Glucarpidase interacts in the following cases:
Glucarpidase may also reduce the concentrations of other folate analogs or folate analog metabolic inhibitors.
Glucarpidase can decrease folinic acid concentration, which may decrease the effect of folinic acid rescue unless it is dosed as recommended.
There are no data from the use of glucarpidase in pregnant women. Glucarpidase is administered in combination with methotrexate (MTX), which is contraindicated in pregnancy. As use of MTX, a genotoxic and teratogenic agent, is a prerequisite for the use of glucarpidase, the medicinal product is not thought to present an additional risk to patients already receiving MTX. Reproductive studies of glucarpidase in animals were not performed. It is unknown whether glucarpidase causes harmful effects during pregnancy and/or on the foetus/newborn child or whether it can affect reproductive capacity. Glucarpidase should only be given to a pregnant woman if clearly needed.
It is unknown whether glucarpidase/metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from glucarpidase therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
There is no or limited amount of data on the impact of glucarpidase on human fertility. Fertility studies in animals were not performed. It is unknown whether glucarpidase affects fertility.
Glucarpidase has no or negligible influence on the ability to drive and use machines.
The most frequent related adverse reactions were burning sensation (<1%), headache (<1%), paraesthesia (2%), flushing (2%), feeling hot (<1%).
The following table gives the adverse reactions observed from the combination of pooled clinical study data (489 patients) and reported adverse reactions during the Post Marketing period. The adverse reactions are presented by system organ class and frequency categories defined using the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000). Within each frequency grouping undesirable effects are presented in order of decreasing seriousness.
Adverse reactions reported for glucarpidase:
| System organ class | Frequency | Adverse reactions |
|---|---|---|
| Immune system disorders | Rare | Hypersensitivity |
| Very Rare | Anaphylactic reaction | |
| Nervous system disorders | Uncommon | Burning sensation, Headache, Paraesthesia |
| Rare | Hypoaesthesia, Somnolence, Tremor | |
| Cardiac disorders | Very Rare | Tachycardia |
| Vascular disorders | Uncommon | Flushing |
| Rare | Hypotension | |
| Respiratory, thoracic and mediastinal disorders | Rare | Pleural effusion, Throat tightness |
| Gastrointestinal disorders | Rare | Abdominal pain upper, Diarrhoea, Nausea, |
| Skin and subcutaneous tissue disorders | Rare | Pruritus, Rash |
| Very Rare | Drug eruption, Skin reaction | |
| Renal and urinary disorders | Very Rare | Crystalluria* |
| General disorders and administration site conditions | Uncommon | Feeling hot |
| Rare | Pyrexia, Rebound effect | |
| Very Rare | Infusion site reaction |
* Crystalluria is the preferred term; the adverse reaction refers to DAMPA crystalluria
As with any intravenous protein product, infusion-related reactions or hypersensitivity reactions are possible.
It is recommended that patients are monitored for signs and symptoms of anaphylaxis and an acute allergic reaction. Medical support must be readily available when glucarpidase is administered. As with all therapeutic proteins, there is potential for immunogenicity. 205 patients who received one (n=176), 2 (n=27), or 3 (n=2) doses of glucarpidase were evaluated for anti-glucarpidase antibodies.
Forty-three of these 205 patients (21%) had detectable anti-glucarpidase antibodies following administration, of which 32 received 1 dose and 11 received 2 or 3 doses of glucarpidase. Antibody titers were determined using a bridging enzyme-linked immunosorbent assay (ELISA) for anti-glucarpidase antibodies. Neutralizing antibodies were detected in 22 of the 43 patients who tested positive for anti-glucarpidase binding antibodies.
The incidence of adverse events related to glucarpidase did not differ between paediatric and adult patients.
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