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PubMed2002

FDA drug approval summaries: fulvestrant.

Patients with hormone-sensitive breast cancer who have responded to tamoxifen may receive additional benefit from a second endocrine agent following progression or relapse after tamoxifen therapy. Fulvestrant (Faslodex((R)), ICI 182780, AstraZeneca Pharmaceuticals; Wilmington, Delaware) is a selective antagonist of estrogen designed to have no estrogenic effects. Lack of aqueous solubility led to the development of a parenteral formulation for monthly intramuscular administration. Fulvestrant has been shown to inhibit the proliferative effects of estrogen on sensitive tissues in vitro and in vivo, and is without apparent measurable estrogenic activity. The data upon which marketing approval for fulvestrant was based are summarized below. Eight hundred fifty-one postmenopausal women with advanced breast cancer were enrolled in two phase III studies, 400 in a North American double-blind study and 451 in a European open-label study, comparing the efficacy and safety of fulvestrant with anastrozole. Four hundred twenty-eight patients were randomized to receive fulvestrant 250 mg monthly by intramuscular injection and 423 patients were to receive anastrozole 1 mg daily. Patients were considered hormone sensitive either by receptor status or previous response to endocrine therapy. Over 96% of patients had previously received tamoxifen, either in the adjuvant setting or as treatment for metastatic disease. The primary study end points were response rate and time to progression. Response rates for patients treated with fulvestrant were 17% and 20% in the North American and European trials, respectively, compared with 17% and 15% in the anastrozole treatment arms. There were no statistically significant differences in response rates, time to progression, or survival between treatment arms in either study. The most common adverse events attributed to the treatment (>10%) were injection-site reactions and hot flashes. Common events (1%-10%) included asthenia, headache, and gastrointestinal disturbances (nausea, vomiting, and diarrhea), as well as rash and urinary tract infections. A small increase in joint disorders was reported in the anastrozole-treated patients. On April 25, 2002, fulvestrant 250 mg by monthly intramuscular injection was approved by the U.S. Food and Drug Administration for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy. Approval was based on similarity of response rates and time to progression between fulvestrant and anastrozole.

Antineoplastic Agents, Hormonal↗
PubMed2004

The evolving role of epoetin alfa in cancer therapy.

Since its initial indication as hormone-replacement therapy in the anemia of chronic kidney disease, epoetin alfa has become a mainstay of therapy for chemotherapy-related anemia. Clinical studies have shown that epoetin alfa administered once weekly or three times weekly improves hemoglobin levels, decreases transfusion requirements, and improves quality of life independent of tumor response to chemotherapy. Ongoing research is now evaluating ways to improve the response rate to epoetin alfa, the potential benefits of alternative dosing regimens and early treatment intervention, and nonanemia-related indications (e.g., cognitive impairment, asthenia). In addition, scientists are exploring the role of epoetin alfa in preventing apoptosis and ischemic brain injury, as well as its activity in other nonerythroid tissues. Thus, the role of epoetin alfa is likely to expand in the cancer setting in the coming years.

Anemia↗
PubMed1999

Risks versus benefits in the clinical application of aromatase inhibitors.

Third-generation aromatase inhibitors are able to reduce circulating plasma estrogen concentrations in postmenopausal women to below detectable limits and significantly inhibit aromatase, the enzyme responsible for estrogen synthesis, in normal breast tissue and breast tumors. Their role in the treatment of advanced breast cancer is well established and their use in adjuvant therapy is currently being explored. On the basis of these trials, evaluation of these inhibitors in the prevention of breast cancer may be appropriate. Aromatase inhibitors have non-specific toxic side effects including (but not limited to): asthenia, headache, nausea, peripheral edema, fatigue, vomiting and dyspepsia. In addition, certain endocrinological side effects in postmenopausal women are notable, namely hot flushes and vaginal dryness. In advanced breast cancer, these side effects result in treatment withdrawal in few (<4%) women. Of concern, however, are the potential long-term endocrinological side effects in women receiving treatment as first-line adjuvant therapy or in sequence or combination with tamoxifen or other selective estrogen receptor modulators (SERMs). Current studies of adjuvant treatments for breast cancer in healthy women are carefully evaluating, in addition to general toxicities, the effects on bone, lipid metabolism, cardiovascular risk, quality of life and menopausal symptoms. Careful evaluation of all-cause morbidity and mortality is necessary to plan trials and justify long-term use of aromatase inhibitors in the treatment or prevention of breast cancer in healthy women.

Anticarcinogenic Agents↗
PubMed1994

Adverse effects of alpha 1-adrenergic blocking drugs.

Earlier nonselective alpha 1-adrenergic blocking drugs such as phentolamine and phenoxybenzamine are now restricted to the pharmacological management of alpha 1-adrenergic crisis and phaeochromocytoma. Prazosin, the first selective alpha 1-blocker approved for the treatment of hypertension, became available in the mid-1970s. Additional alpha 1-blockers such as doxazosin and terazosin have been introduced during recent years. The undesirable effects of all members of this class are similar. Most adverse events can be attributed to reversible competitive antagonism of postsynaptic alpha 1-adrenergic receptors in tissues that sustain high levels of alpha-adrenergic sympathetic tone, e.g. resistance arteries, capacitance veins and the urinary bladder outflow tract. Orthostatic hypotension with a sensation of intense faintness and occasional syncope, can occur shortly after the initial dose. Aggravating factors include upright posture, intravascular volume depletion and concurrent administration of other medications that lower blood pressure, including all other classes of antihypertensive drugs. The problem is reduced or avoided by the choice of low starting doses, beginning treatment at bedtime and by minimising other risks. Among overall adverse effects, asthenia, dizziness, faintness and syncope predominate and occur in 10 to 20% of patients, leading to discontinuation of therapy in about half that number. Infrequent adverse events include headache, drowsiness, palpitations, urinary incontinence and priapism. Some patients experience a 1 to 2kg bodyweight gain which may be associated with secondary hyperaldosteronism. Tolerance appears to develop to the benefits of alpha 1-blockade in patients with congestive heart failure, but not in hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed2001

Management of chemotherapy-induced adverse effects in the treatment of colorectal cancer.

The anticancer agents fluorouracil, raltitrexed, irinotecan and oxaliplatin show limited efficacy in the treatment of colorectal cancer and may be associated with substantial toxicity. Therefore, the prevention and reduction of chemotherapy-induced adverse effects is of major significance, in accordance with the increasing concern for the quality of life of patients with cancer. Therapeutic drug monitoring of fluorouracil and chronomodulation of fluorouracil and oxaliplatin, have been effective in reducing the incidence and gravity of adverse effects in several clinical trials. However, these concepts have not been implemented in clinical practice yet. At the present time, dose adaptation and supportive measures are the main tools for toxicity control in the treatment of colorectal cancer. In this review, supportive measures for alleviation of the adverse effects of fluorouracil, raltitrexed, irinotecan and oxaliplatin, respectively, are described, based on study results. The main adverse effects of these agents are myelosuppression, oral mucositis, diarrhoea, acute cholinergic syndrome, nausea and emesis, neurotoxicity, hand-foot syndrome and other cutaneous adverse effects, ocular toxicity, cardiotoxicity, small bowel toxicity, asthenia, elevated liver transaminase levels and alopecia. The incidence and gravity of these adverse effects are more or less related to the agent and administration schedule involved. The supportive measures and recommendations include the use of specific drugs, alterations of administration schedule and several nonpharmacological methods. In addition, guidelines for dosage adjustments when toxicity occurs are presented. For optimal management of adverse effects, patients should be considered individually, while patients, nurses and physicians should cooperate to identify and treat adverse effects in an early stage of their development.

Antineoplastic Agents↗
PubMed2004

Overview of the tolerability of gefitinib (IRESSA) monotherapy : clinical experience in non-small-cell lung cancer.

Cytotoxic chemotherapy treatment options for patients with non-small-cell lung cancer (NSCLC) have limited efficacy and are often associated with significant toxicity. Therefore, there is an unmet need for novel drugs that are not only effective in treating this disease but are also well tolerated. Gefitinib is an orally active epidermal growth factor receptor tyrosine kinase inhibitor that blocks the signal transduction pathways implicated in cancer cell growth and survival. It has recently been approved for the treatment of advanced/refractory NSCLC. This review presents the tolerability data from phase I and II gefitinib monotherapy trials, along with data from the worldwide 'Expanded Access Programme' and post-marketing use of gefitinib. Gefitinib was found to be generally well tolerated at the approved dosage of 250 mg/day; the most commonly reported adverse drug reactions (ADRs) were mild to moderate skin rash and diarrhoea, which were manageable and non-cumulative. Other ADRs observed with the use of gefitinib included: dry skin, pruritus, acne, nausea, vomiting, anorexia, asthenia and asymptomatic elevations in liver transaminase levels. Well recognised adverse effects seen with cytotoxic chemotherapy (such as bone marrow depression, neurotoxicity and nephrotoxicity) were not observed. Although the frequency and severity of ADRs increased with the dosage across the range studied (50-1000 mg/day), few patients required dosage reductions or the withdrawal of treatment, and those who did usually received gefitinib >or=600 mg/day.Thus, the available data indicate that gefitinib is well tolerated in patients with a range of solid tumours, including locally advanced or metastatic NSCLC.

Antineoplastic Agents↗
PubMed1998

Anastrozole. A review of its use in the management of postmenopausal women with advanced breast cancer.

UNLABELLED: Anastrozole is a new oral nonsteroidal aromatase inhibitor indicated for the second-line endocrine treatment of postmenopausal women with advanced breast cancer. In postmenopausal women, anastrozole significantly reduces plasma estrogen levels; maximal suppression is achieved at dosages > or = 1 mg/day and levels remain suppressed during long term therapy. In two phase III clinical trials, anastrozole 1 or 10 mg/day showed similar clinical efficacy to that of oral megestrol (megestrol acetate) 160 mg/day in postmenopausal women with advanced breast cancer. Primary end-points [including time to disease progression (120 to 170 days) and overall response rates (complete and partial response and stable disease lasting > or = 24 weeks: 29 to 37%)] and secondary end-points [time to treatment failure (115 to 168 days) and duration of response (257 to 261 days)] did not differ significantly between treatment groups. However, a significant survival advantage was observed in patients treated with anastrozole 1 mg/day compared with megestrol in a follow-up combined analysis of patients enrolled in both studies (median time to death 26.7 vs 22.5 months). Quality of life parameters were generally improved to a similar extent in all treatment groups. Anastrozole is generally well tolerated in the majority of patients, the most common adverse events being gastrointestinal (GI) disturbances (incidence 29 to 33%). These events are generally mild or moderate and transient. Other adverse events reported with anastrozole include headache (< or = 18%), asthenia (< or = 16%), pain (< or = 15%), hot flushes and bone pain (both < or = 12%), back pain and dyspnoea (both < or = 11%) and peripheral oedema (< or = 9%). GI disturbance tended to be more common with anastrozole than megestrol, particularly at the 10 mg/day dosage; however, compared with megestrol, anastrozole is less frequently associated with weight gain. CONCLUSIONS: Anastrozole, with its apparent survival advantage versus megestrol (demonstrated in a combined analysis of phase III studies), convenient once daily oral administration and acceptable short term tolerability profile, is a second-line treatment option for postmenopausal patients with tamoxifenrefractory advanced breast cancer. The results of ongoing comparative trials with tamoxifen will determine the relative efficacy of anastrozole as first-line endocrine therapy for advanced breast cancer and as adjuvant therapy for early disease. In addition, direct comparative studies are required to determine the efficacy of anastrozole relative to that of other oral aromatase inhibitors such as letrozole and vorozole.

Anastrozole↗
PubMed2001

Oral tegafur/uracil.

Tegafur is a prodrug of the antineoplastic agent fluorouracil, and is administered in a 1:4 molar ratio with the fluorouracil modulator uracil. Oral tegafur/uracil 300 mg/m(2)/day plus calcium folinate 75 or 90 mg/day for 28 days every 35 days was as effective as intravenous (IV) fluorouracil 425 mg/m(2)/day plus folinic acid 20 mg/m(2)/day for 5 days every 28 or 35 days in the treatment of patients with metastatic colorectal cancer in two large, randomised, nonblind, multicentre trials (n = 816 and 380). Median survival time among patients treated with tegafur/ uracil or fluorouracil was approximately 12 months in both trials. Results from both trials also demonstrated no significant between-group differences in overall response rates among patients treated with oral tegafur/uracil (12 and 11%) or IV fluorouracil (15 and 9%). In elderly patients (aged > or = 70 years) with metastatic colorectal cancer, results from small noncomparative studies showed that treatment with oral tegafur/uracil afforded overall response rates of 12.5 to 29% and was well tolerated. During preoperative treatment with oral tegafur/uracil plus calcium folinate as an adjunct to radiotherapy in patients with stage II or III rectal cancer, the maximum tolerated dosage of tegafur/uracil was 350 mg/m(2)/day (administered 5 days per week for 5 weeks). Among the 15 patients who were followed for 5 to 8 months, three had a complete response to treatment. Treatment with tegafur/uracil was also given postoperatively. The most common adverse events associated with oral tegafur/uracil were anaemia, nausea/vomiting, diarrhoea, thrombocytopenia, mucositis, neutropenia, asthenia, anorexia and abdominal pain. Oral tegafur/uracil was associated with a significantly more favourable tolerability profile than IV fluorouracil in the two large randomised trials. In particular, stomatitis and most adverse haematological events were less frequent.

Administration, Oral↗
PubMed2002

Tamsulosin: a review of its pharmacology and therapeutic efficacy in the management of lower urinary tract symptoms.

UNLABELLED: Tamsulosin is a subtype-selective alpha(1A)- and alpha(1D )-adrenoceptor antagonist. alpha(1)-Receptors predominate in the prostate gland, prostatic capsule, prostatic urethra and bladder, and the relaxation of prostate and bladder smooth muscles is associated with improved maximal urine flow (Q(max)) and alleviation of lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH). Tamsulosin 0.4 mg once daily in a modified-release formulation increased Q(max) and improved symptom scores relative to baseline to a greater extent than placebo in 12- and 13-week double-blind, randomised, multicentre, clinical trials in patients with LUTS, with statistical significance between treatments for Q(max) values in two of three published US and European studies. Tamsulosin is effective in patients with mild to severe LUTS associated with BPH, in patients with diabetes mellitus and in the elderly, and does not interfere with concomitant antihypertensive therapy. Pooled data based on patients receiving tamsulosin 0.4 or 0. 8mg once daily indicate maintenance of efficacy for up to 6 years. Tamsulosin 0.4 mg once daily was of similar efficacy to alfuzosin 2.5 mg three times daily, with less tendency to cause hypotensive effects, in a double-blind, randomised 12-week trial. Benefit of the drug has also been shown in patients with acute urinary retention or chronic abacterial prostatitis, those receiving high energy transurethral microwave thermotherapy, and in patients with prostate cancer with radiation-induced urethritis. Dizziness and abnormal ejaculation are stated to be the most common adverse events, with asthenia, postural hypotension and palpitations being seen less frequently (1 to 2% incidence), in patients receiving tamsulosin 0.4 mg once daily. Tamsulosin has not been associated with clinically significant changes in blood pressure in clinical trials. CONCLUSION: The alpha(1A)- and alpha(1D)-adrenoceptor antagonist tamsulosin, given at a dosage of 0.4 mg once daily in a modified-release formulation, is effective and well tolerated in the treatment of LUTS associated with BPH. Although the drug has been directly compared to date with one other agent only, data show overall that tamsulosin clearly offers advantages over other alpha(1)-adrenoceptor antagonists in terms of the need for a single daily dose only, and its low potential for hypotensive effects or interference with concomitant antihypertensive therapy. Dosage titration at the start of treatment is not necessary. Tamsulosin has a rapid onset of action and is effective in patients with moderate or severe symptoms. The drug is therefore a valuable therapeutic option, with both demonstrated and potential advantages over older nonselective agents, in the management of patients with LUTS associated with BPH.

Adrenergic alpha-Antagonists↗
PubMed1985

Enalapril in hypertension and congestive heart failure. Overall review of efficacy and safety.

Multiclinic controlled studies have shown that enalapril alone 10 to 40 mg/day orally is effective in lowering blood pressure in patients with essential hypertension. Enalapril has been compared with thiazides and beta-blockers (propranolol, metoprolol and atenolol). The effect on systolic blood pressure has been greater with enalapril than with beta-blockers. The proportion of patients who respond to enalapril alone with a decrease in diastolic blood pressure (greater than or equal to 10mm Hg) is around 70%. When a thiazide is added to the treatment, the proportion is above 90%. Enalapril improves the signs and symptoms associated with congestive heart failure. Patients increased their exercise tolerance by an average of 148 sec and improved in their NYHA cardiac status and prognosis classification. The overall incidence of side effects is similar to that seen in the placebo control groups. Side effects such as agranulocytosis, taste loss, rash, proteinuria were not characteristic of enalapril. This supports the hypothesis that the improved safety profile of enalapril is the result of being a nonsulphydryl angiotensin-converting enzyme (ACE) inhibitor. The most common side effects reported were dizziness, headache and asthenia. Abnormalities in electrolytes, uric acid, glucose or in lipids have generally not been associated with enalapril.

Adrenergic beta-Antagonists↗
PubMed1987

Comparative efficacy of cyclandelate versus flunarizine in the prophylactic treatment of migraine.

In a double-blind, parallel-group randomised trial of 3 months' duration, the efficacy of cyclandelate 800 mg twice daily in migraine prophylaxis was compared with that of flunarizine 5mg daily in 40 patients. In comparison with placebo and baseline values, both drugs significantly relieved symptoms of migraine as assessed by indices of pain total index, headache index, analgesic consumption and number of migraine days. Patients taking flunarizine experienced side effects such as drowsiness, weight gain and asthenia, while the most common complaint reported with cyclandelate was gastric upset. These results suggest that cyclandelate may be a useful alternative in migraine prophylaxis.

Adolescent↗
PubMed1987

Terazosin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in essential hypertension.

Terazosin is a post-synaptic alpha 1-adrenoceptor antagonist with a similar pharmacodynamic profile to prazosin. It differs from prazosin in having a longer duration of action, with an elimination half-life some 2 to 3 times that of prazosin, allowing the convenience of once daily administration. Moreover, its absorption from the gastrointestinal tract is more complete and predictable than that of prazosin which may facilitate dose titration. Terazosin therapy results in a significant reduction in blood pressure in patients with mild to moderate essential hypertension, with little influence on heart rate. The drug is an effective antihypertensive when administered as monotherapy or in combination with a range of antihypertensive agents including beta-blockers, diuretics and combinations of the two. In the few patients with congestive heart failure studied, terazosin produced an increase in cardiac output with a reduction in ventricular filling pressure and systemic vascular resistance, but no studies have been performed to assess the therapeutic potential of terazosin in this indication. Reductions in total plasma cholesterol and low density plus very low density lipoprotein cholesterol fractions have been reported after terazosin therapy, while high density lipoprotein cholesterol concentrations have tended to increase. Should such beneficial changes be confirmed in long term clinical studies they would suggest a therapeutic advantage of terazosin over some other antihypertensive drugs, particularly diuretics, which have been reported to adversely affect the plasma lipid profile. The most common side effects associated with terazosin treatment are dizziness, headache, asthenia and nasal congestion, but these are usually mild and do not require treatment discontinuation. Terazosin is normally administered once daily, starting at a dose of 1 mg/day and gradually titrating upwards as the blood pressure stabilises at each new dose, until blood pressure is adequately controlled or to a maximum dose of 20mg daily. First-dose syncope occurs rarely after terazosin, and can largely be avoided by giving the first dose at bedtime. Thus, terazosin offers a useful alternative to the drugs currently available for the management of mild to moderate essential hypertension either as monotherapy or in combination with other antihypertensive drugs.

Adrenergic alpha-Antagonists↗
PubMed1990

Comparative efficacy and safety of enalapril and sustained-release nifedipine in patients with mild to moderate hypertension. The Enalapril vs Nifedipine French Study Group.

The long acting angiotensin-converting enzyme inhibitor enalapril was compared with the calcium channel blocker nifedipine as sustained-release formulation in 136 patients with mild to moderate hypertension. This multicentre study was carried out in a double-blind, double-dummy fashion by 28 cardiologists in private practice. After a 2-week placebo period, patients were randomly allocated to 2 treatment groups; the first group received enalapril 20 mg daily (n = 68), and the second group received sustained-release nifedipine 20 mg twice daily (n = 68). The duration of treatment was 12 weeks. In both groups, hydrochlorothiazide 25 mg was added at week 4 if diastolic blood pressure remained greater than 90 mm Hg. At week 8, if the target diastolic pressure of less than 90 mm Hg was not achieved, the dosage of hydrochlorothiazide was increased to 50mg. The clinical characteristics of the patients in each group were comparable. After 4 weeks of treatment, the reduction in supine diastolic blood pressure was similar in both groups (12.1 mm Hg in the enalapril group vs 10.3 mm Hg in the nifedipine group). Moreover, although the difference between the groups was more noticeable after 12 weeks of treatment (16.3 vs 13.9 mm Hg, respectively), it did not reach significance. The number of patients experiencing clinical adverse effects was significantly greater in the nifedipine group than in the enalapril group [33 (48.5%) vs 18 (26.5%), respectively]. The most common complaints of patients administered nifedipine included swollen ankles, flushing and headaches, whereas complaints in the enalapril group included cough, asthenia, and epigastralgia. Three patients were withdrawn from the study because of side effects in the enalapril group and 10 were withdrawn from the nifedipine group. These results indicate that enalapril and sustained-release nifedipine are equally effective in controlling mild to moderate hypertension. However, enalapril was much better tolerated in this study.

Double-Blind Method↗
PubMed1990

Cadralazine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the treatment of hypertension.

Cadralazine is a peripheral arteriolar vasodilator which, unlike hydralazine or dihydralazine, has a protected hydrazino group. In hypertensive patients the optimal effect, based on the antihypertensive efficacy to tolerability ratio, is seen after a 15 mg dose when the drug is administered as monotherapy. When administered in combination with other antihypertensive agents, a 10 mg daily dosage seems appropriate. Noncomparative trials have shown that, in patients who had failed to respond adequately to a beta-blocker and/or diuretic, the addition of cadralazine 10 to 30 mg once daily reduced systolic/diastolic blood pressure by 11 to 19%/13 to 22%. This antihypertensive effect becomes evident over a 2- to 6-week period of therapy and persists during longer term administration. Comparative studies have shown that cadralazine is superior to placebo, and has a similar blood pressure lowering effect to hydralazine, dihydralazine and prazosin in patients not controlled by beta-blocker and/or diuretic but who continued to receive these treatments. Similarly, cadralazine and chlorthalidone were equally effective in reducing blood pressure in resting hypertensive patients but cadralazine shows an advantage in reducing the pressor response in exercising patients. Cadralazine is well tolerated when administered with a beta-blocker or diuretic. Most adverse effects become less frequent and severe with continued use, occur more frequently at dosages of 20 mg/day or more, and do not generally require withdrawal of therapy. Manifestations of the drug's vasodilating properties such as headache, asthenia, dizziness, palpitations and flushing are the most commonly reported symptoms during cadralazine monotherapy, but these may be reduced during combination therapy. The drug does not appear to induce a systemic lupus-like erythematosus syndrome, as may occur with hydralazine, but additional clinical experience is required to completely exclude this possibility. In conclusion, because of its efficacy as a second- or third-line antihypertensive agent, its simple once daily dosage regimen and favourable risk: benefit ratio, cadralazine may have a useful role, particularly in those hypertensive patients who do not respond adequately to established antihypertensive treatments. However, the therapeutic potential of cadralazine cannot be clearly established until the present limited clinical base is expanded to include comparisons with other classes of vasodilating drugs (ACE inhibitors and calcium antagonists), and its utility in the management of other indications such as severe hypertension during pregnancy has been adequately explored.

Antihypertensive Agents↗
PubMed1992

Review of fluvoxamine safety database.

A review of the safety and tolerability of fluvoxamine in worldwide marketing studies involving 24,624 patients, predominantly receiving fluvoxamine treatment in uncontrolled studies in depression, has been conducted. There was a marked preponderance of female patients and patients aged between 30 and 50 years. The majority of patients were treated for 6 weeks, with the most frequent modal total daily dose being 100mg. The greatest proportion of adverse experiences occurring, by COSTART body system, affected the digestive system (24.1%), the nervous system (23.7%), and the body as a whole (15.3%). The only adverse experience with an incidence greater than 10% was nausea (15.7%), with somnolence (6.9%) and asthenia (6.2%) as the next most frequent experiences. Notably, the rates of agitation and anxiety were only 1.4 and 1.3%, respectively. The incidences of adverse experiences increased with age, and were slightly higher in females than males. 15.1% of patients discontinued treatment prematurely as a result of adverse experiences, principally nausea, dizziness, vomiting, somnolence, abdominal pain, and headache. The overall incidence of serious adverse events associated with fluvoxamine treatment was 2.5%, and the incidence of overall suicidality, including suicidal ideation, overdose, and intentional overdose as well as attempted and completed acts of suicide, was remarkably low at 0.8%.

Adolescent↗
PubMed1993

Double-blind evaluation of nimesulide vs lysine-aspirin in the treatment of paediatric acute respiratory tract infections.

70 children aged 4 to 12 years with acute infection and inflammation of the respiratory tract (laryngitis, tracheitis, bronchitis, pneumonia) were enrolled in a double-blind investigation and randomised to treatment with nimesulide (50mg granules twice daily) or lysine-aspirin (360mg granules twice daily) for 5 days. The drugs were similarly effective in reducing cough, asthenia and dyspnoea, although nimesulide-treated patients experienced fewer gastrointestinal adverse events. These results confirm the efficacy of nimesulide in the treatment of respiratory inflammation and provide preliminary evidence of its value in children.

Acute Disease↗
PubMed1995

Lamotrigine. An update of its pharmacology and therapeutic use in epilepsy.

Lamotrigine is an antiepileptic agent which blocks voltage-dependent sodium channels, thereby preventing excitatory neurotransmitter release. Clinical evidence indicates that lamotrigine is effective against partial and secondarily generalised tonic-clonic seizures, as well as idiopathic (primary) generalised epilepsy. As monotherapy, lamotrigine 100 to 300 mg/day has similar medium term (30 to 48 weeks) efficacy to carbamazepine 300 to 1400 mg/day and phenytoin 300 mg/day against partial onset seizures and idiopathic generalised tonic-clonic seizures in adults with newly diagnosed epilepsy, and appears to be better tolerated than the older agents. As adjunctive therapy, lamotrigine (50 to 500 mg/day) has shown efficacy in short term ( < or = 6-months) placebo-controlled studies in adults with refractory partial epilepsy, reducing total seizure frequency (by < or = 60%) and producing improvement ( > or = 50% reduction in seizure frequency) in < or = 67% of patients. Both simple and complex partial seizures and secondarily generalised tonic-clonic seizures are reduced by lamotrigine, with generalised seizures (particularly absence seizures, atonic seizures and Lennox-Gastaut syndrome) tending to be more responsive than partial seizures. This reduction in seizure frequency is sustained on long term ( < or = 3 years) therapy and is reportedly accompanied by an improvement in psychological well-being. In children with refractory multiple seizure types, lamotrigine ( < or = 15 mg/kg/day; 400 mg/day) has proved effective as add-on therapy, with approximately equal to 40% of patients showing > or = 50% reductions in seizure frequency and approximately equal to 10 % achieving abolition of seizures after 3 months' treatment. Generalised seizures, including atypical and typical absence seizures, atonic and tonic seizures and Lennox-Gastaut syndrome are most responsive. The most common adverse events associated with lamotrigine are primarily neurological, gastrointestinal and dermatological. Maculopapular or erythematous skin rash, occasionally severe, occurs in approximately equal to 10% of patients and is the most common cause of treatment withdrawal. The risk of rash can, however, be minimised through adoption of a low, slow dosage titration schedule on initiating therapy. As monotherapy, lamotrigine produces less drowsiness than carbamazepine or phenytoin, and less asthenia and ataxia than phenytoin. Clinical experience would therefore suggest that lamotrigine is a particularly effective and generally well tolerated broad-spectrum agent for adjunctive treatment of both partial epilepsy and idiopathic generalised epilepsy in adults and children. Initial indications point to the drug filling an increasingly important future role in the monotherapy of newly diagnosed epilepsy.

Adult↗
PubMed1996

Clinical studies of the efficacy and tolerability of ebastine 10 or 20 mg once daily in the treatment of seasonal allergic rhinitis in the US.

396 adult and adolescent patients with seasonal allergic rhinitis participated in this randomised double-blind parallel-group study in which the efficacy and tolerability of ebastine 10 or 20mg administered once daily in the morning or evening for 3 weeks were compared with those of placebo. Clinical efficacy was assessed by measuring improvement in rhinitis symptoms (nasal discharge, nasal stuffiness, sneezing, itchy nose and itchy/watery eyes) recorded by patients twice daily on diary cards. The improvement in individual and total symptom scores at the end of the 3-week treatment period in patients treated with ebastine 10mg in the morning or ebastine 20mg in the morning or evening was significantly greater than the improvement in placebo recipients. The 20mg dose of ebastine administered in the morning was associated with the greatest improvement in symptom scores. There was no significant effect with the 10mg evening dose compared with placebo. Ebastine was well tolerated by the majority of patients - the incidence of adverse events, including headache, dry mouth, somnolence and asthenia being similar to that reported in placebo recipients. Electrocardiograms showed no evidence of any clinically relevant changes in QTc intervals. In a subsequent nonblinded 4-month study that included 230 patients from the initial study, global evaluations at monthly intervals showed overall symptom improvement in > or = 72% of patients who received ebastine 10mg or 20mg once daily. The drug was well tolerated during prolonged therapy, with adverse events being similar in nature and incidence to those reported in the 3-week double-blind study. In conclusion, ebastine 10mg once daily in the morning is an appropriate starting dose for the treatment of rhinitis, and this can be increased to 20mg as required.

Adolescent↗