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AZELAIC ACID

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Azelaic acid is a naturally occurring 9-carbon saturated dicarboxylic acid. It is a dietary constituent (whole grain cereals and animal products) and can be formed endogenously from longer-chain dicarboxylic acids, metabolism of oleic acid, and omega-oxidation of monocarboxylic acids.

Specific Substances

    1) Azelex
    2) 1,7-heptanedicarboxylic acid
    3) Anchoic acid
    4) Lepargylic acid
    5) ZK-62498
    6) CAS 123-99-9

Available Forms Sources

    A) FORMS
    1) Azelaic acid is available as a 20% cream and 15% gel (Prod Info FINACEA(R) topical gel, 2015; Prod Info AZELEX(R) topical cream, 2013).
    B) USES
    1) Azelaic acid cream is indicated for the treatment of mild to moderate acne vulgaris (Prod Info AZELEX(R) topical cream, 2013).
    2) Azelaic acid gel is indicated for the treatment of inflammatory papules and pustules of mild to moderate rosacea in adults (Prod Info FINACEA(R) topical gel, 2015).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Azelaic acid cream is indicated for the treatment of mild to moderate acne vulgaris. Azelaic acid gel is indicated for the treatment of inflammatory papules and pustules of mild to moderate rosacea in adults.
    B) PHARMACOLOGY: Azelaic acid is a naturally occurring 9-carbon saturated dicarboxylic acid. It is a dietary constituent (whole grain cereals and animal products) and can be formed endogenously from longer-chain dicarboxylic acids, metabolism of oleic acid, and omega-oxidation of monocarboxylic acids. The mechanism of action is not fully known but it is thought that azelaic acid causes antibacterial effects by inhibiting the synthesis of cellular protein in aerobic and anaerobic microorganisms, especially Propionibacterium acnes and Staphylococcus epidermidis.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) Components of formulation (surface active agents and higher alcohols) may be irritating to mucous membranes and emetogenic. Eye, skin, and mucous membrane irritation may occur. Common events include burning/stinging/tingling, pruritus, scaling/dry skin/xerosis; less frequent events include erythema/irritation, contact dermatitis, edema, and acne have been reported with topical use.
    E) WITH POISONING/EXPOSURE
    1) Toxicity following overdose/ingestion has not been reported. Components of the formulation belong to chemical classes that produce irritation to mucosal membranes (nausea and vomiting).
    0.2.20) REPRODUCTIVE
    A) Azelaic acid is classified as FDA pregnancy category B. No teratogenicity was observed in animal studies with oral administration, although embryotoxic effects were seen.
    B) When applied topically, less than 4% of azelaic acid is absorbed systemically and is not expected to cause a significant change from baseline azelaic acid levels in milk.

Laboratory Monitoring

    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor serum electrolytes in patients with significant vomiting.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF TOXICITY
    1) Treatment is symptomatic and supportive. The ingestion of azelaic acid resulting in toxicity has not been reported. This may be the result of the self-limiting behavior of the formulation components (surface active agents and higher alcohols: irritating to mucous membranes and emetogenic). Correct any significant fluid and/or electrolyte abnormalities in patients with severe vomiting.
    B) DECONTAMINATION
    1) Gastrointestinal decontamination is generally unnecessary. Spontaneous vomiting likely to occur. For patients with ingestion, dilution with milk or water (no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children) may decrease symptoms. Administration of activated charcoal should only be considered in patients with very large or symptomatic ingestions who are awake and able to protect their airway. EYE/DERMAL EXPOSURE: Flush eyes with copious amounts of water. Skin should be thoroughly irrigated. Contact dermatitis may arise after repeated exposure to irritants.
    C) AIRWAY MANAGEMENT
    1) Should not be required in these cases.
    D) ANTIDOTE
    1) None.
    E) PATIENT DISPOSITION
    1) HOME CRITERIA: A patient with an inadvertent exposure, that remains asymptomatic can be managed at home. For patients with a minor eye or dermal exposure, flush the eyes with copious amounts of water. Skin that has become reddened and/or irritated should be gently cleansed with a mild soap and water. Ongoing symptoms may require further evaluation by a healthcare provider.
    2) OBSERVATION CRITERIA: Patients with a deliberate overdose, and those who are symptomatic, need to be monitored until they are clearly improving and clinically stable.
    3) ADMISSION CRITERIA: Patients with severe symptoms despite treatment should be admitted.
    4) CONSULT CRITERIA: Consult a regional poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    F) PITFALLS
    1) If significant toxicity develops, other causes should be sought. When managing a suspected azelaic acid ingestion, the possibility of multidrug involvement should be considered.
    G) DIFFERENTIAL DIAGNOSIS
    1) Patients with severe vomiting and underlying cardiac dysrhythmias or electrolyte imbalance, may develop more severe symptoms.
    0.4.4) EYE EXPOSURE
    A) Irrigate exposed eyes with copious amounts of room temperature water for at least 20 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 20 minutes of irrigation, an ophthalmic examination should be performed.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) Skin should be thoroughly irrigated. Contact dermatitis may arise after repeated exposure to irritants.

Range Of Toxicity

    A) TOXICITY: An oral dose of 20 grams/daily for 6 months was NOT associated with any adverse events. A toxic dose has not been established.

Clinical Effects

Summary Of Exposure

    A) USES: Azelaic acid cream is indicated for the treatment of mild to moderate acne vulgaris. Azelaic acid gel is indicated for the treatment of inflammatory papules and pustules of mild to moderate rosacea in adults.
    B) PHARMACOLOGY: Azelaic acid is a naturally occurring 9-carbon saturated dicarboxylic acid. It is a dietary constituent (whole grain cereals and animal products) and can be formed endogenously from longer-chain dicarboxylic acids, metabolism of oleic acid, and omega-oxidation of monocarboxylic acids. The mechanism of action is not fully known but it is thought that azelaic acid causes antibacterial effects by inhibiting the synthesis of cellular protein in aerobic and anaerobic microorganisms, especially Propionibacterium acnes and Staphylococcus epidermidis.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) Components of formulation (surface active agents and higher alcohols) may be irritating to mucous membranes and emetogenic. Eye, skin, and mucous membrane irritation may occur. Common events include burning/stinging/tingling, pruritus, scaling/dry skin/xerosis; less frequent events include erythema/irritation, contact dermatitis, edema, and acne have been reported with topical use.
    E) WITH POISONING/EXPOSURE
    1) Toxicity following overdose/ingestion has not been reported. Components of the formulation belong to chemical classes that produce irritation to mucosal membranes (nausea and vomiting).

Heent

    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) IRRITATION
    a) Irritation is likely if azelaic acid formulations are applied to the eyes. Azelaic acid and formulation components have the potential to irritate mucous membranes (Prod Info AZELEX(R) topical cream, 2013).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) GASTROINTESTINAL TRACT FINDING
    1) WITH POISONING/EXPOSURE
    a) Components of the formulation belong to chemical classes that produce irritation to mucosal membranes (nausea and vomiting). Components of the formulation include cetearyl octanoate, glyceryl stearate, cetearyl alcohol, cetyl palmitate. Ingestion of these components is likely to be self-limiting (Prod Info Azelex(TM), azelaic acid cream, 1995).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) SKIN IRRITATION
    1) WITH THERAPEUTIC USE
    a) Adverse reactions at the site of application are generally mild and include: pruritus, burning, stinging and tingling in approximately 1% to 5% of patients (Prod Info AZELEX(R) topical cream, 2013). Burning/stinging/tingling (29%), pruritus (11%), scaling/dry skin/xerosis (8%), erythema/irritation (4%), contact dermatitis, edema, and acne have been reported with gel use (Prod Info FINACEA(R) topical gel, 2016).
    b) Less than 1% of patients reported erythema, dryness, rash, peeling, irritation, dermatitis and contact dermatitis (Prod Info AZELEX(R) topical cream, 2013).
    B) HYPOPIGMENTATION
    1) WITH THERAPEUTIC USE
    a) Hypopigmentation is an infrequent adverse event reported with therapeutic use of azelaic acid (Prod Info AZELEX(R) topical cream, 2013).

Reproductive

    3.20.1) SUMMARY
    A) Azelaic acid is classified as FDA pregnancy category B. No teratogenicity was observed in animal studies with oral administration, although embryotoxic effects were seen.
    B) When applied topically, less than 4% of azelaic acid is absorbed systemically and is not expected to cause a significant change from baseline azelaic acid levels in milk.
    3.20.2) TERATOGENICITY
    A) LACK OF EFFECT
    1) No teratogenicity was observed in oral studies of rats (at 162 times the maximum recommended human dose [MRHD] based on body surface area [BSA]), rabbits (up to 65 times the MRHD) and monkeys (at 65 times the MRHD) administered azelaic acid during organogenesis (Prod Info Finacea(R) topical gel, 2014; Prod Info AZELEX(R) topical cream, 2013).
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    1) Azelaic acid is classified as FDA Pregnancy Category B (Prod Info Finacea(R) topical gel, 2014; Prod Info AZELEX(R) topical cream, 2013).
    2) There are no adequate and well-controlled studies of azelaic acid in pregnant women. Thus, it is recommended that azelaic acid be used in pregnant women only if the potential benefit outweighs the potential risk to the fetus (Prod Info Finacea(R) topical gel, 2014) or if clearly necessary (Prod Info AZELEX(R) topical cream, 2013).
    B) ANIMAL STUDIES
    1) EMBRYOTOXICITY
    a) Embryotoxic effects were observed in oral studies in rats (at 162 times the maximum recommended human dose [MRHD] based on body surface area [BSA]), in rabbits (up to 65 times the MRHD) and monkeys (at 65 times the MRHD) . In rats, the dose was maternally toxic and resulted in slight disturbances in the post-natal development of fetuses; however, no effects on sexual maturation of the offspring were observed (Prod Info Finacea(R) topical gel, 2014).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) When applied topically, less than 4% of azelaic acid is absorbed systemically and is, therefore, not expected to cause a significant change from baseline azelaic acid levels in milk. In vitro studies using equilibrium dialysis show that an azelaic acid concentration of 25 mcg/mL, the milk/plasma distribution coefficient was 0.7 and the milk/buffer distribution was 1.0, indicating that passage of the drug into maternal milk may occur. Use caution when administering azelaic acid to a nursing mother (Prod Info AZELEX(R) topical cream, 2013). It is recommended to either discontinue nursing or azelaic acid topical gel in lactating women, considering the importance of the drug to the mother (Prod Info Finacea(R) topical gel, 2014).
    3.20.5) FERTILITY
    A) ANIMAL STUDIES
    1) Oral studies in male and female rats at 162 times the maximum recommended human dose based on body surface area did not show effects on fertility or reproductive performance (Prod Info Finacea(R) topical gel, 2014).

Carcinogenicity

    3.21.3) HUMAN STUDIES
    A) LACK OF EFFECT
    1) NON-CARCINOGENIC - Azelaic acid is a human dietary component of a simple molecular structure that does not suggest carcinogenic potential and it does not belong to a class of drugs for which there is a concern about carcinogenicity. Therefore, studies to evaluate the carcinogenic potential were not deemed necessary (Prod Info Azelex(R), azelaic acid cream, 2000).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor serum electrolytes in patients with significant vomiting.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients with severe symptoms despite treatment should be admitted.
    6.3.1.2) HOME CRITERIA/ORAL
    A) A patient with an inadvertent exposure, that remains asymptomatic can be managed at home. For patients with a minor eye and/or dermal exposure, flush the eyes with copious amounts of water. Skin that has become reddened and/or irritated should be gently cleansed with a mild soap and water. Ongoing symptoms may require further evaluation by a healthcare provider.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a regional poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with a deliberate overdose, and those who are symptomatic, need to be monitored until they are clearly improving and clinically stable.

Monitoring

    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor serum electrolytes in patients with significant vomiting.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Gastrointestinal decontamination is generally unnecessary. Spontaneous vomiting is likely to occur. For patients with ingestion, dilution with milk or water (no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children) may decrease symptoms. Administration of activated charcoal should only be considered in patients with very large or symptomatic ingestions who are awake and able to protect their airway.
    B) CHARCOAL DOSE
    1) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    a) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    2) ADVERSE EFFECTS/CONTRAINDICATIONS
    a) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    b) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    C) EYE/DERMAL EXPOSURE: Flush eyes with copious amounts of water. Rinse skin with water only to remove cream/gel.
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY: Gastrointestinal decontamination is generally unnecessary. Spontaneous vomiting is likely to occur. For patients with ingestion, dilution with milk or water (no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children) may decrease symptoms. Administration of activated charcoal should only be considered in patients with very large or symptomatic ingestions who are awake and able to protect their airway.
    B) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) MANAGEMENT OF TOXICITY
    a) Treatment is symptomatic and supportive. The ingestion of azelaic acid resulting in toxicity has not been reported. This may be the result of the self-limiting behavior of the formulation components (surface active agents and higher alcohols: irritating to mucous membranes and emetogenic). Correct any significant fluid and/or electrolyte abnormalities in patients with severe vomiting.
    B) MONITORING OF PATIENT
    1) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    2) Monitor serum electrolytes in patients with significant vomiting.
    C) DILUTION
    1) If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. The exact ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004)
    D) IRRITATION SYMPTOM
    1) Observe patients for possible esophageal or gastrointestinal tract irritation.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) Irrigate exposed eyes with copious amounts of room temperature water for at least 20 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 20 minutes of irrigation, an ophthalmologic examination should be performed (Smilkstein, 1994).
    B) If irritation persists after irrigation the pH of the conjunctival sac should be tested after irrigation and irrigation continued until it is no longer acidic. The normal pH of the conjunctival surface ranges between 7.5 and 8 (Smilkstein, 1994).
    6.8.2) TREATMENT
    A) CORNEAL ABRASION
    1) If minor corneal injury is evident on ophthalmologic exam, threat with topical mydriatics and antibiotics.
    2) TOPICAL MYDRIATIC-CYCLOPLEGICS
    a) Use to guard against development of posterior synechiae and ciliary spasm (atropine 1 percent twice daily may be used) (Pfister & Koski, 1982; Smilkstein, 1994).
    3) TOPICAL ANTIBIOTICS
    a) Chloramphenicol or gentamicin 4 times a day may be effective for as long as epithelial defects persist (Pfister & Koski, 1982).
    4) If more extensive ocular injury is evident refer for immediate evaluation by an ophthalmologist.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) Rinse irritated area with water to remove cream. Avoid the use of soaps to prevent further irritation or sensitization.

Range Of Toxicity

Summary

    A) TOXICITY: An oral dose of 20 grams/daily for 6 months was NOT associated with any adverse events. A toxic dose has not been established.

Therapeutic Dose

    7.2.1) ADULT
    A) ACNE
    1) CREAM: Apply a thin film of 20% cream topically to affected area twice daily in the morning and evening (Prod Info AZELEX(R) topical cream, 2003).
    B) ROSACEA
    1) FOAM: Apply thin layer topically to entire facial area (cheeks, chin, forehead, and nose) twice daily in the morning and evening continuously for 12 weeks; use smallest amount necessary (Prod Info FINACEA(R) topical foam, 2015).
    2) GEL: Apply thin layer topically onto affected facial areas twice daily in the morning and evening (Prod Info FINACEA(R) topical gel, 2016).
    7.2.2) PEDIATRIC
    A) ACNE
    1) CREAM: AGE 12 YEARS AND OLDER: Apply a thin film of 20% cream topically to affected area twice daily in the morning and evening (Prod Info AZELEX(R) topical cream, 2003).
    B) FOAM: Safety and efficacy of gel and foam formulations have not been established in pediatric patients (Prod Info FINACEA(R) topical gel, 2016; Prod Info FINACEA(R) topical foam, 2015).

Maximum Tolerated Exposure

    A) SUMMARY
    1) Components of the formulation belong to chemical classes that produce irritation to mucosal membranes (nausea and vomiting) and/or CNS depression. Components of the formulation include cetearyl octanoate, glyceryl stearate, cetearyl alcohol, cetyl palmitate. Ingestion of these components is likely to be self-limiting (Prod Info Azelex(TM), azelaic acid cream, 1995).
    B) ROUTE OF EXPOSURE
    1) ORAL: The largest human oral dose reported was 20 grams/daily for 6 months and was not associated with any adverse effects (Fitton & Goa, 1991; Breathnach et al, 1984).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) ANIMAL DATA
    1) LD50- (ORAL)RAT:
    a) Greater than 5 g/kg (RTECS , 2001)

References

General Bibliography

    1) Breathnach AS, Nazzaro-Porro M, & Passi S: Azelaic acid. Br J Dermatol 1984; 111:115-120.
    2) Caravati EM: Alkali. In: Dart RC, ed. Medical Toxicology, Lippincott Williams & Wilkins, Philadelphia, PA, 2004.
    3) Chyka PA, Seger D, Krenzelok EP, et al: Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2):61-87.
    4) Elliot CG, Colby TV, & Kelly TM: Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96:672-674.
    5) FDA: Poison treatment drug product for over-the-counter human use; tentative final monograph. FDA: Fed Register 1985; 50:2244-2262.
    6) Fitton A & Goa KL: Azelaic acid: a review of its pharmacological properties and therapeutic efficacy in acne and hyperpigmentary skin disorders. Drugs 1991; 41:780-798.
    7) Golej J, Boigner H, Burda G, et al: Severe respiratory failure following charcoal application in a toddler. Resuscitation 2001; 49:315-318.
    8) Graff GR, Stark J, & Berkenbosch JW: Chronic lung disease after activated charcoal aspiration. Pediatrics 2002; 109:959-961.
    9) Harris CR & Filandrinos D: Accidental administration of activated charcoal into the lung: aspiration by proxy. Ann Emerg Med 1993; 22:1470-1473.
    10) None Listed: Position paper: cathartics. J Toxicol Clin Toxicol 2004; 42(3):243-253.
    11) Passi S, Nazzaro-Porro M, & Picardo M: Metabolism of straight saturated medium chain length (C9 to C12) dicarboxylic acids. J Lipid Res 1983; 24:1140-1147.
    12) Passi S, Picardo M, & Mingrone G: Azelaic acid - biochemistry and metabolism. Acta Derm Venereol 1989; 143(Suppl):8-13.
    13) Pfister RR & Koski J: Alkali burns of the eye: pathophysiology and treatment. South Med J 1982; 75:417-422.
    14) Pollack MM, Dunbar BS, & Holbrook PR: Aspiration of activated charcoal and gastric contents. Ann Emerg Med 1981; 10:528-529.
    15) Product Information: AZELEX(R) topical cream, azelaic acid topical cream. Allergan,Inc., Irvine, CA, 2003.
    16) Product Information: AZELEX(R) topical cream, azelaic acid 20% topical cream. Allergan, Inc. (per DailyMed), Irvine, CA, 2013.
    17) Product Information: Azelex(R), azelaic acid cream. Allergan, Inc, Irvine, CA, 2000.
    18) Product Information: Azelex(TM), azelaic acid cream. Allergan, Inc, Irvine, CA, 1995.
    19) Product Information: FINACEA(R) topical foam, azelaic acid topical foam. Bayer HealthCare Pharmaceuticals Inc. (per manufacturer), Whippany, NJ, 2015.
    20) Product Information: FINACEA(R) topical gel, azelaic acid 15% topical gel. Bayer HealthCare Pharmaceuticals Inc. (per FDA), Whippany, NJ, 2015.
    21) Product Information: FINACEA(R) topical gel, azelaic acid topical gel. Bayer HealthCare Pharmaceuticals Inc. (per manufacturer), Whippany, NJ, 2016.
    22) Product Information: Finacea(R) topical gel, azelaic acid 15% topical gel. Bayer HealthCare Pharmaceuticals Inc. (per DailyMed), Whippany, NJ, 2014.
    23) RTECS : Registry of Toxic Effects of Chemical Substances. National Institute for Occupational Safety and Health. Cincinnati, OH (Internet Version). Edition expires 2001; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    24) Rau NR, Nagaraj MV, Prakash PS, et al: Fatal pulmonary aspiration of oral activated charcoal. Br Med J 1988; 297:918-919.
    25) Smilkstein MJ: Ophthalmologic principles. In: Goldfrank LR et al (Eds): Goldfrank's Toxicologic Emergencies, 5th ed, Appleton & Lange, East Norwalk, CT, 1994, pp 365-372.