Phenytoin sodium injection

Phenytoin Sodium injection Propylene Glycol and Alcohol Glass, 1.8 M X 2.0mm I.D. silanised S3 (50-80 mesh) Helium 140-190 6/min FID Ethylene Glycol and Methanol USP (24, p. 1326)... 

Fosphenytoin is a prodrug, a compound that undergoes chemical conversion in the body to become the therapeutically active compound phenytoin. Cerebyx dosage will continue to be expressed in PEs. This terminology was adopted in an effort to simplify therapeutic conversions between phenytoin sodium and fosphenytoin sodium (i.e., 500 mg of phenytoin sodium injection is equal to 500 mg PE of fosphenytoin sodium injection). The manufacturer pointed out that by using PEs, prescribers will not have to make dosing... 

Prescribing Information for Dilantin (Phenytoin Sodium Injection, U.S.P.), Warner-Lambert, 1994. 

Phenytoin sodium injection The injection can be safely mixed with 0.9% NaCl, but will precipitate in dextrose. A maximum infusion rate of 50 mg/min is recommended. 

Acute head injuries A study evaluating the effect of IV valproate in the prevention of posttraumatic seizures in patients with acute head injuries found a higher incidence of death in valproate treatment groups compared with the IV phenytoin treatment group. Until further information is available, it seems prudent not to use valproate sodium injection in patients with acute head trauma for the prophylaxis of posttraumatic seizures. 

Admixture Incompatibilities Physical incompatibilities resulted when linezolid IV injection was combined with the following drugs during simulated Y-site administration amphotericin B, chlorpromazine hydrochloride, diazepam, pentamidine isothionate, erythromycin lactobionate, phenytoin sodium, and trimethoprim-sulfamethoxazole. Additionally, chemical incompatibility resulted when linezolid IV injection was combined with ceftriaxone sodium. 

Absorption of phenytoin is highly dependent on the formulation of the dosage form. Particle size and pharmaceutical additives affect both the rate and the extent of absorption. Absorption of phenytoin sodium from the gastrointestinal tract is nearly complete in most patients, although the time to peak may range from 3 to 12 hours. Absorption after intramuscular injection is unpredictable, and some drug precipitation in the muscle occurs this route of administration is not recommended for phenytoin. In contrast, fosphenytoin, a more soluble phosphate prodrug of phenytoin, is well absorbed after intramuscular administration. 

Pethidine Hydrochloride Pethidine hydrochloride solutions are not compatible with barbiturates, aminophylline, morphine sulfate, sulfadiazine sodium, methicilline sodium, nitrofurantoin, phenytoin sodium, heparin sodium, sodium iodide, diethanolamine, sulfafurazol, acyclovir sodium, liposomal doxorubicin hydrochloride, frusemide, imipenem, and idarubicin. Visual incompatibilities are reported with mixtures of pethidine hydrochloride and cefoperazone sodium or mezlocillin sodium, nafcillin sodium and minocycline hydrochloride or tetracycline hydrochloride in 5% glucose injection.82 83... 

Monoethanolamine is used primarily in pharmaceutical formulations for buffering purposes and in the preparation of emulsions. Other uses include as a solvent for fats and oils and as a stabilizing agent in an injectable dextrose solution of phenytoin sodium. 

Soybean oil emulsions have been reported to be incompatible at 25°C with a number of materials including calcium chloride, calcium gluconate, magnesium chloride, phenytoin sodium, and tetracycline hydrochloride. Lower concentrations of these materials, or lower storage temperatures, may result in improved compatibility. The source of the material may also affect compatibility for example, while one injection from a particular manufacturer might be incompatible with a fat emulsion, an injection with the same amount of active drug substance from another manufacturer might be compatible. 

Capsules and injection Phenytoin sodium (92% phenytoin acid)... 

Morphine Sulfate Morphine sulfate precipitates in alkaline media and drugs that are incompatible with it, including aminophylline, sodium salts of barbiturates, and phenytoin. Precipitate was found after 2 horns when morphine sulfate was formulated with acyclovir sodium.70 Incompatibilities also are reported with chlorpromazine hydrochloride injections containing chlorocresol. Admixture of morphine sulfate (1 mg/mL), doxorubicin in doxorubicin hydrochloride... 

Prodrugs can be used to increase or decrease the aqueous solubility, mask bitterness, increase lipophili-city, improve absorption, decrease local side effects, and alter membrane permeability of the parent molecule. For example, chloramphenicol has an aqueous solubility of 2.5mg/ml, but chloramphenicol sodium succinate, a prodrug, has an aqueous solubility of lOOmg/ml. Hydantoins also possess low aqueous solu-bilites that result in low and variable availability and precipitation following injection. In an effort to increase the aqueous solubility of phenytoin, Stella et prepared the ethyl and triethylamine esters... 

The anticonvulsant drug phenytoin (5,5-diphenylhy-dantoin) is sparingly soluble in water (0.02mg/mL) and is therefore formulated as sodium enolate for intravenous or intramuscular injections. The solvent is a mixture of 40% propylene glycol, 10% ethanol and 50% water and the pH of the solution is alkaline (pH 12), due to the weak acidity... 

FIGURE 41.13 Phosphate esters of cUn-damycin and of 3-hydroxymethyl-phenytoin (as sodium salts) are freely soluble in water and allow painless injections. 

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