What is a terminating side effect?

From the Guidelines

Terminating side effects of D-Penicillamine, such as severe sensitivity reactions, nephrotoxicity, or a lupus-like syndrome, require immediate discontinuation of the medication to prevent further harm and ensure patient safety. These side effects can occur in approximately 30% of patients taking D-Penicillamine, and it is crucial to monitor for them, especially during the initial phase of treatment 1. Common terminating side effects of D-Penicillamine include:

• Early sensitivity reactions marked by fever and cutaneous eruptions, lymphadenopathy, neutropenia or thrombocytopenia, and proteinuria, which may occur during the first 1-3 weeks of treatment
• Late reactions, such as nephrotoxicity, usually heralded by proteinuria or the appearance of other cellular elements in the urine
• A lupus-like syndrome marked by hematuria, proteinuria, and positive antinuclear antibody

If a patient experiences any of these terminating side effects, D-Penicillamine should be discontinued immediately, and alternative treatments should be considered 1. The availability of alternative medications makes a trial of prednisone cotreatment unnecessary in cases of early sensitivity reactions. It is essential to report any terminating side effects to the healthcare provider, including when the reaction began relative to starting the medication, its severity, and any other medications being taken. This information helps the provider determine causality and select alternative treatments. In the context of Wilson's disease treatment, monitoring 24-hour urinary copper excretion and non–ceruloplasmin bound copper concentration can help assess the adequacy of treatment and potential side effects 1.

From the FDA Drug Label

The following adverse reactions have been identified during post-approval use of atropine sulfate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Most of the side effects of atropine are directly related to its antimuscarinic action. Dryness of the mouth, blurred vision, photophobia and tachycardia commonly occur. Anhidrosis can produce heat intolerance. Constipation and difficulty in micturition may occur in elderly patients. Occasional hypersensitivity reactions have been observed, especially skin rashes which in some instances progressed to exfoliation. Most adverse reactions are directly related to atropine's antimuscarinic action Dryness of the mouth, blurred vision, photophobia and tachycardia commonly occur with chronic administration of therapeutic doses.

The terminating side effect of atropine (IV) is not explicitly stated in the provided drug labels. However, based on the listed adverse reactions, potential terminating side effects could be:

• Hypersensitivity reactions, especially skin rashes that progress to exfoliation 2
• Tachycardia 2 2
• Anhidrosis leading to heat intolerance 2 It is essential to note that these are potential terminating side effects and may not be exhaustive, as the drug labels do not provide a comprehensive list of terminating side effects.

From the Research

Terminating Side Effect

• The terminating side effect of penicillin allergy can be managed through discontinuation of the medication and treatment with epinephrine, antihistamines, and/or glucocorticoids, depending on the type of reaction 3.
• Most beta-lactams may be safely used in penicillin-allergic patients, with the possible exception of first-generation and second-generation cephalosporins 3.
• Penicillin testing, including skin testing, patch testing, and graded challenge, can be used to determine the severity of the allergy and guide treatment decisions 3, 4.
• The rate of IgE-mediated penicillin allergies is decreasing, potentially due to decreased use of parenteral penicillins, and severe anaphylactic reactions to oral amoxicillin are rare 4.
• Cross-reactivity between penicillin and cephalosporin drugs occurs in about 2% of cases, and later-generation cephalosporins do not have skin test cross-reactivity with penicillin/amoxicillin 5.

Management of Penicillin Allergy

• Evaluation of penicillin allergy before deciding not to use penicillin or other β-lactam antibiotics is an important tool for antimicrobial stewardship 4.
• Direct amoxicillin challenge is appropriate for patients with low-risk allergy histories, while moderate-risk patients can be evaluated with penicillin skin testing 4.
• Clinicians performing penicillin allergy evaluation need to identify what methods are supported by their available resources 4.
• A risk stratification tool can be used to assess allergies and determine appropriate antibiotic choice, dosage, and timing in the orthopaedic preoperative setting 6.

Discontinuation of Medication

• Discontinuation of chronic medication in primary care can be safe, but there is a risk of relapse of symptoms 7.
• The proportion of patients who successfully stop their medication varies from 20% to 100%, and the range of reported relapse varies from 1.9% to 80% 7.
• More research is needed to advise physicians in making evidence-based decisions about deprescribing in primary care settings 7.