Description: Quinimax is a cinchona alkaloid and a 4-methanolquinoline. It rapidly acts on blood schizontocide by interfering w/ lysosomal function or nucleic acid synthesis in the Plasmodia spp. It has no activity against exoerythrocytic forms.
Absorption: Rapid and almost complete from the GI tract.
Oral bioavailability: 76-88%. Time to peak plasma concentration: Approx 1-3 hr.
Distribution: Widely distributed; crosses the placenta; enters breast milk. Volume of distribution: 2.5-7.1 L/kg. Plasma protein binding: Approx 70%.
Metabolism: Extensively hepatic via CYP450 isoenzymes into 3-hydroxyquinine and other metabolites.
Excretion: Via urine (approx 20% as unchanged drug). Elimination half-life: Approx 11 hr.
Take Quinimax only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance for unwanted effects.
Quinimax comes with a Medication Guide. Read and follow the instructions carefully. Ask your doctor if you have any questions.
Quinimax may be given together with one or more medicines for malaria. Make sure you take all of the medicines your doctor ordered. If you have any questions about this, talk to your doctor.
Take Quinimax with food to lessen stomach upset, unless otherwise directed by your doctor. If you are taking Quinimax at bedtime, take it with a snack, water, milk, or other beverage.
To help clear up the malaria completely, keep taking Quinimax for the full time of treatment, even if you begin to feel better after a few days. If you stop taking Quinimax too soon, your symptoms may return. Do not miss any doses.
The dose of Quinimax will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of Quinimax. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
If you miss a dose of Quinimax, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.
If it has been more than 4 hours since you missed a dose, skip the missed dose and take your next dose at the regular time.
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
Keep out of the reach of children.
Do not keep outdated medicine or medicine no longer needed.
Ask your healthcare professional how you should dispose of any medicine you do not use.
Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.
Take with food if Quinimax upsets your stomach.
Quinimax is usually taken for 7 days. Call your doctor if your malaria symptoms do not improve after 2 days of taking Quinimax, or if your symptoms return after you have finished the medication. Talk with your doctor if you have fever, vomiting, or diarrhea during your treatment.
Take this medication for the full prescribed length of time. Your symptoms may get better before your condition is completely cleared. If you stop using the medication early for any reason, talk to your doctor about other forms of malaria prevention.
If you need surgery, tell the surgeon ahead of time that you are using Quinimax. You may need to stop using the medicine for a short time. This medication can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using Quinimax.
Store at room temperature away from moisture and heat.
Quinimax is an antimalarial agent.
QTc interval prolongation was studied in a double-blind, multiple dose, placebo-and positive-controlled crossover study in young (N=13, 20 to 39 years) and elderly (N=13, 65 to 78 years) subjects. After 7 days of dosing with Quinimax 648 mg three times daily, the maximum mean (95% upper confidence bound) differences in QTcI from placebo after baseline correction was 27.7 (32.2) ms.
Prolongation of the PR and QRS interval was also noted in subjects receiving Quinimax. The maximum mean (95% upper confidence bound) difference in PR from placebo after baseline-correction was 14.5 (18.0) ms. The maximum mean (95% upper confidence bound) difference in QRS from placebo after baseline-correction was 11.5 (13.3) ms..
The oral bioavailability of Quinimax is 76 to 88% in healthy adults. Quinimax exposure is higher in patients with malaria than in healthy subjects. After a single oral dose of Quinimax sulfate, the mean Quinimax Tmax was longer, and mean AUC and Cmax were higher in patients with uncomplicated P. falciparum malaria than in healthy subjects, as shown in Table 1 below.
TABLE 1 : Pharmacokinetic Parameters of Quinimax in Healthy Subjects and Patients with Uncomplicated P. falciparum Malaria after a Single Doseage 1.5 to 12 years
Geriatric Patients: Following a single oral dose of 600 mg Quinimax sulfate, the mean AUC was about 38% higher in 8 healthy elderly subjects (65 to 78 years old) than in 12 younger subjects (20 to 35 years old). The mean Tmax and Cmax were similar in elderly and younger subjects after a single oral dose of Quinimax sulfate 600 mg. The mean oral clearance of Quinimax was significantly decreased, and the mean elimination half-life was significantly increased in elderly subjects compared with younger subjects (0.06 vs. 0.08 L/h/kg, and 18.4 hours vs. 10.5 hours, respectively). Although there was no significant difference in the renal clearance of Quinimax between the two age groups, elderly subjects excreted a larger proportion of the dose in urine as unchanged drug than younger subjects (16.6% vs. 11.2%).
After a single 648 mg dose or at steady state, following Quinimax sulfate 648 mg given three times daily for 7 days, no difference in the rate and extent of absorption or clearance of Quinimax was seen between 13 elderly subjects (65 to 78 years old) and 14 young subjects (20 to 39 years old). The mean elimination half-life was 20% longer in the elderly subjects (24.0 hours) than in younger subjects (20.0 hours). The steady state Cmax (±SD) and AUC0-8 (±SD) for healthy volunteers are 6.8 ± 1.24 mcg/mL and 48.8 ± 9.15 mcg*h/mL, respectively, following 7 days of oral Quinimax sulfate 648 mg three times daily. The steady state pharmacokinetic parameters in healthy elderly subjects were similar to the pharmacokinetic parameters in healthy young subjects.
Renal Impairment: Following a single oral 600 mg dose of Quinimax sulfate in otherwise healthy subjects with severe chronic renal failure not receiving any form of dialysis (mean serum creatinine = 9.6 mg/dL), the median AUC was higher by 195% and the median Cmax was higher by 79% than in subjects with normal renal function (mean serum creatinine = 1 mg/dL). The mean plasma half-life in subjects with severe chronic renal impairment was prolonged to 26 hours compared to 9.7 hours in the healthy controls. Computer assisted modeling and simulation indicates that in patients with malaria and severe chronic renal failure, a dosage regimen consisting of one loading dose of 648 mg Quinimax followed 12 hours later by a maintenance dosing regimen of 324 mg every 12 hours will provide adequate systemic exposure to Quinimax. The effects of mild and moderate renal impairment on the pharmacokinetics and safety of Quinimax sulfate are not known.
Negligible to minimal amounts of circulating Quinimax in the blood are removed by hemodialysis or hemofiltration. In subjects with chronic renal failure (CRF) on hemodialysis, only about 6.5% of Quinimax is removed in 1 hour. Plasma Quinimax concentrations do not change during or shortly after hemofiltration in subjects with CRF.
Hepatic Impairment: In otherwise healthy subjects with mild hepatic impairment (Child-Pugh A; N=10), who received a single 500 mg dose of Quinimax sulfate, there was no significant difference in Quinimax pharmacokinetic parameters or exposure to the primary metabolite, 3-hydroxyquinine as compared to healthy controls (N=10).
In otherwise healthy subjects with moderate hepatic impairment (Child-Pugh B; N=9) who received a single oral 600 mg dose of Quinimax sulfate, the mean AUC increased by 55% without a significant change in mean Cmax, as compared to healthy volunteer controls (N=6). In subjects with hepatitis, the absorption of Quinimax was prolonged, the elimination half-life was increased, the apparent volume of distribution was higher, but there was no significant difference in weight-adjusted clearance. Therefore, in patients with mild to moderate hepatic impairment, dosage adjustment is not needed, but patients should be monitored closely for adverse effects of Quinimax.
In subjects with severe hepatic impairment (Child-Pugh C; N=10), Quinimax oral clearance (CL/F) was reduced as was formation of the primary 3-hydroxyquinine metabolite. Volume of distribution (Vd/F) was higher and the plasma elimination half-life was increased. Therefore, Quinimax is not indicated in this population and alternate therapy should be administered.
Quinimax inhibits nucleic acid synthesis, protein synthesis, and glycolysis in Plasmodium falciparum and can bind with hemazoin in parasitized erythrocytes. However, the precise mechanism of the antimalarial activity of Quinimax sulfate is not completely understood.
Quinimax sulfate acts primarily on the blood schizont form of P. falciparum. It is not gametocidal and has little effect on the sporozoite or pre-erythrocytic forms.
Strains of P. falciparum with decreased susceptibility to Quinimax can be selected in vivo. P. falciparum malaria that is clinically resistant to Quinimax has been reported in some areas of South America, Southeast Asia, and Bangladesh.
Quinimax has been used worldwide for hundreds of years in the treatment of malaria. Thorough searches of the published literature identified over 1300 references to the treatment of malaria with Quinimax, and from these, 21 randomized, active-controlled studies were identified which evaluated oral Quinimax monotherapy or combination therapy for treatment of uncomplicated P. falciparum malaria. Over 2900 patients from malaria-endemic areas were enrolled in these studies, and more than 1400 patients received oral Quinimax. The following conclusions were drawn from review of these studies:
In areas where multi-drug resistance of P. falciparum is increasing, such as Southeast Asia, cure rates with 7 days of oral Quinimax monotherapy were at least 80%; while cure rates for 7 days of oral Quinimax combined with an antimicrobial agent (tetracycline or clindamycin) were greater than 90%. In areas where multi-drug resistance of the parasite was not as widespread, cure rates with 7 days of Quinimax monotherapy ranged from 86 to 100%. Cure was defined as initial clearing of parasitemia within 7 days without recrudescence by day 28 after treatment initiation. P. falciparum malaria that is clinically resistant to Quinimax has been reported in some areas of South America, Southeast Asia, and Bangladesh, and Quinimax may not be as effective in those areas.
Completion of a 7-day oral Quinimax treatment regimen may be limited by drug intolerance, and shorter courses (3 days) of Quinimax combination therapy have been used. However, the published data from randomized, controlled clinical trials for shorter regimens of oral Quinimax in conjunction with tetracycline, doxycycline, or clindamycin for treatment of uncomplicated P. falciparum malaria is limited, and these shorter course combination regimens may not be as effective as the longer regimens.
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Information checked by Dr. Sachin Kumar, MD Pharmacology