Many new drug therapy options introduced in the past year that have specific applications in the senior patient. In some cases these represent advances in efficacy over products previously available. In other cases, they improve safety or simply add to the already crowded and complicated arena of drug therapy. This article identifies some of the pluses and minuses of the new drug therapy options, with particular attention to implications in the older patient.
COX-1 is constituitively expressed, meaning that it is produced in a manner consistent with maintenance of normal bodily functions. COX-2 is produced in an inducible fashion, mainly at the sites of inflammation, so the ability to inhibit COX-2 would tend to focus prostaglandin suppression to areas of the body where it would most logically benefit the patient. Celecoxib has a half-life of 11 hours, which allows it to be dosed on a once- or twice-a-day basis. It is metabolized by cytochrome p450 2C9 to inactive metabolites. This drug demonstrates higher peak concentrations in elderly patients and in black patients, but a dosage adjustment is usually not necessary.
Drug interactions are a noteworthy portion of the profile with this particular medication. Fluconazole used concurrently with celecoxib will result in increased celecoxib levels. Several other interactions are similar to those experienced with other NSAIDs, such as elevated lithium levels and the suppressed pharmacologic effect of furosemide and angiotensin-converting enzyme inhibitors. A noteworthy portion of the profile of celecoxib is the fact that is does not demonstrate an interaction with warfarin. Warfarin is not displaced from the protein-binding site, and the lack of impact of celecoxib on platelet aggregation would serve as a benefit in patients who might otherwise be at risk for bleeding problems in the gastrointestinal tract. One other interaction that should be avoided is the use of celecoxib with other NSAIDs. This is certainly a possibility if patients take over-the-counter NSAIDs in addition to their long-term celecoxib dosing.
The clinical efficacy of celecoxib has been evaluated in both osteoarthritis and rheumatoid arthritis and has been found to be similar that of to naproxen 500 mg twice a day in patients experiencing an osteoarthritis flare, as well as for patients with rheumatoid arthritis. Celecoxib in this model was evaluated at doses of 100 mg twice a day and 200 mg once a day. It should be noted that NSAIDs will not affect the rheumatoid arthritis except to decrease pain and inflammation. The patients will still need to receive disease-modifying drugs for rheumatoid arthritis.
A major effort has been made in the investigation of celecoxib to determine the impact this drug has on gastrointestinal ulceration rates. Endoscopic data have been accumulated on over 4,700 patients, with greater than 2,100 of those patients being over 65 years of age. In a 12-week trial, patients received either placebo, naproxen 500 mg twice a day, or celecoxib 50, 100, or 200 mg twice a day, and were evaluated on a monthly basis by endoscopy. Ulceration rates were found to be 2.3% with placebo, 16.2% with naproxen, and 3.4% with 50 mg twice a day, 3.1% with 100 mg twice a day, and 5.9% with 200 mg twice a day of celecoxib. The patients studied had osteoarthritis and were evaluated at baseline and at one, two, and three months. Similar results were demonstrated in patients with rheumatoid arthritis using the same drugs. Particularly noteworthy was the improved overall tolerability with celecoxib. In information submitted to the Food and Drug Administration, the incidence of abdominal pain was 4% with celecoxib, as compared with 8%–9% in the NSAID group and 2.8% in the placebo group. The incidence of dyspepsia was 13% with older NSAIDs, compared to 8.8% with celecoxib and 6.2% with placebo. Of particular note was the low rate of discontinuation with celecoxib, at 7.1% compared to 6.1% with placebo. Only 0.8% of patients discontinued celecoxib because of dyspepsia, compared to 0.6% with placebo. Clinically significant bleeding developed in only two of 5,285 patients evaluated—a rate of 0.04%, much lower than the 2% bleeding rate seen with naproxen.
Celecoxib does contain a sulfonamide group and this should be taken into consideration regarding potential allergy problems. In addition, patients who are allergic to aspirin should not receive celecoxib because of the potential for cross-sensitivity. The dosage for osteoarthritis is either 200 mg once daily or 100 mg twice daily; for rheumatoid arthritis, 100 or 200 mg twice daily.
One noteworthy consideration in the clinical trials with etanercept was the rapid onset of beneficial effects. In these studies, 49% of the patients on 25 mg demonstrated an ACR 20 within one month of initiating therapy. In a second study, in which etanercept was added to methotrexate that had been used for at least six months at a stable dosage, the ACR 20 was seen at three months in 66% of patients on the etanercept/methotrexate combination and in 33% of the patients receiving placebo and methotrexate. The ACR 50 was demonstrated at six months in 42% on etanercept/methotrexate combination and in 3% on placebo/ methotrexate.
Some important adverse reactions have been demonstrated with this drug and should be clearly communicated to patients when they are being considered for therapy with etanercept. Infections were seen in 35% of patients. Among these were 22 serious infections among 745 patients followed in open-label trials. There is concern that because of the drug- modulating cellular immune response, patients will not be able to mount an adequate immune response when they are receiving etanercept. New positive antinuclear antibodies were demonstrated in 11% of patients on etanercept, compared with 5% receiving placebo, and new positive, double-stranded DNA was present in 15% of cases, as compared to 4% of the placebo group.
Other side effects include injection site reactions, headaches, and rhinitis. Patients receiving etanercept should not receive live-virus vaccines concurrently.
The recommended dosage of etanercept is 25 mg twice weekly given subcutaneously. The maximum dosage has not been studied yet. The drug should be injected into the thigh, abdomen, or upper arm. Sites of injections should be rotated. With a price tag of approximately $10,000 per year, the economic aspects of drug therapy will play an important role in patient selection.
Leflunomide exhibits its pharmacologic effect by inhibiting dihydro- orotate dehydrogenase, which causes inhibition of pyrimidine biosynthesis and has anti-proliferative activity. This suppresses proliferation of cells stimulated by activation of T-cell receptor complexes, and it has an anti-inflammatory effect.
Leflunomide is a prodrug that is metabolized to active metabolites. It demonstrates a high degree of bioavailability and has a half-life of 14 days. The site of metabolism for this drug is unknown. It is either in the gut wall or the liver. It demonstrates an increased free fraction in patients who have chronic renal insufficiency but demonstrates no changes in pharmacokinetic parameters on the basis of age or gender.
Leflunomide can inhibit CYP450 2C9. This is an important interaction, as many of the NSAIDs that might be taken concurrently with leflunomide are metabolized through that pathway. An interesting interaction with leflunomide involves smokers, who have a 38% increase in the clearance of leflunomide. Clinical trials with leflunomide have been conducted comparing its efficacy to methotrexate using a dosage of leflunomide 20 mg per day and methotrexate at 7.5–15 mg per week or placebo in patients who have rheumatoid arthritis evaluated over 52 weeks. The ACR 20 responder rate was similar for leflunomide at six months and 12 months (41% and 49%, respectively). Similar results were seen with methotrexate. Leflunomide and methotrexate were also superior to placebo in reducing the progression of structural disease based on the Sharp x-ray score.
Leflunomide 20 mg per day has also been compared with sulfasalazine 2 g per day or placebo over 52 weeks. The ACR 20 responder rate was 58% for leflunomide and 54% for sulfasalazine. The progression of structural change was significantly different between leflunomide and placebo but not statistically different between sulfasalazine and placebo. Patients who should not receive leflunomide include those who have significant hepatic impairment or hepatitis B or C. Patients should not receive live-virus vaccines while they are receiving leflunomide. Liver enzyme elevations of greater than three times the upper limit of normal were demonstrated in 5% of patients receiving leflunomide.
The most common adverse effects are diarrhea, alopecia that is reversible when the drug is discontinued, and rash. The dosing of leflunomide involves a 100 mg loading dose given daily for three days, then 20 mg per day thereafter. The patient should be monitored with a monthly assessment of ALT to detect hepatic toxicity.
Cefdinir demonstrates a higher degree of bioavailability from the suspension than from the capsules. Peak plasma concentrations are higher from the suspension than from capsules. Cefdinir is not metabolized; it is eliminated renaly unchanged. Cefdinir has a half-life of 1.7 hours. The dosage should be reduced if creatinine clearance is less than 30 ml per minute, but dosage adjustments are not otherwise necessary on the basis of age, gender, race, hepatic disease, or administration with food. Concurrent use of antacids will decrease cefdinir absorption and concurrent use of probenecid will delay cefdinir elimination.
A peculiar interaction with this cephalosporin is the potential for iron to bind to the antibiotic, resulting in decreased antibiotic levels. Patients taking iron and cefdinir should ingest the products two hours apart. The most common side effect of cefdinir is diarrhea, occuring in 16% of patients taking capsules, but only 8% of patients receiving suspension. Vaginal candidiasis occurred in 5% of female patients taking cefdinir, and nausea occurred in 3% of patients. An interesting side effect reported by a few patients was the development of reddish stools. This is thought to be due to a nonabsorbable complex of drug and iron in the gastrointestinal tract.
Cefdinir can be given as a once-daily dose of 600 mg to adults or a twice-daily dose of 300 mg—with two noteworthy exceptions: Patients who are being treated with cefdinir for pneumonia or skin infections should be dosed on a twice-daily basis. In patients with a creatinine clearance of less than 30 ml per minute, the dosage should be 300 mg once daily, and in patients maintained on long-term hemodialysis, the recommended initial dosage is 300 mg every other day. Cefdinir is available in capsules containing 300 mg and in suspension containing 125 mg per 5 ml.
Noteworthy drug interactions include interaction with monoamine oxidase inhibitors, which should not be given within two weeks of the patient receiving citalopram. Drugs that inhibit cytochrome P450 3A4, such as erythromycin and ketoconazole, as well as drugs metabolized via the 2C19 system, such as omeprazole, can decrease citalopram clearance. Metoprolol levels can increase twofold in the presence of citalopram. No change in levels or activity was seen when citalopram was given with warfarin, digoxin, or lithium. Only a small fraction of the dose of citalopram is excreted unchanged in the urine; therefore, dosage adjustment for mild-to-moderate renal impairment is not necessary.
Adverse effects associated with citalopram are similar to those associated with other SSRIs. Nausea is the most common adverse effect. This usually occurs early in therapy and will diminish with time. Insomnia will be reported in some patients and somnolence in others. This is consistent with the adverse effect profile seen with other drugs of the class. Increased sweating, tremor, and ejaculation disorder have also been reported with this drug. The adverse effect that may be somewhat distinguishing when compared with others in this pharmacologic category is the incidence of dry mouth, which in clinical trials was reported in 20% of patients compared with 14% of patients receiving placebo.
The dosage of citalopram for treating depression is 20 mg once daily. It can be given in the morning or in the evening, with or without food. It is also acceptable to increase the dosage to 40 mg after one week,with a maximum daily dosage of 60 mg per day. In elderly patients and patients with impaired hepatic function, the recommended dosage is 20 mg daily. As with other drugs of this class, the full pharmacologic effect will not be seen until 3–4 weeks after the drug is started.
| New Chemical Entities Approved by the FDA in 1998 | |||||
| Brand name | Generic name | Approval Date | Manufacturer | Dosage form | Approved indication(s) |
| Tasmar | Tolcapone | Jan. 29 | Hoffmann La Roche | Tablet | As an adjunct to levodopa and carbidopa for treatment of idiopathic Parkinson’s disease |
| Amerge | Naratriptan hydrochloride | Feb. 10 | Glaxo Wellcome | Tablet | Acute treatment of migraine headache |
| Singulair | Mentelukast sodium | Feb. 20 | Merck & Co. | Tablet | Treatment of asthma |
| Refludan | Lepirudin | March 6 | Hoechst Marion Roussel | Injectable | Anticoagulation for treatment of heparin-induced thrombocytopenia and thromboembolic disease |
| Lotemax | Lortreprednol etabonate | March 9 | Bausch and | Suspension | Treatment of steroid-responsive inflammatory ocular conditions |
| Detrol | Tolterodine tartrate | March 25 | Pharmacia & Upjohn | Tablet | Treatment of overactive bladder |
| Viagra | Sildenafil citrate | March 27 | Pfizer | Tablet | Treatment of erectile dysfunction |
| Actonel | Risedronate sodium | March 28 | Procter & Gamble | Tablet | Treatment of Paget’s disease of bone |
| Azopt | Brinzolamide | April 1 | Alcon Laboratories | Suspension | Treatment of elevated intraocular pressure in ocular hypertension or open-angle glaucoma |
| Sucraid | Sacroside | April 4 | Orphan Medical | Oral solution | Treatment of hereditary sucrase deficiency |
| Zemplar | Paricalcitol | April 17 | Abbott Laboratories | Injectable | Prevention and treatment of hyperparathyroidism secondary to chronic renal failure |
| Xeloda | Capecitabine | April 30 | Hoffmann La Roche | Tablet | Treatment of metastatic breast cancer resistant to paclitaxel and/or antracycline-containing chemotherapy regimen |
| Aggrastat | Tirofiban hydrochloride | May 14 | Merck | Injectable | For use in combination with heparin for treatment of acute coronary syndrome |
| Integrilin | Eptifibatide | May 18 | Cor Therapeutics | Injectable | Treatment of acute coronary syndrome |
| Atacand | Candesartan cilexetil | June 4 | Astra Merck Group | Tablet | Treatment of hypertension |
| Priftin | Refapentine | June 22 | Hoechst Marion Roussel | Tablet | Treatment of pulmonary tuberculosis |
| Maxalt/Maxalt- Maltrapidisc | Rizatriptan benzoate | June 29 | Merck & Co. | Tablet | Acute treatment of migraine headache |
| Infasurg | Calfactant | July 1 | Ony Inc. | Suspension | Prevention and treatment of neonatal respiratory distress syndrome |
| Thalomid | Thalidomide | July 16 | Celgene Corp | Capsule | Acute and/or maintenance treatment of cutaneous manifestations of erythema nodosum leprosum |
| Celexa | Citalopram hydrobromide | July 17 | Forest Laboratories | Tablet | Treatment of depression |
| Vitravene | Fomivirsen sodium | August 26 | Isis Pharmaceuticals | Injectable | Treatment of cytomegalovirus retinitis in AIDS |
| Arava | Leflunomide | Sept. 10 | Hoechst Marion Roussel | Tablet | Treatment of rheumatoid arthritis |
| Acutect | Technetium TC-99M apcitide | Sept. 14 | Diatide Inc | Injectable | For use in scintigraphic imaging of acute venous thrombosis |
| Sustiva | Efavirenz | Sept. 17 | DuPont Merck Pharmaceutical | Capsule | Treatment of HIV infection |
| Valstar | Valrubicin | Sept 25 | Anthra Pharmaceuticals | Solution | Intravesical therapy of BCG-refractory carcinoma in situ of urinary bladder |
| Renagel | Sevelamer hydrochloride | Oct. 30 | Geltex Pharmaceuticals | Capsule | Reduction of serum phosphorus during hemodialysis in end-stage renal disease |
| Micardis | Telmisartan | Nov. 10 | Genzyme/Knoll | Injectable | Recombinant thyroid-stimulating hormone for thyroid cancer testing |
| Ziagen | Abacavir | Dec. 17 | Glaxo Wellcome | Tablet | Treatment of HIV infection |
| Provigil | Modafinil | Dec. 24 | Cephalon Inc. | Tablet | Treatment of narcolepsy |
| Celebrex | Celecoxib | Dec. 31 | Searle | Capsule | Treatment of osteoarthritis and rheumatoid arthritis |
Drug interactions of note include monoamine oxidase inhibitors, which should not be given with rizatriptan; propranolol increases rizatriptan levels by 70%, and ergot compounds should not be administered within 24 hours. No interactions were detected in clinical evaluation studies when patients were taking nadolol, metoprolol, paroxetine, or oral contraceptives.
Patients evaluated for migraine relief in clinical trials demonstrated efficacious pain relief in 67%–77% of patients in the 10-mg group two hours after receiving a single dose. It is noteworthy that some patients who did not respond the first time rizatriptan was tried did well with follow-up doses. As with other drugs in this class, return of headache within 24 hours of dosing occurred in 32%–35% of patients. Patients with ischemic heart disease or uncontrolled hypertension should not receive rizatriptan. However if the patient normally has controlled blood pressure and is on medication, the pain of the migraine may be the reason their blood pressure is increased. Patients with basilar artery or hemiplegic migraine should also not receive rizatriptan.
The most common side effects are paresthesias, dizziness, chest tightness, somnolence, and asthenia. It is advisable that the patient receive the first dose of medication in the prescriber's office. If there are symptoms of chest tightness, the patient can be properly counseled. The dosage of rizatriptan is 5 mg or 10 mg taken as the tablet or the MLT (orally disintegrating) dosing form. A second dose can be taken in two hours if the patient has not achieved relief. A maximum daily dosage of rizatriptan is 30 mg. An important dosage adjustment is indicated in the patient taking propranolol. These patients should only receive a 5-mg dosage of rizatriptan.
An important point of patient counseling regarding the use of rizatriptan involves peeling the foil backing off the MLT dosing form, rather than trying to push the tablet through the foil, because the tablet will crumble if pushed. It is also important that the patient have dry hands when holding the MLT dosing form, so it does not dissolve in the hand.
The dosage of fenofibrate microsized is initiated at 67 mg taken once daily with food. Repeated triglyceride measurements should be taken at 4–8 week intervals. The dosage can be increased to two or three capsules taken once daily as appropriate for the control of triglycerides. If the triglyceride level has not been reduced by two months of the maximum dosage, the fenofibrate should be disontinued.
There are several important considerations in the adverse effects profile of infliximab. Increased risk of infections associated with the inhibition of TNF is a primary area of concern. Infections occurred in 21% of patients receiving infliximab, compared with 11% in the placebo group. Lymphoma was diagnosed in three cases out of 394 patients treated with infliximab. It is known that patients receiving immunosuppressives are at greater risk for the development of lymphoma, and the association with infliximab use is uncertain. Patients can also develop a positive test for human chimeric antibody. Infusion reactions were more common in patients who were human chimeric antibody–positive. There was also the development of positive antinuclear antibodies as well as anti-double strand DNA (an antibody against DNA). Headache, nausea, and abdominal pain round out the adverse effects profile. Only 5% of patients discontinued infliximab as a result of adverse effects. The primary adverse effect necessitating discontinuation was infusion reaction.
The dosage for treatment of moderate-to-severe Crohn's disease was 5 mg/kg given as a one-time dose. No limit has been described as to how many acute treatments can be given over time. In patients with fistulizing Crohn's disease, the dosage is 5 mg/kg repeated at two and six weeks for a total regimen of three doses. The medication should be carefully reconstituted using a swirling motion rather than shaking the vial. Infliximab should be used within three hours of reconstitution. An important administration consideration is the necessity to avoid equipment or devices containing polyvinyl chloride. Infliximab should be infused through a polyethylenelined infusion set using a low-protein-binding filter.
Drug interactions that have been identified in patients taking telmisartan include digoxin, which will demonstrate an increased peak level when taken with telmisartan. Some inhibition of cytochrome p450 2C19 has been identified. This may inhibit metabolism of diazepam and omeprazole. Clinical trials of telmisartan have demonstrated blood pressure reductions with 40 mg and 80 mg of telmisartan that are similar to other drugs in this pharmacologic family. Larger dosages do not appear to cause a further decrease in blood pressure. A noteworthy feature of telmisartan is the good trough-to-peak ratio demonstrated in clinical trials, which ranged from 70%–100%. The onset of blood pressure reduction occurs within three hours, and the patient achieves a maximal reduction in blood pressure by about four weeks into dosing.
As with other drugs in this pharmacologic class, there is a very low incidence of adverse effects. The most commonly reported one was upper respiratory tract infection, which was reported in 7% of those taking telmisartan as compared with 6% in the placebo group. The incidence of cough was the same in the treatment group as in the placebo group. The initial dosage is 40 mg once daily, with or without food. The maximum recommended daily dosage is 80 mg. A diuretic can be added if the 80-mg dosage does not provide control of blood pressure.
An important pharmaceutical consideration regarding telmisartan concerns splitting tablets. Telmisartan is highly susceptible to moisture, and the tablets should not be split. The tablets come in a 28-tablet blister pack.
Tolcapone has been evaluated in patients with "on/off phenomenon" (cycling from control to lack of control) and has demonstrated a significant improvement in the number of "on" hours. In addition, total daily dosages of levodopa have been decreased by a significant degree in patients receiving tolcapone. Separate groups have been evaluated who do not have on/off phenomenon and were evaluated for activities of daily living. These patients were found to have an improvement in activities of daily living as well as a reduction in the daily dosage of levodopa that maintains control of their condition.
Serious adverse effects have been reported with tolcapone, including deaths from liver failure. These have necessitated restrictions and careful monitoring of patients who receive this medication. Patients should have AST and ALT concentrations monitored every two weeks for the first year, then every four weeks for six months, then every eight weeks from that point forward. The most common adverse effects are dyskinesia, nausea, sleep disorder, dystonia, anorexia, muscle cramps, diarrhea, hallucinations, and orthostatic hypotension. Syncope has been reported in 5% of patients taking tolcapone. It is essential that tolcapone be used in combination with carbidopa/levodopa. The starting dosage of tolcapone is 100 mg three times daily, with or without food. The dosage can be increased to 200 mg three times daily if necessary. If the patient does not improve within three weeks after receiving the larger dosage, the medications should be discontinued.
The release of nitric oxide from the nerve endings and endothelial cells as a result of sexual stimulation initiates the sequence of events that would normally result in an erection. Nitric oxide stimulates guanylate cyclase to produce cyclic GMP. When sildenafil inhibits phosphodiesterase-5, the inhibition allows increased actions of cyclic GMP, which allows relaxation of the smooth muscle cells of the corpus cavernosum. This facilitates development of an effective erection. Sildenafil is rapidly absorbed and achieves peak concentrations in about one hour. However, food can delay the time to peak concentration. The chemical half-life of sildenafil is 3–5 hours. Sildenafil is metabolized by the liver primarily by cytochrome p450 3A4, and excretion is primarily through feces. Higher plasma concentrations are seen in patients over 65 years of age, as well as in patients with hepatic or severe renal impairment.
A very important drug interaction with sildenafil has been described. Patients taking sildenafil should not receive nitrates because of an increased risk of acute decreases in blood pressure. Increased sildenafil levels have also been described in patients receiving cimetidine and erythromycin. In clinical trials, sildenafil was efficacious in approximately 75% of patients, compared with 25% of patients receiving placebo. Efficacy was demonstrated in a wide variety of conditions associated with impotence. These include spinal cord injuries, diabetes, radical prostatectomy, and medication-induced and psychogenic impotence. Efficacy ranged from 40%–50% in patients with radical prostatectomy and 90% in patients who had psychogenic impotence.
Adverse effects associated with sildenafil include headache, flushing, dyspepsia, and blue/green–tinged vision that is temporary. The dosage of sildenafil is 50 mg taken one hour before sexual activity. Sildenafil can be taken as early as four hours before sexual activity, and it will not start working until sexual stimulation takes place. The dosage can be increased to 100 mg or decreased to 25 mg on the basis of efficacy and tolerance.
The mechanism of action of trovafloxacin involves inhibition of DNA gyrase and topoisomerase 4 in the bacteria. The microbiologic activity of trovafloxacin includes but is not limited to Streptococcus pneumoniae (both penicillin-sensitive and penicillin-resistant), methicillin-sensitive Staphylococcus aureus, Bacteroides fragilis, Chlamydia pneumoniae, C. trachomatis, Legionella pneumophilia, Mycloplasma pneumoniae, and a wide range of gram-negative, aerobic organisms.
The pharmacokinetic profile is one of the most interesting aspects of this drug. Trovafloxacin has 90% bioavailability and achieves peak serum concentrations in one hour. The serum levels generated by 200 mg of trovafloxacin given I.V. or orally are almost identical. The high concentrations generated in lung and biliary tissue are dramatically higher than in blood levels. The half-life of trovafloxacin is 11 hours. Unlike other fluoroquinolones, trovafloxacin is hepatically eliminated by conjugation and excreted unchanged mainly in the feces. No dosage adjustment is necessary for patients with decreased renal function, even if they are on dialysis. No dosage adjustment is necessary for advanced age or patients who have eaten recently. The dosage should be decreased for patients with mild-to-moderate cirrhosis, however.
Drug interactions with trovafloxacin include divalent cations such as iron, aluminum, magnesium, and sucralfate. These interactions are seen with other fluoroquinolones as well. Sodium citrate and citric acid oral solution (Bicitra) can also inhibit the absorption of trovafloxacin when given orally. I.V. morphine can slow the gastrointestinal absorption of trovafloxacin as well.
The most noteworthy adverse effect associated with trovafloxacin is dizziness, which can be lessened by taking the medication at bedtime with food. Cases of dizziness secondary to trovafloxacin often will decrease if the patient continues therapy beyond the third dose. Other adverse effects include nausea, headache, and lightheadedness. A few cases of elevated liver enzymes or pancreatitis have been described in post-marketing surveillance studies. If the patient is going to take trovafloxacin for more than 21 days, liver enzymes should be checked.
The dosage of trovafloxacin is 300 mg I.V. daily for nosocomial pneumonia and complicated intra-abdominal infections. When the patient is changed to oral therapy, the dosage is 200 mg once daily. The dosage for urinary tract infections, uncomplicated skin infections, or bronchitis is 100 mg once daily. The 200-mg dosage, either I.V. or orally, is used for the other indications listed above. This includes surgical prophylaxis for elective abdominal surgery and vaginal hysterectomy, which can be given as 200 mg I.V. or orally one time prior to the procedure. Trovafloxacin is an attractive option for broad-spectrum coverage in seriously ill patients. The low incidence of seizures and low incidence of diarrhea, along with the easy transition from parenteral to oral therapy, will make it an attractive option for a variety of patients.
Caffeine and theophylline metabolism are inhibited when taken with grepafloxacin. Smoking enhances the clearance of grepafloxacin. Drugs that are metabolized by cytochrome p450 1A2 and 3A4 may be metabolized more slowly. Drugs that prolong the QTC interval such as class I and class III antiarrhythmics may place the patient at increased risk for torsade de pointes. Grepafloxacin will also slow the clearance of erythromycin, cisapride, pentamidine, and tricyclic antidepressants. The adverse effects profile includes nausea, taste changes, headache, and dizziness. The dosage for treating pneumonia is 600 mg daily for 10 days. The dosage for treating bronchitis is 400–600 mg daily for 10 days.
An important drug interaction with tolterodine involves fluoxetine, which can increase tolterodine levels by over 50%. In clinical trials, tolterodine 2 mg twice daily compared with placebo produced a statistically significant reduction in the number of micturitions over a 12-week interval study. It also demonstrated an increase in the volume of urine per micturition. Another small study compared the efficacy of tolterodine to oxybutynin 5 mg twice daily and placebo in patients with overactive bladder. After 12 weeks, the efficacy of the two drugs was similar, but there was a higher incidence of adverse effects in the oxybutynin group.
The most common adverse effects associated with tolterodine include dry mouth, dyspepsia, constipation, abnormal vision, dry eyes, and headache. The dosage is 2 mg twice daily, but 1 mg twice daily can be used if the patient does not tolerate the initial dose well, has hepatic dysfunction, or is receiving cytochrome p450 3A4 inhibitors.
Drug therapy options for senior patients are numerous, complex, and challenging. Patients need a drug therapy expert as their advocate now more than ever. Hopefully, the information contained in this article can be used to advance the care of patients in your practice setting.
Tom Frank, PharmD, BCPS, is Associate Professor of Pharmacy Practice, University of Arkansas for Medical Sciences College of Pharmacy, Jonesboro, Arkansas.
Copyright © 1999, American Society of Consultant Pharmacists, Inc. All rights reserved.