Dosing schedule/frequency

Initiate pain control with non-narcotic analgesics such as acetaminophen, nonsteroidal anti-inflammatory agents, or selective cyclooxygenase-2 inhibitors. The dose and frequency of administration should be increased before the patient is switched to a narcotic. Parenteral narcotics should be reserved for patients with severe pain that is unresponsive to oral agents. Patients with frequent or constant pain should receive the lowest effective analgesic dose scheduled around the clock. 

Adhere to file dosage schedule recommended by the primary health care provider. Do not increase the frequency of use or the dose if symptoms become worse instead, see file primary health care provider as soon as possible... 

Animals, usually rodents, are exposed to the test substance by an appropriate route, usually by gavage or by intraperitoneal injection. Each treated and control group must include at least five animals per sex. Positive controls should produce micronuclei in vivo at exposure levels expected to give a detectable increase over background. No standard treatment schedule (i.e., 1, 2, or more treatments at 24-h intervals) has been recommended. Three dose levels are generally used these should cover a range from the maximum to little or no toxicity. The erythrocytes are sampled from the bone marrow and/or peripheral blood of the animals. If bone marrow is used, the animals are sacrificed at appropriate times after treatment, the bone marrow extracted, and preparations made and stained. When peripheral blood is used, the blood is collected at appropriate times after treatment and smear preparations are made and stained. Preparations are analyzed for the presence of micronuclei. An increase in the frequency of micronucleated polychromatic erythrocytes in treated animals is an indication of induced chromosome damage. 

A 14-day lead-in period reduces the frequency of rash, and other effective interventions include antihistamines and a longer lead-in period (4 weeks) (22). In an attempt to reduce the rate of nevirapine-associated rash, 469 patients were randomly assigned to different schedules of induction therapy (23). Using a standard procedure, 19% developed a rash compared with 11, 8.6, and 7.7% in subjects assigned to a slowly escalating dose, concomitant administration of prednisone, or both. The rate of drug withdrawal was also reduced by a half using the new approaches. 

In a study of 32 patients, 84% of those who received paclitaxel developed hypersensitivity reactions characterized by hypotension, respiratory distress, and urticaria (35). These symptoms further confirm that histamine is likely to be the cause of the reaction. The majority of reactions (53%) occurred within 2-3.minutes after the administration of paclitaxel and 78% within 10 minutes. There was one fatal reaction, characterized by hypotension and asystole. Most reactions to paclitaxel occurred after the first or second dose, and hypersensitivity reactions were more common with shorter infusion schedules. Since the duration of the infusion affected the incidence of hypersensitivity reactions, an extension of the infusion duration was investigated. Longer infusion schedules were associated with a reduced incidence of hypersensitivity reactions, the frequency of severe reactions being reduced from 12% or more to 5% with longer infusion times (5,15,49). 

The patient omits a scheduled dose. For example, if the prescription is twice daily , the patient often takes the medication once a day if the recommended dosage is one tablet daily, he often takes one tablet every second day. Again, the consequences of this frequent error are specific to each pharmaceutical product, varying according to the frequency and timing of skipped doses and the products forgiveness. 

Failure to account for nonadherence to study drug administration schedules will lead to biased and imprecise trial simulation outcome measures (19). Models to assimilate compliance often involve a hierarchical Markov model, where the probability for an individual to take a scheduled dose is conditional on whether this individual had taken the previous dose (20,21). The model may also contain covariates as predictors of compliance. For example, compliance has been shown to be affected by dosing frequency, where an increased frequency (e.g., three times daily vs. once daily) has been associated with worse compliance (22, 23). Alternatively, the consequence of missing a once-a-day dose may have more significant impact on efficacy. PK/PD-based simulations play an important role in understanding the balance of these situations. 

Treatment schedules (drug formulation, route of administration, amount and frequency of each dose, treatment duration, possible side effects, and their treatment, etc.)... 

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