P&T News: June 1995, Vol. 15, No. 12

Ofloxacin to Become UIHC's Primary Quinolone Antibiotic

Karen M. Sedlacek, Pharm.D.
Peer Review Status: Internally Peer Reviewed by Bradley E. Britigan, M.D., Professor and Director, Division of Infectious Diseases, Department of Internal Medicine

Background
The introduction of quinolone antimicrobial agents has been a major advance in the treatment of bacterial infection because of their potential to treat serious infections by the oral route.1 The first quinolone, nalidixic acid, was introduced in 1962 for the treatment of urinary tract infections. Nalidixic acid suffered from a narrow spectrum of activity, extensive metabolism, and rapid development of drug resistance.2,3 By altering the molecular structure of nalidixic acid, the newer fluoroquinolones were developed. The fluoroquinolones [e.g., ofloxacin (Floxin03' ) and ciprofloxacin (Cipro(R)) have more desirable properties, including better oral absorption, enhanced antimicrobial activity, an improved pharmacokinetic profile, and limited adverse effects.2

Mechanism of Action and Spectrum of Activity
Quinolones exhibit their bacteriocidal mechanism by inhibiting DNA gyrase during DNA replication. Because DNA gyrase plays an important role in maintaining the supercoiled DNA, the quinolones are also bacteriocidal against nonreplicating organisms.4 There is evidence for additional mechanisms by which quinolones exert their bacteriocidal effect. This secondary mechanism does not require protein or RNA synthesis and is active against non-dividing bacteria.5

The quinolones have a wide spectrum of activity against both gram-positive and gram-negative pathogens. They have bacteriocidal activity against most species of bacteria, with minimal bacteriocidal concentrations typically equal to or two-fold higher than the minimum inhibitory concentrations (MIC).6,7 The breakpoint for susceptibility to ofloxacin is an MIC less than or equal 2 ug/ml, while an MIC greater than or equal to 8 ug/ml is considered resistant. In contrast, the breakpoints for susceptibility and resistance to ciprofloxacin are less than or equal to 1 ug/ml and greater than or equal to 4 ug/ml, respectively.2,8

Quinolones have good activity against Staphylococcus aureus and other staphylococcal species, but are less potent against streptococcal and enterococcal species.9 Ofloxacin (MICs 0.12 to 1 ug/ml) and ciprofloxacin (MICs 0.06 to 2 ug/ml) show similar activity against staphylococcus; their activity is unaffected by methicillin suspectibility of S. aureus. 10 MIC90 values of 1 to 4 ug/ml have been reported consistently with ofloxacin against streptococci essentially the same as with ciprofloxacin. Against enterococci, the MIC90 of both drugs are in the intermediate to resistant range (2.0 to 8.0 ug/ml).2 Even though the MIC90 values are almost identical for gram-positive cocci, ofloxacin is theoretically superior to ciprofloxacin against gram-positive cocci in tissue due to its pharmacokinetic advantages (greater bioavailability and higher serum concentrations). 11

In general, quinolones exhibit excellent activity in vitro against members of the family Enterobacteriaceae, fastidious gram-negative bacilli including Haemophilus influenzae, and gram-negative cocci, including Neisseria gonorrhoeae, Neisseria meningitidis, and Moraxella catarrhalis.9 The activity of quinolones against Pseudomonas species is declining. Against anaerobic species, activity tends to be fair to poor and quinolones have no activity against Candida albicans.6,9 Ofloxacin and ciprofloxacin are active in vitro against Mycobacterium tuberculosis and atypical mycobacteria, but potency against Mycobacterium avium complex is fair to poor.9 Intracellular pathogens such as Chlamydia, Mycoplasma, and Legionella species are susceptible.7

Pharmacokinetic Properties
The bioavailability of ofloxacin after oral administration is 95 to 100%, while the bioavailability of ciprofloxacin after oral administration is only 63 to 69%.8,12 Times to peak serum concentrations are similar and usually range from 1 to 2 hours. Food delays the time to maximum concentration but does not alter the extent of quinolone absorption.3,l2 However, the concomitant ingestion of milk, yogurt, or other liquid dairy products high in calcium content can significantly reduce the extent of absorption; therefore, concurrent consumption of these products should be avoided. 13 After intravenous (IV) dosing, ofloxacin exhibits a pharmacokinetic profile similar to that seen after oral dosing, supporting the interchangeability of both dosage forms in therapy.2 Protein binding is low (25 to 30%) for both agents.

The quinolones are widely distributed throughout the body. They rapidly penetrate neutrophils and alveolar macrophages, and intracellular concentrations are extremely high. The combination of a large volume of distribution and a low level of protein binding results in a wide distribution of the quinolones to various body fluids and tissues.13 The drug concentrations are very high in urine, high in kidney and prostate tissue, but lower in prostatic fluid. In the gastrointestinal tract, fecal concentrations are very high for all quinolones. Peak drug concentrations in saliva and bronchial secretions tend to be lower than those in serum, but concentrations in lung tissue substantially exceed serum concentrations.6 Studies on diffusion into the biliary tract show that the quinolones are concentrated in both the gallbladder wall and the bile. In addition, these drugs penetrate into the peritoneum and mesenteric Iymph nodes. Concentrations of the quinolones in bone are around 30 to 60% of concomitant serum concentrations.l3 The ability for ciprofloxacin to penetrate the cerebral spinal fluid (CSF) is low while ofloxacin achieves approximately 40% of the serum level in the CSF.6,9

Hepatic metabolism plays a minor role in the excretion of ofloxacin (<5%), while approximately 12 to 20% of a dose of ciprofloxacin is metabolized.4,9 Ofloxacin is primarily excreted renally,4 and doses must be adjusted when the creatinine clearance falls below 50 ml/min. Terminal half-lives of elimination are about 5 hours for ofloxacin and 3 to 4 hours for ciprofloxacin, permitting twice daily dosing for most indications.9

In elderly persons, the quinolones have been associated with higher serum concentrations, reduced volume of distribution, prolonged elimination half-life and/or decreased total body clearance. Dosage adjustments in elderly patients are not necessary unless creatinine clearance falls to levels associated with renal impairment. 13

Clinical Applications

Urinary Tract Infections and Prostatitis
The quinolones achieve high concentrations in urine, and the urinary drug concentrations exceed the MICs for both gram-negative and gram-positive urinary tract pathogens.9 For the treatment of uncomplicated urinary tract infections, ofloxacin (200 mg every 12 hours) has been highly effective (92 to 100%) and comparable to trimethoprim-sulfamethoxazole in double-blind studies in which patients were treated for 3 to 14 days and in unblinded studies. For complicated urinary tract infections, treatment with quinolones, usually for 7 to 10 days, was similar or in several instances superior to treatment with trimethoprim-sulfamethoxazole, B-lactam antibiotics, or other drugs, including parenteral agents, in their ability to eliminate bacteriuria. Quinolones have been effective for the treatment of complicated urinary tract infections caused by Pseudomonas aeruginosa and other bacteria resistant to multiple agents. P. aeruginosa is eradicated in about 70% of patients with complicated urinary tract infections. Bacterial resistance to quinolones has been seen more commonly in complicated urinary tract infections, particularly in those infections caused by P. aeruginosa.6,9,l2

Quinolones should not be used in the treatment of uncomplicated urinary tract infections in which other less expensive alternatives are appropriate, based on culture and sensitivity information. However, the quinolones are an excellent choice for patients with recurrent UTIs, for those with infections caused by resistant organisms, or for patients who cannot tolerate trimethoprim-sulfamethoxazole or cephalosporins. 14

Quinolones have been shown to penetrate into prostatic tissue in concentrations approaching or exceeding by several fold those in serum.9 Ofloxacin (300 mg every 12 hours) has been shown to be successful in eradicating the organisms that cause acute or chronic prostatitis. Infections caused by gram-positive cocci and P. aeruginosa may be more difficult to cure than Escherichia cola or other gram-negative bacterial prostatitis. Ofloxacin is the only available quinolone that is indicated for Chlamydia trachomitis infections, which may be involved in chronic prostatitis.4

Sexually Transmitted Diseases
Strains of Neisseria gonorrhoeae are very sensitive to the quinolones, making these agents very useful for patients with uncomplicated gonococcal infections.2 Only ofloxacin has received FDA approval for the treatment of nongonococcal urethritis caused by C. trachomatis (300 mg every 12 hours) and may be useful as an alternative to doxycycline therapy. Quinolones are not indicated in the treatment of syphilis because Treponema pallidum is resistant. 12,14

Lower Respiratory Tract Injections
Ofloxacin has been shown to achieve concentrations in bronchial secretions approaching those in serum, and concentrations in lung tissue exceed those in the serum. Certain respiratory pathogens (Haemophilus influenzae, Moraxella catarrhalis, and Klebsiella pneumoniae) are highly susceptible to ofloxacin, while other organisms (Mycoplasma pneumonias, Pseudomonas aeruginosa, Staphylococcus agrees, Legionella spp., and Mycobacterium tuberculosis) are only moderately susceptible. Least susceptible of the common respiratory pathogens is Streptococcus pneumoniae.9

Both ofloxacin and ciprofloxacin have demonstrated similar in vivo efficacy in the treatment of bronchitis or pneumonia caused by susceptible pathogens, and have comparable results to other traditional agents.6,12 They have less microbiologic activity against pneumococci than B-lactam antibiotics or erythromycin, thus therapy should not rely on quinolones as the sole therapeutic agent. In hospitalized patients, who tend to develop the more resistant gram-negative lung infections, treatment with a quinolone antibiotic is more valuable.1 Currently, the quinolones are not the therapy of choice in community acquired pneumonias.6 Exacerbation of pulmonary infection due to P. aeruginosa in patients with cystic fibrosis has been successfully treated with ofloxacin; however, many of the P. aeruginosa strains have become resistant.4 Ofloxacin and ciprofloxacin inhibit M. tuberculosis and M avium-intracellulare (MAI) and offer the potential for use in drug-resistant mycobacterial infection with these organisms.15

Generally, the quinolones should not be agents of first choice in the treatment of acute sinusitis. Similarly, these agents should not be used for otitis media, since they are not currently recommended for use in pediatrics.

Bone and Joint Infections
The concentration of quinolone in infected and uninfected bone is generally 30 to 60% of the levels in serum.4 Oral agents are beneficial due to the need for prolonged therapy in the treatment of acute and chronic osteomyelitis in adults, particularly when caused by gram-negative bacilli. Clinical cure rates of 75 to 95 % have been reported with ofloxacin and ciprofloxacin, although development of resistance in infections caused by P. aeruginosa, S. agrees, and S. marcescens was associated with failure.6,7 Ciprofloxacin is currently the only quinolone FDA-labeled for bone and joint infections. 12

Skin and Skin Structure Infections
Infected pressure and ischemic ulcers, subcutaneous abscesses, cellulitis and wound infections have been treated with quinolones.7 The broad antimicrobial spectrum of the quinolones and their penetration into soft tissues have suggested the potential for treatment of these infections, although lesser potency against gram-positive bacteria and anaerobes makes them less than ideal single agents.9

Moderate efficacy has been demonstrated in the treatment of skin and soft tissue infections, and the quinolones appear comparable to parenteral cefotaxime in the treatment of these infections caused by aerobic gram-negative bacilli.9 The most common organisms causing cellulitis and wound infections are streptococci and staphylococci. Quinolones have reduced activity against these organisms, and comparisons with first line agents have not been reported. 6,7

Adverse Drug Reactions
The quinolones are generally well tolerated and do not cause serious or life threatening adverse reactions.4 Gastrointestinal symptoms have been reported most often (3 to 6%) and have included, in descending order: nausea, abdominal discomfort, vomiting and diarrhea. Symptoms referable to the central nervous system have been the next most common effect (1 to 4%) and have included: headache, dizziness, agitation, and sleep disturbances.6 Severe neurotoxic adverse events are rare, but include psychotic reactions, hallucinations, depression, and grand-mal seizures, which are reversible on cessation of therapy.l6 Caution should be used in therapy of patients with a history of seizures. Allergic reactions have been infrequent (0.5 to 2%) and most often manifest as rash or pruritus.6 With parenteral ofloxacin and ciprofloxacin, infusion site reactions are not uncommon. 12

Because of cartilage erosions in the weight bearing joints of young animals given quinolones, routine use of these agents in children or pregnant or nursing patients is not recommended.6 The potential exists for tendon rupture in patients receiving quinolones and the FDA has required the prescribing information for all quinolones to carry this warning.

Drug Interactions
Multivalent cations including aluminum, magnesium, and calcium, found in antacids and mineral supplements, reduce the absorption of orally administered quinolones, possibly through the formation of nonabsorbable chelates.6 Administration of antacids within two hours before or after the administration of the quinolones should be avoided. Concomitant administration of ciprofloxacin or ofloxacin with sucralfate, iron and zinc-containing products should also be avoided.3 Ferrous sulfate and multivitamins containing zinc have been described as significantly reducing the bioavailability of ofloxacin and ciprofloxacin. Sucralfate (which contains approximately 200 mg aluminum/gram) also diminishes the absorption of ciprofloxacin and a comparable effect could be expected with ofloxacin. Histamine2 receptor antagonists such as cimetidine have not been shown to alter quinolone absorption. 13

Ciprofloxacin decreases the clearance of theophylline, most likely through the inhibition of the cytochrome P-450 system. This results in increased theophylline serum half-life and elevated serum theophylline concentrations.l3 Similar to the interaction with theophylline, ciprofloxacin also inhibits caffeine clearance. This results in a three-hour prolongation of the serum half-life of caffeine. Ofloxacin does not significantly impair the clearance of either of these agents.4

Other possible interactions include potentiation of cyclosporine renal toxicity and augmentation of the anticoagulant effects of warfarin by quinolones;9 patients should be monitored frequently for these adverse effects.

Dosing Guidelines
Quinolone dosages generally range from 400 to 800 mg/day in a single or two divided doses for 3 to 14 days for patients with normal renal function (Table 1). Due to its complete oral absorption, ofloxacin is dosed the same for IV or oral use, and oral therapy should be instituted as soon as the patient is taking other medications orally. 12

Dosage adjustments need to be made for both ofloxacin and ciprofloxacin in patients with renal impairment. The usual dose for ofloxacin (po or IV) is 200 to 400 mg every 12 hours. With a creatinine clearance of 10 to 50 ml/ min, the dosing interval should be increased to every 24 hours. If the creatinine clearance falls to less than 10 ml/ min, one-half (100 to 200 mg) the usual dose should be used with a dosing interval of every 24 hours.l7 The usual dose for oral ciprofloxacin is 250 to .750 mg every 12 hours. When the creatinine clearance falls below 30 ml/min the dose should be changed to 250 to 500 mg every 18 hours.l8

Quinolone Status at UIHC
During the last few years, the Antibiotic Advisory Subcommittee (AAS) has periodically reviewed the use of quinolone antibiotics at UIHC. The antibacterial spectrum of activity, efficacy and safety have been evaluated. The microbiologic activity of ofloxacin and ciprofloxacin compare favorably, except ciprofloxacin's in vitro activity against P. aeruginosa is slightly better. However, the last several years have seen a progressive decrease in the susceptibility of P. aeruginosa isolates at UIHC to ciprofloxacin (70% susceptible in most recent survey). The AAS concluded that the slight difference in susceptibility between ofloxacin and ciprofloxacin is counterbalanced by differences in pharmacokinetic properties. Published literature indicates that ofloxacin provides superior gram-positive coverage, has fewer clinically significant drug-drug interactions, and superior bioavailability by comparison to ciprofloxacin. Success rates in clinical studies are similar for ofloxacin and ciprofloxacin when they are used to treat gram-negative bacterial infections. Therefore, the AAS determined these two drugs to be therapeutically equivalent. In April 1995, AAS recommended awarding a bid to the vendor of ofloxacin and designating that agent as the preferred quinolone antibiotic at UIHC.

Subsequently, the Pharmacy and Therapeutics Subcommittee confirmed the therapeutic equivalence of ofloxacin and ciprofloxacin and took the following actions to ensure the appropriate use of quinolones at the UIHC:

1. Replaced the currently available intravenous ciprofloxacin as a protocol drug with intravenous ofloxacin as a protocol drug with the following indications for use:

• Serious gram-negative infection with organisms documented to be resistant to aminoglycosides, third generation cephalosporins, and extended spectrum penicillins.
• Serious gram-negative infection in which there is an intolerance and/or a contraindication to aminoglycosides, third generation cephalosporins, and extended spectrum penicillins.

2. Identified those indications for which intravenous ofloxacin should NOT be used including:

• treatment of uncomplicated infections such as urinary tract infections in which other less expensive alternatives are appropriate based on culture and sensitivity information.
• treatment of infections where oral therapy is indicated or feasible.
• treatment of subacute bacterial endocarditis.
• as monotherapy in the treatment of febrile neutropenic patients.
• surgical prophylaxis regimens.
• treatment of serious systemic enterococcal infections.
• treatment of meningitis.
• treatment of outpatient-acquired pneumonia.

3. Added oral ofloxacin as an open formulary product, making it the oral quinolone of choice at the UIHC.

4. Retained oral ciprofloxacin on formulary as a protocol antibiotic for the following indications:

• Gram-negative osteomyelitis.
• Malignant external otitis.
• Mycobacterium avium-intracellulare (MAI).
• Infections with organisms with documented susceptibility to ciprofloxacin and resistance to ofloxacin.

Indications for which oral ciprofloxacin should NOT be considered are the same as for IV protocol ofloxacin with one addition: patients receiving theophylline therapy with oral ciprofloxacin may experience a significant increase in theophylline serum levels and significant toxicity.

Table 1. Quinolone Dosing Guidelines for UIHC Indications for Use 17, 18*
Disease State	Ofloxacin Oral	Ofloxacin IV (only until patient able to take oral therapy)	Ciprofloxacin Oral
UTI, uncomplicated	200 mg PO q12h x 3 to 7 days	---	---
UTI, complicated	200 mg PO q12h x 10 days	200 mg IV 12h	---
Prostatitis due to E. coli	300 mg PO q12h x 6 weeks	300 mg IV q12h	---
Uncomplicated gonorrhea	400 mg PO x 1 dose	---	---
Cervicitis/Urethritis due to N. gonorrhoeae and/or C. trachomatis	300 mg PO q12h x 7 days	---	---
Lower Respiratory Tract Infection	400 mg PO q12h x 10 days	400 mg IV q12h	---
Skin, Skin structure Infection	400 mg PO q12h x 10 days	400 mg IV q12h	500 to 750 mg PO q12h x 7 to 14 days (malignant external otitis)
Bone, Joint Infection	---	---	500 to 750 mg PO q12h x 4 to 6 weeks (gram-negative osteomyelitis)
Infectious Diarrhea	300 mg PO q12h x 3 days	---	---
Mycobacterium avium-intracellulare (MAI)	---	---	500 to 750 mg PO q12h (in combination with other anti-mycobacterial agents)
________ *For additional information consult manufacturer's prescribing information.

Summary
The Antibiotic Advisory and Pharmacy and Therapeutics Subcommittees have endorsed the replacement of ciprofloxacin with ofloxacin as the quinolone of choice due to similar antimicrobial spectrum, improved pharmacokinetic profile, limited adverse effects, and few drug interactions. Ofloxacin IV will become a protocol antibiotic for treatment of infections in which oral therapy is contraindicated or not feasible and in which there is resistance or contraindications to aminoglycosides, third-generation cephalosporins, and extended spectrum penicillins. Ciprofloxacin IV will no longer be stocked.

Oral ofloxacin will become the oral quinolone of choice. Its excellent oral absorption, tissue penetration, and long half-life allow ofloxacin to be used as oral replacement for parenteral therapy. Use as initial therapy or early replacement after initial parenteral therapy will result in considerable cost savings. These savings are generated both by decreased acquisition cost for oral versus parenteral therapy (one-sixth the cost), as well as decreased expense of preparation, administration, and monitoring of parenteral therapy. Earlier discharge from the hospital due to conversion to oral therapy can also magnify cost savings.

Oral ciprofloxacin will remain on formulary as a protocol antibiotic for gram-negative osteomyelitis, malignant external otitis, MAI, and documented susceptibility to ciprofloxacin accompanied by resistance to ofloxacin.

The transition from ciprofloxacin to ofloxacin will begin on July 1, 1995. After July 1, 1995, patients already receiving IV or oral ciprofloxacin will be allowed to complete their course of therapy; new orders for IV ciprofloxacin will need to be rewritten for IV ofloxacin. In addition, after July 1, 1995, oral ciprofloxacin and IV ofloxacin will become protocol drugs, and a completed protocol antibiotic form will be required for these agents to be dispensed. Table 2 provides dosage conversion guidelines.

Table 1. Quinolone Dosing Guidelines for UIHC Indications for use 17, 18*
Ordered	Approximate Equivalent Dosage
Ciprofloxacin oral 250 mg q12h Ciprofloxacin oral 500 mg q12h Ciprofloxacin oral 750 mg q12h Ciprofloxacin injection 200 mg q12h Ciprofloxacin injection 400 mg q12h	Ofloxacin oral 200 mg q12h Ofloxacin oral 300 to 400 mg q12h Ofloxacin oral 400 mg q12h Ofloxacin injection 200 mg q12h Ofloxacin injection 400 mg q12h

References

1. Hosp Formal. 1992; 27:509-16.

2. InfectControlHospEpidemiol. 1991; 12:549-57.

3. Clin Pharmacokina. 1988; 22:32-46.

4. Clin Ther. 1992; 14:348-75.

5. Chemotherapy. 1991; 37(Suppl 1):2-13.

6. NEngl J Med . 1991; 324:3X4-94.

7. Pharmacotherapy. 1992, 12(6 Pt 2) 71S-85S.

8. EurJClinMicrobiolInfectDis. 1991, 10:267-74.

9. Cltn Microbial Rev. 1989; 2:378424.

10. JAndmicrob Chemother. 1988, 22(Suppl C):9-19.

11. ClininfcotDis. 1992- 14:285-97.

12. Phannacotherapy. 1993; 13(2 Pt 2): 4S-17S.

13. ClininfcotDis. 1993; 17(Suppl l):S192-9.

14. Pharmacotherapy. 1993, 13(2 Pt 2):39S-44S.

15. The Quinoloncs. San Diego: Acadernic Press; 1988.

16. Drugs. 1993; 45(Suppl 3):1-7.

17. Ortho Pnarrnaceutical Corporation. Ofloxacin Package Insert Raritan, NJ. 1992 Aueust.

18. Miles Inc. Pharmaceutical Division. Ciprofloxacin Package Insert. West Haven, CT. 1991 January.

Table 1. Required Information on the Doctor's Order for Therapeutic Drug Assay

peak, trough, or other draw time notation time level drawn time last dose administered infusion duration

Beginning in July, a new mandatory therapeutic drug assay request form (A-la Doctor's Order for Therapeutic Drug Assay) must be used for all drug assay requests, and will replace the current miscellaneous request form (Form 04) for ordering drug serum sample assays. The form also replaces the voluntary Form 616 used to supplement draw time and dose time information not documented on Form W. The Doctor's Order for Therapeutic Drug Assay was developed by a multidisciplinary team with DUE, Pharmacy, Nursing, Pathology, Medical Records, and Medical Staff input. The mandatory order form will require the recording of specific information necessary for appropriate interpretation of therapeutic drug assay results (Table 1) and addresses all commonly monitored drugs (Table 2). One copy of the 3-ply form becomes part of the patient's permanent medical record in the A-la section of the chart. In addition, on the reverse side, the form provides suggested guidelines for serum sampling and outlines specimen volume and container requirements.

Table 2. Commonly Monitored Drugs on the Doctor's Order for Therapeutic Drug Assay

carbamazepine cyclosporine digoxin gentamicin lidocaine lithium phenobarbital phenytoin procainamide quinidine theophylline tobramycin valproic acid vancomycin

Procedures for Use of A-1a Doctor's Order for Therapeutic Drug Assay

• The physician is responsible for completing the drug section, noting peak or trough (as applicable), and signing the Doctor's Order for Therapeutic Drug Assay Form when requesting a drug assay. [NOTE: One form must be used for each specimen submitted.]
  
• When a medical team member (e.g., MD, RN, student) draws the specimen, the specimen draw time should be documented on the white copy.For specimens drawn by a phlebotomist, draw times will be entered by Pathology into the INFORMM System.
  
• The nurse administering the dose, for which the specimen is drawn, will record the time the dose was administered and the duration of the infusion (applicable for IV doses) on the white copy.
  
• After draw time and dose time information has been documented, the original physician-signed form is placed in the A-la section of the patient's medical record.
  
• When a medical team member conducts the draw, the first copy (blue) is sent to Specimen Control (6248 RCP) with the labeled specimen. For specimens to be drawn by a phlebotomist, the blue copy is sent, without a specimen, to Specimen Control as a written request for phlebotomy services.
  
• The second copy (pink) will be sent simultaneously to the pharmacy serving the patient care unit.
  
• The pharmacist will review the form for completeness, with respect to draw time and dosing information. If the pharmacist suspects a problem with draw time, the Medical team will be contacted.
  
• Once assay results are available, the pharmacist will perform any necessary pharmacokinetic assessments and consult with the medical team on potential dosing adjustments.

Drugs Added to Stock

VARICELLA VIRUS VACCINE Injection: 1350 PFU per 0.5ml Varicella virus live vaccine (Varivax(D-Merck) is indicated for active immunization against varicella in individuals 12 months of age and older.

COLESTIPOL Tablets: 1 gram Colestipol (Colestid63)-Upjohn) is an anion exchange resin that binds bile acids. It is indicated as adjunctive therapy to diet for the reduction of serum cholesterol.

Drugs Deleted from Stock

CYANOCOBALAMIN 100 mcg per 1ml INJECTION Discontinued by all manufacturers. The 1000 mug per ml strength is still available.

CHOLESTYRAMINE REGULAR POWDER This product (Questran BMS) was deleted due to therapeutic duplication with the more palatable cholestyramine light powder (Questran (R)Light-BMS).

NOTE: The Pharmacy and Therapeutics Subcommittee considers cholestyramine regular powder to be therapeutically equivalent and interchangeable with cholestyramine light powder; cholestyramine light powder will be dispensed for all orders for cholestyramine powder.

______________

Correction: The strength of colchicine injection was incorrect in the "Drugs Added to Stock" section of the May issue of the P&T News. The correct strength is 500 mcg per ml, 2 ml ampul.

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