Fixed Combination Preparations Research Articles

Non-specialized care of skin disorders: a cross-sectional survey of new patients attending dermatology clinic in a tertiary hospital in Jos, Northcentral Nigeria.

Given the paucity of skin health specialists in Nigeria and the low level of awareness amongst its populace, patients seek for care for skin related disorders from different sources and are given a variety of remedies before accessing specialist care. This study was aimed at describing outlets visited and medication received by patients with skin disorders prior to attending the dermatology outpatient clinic in JUTH. This was a cross sectional study conducted over one year. Information on socio-demography, sources and medication received prior to presentation was obtained and analysed using SPSS 23. The male: female ratio among 166 consenting new patients was 1:1.4. Prior to presentation patients sought care most frequently from Health facilities (68.1%), Patent medicine vendors-PMV (30.7%) and Traditional healers (21.7%). Overall, different steroid preparations were the most commonly used medications (56.6%) across all age groups with fixed combination preparations most frequently used (32.5%). Unconventional substances reportedly used by patients for skin disorders were urine, toothpaste, tomatoes, salt, water in which a life catfish had been kept and fats from a dead dog. Only 21.1% of the patients did not use any medication prior to presentation. There is need to increase capacity in the care of common skin diseases at all levels of the health care system to decrease patronage of unconventional providers. Raising awareness of the general public on the potential dangers of inappropriate treatment of skin diseases and strengthen referral system is imperative to reduce the burden of skin diseases in the country.

Clinical effectiveness of brinzolamide 1%–brimonidine 0.2% fixed combination for primary open-angle glaucoma and ocular hypertension

The main first-line treatment strategy for glaucoma is to reduce intraocular pressure (IOP) by topical ocular hypotensive medications, but many patients require multiple medications for adequate IOP control. Fixed-combination therapies provide several benefits, including simplified treatment regimens, theoretical improved treatment adherence, elimination of the potential for washout of the first drug by the second, and the reduction in ocular exposure to preservatives. β-Adrenoceptor antagonists (particularly 0.5% timolol) are the most commonly used agents in combination with other classes of drugs as fixed-combination eyedrops, but they are contraindicated in many patients, owing to local allergy or systemic side effects. A fixed-combination preparation without a β-blocker is therefore warranted. This paper reviews the clinical effectiveness of brinzolamide 1% and brimonidine 0.2% fixed combination (BBFC) for use in patients with primary open-angle glaucoma and ocular hypertension. We searched PubMed and the ClinicalTrials.gov registry, and identified three randomized controlled trials comparing BBFC vs its constituents (brimonidine vs brinzolamide), and one comparing BBFC with unfixed brimonidine and brinzolamide. All of the studies demonstrated mean diurnal IOP to be statistically significantly lower in the BBFC group compared with constituent groups and noninferior to that with the concomitant group using two separate bottles. The safety profile of BBFC was consistent with that of its individual components, the most common ocular adverse events being ocular hyperemia, visual disturbances, and ocular allergic reactions. Common systemic adverse effects included altered taste sensation, oral dryness, fatigue, somnolence, and decreased alertness. BBFC seems to be a promising new fixed combination for use in glaucoma patients. However, long-term effects of BBFC on IOP, treatment adherence, and safety need to be determined.

Efficacy and Safety of a Combination of Sabal and Urtica Extract in Lower Urinary Tract Symptoms

The aim of this prospective, randomized, double-blind, double-dummy, multicenter clinical trial was to investigate the efficacy and safety of PRO 160/120 (Prostagutt forte), a fixed combination preparation of 160 mg Sabal fruit extract WS 1473 and 120 mg Urtica root extract WS 1031 per capsule, in comparison to the alpha1-adrenoceptor antagonist tamsulosin (CAS 106463-17-6) in lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH). 140 elderly out-patients suffering from LUTS caused by BPH, with an initial score > or = 13 points in the International Prostate Symptom Score (I-PSS), received 2 x 1 capsule/d PRO 160/120 or 1 x 0.4 mg/d tamsulosin and were treated for 60 weeks with interim visits at weeks 8, 16, 24, 36, and 48. The primary outcome measure for efficacy was the change in I-PSS total score, the percentage of patients with an I-PSS score < or = 7 points at endpoint ('responders') was analyzed as well. During 60 weeks of randomized treatment the I-PSS total score was reduced by a median of 9 points in both groups. In total, 32.4 % of the patients in the PRO 160/120 group and 27.9% in the tamsulosin group were responders (test for non-inferiority of PRO 160/120: p = 0.034; non-inferiority margin 10%). Both drugs were well tolerated, with one adverse event in 1514 treatment days for PRO 160/120 and one event in 1164 days for tamsulosin. The study supports non-inferiority of PRO 160/120 in comparison to tamsulosin in the treatment of LUTS caused by BPH.

Dinamika indeksa massy miokarda levogozheludochka u patsientov s arterial'noygipertoniey II-III stepeni na fone terapiiKo-renitekom i Gizaarom

The regress or left ventricular (LV) hypertrophy is a main end-point of antihypertensive therapy. The aim of the present study was to compare antihypertensive effects of two fixed combination preparations of ACE inhibitor and thiazide diuretic, enalapril 20 mg/hydrochlorthiazide 12,5 mg (Co-renitec) and losartan 50 mg/hydrochlorthiazide 12,5 mg (Hyzaar) on LV mass index (LVMI), types of left ventricular remodeling in patients with grade II-III arterial hypertension. First group was treated with Co-renitec, second group with Hyzaar during 24-weeks period. Results showed that both preparations significantly and to the same degree decrease LVMI. Number of patients with normal LV geometry increases with accompanying decrease in number of patients with concentric hypertrophy and concentric remodeling. The favorable effects were more remarkable in group treated with Hyzaar.

Long-term Efficacy and Safety of Fixed-combination Timolol/Latanoprost

The fixed-combination preparation of timolol and latanoprost has been available in Europe since 2001. Evidence supporting its level of clinical efficacy has been slowly accumulating, with some studies suggesting clear benefit and others showing only a modest additional effect relative to its individual components. Studies demonstrating long-term protection of visual function are sparse and more work is required in this area. Several reports indicate that fixed-combination timolol/latanoprost is safe and well tolerated. Other similar combination products are now competing directly with fixed-combination timolol/latanoprost, and further comparative studies will be required to assess their relative merits.

Treatment of glaucoma patients with insufficient intraocular pressure control: a survey of German ophthalmologists in private practice

ABSTRACTObjective: To assess the degree to which glaucoma treatment guidelines have been incorporated into daily practices and to describe the therapeutic practices chosen for patients with insufficient intraocular pressure (IOP) control.Methods: Ophthalmologists in private practice in Germany were surveyed to obtain information about patients who exhibited unsatisfactory progress with IOP-lowering pharmacotherapy. Using a questionnaire, physicians provided data concerning treatment difficulty, target IOP, number and type of medications used, two most recent IOP readings, and optic nerve head and visual field observations.Results: Of the 853 patients analyzed, primary open-angle glaucoma was the diagnosis for 67.1%, and other diagnoses included ocular hypertension, normal tension glaucoma, and pseudoexfoliation glaucoma. Target IOP levels had been determined for 95.5% of patients, and not achieving the target pressure was identified as a treatment difficulty for 81.0% of patients. Of patients on monotherapy, β-blockers were prescribed most often (42.3%). Of all patients, 53.3% were treated with two or more agents as either fixed or non-fixed combinations. The non-fixed combination of a prostaglandin and carbonic anhydrase inhibitor was the most frequently prescribed dual therapy (19.2%). Non-fixed prostaglandin plus β-blocker was used by 18.0% of dual therapy patients, whereas the available fixed combination was used by 10.5%. Non-compliance was identified as a cause of unsatisfactory IOP-lowering in 26.8% of all patients. This study is limited by its descriptive, non-interventional design.Conclusions: Treatment alterations are necessary to achieve sufficient IOP control in some patients. If these patients were to take advantage of more aggressive therapies as outlined by treatment guidelines, including newer formulations and fixed combination preparations, both efficacy and compliance may be improved.

Influence of a herbal fixed combination preparation on intestinal afferent nerve sensitivity in a pharmacological in vivo model

Influence of a herbal fixed combination preparation on intestinal afferent nerve sensitivity in a pharmacological in vivo model

Olanzapine/fluoxetine combination for bipolar depression

Bipolar depression remains one of the most difficult to treat of all mental disorders. Until recently, no treatments, including antidepressants, have consistently shown to be effective in this condition. Olanzapine, an atypical antipsychotic, has been approved by the US Food and Drug Administration for the acute treatment of mania and maintenance prevention of relapse into depression or mania. A clinical trial tested the relative effectiveness of the combination of olanzapine and fluoxetine in bipolar type I depression, against olanzapine alone or placebo. The combination produced a very robust clinical effect acutely and a long-term follow-up study indicated that there was a low rate of induction of mania or mixed states. Therefore, the olanzapine/fluoxetine combination represents a viable alternative for bipolar depression. However, uptake of this combined product in practice has been modest. This is likely to be the result of several factors, including resistance to the use of fixed combination preparations and, more recently, evidence of effectiveness of the atypical quetiapine and the anticonvulsant lamotrigine. Perhaps the greatest resistance to the use of olanzapine alone or in combination has been the problem of weight gain and the attendant risk of type 2 diabetes and the metabolic syndrome. Vigorous management of this problem has been shown to mitigate the potential for weight gain and is required if this combination is to be used. However, many clinicians find management of weight gain in olanzapine treated patients a challenge. In addition, weight, waist circumference, lipids and glucose should be monitored.

Use of Highly Active Antiretroviral Therapy in Patients with Renal Insufficiency

Antiretroviral agents, especially nucleoside reverse transcriptase inhibitors, require significant dosage adjustments in patients who have renal dysfunction and the human immunodeficiency virus (HIV). Some antiretroviral agents and fixed combination preparations are contraindicated in this population. In addition, many preferred antiretroviral regimens may be difficult to administer conveniently in patients with decreased creatinine clearance or in those receiving renal replacement therapies. Some highly active antiretroviral therapy regimens, however, can be used conveniently in patients with HIV and altered renal function.

Low dose indapamide plus perindopril combination effects on cardiovascular structure and function in genetic hypertension.

1. Although the fixed combination preparations of thiazide and angiotensin-converting enzyme inhibitor are gaining wide acceptance in clinical practice, data on the basic pharmacology of the combinations are relatively limited. The long-term structural and functional effects of a fixed low dose (0.24 + 0.76 mg/kg per day) combination of indapamide + perindopril (I + P,S5590) is spontaneously hypertensive rats (SHR) were examined in the present study. 2. Male SHR (10-12 weeks) were treated with I + P or vehicle for 8 weeks. The blood pressure and heart rate were monitored by weekly measurements. At the end of the treatment period, left ventricular, aortic and intramyocardial coronary arteriole structures were assessed. Contractile and relaxant properties of mesenteric arteries were determined by wire-myography. 3. Indapamide + perindopril combination caused a significant lowering of both systolic (P < 0.001) and diastolic (P < 0.001) blood pressures. Left ventricle plus septum:bodyweight ratio (P < 0.001), aortic medial cross-sectional area (P < 0.05) and media:lumen ratios (P < 0.005) were all significantly reduced by I + P treatment. In contrast, the effect of I + P on intramyocardial coronary vascular structure did not reach statistical significance. There was some improvement in endothelium-independent vasorelaxation of mesenteric vessels but contractile responses to noradrenaline and calcium were unaffected by treatment. 4. In summary, a low dose I + P combination treatment of SHR partly normalizes both systolic and diastolic blood pressures. Cardiac and larger vessel hypertrophy was reversed but intramyocardial coronary arteriole structure was not as readily regressed by the end of the study.

Possible association between poor metabolism of mephenytoin and hepatotoxicity caused by Atrium®, a fixed combination preparation containing phenobarbital, febarbamate and difebarbamate

Drug hepatotoxicity is partially determined by genetic factors involved in drug metabolism, which may involve the debrisoquine oxidation polymorphism mediated by cytochrome (CYP) 2D6. The purpose of this study was to assess the relationship between drug hepatotoxicity and another genetic polymorphism of drug oxidation, namely that of S-mephenytoin metabolism mediated by CYP2CMP. Mephenytoin hydroxylation capacity was assessed by a hydroxylation index in 24 patients with drug-induced hepatitis and in 23 healthy controls. Hydroxylation index was calculated as the ratio of S-mephenytoin dose to the (0-10 h) urinary excretion of 4-hydroxymephenytoin after oral administration of 100 mg racemic mephenytoin. The test was performed following the patient's recovery. In three patients, hepatitis was related to Atrium, a drug containing phenobarbital, febarbamate and difebarbamate. The mean hydroxylation index (+/- SD) value in patients with Atrium hepatitis (12.4 +/- 8.3) was markedly higher than that found in healthy controls (1.8 +/- 0.4) or in patients with other drug-induced hepatitis (2.5 +/- 3.3). Mean hydroxylation index values were similar in the two latter groups. Considered individually, oxidation capacity was low (hydroxylation index > 9) in two of the three patients with Atrium hepatitis and intermediate (hydroxylation index between 4 and 9) in the third patient. In contrast, all 23 healthy subjects exhibited a high oxidation capacity (hydroxylation index < 4). In the 21 patients with other drug-induced hepatitis, oxidation capacity was high in 19 subjects, intermediate in one subject with chlorpromazine hepatitis, and low in one subject with dapsone hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Fixed combination drug therapy.

Almost half of all marketed drugs are fixed combination preparations, yet the World Health Organization included only 7 in its list of 240 "essential' drugs. There has been little scientific study of these preparations but much emotion and rhetoric has been expended both for and against them. Potential advantages of fixed combination preparations include: increased compliance, synergy and increased efficacy, and reduced side effects and cost. Potential disadvantages include: inflexible fixed dose ratio, incompatible pharmacokinetics, increased toxicity, and physician and pharmacist ignorance of content. There are a few combinations of undisputed value such as oral contraceptives, levodopa with decarboxylase inhibitors, and pyrimethamine with sulphadoxine. In other cases fixed-dose combinations may have value in strictly specified circumstances, but are probably overprescribed. There is also widespread, unjustified use of combinations in over-the-counter preparations which may have unrecognised adverse effects. Combinations should only be used if each component is necessary for the desired effect and if the advantages outweigh the added risks of using 2 or more drugs. Before prescribing combination drugs, clinicians should always ask themselves a series of questions of which the most important is whether the patient needs each drug in a particular combination, or if 1 component alone would be adequate. In general, government regulatory bodies in "developed' countries are attempting to curb the use of combination drugs, but a more profitable approach might be to better educate doctors on both the advantages and disadvantages of fixed combination preparations leading to improved prescribing habits.

Combination therapy in hypertension. A population-based study in eastern Finland.

In a cross-sectional study, antihypertensive drug treatment was studied in a representative population sample of people aged 30-64 years, using a combination of postal survey, personal interview, clinical assessment and drug prescriptions. 11% of the men and 16% of the women were currently taking antihypertensives; 54% of patients used one, 38% used two, and 8% used three or more preparations. Men used slightly more drugs than women. Diuretics were used by 62% and betablockers by 49% of the sample population. Fixed combinations of thiazides and potassium-sparing agents formed 70% of all diuretic preparations used. Only 12% of the patients used fixed antihypertensive combinations, of which over half were diuretic-reserpine-vasodilator combinations; women and older patients used them most often. The most common freely combined preparations were diuretics and betablockers, which formed almost half of all two-drug combinations, and were also present in 70% of all triple combinations. Adequate control of blood pressure (DBP less than 100 mmHg) was achieved by slightly under 50% of the patients, the BP of women being more adequately controlled than that of men. Differences in BP control were found between the different drugs and combinations. Antihypertensive combination therapy is important in successful treatment, but we still cannot be sure whether fixed combination preparations or, as in this study, free combinations of marketed preparations are better alternatives for treatment.

Changes in clinical symptomatology and psychometric assessments in depressed patients during mianserin and combined amitriptyline/ chlordiazepoxide therapy: a double-blind comparison

SummaryA double-blind controlled trial was carried out in 80 depressed out-patients to compare the efficacy and tolerance of mianserin with that of a fixed combination preparation of amitriptyline and chlordiazepoxide. After a wash-out period of at least 1 week, the patients were allocated at random to treatment with one or other of the trial drugs for 4 weeks. During the first week, patients received 30 mg mianserin per day or 37.5 mg amitriptyline plus 15 mg chlordiazepoxide per day. Thereafter, they received 50 mg mianserin per day or 62.5 mg amitriptyline plus 25 mg chlordiazepoxide per day. Assessments, using the Hamilton Rating Scale for Depression, the Zung Self-Rating Depression Scale, the Clinical Global Impressions Scale and a questionnaire for somatic findings and side-effects, were carried out before treatment and at the end of Weeks 1, 2 and 4. Psychometric tests, including the Taylor Manifest Anxiety Rating Scale, the von Zerssen Mood Self-Rating Scale, and the 11-item Freiburger Personality...