Based on data from the manufacturer, it is expected that 0.6% of the maternal weight-adjusted dose would reach a breastfed infant, though the effects in the infant are unknown. Renal impairment
Renal impairment does not appear to affect the pharmacokinetic profile of zafirlukast. Hepatic impairment
The hepatic clearance of zafirlukast is impaired by significant hepatic impairment. Cirrhosis of the liver can result in an increase in the maximum plasma concentration and the total area under the curve (a measure of drug exposure) by 50–60%. Contraindications
Zafirlukast is contraindicated in people that are hypersensitive or allergic to it. Adverse effects
Zafirlukast is generally well tolerated, though headache and gastrointestinal (GI) upset can occur. The incidence of headache is between 12 and 20%, which is similar to the incidence of headache found in patients taking placebos in the studies that lead to zafirlukasts approval. GI upset may include nausea, stomach discomfort/pain, and diarrhea. GI complaints can be lessened by taking zafirlukast with food, though this can dramatically impair the amount of drug that gets absorbed into the body (see the section on drug-food interactions below).Other common side effects include flu-like symptoms, sleep disturbances (abnormal dreams, insomnia), hallucinations, and daytime drowsiness. Neuropsychiatric effects
Neuropsychiatric side effects have been reported with the use of zafirlukast and other LTRAs. While some side effects are less severe (e.g. abnormal dreams), others are more serious (e.g. hallucinations, tremor, suicidality). These effects were discovered through post-marketing reports, as the initial trials were not designed to monitor for neuropsychiatric side effects.
The average half-life of avalglucosidase alfa was 1.6 hours, measured in patients with late stage Pompe disease. There is little information availible on the metabolism of the avalglucosidase alfa. The protein portion of the drug however does break down into small peptides via catabolic pathways. The clearance of the drug is 0.9 L/hour in patients that exhibited late-stage Pompe disease. Blackbox warnings
Avalglucosidase alfa has a blackbox warning for hypersensitivity, infusion-related reactions, and cardiorespiratory failure. Society and culture
Legal status
In July 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Nexviadyme, intended for the treatment of glycogen storage disease type II (Pompe disease). The applicant for this medicinal product is Genzyme Europe BV. In August 2021, Genzyme Europe BV requested a re-examination. Avalglucosidase alfa was approved for medical use in the European Union in June 2022.The U.S. Food and Drug Administration (FDA) granted the application for avalglucosidase alfa fast track, priority review, breakthrough therapy, and orphan drug designations. The FDA granted the approval of Nexviazyme to Genzyme Corporation. Names
Avalglucosidase alfa is the international nonproprietary name (INN). References
External links
"Avalglucosidase alfa". Drug Information Portal. U.S. National Library of Medicine.