|Dihydroartemisinin + Piperaquine Phosphate + Trimethoprim||Tablet||16mg + 160mg + 45mg||1000.0097|
|Dihydroartemisinin + Piperaquine Phosphate + Trimethoprim||Tablet||32mg + 320mg + 90mg||1000.0098|
Drug Description: TORAQUINE is a compound product containing 32mg of dihydroartemisinin, 320mg of piperaquine phosphate and 90mg of trimethoprim and necessary excipients in each tablet.
General Name: Compound Dihydroartemisinin Tablets
Trade Name: TORAQUINE
Character: TORAQUINE is a green coated tablet, it is off-white or light yellow if the coating is removed.
Pharmalcological and toxicological actions: The product is a compound antimalarial drug containing dihydroartemisinin, piperaquine phosphate and trimethoprim. Dihydroartemisinin has strong gametocidal action against plasmodium agamic body, and can kill plasmodium rapidly, controlling the symptoms immediately.
The antimalarial action of piperaquine phosphate is similar to chlorquine. After oral administration, piperaquine phosphate is absorbed and is stored in the liver, then it is slowly released into the blood, with a long-lasting action and is therefore used for prevention and treatment against the symptoms of malaria.
Trimethoprim has the function of inhibiting dihyrdrofolate reductase. It combines with the dihydrofolate reductase of plasmodium interfering with the synthesis of purine so as to inhibit the growth of plasmodium.
Pharmalcological studies show that the combination of the three ingredients has synergistic effect, and postpone drug resistance of plasmodium. Toxicological studies show that compared with individual ingredient, theoretical LD₅₀ of compound dihydroartemisinin is 806.7mg/kg, while the test result is 964.26mg/kg; the ratio is 0.84, which is far less than 2.5. The toxicity of TORAQUINE does not increase.
Psychoneurotic system: The doses of 13.36mg/kg(ED₉₀ dose) and 133.60mg/kg(ten times of ED₉₀dose) were used for oral administration. The result showed that TORAQUINE had no abnormal influence on the general behavior of mice according to Irwin’s Behavior Grading Method. Cage-shaking test showed that the dose of 13.36mg/kg and 133.6mg/kg of TORAQUINE had no significant influence on the spontaneous activity of mice. Pentobarbital sodium subthreshold hypnotic test showed that TORAQUINE had no significant influence on sleeping rate, sleeping time of sleeping duration of mice, while it tended to prolong the sleeping duration with ten times of ED₉₀ dose, which indicates that TORAQUINE may have a certain sedative effect.
Cardiovascular System: The doses of 11.50mg/kg (Monkey curative dose) and 34.5mg/kg (three times of monkey curative dose) were used for oral administration. The result showed that TORAQUINE had no significant influence on heart rate, blood pressure, frequency and depth of breath. P-R, QRS, TST of ECG on the anesthetic Beagle dogs on 15, 30, 60, 90, 120, 150, 180, 210 and 240 minutes after medication.
TORAQUINE has a rapid and powerful plasma schizonticide with rapid symptom control and effectiveness for multi-drug resistant falciparum malaria, and remarkable inhibitory effect on falciparum gametocyte thus minimizing the malaria transmissibility. Pharmacodynamic studies on mice and monkeys demonstrated that the three ingredients of TORAQUINE have obvious synergistic effect. In the studies of 975 cases of falciparum malaria and 171 cases of vivax malaria in multi-drug resistant falciparum malaria endemic areas, with follow-up for 28 days, the cure rate of falciparum malaria was 96.9% with recrudescence rate of 3.1%; the recurrence rate of vivax malaria was 2.7%. The fever clearance time was 16-25 hours and the parasite clearance time was 24-56 hours.
No adverse reactions were found in dogs with 53mg/kg (base 36.77mg/kg), 80mg/kg (base 55.49mg/kg) and 120mg/kg (base 83.25mg/kg) dose. But the doge with 80mg/kg (base 55.49mg/kg) appeared elevation of ALT and CPK.
After administration of the drug, the dog with 270mg/kg(base 187.30mg/kg) had vomiting at 2nd, 4th hour, lassitude and anorexia on the 2nd, 3rd days, which returned to normal on the 4th day. No abnormal changes were found except for transient CPK elevation. The dog with 405mg/kg (base 280.96mg/kg) appeared vomiting once at 2nd, 4th, 6th hours respectively, lassitude and anorexia on the 2nd, 3rd, 4th days with transient elevation of ALT, AST and CPK after administration. The dog of 607.5mg/kg(base 421.43kg) died at 18th hour after medication.
It presented with incontinence, general tremor, somnolence and exhaustion before death. Its ALT, AST, LDH, CPK, BUN and CREA elevated obviously. There was shortened Q-T interval at 2nd hour and proximal ventricular tachycardia at 18th hour on ECG after medication. The ALD is 405mg/kg (base 280.96mg/kg), the MTD is 80mg/kg(base 55.49mg/kg) in a single oral dose of TORAQUINE tablet in Beagle dogs.
Acute Toxicity: LD₅₀ of TORAQUINE in mice was 1390mg/kg (base 964.26mg/kg) by intragastric administration and 582mg/kg (base 403.74mg/kg) by intraperitoneal injection. It showed no significant difference in different sex of mice. The ratio of theoretical value and tested value of LD₅₀ of TORAQUINE was 0.84, it indicates that toxicity is additive only.
Chronic Toxicity: In Beagle dogs, 20 (base 13.88)MKD x 14 is a safety dose. 40 (base 27.75)MKD x 14 is a mild-moderate intoxication dose. 80 (base 55.49)MKD x 14 is severe intoxication dose. Toxic target organ is mainly the liver. The sensitive index is reticulocyte. The toxic lesion is reversible. 120 (base 83.25) MKD x 14 is a safety dose. 240 (base 166.49) MKD x 14 is a mild intoxication dose. 480 (base 332.98) MKD x 14 is a moderate-severe intoxication dose. Toxic target organ is the liver. The toxic lesion caused by TORAQUINE in rats is reversible.
Pharmacokinetics: After oral administration, TORAQUINE is absorbed by gastrointestinal tract, where dihydroartemisinin is well absorbed with rapid effect, wide distribution and rapid excretion and metabolism. In 30 minutes after oral administration, piperaquine phosphate is detected. While trimethoprim is rapidly and completely absorbed, blood peak concentration is reached in 1-2 hours. After absorption, TORAQUINE is mainly distributed in liver, kidney, intestine, blood and body fluids. It is mainly excreted via kidney and intestinal tract. As artemisinin derivatives are antimalarial drug with short half-life and rapid effect, and can kill plasmodium rapidly, in combonation with piperaquine phosphate that has long half-life, together with the synergistic effect of trimethoprim, TORAQUINE is effective in inhibiting growth of plasmodium and reducing the relapse rate of malaria.
Indications: TORAQUINE is used in treatment of all kinds of malaria including choroquine-resistant P. falciparum and P.vivax malaria.
Usage: Take orally after meals. For adults, take 2 tablets for the first time, followed by 2 tablets at the 8th, 24th and 32nd hour. The total dose is 8 tablets. For children, the dosage should be decreased accordingly. Dosage adjustment is as shown in the table below.
Dosage of TORAQUINE for different weight groups (Tablet)
Weight (Kg) Initial dose 8h 24h 32h
10-19 Kg ½ ½ ½ ½
20-29 Kg 1 1 1 1
30-39 Kg 1⅟₂ 1⅟₂ 1⅟₂ 1⅟₂
≥40Kg (Adult) 2 2 2 2
≥90Kg (Adult) Please follow the doctor’s advice
Adverse Reactions: Rare (≤6%), may include:
-Digestive tract: such as nausea, vomiting, impaired appetite, abdominal pain, diarrhea and salivation, etc.
-Nerve system: such as dizziness, headache, tinnitus, asthenia, and hyposomnia, etc.
-Allergic reaction: skin itch and eruption, etc.
-Laboratory abnormal: transient peripheral erythropenia, transient increase of SGPT and SGOT, leucopenia and thrombocytopenia, etc.
1. Those who are allergic to any of the three active ingredients are prohibited to use.
2. Those with severe liver or kidney diseases, hematopathy (e.g. leucopenia or thrombocytopenia) are prohibited to use.
1. Those with insufficient liver or kidney functions should take with care.
2. Follow strictly the specified usage and dosage.
3. Contact promptly with doctor when the clinical symptoms are not significantly improved.
Usage for pregnant or lactating women: Pregnant or lactating patients should take with care when administration is necessary. Doctor’s advice should be followed.
Children: The dosage should be decreased strictly according to the specified usage.
Old aged: Old aged patients or those who are infirm should take care under monitor of doctors or nurses.
Storage: Protect from light in tight containers and keep in dry and cool place.
Package size: 8 tablets / blister / box
Expiry period: 36 months
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