Drug discontinuation

Metformin—there is a risk of lactic acidosis when using this drug. Discontinue die drug therapy and notify the health care provider immediately if any of the following should occur respiratory distress, muscular aches, unusual somnolence, unexplained malaise, or nonspecific abdominal distress. 

Cyclosporine and tacrolimus are calcineurin inhibitors that are administered as part of immunosuppressive regimens in kidney, liver, heart, lung, and bone marrow transplant recipients. In addition, they are used in autoimmune disorders such as psoriasis and multiple sclerosis. The pathophysiologic mechanism for ARF is renal vascular vasoconstriction.41 It often occurs within the first 6 to 12 months of treatment, and can be reversible with dose reduction or drug discontinuation. Risk factors include high dose, elevated trough blood concentrations, increased age, and concomitant therapy with other nephrotoxic drugs.41 Cyclosporine and tacrolimus are extensively metabolized by... 

Carbamazepine Manufacturer recommends CBC and platelets (and possibly reticulocyte counts and serum iron) at baseline, and that subsequent monitoring be individualized by the clinician (e.g., CBC, platelet counts, and liver function tests every 2 weeks during the first 2 months of treatment, then every 3 months if normal). Monitor more closely if patient exhibits hematologic or hepatic abnormalities or if the patient is receiving a myelotoxic drug discontinue if platelets are less than 100,000/mm3, if white blood cell (WBC) count is less than 3,000/mm3 or if there is evidence of bone marrow suppression or liver dysfunction. Serum electrolyte levels should be monitored in the elderly or those at risk for hyponatremia. Carbamazepine interferes with some pregnancy tests. 

Alopecia Reversible when drug discontinued or dose decreased... 

Photosensitivity reactions typically resolve with drug discontinuation. Some patients benefit from topical corticosteroids and oral antihistamines, but these are relatively ineffective. Systemic corticosteroids (e.g., oral prednisone 1 mg/kg/day tapered over 3 weeks) is more effective for these patients. 

Several case reports of hepatotoxicity with pioglitazone or rosiglitazone have been reported, but improvement in alanine aminotransferase (ALT) was consistently observed upon drug discontinuation. Baseline ALT should be obtained prior to therapy and then periodically thereafter at the practitioner s discretion. Neither drug should be started if the baseline ALT exceeds 2.5 times the upper limit of normal. The drugs should be discontinued if the ALT is more than 3 times the upper limit of normal. 

Patients with panic disorder should be seen every 2 weeks during the first few weeks to adjust medication doses based on symptom improvement and to monitor side effects. Once stabilized, they can be seen every 2 months. The Hamilton Rating Scale for Anxiety (score less than or equal to 7 to 10) can be used to measure anxiety, and the Sheehan Disability Scale (with a goal of less than or equal to 1 on each item) can be used to measure for disability. During drug discontinuation, the frequency of appointments should be increased. 

Allergic reactions are rare and usually occur within 8 weeks of initiating therapy. They manifest as maculopapular, erythematous, or pruritic rashes. Drug discontinuation and topical steroids are recommended when they occur. 

The reasons for drug attrition have evolved over the years over the last decade, lack of safety (both non-clinical and clinical) remains the major cause of attrition during clinical development, which accounts for approximately 35 to 40% of all drug discontinuation (see Table 13.1).la lc More worrying is the fact that there is no clear trend toward a reduction of the attrition owing to safety reasons. 

Q68 Benzodiazepines with a short elimination half-life present a less severe withdrawal after drug discontinuation than drugs with a long elimination half-life. Symptoms of benzodiazepine withdrawal syndrome include anxiety, depression, insomnia and headache. 

Ophthalmologic effects Optic neuropathy or neuritis may occur at any time following initiation of therapy, in some cases, visual impairment has progressed to permanent blindness. Corneal microdeposits appear in virtually all adults treated with amiodarone. They give rise to symptoms such as visual halos or blurred vision in as many as 10% of patients. Corneal microdeposits are reversible upon reduction of dose or drug discontinuation. Asymptomatic microdeposits are not a reason to reduce dose or stop treatment. Some patients develop photophobia and dry eyes. Vision is rarely affected and drug discontinuation is rarely needed. 

L/Verft/ncf/on-Abnormal elevations of AST, ALT, LDH, bilirubin, and alkaline phosphatase have occurred, and are usually reversible on drug discontinuation. Perform periodic liver function studies and terminate therapy if abnormalities persist. 

Lupus erythematosus Certain patients will develop a positive antinuclear antibody (ANA) test and some may show a lupus erythematosus-like syndrome similar to other drug-induced lupus, but it is not associated with hypocomplementemia and may be present without nephropathy. A positive ANA test does not mandate drug discontinuance however, a lupus erythematosus-like syndrome may develop later. Sensitivity reactions Once instituted for Wilson s disease or cystinuria, continue treatment with penicillamine on a daily basis. Interruptions for even a few days have been followed by sensitivity reactions after reinstitution of therapy. 

A iate rash A late rash is less commonly seen, usually after 6 months or more of treatment, and requires drug discontinuation. It usually appears on the trunk, is accompanied by intense pruritus, and is usually unresponsive to topical corticosteroids. 

Anxiety and Insomnia Anx ety, nervousness, and insomnia were reported for venlafaxine-treated patients, and led to drug discontinuation. 

Adverse reactions in clinical trials were minor and rarely led to drug discontinuation. 

Ischemic colitis Ischemic colitis and other forms of intestinal ischemia have been reported in patients receiving tegaserod during marketed use of the drug. Discontinue tegaserod immediately in patients who develop symptoms of ischemic colitis, such as rectal bleeding, bloody diarrhea, or new or worsening abdominal pain. 

An urticarial rash, not representing a true penicillin allergy, occasionally occurs with ampicillin (9%). Typically, the rash appears 7 to 10 days after the start of oral ampicillin therapy and remains for a few days to a week after drug discontinuance. In most cases, the rash is maculopapular, pruritic, and generalized. 

Serum sickness-like reactions (erythema multiforme or skin rashes accompanied by polyarthritis, arthralgia and, frequently, fever) have been reported these reactions usually occurred following a second course of therapy. Signs and symptoms occur after a few days of therapy and resolve a few days after drug discontinuation with no serious sequelae. 

Based on data with buffered didanosine formulations, patients with symptoms of peripheral neuropathy may tolerate a reduced dose after resolution of these symptoms following drug discontinuation. If neuropathy recurs after resumption of didanosine, consider permanent discontinuation. 

Musculoskeletal- Mild to moderate musculoskeletal symptoms, including arthralgia, that occasionally require drug discontinuation and rarely persist after discontinuation (16%) skeletal hyperostosis (see Warnings) calcification of tendons and ligaments premature epiphyseal closure arthritis tendonitis other bone abnormalities decreases in bone mineral density back pain rhabdomyolysis (rare postmarketing reports). 

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