P&T News: December 1996

Management of Intravenous Extravasations

Joan M Murhammer, RPh
Peer Review Status: Internally Peer Reviewed by Gerald H Clamon, MD and Amy J Becker, PharmD

Hyperosmolar solutions, vasopressor agents, and cytotoxic agents are the cause of the most frequently encountered wounds.6-8 Cytotoxic agents are classified as vesicants, irritants, and non-vesicants according to their potential to cause local toxicity.9, 10 Not all cytotoxic agents have vesicant potential. Non-vesicants do not generally cause a local reaction on administration. Irritants can produce pain, burning, or inflammation without necrosis when extravasated. Vesicants can result in progressive and severe tissue destruction, produce significant pain, and ultimately interfere with the affected extremity's function. Only a small number of these agents are actually responsible for severe tissue necrosis following infiltration. Noncytotoxic agents can also cause local tissue necrosis if infiltrated, but these are not categorized as vesicants, irritants, or non-vesicants. (Table 1).

The process of tissue destruction caused by the leakage of a vesicant into tissue is by nature indolent and progressive.4 The first sign of extravasation is usually pain and burning at the site of infiltration. This may be followed quickly over the next few hours by redness, swelling, and superficial skin loss. The induration may increase and necrosis may begin to develop one to four weeks later. There may be a lack of spontaneous healing and over the course of weeks to months, ulcers may become wider and deeper, sometimes involving underlying structures such as tendons and nerves.

Table 1. Irritation and Necrosis Potential of Medications # 1,2,4,9,10,13,15,27
	Cytotoxic Agents
Vesicants dactinomycin daunorubicin doxorubicin epirubicin (IND) idarubicin mechlorethamine mitomycin-C paclitaxel* vinblastine vincristine vinorelbine	Irritants carmustine cisplatin* dacarbazine etoposide fluorouracil liposomal doxorubicin mitoxantrone* paclitaxel** plicamycin streptozocin vinorelbine	Non-Irritants asparaginase bleomycin** cyclophosphamide cytarabine methotrexate thiotepa
Noncytotoxic Agents: (not classified as vesicants or irritants)
Antibiotics chloramphenicol gentamicin nafcillin vancomycin Miscellaneous aminophylline dextrose >10% diazepam phenytoin radiocontrast media total parenteral nutrition solutions (not LV. lipids) Electrolytes calcium chloride calcium gluconate potassium chloride sodium bicarbonate Vasopressors dopamine norepinephrine
# The vesicant or irritant properties of additional medications are not well-established in the literature. * Rare vesicant; more likely to occur if a large amount of concentrated solution is extravasated. ** Rare irritant IND = Investigational drug

The treatment of extravasation injuries includes pharmacologic measures, physiologic measures, and surgery. The infrequent occurrence of vesicant extravasation in clinical practice and restrictions imposed by ethical considerations of studying these adverse reactions in humans contribute substantially to the inadequacy of the currently available information. Studies have demonstrated varying degrees of effectiveness for a variety of extravasation treatments in several animal models. Because of anatomical, nutritional, and immunological differences, extrapolation from animals to humans has limitations. Clear measures to counteract tissue damage do not exist for vesicant agents. A variety of surgical and pharmacologic interventions used in treating vesicant extravasations has been anecdotally reported.

Unless complicated by cellulitis or infection, most non-vesicant extravasations result in nothing more than transient swelling, erythema, and mild to moderate temporary pain.2 Application of heat or cold and elevation of the affected extremity are the most common clinical interventions for non-vesicant infiltrations and usually provide adequate relief from symptoms.5 The majority of these infiltrations are recognized early, remain well localized, and heal spontaneously.32 Therapeutic interventions recommended for cytotoxic vesicant extravasation vary, depending on the agent. Unfortunately, prompt recognition and effective management of extravasation injury are hampered by unanswered questions about the nature of vesicant extravasations and lack of scientific data upon which to base treatment approaches.

Risk Factors
The most effective key to the management of extravasations is prevention. A thorough assessment of both the patient and the venous access, as well as related risk factors and knowledge of the vesicant potential of the drug, can do more to decrease morbidity than any of the purported antidotes.13 Various risk factors may increase the likelihood of an extravasation injury in some patients7 (Table 2). Patient-related risk factors-include the inability to communicate, vascular impairment, and obstructed venous drainage. The type of intravenous (IV) catheter used is important, as steel needles have been found to be associated with an extravasation twice as often as Teflon (plastic) catheters.7 Catheter size is also a factor, a small gauge catheter to permit ample blood flow around the catheter is recommended.7 The site chosen for IV injection is an additional risk factor. The most common sites involved in extravasations are those where superficial veins are most readily available. These include the dorsum of hand, forearm, and foot where there is relatively little soft tissue protection for the underlying tendons and other vital structures, and where serious consequences can result if an extravasation occurs.8 Large diameter veins in the midforearm are preferred for vesicant administration because an inadvertent extravasation in this area would result in less functional impairment.2 An infusion pump can increase the risk of extravasation. High maximum flow pressures are more likely to cause injury.7 When several cytotoxic agents are to be given, vesicant drugs should be administered first- because the patient is more aware of symptoms at the beginning of treatment and because vascular integrity decreases with sequential administration. The skill of the person performing the venipuncture and administering the drug may affect the risk of extravasation. Health care professionals must be proficient at performing venipuncture, identifying extravasation, and understanding exactly what measures to follow if it occurs.' Vesicant agents should be recognized and only given through a newly established line.4, 14 A vein that is punctured several times before an IV is established creates a situation that is more likely to lead to drug leakage.26 Continuous monitoring of the IV site during infusions is vital for early detection of extravasations and interruption of the infusion at the first sign of discomfort, altered infusion flow, or a local reaction.15

Table 2. Patient Risk Factors that May Increase the Likelihood of an Extravasation Injury6,7,16

• Infants, neonates, and comatose or sedated patients who are unable to communicate pain or discomfort
• Elderly patients, because of impaired vascularity
• Patients who undergo cardiac resuscitation, because of vasoconstriction or impaired circulation
• Patients with a history of peripheral vascular disease
• Diabetic patients
• Patients with Raynaud s disease
• Patients who have had previous radiation therapy at the IV site
• Patients who have received repeated IV therapy
• Patients with obstructed venous drainage following axillary surgery or radical mastectomy
• Superior vena cave syndrome (elevated venous pressure)
• Multiple attempts at venipuncture

General Treatment Approaches
A variety of interventions has been proposed in treating extravasations. These measures include thermal manipulation to alter temperature in the superficial skin, manipulating the pH of exposed tissue, and injecting antidotes into the affected area to reverse the action of the infiltrated agent or to otherwise interfere with the process of cell destruction.2 It is difficult if not impossible to forecast at an early stage whether the extravasation of a vesicant will eventually progress to ulceration.9 Only one-third of known vesicant extravasations will produce ulcers when conservative local management is used (ice and elevation).11,17 This means that there is a high likelihood of overestimating the true efficacy of putative local antidotes since the majority of patients will have a good outcome following a vesicant extravasation treated with only conservative therapy.11 Often, antidotes have been discussed in case reports which, while helpful, do not have rigorous controls needed for an unequivocal test of efficacy.11

Once the signs of an extravasation are noted, the intervention must be initiated immediately to prevent, or at least minimize, tissue damage. The first step is to stop the infusion.7 Immediate removal of any extravasated fluid using the original indwelling needle/catheter is strongly recommended in managing any vesicant extravasation.3,11,13 While evacuation is usually not possible due to blockage at the needle tip, it can occasionally be useful, with the recovery of substantial amounts of drug. The original needle/catheter can also be left in place to aid in the delivery of a local antidote, thereby eliminating the need for additional injections. Use of the original needle is especially important with mechlorethamine and vinca alkaloid (vinblastine, vinorelbine, vincristine) extravasations where highly effective antidotes are well known, and require close regional delivery if not direct contact with the extravasated drug for maximum efficacy.11

Pressure is always contraindicated, even slight pressure on an extravasated area could spread the vesicant agent over a much broader area. Elevation of the affected extremity is recommended to decrease swelling and increase net blood flow away from the area, thus increasing absorption and distribution of the drug away from the infiltrate site.11 For minor extravasations, elevation may be the only treatment that is necessary.16

The application of either warm or cold compresses to an extravasation site has been debated in the literature. Heat produces vasodilatation, which increases distribution and absorption of the drug from the extravasation site, minimizing the risk of local toxicity.5-7 Moist heat should be avoided because it can lead to maceration and necrosis. Cold promotes localization of the drug in the immediate area of the extravasation through vasoconstriction. Such localization may be desired if an antidote is to be injected into the area. For irritating drugs that require no antidote, initial cold will reduce inflammation and pain.6 Larson used conservative therapy with only limb elevation and intermittent cooling after extravasations in 119 patients.18 Eighty-nine percent of the patients wounds resolved spontaneously without further treatment. In 56 other patients who were initially treated with local antidotes before being referred to plastic surgery, 26 (46%) of the patients required surgery. This study included a variety of cytotoxic agents, including vincristine and mechlorethamine, where well-recognized effective local antidotes are known.

It has been shown that cold will actually increase the toxicity of vinca alkaloid extravasations and should be avoided.4, 7 On the other hand, the cytotoxicity of doxorubicin is significantly reduced by cold and increased by heat.4,7 Cold is preferred for all extravasations by cytotoxic agents, except for vincristine, vinblastine, vinorelbine, and etoposide. Intermittent cold is preferred because continuous application of ice to the area may cause an increase in tissue necrosis. Ice applications are readily available, simple, and nontoxic.4 The conservative approach to extravasations is endorsed by Larson because even proven local antidotes are not consistently effective.18 The application of ice, elevation, and close wound observation can minimize surgery and decrease morbidity.18

Pharmacologic Interventions (See Table 3 for dosage and administration information.)

Sodium Thiosulfate
Sodium thiosulfate, a sulfur nucleophile, is an effective antidote for mechlorethamine extravasation.9 It acts as an alternative substrate for alkylation by mechlorethamine to form nontoxic thioethers which can be excreted into the urine.'5 Mechlorethamine extravasation can produce severe and prolonged skin ulcers along with immediate pain and swelling as a result of rapid fixation to all tissues by alkylation of protein and DNA.5, 10, 15 Vein irritation is common with mechlorethamine administration and eventually may progress to a dark bluish-gray hyperpigmentation even in patients without an extravasation.10 There is a clinical report of an inadvertent intramuscular injection of 30 mg of mechlorethamine into a buttock. A 0.17 molar concentration of sodium thiosulfate injected into the site and an ice pack placed on the injection site for 12 hours provided complete protection of subsequent skin ulceration.23 Rapid use of sodium thiosulfate following mechlorethamine extravasation is vital for maximal efficacy because of the drug s rapid local toxic effects; thus, the antidote should be readily available whenever mechlorethamine is administered.'0'5 Experimental use of sodium thiosulfate has also been shown to successfully reduce dacarbazine skin toxicity.9 It is also a possible antidote for concentrated cisplatin (>0.4 mg/ml) extravasations because it inactivates cisplatin.9

Hyaluronidase
Hyaluronidase is an enzyme that breaks down hyaluronic acid, a major component of the normal interstitial barrier of the body s connective tissue. This breakdown results in enhanced drug distribution and absorption. Hyaluronidase has been shown to be useful in the management of the extravasation of commonly used IV fluids and medications because it reduces or prevents tissue injury by allowing the rapid diffusion of extravasated fluid. Even though the irritating material is spread over a large area, tissue reaction is minimized due to rapid absorption and dilution in tissue fluids.9, 16, 24 Hyaluronidase has been anecdotally reported to be successful in preventing extravasation-induced tissue injury from 10% dextrose, parenteral nutrition, calcium and potassium solutions, aminophylline, radiocontrast media, and natcillin.26, 27 Hyaluronidase has been shown to significantly increase the skin ulceration from doxorubicin extravasations and to have no benefit for mitomycin and mechlorethamine extravasations.11 Hyaluronidase and warm compresses have been shown to be effective in decreasing the toxicity of vinca alkaloid extravasations.3,5,11,15 Vinca alkaloids (vincristine, vinblastine, and vinorelbine) are known vesicants which produce pain and necrosis following extravasation. They typically produce pain, erythema, and localized swelling within minutes.11 Skin blisters form after several days and evolve slowly over weeks to necrotic ulcers.15 Healing may eventually occur even though neurologic sequelae may remain. Tingling, paresthesias, and sensory deficits at the site may be permanent.15

Timely administration is a key factor in achieving positive results with hyaluronidase. Treatment should occur immediately (< 1 hour) after infiltration to be most effective.25 Hyaluronidase is remarkably free of side effects and rarely causes allergic reactions (urticaria).24, 26 It should not be injected into acutely inflamed or cancerous areas because there is the potential danger of spreading infection or possibly increasing the invasiveness or metastasis of malignant tumors. Injecting hyaluronidase at a different site from the area of infection does not worsen the infection.8

Phentolamine
Norepinephrine and dopamine are vasopressors that when extravasated cause circulation to the area to become impaired through their strong vasoconstrictive action. If not corrected, tissue damage may be severe enough to cause peripheral ischemia and gangrene, necessitating skin grafts and occasional extremity amputation.28 The extravasation site will appear cold, hard, and pale. Phentolamine is an alpha-adrenergic blocking agent which causes vasodilatation, thereby decreasing the local vasoconstriction and ischemia, and subsequently restoring circulation.16 Local administration of phentolamine may prevent or significantly decrease the degree of damage from vasopressor extravasations. The effectiveness of phentolamine can be seen immediately with a dramatic change in local skin color and temperature.28 It should be administered as soon as possible or at least within six to twelve hours of the extravasation.16, 28

Dimethyl Sulfoxide
Dimethyl sulfoxide (DMSO) is a solvent that can penetrate tissues when applied topically to the skin. It has been evaluated for the management of extravasations because of its potent free-radical scavenging properties and possibly its ability to speed up the removal of extravasated drugs from the tissues.11 The application of DMSO topically with cooling has been shown effective at reducing skin ulcerations due to doxorubicin.3, 22 Olver used DMSO topically in 20 patients with doxorubicin extravasations.22 DMSO was applied every six hours for 14 days and no injuries progressed to ulcers. Patients experienced mild burning, skin scaling, and an unpleasant garlic breath odor. Bertilli used DMSO in 75 patients with extravasations of various cytotoxic agents ( including 44 patients with extravasations due to mitoxantrone, cisplatin, or ifosfamide, which rarely cause ulceration).3 DMSO was applied every eight hours for seven days and ice packs were applied for one hour three times a day for three days. Only one extravasation (epirubicin) progressed to an ulceration; skin necrosis was avoided in all other patients. Tolerance and compliance were good.

Corticosteroids
It has been theorized that the anti-inflammatory effects of corticosteroids can ameliorate the effects of vesicant extravasations. Corticosteroids have been advocated in a number of clinical reports for the treatment of doxorubicin extravasations on the basis of their purported positive effect on the inflammatory component of localized injuries.9 Based on this reasoning, they have been widely used; however, histologic studies have shown that inflammation is not prominent in the etiology of tissue necrosis.4, 9 Corticosteroids have been shown to be of limited value in the treatment of doxorubicin extravasations.19 When high doses or multiple injections of hydrocortisone were given, they significantly increased doxorubicin and vincristine skin ulcers in experimental settings.11,14 Corticosteroids inhibit the biosynthesis of collagen; therefore, caution must be used when employing them to treat extravasations.4,19 However, if a single injection of low dose (50 mg) hydrocortisone is administered, it should not increase doxorubicin soft tissue damage.11 Hydrocortisone is no longer suggested as a local antidote for extravasation in the prescribing information for doxorubicin (Adriamycin[R]).20

Miscellaneous Pharmacologic Interventions
Sodium bicarbonate has been proposed as an antidote, primarily for doxorubicin extravasation. Manipulation of local pH by injection of sodium bicarbonate at the extravasation site has been postulated to decrease the cellular uptake of doxorubicin and increase its removal from the area.9 A number of studies in animals have described no antidotal efficacy with sodium bicarbonate used for doxorubicin extravasations, and in fact studies in mice have shown that sodium bicarbonate increases doxorubicin skin toxicity.5, 11, 21 The use of sodium bicarbonate is discouraged because of the potential for the drug itself to produce tissue necrosis when extravasated.5, 9

Doxorubicin releases endogenous histamine and catecholamines following administration.11 Antihistamines have not been effective as local antidotes to experimental doxorubicin skin ulcers.11 Isoproterenol was effective in treating rat skin toxicity induced by doxorubicin, but neither isoproterenol nor propranolol was effective in other animal models.11 Because of divergent findings with the beta-adrenergic agents, and the lack of efficacy for antihistamines, there does not appear to be a role for these agents in managing extravasations.11

Surgery
Referral to a plastic surgeon is often necessary when treatment fails to prevent the progression of an extravasation to ulceration.6 Early surgical referral for large, painful lesions may dramatically help mitigate subsequent tissue damage and can help to spare the involvement of important subcutaneous neural, vascular, and motor structures. Early intervention is particularly relevant to vesicant extravasations on the dorsum of the hand.11 However, since as few as one-third of all vesicant extravasations will ulcerate, the routine use of excision is obviously not warranted.11 One of the best clinical indicators for subsequent surgery is reported to be pain at the extravasation site one to two weeks following the event.17 Once painful necrosis appears, surgical debridement is indicated. If debridement is not performed, the necrotic process will almost always progress.21 For example, doxorubicin has been reported to be trapped in skin tissues for several months following serious extravasations. It is hypothesized that active drug is sequentially released from dying cells and is taken up again by adjacent healthy cells.11

Table 3. Literature Supported Extravasation Antidotes/Treatments 9,11,13,15,25-28
Medication	Antidote/Treatment	Method of Administration
Mechlorethamine Cisplatin*	0.17 M Sodium thiosulfate	Dilute 1.6 ml of 25°/. sodium thiosulfate injection with 8.4 ml of sterile water for injection to make a 0.17Msolution. Injeet2 ml into site for each I mg of mechlorethamine or 100 mg of cisplatin extravasated.
Mitomycin-C	Dimethyl sulfoxide 50% (w/v)	Apply 1.5 ml to the site every 6 hours for 14 days. Allow to air-dry; do not cover.
Doxorubicin Daunorubicin	Cold compresses and Dimethyl sulfoxide 50% (w/v)	Apply immediately for 30 to 60 minutes, then alternate off/on every 15 minutes for 1 day. Apply 1.5 ml to the site every 6 hours for 14 days. Allow to air4ry; do not cover.
Vinblastine Vincristine Vinorelbine Etoposide*	Warm compresses and Hyaluronidase	Apply immediately for 30 to 60 minutes, then alternate off/on every 15 minutes for 1 day. Inject 150 units (1 ml) into the needle. If needle removed, inject subcutaneously around the site.
Dopamine Norephinephrine	Warm compresses and Phentolamine	Apply immediately for 30 to 60 minutes, then alternate off/on every 15 minutes for I day. Reconstitute 5 mg with 5 ml of 0.9% sodium chloride to make a I mg/ml solution. Inject 0.5 to I ml of the solution subcutaneously around the site until the entire site is infiltrated (generally to 10 ma) changing the needle between each injection. If the IV access device was left in place, the total dose may be injected directly through the needle.
Dextrose >10% Calcium salt solutions Total parenteral nutrition Nafcillin Potassium salt solutions	Hyaluronidase	Reconstitute a 150 unit vial with 1 ml of 0.9% sodium chloride. Further dilute 0.1 ml of this solution with 0.9% sodium chloride to a volume of 1 ml resulting in a 15 units/ml final concentration. A 25 gauge needle is used to inject 0.2 ml of solution subcutaneously or intradermally in 4 or 5 separate sites around the extravasation site. If the IV catheter was left in place, 1 ml of the solution should be injected through it. The needle should be changed after each injection.
Medications, other (paclitaxel**)	Cold Compresses	Apply immediately for 30 to 60 minutes, then alternate off/on every 15 minutes for 1 day.
* Treatment not typically recommended unless a large amount of highly concentrated solution is extravasated. **No specific treatment guidelines established; anecdotal information supports the use of cold compresses.

Conclusions
There is considerable controversy regarding the most appropriate management of extravasation injuries. Severe tissue damage is possible, yet it occurs infrequently. Foremost in the overall management of extravasation injury is the recognition that prevention is the most effective way to reduce the incidence of this problem. Vesicant agents should be given by experienced personnel with careful patient observation. The patient's cooperation should be solicited, if possible, so that pain or adverse sensations are immediately reported. The amount of damage is directly related to the amount of drug extravasated, so early detection and cessation of the infusion are paramount to mitigating tissue damage. Consideration should be made to factors that increase the risk of extravasation so areas of compromised circulation and areas of underlying tendons and nerves are avoided.

There are few clear-cut interventions in the case of extravasations. Only a few antidotes have proven effective in decreasing vesicant drug extravasation injury.15 In fact, some interventions may lead to increased ulceration. In cases where there is no evidence to support local antidote treatment, conservative therapy with elevation and cold (unless contraindicated) remain' the best option. When there is a proven antidote available (Table 3), the original IV needle/cannula should be left in place and optimally the antidote should be administered immediately.4 In order to prevent further damage, surgical consultation should be initiated early in cases where pain and induration are unresponsive to conservative management.4 '5 A systematic approach to the treatment of extravasation is recommended, and should include the elements of early detection to halt further drug delivery, conservative treatment, use of proven antidotes, and, when necessary, early surgical excision.'5

References

1. Hosp Pharm 1987; 22:125-31.

2. Oncol Nurs Forum 1995; 22(1):57-67.

3. J Clin Oncol 1995; 13(11):2851-S.

4. Semin Oncol Nurs 1987; 3(2):128-32.

5. Hosp Pharm 1986;21:784-9.

6. Hosp Formul 1988; 23:380-4.

7. J Intraven Nurs 1990;13(2):1114.

8. Surg Clin North Am 1979; 59(5):939 49.

9. Drug Saf 1995; 12(4):245-55.

10. Cancer Treat Rev l980;7:17-27.

11.. Blood Re l990;4(1):41-60.

12. Am J Surg 1979; 137:497-506.

13. Cancer Chemotherapy Guidelines. Recommendations for the Management of Vesicant Extravasation Hypersensitivity, and Anaphylaxis. Pittsburgh: Oncology Nursing Society, 1992.

14. MCN 1987; 12:23.

15. Cancer Chemotherapy Handbook. 2~ Editio4 East Norwalk: Appleton & Lange; 1994:109-18.

16. Drug Intell Clin Pharm 1983; 17:713-7.

17. Cancer 1983; 49:1796-9.

18. Plast Reconstr Surg 1985;75(3):397-402.

19. Cancer Chemother Pharmacol 1980; 5: 17-20.

20. Pharmacia. Adriamycin package insert. Dublin, OH: 1994 December.

21. J Clin Oncol 1987; 5(7): 1116-26.

22. J Clin Oncol 1988;6(11):1732-5.

23. Cancer 1980; 45:2225-6.

24. Surgery 1953; 33:91742.

25. Neonatal Net 1992: 11(6):103-5.

26. Infusion 1981; 5(4):77-9.

27. Am J Dis Child l981; 135:1113-4.

28. Crit Care Nurse 1991;11(10):58-61.

Pharmacy and Therapeutics Subcommittee Actions

DRUGS ADDED TO STOCK

• BICALUTAMIDE Tablets: 50 mg Bicalutamide (Casodexe - Zeneca) is an antiandrogen indicated for U# in combination with a luteinizing hormone-releasing hormone analogue for the treatment of advanced prostate cancer.
• DILTIAZEM Sustained-Release Capsula: 120 m6 180 m6 240 m& 300 m6 360 mg The Tiazac. (Forest) brand of "stained-release diltiazem provides a cost, effecting alternative to Cardizem CDe (HMR).
• ETHINYL ESTRADIOL WIT H NORGESTIMATE Tablets Ethinyl estradiol with norgestimate tablets (Ortho-Cyclan[R] and Ortho- Tri-Cyclen[R] - Ortho) are used for contraception and the regulation of abnormal uterine bleeding.
• FELODIPINE Sustained-Release Tablets: 2.5 m6 5 ma, 10 mg Felodipine (Plendi l ER° - Astra Merck) is a second-generation dihydropyridine calcium channel blocking agent indicated for the treatment of essential hypertension.
• FERUMOXIDES Injection: 5 ml Ferumoxides injection (Feridex - Berlex) is indicated as an adjunct of MRI to enhance the detection and evaluation of lesions of the liver.
• FLUTICASONE Nasal Spray: 50 mcg per actuation Fluticasone nasal spray (Flonase. - GlaxoWellcome) is a glucocorticoid indicated for the management of seasonal and perennial allergic rhinitis.
• IBUTILIDE Injection: 0.1 mg per ml Ibutilide (Corvert. - Pharmacia & Upjohn) is an antiarrhythmic drug with predominantly class 111 properties. It is indicated for the rapid conversion of recent onset atrial fibrillation or atrial flutter to sinus rhythm NOTE: Due to the agent's potential proarrhythmic effects and the need for cardiac monitoring and resuscitative equipment. the use of ibutilide is restricted to Cardiology.
• NILUTAMIDE Tablets: 50mg Nilutamide (Nilandron[R] - HMR) is an antiandrogen indicated for use ID combination with surgical castration for the treatment of metastatic prostate cancer.
• NITROGLYCERIN Topical Ointment: 0.2% This extemporaneously compounded preparation is used for the treatment of chronic anal fissures.
• OLANZAPlNE Tablets: 5 ma, 7.5 mL 10 mg Olanzapine (Zyprexa[R] - Lilly) is an antipsychotic aged NOTE: The use of olanzapine is restricted to Psychiatry.
• PENTOSAN POLYSULFONATE SODIUM Capsules: 100 mg Pentosan polysulfonate sodium (Elmirone - Baker Norton) ir indicated for the relief of bladder pain or discomfort associated with interstitial cystitis.
• REMIFENTANIL Injection: 1 mg, 2 mg, 5 mg Remifentafnil injection (Ultiva[R] - GlaxoWellcome) is an anesthetic agent. NOTE: The use of remifentanil ~ restricted to prescribing by Anesthesia.
• SODIUM PHENYLBUTYRATE Tablets: 500 mg Oral Powder 250 grams Sodium phenylbutyrate (Buphenyl[R].. - Ucyclyd) is indicated as adjunctive therapy within dietary restriction in tine management of patients with urea cycle enzyme deficiencies.
• TERBINAFINE Tablets: 250 mg Terbinafine (Lamisil - Sandoz) is a fungicidal agent indicated for of onychomycoses of the toenail and fingernail. It is significantly less expensive than itraconazole.

ADDITIONAL ACTIONS

• ALTEPLASE INJECTION A 50 mg vial was added to stock
• AMOXICILLIN/CLAVULANATE The 200 mg and 400 mg chewable tablets and the 400 mg per 5 ml oral suspension were added to ~* to provide twice-daily dosing. The three times-per-year formulations will be deleted in January 1997. See the November 1996 issue of the P&TNews for the dosage conversion chart.
• BUPIVACAINE 0.7S% INJECTION A 10 ml vial has been added to stock.
• CIMETIDINE TABLES The 800 mg tablets. were added to stock.
• DEXTROAMPHETAMlNE SUSTAINED-RELEASE CAPSULES The 5 mg strength was added to stock.
• FOSINOPRIL TABLETS The 40 mg strength was added to stock.
• HYDROCORTISONE RECTAL SUPPOSITORIES 25 mg suppositories (Anusol-HC[R], hemorrhoidal-HC) were added to stock.
• ZIDOVUDINE 300 MC TABLETS This product, designed for twice daily dosing, was added to stock.
• NOTE: The coat following each brief monograph is the UIHC acquisition cost.

DRUGS DELETED FROM STOCK

• CHARCOAL CAPSULES Deleted due to low use. Charcoal oral suspension in aqueous or sorbitol solutions are available.
• CHYMOTRYPSIN OPHTHALMIC SOLUTION (Catarase[R]) Discontinued by the sole manufacturer.
• CYCLOSPORINE 50 MC CAPSULES This strength was discontinued by the sole manufacturer. The 25 mg and 100 mg capsules are still available.
• DEXAMETHASONE NASAL INHALER Discontinued due to low use and the availability of safer products. Beclomethasone and fluticasone nasal sprays are available.
• FLUTAMIDE CAPSULES Discontinued due to the availability of nilutamide and bicalutamide tablets.
• ISRADIPINE CAPSULES Discontinued due to the availability of amlodipine and felodipine.
• SLO-PHYLLIN- GYROCAPS The 125 mg strength was discontinued by the manufacturer. Numerous other sustained-release theophylline products are available.
• SUFENTANIL INJECTION Discontinued due to low use. Fentanyl, alfentanil and remifentanil injections are available.
• TRIFLUOPERAZINE 10 MO/ML ORAL SYRUP Not available from any manufacturer. Trifluoperazine tablets are available.

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