Fixed Drug Eruption Due to Ambroxol

Puteri Wulandari

, Kristo A. Nababan

Department of Dermatology & Venereology, Universitas Sumatera Utara,

Faculty of medicine, Universitas Sumatera Utara Hospital

Adam Malik Hospital, Medan.

Keyword: Fixed drug reaction, ambroxol

Abstract: Introduction: Fixed drug eruption (FDE) is a common cutaneous drug eruption characterized by the

development of one or more annular, oval, erythematous and hyperpigmented patches as a result of systemic

exposure to a drug. The lesion may recur at the same site and/or at the new sites with re-exposure to the

offending drug(s). More than 100 drugs have been implicated in causing FDEs including ibuprofen,

sulfonamides, naproxen and tetracyclines. There was only one case report fixed drug eruption due to

Ambroxol in Japan. This is a second case report fixed drug eruption due to ambroxol. Case: A 37-years old

Male came to Adam Malik Hospital Medan with the chief complaint an itchy, two similar

violaceousmacular lesions on the left back of the hand anderythematosus macular lesion in his genital part.

Three days ago, he was taking ambroxolthat he buy over-the-counter for treating his sore throats. Then the

cutaneous lesion in the left back of the hand appeared about one day later followed by a cutaneous lesion in

his genital part. He recalled a history of 2 similar episodes in the same location 1 year and 6 months ago due

to the same medication (ambroxol) that resolved about 7-10 days without any treatment, leaving post-

inflammatory hyperpigmentation. This patient was given an education to avoid the offending drug

(ambroxol) because this has been the third times he was experienced. Then he was given cetirizine 10 mg

once daily and topical desoximetasone cream applied on the lesion twice daily. Conclusion: There is an

increased risk of cutaneous drug reactions with expectorants containing ambroxol. We must increase

awarenessof fixed drug reaction cases due to the medications that are often used freely especially an over-

the-counter medication.

1 INTRODUCTION

Fixed drug eruption (FDE) is a common cutaneous

drug eruption characterized by the development of

one or more annular, oval, erythematous and

hyperpigmented patches as a result of systemic

exposure to a drugand account for 16% of all

cutaneous drug eruption (Breathnach, 2004).

The

lesion may recur at the same site and/or at the new

sites with re-exposure to the offending drug(s)

(Ayanlowo, 2015). The reaction may be

erythematous, eczematous, urticarial, bullous and

pigmented with a necrotic center sometimes

mimicking the target lesions of erythema

multiforme. The lesion resolve with

postinflammatory hyperpigmentation (Ayanlowo,

2015; Butler et al, 2015).

The number of diagnosed FDE cases is

increasing steadily, due in part to increased

awareness by physicians as well as increased

requests by patients to identify the precise cause of

repeated eruptions and pigmentation (Lee, 2000).

Fixed drug eruption is the second most common

adverse cutaneous eruption reported in both in- and

outpatients units, occurring at all ages and in all

races (Ayanlowo, 2015). The list of drugs keeps

growing with the introduction of new medications

(Ayanlowo, 2015). Barbiturates, antibiotics

(sulfonamides, tetracyclines, penicillin, and

erythromycin) and non-steroidal anti-inflammatory

drugs are common and well-known causative agents

(Lee, 2000).

Mucoactive substances such as ambroxol,

available in several countries as an over-the-counter

medicines that used for the treatment of acute and

chronic bronchitis.

There was an old publication in

2006 about safety and usage pattern of an over-the-

counter ambroxol cough syrup. This study confirms

that ambroxol is used according to the advice given

in the patient’s leaflet and supports the already

established safety and efficacy of this product in

416

Wulandari, P. and Nababan, K.

Fixed Drug Eruption Due to Ambroxol.

DOI: 10.5220/0009990504160419

In Proceedings of the 2nd International Conference on Tropical Medicine and Infectious Disease (ICTROMI 2019), pages 416-419

ISBN: 978-989-758-469-5

acute bronchitis (Schulz et al., 2006). But in 2015,

there was an emerge to update ambroxol safety

because accumulating evidence from case reports

and literature demonstrating that ambroxol is

potentially responsible for severe cutaneous adverse

reactions (SCARs) (Health Product Regulatory

Authority, 2015).

2 CASE REPORT

A 37-years old Male came to Adam Malik Hospital

Medan with the chief complaint an itchy, two similar

violaceous macular lesions on the left back of the

hand and erythematosus macular lesion in his genital

part. Three days ago, he was taking ambroxol that he

buy over-the-counter for treating his sore throats.

Then the cutaneous lesion in the left back of the

hand appeared about one day later. He recalled a

history of 2 similar episodes in the same location 1

years and 6 months ago due to the same medication

(ambroxol) that resolved about 7-10 days without

any treatment, leaving post-inflammatory

hyperpigmentation.

Picture 1. (A) two similar violaceous macular lesions, circumscribed, annular, on the dorsum manussinistra. (B)

Erythematosus macular lesion, circumscribed, annular with a central necrotic on the corpus penis region

From a dermatology examination we found two

similar violaceous macular lesions, circumscribed,

annular, on the dorsum manussinistra, and single

erythematosus macular lesion, circumscribed,

annular with a central necrotic in corpus penis

region. From a physical examination, we found the

awareness is compos mentis, blood pressure was

110/60 mmHg, heart rate was 90x/minute,

respiratory rate was 22x/minute and the body

temperature was 37

C. The nutritional status was

good and no abnormalities was found in other

physical status.

This patient was given an education to avoid the

offending drug (ambroxol) because this has been the

third times he was experienced. Then he was given

cetirizine 10 mg once daily and topical

desoximetasone cream applied on the lesion twice

daily.

3 DISCUSSION

The number of diagnosed FDE cases are increasing

steadily, due in part to increased awareness by

physicians as well as increased requests by patients

to identify the precise cause of repeated eruptions

and pigmentation.(Lee, 2000) Fixed drug eruption is

the second most common adverse cutaneous

Fixed Drug Eruption Due to Ambroxol

417

eruption reported in both in- and outpatients units,

occurring at all ages and in all races. (Ayanlowo,

2015;Sehgal et al., 2006)

Acute FDE lesions can develop within 30

minutes to 8 hours after drug administration. Lesions

are clinically characterized as single or multiple,

sharply demarcated, round or oval erythematous

patches or plaques that may become vesicular or

bullous. Because of the diversity of clinical pictures,

the correct diagnosis may sometimes be difficult to

achieve. But the FDE is characterized by recurrence

the same lesion at the same site after repeated

exposure to a causative drug. With repeated

exposure, new lesions can appear, and the previous

lesions may increase in size. In our case, this patient

has complained an itchy, two similar violaceous

macular lesions on the left back of the hand and

erythematosus macular lesion in his genital part.

These lesions appearone day after he tookambroxol

that he buy over-the-counter. The lesions in the left

back of the hand appeared firstfollowed by the

lesion in his genital. He recalled a history of two

similar episodes in the same location 1 years and 6

months ago due to the same medication

(ambroxol).Fixed drug eruption are commonly

found on the genitalia and in the perianal area,

although they can occur anywhere on the skin

surface.(Shear NH&Knowles SR,2012)

The diagnosis of a cutaneous drug eruption

involves the precise characterization of reaction

type. Some cutaneous reaction such as FDE, are

almost always due to drug therapy. Timing of drug

exposure and reaction onset, course of reaction with

drug withdrawal or continuation, timing and nature

of recurrent eruption on rechallenge, a history of a

similar response to a cross-reacting medication and

previous reports of similar reactions to the same

medication are helpful to diagnosed.(Shear

&Knowles,2012)Clinical history is most important

in diagnosing FDE, but patch tests and drug

challenge tests are also helpful and are used

frequently for a more objective diagnostic

approach.We didn’t do a drug challenge test in this

case because our patient clearly remembered that the

cutaneous lesions appeared after he ingested

ambroxol.

Ambroxol belongs to a group of medications

called mucolytic. Ambroxolworks by thinning down

the mucus in the airway passages, thus making the

mucus less sticky and it also facilitates the removal

of the mucus from the airways. Ambroxol is

available for pain relief of sore throats and available

over-the-counter in many countries includes

Indonesia. The review of ambroxol safety was

initiated following post marketing reports of

hypersensitivity reactions including anaphylactic

reactions and accumulating evidence from case

reports and literature demonstrating that ambroxol is

potentially responsible for severe cutaneous adverse

reactions (SCARs). (Sehgal et al.,

2006;Shear&Knowles, 2012). The European

Medicines Agency’s Pharmacovigilance Risk

Assessment Committee (PRAC) has completed a

review of the safety of ambroxol and bromhexine-

containing medicines. The PRAC considered that

ambroxol and bromhexine are associated with a

small increased risk of hypersensitivity reactions and

possibility of a risk of SCARs. The PRAC was

considered that the risk of SCARs should be

addressed by its inclusion in the product information

accompanied by a warning for patients and

caregivers to recognise the prodromes of SCARs and

to discontinue treatment immediately in the event of

such signs.(Shear &Knowles,2012)

4 CONCLUSION

There is an increased risk of cutaneous drug

reactions with ambroxol. We must increase

awareness of fixed drug reaction cases due to the

medication that are often used freely especially an

over-the-counter medication.

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