Description of Dihydroartemisinin and Piperaquine
Table of Contents
Dihydroartemisinin and Piperaquine is a drug used in the treatment of uncomplicated malaria. Dihydroartemisinin and Piperaquine is available in different dosage forms including tablets, and powder for Suspension. Each film coated tablet contains:
- Single strength: Dihydroartemisinin 40 mg + Piperaquine 320 mg
- Tetra Strength: Dihydroartemisinin 120 mg + Piperaquine 960 mg.
Pharmacodynamics of Dihydroartemisinin and Piperaquine
Dihydroartemisinin mainly interferes with the membrane structures of trophozoites (erythrocytic asexual forms), i.e, whorled food vacuole membrane, distended mitochondria, swollen nuclear membranes, dissociation of ribosomes from endoplasmic reticulum leading to cytoplasmic vacuolization and autophagocytosis. In addition, biochemical depression of protein synthesis and nucleic acid synthesis are exhibited.
Experimental results show that Piperaquine Phosphate interferes with physiological function of the food vacuole membrane of the trophozoites leading to autophagocytosis of the parasites. It has no marked effect on the ring forms, immature or mature schizonts and the male or female gametocytes.
Pharmacokinetics of Dihydroartemisinin and Piperaquine
Upon oral administration Dihydroartemisin is rapidly absorbed and maximum blood concentration attained 1 hour afterwards, with a half-life of about 4 hours. It is widely distributed in the liver, kidneys and bile. Approximately 80% is excreted through the urine and feces within 24 hrs after administration. It is metabolized to two inactive metabolites, deoxydihydroartemisinin and dihydroxydihydroartemisinin.
Upon oral administration, about 80-90% is absorbed within 24 hrs. It is widely distributed in the body mainly in the liver, kidneys, lungs and spleen. About 25% of the total dose is partitioned in the liver within 8 hrs of intake. Elimination is very slow with the half life of about 9.4 days. It is excreted through bile by hepatoenteral circulation.
Uses and Indications of Dihydroartemisinin and Piperaquine
Dihydroartemisinin and Piperaquine tablets are indicated for the treatment of uncomplicated Plasmodium falciparum malaria.
Administration and Dosage of Dihydroartemisinin and Piperaquine
Oral administration: Dihydroartemisinin and Piperaquine Tablets and Suspension should be given daily for 3 days.
Patient should follow doctor’s instruction. The recommended dosages according to body Weight are as follows:
- 5 to < 8 kg: ½ tablet once daily for 3 days
- 8 to < 11 kg: 1½ tab of 20mg/160mg
- 11 to <17 kg: 1 tablet daily for 3 days
- 17 to < 25 kg: 1.5 tablets daily for 3 days
- 25 to < 36 kg: 2 tablets daily for 3 days
- 36 to < 60 kg: 3 tablets daily for 3 days
- 60 to < 80 kg: 4 tablets daily for 3 days
- >80 kg: 5 tablets daily for 3 days
DHA-PQP 80 mg + 640 mg/80 mL Oral suspension
- 5 to < 8 kg: 20ml once daily for 3 days
- 8 to < 11 kg: 30ml once daily for 3 days
- 11 to < 17 kg: 40ml once daily for 3 days
- 17 to < 25 kg: 60ml once daily for 3 days
- 25 to < 36 kg: 80ml once daily for 3 days
- One tablet in the above dosage guideline represents Dihydroartemisinin and Piperaquine 40mg/320mg. That’s the single strength.
Warning and Precautions
Caution should be taken while administering drug to patients with hepatic, kidney impairment. Do not exceed the stated dosage.
Dihydroartemisinin and Piperaquine Use in Pregnancy and Lactation
There are insufficient data on the use of dihydroartemisinin and piperaquine in pregnant women. Based on animal data, Dihydroartemisinin and Piperaquine is suspected to cause serious birth defects when administered during the first trimester of pregnancy. Reproductive studies with artemisinin derivatives have demonstrated teratogenic potential with an increased risk during early gestation Dihydroartemisinin and Piperaquine should not be used during pregnancy in situations where other suitable and effective anti-malarials are available..
Animal data suggest excretion of piperaquine into breast milk but no data are available in humans. Women taking Dihydroartemisinin and Piperaquine should not breast-feed during their treatment.
Drugs Interactions with Dihydroartemisinin and Piperaquine
Caution should be taken while administering Dihydroartemisinin and Piperaquine tablets with drugs such as inhibitors of CYP3A4, CYP2C19. rifampicin, carbamazepine, phenytoin and phenobarbital.
Side Effects of Dihydroartemisinin and Piperaquine
Nausea or vomiting may occur occasionally with incidence of less than 6% No noticeable side effect of Dihydroartemisinin is reported. The Dihydroartemisinin would, for certain individuals, bring effects of greater or lesser severity: for example, a reversible reduction in reticulocyte counts.
Possible side-effect of Piperaquine Phosphate include mild dizziness, vertigo, headache, nausea, vomiting and abdominal discomfort. Reversible leucopenia was infrequently reported; dyspnea and palpitations were also reported but not further specified.
Overdose of Dihydroartemisinin and Piperaquine
In cases of suspected overdose, symptomatic and supportive therapy should be given as appropriate, including ECG monitoring because of the possibility of QTc interval prolongation.
How to Store Dihydroartemisinin and Piperaquine
Store in a dry place, below 30°C. Protect from light. Keep out of reach of children.