Maximum recommended therapeutic dose

Chronic administration of meperidine in dogs at up to six times the maximum recommended therapeutic dose resulted in minor anorexia and weight loss. 

This package from SimulationsPlus allows prediction of many of the same toxicity endpoints available in TOPKAT but employs different modeling methodology. In addition, QSTRs for estrogen receptor modulation, maximum recommended therapeutic dose, carcinogenic potency, and cardiotoxicity (hERG-encoded K+ channel affinity) are available in ADMET Predictor (,http //www.simulationsplus.com/index.html). 

MRTD The database includes maximum recommended therapeutic doses of 1220 drugs. Developed for US FDA/CDER/OPS/SRS/ICSAS http //www.fda. gov/AboutEDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ ucm092199.htm... 

Cardiac effects were reported from early experimental work using very high doses of ebastine, but they are not believed to be clinically relevant in normal use. In one study serial electrocardiograms showed no changes with doses up to the maximum used (30 mg). Ebastine in doses up to five times the recommended therapeutic dose did not cause clinically relevant changes in QTc interval in healthy subjects (2). Co-administration of ebastine with ketoconazole or erythromycin did not lead to significant changes in the QTc interval (3,4). 

With chronic exposure, side effects may include rash, thrombocytopenia, leukopenia, and a lupus-like disorder. Chronic therapy is likely to result in tolerance, and withdrawal symptoms if primidone therapy is abruptly stopped. Doses in excess of 1500 mg (twice the maximum recommended daily dose) should be considered toxic. Less common side effects are hypotension, hypothermia, and dermal bullae. Encephalopathy has been observed in an epileptic patient with high plasma levels and poor renal function. With plasma concentrations exceeding 80pgml primidone may precipitate and cause crystalluria. Plasma levels >10 rgpml are associated with toxic effects. The therapeutic range is reportedly 5-10pgml , but clinical effects correlate more closely with phenobarbital blood levels. 

Saw palmetto is generally regarded as safe with high long-term tolerability. " One case, however, was recently reported in which saw palmetto appeared to be responsible for development of recurrent pancreatitis in a 55-year-old male." A study to investigate its effect on liver functions in rat showed that saw palmetto did not result in any toxicity at 5 x the maximum recommended human doses. The pharmacology and therapeutic signifi-... 

Heart failure As adjunctive therapy with diuretics and digitalis, the recommended starting dose is 2.5 mg twice daily. The usual therapeutic dosing range for the treatment of heart failure is 2.5 to 20 mg/day given in 2 divided doses. The maximum daily dose is 40 mg. 

Dose titration - Depending on response, the dose may be increased at intervals of 3 to 4 days in increments of no more than 1 mg/day. Slower titration to the dose levels may be advisable to allow full expression of the pharmacodynamic effect. Advance dose until an acceptable therapeutic response (ie, a substantial reduction in or total elimination of panic attacks) is achieved, intolerance occurs, or the maximum recommended dose is attained. 

Mania (divalproex sodium delayed-release tablets) 750 mg/day in divided doses increase as rapidly as possible to achieve the lowest therapeutic dose that produces the desired clinical effect or the desired range of plasma concentrations (trough plasma concentrations 50 to 125 mcg/mL). Maximum concentrations generally were achieved within 14 days. Maximum recommended dosage is 60 mg/kg/day. 

The usual starting dose for the treatment of ADHD in children over 5 years of age is 37.5 mg/ day, increased gradually by 18.75 mg/week until the desired response is reached. The usual therapeutic dose range is from 56.25 to 75 mg/day, with a maximum dose of 112 mg/day (57). Since pemoline is not approved for the treatment of narcolepsy, dosage recommendations for this indication are not readily available however, in the subsequent section, dosage information can be extrapolated from a small number of sleep deprivation studies. 

The recommended initial dose of buspirone is 7.5 mg two times daily with dosage increments of 5 mg/day every 2 to 3 days as needed. The usual therapeutic dose of buspirone is 30 to 60 mg/dayThe onset of improvement in cognitive symptoms (2 weeks or longer) precedes the rehef of somatic symptoms maximum therapeutic benefit may not be evident for 4 to 6 weeks. 

Tolmetin (tohnetin sodium Tolectin) is approved in the United States for the treatment of osteoarthritis, rheumatoid arthritis and juvenile rheumatoid arthritis it also has been used in the treatment of ankylosing spondylitis. In general, tolmetin is thought to have similar therapeutic efficacy to aspirin. The maximum recommended dose is 2 g per day, typically given in divided doses with meals, milk, or antacids to lessen abdominal discomfort. However, peak plasma concentrations and bioavailability are reduced when the drug is taken with food. 

The drug should be administered at three levels by the route proposed for humans. The high dose level should be set so as to have relevance in humans. For drugs that display significant toxic effects, this may be related to the maximally tolerated dose in the toxicity tests, for example, the dose causing less than 10% deviation in body weight versus controls. If there is little evidence of toxicity it may be more appropriate to base the dose level on a multiple (usually 25-fold) of the maximum therapeutic dosage recommended in humans. 

The recommended dose is 25 mg IM every 2 weeks. Some patients not responding to 25 mg may benefit from a higher dose of 37.5 or 50 mg. The maximum dose should not exceed risperidone injection 50 mg every 2 weeks. Give oral risperidone or another antipsychotic medication with the first risperidone injection and continue for 3 weeks (then discontinue) to ensure that adequate therapeutic plasma concentrations are maintained prior to the main release phase of risperidone from the injection site. 

Fluconazole is well absorbed following oral administration, with a plasma half-life of 30 hours. In view of this long half-life, daily doses of 100 mg are sufficient to treat mucocutaneous candidiasis alternate-day doses are sufficient for dermatophyte infections. The plasma half-life of itraconazole is similar to that of fluconazole, and detectable therapeutic concentrations remain in the stratum corneum for up to 28 days following termination of therapy. Itraconazole is effective for the treatment of onychomycosis in a dosage of 200 mg daily taken with food to ensure maximum absorption for 3 consecutive months. Recent reports of heart failure in patients receiving itraconazole for onychomycosis have resulted in recommendations that it not be given for treatment of onychomycosis in patients with ventricular dysfunction. 

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