Adverse reactions and complications

Results of clinical investigations involving human subjects, including investigator and enrollment information, protocol information, study population, study period, safety and effectiveness data, adverse reactions and complications, patient discontinuations, patient complaints, device failures and -replacements, data tabulations, subject report forms for deaths and discontinuations, statistical analyses, contraindications, and precautions for use of the device. Studies conducted under an IDE should be identified. 

Table 16.1 Sequelae versus adverse reactions and complications of chemical peels ...

Ophthalmic examination was performed on Days 7, 21, 42 and 63. At each presentation the following ocular assessments were documented Condition and disorders of visual function, lids, third eyelid, STT, conjunctiva, cornea (including pachymetry of corneal thickness) and the response to therapy was evaluated by both, the investigator and the client. In addition any adverse reaction or complicating medical factors were recorded individually. 

Transfusion-induced autoimmune disease has been a significant complication in the treatment of patients who require multiple platelet transfusions. Platelets and lymphocytes carry their own blood group system, ie, the human leukocyte antigen (HLA) system, and it can be difficult to find an HLA matched donor. A mismatched platelet transfusion does not induce immediate adverse reactions, but may cause the patient to become refractory to the HLA type of the transfused platelets. The next time platelets with an HLA type similar to that of the transfused platelets are transfused, they are rejected by the patient and thus have no clinical efficacy. Exposure to platelets originating from different donors is minimized by the use of apheresis platelets. One transfusable dose (unit) of apheresis platelets contains 3-5 x 10 platelets. An equal dose of platelets from whole blood donation requires platelets from six to eight units of whole blood. Furthermore, platelets can be donated every 10 days, versus 10 weeks for whole blood donations. 

The goals of treatment of status epilepticus include the cessation of any seizure activity, both clinical and subclinical, and the prevention of further seizures. Ideally, this is accomplished through directed pharmacotherapy with minimization of any side effects or adverse reactions. Complications ofSE should also be treated. 

Owing to its ability to cause widespread T cell lysis after the first dose, OKT-3 has several severe adverse effects that manifest within 3 hours after administration.10,11,14 These adverse reactions often are referred to as the first-dose effect and usually are secondary to cytokine release. The adverse-reaction profile of OKT-3 includes fever (77%), chills (43%), dyspnea (16%), nausea (32%), vomiting (25%), diarrhea (37%), and tachycardia (26%). One of the major complications of OKT-3 is the development of severe pulmonary edema.11,15,16 In reported cases of this complication, patients were fluid overloaded at the time of the initial dose. Another problematic adverse reaction is the development of nephropathy.11,17... 

Adverse reaction. Unwanted effect(s) (i.e., physical and psychological symptoms and signs) resulting from treatment. A less rigid definition of adverse reaction includes the previous definition plus any undesirable effect or problem that is present during the period of treatment and may or may not be a well-known or obvious complication of the disease itself. Thus, many common personality, physical, psychological, and behavioral characteristics that are observed in medicine studies are sometimes characterized as adverse reactions even if they were present during baseline. 

Adverse reactions were relatively frequent, with more than 50% of patients reporting at least one. Most involved the Gl tract. Most adverse effects are mild, but 21% of patients discontinued therapy because of an adverse event, principally diarrhea, rash, nausea, vomiting, Gl pain, and neutropenia. Most adverse effects occur early in the course of treatment, but a new onset of adverse effects can occur after several months. Ticlopidine has been associated with a number of bleeding complications such as ecchymosis, epistaxis, hematuria, conjunctival hemorrhage,... 

Concurrent leucovorin Trimetrexate must be used with concurrent leucovorin to avoid potentially serious or life-threatening complications, including bone marrow suppression, oral and Gl mucosal ulceration, and renal and hepatic dysfunction. Leucovorin therapy must extend for 72 hours past the last dose of trimetrexate. Inform patients that failure to take the recommended dose and duration of leucovorin can lead to fatal toxicity. Closely monitor patients for the development of serious hematologic adverse reactions. 

In addition to possible high therapeutic plasma levels, accumulation in target organs also complicates the side effect picture. Thus, early estimates of safety margins should be approached with a pinch of salt and predicted adverse reactions should be carefully monitored during late phase in vivo studies and clinical trials. 

Levodopa, the metabolic precursor of dopamine, is the most effective agent in the treatment of Parkinson s disease but not for drug-induced Parkinsonism. Oral levodopa is absorbed by an active transport system for aromatic amino acids. Levodopa has a short elimination half-life of 1-3 hours. Transport over the blood-brain barrier is also mediated by an active process. In the brain levodopa is converted to dopamine by decarboxylation and both its therapeutic and adverse effects are mediated by dopamine. Either re-uptake of dopamine takes place or it is metabolized, mainly by monoamine oxidases. The isoenzyme monoamine oxidase B (MAO-B) is responsible for the majority of oxidative metabolism of dopamine in the striatum. As considerable peripheral conversion of levodopa to dopamine takes place large doses of the drug are needed if given alone. Such doses are associated with a high rate of side effects, especially nausea and vomiting but also cardiovascular adverse reactions. Peripheral dopa decarboxylase inhibitors like carbidopa or benserazide do not cross the blood-brain barrier and therefore only interfere with levodopa decarboxylation in the periphery. The combined treatment with levodopa with a peripheral decarboxylase inhibitor considerably decreases oral levodopa doses. However it should be realized that neuropsychiatric complications are not prevented by decarboxylase inhibitors as even with lower doses relatively more levodopa becomes available in the brain. 

Didanosine (2 3 -dideoxyinosine or ddl) is a dideoxynucleoside purine analogue. Its mechanism of action is identical to that of zidovudine and resistance to didanosine is known to occur rapidly in patients who were already treated with zidovudine. Didanosine shows in vitro synergy with zidovudine while their toxicity profiles are different. Oral absorption is decreased by food and didanoside penetrates into the brain to a limited extend. Pancreatitis is the most serious complication. Other adverse reactions include peripheral neuropathy, diarrhoea and other gastrointestinal disturbances. 

Orally active agents used in the treatment of ED are more affected by aging and disease processes than are those injected intracavernosally. In addition, alterations in hepatic metabolism and/or renal clearance in the elderly man (see Chapter 6) influence the frequency of appearance of adverse reactions between several coadministered drugs in the treatment of ED. For example, the concomitant use of sildenafil and nitroglycerin is contraindicated by cardiovascular complications. Also, the use of testosterone in the presence of androgen-dependent tumors may promote tumor growth. 

Another example of a serious adverse effect that can surface through close systematic monitoring is the association of clozapine treatment with venous thromboembolytic complications (514, 515). Six cases of pulmonary embolism and six cases of venous thrombosis were reported to the Swedish Adverse-Reaction... 

Livedo reticularis sometimes occurs in patients taking amantadine and usually clears within 1 month after the drug is withdrawn. Other dermatologic reactions have also been described. Peripheral edema, another well-recognized complication, is not accompanied by signs of cardiac, hepatic, or renal disease and responds to diuretics. Other adverse reactions to amantadine include headache, heart failure, postural hypotension, urinary retention, and gastrointestinal disturbances (eg, anorexia, nausea, constipation, and dry mouth). 

The eye can be involved in generalized adverse reactions to systemically administered glucocorticoids. For example, conjunctivitis can occur as part of an allergic reaction and infections of the eye can be masked as a result of antiinflammatory and analgesic effects. Ophthalmoplegia can occur as one of the consequences of glucocorticoid myopathy (SEDA-16, 450). Two complications that require special discussion are cataract and glaucoma. 

It has been reported that there is a ninefold increased risk of having an adverse drug reaction when four or more drugs are taken simultaneously. In addition, 3-5 percent of all hospital admissions are related to adverse drug reactions, and of all the admissions for the elderly, 15-25 percent are complicated by an adverse drug reaction. Some of these reactions are life-threatening, and it is estimated that fatal adverse drug reactions in the United States may run in the thousands each year. 

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