Journal Information
Vol. 58. Issue 10.
Pages 710.e1-710.e2 (October 2022)
Share
Share
Download PDF
More article options
Vol. 58. Issue 10.
Pages 710.e1-710.e2 (October 2022)
Case report
Full text access
Desensitization to Pirfenidone in a Patient Diagnosed With Idiopathic Pulmonary Fibrosis and Hypersensitivity to Antifibrotic Drugs
Visits
...
Francisco León-Romána,
Corresponding author
franciscoleonroman19@gmail.com

Corresponding author.
, Alicia Alonso-Gómezb, Alejandra Carrón-Herreroc
a Pulmonology Department, Hospital Recoletas Campo Grande, Valladolid, Spain
b Allergology Department, Hospital Recoletas Felipe II, Valladolid, Spain
c Allergology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain
Article information
Full Text
Bibliography
Download PDF
Statistics
Full Text

A 72-year-old man ex-smoker with hypertension and a history of beta-lactam allergy reported dry cough and progressive dyspnea that had first begun 6 months previously. His usual medication included olmesartan 20mg/d. No environmental exposure or family history of interstitial lung disease was demonstrated. Physical examination revealed baseline oxygen saturation of 96% and bibasilar dry crackles. There were no signs or symptoms of autoimmune disease or involvement of other organs. Serology findings for autoimmunity were completely normal with no other relevant laboratory abnormalities. Spirometry revealed forced expiratory volume in 1 second [FEV1], 2.37L [80%]; FVC, 3.35L [86%]; FEV1/FVC, 0.70). The diffusing capacity of the lung for carbon monoxide was 80% predicted. High-resolution computed tomography (HRCT) of the chest revealed a subpleural reticular pattern with bibasilar honeycombing indicative of usual interstitial pneumonia (UIP).

The patient was diagnosed with idiopathic pulmonary fibrosis (IPF) and nintedanib 150mg every 12h was prescribed. After initiating treatment, he reported facial angioedema, pruritic facial erythema, and edema affecting both hands. Treatment was suspended until further evaluation. At the following visit, he was prescribed pirfenidone and experienced similar symptoms. Given the lack of alternative drugs, the case was discussed with the Allergology Department, and a decision was made to perform a protocol for desensitization to antifibrotic drugs. Skin testing with nintedanib (15mg/mL and 1.5mg/mL) and pirfenidone (80mg/mL and 8mg/mL) was performed on the patient's forearm in the Allergology Department. Histamine (10mg/mL) was used as a positive control and sterile saline solution 0.9% as a negative control. Skin prick test was positive for both drugs, with a wheal and flare reaction (4mm×4mm for pirfenidone and 8×7 for nintedanib). The same tests were performed as a control on two patients with negative results. We decided to initiate desensitization with pirfenidone since the reaction was smaller. The Pharmacy Department prepared the doses using the 801-mg pirfenidone capsule. Although current evidence for premedication is controversial, we administered cetirizine 10mg/d and montelukast 10mg/d before starting desensitization. The first dose was administered in the Allergology Department. Given that the patient only experienced late-onset skin reactions, he continued the protocol at home, with check-ups at the outpatient clinic (Table 1). During the desensitization process, the patient experienced new cutaneous reactions similar to those reported above, thus necessitating de-escalation to doses tolerated during the previous steps and prolongation of the exposure periods. The dose was subsequently increased depending on tolerance. The patient tolerated the full dose of pirfenidone (801mg tid) after approximately 8 months with functional and radiologic stability of IPF.

Table 1.

Slow pirfenidone desensitization protocol (target dose, 2403mg).

Day(s)  Dose in tablets  Dose in mg  Reaction 
1/16  50.06  No 
1/16  50.06  No 
1/16  50.06  No 
1/8  100.12  No 
1/8  100.12  No 
1/8  100.12  No 
1/4  200.25  No 
1/4  200.25  No 
1/4  200.25  No 
10  1/2  400.50  No 
11  1/2  400.50  No 
12  1/2  400.50  No 
13  1/2  400.50  No 
14  1/2  400.50  No 
15  1/2  400.50  Yes 
16  1/16  50.06  Yes 
17–31  1/40  20.02  No 
32  1/30  26.70  Yes 
33  1/40  20.02  Yes 
34  1/30  26.70  Yes 
35  1/40  20.02  No 
36  1/30  26.70  No 
37  1/40  20.02  No 
38–53  1/40  20.02  No 
54–69  1/20  40.05  No 
70–85  1/10  80.10  No 
86–100  1/10 alternating with 1/5  80.10 alternating with 160.20  No 
101–115  1/5 alternating with 1/2  160.20 alternating with 400.50  No 
116–130  1/2 alternating with 3/4  400.50 alternating with 600.75  No 
131–133  3/4 alternating with 1  600.75 alternating with 801  No 
134–136  801  No 
137–143  801  No 
144–146  1 alternating with 1+1/4  801 alternating with 1001.25  No 
147–156  1+1/4  1001.25  No 
157–159  1+1/4 alternating with 1+1/2  1001.25 alternating with 1201.5  No 
160–179  1+1/2  1201.50  No 
180–186  1+3/4  1401.75  No 
187–189  2 alternating with 1+3/4  1602 alternating with 1401.75  No 
190–199  1602  No 
200–202  2 alternating with 2+1/8  1602 alternating with 1702.12  No 
203–205  2+1/8 alternating with 2+1/4  1702.12 alternating with 1802.25  No 
206–212  2+1/4  1802.25  No 
213–215  2+1/4 alternating with 2+1/2  1802.25 alternating with 2002.5  No 
216–222  2+1/2  2002.5  No 
223–225  2+1/2 alternating with 2+3/4  2002.5 alternating with 2202.75  No 
226–232  2+3/4  2202.75  No 
233–235  2+3/4 alternating with 3  2202.75 alternating with 2403  No 
236–present  2403  No 

Desensitization has proven successful with agents such as antibiotics, chemotherapy drugs, and biologics1. However, there are no published protocols for desensitization to pirfenidone or nintedanib. In the present case report, we performed a slow desensitization protocol because the associated skin reactions led us to reduce the dose and prolong exposure. Slow desensitization protocols can prove equally or more effective than rapid protocols according to published articles2,3.

Finally, the patient was clinically, functionally, and radiologically stable despite having received a low dose of pirfenidone during desensitization. A recent observational study reported that low doses of pirfenidone could prove beneficial for reducing functional progression and for survival in IPF4. Song et al.5 postulated that low doses of pirfenidone (<1200mg/d) improved gastrointestinal tolerance to the drug with a similar benefit in slowing deterioration of FVC.

Funding

No funders pertaining to this article.

Conflict of interest

The authors declare not to have any direct or indirect conflict of interest related to the manuscript contents.

References
[1]
A.D. Broyles, A. Banerji, S. Barmettler, C.M. Biggs, K. Blumenthal, P.J. Brennan, et al.
Practical guidance for the evaluation and management of drug hypersensitivity: specific drugs.
J Allergy Clin Immunol Pract, 8 (2020), pp. S16-S116
[2]
K. Scherer, K. Brockow, W. Aberer, J.H. Gooi, P. Demoly, A. Romano, et al.
Desensitization in delayed drug hypersensitivity reactions – an EAACI position paper of the Drug Allergy Interest Group.
Allergy, 68 (2013), pp. 844-852
[3]
M. Cansever, N. Şahin, I. Dursun, C. Geyik, R. Düşünsel, F. Bektaş Kut, et al.
Successful slow desensitization to tocilizumab in a 15-year-old patient.
J Investig Allergol Clin Immunol, 28 (2018), pp. 436-438
[4]
E.G. Lee, T.H. Lee, Y. Hong, J. Ryoo, J.W. Heo, B.M. Gil, et al.
Effects of low-dose pirfenidone on survival and lung function decline in patients with idiopathic pulmonary fibrosis (IPF): results from a real-world study.
PLOS ONE, 16 (2021), pp. e0261684
[5]
M.J. Song, S.W. Moon, J.S. Choi, S.H. Lee, S.H. Lee, K.S. Chung, et al.
Efficacy of low dose pirfenidone in idiopathic pulmonary fibrosis: real world experience from a tertiary university hospital.
Copyright © 2022. SEPAR
Archivos de Bronconeumología

Subscribe to our newsletter

Article options
Tools

Are you a health professional able to prescribe or dispense drugs?