Drug dose adjustment therapy

Drug doses need to be increased or supplemented for patients requiring renal replacement therapy only if CLec/ representing extracorporeal clearance from either intermittent hemodialysis or continuous renal replacement therapy/ is substantial when compared to CLr + CLjVR (Equation 6.12). Levy (34) has proposed that supplementation is needed only when CLec is greater than 30% of CL + CLjvr- Several approaches will be considered that can be used to make appropriate drug dose adjustments for patients requiring renal replacement therapy. 

Golper TA, Marx MA. Drug dosing adjustments during continuous renal replacement therapies. Kidney Int 1998 53(suppl 66) S165-8. 

Once the loading dose of the AED is administered, it is important to remember to initiate maintenance doses to ensure that therapeutic levels are sustained. Chronic and idiosyncratic side effects as well as potential drug interactions should be considered if the patient will continue AED therapy indefinitely. All drug therapy should be adjusted for any hepatic or renal disease states. Table 28-1 summarizes the drug doses used in SE, and Table 28-2 provides an example of an algorithm for the treatment of patients in SE. Published studies comparing these treatment strategies are summarized in Table 28-3. 

Monitor patient for response to therapy, need for dose adjustments, and presence of adverse drug reactions. 

Drug therapy individualization for patients with renal insufficiency sometimes requires only a simple proportional dose adjustment based on creatinine clearance (CLcr). Alternatively, complex adjustments are required for drugs that are extensively metabolized or undergo dramatic changes in protein binding and distribution volume. 

The starting dose and dose adjustments for combination therapy are the same as repaglinide monotherapy. Carefully adjust the dose of each drug to determine the minimal dose required. 

Dose adjustment for combination therapy with saquinavir For serious toxicities that may be associated with saquinavir mesylate, the drug should be interrupted. Saquinavir mesylate at doses less than 1,000 mg with ritonavir 100 mg twice daily are not recommended since lower doses have not shown antiviral activity. For recipients of combination therapy with saquinavir mesylate and ritonavir, dose adjustments may be necessary. These adjustments should be based on the known toxicity profile of the individual agent and the pharmacokinetic interaction between saquinavir and the coadministered drug. Health care providers should refer the complete monographs for these drugs for comprehensive dose adjustment recommendations and drug-associated adverse reactions of nucleoside analogues. 

Combination therapy - For toxicities likely to be associated with zalcitabine (eg, peripheral neuropathy, severe oral ulcers, pancreatitis, elevated liver function tests, especially in patients with chronic hepatitis B see Warnings and Precautions), interrupt or reduce dose. For severe toxicities or those persisting after dose reduction, interrupt zalcitabine therapy. For recipients of combination therapy with zalcitabine and other antiretrovirals, base dose adjustments or interruption for either drug on the known toxicity profile of the individual drugs. 

Anticipate adverse effects, and adjust therapy to prevent, minimize, or ameliorate side effects Continue to add effective and tolerated drugs, stepwise, in sufficient doses to achieve the goal of therapy Encourage a positive attitude about achieving therapeutic goals Consider using nurse management... 

For parenteral therapy, nafciUin and oxacillin offer comparable efficacy and antimicrobial spectra of activity. Although both drugs undergo hepatic metabolism, only nafcillin requires dose adjustment in patients with combined hepatic and renal insufficiency. Other pharmacokinetic data for nafcillin and oxacillin appear in Table 45.1. Indications for nafcillin or oxacillin include severe staphylococcal infections like cellulitis, empyema, endocarditis, osteomyelitis, pneumonia, septic arthritis, and toxic shock syndrome. 

For oral therapy, cloxaciUin and dicloxacillin are comparable alternatives. Both undergo hepatic metabolism, and neither drug requires dose adjustment in patients with hepatic insufficiency. Additional pharmacokinetic data are in Table 45.1. Indications for cloxacillin or dicloxacillin include clinically mild staphylococcal infections like impetigo. 

In oncology, drug dosage individualization for conventional cytotoxic anticancer therapy is performed according to mg/m2 or mg/kg. However, even after dose adjustment, the pharmacokinetic variability observed for many cytotoxic... 

AA/hen directly obseived therapy is used, drugs may be given 5 days per week and the necKssary number of doses adjusted aooordingly. Although there are no studies that compare five with seven daily doses, extensive experience indicates this would be an effective practice. Patients with cavitation on initial chest radiograph and positive cultures at completion of 2 months of therapy should recKive a 7-month (31-week either 217 doses [daily] or 62 doses [twice weekly]) continuation phase. 

Initial regimens usually consist of two NRTIs plus either a potent PI or NNRTI. Frequent changes in therapy are required over time due to adverse effects, lack of response, or both. As a general rule, NRTIs do not require dose adjustments when combined with other ARVs. However, Pis and NNRTIs tend to have complex metabolisms and in combination affect each other s levels and potency. Drug resistance occurs with all available agents, and resistance to one agent will often confer resistance to the entire class (Table 59-1). 

D The most appropriate therapy would be a neuraminidase inhibitor such as oseltamivir since amantadine and rimantadine do not cover influenza B. Treatment of influenza must be initiated within 48 hours of symptoms for maximum efficacy. Influenza vaccination is only effective for the prevention of influenza and not for symptomatic therapy. If this were influenza A and amantadine was chosen to treat this patient, dose adjustments would be necessary due to her renal insufficiency. She would also be at increased risk of CNS toxicity due to her age and possible accumulation of the drug due to her renal insufficiency. 

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