International Journal of Health & Allied Sciences

: 2013  |  Volume : 2  |  Issue : 2  |  Page : 130--132

Fixed drug eruption due to fixed dose combination: A novel case

Sushil Kumar Varma, Shailesh Nagpure, Arup Kumar Misra, Pallavi Dhanvijay 
 Department of Pharmacology, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Wardha, Maharashtra, India

Correspondence Address:
Arup Kumar Misra
Department of Pharmacology, Mahatma Gandhi Institute of Medical Sciences, Sevagram - 442 102, Maharashtra


Fixed drug eruption is a well documented drug side effect and accounts for about 5-10% of cutaneous drug reactions. We describe a case of fixed drug eruption on lips and perioral region following consumption of a fixed dose combination in acute gastroenteritis. Fixed dose combination of Ofloxacin and Ornidazole is one of the most commonly used medications for acute gastroenteritis. Fixed drug reaction caused in this case was red, raised macule, which turned into blister and later followed by post-inflammatory hyperpigmentation. Delayed type IV hypersensitivity reaction is most probably the reason for the mechanism of fixed drug reaction.

How to cite this article:
Varma SK, Nagpure S, Misra AK, Dhanvijay P. Fixed drug eruption due to fixed dose combination: A novel case.Int J Health Allied Sci 2013;2:130-132

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Varma SK, Nagpure S, Misra AK, Dhanvijay P. Fixed drug eruption due to fixed dose combination: A novel case. Int J Health Allied Sci [serial online] 2013 [cited 2023 Oct 1 ];2:130-132
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Fixed drug eruption (FDE) is an unusual and rare adverse drug reaction. The term FDE was first introduced by Brocq in 1894. [1] This type of reaction is actually a delayed type of hypersensitivity reaction which occurs as lesions recurring at the same skin site due to repeated intake of an offending drug. [2],[3] Ornidazole is a relatively newer 5-nitroimidazole having low molecular weight with excellent activity against anaerobic micro-organisms and protozoa. They are the first line drugs for hepatic and intestinal amoebiasis in developing countries. On the other hand, Ofloxacin is a synthetic chemotherapeutic antibiotic belonging to the second-generation fluoroquinolone and used to treat various bacterial infections. This combination is irrational according to Food and Drug Association (FDA) but still used extensively for treatment of acute gastroenteritis. We would like to present a case of FDE following treatment with fixed dose combination of Ofloxacin and Ornidazole as both the drugs are causative in fixed drug eruption. [4],[5]

 Case Report

A 19-year-old male patients presented in the outpatient department with complain of hyperpigmentation on lips and angle of mouth with history of almost 1 year. On history, he revealed that he had gastroenteritis 1 year back following which he self-medicated fixed dose combination of Tablet Ofloxacin 400 mg and Tablet Ornidazole 500 mg twice a day. However, on day 3 of therapy, he completely recovered from acute gastroenteritis so did not complete the 7 days course of antibiotics, but instead noticed raised, red rash on his lips and perioral region with burning sensation on day 3 on initiation of therapy. The patient reported that the rash became blisters and later to irregular black patches, it healed within 1 week leaving with residual hyperpigmentation on lips and perioral region.

After 1 month, he again had acute gastroenteritis following which he took the same medication. After 1 day of initiation of the therapy, he again developed red rash on his lips and perioral region with burning sensation which became blister and turned to black patches and healed after 1 week with residual hyperpigmentation. He came to skin outpatient department with complains of hyperpigmentation on lips and perioral region for nearly 1 year. He denied the recent use of new soaps, new creams, or change in food habits. He had no history of skin lesions prior to onset of pigmentation and did not report scratching in the region. Our patient, however, did not have systemic illness prior to the onset of skin lesions.

On examination, the patient was alert, his pulse and blood pressure were normal; he had no pallor, no icterus, no lymphadenopathy, no clubbing, and no pedal edema. On systemic examination, his respiratory, central nervous, and cardiovascular systems were within normal limits. On examination of skin, he has dark pigmentation on his lips and perioral region [Figure 1].{Figure 1}

Based on patient's history and clinical suspicions, a provisional diagnosis of FDE due to fixed dose combination of Ofloxacin and Ornidazole was achieved. No Investigation and skin biopsy was done. He was advised against self medication and not to take this combination even if he suffers from acute gastroenteritis in future and to apply moisturizer to the affected areas of lesion twice daily for soothing effects. He was given local steroid mometasone furoate 0.1% once a day for 3 weeks for application for depigmentation. He was asked to review in outpatient department after 1 month.


Fixed drug reactions have been reported by Ornidazole and Ofloxacin individually but this is the first time, it is being reported by their fixed dose combination. The exact mechanism for this fixed drug eruption is still unclear but, it has been postulated that FDE is due to a delayed classical Type IVc hypersensitivity reaction mediated by CD8+ T cells. [6] The drug binds with basal keratinocytes and stimulates the inflammatory process by causing release of lymphokines, mast cell, and antibodies, which in turn causes damage to basal cell. CD8+ on activation causes release of interferon (IFN) and cytotoxic granules into the local microenvironment which may add to further damage to basal cell. [7]

Fixed drug eruptions are cutaneous reaction to ingested drugs and are most common. FDE has been associated with the usage of trimethoprim, tetracycline, barbiturates, salicylates, ibuprofen, oxyphenbutazone, acyclovir, griesofulvin, tranexemic acid, and colchicines. [8] Although all ages are vulnerable to FDE but the peak usually involves 21-40 years. Males have slightly predilection than female counterparts. It mostly occurs in patients who intermittently receive the causative agent rather than on continuous administration. It also tends to occur in other drugs similar in structure to the causative agent (Cross-sensitivity). [3]

Morphologically, FDE usually begins with single erythematous macule, which gradually forms into an edematous plaque or rarely bullous form. [9] The lesions are normally asymptomatic but they may be associated with pruritus and burning sensation. The lesions may be single or multiple and mostly affects the genitalia, lips, and hands. [10] The onset of lesions usually is few hours to days after ingestion of the offending drugs. Following the initial inflammatory changes, hyperpigmentation of the lesion occurs at the same region. These type of reactions are known as "fixed" as a recurrent lesions occur at the original region following exposure to the same suspecting drugs (re-challenge) and the lesion occur more rapidly than the previous exposure as it occurred in our case. The healing process occurs spontaneously after few days to weeks after the offending drug is discontinued and may leave a hyperpigmented patch.

Combination of Ofloxacin and Ornidazole is used commonly for acute gastroenteritis in a developing country, although it is irrational to use. Those individuals who are known to be allergic to the constituents of the combination or had skin eruption following consumption of the drug previously should be warned against its future use. In our case, patient was advised not to take self-medication, use moisturizers for soothing effects to skin due to the associated pruritus or burning sensation and also he was prescribed local steroid mometasone furoate 0.1% once a day for 3 weeks for depigmentation.

In our case, the fixed drug eruption and hyperpigmentation is probably associated with the fixed dose combination of Ofloxacin and Ornidazole. According to the Naranjo, adverse drug reaction probability scale, the fixed dose combination of Ofloxacin and Ornidazole is the probable cause of fixed drug eruptions in this case (Overall Score = 8). [11]


Most of fixed dose combinations present in the market are usually irrational combination of drugs which are prescribed to get quick response from the therapy, improper diagnosis and over the counter for self-medication. It causes many adverse effects which goes unnoticed. Combination of Ornidazole and Ofloxacin are commonly used in developing countries for acute gastroenteritis. Fixed Drug Eruption (FDE) is an adverse cutaneous drug reaction, which usually goes unreported due to the negligence of patient as well as health providers. FDE with the individual agents of the combination have been reported in the past but due to combination, it is reported for the first time. The patient should be advised if he/she had reactions to a drug than the same drug should not be used in future and he/she should consult medical practitioners in future if he suffering from the same indication and give proper history of allergy. On the other hand, healthcare providers should have the knowledge regarding the diagnosis and proper management of FDE. Healthcare providers should omit the offending agent causing it and should start symptomatic treatment along with use of local steroid for quick recovery from the lesion and hyperpigmentation.


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