Fentanyl Oral Lozenges
The availability of an analgesic in a lozenge form gives clinicians another means of providing patients with relief from breakthrough cancer pain. The use of fentanyl in this form also reduces side effects associated with other strong opioid analgesics.
At the central nervous system (CNS) level, fentanyl interacts with the mu opiate receptor, increasing tolerance to pain and diminishing its perception. Although it has pharmacodynamic properties similar to other strong analgesics, fentanyl exerts little hypnotic activity in lozenge form, and histamine release occurs only rarely.
The use of fentanyl lozenges should be reserved for the management of breakthrough cancer pain. Patients must be tolerant of opiates, with tolerance translating as a daily dose of 60 mg of morphine, 50 mcg hourly transdermal fentanyl, or their narcotic equivalent. Fentanyl lozenges are available in several strengths, with dosage being customized based on patient response.
In general, an initial 200-mcg dose is recommended for breakthrough pain, with a maximum of 2 lozenges per episode being used, or 4 lozenges per day. Dosage titrations should be made every 1 to 2 days, depending on the results reported to the clinician.
Patients should be instructed to suck on the lozenge, not to bite or chew it. Biting, chewing, or swallowing the lozenge will reduce its effectiveness. Also, 15 minutes should elapse for this transmucosal administration route; shorter or longer durations in the mouth also reduce the effectiveness of the fentanyl dose. Patients older than 65 years of age generally respond to a lower titrated dose than younger patients.
The use of fentanyl requires careful clinical consideration: the lozenges are not indicated for the management of acute or postoperative pain, including use in outpatient surgeries, and they are not considered appropriate for the control of mild or intermittent pain that can respond to intermittent or nonopioid treatment.
Fentanyl, regardless of its administration route, is a Schedule II narcotic. Concurrent use of alcohol or other CNS depressants will result in enhanced sedation and respiratory depression. Management of breakthrough pain with patients having a concurrent psychiatric condition requires additional considerations, because other forms of fentanyl have been successfully used in suicide. Fentanyl will also appear in the breast milk of nursing mothers due to its lipophilic nature.
After its first pass, fentanyl is metabolized by the CYP3A4 isoenzyme. Therefore, decreased metabolism can be expected with concurrent administration of azole-based antifungals, macrolide antibiotics, and protease inhibitors. Increased hepatic clearance, and a diminished effect, can be expected when using phenytoin, carbamazepine, or rifampin.
Nevertheless, the side-effect profile for topical fentanyl remains largely favorable, because the drug remains primarily within the CNS and not in the cardiovascular system. With a comparatively low incidence of constipation, other clinical trials have found that >25% of users experience nausea, sleepiness, xerostomia, and confusion. Most often, the fentanyl lozenge results in facial itching and flushing. Possible xerostomia from opioid therapy is also associated with an increase in dental decay.
Fentanyl in lozenge form is beneficial for cancer patients, especially those with intractable nausea and vomiting, who require breakthrough pain management while on other opiate therapies. Several strengths, ranging from 200 to 1600 mcg, are available from Barr Pharmaceuticals Inc and allow for a wide titration of doses.
Venlafaxine Regular-release Tablets
The debilitating clutch of depression grips >18 million Americans. More than half of these patients are likely to experience a relapse, encouraging a treatment goal of complete remission, rather than just symptomatic relief. The standard of therapy involves manipulating neurotransmitters.
Serotonin occurs naturally in the body, with only about 2% serving as a neurotransmitter. Even that small amount can have a profound effect, with deficiencies in serotonin contributing to clinical depression.
Venlafaxine is a serotonin and norepinephrine reuptake inhibitor used for the treatment of depression. As a phenylethylamine derivative, it is chemically and pharmacologically distinct from other commercially available agents used to treat depression. Although it is dissimilar to other agents, it shares with them the postulated action of potentiating neurotransmitter activity within the CNS. Studies indicate that venlafaxine and its primary metabolite are both potent inhibitors of serotonin and norepinephrine reuptake, while being weak inhibitors of dopamine reuptake.
Dosing and Administration
The regular-release generic version of venlafaxine is available in 5 tablet strengths. For major depression, venlafaxine dosing is generally started at 37.5 mg daily, increased at 4 days to 75 mg, and then at 75-mg increments in divided doses, to a general maximum daily dose of 225 mg. Some patients with severe depression may require daily dosing as high as 350 mg.
If discontinued, venlafaxine should be removed slowly, by tapering daily doses each week in increments of 75 mg, to minimize withdrawal effects.
To minimize nausea, venlafaxine can be taken with food with no interference with the drug's absorption.
The increase in norepinephrine levels from venlafaxine use is associated with a 10-to 15-mm Hg elevation in diastolic blood pressure with the regular-release tablets, requiring any preexisting hypertension to be under proper management. Patients need to be regularly monitored for changes in blood pressure while using venlafaxine.
In July 2006, the FDA released new safety information about combining triptan-based migraine treatment with drugs such as venlafaxine that can also increase serotonin levels. The combined effect of these agents creates the environment for a rare but life-threatening condition known as the "serotonin syndrome."
As the name implies, this syndrome results from an excess of neurologic serotonin, with symptoms of restlessness and overreactive reflexes, hallucinations, ataxia, tachycardia, hyperthermia, and the gastrointestinal triad of nausea, vomiting, and diarrhea. Patients are advised to seek medical assistance immediately if these symptoms emerge during treatment, and clinicians are urged to follow any patients on this drug combination carefully.
The serotonin syndrome is also a probability among patients using monoamine oxidase inhibitors (MAOIs) with venlafaxine. Two weeks should elapse between using an MAOI and venlafaxine, and at least 1 week should elapse between venlafaxine use and the start of any MAOI.
If venlafaxine is used to treat major depression, clinicians should be aware that underlying bipolar disorders may emerge; also, the risk for suicide increases during treatment until some level of remission is assured. The suicide risk is especially acute among adolescent patients being treated for depression.
Venlafaxine is available in strengths of 25, 37.5, 50, 75, and 100 mg as regular-release tablets from Teva Pharmaceutical Industries Ltd. Teva is eligible for 180 days of generic drug exclusivity for venlafaxine tablets; Mylan Laboratories Inc has also announced tentative approval from the FDA for the same strengths.
Mr. Middleton is an instructor of pharmacology at Kellogg Community College in Battle Creek, Mich.
One study linked multiple pregnancies to an increased risk of developing atrial fibrillation later in life, and another investigated the association between premature delivery and cardiovascular disease.
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