Is there any documentation indicating that doxycycline, budesonide or dexchlorpheniramine could cau

Fråga: Is there any documentation indicating that doxycycline, budesonide or dexchlorpheniramine could cause infiltrates in the lungs?

Background: A 22-year-old woman who used to work in Bosnia was treated with doxycycline orally in March and May due to a respiratory infection. After the second course of treatment her symptoms aggravated including breathlessness. Treatment with inhalation of budesonide 200 ug/dose two times daily due to suspected asthma symptoms gave no clinical response. On demand treatment with dexchlorpheniramine (Polaramin) ie an antihistaminergic agent has diminished her symptoms.

She has also been using oral contraceptives since April. In August only one week after treatment with Desolett had stopped her symptoms diminished. Since August the patient has been examined several times at the Clinic of Lung Diseases in Linköping. X-ray has shown infiltrates in both lungs and endobronchial biopsy has shown leucocytoplastic vasculitis. In October these alterations had disappeared. Now the patient has completely recovered.

Sammanfattning: Both budesonide and doxycycline are potent drugs that could cause respiratory adverse effects. After discontinuation of treatment these symptoms seem to be reversible. In the present case pulmonary infiltrates were found. Previously these symptoms have been reported in connection to treatment with tetracycline. No information concerning this side effect could be found during treatment with budesonide or dexchlorpheniramine. Considering the use of oral contraceptives only one report of pulmonary infiltrates was found in connection to medroxyprogesterone treatment (Depo-Provera). In the present case the time relationship between drug exposure and reaction points towards doxycycline, as it was the drug preceeding the clinical symptoms. On the other hand the symptoms disappeared within a week when treatment with Desolett had stopped. Therefore none of the drugs could be excluded as causative agents.

Svar: A thorough search in Medline, Drugline and pharmacological handbooks has been performed. The mechanism of drug induced pulmonary disease may be toxicity, idiosyncrasy, or allergy, or a combination of these according to one reference (1). Attacks of asthma precipitated by tetracyclines and other antibiotics probably represent type I hypersensitivity (1). Pulmonary infiltrates with eosinophilia associated with tetracycline treatment were described by Ho and coworkers (2). This article reports two cases of pulmonary infiltrates and eosinophilia that appeared after several weeks of treatment with the tetracycline drug alone and subsided within weeks after discontinuation. In both cases the pulmonary symptoms were preceeded by skin rash. Another case of acute eosinophilic pneumonia induced by minocycline, confirmed by transbronchial lung biopsy and rechallenge test has been reported (3). Asthma attacks were reported upon industrial exposure to tetracycline dust. The patient had an immediate (type I) asthmatic response to intradermal, inhalation and oral challenge test with tetracycline. On leaving the tetracycline production area his symptoms disappeared (4). According to two previous Drugline documents treatment with tetracyclines can cause asthma (5) and blood eosinophilia (6)

The files of SADRAC (Swedish Adverse Drug Reactions Advisory Committee) contain seven reports of side effects from the respiratory tract associated with tetracycline treatment. Only one case of pulmonary infiltrates and eosinophilia concerned a 45-year-old male who had been treated with doxycycline for 10 days. He had a positive dechallenge and recovered completely. The other reports include laryngitis, bronchial asthma, pulmonary sensitivity, dyspnea, bronchospasm and haemoptysis, one case of each.

In the reference literature several cases of paradoxical bronchospasm after use of inhalation aerosols have been reported. The files of SADRAC contain 51 cases of respiratory adverse effects in connection with treatment of budesonide. In total six cases concerned symptoms of aggravated bronchial asthma, bronchospasm and dyspnea. In general these symptoms are very rare side effects according to the Swedish catalogue of approved medical products. These side effects seem to develop at the start of treatment.

Concerning dexchlorpheniramine, no clinical documentation of respiratory adverse effects could be found.

The question concerning asthma symptoms in connection with oral contraceptives has previously been dealt with in Drugline (7). A complementary search in SADRAC revealed seven reports of adverse effects in the respiratory tract. These were two cases of dyspnea, rhinitis, pulmonary infiltrate, cough, interstitial pneumonitis and nasal congestion, one case of each. A 41-year-old female developed effort dyspnea after three years of treatment with Depo-Provera every third month. Repeated chest X-ray showed migrating pulmonary infiltration in both lungs. About nine months after discontinuance of medication the patient had recovered. In this case the depot effect of medroxyprogesterone was detectable nine months after a single intramuscular injection of 150mg of Depo-Provera.

We recommend this case be reported to the regional centre of adverse drug effects. 1 Filipek WJ: Drug-induced pulmonary disease. Postgrad Med 1979; 65: 131-140 2 Ho D, Tashkin DP, Bein ME, Sharma O: Pulmonary infiltrates with eosinophilia associated with tetracycline. Chest 1979; 76: 33-36 3 Yokoyama A, Mizushima Y, Suzuki H, Arai N, Kitagawa M, Yano S: Acute eosinophilic pneumonia induced by minocycline: prominent Kerley B lines as a feature of positive re-challenge test. Jpn J Med 1990; 29: 195-198

4 Menon MPS, Das AK: Tetracycline asthma - a case report. Clin Allergy 1977; 7: 285-290
5 Drugline nr 10970 (year 1993)
6 Drugline nr 09345 (year 1992)

7 Drugline nr 13776 (year 1996)