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Duzallo is a drug that is manufactured by Iron Wood Pharmaceuticals Inc. Its benefits were determined to be more than the risks that were associated with it by the European Medicines Agency. It was authorized in August 2017 (Khurana, Rohilla, & Deep, 2018). It has become the preferred choice when it comes to the need to reduce the levels of uric acid and keep it under control to avoid its excessive production. This paper seeks to do a thorough research on Duzallo. It will be divided into subsections concerning the drug’s characteristics and applicability. The work dwells on the working mechanism Duzallo, its usage, benefits, and side effects as well as its interactions with various populations, and eventually ends with the conclusion summarizing the analysis.
Duzallo is a drug that is prescribed to adults with gout. It helps in the reduction of the high amounts of uric acid that accumulate in the blood (Kiltz et al., 2017). It is utilized if allopurinol cannot control the amounts of uric acid on its own sufficiently. Gout is caused by the crystals of uric acid formed in the joints and around the joints causing pain as well as swelling. It is available in two colors. One is a light orange-coated tablet that contains lesinurad in the amount of 200mg and 200mg of allopurinol. Another one is dark orange, also with lesinurad (200mg) and 100mg more of allopurinol than the former (300mg).
Therefore the substances that are active in Duzallo are called allopurinol and lesinurad. These are the ones that combine to form the drug, with their reaction in the body reducing the level of uric acid which causes gout (Richette et al., 2016). The inactive ingredients in Duzallo include crospovidone, lactose monohydrate, microcrystalline cellulose, hydroxypropyl cellulose, and magnesium stearate. The film coating also contains inactive ingredients. They are hypromellose, iron oxide yellow, triacetin, iron red, and titanium dioxide.
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Duzallo Variations
Generic name: Allopurinol/lesinurad
Imprint: LES 200 ALO300
Strength: 300mg allopurinol/ 200mg lesinurad
Color: Orange
Shape: Capsule
Generic name: Allopurinol/lesinurad
Imprint: LES 200 ALO200
Strength: 200mg allopurinol/ 200mg lesinurad
Color: Orange
Shape: Capsule
Molecular Cell Level
Allopurinol
The chemical name of allopurinol is 1, 5-dihydro-4H-Pyrazolo [3, 4-d] pyrimidin-4-one. molecular formula is C5H4N4O. Its molecular weight is 136.11146 Daltons. Its structural formula is as shown below (Voelker, 2017).
Lesinurad
Its chemical name is 2-((5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1, 2, 4-triazol-3yl)thio) acetic acid. Its molecular formula and weight are C17H14BrN3O2S and 404.28 respectively. Its structural formula is as shown below (Qurie & Musa, 2018).
Working Mechanism
The active substances that are in Duzallo function in ways that are different in preventing uric acid build up. Lesinurad helps in the removal of uric acid from the body (Qurie & Musa, 2018). It achieves this by blocking uric acid transporter-1(URAT1), a protein that is found in the kidneys. This protein allows the return of uric acid to the blood after it has been filtered from the kidneys. URAT1 blocking results in the passing of more uric acid in the urine. The end result is that the amount of URAT 1 is reduced in the blood system.
Allopurinol works by reducing uric acid production in the body. This is through the blockage of xanthine enzyme responsible for the manufacturing of uric acid (Richette et al, 2016). The reduction of uric acid production subsequently lowers the amount of uric acid in the blood system. Allopurinol ensures uric acid low levels and the building up of crystals stops.
How the Drug Used
The availability of Duzallo is in the form of a tablet is convenient for most patients. The tablets are normally produced either with 200mg or 300mg of allopurinol. This is combined with lesinurad (200mg) (Voelker, 2017). The dosage of the tablets of Duzallo is chosen so as it matches the allopurinol dose that is taken by the patient. The dosage that is recommended is usually one tablet that is taken daily every morning. Patients under this prescription are supposed to take a lot of water all through the day.
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Benefits
Two main studies were taken on the benefits of Duzallo. The studies revealed that when combining allopurinol with lesinurad, the received drug helps in the lowering of the levels of uric acid (Qurie & Musa, 2018). However, the latter is added only when allopurinol does not work well. The two studies that were conducted involved approximately over 800 adults. The adults had gout and had a blood test result that indicated high levels of uric acid. The uric acid level was above 65mg/liter. This is despite being treated with allopurinol.
Lesinurad (200mg) was then added to the daily treatment of allopurinol that was being administered to the patients. After the treatment, 55% of the patients that had high levels of uric acid showed a decrease in the levels of it in the blood flow (Richette et al., 2016). The level of uric acid in these patients decreased to a level that was less than 60mg/ liter and this was only after six months. This was done in comparison with 26% of the patients that were given placebo which is a dummy treatment that was added on top of allopurinol.
Besides these two studies, Duzallo was now administered to the patients that had gout and had high levels of uric acid. This was in comparison with when lesinurad was added later in addition to allopurinol (Voelker, 2017). The studies revealed that the application of Duzallo activated the uric acid mechanism in the blood. This was on the level as when the active substances were administered separately. The effect which is lowering of the levels of uric acid and the prevention of them building up in the body was shown.
The table below shows the proportion of patients who achieved the required levels of uric acid.
| Study | Patients achieving the target of serum uric acid | Difference of Proportion
(95% C. I) |
||
| Time point | Placebo+ allopurinol | Lesinurad 200mg+ allopurinol | ||
| Study 1 | Month 6 | 28% | 54% | 0.26
(0.17, 0.36) |
| Study 2 | Month 6 | 23% | 55% | 0.32
0.23, 0.41) |
Pharmacokinetics of Duzallo
Absorption
Lesinurad bioavailability as monotherapy is 100%. Its absorption is rapid. From the tests that were carried out, a tablet of lesinurad that was in fasted state or fed attained Cmax within 4hrs (Khurana et al., 2018). When being administered with meals with high fats, its Cmax is decreased by 18%. The absorption of allopurinol is 90%. There is the production of Allopurinol of 3mcg/mL and oxypurinol of 6.5 mcg/mL after a single dose administered orally.
Elimination
Lesinurad elimination half-life is about 5hrs. The total clearance of the body is about 6L/hr (Kiltz et al., 2017). The half-life of allopurinol is approximately between 1-2 hours. This is because oxypurinol oxidizes rapidly. Clearance of allopurinol is through glomerular filtration. For oxypurinol, the kidney tubules reabsorb it.
Distribution
Lesinurad is bound to proteins in plasma extensively (approximately 98% or higher). The main protein is albumin (Richette et al., 2016). There is no meaningful alteration of the plasma protein in patients who have renal impairment.
Metabolism
Lesinurad experiences oxidative metabolism through an enzyme called polymorphic cytochrome. Metabolites contribute to the effect of uric acid of lowering uric acid effects (Voelker, 2017). Patients that are poor metabolizers usually have a deficiency of polymorphic cytochrome enzyme. Metabolism of allopurinol corresponds to xanthine analogue (inhibitor).
Excretion
The approximate 63% of lesinurad is excreted through urine within 7 days while 32% in feces. 20% of the allopurinol that has been ingested is excreted in feces (Qurie & Musa, 2018). The remaining undergoes metabolism to oxypurinol.
Loading Dose
For those patients that have not attained the required levels of uric acid on allopurinol of 300mg, one tablet of Duzallo can be initiated. For allopurinol of 300mg, a tablet of Duzallo with 200mg lesinurad and 300mg allopurinol is administered per day (Khurana et al., 2018). For allopurinol of 200mg, a tablet of Duzallo with 200mg lesinurad and 200mg allopurinol is administered per day.
Route of Drugs
Duzallo is a tablet that is taken orally (Kiltz et al., 2017).
Steady State
Once Duzallo is taken, it is fairly eliminated from the body once it is taken. Lesinurad is eliminated in 5 hours while allopurinol is eliminated in 2hrs (Richette et al., 2016).
Indications
Duzallo is made up of allopurinol which is a xanthine oxidase inhibitor and lesinurad which is a uric acid transporter inhibitor. Its indication is for hyperuricemia treatment associated with gout in the patients that do not have the required levels of uric acid and who are taking allopurinol (Qurie & Musa, 2018).
Known Contradictions
It should not be used by patients that have asymptomatic hyperuricemia (Voelker, 2017).
Side Effects/ Risks
There are side effects that are related to Duzallo. Research has shown that the side effects affect 1 person out of 10 persons (Khurana et al., 2018). Some of the side effects include flu, headache, and the disease of gastro-oesophageal reflux which is when the acid from the stomach goes back to the mouth. Another side effect is that the tests of blood may indicate the levels of blood creatinine increasing. This is normally a marker of how the kidney functions.
The side effect that is most serious from the intake of Duzallo is related to the failure of the function of the kidney or the reduction of the kidney function as well as the stones of these organs (Kiltz et al., 2017). This side effect has been known to affect fewer patients approximately, 1 in 100 patients. Duzallo is not supposed to be taken by those patients whose kidney is not functioning well. Also, the patient whose kidney function is impaired and are on dialysis or those that have been given a kidney transplant.
It must also not be taken by those patients who have a syndrome of tumor lysis. This is a complication that arises from the breaking down of the cells of cancer when a patient is receiving treatment of cancer (Qurie & Musa, 2018). Duzallo should also not be administered to patients with the syndrome of Lesch- Nyhan which is a genetic disease that is rare.
Reason for Authorization by the European Union
The benefits of Duzallo were measured by the European Medicines Agency. They were found to overweigh the side effects (Richette et al., 2016). The active substances that are found in Duzallo are more effective when the tablets are administered separately. When allopurinol and lesinurad are combined in a tablet, their main advantage is that they simplify treatment.
Measures for the Safety and Effectiveness of Duzallo
Duzallo is supposed to be taken only under the instructions or as prescribed by a physician. It is only a doctor that can prescribe it to a patient (Voelker, 2017). This is necessary for minimizing any side effects that are associated with taking the drug without instructions. For instance, a patient is supposed to undergo some tests to determine whether they are qualifying for the drug. This is by putting into consideration the various persons that are not supposed to take the drug such as those that have tumor analysis.
Interactions
Drug Interactions with Lesinurad
High doses of aspirin may reduce the effectiveness of Duzallo. Aspirin that can be administered with Duzallo is the one with less than 325mg (Khurana et al., 2018). Duzallo does not work well with hormonal contraceptives as well as oral, transdermal, or other forms that are implantable. Females that are on contraceptives may require additional medication on top of Duzallo. Lesinurad does not inhibit epoxide hydrolase. Instead, epoxide hydrolase inhibitors may affect the metabolism rate of Duzallo.
Drug Interactions with Allopurinol
Since allopurinol inhibits xanthine oxidase, it prolongs the activity of azathioprine as well as mercaptopurine. This is because of the metabolism of azathioprine to mercaptopurine (Qurie & Musa, 2018). When being administered with Duzallo, azathioprine needs to be reduced by a third or a quarter. Allopurinol suppresses bone marrow in patients having neoplastic disease. It also increases the levels of cyclosporine during treatment that is concomitant. Hence, the levels of cyclosporine should be monitored. When administered with dicumarol, it prolongs its half-life. Administration of allopurinol with thiazide diuretics results into allopurinol toxicity enhancements in some of the patients (Voelker, 2017). When administered on patients taking amoxicillin, they experience skin rashes. The half-life of chlorpropamide is prolonged by allopurinol.
Use with Different Populations
Pediatric Patients
For pediatric patients, there are variations in terms of pharmacokinetics as well as pharmacodynamics in this group of patients. The way they react with the medicine is unpredictable (Khurana et al., 2018). Most important is the dosage because of their little weight.
Geriatric Patients
These patients have altered responses in terms of pharmacokinetics as well as pharmacodynamics. Aging changes how the response of the body to drugs (Kiltz et al., 2017). A limitation of memory and sensitivity that is increased due to therapy causes unique problems.
Renal Dysfunction Patients
The excretion of medications is done through the renal glands. They are also metabolized and excreted through the renal gland (Qurie & Musa, 2018). Adjusting the dose is significant to these populations.
Liver Dysfunction Patients
Liver disease brings alterations to the drugs physiology in the body. The attention accorded to these populations should be special (Richette et al., 2016).
Obese Patients
These patients have responses altered in terms of both pharmacokinetics and pharmacodynamics. Responses related to medication for this medication is related to the nutritional status that are altered as well as comorbidities (Kiltz et al., 2017). An accurate dosage is necessary.
Pregnancy or Lactation
These are challenging conditions. The effects that may have on the fetus must be taken into consideration (Khurana et al., 2018).
Conclusion
Duzallo, which is the combination of allopurinol and lesinurad, works efficiently and effectively in the prevention of rising levels of uric acid. This helps in the treatment of gout which is a result of the accumulation of uric acid in the body in high amounts. The active components of Duzallo can also be administered separately. This means that, if allopurinol does not work properly, lesinurad can be added to help in the lowering of the amount of uric acid in the organism. Some of the side effects of Duzallo manifest in flu, headache, gastro-oesophageal reflux, and kidney failure. In ensuring the safety of the drug, the doctor’s instructions should be followed strictly on dosage. This drug reacts differently with different populations and therefore, their conditions should be considered when administering it.
