generic times: product profiles

Pharmacy Times, Volume 0, 0

Fentanyl Oral Lozenges

The availability of an analgesic in alozenge form gives clinicians anothermeans of providing patients with relieffrom breakthrough cancer pain. The useof fentanyl in this form also reduces sideeffects associated with other strong opioidanalgesics.

Pharmacology

At the central nervous system (CNS)level, fentanyl interacts with the mu opiatereceptor, increasing tolerance to painand diminishing its perception. Although ithas pharmacodynamic properties similarto other strong analgesics, fentanyl exertslittle hypnotic activity in lozenge form, andhistamine release occurs only rarely.

Administration

The use of fentanyl lozenges should bereserved for the management of breakthroughcancer pain. Patients must betolerant of opiates, with tolerance translatingas a daily dose of 60 mg of morphine,50 mcg hourly transdermal fentanyl,or their narcotic equivalent.Fentanyl lozenges are available in severalstrengths, with dosage being customizedbased on patient response.

In general, an initial 200-mcg dose isrecommended for breakthrough pain,with a maximum of 2 lozenges perepisode being used, or 4 lozenges perday. Dosage titrations should be madeevery 1 to 2 days, depending on theresults reported to the clinician.

Patients should be instructed to suckon the lozenge, not to bite or chew it.Biting, chewing, or swallowing thelozenge will reduce its effectiveness.Also, 15 minutes should elapse for thistransmucosal administration route; shorteror longer durations in the mouth alsoreduce the effectiveness of the fentanyldose. Patients older than 65 years of agegenerally respond to a lower titrateddose than younger patients.

Safety Profile

The use of fentanyl requires carefulclinical consideration: the lozenges arenot indicated for the management ofacute or postoperative pain, includinguse in outpatient surgeries, and they arenot considered appropriate for the controlof mild or intermittent pain that canrespond to intermittent or nonopioidtreatment.

Fentanyl, regardless of its administrationroute, is a Schedule II narcotic.Concurrent use of alcohol or other CNSdepressants will result in enhancedsedation and respiratory depression.Management of breakthrough pain withpatients having a concurrent psychiatriccondition requires additional considerations,because other forms of fentanylhave been successfully used in suicide.Fentanyl will also appear in the breastmilk of nursing mothers due to itslipophilic nature.

After its first pass, fentanyl is metabolizedby the CYP3A4 isoenzyme.Therefore, decreased metabolism can beexpected with concurrent administrationof azole-based antifungals, macrolideantibiotics, and protease inhibitors.Increased hepatic clearance, and adiminished effect, can be expected whenusing phenytoin, carbamazepine, orrifampin.

Nevertheless, the side-effect profile fortopical fentanyl remains largely favorable,because the drug remains primarilywithin the CNS and not in the cardiovascularsystem. With a comparatively lowincidence of constipation, other clinicaltrials have found that >25% of usersexperience nausea, sleepiness, xerostomia,and confusion. Most often, the fentanyllozenge results in facial itching andflushing. Possible xerostomia from opioidtherapy is also associated with anincrease in dental decay.

Outlook

Fentanyl in lozenge form is beneficialfor cancer patients, especially those withintractable nausea and vomiting, whorequire breakthrough pain managementwhile on other opiate therapies. Severalstrengths, ranging from 200 to 1600 mcg,are available from Barr PharmaceuticalsInc and allow for a wide titration ofdoses.

Venlafaxine Regular-releaseTablets

The debilitating clutch of depressiongrips >18 million Americans. More thanhalf of these patients are likely to experiencea relapse, encouraging a treatmentgoal of complete remission, rather thanjust symptomatic relief. The standard oftherapy involves manipulating neurotransmitters.

Pharmacology

Serotonin occurs naturally in the body,with only about 2% serving as a neurotransmitter.Even that small amount canhave a profound effect, with deficienciesin serotonin contributing to clinicaldepression.

Venlafaxine is a serotonin and norepinephrinereuptake inhibitor used for thetreatment of depression. As a phenylethylaminederivative, it is chemicallyand pharmacologically distinct fromother commercially available agentsused to treat depression. Although it isdissimilar to other agents, it shares withthem the postulated action of potentiatingneurotransmitter activity within theCNS. Studies indicate that venlafaxineand its primary metabolite are bothpotent inhibitors of serotonin and norepinephrinereuptake, while being weak inhibitorsof dopamine reuptake.

Dosing and Administration

The regular-release generic version ofvenlafaxine is available in 5 tabletstrengths. For major depression, venlafaxinedosing is generally started at37.5 mg daily, increased at 4 days to 75mg, and then at 75-mg increments individed doses, to a general maximumdaily dose of 225 mg. Some patients withsevere depression may require daily dosingas high as 350 mg.

If discontinued, venlafaxine should beremoved slowly, by tapering daily doseseach week in increments of 75 mg, tominimize withdrawal effects.

Side-effect Profile

To minimize nausea, venlafaxine canbe taken with food with no interferencewith the drug's absorption.

The increase in norepinephrine levelsfrom venlafaxine use is associated with a10-to 15-mm Hg elevation in diastolicblood pressure with the regular-releasetablets, requiring any preexisting hypertensionto be under proper management.Patients need to be regularly monitoredfor changes in blood pressurewhile using venlafaxine.

In July 2006, the FDA released newsafety information about combining triptan-based migraine treatment with drugssuch as venlafaxine that can alsoincrease serotonin levels. The combinedeffect of these agents creates the environmentfor a rare but life-threateningcondition known as the "serotonin syndrome."

As the name implies, this syndromeresults from an excess of neurologicserotonin, with symptoms of restlessnessand overreactive reflexes, hallucinations,ataxia, tachycardia, hyperthermia,and the gastrointestinal triad of nausea,vomiting, and diarrhea. Patients areadvised to seek medical assistanceimmediately if these symptoms emergeduring treatment, and clinicians areurged to follow any patients on this drugcombination carefully.

The serotonin syndrome is also a probabilityamong patients using monoamineoxidase inhibitors (MAOIs) withvenlafaxine. Two weeks should elapsebetween using an MAOI and venlafaxine,and at least 1 week should elapsebetween venlafaxine use and the start ofany MAOI.

If venlafaxine is used to treat majordepression, clinicians should be awarethat underlying bipolar disorders mayemerge; also, the risk for suicide increasesduring treatment until some level ofremission is assured. The suicide risk isespecially acute among adolescentpatients being treated for depression.

Outlook

Venlafaxine is available in strengths of25, 37.5, 50, 75, and 100 mg as regular-releasetablets from Teva PharmaceuticalIndustries Ltd. Teva is eligible for 180days of generic drug exclusivity for venlafaxinetablets; Mylan Laboratories Inchas also announced tentative approvalfrom the FDA for the same strengths.

Mr. Middleton is an instructor of pharmacologyat Kellogg CommunityCollege in Battle Creek, Mich.