Drug incompatibilities

More progressive MCOs have moved to concurrent DUR, in which a pharmacist can screen for drug incompatibilities, duplicate prescriptions, and other problems before dispensing the medication. Obviously, the prevention of problems or the intervention directly with patients is attractive. While the identification of drug-related problems is vital to managing pharmacotherapy, intervention with the prescriber or patient also is required. The most common approach to intervening with prescribers and patients is through educational activities. 

A. Taylor, and R. Lewis, Amiodarone and injectable drug incompatibility. Pharmacol. J. 248 533, 1992. 

DOT CLASSIFICATION 6.1 Label Poison SAFETY PROFILE Poison by subcutaneous and intramuscular routes. An FDA over-the-counter drug. Incompatible with alkali iodides. When heated to decomposition it emits toxic fumes of Hg. See also MERCURY COMPOUNDS. 

Characteristics of the drug and the fluid such as drug volume, osmolality, pH, and density may affect i.v. drug delivery. The frequency and duration of drug administration is also important as is the need for the infusion system to handle multiple drugs. This may lead to drug incompatibilities and problems in medication scheduling. 

Fig. 3S.27. A chemical drug-drug incompatibility between gentamicin C-2a and P-lactams.

The term drug incompatibility is applied to unfavorable reactions which occur between two or more drugs before the administration of the drugs. 

The problems of drug incompatibility and binding of active drug to inert formulation components are significant here. 

Newton DW (2009) Drug incompatibility chemistry. Am J Health-Syst Pharm 66 348-357... 

Clinical Analysis Clinical, pharmaceutical, and forensic labs make frequent use of gas chromatography for the analysis of drugs. Because the sample s matrix is often incompatible with the GC column, analytes generally must be isolated by extraction. Figure 12.25b shows how gas chromatography can be used in monitoring blood alcohol levels. 

Lubiprostone, a drug used for treating obstipation, has been claimed to be an activator of C1C-2. This is based on a single paper showing activation by lubiprostone of currents thought to represent C1C-2. These currents, however, differ starkly from typical C1C-2 currents. Furthermore, C1C-2 is located in basolateral membranes of the intestine. This localization is incompatible with the hypothesis that its activation increases intestinal chloride and fluid secretion. Thus, the claim that lubiprostone is a Cl- channel activator must be subject to considerable doubt. 

The process of formulation for any of the above is generically the same, beginning with some form of product specification and ending with one or more formulations that meet the requirements. Correct choice of additives or excipients is paramount in the provision of efficacy, stability, and safety. For instance, the excipients may be chemically or physically incompatible with the drug or they may exhibit batchwise variability to such an extent that at the extremes of their specification they may cause failure in achieving the desired drug release profile. In addition, some excipients, especially those that are hydroscopic, may be contraindicated if the formulation is to be manufactured in tropical countries. Flence formulators must work in a design space that is multidimensional in nature and virtually impossible to conceptualize. 

Incompatibilities have also been observed in solid dosage forms. A typical tablet contain binders, disin-tegrants, lubricants and fillers. Compatibility screening for a new drug should consider two or more excipients from each class. Serajuddin et al. have developed a drug-excipient compatibility screening model to predict interactions of drug substances with excipients [49],... 

It is important for the formulator of a new drug substance to know with which excipients he can work and with which he cannot. Some pharmaceutical incompatibilities are known to the formulator, e.g., magnesium stearate/aspirin, and glucose/amines [53],... 

To assess unknown incompatibilities it is customary to make a small mix of drug substance with an excipient [54,55], place it in a vial, place a rubber stopper in the vial, and dip the stopper in molten carnauba wax (to render it hermetically sealed). The wax will harden and form a moisture barrier up to 70°C. A list of common excipients characteristic of this type of test is shown in Table 1. At times it is possible to obtain quantitative relationships of... 

Some of the most commonly used added substances are listed in Table 2. Pharmacists involved in IV admixture programs must be aware of the types of additives that may be present in the products being combined, since the source of incompatibility between different drugs mixed in solution may be the excipients present. For example, drug formulations containing... 

S. Motola and C. Clawans, Identification and surface removal of incompatible group II metal ions from butyl stoppers, Bull. Parenter. Drug Assoc., 26,163-171 (1972). 

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