate an acne treatment regimen involving prescription drugs.

Consultation with a certified skin specialist becomes imperative when the management from OTC becomes insufficient in keeping acne vulgaris at bay. Continuous stress on the mental health, itchiness, and irritation of the skin around the acne lesions and the development of scars are some of the telltale signs of switching over to the prescription drugs and systemic antibiotics for acne and in some cases to start a combination therapy of OTC and prescribed drugs.

The prescribed drugs are of available in numerous commercial forms:

  • Systemic Antibiotics
  • Topical Treatments
  • Combination Oral Contraceptives
  • Hormonal Modulatory Drugs

Prescribed antibiotics are available in both topical and oral forms and include; tetracycline, trimethoprim, and erythromycin.

Prescribed topical treatments include retinoids, prescribed composition of salicylic acid, benzoyl peroxide and sulfur.

In the case of contraceptives; birth control pills have been used for the treatment of hormonal acne.

Systemic Antibiotics (Injectables) For Acne Treatment 

Systemic antibiotics for acne serve as a core therapy for moderate to severe acne manifesting as inflammatory lesions when topical therapy proves ineffective or fails to provide effective treatment.

It includes a number of antibiotics, each possessing a peculiar and varied mechanism of action to target multiple elements in acne-developing process.

Systemic antibiotics are recommended to be used for a limited period of time and must be followed-up after three to four months of therapy to prevent bacterial resistance and must always be used in conjunction to benzoyl peroxide or retinoids, both during and after completion of systemic therapy, as a maintenance therapy.

Antibiotics that are clinically employed for this purpose include:

  • Tetracyclines (tetracycline, doxycycline or minocycline)
  • Macrolides (Azithromycin, erythromycin)
  • Trimethoprim/sulfamethoxazole
  • Penicillins (amoxicillin / ampicillin)
  • Cephalosporins (cephalexin)
  • Tetracyclines 

This class of antibiotics works as a protein synthesis inhibitor that deprives the bacteria of essential proteins required for its growth.

Among tetracyclines, doxycline and minocycline have proved more beneficial or effective in management of acne than tetracycline.

This class of antibiotic is the first–line treatment for moderate to severe acne that manifests as rosacea or inflammatory acne and is evident in the form of redness, swelling and painful pimples, but its use is contraindicated in pregnancy or in children aged 8 years or less.

As mentioned earlier, topical therapy–retinoids or benzoyl peroxide should be used concomitantly and as maintenance therapy after completion of systemic therapy.

As regards to adverse events associated with this class of antibiotics for acne, photosensitivity or sun allergy is a major drawback that limits its use. It results in sunburns, itching and redness of the skin. Doxycycline is more photosensitive than minocycline and also associated with gastrointestinal symptoms such as nausea, vomiting and diarrhea when taken in high doses over a long period of time. However, doxycline is safe in patients with renal impairment or kidney malfunction since it is metabolized and excreted by liver. Minocycline overdosage, on the other hand, results in dizziness, ringing sound in the ears-tinnitus, and pigmentation or coloring of the skin, teeth and mucous membranes.

  • Macrolides

Macrolides are also a class of antibiotics that serves as a protein synthesis inhibitor but it targets a different ribosome than tetracyclines. These antibiotics are also anti-inflammatory in nature. This class of antibiotics is employed when tetracyclines are contraindicated such as in pregnancy or in children aged 8 years or less or as a second-line treatment when conventional or established antibiotics fail.

Azithromycin is the drug of choice in this class since erythromycin is associated with high threat of bacterial resistance.

Erythromycin is also associated with greater frequency of adverse effects which are, like many antibiotics, gastrointestinal in nature – manifesting as nausea, vomiting, and diarrhea.

Azithromycin is associated with allergic reactions on the skin.

Systemic antibiotics are mostly just limited to tetracyclines and macrolides. Rarely are other anitbiotics used because there is limited evidence to support their use.

These antibiotics include:

  • Trimethoprim /sulfamethoxazole 

Trimethoprim is a union of two antibiotics that act in a sequential manner in inhibiting folic acid synthesis – an essential nutrient for the growth of bacteria.

Thus, these drugs act as folic acid synthesis inhibitor, targeting two different enzymes in a sequential manner; firstly sulfamethoxazole inhibits the enzyme dihydropteroate synthase followed by trimethoprim inhibiting the enzyme dihydrofolate reductase, thereby resulting in inhibition of folic acid production –the end product.

Their use, however, is only supported by case reports. The Guidelines Of Care For The Management Of Acne Vulgaris report that little evidenced-based data is available regarding the effectiveness of this antibiotic in acne vulgaris.

This combination of antibiotic is also associated with stomach disturbance, photosensitivity and severe allergic reaction, the most significant is Steven–Johnson syndrome and epidermal necrolysis.

The propensity of such significant adverse events is higher among HIV positive patients. The combo is also associated with blood disorders and liver failure, though the incidence is rare, but long term use requires careful monitoring of the patient.

  • Penicillins (Amoxicillin, Ampicillin) And Cephalosporins (Cephalexin) For Acne Treatment

with regards to these two class of antibiotics that act as a bacterial cell wall inhibitor or bactericidal (killing the bacteria), the clinical application is limited since antibiotics are associated with increased incidence of hypersensitivity or allergic reactions which might lead to the fatal allergic reaction – the anaphylaxis reaction.

Penicillins are mainly employed as adjunctive treatment of acne, especially during pregnancy. The dosage of amoxicillin varies with age and weight in children whereas it is standard in adults. Both amoxicillin and cephalexin are pregnancy category B.

Hormonal Agents For Acne Treatment

Hormonal agents comprise of two types of therapies:

  • Oral Contraceptive Pill
  • Anti-Androgen Therapy

Oral Contraceptives (OCs) For Hormonal Acne Treatment 

Oral contraceptives are a combination of two female hormones, i.e., estrogen and progestin.These are originally employed for contraception in females since they arrest the release of a number of hormones that play role in the process of ovulation and pregnancy, thereby, preventing pregnancy.

These hormones work by means of their anti-androgenic properties – implying that they reduce the production of androgens at the ovary level and prevent testosterone from binding to androgen receptors, thereby, preventing the testosterone from executing its action. Both androgen and testosterone are male hormones and are accountable for acne production.

The recommended guidelines suggest that the combined or binary pills containing estrogen are more effective in females exhibiting inflammatory acne vulgaris. FDA has officially approved only four contraceptive pills to be used as acne therapeutic agent or for acne treatment. These are

Ø  Ethinyl estradiol/norgestimate(Mononessa, Ortho Tri-Cyclen, Tri-Previfem, Tri-Sprintec)

  • Ethinyl estradiol/norethindrone acetate/ferrous fumarate  ( Generess Fe, Loestrin 24 Fe, Minastrin 24 Fe)
  • Ethinyl estradiol/drospirenone(Yasmin, Zarah)

The pills are taken as once daily pill for a specific period of time as prescribed by the physician.

These contraceptive pills are required to be taken for longer duration of time to induce their anti-acne properties and can thus be administered as combination therapy with antibiotics such as tetracyclines or corticosteroids such as spironolactone.

However, these contraceptive pills are pregnancy category X and are absolutely contraindicated in pregnancy but can be utilized during breast feeding with careful monitoring or caution.

Moreover, WHO has published a list of clinical conditions which deem these contraceptive pills to be contraindicated in these peculiar conditions, mainly;

  • Pregnancy
  • Breast feeding at less than 6 weeks post –delivery
  • Cancereither breast or liver
  • Liver cirrhosis
  • Diabetes
  • In heavy smoker females  ( ≥15 cigarettes per day) aged > than 35
  • Heart diseases ( ischemic heart disease or valvular heart complications)
  • Head injuries ( cerebrovascular injury)
  • Migraine
  • Increased blood pressure; systolic, ≥160 mm Hg; diastolic, ≥100 mm Hg

Anti-androgens Therapy For Acne Treatment

  • Spironolactone popular by the brand name, Aldactone, is a steroidal drug mainly prescribed for hypertension as a diuretic.

It increases urine frequency thereby lowering the blood pressure. However, it is also prescribed in acne due owing to its anti-androgenic properties.

Since, it is not approved by FDA, the Recommended Guidelines For Acne Care Management state that spironolactone be used in a selected female population.

The drug is generally well–tolerated but side effects include increased urine frequency or diuresis, endocrine disorders such as irregular periods, enlargement and tenderness of breasts, increased potassium levels or hyperkalemia as electrolytic imbalance, severe allergic reactions such as Steven –Johnson syndrome, nausea, vomiting, diarrhea, feminization of male fetus if taken during pregnancy and a number of other adverse effects not mentioned here.

  • Other Oral Corticosteroids  such as prednisolone are recommended in patients exhibiting adrenal hyperandrogenism and only for severe inflammatory acne as a supplementary treatment to the standard therapy.

Long-term use of steroids is discouraged due to their potential side effects and should only be used on need basis –weighing risk to benefit ratio. It is pregnancy category C.

The steroids are always required to be withdrawn in a tapering manner, implying that dosage must be reduced in a gradual descending manner.

  • Flutamide  is also an androgen receptor blocker that has prime indication for prostate cancer but it is not steroidal in nature.

The best outcomes for acne vulgaris are achieved when administered as combination therapy with triphasic contraceptive pills. It reduces acne by 80% and is therefore the best acne treatment.

This combination is superior to the combined therapy with spironolactone and contraceptive pills which reduce acne by only 50% and that also after a period of 3 months.

Frequent side effects that may be experienced by the patients range from:

  • General gastrointestinal symptoms of nausea, vomiting, diarrhea
  • Endocrine disorders such as breast tenderness, hot flushes, decreased sex drive or libido
  • Abnormally dry skin (xerosis)
  • Liver failure (rarely).

It is pregnancy category D and should not be used in pregnancy.