Baseline discontinuities

If liver function tests increase to > twice baseline, discontinue treatment... 

After the desired overlap and target INR has been reached, withhold the DTI and recheck the INR and aPTT in 4—6 h. Prolonged cessation may be required if the patient initially required a low-dose DTI infusion. If the INR is between 2 and 3 and the aPTT is at/near baseline, the DTI can be discontinued. 

Tolcapone has been associated with several cases of severe liver failure, including fatalities, and has been removed from the market in some countries. Thus, it should only be used in patients who cannot take or do not respond to entacapone. Serum alanine aminotransferase and aspartate aminotransferase concentrations should be monitored at baseline, then every 2 to 4 weeks for 6 months, and then periodically for the remainder of therapy. Patients who fail to show symptomatic benefit after 3 weeks should discontinue tolcapone. Entacapone has not been associated with liver damage, so monitoring of liver enzymes is not currently recommended.24,25,29... 

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. 

A few cases of hepatotoxicity have been reported with rosiglitazone and pioglitazone, but no serious complications have been reported, and symptoms typically reverse within several weeks of discontinuing therapy. Therefore, periodic liver function tests should be performed at baseline and during thiazolidinedione therapy. Patients with a baseline alanine aminotransferase (ALT) level greater than 2.5 times the upper limit of normal should not receive a TZD. If ALT levels rise to greater than 3 times the upper limit of normal in patients receiving a TZD, the medication should be discontinued. 

Several studies have evaluated the long-term efficacy and safety of bisphosphonates in postmenopausal women. One study evaluated the use of alendronate over a 10-year period and found no difference in adverse effects between women who received alendronate for 10 years and women who discontinued alendronate after 5 years. Women who discontinued alendronate after 5 years continued to experience sustained increases in bone mineral density compared with baseline values and a reduction... 

Blood pressure and serum creatinine (SCr) should be assessed prior to beginning cyclosporine therapy to obtain accurate baselines, and should be reassessed biweekly once therapy is started for at least the first 12 weeks of therapy (until values stabilize), and then closely monitored during therapy. If SCr increases to 30% above the patient s baseline, the cyclosporine dosage needs to be decreased and SCr rechecked in a month. If the SCr is still above 30% of the patient s baseline, cyclosporine should be discontinued and only resumed when the SCr returns to within 10% of the patient s baseline. Cyclosporine should also be discontinued for inadequate response after 3 months use at the maximum dose.10,36... 

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 should have blood urea nitrogen, serum creatinine, aspartate transaminase or alanine transaminase, and a complete blood count determined at baseline and periodically, depending on the presence of other factors that may increase the likelihood of toxicity (advanced age, alcohol abuse, and possibly pregnancy). Hepatotoxicity should be suspected in patients whose transaminases exceed five times the upper limit of normal or whose total bilirubin exceeds 3 mg/dL. At this point, the offending agent(s) should be discontinued, and alternatives selected. 

On rare occasions, pemoline can cause a chemical hepatitis (liver dysfunction). For this reason, patients with known liver disease should not be prescribed pemoline. A baseline laboratory assessment of liver enzymes before starting therapy with pemoline is advised, and liver function monitoring must be repeated periodically. If liver abnormalities are detected, then pemoline must be discontinued. The recognition of this side effect resulting from therapy with pemoline has markedly restricted its use. 

Dose-dependent inhibition of platelet aggregation can be seen 2 hours after single oral doses of clopidogrel. Platelet aggregation and bleeding time gradually return to baseline values after treatment is discontinued, generally in about 5 days. Pharmacokinetics ... 

Converting to oral anticoagulant therapy Perform baseline coagulation tests to determine prothrombin activity when heparin activity is too low to affect PT or INR. When the results of the initial prothrombin determinations are known, initiate the oral anticoagulant in the usual amount. Thereafter, perform coagulation tests and prothrombin activity at appropriate intervals. When the prothrombin activity reaches the desired therapeutic range, discontinue heparin and continue oral anticoagulants. 

Initial dosage in HIT or heparin-induced thrombocytopenia and thrombosis syndrome (HITTS) Before administering argatroban, discontinue heparin therapy and obtain a baseline activated partial thromboplastin time (aPTT). The recommended initial dose of argatroban for adults without hepatic impairment is 2 mcg/kg/min administered as a continuous infusion (see table). 

Hepatotoxicity Available clinical data show no evidence of pioglitazone- and rosiglitazone-induced hepatotoxicity or ALT elevations. It is recommended that patients undergo periodic monitoring of liver enzymes. Check liver enzymes prior to the initiation of therapy in all treated patients. Do not initiate therapy in patients with increased baseline liver enzyme levels (ALT more than 2.5 times the ULN). In patients with normal baseline liver enzymes, it is recommended that liver enzymes be monitored every 2 months for the first 12 months and periodically thereafter. Evaluate patients with mildly elevated liver enzymes (ALT levels less than or equal to 2.5 times the ULN) at baseline or during therapy to determine the cause of the liver enzyme elevation. Proceed with caution in the initiation of, or continuation of, therapy in patients with mild liver enzyme elevations and include appropriate close clinical follow-up, including more frequent liver enzyme monitoring, to determine if the liver enzyme elevations resolve or worsen. If at any time ALT levels increase to more than 3 times the ULN, recheck liver enzyme levels as soon as possible. If ALT levels remain more than 3 times the ULN, discontinue therapy. 

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... 

Oral - Elevated hepatic enzyme levels (AST and ALT) are frequent, and in most cases are asymptomatic. If the increase exceeds 3 times normal, or doubles in a patient with an elevated baseline, consider discontinuation or dosage reduction. 

IV The maximum effect of each IV injection of labetalol at each dose level occurs within 5 minutes. Following discontinuation of IV therapy, BP approaches pretreatment baseline values in 16 to 18 hours. 

Positive Coombs test/Hemolytic anemia With prolonged therapy, 10% to 20% of patients develop a positive direct Coombs test, usually between 6 and 12 months of therapy. This is associated rarely with hemolytic anemia, which could lead to potentially fatal complications and is difficult to predict. Perform baseline and periodic blood counts to detect hemolytic anemia. If Coombs -positive hemolytic anemia occurs, discontinue methyidopa anemia usually remits promptly. 

The fall in LDL concentration is apparent in 4 to 7 days. The decline in serum cholesterol is usually evident by 1 month. When the resins are discontinued, serum cholesterol usually returns to baseline within 1 month. Cholesterol may rise even with continued use determine serum levels periodically. 

Monitoring Perform baseline and periodic leukocyte and differential counts and liver function studies. Fever or sore throat may signal serious neutrophil depression discontinue therapy if there is evidence of pathological neutropenia. 

Patients who are being treated with clozapine must have a baseline white blood cell (WBC) and differential count before initiation of treatment and regular WBC counts during treatment and for 4 weeks after the discontinuation of clozapine. 

A total of 3.2% of treated and 1.8% of placebo patients had at least 1 possibly significant (2.8 x 10 /L or less) decreased WBC, and 2.4% of treated and 1.4% of placebo patients had at least 1 possibly significant (1 x 10 /L or less) decreased neutrophil count. Of the treated patients with a low neutrophil count, all but 1 rose toward or to baseline with continued treatment. No patient was discontinued secondary to low neutrophil counts. 

Hematology Evaluate baseline and periodic blood studies approximately every 2 days during therapy. Discontinue the drug upon appearance of reticulocytopenia, leukopenia, thrombocytopenia, anemia, or any other findings attributable to... 

Hyperuricemia Pyrazinamide inhibits renal excretion of urates, frequently resulting in hyperuricemia that is usually asymptomatic. Patients started on pyrazinamide should have baseline serum uric acid determinations. Discontinue the drug and do not resume if signs of hyperuricemia accompanied by acute gouty arthritis appear. 

Hepatic function impairment Patients started on pyrazinamide should have baseline liver function determinations. Closely follow those patients with pre-existing liver disease or those at increased risk for drug-related hepatitis. Discontinue pyrazinamide and do not resume if signs of hepatocellular damage appear. 

Renai function - Monitor renal function in all patients during treatment with adefovir, particularly for those with preexisting or other risks for renal impairment. Patients with renal insufficiency at baseline or during treatment may require dose adjustment. Evaluate the risks and benefits of adefovir treatment prior to discontinuing adefovir in a patient with treatment-emergent nephrotoxicity. 

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