Combined therapies avoiding

Monitor edema after initiation of diuretic therapy. Monitor fluid intake to ensure obligatory losses are being met and avoid dehydration. If adequate diuresis is not attained with a single agent, consider combination therapy with another diuretic. 

Azathioprine, mycophenolate mofetil, and enteric-coated MPA are not metabolized through the CYP isozyme system therefore, they do not experience the same DDI profiles as cyclosporine, tacrolimus, and sirolimus. Azathioprine s major DDIs involve allopurinol, angiotensin-converting enzyme (ACE) inhibitors, aminosalicylates (e.g., mesalamine and sulfasalazine), and warfarin.11 The interaction with allopurinol is seen frequently and has clinical significance. Allopurinol inhibits xanthine oxidase, the enzyme responsible for metabolizing azathioprine. Combination of azathioprine and allopurinol has resulted in severe toxicities, particularly myelosuppression. It is recommended that concomitant therapy with azathioprine and allopurinol be avoided, but if combination therapy is necessary, the azathioprine doses must be reduced to one-third or one-fourth of the current dose. Use of azathioprine with the ACE inhibitors or aminosalicylates also can result in enhanced myelosuppression.11 Some case reports exist demonstrating that warfarin s therapeutic effects may be decreased by azathioprine.43-45... 

Phentermine use should be avoided in patients concomitantly receiving or having received an MAOI within the preceding 14 days. Combination therapy with any stimulant or MAOI has the potential for causing hypertensive crisis. Alcohol is not recommended for patients prescribed phentermine.38... 

Stavudine possesses several clinically significant interactions with other drugs. Although hydroxyurea enhances the antiviral activity of stavudine and didanosine, combination therapy that includes stavudine and didanosine, with or without hydroxyurea, increases the risk of pancreatitis. Combinations of stavudine and didanosine should not be given to pregnant women because of the increased risk of metabolic acidosis. Zidovudine inhibits the phosphorylation of stavudine thus, this combination should be avoided. 

The use of combination therapy with carbamazepine and valproate (Keck et al. 1992b Ketter et al. 1992) may also be helpful in avoiding or delaying the development of episodic breakthroughs progressing toward tolerance. We have observed that many animals show cyclic response to the anticonvulsants while they are progressing toward the development of complete loss of efficacy via tolerance [Post and Weiss 1996). If doses of... 

The spectrum of activity of flucytosine is restricted to C neoformans, some Candida species, and the dematiaceous molds that cause chromoblastomycosis. Flucytosine is not used as a single agent because of its demonstrated synergy with other agents and to avoid the development of secondary resistance. Clinical use at present is confined to combination therapy, either with amphotericin for... 

The adverse effects of amprenavir in patients treated with combination therapy included nausea, vomiting, diarrhea, epigastric pain, flatulence, paresthesia, headache, rash, and fatigue (4). The contribution of a single drug to the observed adverse effects is difficult to establish. Amprenavir inhibits CYP3A4 to a greater extent than saquinavir, and to a much lesser extent than ritonavir (5). Co-administration with rifampicin and rifabutin should be avoided. Those who take... 

The choice of drug depends on the type of epilepsy. Combination therapy with two or more drugs may be necessary. In this case, careful monitoring is needed because unpredictable interactions between antiepileptic drugs are possible. Withdrawal from antiepileptic drugs should be gradual to avoid the risk of precipitating rebound seizures. 

The intravenous dose (Vepesid, Toposar, Etopophos) for testicular cancer in combination therapy is 50 to 100 mg/m for 5 days, or 100 mg/m on alternate days for three doses. For small-cell carcinoma of the lung, the dose in combination therapy is 50 to 120 mo/m per day intravenously for 3 days, or 50 mg per day orally for 21 days. Cycles of therapy usually are repeated every 3 to 4 weeks. When given intravenously, the drag should be administered slowly during a 30- to 60-minute infusion to avoid hypotension and bronchospasm, which likely result from the additives used to dissolve etoposide, a relatively insoluble compound. 

Adverse effects usually become manifest in the first weeks of therapy, although gastric ulceration and bleeding may present much later. If the patient does not achieve therapeutic benefit from one NSAID, another should be tried. It is best to avoid combination therapy with more than one NSAID. There is little evidence of extra benefit for the patient, and the risk of side effects is at least additive. 

Albendazole is combined with either diethylcarbamazine or ivermectin in programs directed toward controlling LF. By annual dosing with combination therapy for 4-6 years, the goal is to maintain the microfilaremia at such low levels that transmission cannot occur for a period that corresponds to the duration of fecundity of adult worms. Albendazole is given with diethylcarbamazine to control LF in most parts of the world. To avoid serious reactions to dying microfilariae, an albendazole/ivermectin combination is recommended in locations where filaiiasis coexists with either onchocerciasis or loiasis. 

Once-daily regimens are safer with equal efficacy, cost less, and are administered more easily. Exceptions include use in pregnancy, neonatal and pediatric infections, cmd low-dose combination therapy of bacterial endocarditis. Once-daily dosing also should be avoided in patients with creatinine clearances of <20-25 mL/min, where dosing every 48 hours is more appropriate. 

Jamerson KH, Bakris GL, Wun C-C et al. Rationale and design of the avoiding cardiovascular events through combination therapy in patients living with systolic hypertension (ACCOMPLISH) trial. Am J Hypertens 2004 17 793-801. 

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