Fixed dose combination

Because of their limited effects on allergic symptoms, decongestants often are used in combination with antihistamines.8 Many antihistamines are available in fixed-dose combinations with pseudoephedrine, which enhances the reduction in nasal congestion and allows for the patient convenience of one tablet. Optimally, therapy should be initiated with an antihistamine alone, adding the adrenergic agent only if nasal congestion does not resolve with antihistamine monotherapy. Use of separate antihistamine and pseudoephedrine also permits independent dose titration.4,11,12... 

The combination of nitrates and hydralazine improves the composite endpoint of mortality, hospitalizations for HF, and quality of life in African Americans who receive standard therapy. A fixed-dose combination product is available that contains ISDN 20 mg and hydralazine 37.5 mg (BiDil). Practice guidelines recommend adding ISDN and hydralazine as part of standard therapy in African Americans with moderately severe to severe HF. The combination may also be reasonable for patients of other ethnicities with persistent symptoms despite optimized therapy with an ACE inhibitor (or ARB) and /Tblocker. The combination is also appropriate as first-line therapy in patients unable to tolerate ACE inhibitors or ARBs because of renal insufficiency, hyperkalemia, or possibly hypotension. 

Obstacles to successful therapy with this drug combination include the need for frequent dosing (i.e., three times daily with the fixed-dose combination product), a high frequency of adverse effects (e.g., headache, dizziness, GI distress), and increased cost for the fixed-dose combination product. 

Loxapine (Loxitane). Loxapine is a medium potency antipsychotic, and it has several interesting features. First, it is chemically very similar to clozapine, the first of the atypical antipsychotics. In the test tube, loxapine actually behaves more like an atypical antipsychotic (more on that later), but when patients are treated with it, loxapine acts more like a traditional typical antipsychotic. A second point of interest is that loxapine is actually the major active metabolite of the antidepressant amoxa-pine (Ascendin). As a result, one can use a single medication (amoxapine) to treat both depression and psychosis. In practice, however, the use of what is essentially a fixed dose combination medication should be avoided. Using amoxapine does not allow separate adjustment of the antipsychotic and antidepressant, and most importantly, amoxapine is the only antidepressant associated with the risk of TD. 

Renal function Impairment Because it is a fixed-dose combination, do not prescribe lamivudine/zidovudine for patients requiring dosage adjustment, such as those with reduced renal function (Ccr less than 50 mL/min) or those experiencing dose-limiting adverse events. 

Hepatic function impairment A reduction in the daily dose of zidovudine may be necessary in patients with mild to moderate hepatic function impairment or liver cirrhosis. Because lamivudine/zidovudine is a fixed-dose combination that cannot be adjusted for this patient population, it is not recommended for patients with impaired hepatic function. 

Because this product is a fixed-dose combination doseform, avoid use in patients requiring dosage reduction. 

Fixed dose combination This combination contains fixed doses of 2 nucleoside analogs emtricitabine and tenofovir disoproxil fumarate. Do not administer concomitantly with emtricitabine or tenofovir disoproxil fumarate. 

Liver function /mpa/rmenf.-Abacavir is contraindicated in patients with moderate to severe hepatic impairment, and dose reduction is required in patients with mild hepatic impairment. Because abacavir/lamivudine is a fixed-dose combination and cannot be dose adjusted, abacavir/lamivudine is contraindicated for patients with hepatic impairment. 

Biphasic insulins are fixed dose combinations of a short-acting and intermediate-acting insulin in various proportions. Examples are Humulin, a biosynthetic human insulin (rDNA origin) suspension with respectively 20%, 30% and 40% regular and 80%, 70% and 60% isophane insulin and Mixtard, a biphasic biosynthetic human insulin suspension with respectively 10%, 20% and 40% soluble and 90%, 80% and 60% isophane insulin. 

High-dose monophasic preparations are indicated for the management of dysfunctional uterine bleedings and when persistent breakthrough bleedings occur with low-dose oral contraceptives. The monophasic combinations are taken in a fixed dose combination once daily over 21 or 22 days, followed by an interval of 7 or 6 days. 

Fansidar is the fixed dose combination of pyrimethamine with sulfadoxine. This formulation is well absorbed with peak plasma levels of the components 2-8 hours after dosing. 

Maloprim, the fixed dose combination of pyrimethamine with dapsone, is not recommended for routine prophylaxis because of the potential for fatal agranulocytosis. 

Halofantrine is usually well tolerated. Gastrointestinal complaints as well as pruritus and skin rashes may occur. It can prolong the QTc interval which can result in ventricular dysrythmias. Lume-fantrine has many similarities to halofantrine but seems not to prolong QTc. It is thus far only used in a fixed dose combination with artemether (see Section VI.a.2.5). 

Fixed dose combination of ZDV plus 3TC 300/150 mg twice daily > 13 yrs or >60 kg maximum dose... 

O Brien DP, Sauvageot D, Zachariah R, Humblet P. In resource-limited settings good early outcomes can be achieved in children using adult fixed-dose combination antiretroviral therapy. AIDS 2006 20(I5) 1955-60. 

Trimethoprim-sulfamethoxazole (TMP-SMX) was introduced as a fixed dose combination in 1968. Trimethoprim was added to sulfamethoxazole to synergisti-cally and sequentially inhibit bacterial synthesis of tetrahydrofolic acid. The combination was also designed to delay development of bacterial resistance. Sulfamethoxazole was selected in part because it is a congener of the frequently used sulhsoxazole but exhibits slower enteric absorption and urinary excretion. Sulfamethoxazole has a half-life similar to that of trimethoprim. 

Abacavir (Ziagen) is a guanosine nucleoside analogue indicated for the therapy of HIV-1 infection in adults and children. It is used as part of a multidrug regimen and is available in a fixed-dose combination with zidovudine and lamivudine (Trizivir). It is also used for postexposure HIV infection prophylaxis. 

Lopinavir is available in the United States only as a fixed-dose combination with ritonavir (Kaletra). In this regimen, a low dose of ritonavir is used to inhibit the rapid inactivation of lopinavir by CYP3A4. Side effects, which are generally mild, include diarrhea, nausea, asthenia, and headache. Pancreatitis occurs rarely. Ritonavir is a potent inhibitor of CYP3A4 and also inhibits CYP2D6. In addition to the drugs contraindicated for all protease inhibitors, fiecainide, propafenone, pimozide, and rifampin should not be given with lopinavir-ritonavir combination therapy. 

VI. Four groups of fixed dose combinations and their data requirements. 

The fixed dose combination of fentanyl (0.05 mg) and droperidol (2.5 mg/ml), 4 to 6 ml is diluted in glucose solution and infused IV over 10 minutes. 

List of Banned Drugs and Fixed Dose Combinations in India... 

Fixed dose combinations of vitamins with antiinflammatory agents and tranquilizers. 

Fixed dose combinations of atropine and analgesics and antipyretics. 

Fixed dose combinations of strychnine and caffeine in tonics. 

Fixed dose combinations of yohimbine and strychnine with testosterone and vitamins. 

Fixed dose combinations of iron with strychnine, arsenic and yohimbine. 

Fixed dose combinations of sodium bromide/chloral-hydrate with other drugs. 

Fixed dose combinations of antihistaminics with antidiarrhoeals. 

Fixed dose combinations of penicillin with sulphonamides. 

Fixed dose combinations of tetracyclines with vitamin C. 

Fixed dose combinations of hydroxyquinoline group of drugs with any other drug except for preparations meant for external use only. 

Fixed dose combinations of corticosteroids with any other drug for internal use. 

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