March 1997

FORMULARY ADDITIONS

Insulin Lispro (Humalog7)

100units/ml: 10ml vials

Eli Lilly

Insulin lispro is an analog of insulin indicated for the management of diabetes mellitus. It exhibits a faster onset, peak effect, and duration of action in comparison to regular insulin. After subcutaneous injection, insulin lispro is more rapidly absorbed than regular human insulin and more closely mimics the normal physiologic insulin response after a meal. Extensive studies have shown that insulin lispro has a rapid absorption after subcutaneous injection with good overall control of blood glucose and postprandial hypoglycemia.

Studies have shown there are no significant differences in the adverse reactions of insulin lispro and regular human insulin. The main complication of insulin lispro is hypoglycemia, but this occurs less frequently with insulin lispro than with regular human insulin.

Unlike other available insulin products, insulin lispro is a prescription only drug. Insulin lispro is intended for subcutaneous injection. Doses need to be administered 15 minutes prior to meals and are individualized based on metabolic needs, eating habits, and other lifestyle variables. Insulin lispro exhibits potency comparable to regular human insulin but its onset of action is more rapid following subcutaneous injection. When added to long acting preparations, insulin lispro=s absorption may be decreased.

A 10ml vial of insulin lispro costs KUMC $20.61.

Menotropins (Humegon7)

75 IU/2ml vial

150 IU/2ml vial

Organon Inc.

Menotropins are a purified, lyophilized preparation of gonadotropins extracted from the urine of post menopausal women. The Menotropins are a mixture of equal active follicle stimulating hormones (FSH) and luteinizing hormones (LH). Humegon7 and hCG are given in sequential order for the induction of ovulation and pregnancy in the anovulatory infertile patient in whom the cause of anovulation is functional and not due to primary ovarian failure. Humegon7 and hCG may also be used to stimulate the development of multiple follicles in ovulating patients participating in in vitro fertilization programs. Humegon7 and hCG are indicated for the stimulation of spermiogenesis in men who have primary or secondary hypogonadotropic hypogonadism and idiopathic infertility.

Adverse events associated with Humegon7 include pulmonary and vascular complications, ovarian hyperstimulation syndrome, hemoperitoneum, adnexal torsion, mild to moderate ovarian enlargement, ovarian cysts, abdominal pain, sensitivity reactions, gastrointestinal reactions (nausea, vomiting, diarrhea, abdominal cramps and bloating), painful rash, swelling and/or irritation at the injection site, dizziness, tachycardia, dyspnea, and tachypnea. Men may also experience gynecomastia, breast pain, mastitis, abnormal lipoprotein fraction, and abnormal SGOT and SGTP.

The recommended initial dose of Humegon7 in women is 75IU per day administered IM for 7-12 days. (Do not exceed 12 days in a single dose course of therapy.) This should be followed by hCG 5,000-10,000U one day after the last dose of Humegon7. If there is no evidence of ovulation or pregnancy, repeat this dosing regimen for at least two more courses before increasing the dose. If a dose increase is warranted, 150IU of Humegon7 replaces the 75IU of Humegon7 in the dosing regimen. In men, pretreatment with hCG (5,000U three times a week) is required before concomitant therapy with Humegon7. Pretreatment is continued for a period sufficient to achieve normal serum testosterone and masculinization as judged by secondary characteristics, and may last 4-6 months. Once the pretreatment period is complete, Humegon7 is administered at a dose of 75IU IM three times weekly with 2,000 U hCG two times weekly. Therapy should last a minimum of four more months. If there are no positive results at the end of four months, the dose of Humegon7 may be increased to 150IU three times weekly with the dose of hCG unchanged.

Humegon7 carries a KUMC cost index of H.

Remifentanil (Ultiva7)

1mg/3ml vial

Glaxo Wellcome

Remifentanil is an ultra short acting mu opioid agonist analgesic for use during surgical anesthesia. It has a short duration of action, predictable pharmacokinetic profile, and lack of accumulation with repeated or prolonged administration. Peak effect is observed within 1 to 3 minutes after an intravenous bolus dose. The very short onset and duration of action of remifentanil offers advantages over the other opioids in surgical anesthesia. Some of these include easy titration intraoperatively, lack of accumulation during repeat bolus injection or prolonged infusion, a more rapid reduction in effect site concentration after infusion termination, and lack of dependence upon hepatic metabolism. As with fentanyl, sufentanil, and alfentanil, remifentanil is not associated with histamine release.

Adverse events associated with remifentanil administration include rigidity, nausea, vomiting, respiratory depression, reduced systolic blood pressure and reduced heart rate. Naloxone reverses hypoxic ventilatory depression induced by remifentanil.

Coadministration of remifentanil with beta blockers may result in hypotension and bradycardia. The severity and frequency of this potential drug interaction is unknown. Based on remifentanil=s pharmacologic action, an additive sedative effect would be expected when used in combination with other central nervous system depressants. The enzyme inhibition drug interactions reported with alfentanil should not occur with remifentanil since its metabolism is not dependent on the cytochrome P450 system.

For the induction of anesthesia, remifentanil should be administered at a rate of 0.5 to 1mcg/kg/min in addition to a hypnotic or volatile agent, followed by a maintenance infusion of 0.05 to 2mcg/kg/min.

Remifentanil carries a KUMC cost index of E.

Pilocarpine-Oral (Salagen7)

5mg Tablets

MGI Pharma

Oral pilocarpine is indicated for the treatment of the symptoms of xerostomia from salivary gland hypofunction caused by radiotherapy for cancer of the head and neck. Pilocarpine is a cholinergic parasympathomimetic agent exerting a broad spectrum of pharmacologic effects with predominant muscarinic action. In appropriate doses, pilocarpine may increase secretion of the exocrine glands; including the sweat, salivary, lacrimal, gastric, pancreatic, intestinal glands and the mucous cells of the respiratory tract. The tone of the urinary tract, gallbladder and biliary duct smooth muscle may also be enhanced.

The most important clinical adverse events caused by the oral administration of pilocarpine are related to the systemic cholinergic effects of the drug. These events are dose related and include: sweating, nausea, rhinitis, chills, flushing, urinary frequency, dizziness, hypotension, hypertension, bradycardia, tachycardia and asthenia.

Currently this product is contraindicated in patients with uncontrolled asthma, hypersensitivity to pilocarpine and when miosis is desirable (acute iritis and narrow angle glaucoma). Patients with significant cardiac disease may be unable to compensate for the transient changes in hemodynamics or rhythm induced by pilocarpine. Pulmonary edema has been reported as a complication of pilocarpine toxicity from high ocular doses given for acute angle closure glaucoma.

Pilocarpine has been reported to increase airway resistance, bronchial smooth muscle tone and bronchial secretions. Administer with caution and under close medical supervision in patients with controlled asthma, chronic bronchitis and/or chronic obstructive pulmonary disease.

Oral pilocarpine has a pregnancy category of C and should not be taken in nursing mothers.

The recommended dosage for the initiation of treatment is 5mg three times daily. Titration up to 10mg three times daily may be considered for patients who have not responded adequately to 5mg three times daily and who have tolerated the lower doses. Since the incidence of adverse effects increases with dose, the lowest effective dose should be used.

Oral pilocarpine carries a KUMC cost index of D.

Hydrocodone/Acetaminophen (Vicodin7)

5mg/500mg

The precise mechanism of action of hydrocodone and the opiates in not known, although they are believed to act on the opiate receptors in the central nervous system. The effects are remarkably diverse and include analgesia, drowsiness, changes in mood, respiratory depression, decreased gastrointestinal motility, nausea, vomiting, and alterations of the endocrine and autonomic nervous system.

Hydrocodone is a semisynthetic narcotic analgesic and antitussive with multiple actions qualitatively similar to that of codeine, most of these involve central nervous system and smooth muscle. The analgesic action of acetaminophen involves peripheral and central action, but the specific mechanisms are unknown. Acetaminophen also possesses antipyretic activity. When used in combination, the two agents have synergistic effects on pain.

Hydrocodone/APAP combination products are indicated for the relief of moderate to moderately severe pain. The analgesia effect is comparable to that of codeine and less than that of oxycodone.

The most frequently observed adverse events associated with hydrocodone include lightheadedness, dizziness, sedation, nausea and vomiting. Other side effects include dry mouth, lethargy, constipation, tachycardia, bradycardia, hypotension and respiratory depression.

All narcotic analgesics have abuse potential. Psychological dependence and physical tolerance and dependence may develop upon repeated or prolonged use. Most patients who receive opiates for medical reasons do not develop dependence syndromes.

Dosage should be adjusted to the severity of the pain and the response of the patient. However, tolerance to hydrocodone can develop with continued usage and the incidence of side effects is dose related. The usual dosage for hydrocodone 5mg/500mg APAP is one to two tablets every four to six hours as needed for pain. The 24 hour total should not exceed 8 tablets.

Hydrocodone 5mg/500mg APAP carries a KUMC cost index of C.

Meropenem (Merrem IV7)

500mg and 1gm vials

Zeneca Pharmaceuticals

Meropenem is a semisynthetic 1-$-methyl carbapenem antimicrobial agent with acitivity against aerobic and anaerobic organisms. Meropenem differs structurally from imipenem in that it contains a 1-$-methyl group at C1 and a substituted side chain at C2.

Meropenem is indicated as single-agent therapy for the treatment of intra-abdominal infections, including complicated appendicitis and peritonitis, caused by viridans group streptococci, E coli, Klebsiella pneumonia, P aeruginosa, Bacteroides fragilis, Bacteroides thetaiotaomicron, and Peptostreptococcus species in adults and children. The drug is also labeled for use in bacterial menningitis caused by S pneumoniae, H influenzae and N meningitidis in pediatric patients at least 3 months of age.

Meropenem has shown clinical and bacteriological efficacy at least equal to that of currently available treatment options in the treatment of a wide range of infections in adults and children in randomized, generally non-blinded, clinical trials.

The most common drug-related adverse events associated with meropenem include diarrhea, nausea/vomiting, and rash. When administered by IV bolus, the gastrointestinal adverse events are drastically decreased. Meropenem does not appear to have a significant epileptogenic potential, even at high doses.

There is limited information regarding meropenem and drug interactions. Labeling states that probenecid has been found to inhibit the renal excretion of meropenem, leading to statistically significant increases in the elimination half-life and extent of systemic exposure. The coadministration of probenecid and meropenem is therefore not recommended.

The recommended dose in adults is 1 gm every 8 hours, with appropriate dose reduction in renal impairment. The agent is most commonly administered intravenously over 15 to 30 minutes, but it may be infused by bolus over 5 minutes. Pediatric patients should receive 20-40mg/kg IV every 8 hours (maximum dose 2 gm Q8H), depending on the type of infection (intra-abdominal or meningitis).

Meropenem 1 gm IV Q8H is a daily cost of $131.22 to KUMC.

Nevirapine (Viramune7)

200mg Tablets

Roxane Laboratories

Nevirapine, a non-nucleoside reverse transcriptase inhibitor of HIV-1, binds directly to reverse transcriptase and blocks the RNA-dependent and DNA-dependent DNA polymerase activities by causing a disruption of the enzyme=s catalytic site. Nevirapine in combination with nucleoside analogues is indicated for the treatment of HIV-1 infected adults who have experienced clinical and/or immunologic deterioration. Studies show that nevirapine increases the effectiveness of zidovudine in bolstering CD4 cell counts and decreases viral load, although the clinical significance of changes in viral RNA has not been established.

The major clinical toxicity of nevirapine is rash, with an attributable rash occurring in 17% of patients in combination regimens in Phase II/III controlled studies. Severe or life-threatening rash occurred in 7.6% of nevirapine treated patients, typically occurring within the first 28 days of treatment, and reversing within two weeks to one month after discontinuation. Other common adverse events include fever, headache, and increases in liver enzymes.

Although clinical studies have not been conducted, induction of CYP3A by nevirapine may result in lower plasma concentrations of other concomitantly administered drugs that are extensively metabolized by CYP3A (including alprazolam, astemizole, cyclosporine, diltiazem, estrogens, lidocaine, midazolam, nifedipine, quinidine, tacrolimus, terfenadine, testosterone, triazolam, and warfarin.) There is insuffient data to assess whether dose adjustments are necessary when nevirapine and rifampin or rifabutin are coadministered. Therefore, until clinical data is available which evaluates the need for dose adjustments, the manufacturer recommends that these drugs should not be administered concomitantly with nevirapine. No dosage adjustments are necessary when nevirapine is taken in combination with ZDV, ddI, or ddC.

The recommended dose of nevirapine is 200mg once daily for 14 days, followed by 200mg twice daily in combination with nucleoside antiretroviral agents. The initial lower doses have been shown to decrease the incidence of rash.

For the standard dose of 200mg daily, nerivapine costs KUMC $6.82 per day.

Changes in the KUMC Formulary since 1996-1997 publication

FORMULARY ADDITIONS

FORMULARY DELETIONS

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