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Back To Vidyya May 2000 Safety-Related Drug Labeling Changes

News From The FDA

(Posted: July 14, 2000)

Note: The following summaries include only those safety-related sections that have been modified, and therefore do not contain all the information needed for safe and effective prescribing. Contact the manufacturer for the complete labeling/package insert.

NB: Comparison made to 2000 Physicians' Desk Reference (PDR), if drug's labeling included in the PDR.

Quick Reference:
(Click on name of the product to go directly to the summary.)

  • ACCUTANE
    (isotretinoin)

  • AMOXIL
    (amoxicillin)

  • ASTELIN
    (azelastine HCl)

  • AVALIDE
    (irbesartan/hydrochlorothiazide)

  • AVAPRO
    (irbesartan)

  • AVELOX
    (moxifloxacin HCl)

  • GONAL-F
    (follitropin alpha)

  • HALDOL
    (haloperidol)

  • IOPIDINE
    (apraclonidine)

  • LOVENOX
    (enoxaparin sodium)

  • MAXAIR AUTOHALER
    (pirbuterol acetate)

  • MERREM I.V.
    (merpenem)

  • NAVELBINE
    (vinorelbine tartrate)

  • NORDITROPIN
    (somatropin)

  • NORPACE
    (disopyramide phosphate)

  • NORVIR
    (ritonavir)

  • RAPAMUNE
    (sirolimus)

  • RENAGEL
    (sevelamer HCl)

  • REQUIP
    (ropinirole HCl)

  • ROMAZICON
    (flumazenil)

  • SINEMET CR
    (carbidopa-levodopa)

  • SINGULAIR
    (montelukast sodium)

  • SURMONTIL
    (trimipramine maleate)

  • TALWIN
    (pentazocine lactate)

  • VIRACEPT
    (nelfinavir mesylate)

  • XANAX
    (alprazolam)

  • ZOMIG
    (zolmitriptan)

  • Return to Quick Reference


    ACCUTANE (isotretinoin) Capsules
    [May 1, 2000: Roche]

    Portions of WARNINGS, PRECAUTIONS and ADVERSE EVENTS sections extensively revised. Contact the company for a copy of the new labeling/package insert.

    Return to Quick Reference


    AMOXIL (amoxicillin) Capsules, Tablets and Suspension
    [May 16, 2000: SmithKline Beecham]
    ADVERSE REACTIONS:
    Addition of adverse reactions (new text in italics) -

    "Hypersensitivity Reactions: Serum sickness like reactions, erythematous maculopapular rashes, erythema multiforme, Stevens-Johnson Syndrome, exfoliative dermatitis, toxic epidermal necrolysis, hypersensitivity vasculitis and urticaria have been reported.

    "Liver: A moderate rise in AST (SGOT) and/or ALT (SGPT) has been noted, but the significance of this finding is unknown. Hepatic dysfunction including cholestatic jaundice, hepatic cholestasis and acute cytolytic hepatitis have been reported.

    "Hemic and Lymphatic Systems: Anemia, including hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia leukopenia, and agranulocytosis have been reported during therapy with penicillins. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena

    "Central Nervous System: Reversible hyperactivity, agitation, anxiety, insomnia, confusion, convulsions, behavioral changes, and/or dizziness have been reported rarely. "

    Return to Quick Reference


    ASTELIN (azelastine HCl) Nasal Spray
    [May 30, 2000: Wallace Laboratories]
    Labeling revised to provide for a new indication - use in treatment of the symptoms of seasonal allergic rhinitis such as rhinorrhea, sneezing, and nasal pruritis in adults and children 5 years and older. Contact the company for a copy of the new labeling/package insert.
    Return to Quick Reference


    AVAPRO (irbesartan) Tablets
    AVALIDE (irbesartan/hydrochlorothiazide) Tablets
    [May 9, 2000: Bristol-Myers Squibb]
    ADVERSE REACTIONS:
    Post-Marketing Experience: Subsection revised (new text in italics) -

    "The following adverse reactions have been reported in post-marketing experience: Rare cases of urticaria and angioedema (involving swelling of the face, lips, pharynx, and/or tongue); hyperkalemia."

    Return to Quick Reference


    AVELOX (moxifloxacin HCl) Tablets
    [May 4, 2000: Bayer]
    CLINICAL PHARMACOLOGY:
    Hepatic Insufficiency: Subsection revised. The revisions are included in the following paragraphs -

    "In 400 mg single dose studies in 6 patients with mild, (Child Pugh Class A) and 10 patients with moderate (Child Pugh Class B) hepatic insufficiency, moxifloxacin mean systemic exposure (AUC) was 78% and 102%, respectively, of 18 healthy controls and mean peak concentration (Cmax) was 79% and 84% of controls.

    The mean AUC of the sulfate conjugate of moxifloxacin (M1) increased by 3.9-fold (ranging up to 5.9-fold) and 5.7-fold (ranging up to 8.0-fold) in the mild and moderate groups, respectively. The mean Cmax of M1 increased by approximately 3-fold in both groups (ranging up to 4.7- and 3.9-fold). The mean AUC of the glucuronide conjugate of moxifloxacin (M2) increased by 1.5-fold (ranging up to 2.5-fold) in both groups. The mean Cmax of M2 increased by 1.6- and 1.3-fold (ranging up to 2.7- and 2.1-fold), respectively. The clinical significance of increased exposure to the sulfate and glucuronide conjugates has not been studied. No dosage adjustment is recommended for mild or moderate hepatic insufficiency (Child Pugh Classes A and B). The pharmacokinetics of moxifloxacin in severe hepatic insufficiency (Child Pugh Class C) have not been studied. (See DOSAGE AND ADMINISTRATION.)"

    Drug-drug Interactions: Last paragraph revised (new text in italics) -

    "There is limited information available on the potential for a pharmacodynamic interaction in humans between moxifloxacin and other drugs that prolong the QTc interval of the electrocardiogram. Sotalol, a Class III antiarrhythmic, has been shown to further increase the QTc interval when combined with high doses of intravenous (IV) moxifloxacin in dogs. Therefore, moxifloxacin should be avoided ["not be used" deleted] with Class 1A and Class III antiarrhythmics. (See ANIMAL PHARMACOLOGY, WARNINGS, and PRECAUTIONS.)

    DOSAGE AND ADMINISTRATION:
    Impaired Hepatic Function: Subsection revised (new text in italics) -

    "No dosage adjustment is required in patients with mild or moderate hepatic insufficiency (Child Pugh Classes A and B). The pharmacokinetics of moxifloxacin in patients with ["moderate and" deleted] severe hepatic insufficiency (Child Pugh Class C ["Classes B" deleted] have not been studied. ["Due to the lack of clinical data the use of moxifloxacin is not recommended in patients with moderate and severe hepatic insufficiency" deleted] (See CLINICAL PHARMACOLOGY, Hepatic Insuffciency.)"

    Return to Quick Reference


    GONAL-F (follitropin alfa) Injection
    [May 24, 2000: Serono Laboratories]

    Labeling revised to provide for a new indication - use for induction of spermatogenesis in men with primary and secondary hypogonadotropic hypogonadism in whom the cause of infertility is not due to primary testicular failure. Contact the company for a copy of the new labeling/package insert.

    Return to Quick Reference


    HALDOL (haloperidol) Tablets, Concentrate & Injection
    [May 2, 2000: McNeil]

    [Not in 1999 PDR]

    PRECAUTIONS:
    Geriatric Use: New subsection -

    "Clinical studies of haloperidol did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not consistently identified differences between the elderly and younger patients. However, the prevalence of tardive dyskinesia appears to be highest among the elderly, especially elderly women (see WARNINGS, Tardive dyskinesia). Also, the pharmacokinetics of haloperidol in geriatric patients generally warrants the use of lower doses (see DOSAGE AND ADMINISTRATION)."

    Return to Quick Reference


    IOPIDINE (apraclonidine) Ophthalmic Solution
    [May 16, 2000: Alcon]
    ADVERSE REACTIONS:
    First paragraph deleted [this paragraph is already stated in the General subsection of the PRECAUTIONS section] -

    "Use of Iopidine 0.5% Ophthalmic Solution can lead to an allergic-like reaction characterized wholly or in part by the symptoms of hyperemia, pruritus, discomfort, tearing, foreign body sensation, and edema of the lids and conjunctiva. If ocular allergic-like symptoms occur, Iopidine 0.5% Ophthalmic Solution therapy should be discontinued."

    Second and third paragraphs unchanged -

    Ocular: Subsection revised (revised text in italics) -

    "The following adverse reactions were reported in 5 to 15% of the patients: discomfort, hyperemia, and pruritus."["Hyperemia (13%), pruritus (10%), discomfort (6%), tearing (4%)" deleted] The following adverse reactions were reported in ["less than 3" deleted] 1 to 5% of the patients: blanching, blurred vision, conjunctivitis, discharge, dry eye, foreign body sensation, lid edema, and tearing. [ formerly "blurred vision, foreign body sensation, dry eye, conjunctivitis, discharge, blanching"]

    The following adverse reactions were reported in less than 1% of the patients: [alphabetized] abnormal vision, blepharitis, blepharoconjunctivitis, conjunctival edema, conjunctival follicles, corneal erosion, corneal infiltrate, corneal staining, edema, irritation, keratitis, keratopathy, lid disorder, lid erythema, lid margin crusting, lid retraction, lid scales, pain, photophobia.

    Nonocular: All subsection headings "Body As A Whole, Cardiovascular and others were deleted and adverse events were revised and summarized under Nonocular as follows:

    "Dry mouth occurred in approximately 10% of the patients.

    "The following adverse reactions were reported in less than 3% of the patients: abnormal coordination, asthenia, arrhythmia, asthma, chest pain, constipation, contact dermatitis, depression, dermatitis, dizziness, dry nose, dyspnea, facial edema, headache, insomnia, malaise, myalgia, nausea, nervousness, paresthesia, parosmia, peripheral edema, pharyngitis, rhinitis, somnolence, and taste perversion."

    New last paragraph -

    Clinical practice: The following events have been identified during postmarketing use of Iopidine 0.5% Ophthalmic Solution in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. The events, which have been chosen for inclusion due to their seriousness, frequency of reporting, possible causal connection to Iopidine 0.5% Ophthalmic Solution, or a combination of these factors, include: bradycardia.

    OVERDOSAGE:
    New first paragraph -

    "Ingestion of Iopidine 0.5% Ophthalmic Solution has been reported to cause bradycardia, drowsiness, and hypothermia."

    Second paragraph addresses oral clonidine overdose (effects alphabetized) -

    "Accidental or intentional ingestion of oral clonidine has been reported to cause apnea, arrhythmias, asthenia, bradycardia, conduction defects, diminished or absent reflexes, dryness of the mouth, hypotension, hypothermia, hypoventilation, irritability, lethargy, miosis, pallor, respiratory depression, sedation or coma, seizure, somnolence, transient hypertension, and vomiting.

    Third (last) paragraph unchanged.

    Return to Quick Reference


    LOVENOX (enoxaparin sodium) Injection
    [May 30, 2000: Aventis Pharmaceuticals]
    PRECAUTIONS:
    Geriatric Use: New subsection -

    "Over 2800 patients, 65 years and older, have received enoxaparin sodium in pivotal clinical trials. The efficacy of Lovenox Injection in the elderly (greater than or equal to 65 years) was similar to that seen in younger patients (< 65 years). The incidence of bleeding complications was similar between elderly and younger patients when 30 mg every 12 hours or 40 mg once a day doses of Lovenox Injection were employed. The incidence of bleeding complications was higher in elderly patients as compared to younger patients when Lovenox Injection was administered at doses of 1.5 mg/kg once a day or 1 mg/kg every 12 hours. The risk of Lovenox Injection-associated bleeding increased with age. Serious adverse events increased with age for patients receiving Lovenox Injections. Other clinical experience (including postmarketing surveillance and literature reports) has not revealed additional differences in the safety of Lovenox Injection between elderly and younger patients. Careful attention to dosing intervals and concomitant medications (especially antiplatelet medications) is advised. Monitoring of geriatric patients with low body weight (< 45 kg) and those predisposed to decreased renal function should be considered. (See CLINICAL PHARMACOLOGY and General and Laboratory Tests subsections of PREACUTIONS)."

    Return to Quick Reference


    MAXAIR AUTOHALER (pirbuterol acetate) Inhalation Aerosol
    [May 26, 2000: 3M Pharmaceuticals]
    Patient's Instructions for Use: New labeling provides for the number of actuations needed to prime and reprime the Maxair Autohaler and the non-use interval after which repriming is necessary. Also, new labeling describes addition of a "Test Fire Slide" which allows manual priming of the device. Contact the company for a copy of the new labeling/package insert.

    Return to Quick Reference


    MERREM I.V. (meropenem) Injection
    [May 23, 2000: Zeneca Pharmaceuticals]
    CLINICAL PHARMACOLOGY:
    Microbiology: Susceptibility Tests: Dilution Techniques The quality control ATCC number and the MIC range (microgram/mL) for Haemophilus influenzae revised from "49247 0.06-0.25" to "49766 0.03-0.12".

    PRECAUTIONS:
    Geriatric Use: New subsection -

    "Of the total number of subjects in clinical studies of Merrem I.V., approximately 1100 (30%) were 65 years of age and older, while 400 (11%) were 75 years and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects; spontaneous reports and other reported clinical experience have not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out."

    Return to Quick Reference


    NAVELBINE (vinorelbine tartrate) Injection
    [May 12, 2000: Glaxo Wellcome]
    CLINICAL PHARMACOLOGY:
    Pharmacokinetics: Second and third sentences deleted -

    "One metabolite, deacetylvinorelbine, has been shown to possess antitumor activity. This metabolite has been detected, but not quantified, in human plasma."

    Replaced with -

    "Two metabolites of vinorelbine have been identified in human blood, plasma, and urine; vinorelbine N-oxide and deacetylvinorelbine. Deacetylvinorelbine has been demonstrated to be the primary metabolite of vinorelbine in humans, and has been shown to possess antitumor activity similar to vinorelbine. Therapeutic doses of Navelbine (30 mg/m2) yield very small, if any, quantifiable levels of either metabolite in blood or urine. The metabolism of vinca alkaloids has been shown to be mediated by hepatic cytochrome P450 isoenzymes in the CYP3A subfamily. This metabolic pathway may be impaired in patients with hepatic dysfunction or who are taking concomitant potent inhibitors of these isoenzymes (see PRECAUTIONS)."

    WARNINGS:
    New third and fourth paragraphs -

    "Acute shortness of breath and severe bronchospasm have been reported infrequently, following the administration of Navelbine and other vinca alkaloids, most commonly when the vinca alkaloid was used in combination with mitomycin. These events may require treatment with supplemental oxygen, bronchodilators, and/or corticosteroids, particularly when there is preexisting pulmonary dysfunction. Reported cases of interstitial pulmonary changes and ARDS, most of which were fatal, occurred in patients treated with single-agent Navelbine. The mean time to onset of these symptoms after vinorelbine administration was one week (range 3-8 days). Patients with alterations in their baseline pulmonary symptoms or with new onset of dyspnea, cough, hypoxia, or other symptoms should be evaluated promptly.

    Navelbine has been reported to cause severe constipation (e.g., grade 3-4), paralytic ileus, intestinal obstruction, necrosis, and/or perforation. Some events have been fatal."

    ADVERSE REACTIONS:
    Addition of adverse events to two subsections (new text in italics) -

    Neurologic: "Peripheral neurotoxicities such as, but not limited to, muscle weakness and disturbance of gait, have been observed in patients with and without prior symptoms. There may be increased potential for neurotoxicity in patients with pre-existing neuropathy, regardless of etiology, who receive Navelbine. Vestibular and auditory deficits have been observed with Navelbine, usually when used in combination with cisplatin."

    Cardiovascular: "Hypertension, hypotension, vasodilation, tachycardia, and pulmonary edema have been reported.

    Return to Quick Reference


    NORDITROPIN (somatropin) Injection
    [May 16, 2000: Novo Nordisk]

    [Labeling changes not in 1999 PDR]

    CONTRAINDICATIONS:
    New last paragraph -

    "Growth hormone should not be initiated to treat patients with acute critical illness due to complications following open heart or abdominal surgery, multiple accidental trauma or to patients having acute respiratory failure. Two placebo-controlled trials in non-growth hormone deficient adult patients (n=522) with these conditions revealed a significant increase in mortality (41.9% vs. 19.3%) among somatropin treated patients (doses 5.3-8 mg/day) compared to those receiving placebo (see WARNINGS)."

    WARNINGS:
    New second paragraph -

    "See CONTRAINDICATIONS for information on increased mortality in patients with acute critical illness in intensive care units due to complications following open heart or abdominal surgery, multiple accidental trauma or with acute respiratory failure. The safety of continuing growth hormone treatment in patients receiving replacement doses for approved indications who currently develop these illnesses has not been established. Therefore, the potential benefit of treatment continuation of growth hormone in patients having acute critical illnesses should be weighed against the potential risk."

    Return to Quick Reference


    NORPACE (disopyramide phosphate) Capsules
    [May 17, 2000: G.D. Searle & Co.]
    PRECAUTIONS:
    Geriatric Use: New subsection -

    "Clinical studies of Norpace/Norpace CR did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

    "Because of its anticholinergic activity, disopyramide phosphate should not be used in patients with glaucoma, urinary retention, or benign prostatic hypertrophy (medical conditions commonly associated with the elderly) unless adequate overriding measures are taken (see Warnings: Anticholinergic Activity). In the event of increased anticholinergic side effects, plasma levels of disopyramide should be monitored and the dose of the drug adjusted accordingly. A reduction of the dose by one third, from the recommended 600 mg/day to 400 mg/day, would be reasonable, without changing the dosing interval. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see Precautions: Renal Impairment and Dosage and Administration)."

    Return to Quick Reference


    NORVIR (ritonavir) Capsules & Oral Solution
    [May 8, 2000: Abbott]
    WARNINGS:
    Drug Interactions: New last paragraph -

    "Concomitant use of Norvir, and St. John's wort (hypericum perforatum) or products containing St. John's wort is not recommended. Coadministration of protease inhibitors, including Norvir, with St. John's wort is expected to substantially decrease protease inhibitor concentrations and may result in sub-optimal levels of Norvir and lead to loss of virologic response and possible resistance to Norvir or to the class of protease inhibitors."

    PRECAUTIONS:
    Information for Patients: New last paragraph -

    Norvir may interact with some drugs; therefore, patients should be advised to report to their doctor the use of any other prescription, non-prescription medication or herbal products, particularly St. John's wort."

    Patient Package Insert:
    "Can I take Norvir with other medications?" New last bullet -

    "Taking Norvir with St. John's wort (hypericum perforatum), an herbal product sold as a dietary supplement or products containing St. John's wort is not recommended. Talk with your doctor if you are taking or are planning to take St. John's wort. Taking St. John's wort may decrease Norvir levels and lead to increased viral load and possible resistance to Norvir or cross-resistance to other antiretroviral drugs."

    Return to Quick Reference


    RAPAMUNE (sirolimus) Oral Solution
    [May 3, 2000: Wyeth-Ayerst]
    WARNINGS:
    Fourth paragraph has been revised from -

    "Rapamune has been administered concurrently with the following agents in clinical trials: cyclosporine (Sandimune Injection, Sandimune Oral Solution, Sandimune Soft Gelatin Capsules, Neoral Soft Gelatin Capsules, Neoral Oral Solution) and corticosteroids. The efficacy and safety of the use of Rapamune in combination with other immunosuppressive agents has not been determined."

    The current text reads as:

    "In clinical trials, Rapamune has been administered concurrently with corticosteroids and with the following formulations of cyclosporine:

    "Sandimune Injection (cyclosporine injection)
    Sandimune Oral Solution (cyclosporine oral solution)
    Sandimune Soft Gelatin Capsules (cyclosporine capsules)
    Neoral Soft Gelatin Capsules (cyclosporine capsules [MODIFIED])
    Neoral Oral Solution (cyclosporine oral solution [MODIFIED])

    "The efficacy and safety of the use of Rapamune in combination with other immunosuppressive agents has not been determined."

    PRECAUTIONS:
    Drug Interactions:
    Cyclosporine capsules MODIFIED: Text revised (new text in italics) -

    ["(e.g., Neoral Soft Gelatin Capsules):" deleted] In a single dose drug-drug interaction study, 24 healthy volunteers were administered 10 mg sirolimus either simultaneously or 4 hours after a 300 mg dose of ["cyclosporine (Neoral)" deleted] Neoral Soft Gelatin Capsules (cyclosporine capsules [MODIFIED]). For ["concomitant" deleted] simultaneous administration, the mean Cmax and AUC of sirolimus were increased by 116% and 230% respectively relative to administration of sirolimus alone. However, when given 4 hours after ["cyclosporine" deleted] Neoral Soft Gelatin Capsules (cyclosporine capsules [MODIFIED]) administration, sirolimus Cmax and AUC were increased by 37% and 80 % respectively compared to administration of sirolimus alone.

    "Mean cyclosporine Cmax and AUC were not significantly affected when sirolimus was given ["concomitantly" deleted] simultaneously or when administered 4 hours after ["cyclosporine" deleted] Neoral Soft Gelatin Capsules (cyclosporine capsules [MODIFIED]). However, after multiple-dose administration of sirolimus given 4 hours after ["cyclosporine" deleted] Neoral in renal post-transplant patients over 6 months, cyclosporine oral-dose clearance was reduced, and lower doses of ["cyclosporine (Neoral)" deleted] Neoral Soft Gelatin Capsules (cyclosporine capsules [MODIFIED]) were needed to maintain target cyclosporine concentration.

    " Because of the effect of cyclosporine capsules (MODIFIED)["(e.g., Neoral Soft Gelatin Capsules)" deleted], it is recommended that sirolimus should be taken 4 hours after administration of cyclosporine oral solution (MODIFIED)["(e.g., Neoral Oral Solution, SangCya Oral Solution)" deleted] and/or cyclosporine capsules (MODIFIED), ["administration" deleted] (see DOSAGE AND ADMINISTRATION).

    " Cyclosporine oral solution: USP (e.g., Sandimmune Oral Solution)" deleted] In a multiple-dose study in 150 psoriasis patients, sirolimus 0.5, 1.5, and 3 mg/m2/day was administered simultaneously with Sandimmune Oral Solution (cyclosporine oral solution) ["USP" deleted] 1.25 mg/kg/day. The increase in average sirolimus trough concentrations ranged between 67% - 86% relative to when sirolimus was administered without cyclosporine. The intersubject variability (%CV) for sirolimus trough concentrations ranged from 39.7% to 68.7%. There was no significant effect of multiple-dose sirolimus on cyclosporine Sandimmune (cyclosporine oral solution, USP deleted] trough concentrations following Sandimune Oral Solution (cyclosporine oral solution) administration. However, the %CV was higher (range 85.9%-165%) than those from previous studies.

    (USP Deleted) "Sandimmune Oral Solution (cyclosporine oral solution, is not bioequivalent to Neoral Oral Solution (cyclosporine oral solution [MODIFIED]) ["Capsules (cyclosporine capsules) MODIFIED" deleted], and should not be used interchangeably. Although there is no published data comparing Sandimmune Oral Solution (cyclosporine oral solution) to SangCya Oral Solution (cyclosporine oral solution [MODIFIED]), they should not be used interchangeably. Likewise, Sandimmune Soft Gelatin Capsules (cyclosporine capsules) are not bioequivalent to Neoral Soft Gelatin Capsules (cyclosporine capsules [MODIFIED]) and should not be used interchangeably."

    DOSAGE AND ADMINISTRATION:
    Third paragraph revised (new text in italics) -

    " It is recommended that sirolimus be taken 4 hours after administration of cyclosporine oral solution (MODIFIED) ["(e.g., Neoral Oral Solution, SangCya Oral Solution)" deleted] and/or cyclosporine capsules (MODIFIED), ["administration" deleted]."

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    RENAGEL (sevelamer HCl) Capsules
    [May 5, 2000: GelTex Pharmaceuticals]

    Extensive revisions to DOSAGE AND ADMINISTRATION section and PRECAUTIONS: Drug Interactions subsection. Contact the company for a copy of the new labeling/package insert.

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    REQUIP (ropinirole HCl) Tablets
    [May 15, 2000: SmithKline Beecham]
    WARNINGS:
    Falling Asleep During Activities of Daily Living: New subsection -

    "Patients treated with Requip have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles which sometimes resulted in accidents. Although many of these patients reported somnolence while on Requip, some perceived that they had no warning signs such as excessive drowsiness, and believed that they were alert immediately prior to the event. Some of these events have been reported as late as one year after initiation of treatment.

    "Somnolence is a common occurrence in patients receiving Requip. Many clinical experts believe that falling asleep while engaged in activities of daily living always occurs in a setting of pre-existing somnolence although patients may not give such a history. For this reason, prescribers should continually reassess patients for drowsiness or sleepiness especially since some of the events occur well after the start of treatment. Prescribes should also be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities.

    "Before initiating treatment with Requip, patients should be advised of the potential to develop drowsiness and specifically asked about factors that may increase the risk with Requip such as concomitant sedating medications, the presence of sleep disorders, and concomitant medications that increase ropinirole plasma levels (e.g., ciprofloxacin - see PRECAUTIONS, Drug Interactions). If a patient develops significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating, etc.), Requip should ordinarily be discontinued. See DOSAGE AND ADMINISTRATION for guidance in discontinuing Requip. If a decision is made to continue Requip, patients should be advised to not drive and to avoid other potentially dangerous activities. There is insufficient information to establish that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living."

    PRECAUTIONS:
    Information to Patients: Fourth paragraph added -

    "Patients should be alerted to the potential sedating effects associated with Requip including somnolence and the possibility of falling asleep while engaged in activities of daily living. Since somnolence is a frequent adverse event with potentially serious consequences, patients should neither drive a car nor engage in other potentially dangerous activities until they have gained sufficient experience with Requip to gauge whether or not it affects their mental and/or motor performance adversely. Patients should be advised that if increased somnolence or new episodes of falling asleep during activities of daily living (e.g., watching television, passenger in a car, etc.) are experienced at any time during treatment, they should not drive or participate in potentially dangerous activities until they have contacted their physician. Because of possible additive effects, caution should be advised when patients are taking other sedating medications or alcohol in combination with Requip and when taking concomitant medications that increase plasma levels of ropinirole (e.g., ciprofloxacin)."

    ADVERSE REACTIONS:
    Falling Asleep During Activities of Daily Living: Last subsection added -

    "Patients treated with Requip have reported falling asleep while engaged in activities of daily living, including operation of a motor vehicle which sometimes resulted in accidents (see bolded WARNING)."

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    ROMAZICON (flumazenil) Injection
    [May 22, 2000: Roche Laboratories]
    PRECAUTIONS:
    Geriatric Use: New first paragraph -

    "Of the total number of subjects in clinical studies of flumazenil, 248 were 65 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out."

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    SINEMET CR (carbidopa/levodopa) Tablets
    [May 2, 2000: DuPont]
    ADVERSE REACTIONS:
    Addition of new adverse reactions to the following subsections -

    Hypersensitivity: "bullous lesions (including pemphigus-like reactions)"

    Nervous System/Psychiatric: "increased libido"

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    SINGULAIR (montelukast sodium) Tablets
    [May 9, 2000: Merck]

    [Other labeling changes not appearing in 2000 PDR: Mar00]

    ADVERSE REACTIONS:
    Post-Marketing Experience: First paragraph (new text in italics) -

    "The following additional adverse reactions have been reported in post-marketing use: hypersensitivity reactions (including anaphylaxis, angioedema, pruritus, urticaria, and very rarely, hepatic eosinophilic infiltration), dream abnormalities, drowsiness, irritability, and restlessness."

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    SURMONTIL (trimipramine maleate) Capsules
    [May 1, 2000: Wyeth Laboratories]
    CLINICAL PHARMACOLOGY:
    New paragraph added -

    "The single-dose pharmacokinetics of trimipramine were evaluated in a comparative study of 24 elderly subjects and 24 younger subjects; no clinically relevant differences were demonstrated based on age or gender."

    PRECAUTIONS:
    Geriatric Use: New subsection -

    "Clinical studies of Surmontil were not adequate to determine whether subjects aged 65 and over respond differently from other subjects.

    "The pharmacokinetics of trimipramine were not substantially altered in the elderly (see CLINICAL PHARMACOLOGY).

    "Surmontil is known to be substantially excreted by the kidney. Clinical circumstances, some of which may be more common in the elderly, such as hepatic or renal impairment, should be considered (see PRECAUTIONS-General). Greater sensitivity (e.g., confusional states, sedation) of some older individuals cannot be ruled out (see ADVERSE REACTIONS). In general, dose selection for an elderly patient should be cautious, usually starting at a lower dose (see DOSAGE AND ADMINISTRATION)."

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    TALWIN (pentazocine lactate) Injection
    [May 24, 2000: Abbott]
    CLINICAL PHARMACOLOGY:
    New second paragraph -

    "Clinical data indicate that differences in various pharmacokinetic parameters may be observed with increasing age. In one study, elderly patients exhibited a longer mean elimination half-life, a lower mean total plasma clearance, and a larger mean area under the concentration-time curve than younger patients."

    WARNINGS:
    Geriatric Use: New subsection -

    "Elderly patients may be more sensitive to the analgesic effects of Talwin than younger patients. See DOSAGE AND ADMINISTRATION.

    "Clinical data indicate that differences in various pharmacokinetic parameters of Talwin may exist between elderly and younger patients. See CLINICAL PHARMACOLOGY.

    "Sedating drugs may cause confusion and oversedation in the elderly; elderly patients generally should be started on low doses of Talwin and observed closely.

    "This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function."

    DOSAGE AND ADMINISTRATION:
    Adults, Excluding Patients in Labor: First paragraph, new fifth and sixth sentences -

    "Elderly patients may be more sensitive to the analgesic effects of Talwin than younger patients. Elderly patients generally should be started on low doses of Talwin and observed closely."

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    VIRACEPT (nelfinavir mesylate) Tablets & Oral Powder
    [May 17, 2000: Agouron ]

    [Other labeling not appearing in 2000 PDR: Mar00

    Labeling revised to provide for use in combination with other antiretroviral agents, for the treatment of HIV-1 infection. Contact the company for a copy of the new labeling/package insert.

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    ZOMIG (zolmitriptan) Tablets
    [May 1, 2000: Zeneca Pharmaceuticals]
    ADVERSE REACTIONS:
    [For the 1999 PDR] The first (bolded text) paragraph revised -

    "Although not reported with zolmitriptan in clinical trials, serious cardiac events, including some that have been fatal, have rarely occurred following use of 5-HT1 agonists. Events reported have included coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, and ventricular fibrillation (see CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS)."

    Replaced with (as seen in the 2000 PDR) -

    "Serious cardiac events have occurred during post-marketing surveillance following the use of Zomig Tablets. These events are extremely rare and most have been reported in patients with risk factors predictive of CAD. Events reported have included coronary artery vasospasm, transient myocardial ischemia, angina pectoris and myocardial infarction (see CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS)."


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Editor: Susan K. Boyer, RN
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