Dosage, fixed-combination

Fixed-Combination Dosage Enantiopnre Drug Substances... 

Salmeterol is also available in a fixed ratio combination product containing fluticasone, and a new drug application has been filed for a fixed combination product containing budesonide and formoterol. Combination products have the potential advantage of increasing patient adherence due to the decreased number of inhalers and inhalations however, these products offer less flexibility with respect to dosage adjustments when necessary. 

Fixed-Combination Dosage Enantiopure Drug Substances 256... 

The evident disadvantage of a fixed combination is that it renders it impossible to carry out any fine adjustment of dosages, such as might be called for in the light of the clinical response and adverse effects in a given individual. 

While that particular combination isn t currently on the market, one product (Caduet) combines Lipitor (atorvastatin) for cholesterol lowering and Norvasc (amlodipine) for blood pressure reduction. Caduet is available in a wide variety of dosages of both agents, allowing physicians to choose the one that would best suit a particular patient. That s much better than a fixed combination, since typically one size does not fit all. 

Renal function Impairment Because it is a fixed-dose combination, do not prescribe lamivudine/zidovudine for patients requiring dosage adjustment, such as those with reduced renal function (Ccr less than 50 mL/min) or those experiencing dose-limiting adverse events. 

Because this product is a fixed-dose combination doseform, avoid use in patients requiring dosage reduction. 

Two patients with hypothyroidism taking a fixed dosage of levothyroxine took aluminium hydroxide and magnesium oxide (72). In both cases there was a marked increase in the serum concentration of TSH and low serum T4. After withdrawal of the antacids, TSH again fell. In vitro studies showed a dose-related adsorption of levothyroxine by a combination of aluminium hydroxide, magnesium hydroxide, and magnesium carbonate, but no effect of magnesium oxide alone. 

Following the successful outcomes of the studies of murine A/342 immunization in several laboratories, clinical trials were initiated. The immunogen used in these studies, AN-1792 (Elan Pharmaceuticals/Wyeth), contained synthetic A/342 in combination with an adjuvant (QS-21). Two Phase I studies were undertaken to evaluate the safety and tolerability of AN-1792 in patients with AD. The first was a single-dose study with three escalating A/342 dosage levels, but with a fixed adjuvant concentration. There were eight patients per dose level and a six-week period between escalations. The second Phase I study was a multi-dose (for both A/342 and QS-21 adjuvant), dose-escalation study, with a two to three month interval between each dose level. 

The Committee noted the information presented by the HIV/AIDS department, The importance of the quality of APIs was stressed, including the necessity for appropriate analytical methodology. It was noted that the development of monographs for APIs and final dosage forms, including fixed-dose combinations (FDCs), together with the introduction of alterna-... 

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