Rechallenge

D/C antiretrovirals D/C all hepatotoxic agents rule out other causes do not rechallenge with NVP... 

D/C all antiretrovirals as well as any other possible cause aggressive symptom support do not rechallenge patient with offending agent if caused by NVP, avoid NNRTI class, if possible... 

Many medications have been implicated (Table 28-1), but a causal association is difficult to confirm because ethical and practical considerations prevent rechallenge. 

Rechallenge with the lowest effective dose of SGA may be considered only for patients in need of reinstitution of antipsychotics following observation for at least 2 weeks without antipsychotics. There must be careful monitoring and slow-dose titration. 

Lawson, T.M. et al., Minocycline-induced lupus Clinical features and response to rechallenge, Rheumatology (Oxford), 40, 329, 2001. 

Rechallenge. The principle involved in the rechallenge method of linkage of a therapeutic to an ADR is implied in the phrase post hoc ergo propter hoc (after this therefore because of this). 

As applied, if a drug has been incriminated with a reaction, and the ADR disappeared when the drug was discontinued, a rechallenge with this drug followed by a return of the ADR would increase the probability that the drug and the ADR were empiric correlates. While intentional challenge is not often done, such a rechallenge may occur inadvertently. 

Certainty is rarely obtainable perhaps an AE with a positive rechallenge where there is objective evidence and an absence of confounders in an individual case would be considered as certainty due to the drug. In the majority of cases action is needed before there is absolute certainty that a drug can cause an AE. This lack of certainty in individual cases has been described suing rather vague terms such as almost certain , probably , possible , unlikely , etc. These terms have also been defined, but each author has a slightly different definition (Venulet et al., 1982 Stephens et ah, 1998). 

The risk of rechallenge has to be very carefully considered. Its use will depend on the severity of the reaction, availability of a specific antidote, ease and speed of reversing the effect and the subject s willingness to be exposed for a second time. RechaUenge is not infrequently imdertaken in Phase I studies when an exaggerated response (Type A reaction) occurs and a smaller dose can... 

Rechallenge. As for behaviour of the event on restarting the suspected drug. 

Prior Time to onset Specific background Evolution of event Drug withdrawal Rechallenge Other 1. 2. 3. Total... 

Humans have developed strong skin reactions when rechallenged with the liquid. Allergic contact dermatitis has been reported in workers handling methacrylate sealants, including methyl methacrylate. In another report, five subjects were shown by bronchial provocation tests to have occupational asthma due to methyl methacrylate or cyanoacrylates. ... 

Lead exposure Not a substitute for effective abatement of lead exposure. Neutropenia Mild to moderate neutropenia has been observed in some patients receiving succimer. While a causal relationship to succimer has not been definitely established, neutropenia has been reported with other drugs in the same chemical class. Obtain a complete blood count with white blood cell differential and direct platelet counts prior to and weekly during treatment. Withhold or discontinue therapy if the absolute neutrophil count (ANC) is below 1200/mcL and follow the patient closely to document recovery of the ANC to above 1500/mcL or to the patient s baseline neutrophil count. There is limited experience with reexposure in patients who have developed neutropenia. Therefore, rechallenge such patients only if the benefit of succimer therapy clearly outweighs the potential risk of another episode of... 

Hypersensitivity pneumonitis - Hypersensitivity pneumonitis usually appears earlier in the course of therapy, and rechallenging these patients results in a more rapid recurrence of greater severity. 

Use of carvedilol in patients with clinically manifest hepatic impairment is not recommended. Mild hepatocellular injury, confirmed by rechallenge, has occurred rarely with carvedilol therapy. 

Do not rechallenge with clozapine because agranulocytosis may develop with a shorter latency. 

Experience is limited in patients with ALT more than 10 x ULN. The risk of rechallenge must be considered against demonstrated clinical benefit. Patients with clinical jaundice confirmed by a significant elevation in total bilirubin (more than 3... 

Local injection site reactions The most common adverse events associated with enfuvirtide use are local injection site reactions. Manifestations may include pain and discomfort, induration, erythema, nodules and cysts, pruritus, and ecchymosis. Pneumonia An increased rate of bacterial pneumonia was observed in subjects treated with enfuvirtide in the phase 3 clinical trials compared with the control arm. Hypersensitivity reactions Hypersensitivity reactions have been associated with enfuvirtide therapy and may recur on rechallenge. Hypersensitivity reactions have included individually and in combination Rash, fever, nausea and vomiting, chills. 

Jabboury K, Holmes FA, Hortobagyi G. 5-Fluorouracil rechallenge by protracted infusion in refractory breast cancer. Cancer 1989 64 793-797. 

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