Adverse Experiences

EDWARDS s, KOCH G G, SOLLECITO w A, PEACE K E (1990) Siunmarizatiou, analysis, and monitoring of adverse experiences, in Statistical Issues in Drug Research and Development, New York, Marcel Dekker, Inc, 19-170. 

Gourlay S. G., Forbes A., Marriner T., Me Nei J. J. (1999). Predictor of adverse experiences during transdermal nicotine therapy. Drug Saf. 20, 545-55. 

The potential toxicological effects [59] as well as an overview of the adverse experiences [60] for ciprofloxacin have been reported. Since some quinolones... 

Adverse event (or Adverse experience) Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. 

CFR 600.80 Post-marketing reporting of adverse experiences for licensed biological products (includes vaccines) (published 1994). 

See also CFR Web site, http //www.access.gpo.gov/nara/cfr/index.html. An August 1997 guideline, Post-Marketing Adverse Experience Reporting for Human Drug and Licensed Biological Products Clarification of What to Report, defined the minimum data relevant for a safety report as... 

A periodic report contains certain information, such as the event terms submitted during the period, the dates that events of the period were submitted, an event term count by body system, and labeling changes made due to the period s adverse experiences. In addition to (and prior to) being incorporated into a periodic report, 15-day reports are submitted within 15 calendar days of the date the applicant received the data. All 15-day reports contain serious, unexpected events. Non-15-day reports are submitted periodically in FDA periodic reports. 

Adverse event. Unwanted effects that occur and are detected in populations. The term is used whether there is or is not any attribution to a medicine or other cause. Adverse events may be known parts of a disease that are observed to occur within a period of observation, and they may be analyzed to test for their frequency in a given population or trial. This is done to determine if there is an unexpectedly increased frequency resulting from nondisease factors such as medicine treatment. The term adverse event or adverse experience is used to encompass adverse reactions plus any injury, toxicity, or hypersensitivity that may be medicine-related, as well as any medical events that are apparently unrelated to medicine that occur during the study (e.g., surgery, illness, and trauma). See definition of Adverse reaction. 

Synonyms of adverse reactions generally include adverse medical effects, untoward effects, side effects, adverse drug experiences, and adverse drug reactions. Specific distinctions among some of these terms may be defined operationally. For example, the term adverse reaction is used to denote those signs and symptoms at least possibly related to a medicine, whereas the term adverse experience is used to include nonmedicine-related medical problems in a trial such as those emanating from trauma or concurrent illness. Distinctions among side effects, adverse events, and adverse reactions are illustrated in the definitions of the two former terms. 

A number of terms are used to describe an adverse event, including adverse drug reaction (ADR), adverse experience, adverse effect, and albeit rarely, drug misadventure. In this paper, the term adverse event is used in most cases to avoid confusion. 

Provides that any report or information relating to the safety of a drug that is submitted to FDA shall not be construed to reflect necessarily a conclusion that the report constitutes an admission that the product caused or contributed to an adverse experience. 

The FDA IND regulations contain requirements for various types of records and reports, which must be adhered to without exception. Immediate reports to FDA are required for any serious and unexpected adverse experience associated with the drug. Annual reports are required for every IND. Records must be kept to document all aspects of the IND. 

Zidovudine-treated HIV-infected patients - Adverse experiences greater than 3% were consistent with the progression of HIV infection pyrexia, fatigue, headache, cough, diarrhea, rash, nausea, respiratory congestion, shortness of breath, asthenia, skin reaction, and dizziness. 

The risk of severe esophageal adverse experiences appears to be greater in patients who lie down after taking bisphosphonates or who fail to swallow it with a full glass (6 to 8 oz) of water, or who continue to take bisphosphonates after developing symptoms suggestive of esophageal irritation. 

Once the arrhythmia is controlled, it may be possible to reduce the dose, as necessary, to minimize side effects or effects on conduction. PSVT and PAF The recommended starting dose is 50 mg every 12 hours. Doses may be increased in increments of 50 mg twice daily every 4 days until efficacy is achieved. For PAF patients, a substantial increase in efficacy without a substantial increase in discontinuation for adverse experiences may be achieved by increasing the flecainide dose from 50 to 100 mg twice/day. The maximum recommended dose for patients with paroxysmal supraventricular arrhythmias is 300 mg/day. 

Plasma level monitoring The majority of patients treated successfully had trough plasma levels between 0.2 and 1 mcg/mL. The probability of adverse experiences, especially cardiac, may increase with higher trough plasma levels, especially levels greater than 1 mcg/mL. Monitor trough plasma levels periodically, especially in patients with severe or moderate chronic renal failure or severe hepatic disease and CHF, as drug elimination may be slower. 

If signs of excessive opioid-related adverse experiences are observed, the next dose may be reduced. If this adjustment leads to inadequate analgesia, a supplemental dose of IR oxycodone may be given. Alternatively, nonopioid analgesic adjuvants may be employed. Make dose adjustments to obtain an appropriate balance between pain relief and opioid-related adverse experiences. 

Adjunctive therapy/monotherapy in pediatric patients previously treated with other AEDs - The most commonly observed (5% or more) adverse experiences seen in association with oxcarbazepine in pediatric patients were similar to those seen in adults. 

Monotherapy in adults not previously treated with other AEDs - Approximately 9% of 295 adult patients discontinued treatment because of an adverse experience. The adverse experiences most commonly associated with discontinuation were the following Dizziness, nausea, rash (1.7%) headache (1.4%). 

The most frequent adverse experiences associated with pilocarpine were a consequence of the expected pharmacologic effects. Adverse reactions occurring in at least 3% of patients include the following Sweating, nausea, rhinitis, chills, flushing, urinary frequency, dizziness, asthenia, headache, dyspepsia, lacrimation, diarrhea, edema, abdominal pain, amblyopia, vomiting, pharyngitis, and hypertension. 

Seizures Seizures and other CNS adverse experiences have been reported during treatment with meropenem. These adverse experiences have occurred most commonly in patients with CNS disorders (eg, brain lesions or history of seizures) or with bacterial meningitis or compromised renal function. 

CNS adverse experiences CNS adverse experiences have occurred with the IV formulation, especially when recommended dosages were exceeded. They are most common in patients with CNS disorders who also have compromised renal function and are rare when no underlying CNS disorder exists. (Continue anticonvulsants in patients with a known seizure disorder.) If focal tremors, myoclonus, or seizures occur, neurologically evaluate the patient, institute anticonvulsants, re-examine the dose, and determine whether to decrease dosage or discontinue the drug. If these effects occur with the IM formulation, discontinue the drug. 

Seizures Seizures and other CNS adverse experiences have been reported during treatment with ertapenem. 

The most common drug-related adverse experiences in patients treated with ertapenem, including those who were switched to therapy with an oral antimicrobial, were diarrhea, infused vein complication, nausea, headache, vaginitis, phlebitis/thrombophlebitis, and vomiting. 

Psychiatric symptoms Serious psychiatric adverse experiences have been reported in patients treated with efavirenz. Patients with a history of psychiatric disorders appear to be at greater risk for serious psychiatric adverse experiences. 

Children - Clinical adverse experiences observed in 10% or more of pediatric patients 3 to 16 years of age who received efavirenz capsules were the following Rash, diarrhea/loose stools, fever, cough, dizziness/lightheadedness/fainting ache/pain/discomfort, nausea/vomiting, headache. 

Patients who may be at greater risk for CNS adverse experiences - Patients who may be at greater risk for CNS adverse experiences include the following Known or suspected... 

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