Author: Shi Wenxiu
Affiliation: Department of Pharmacy, Zhongshan Hospital, Fudan University
Source: Medical Respiratory Channel
An old patient who had been diagnosed with bronchial asthma and invasive pulmonary aspergillosis came to the hospital again, with old problems, coughing and coughing, excessive sputum, fever, maximum body temperature of 38 °C, stable vital signs, and dry and wet rales could be heard in both lungs on examination.
After a series of examinations and past medical history, the doctor finally diagnosed as: 1) pulmonary aspergillosis; 2) Acute exacerbation of bronchial asthma.
First dose regimen:
给予伏立康唑进行抗曲霉治疗，前24小时负荷剂量400mg，ivgtt，q12h；后维持剂量300mg，ivgtt，q12h。
The patient was treated with voriconazole with significant results, his body temperature returned to normal, and his symptoms such as cough and asthma improved, but the patient said
The first adjustment of the dosing regimen: q12h→Bid
Whether it is a psychological cause or a side effect of the drug, the doctor took out the instructions and began to carefully study the frequency of voriconazole to see if there was any change.
The results showed that the frequency of administration of the maintenance dose of intravenous infusion varied in the instructions of voriconazole in different regions.
Authoritative books on the frequency of dosing:
After excluding other interfering factors, the doctor decided that Bid administration was feasible, so he decided to try to use this group of "a little excited at night" drugs in advance to see if sleep could be improved, so the frequency of voriconazole was changed from the original q12h to Bid.
In this hospital, q12h means that the first dose is administered at 9:00 and the second dose at 21:00, with an interval of 12 hours; Bid means: the first dose is administered at 9:00 and the second dose is administered at 15:00, with an interval of 6 hours.
After the adjustment of the protocol, the patient was able to fall asleep, but there was a new problem.
Well, let's look into it again.
The second adjustment of the dosing regimen: Bid→ q12h
The plasma concentration of voriconazole affects its efficacy and safety, which is clinically assessed by monitoring its trough concentration. Trough concentration = 1 μg/mL can be used as a cut-off point for predicting efficacy, while the risk of adverse reactions such as hepatotoxicity and neurotoxicity increases when the trough concentration ≥ 4 μg/mL.
Voriconazole is administered Bid, and shortening the dosing interval may cause fluctuations in blood concentrations and cause a series of adverse reactions, while gastrointestinal symptoms are relatively common.
In order to prevent further aggravation of adverse reactions, the dosing frequency was adjusted back to q12 hours from BID.
After adjusting to the medication in Q12h, we think that the adverse reactions of the patient's digestive tract should be alleviated, right? However, after 1 day of medication, the gastrointestinal reaction is aggravated, what is the reason for this?
The third adjustment of the dosing regimen: the dose is corrected!
The drug label does not specifically indicate whether the dosage should be adjusted for overweight patients.
According to the pharmacokinetic data of voliconazole obese population, although voriconazole is relatively lipophilic, it will not be widely distributed in adipose tissue, which will affect the treatment effect and cause toxic side effects.
患者身高170cm，体重75kg，BMI：25.95（偏胖）。
According to the adjusted body weight, the maintenance dose of voriconazole was 544mg/day.
However, this dose may still be a bit high for the patient, and voriconazole metabolism is saturated, and the rate of elimination in the body decreases after multiple doses, resulting in drug accumulation. So how to adjust the dosage?
In the study of the pharmacokinetic characteristics of voriconazole population and the optimization of the dosing regimen in patients with invasive fungal infection, the CFR value (cumulative response fraction) of the empirical dosing regimen: IV 200mg every 12 hours for the treatment of Aspergillus infection was 95.8%, indicating that this dose is relatively reasonable and effective in the treatment of Aspergillus infection.
Therefore, after discussion with doctors and pharmacists, the maintenance dose of voriconazole was finally set at 200mg IVGTT every 12 hours.
Subsequently, the patient's condition continued to improve, the gastrointestinal reactions disappeared, and the sleep problems gradually improved......
Finally, let's sort it out:
Male patient, 61 years old, height: 170 cm, weight: 75 kg.
Diagnosis: 1. Pulmonary aspergillosis, 2. Acute attack of bronchial asthma.
The adjustment regimen for voriconazole use is as follows:
Doctors are not prophetic, nor are they omniscient, and we must also continue to learn and explore in the clinic, optimize every small choice, and finally get a good big result.
Tips:
1. Regardless of intravenous infusion or oral administration, the first loading dose should be given on the first day so that its blood concentration is close to the steady-state concentration.
2. Voriconazole must be instilled at a concentration of no more than 5mg/mL, and the infusion time must be 1~2 hours.