Thrombophlebitis, intravenous injection

Local irritation can produce severe pain after intramuscular injection and thrombophlebitis after intravenous injection. Renal toxicity, including interstitial nephritis and even tubular necrosis, has been demonstrated and has caused the withdrawal of cephaloridine from clinical use. 

Hypotension follows the intravenous injection of benzodiazepines, but is usually mild and transient (SED-11, 92) (56), except in neonates who are particularly sensitive to this effect (57). Local reactions to injected diazepam are quite common and can progress to compartment syndrome (SEDA-17, 44). In one study (58), two-thirds of the patients had some problem, and most eventually progressed to thrombophlebitis. Flunitrazepam is similar to diazepam in this regard... 

Cephalothin i.s absorbed poorly from the gastrointestinal tract and must be administered parcntcrally for. systemic infections. It is relatively nontoxic and acid stable. It is excreted rapidly through tlie kidneys about 60% i.s lo.si within 6 hours of administration. Pain at the. site of intramuscular injection and thrombophlebitis following intravenous injection have been reported. Hypersensitivity reactions have been observed, and there is some evidence of cross-.scn.siti v-ity in patients noted previously to be penicillin sensitive. 

Cephapirin Sodium, Sterile, USP. Cephapirin (Cefa-dyl) is a scmisynthctic 7-ACA derivative released in the United States in 1974. It closely resembles ccphalothin in chemical and phannacokinetic properties. Like cephalothin, cephapirin is unstable in acid and must be administered par-enterally in the form of an aqueous solution of the. sodium salt. It is moderately protein bound (45 to 50%) in plasma and cleared rapidly by the kidneys. Cephapirin and cephalothin arc very similar in antimicrobial spectrum and potency. Conflicting reports concerning the relative tK-currence of pain at the site of injection and thrombophlebitis after intravenous injection of cephapirin and cephalothin are dirTicuIt to as.sess on the basis of available clinical data. 

Other adverse reactions that may be seen with administration of the cephalosporins are headache, dizziness, nephrotoxicity (damage to the kidneys by a toxic substance), malaise, heartburn, and fever. Intramuscular (IM) administration often results in pain, tenderness, and inflammation at the injection site Intravenous (IV) administration has resulted in thrombophlebitis and phlebitis. 

Although cephalosporins are more toxic than penicillin, they are well tolerated. Parenteral injection may cause pain when given intramuscularly and may cause thrombophlebitis when given intravenously. The oral cephalosporin administration causes diarrhea by altering the gut ecology. Hypersensitivity reactions are caused and are similar to those of penicillins. Cephaloridine causes nephrotoxicity, but presently available cephalosporins have less renal toxicity. 

Intravenous clarithromycin caused thrombophlebitis in four patients when it was given inappropriately as a rapid bolus injection instead of a short infusion the manufacturers have received other reports of similar reactions, even with infusions, but the incidence seems to be considerably lower than with erythromycin (12). In a prospective, non-randomized study, phlebitis occurred in 15 of 19 patients treated with intravenous erythromycin (incidence rate of 0.40 episodes/patient-day) and in 19 of 25 patients treated with intravenous clarithromycin (0.35 episodes/patient-day) (13). 

In several cases the special nature of a formulation will preclude dilution by an aqueous infusion fluid. Injectable products containing phenytoin, digoxin and diazepam may come into this category if they are formulated in a nonaqueous but water-miscible solvent (such as an alcohol-water mixture) or as a solubilised (e.g. micellar) preparation. Addition of the formulation to water may result in precipitation of the dmg, depending on the final concentration of the dmg and solvent. It has been suggested that precipitation of the relatively insoluble diazepam may account for the high (3.5%) incidence of thrombophlebitis which occurs when diazepam is given intravenously. 

Tile usefulness of amphotericin B is limited by a high prevalence of adverse reactions. Nearly 80% of patient-treated with amphotericin B develop nephrotoxicity. Fever headache, anorexia, gastrointestinal distress, malaise, and muscle and joint pain arc common. Pain at the site of injection and thrombophlebitis are frequent complications of intravenous administration. The drug must never be administered intramuscularly. The hemolytic activity of amphotericin B may be a consequence of its ability to Icadi cholesterol from erythrocyte cell membranes. 

Oral and parenteral do.sagc forms of ganciclovir are available. but oral bioavailability is poor. Only 5 to IO r of an oral dose is absorbed. Intravenous administration is preferable. More than 90% of the unchanged drug is excreted in the urine. Ganciclovir for injection is available as a lyophili/ed sodium salt for reconstitution in normal saline. S% dextrose in water, or lactated Ringer s solution. These. solutions are stningly alkaline (pH 11) and must be administered by slow, constant, intravenous infusion to avoid thrombophlebitis. 

CaNa2EDTA is available as edetate calcium disodium (calcium disodium versenate). Intramuscular administration of CaNa2EDTA results in good absorption, but pain occurs at the injection site consequently, the chelator injection often is mixed with a local anesthetic or administered intravenously. For intravenous use, CaNa2EDTA is diluted in either 5% dextrose or 0.9% saline and is administered slowly by intravenous drip. A dilute solution is necessary to avoid thrombophlebitis. To miiumize nephrotoxicity, adequate urine production should be established prior to and during treatment with CaNa2EDTA. However, in patients with lead encephalopathy and increased intracranial pressure, excess fluids must be avoided. In such cases, conservative replacement of fluid is advised, and intramuscular administration of CaNa2EDTA is recommended. 

Concentrated solutions of quinine may cause abscesses when injected intramuscularly or thrombophlebitis when infused intravenously. GI absorption of quinine can be delayed by antacids containing aluminum. Quinine and quinidine can elevate plasma levels of digoxin. Likewise, the alkaloid may raise plasma levels of warfarin. The action of quinine at neuromuscular junctions will enhance the effect of neuromuscular blocking agents and oppose the action of acetylcholinesterase inhibitors. Prochlorperazine can amplify quinine s cardiotoxicity, as can halo-fantrine. The clearance of quinine is decreased by cimetidine and increased by acidification of the urine and by rifampin. 

Propylene glycol and 20 % Cremophor EL have been compared as vehicles for diazepam [170] in view of the number of reports of thrombophlebitis associated with intravenous diazepam. The Cremophor vehicle caused significantly less postinjection thrombophlebitis possibly because it prevents the precipitation of the drug substance at the site of injection by its solubilizing effect. Ease of injection... 

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