Dihydroartemisinin-piperaquine

Active Substance
Dihydroartemisinin-piperauqin
Pharmaceutical dosage form
1. Generic:
DHP Frimal film coated tablet combination:
a. Dihydroartemisin 40mg
b. Piperaquin 320 mg

2. Brand:
Eurartesim
Arterakin
 contents are the same
Pharmacokinetics

1. Absorption:
DHA is very rapidly absorbed with the Tmax approcimately 1 -2 hours.
The reported biovailability was 45% in healthy adults. The Tmax is
known to increase in malaria infected patients which could be attributed
to reduced metabolism by the liver or the drug's collection in infected
erythrocytes. When administered with food, Tmax was observed to
delay by 1 hour.
Piperaquine is slowly absored with Tmax of approximately 5 hours.
When taken with food piperaquine exposure is increased until 3-fold.
Both piperaquine and dihydroartemisinine are observed to acculumate
more in female and male and collects in RBCs.

2. Distribution:
Both piperaquine and DHA are highly bound to human plasma proteins:
the protein binding observed in in vitro studies was 44-93 % for DHA
and >99 % for piperaquine.
DHA was observed to have a small volume of distribution in humans (0.8
l/kg in adults and 0.7 in pediatrics). Pharmacokinetic parameters
observed for piperaquine in humans indicate that this active substance
has a large volume of distribution (730 l/kg).

3. Metabolism :
The primary metabolite of DHA is the glucuronide conjugate which is
largely metabolized by UGT1A9 with some contribution by UGT2B7.
Piperaquine undergoes N-dealkylation, separating its aliphatic bridge
from one of the nitrogen-containing ring, producing aldehyde which then
oxidized to a carboxylic acid to form metabolite. The same nitrogen-
containing rings can also undergo hydroxylation at one of two sites to
form M3 or M4. M2 is formed via N-oxidation of one of the nitrogens in
the quinoline groups at either side of the molecule. M5 results when
both of these nitrogens are oxidized. M1 and M2 are the major
metabolism products
 4. Elimination :
Elimination of DHA is approximately 1 hour, but the data regarding DHA
elimination are still limited. However, it is reported in the literature that
the excretion of unchanged active substance in human urine and faeces
is negligible for artemisinin derivatives.
Elimination of piperaquine is around 22 days for adut patients and
around 20 days for paediatric patients. Piperaquine is mainly excreted in
the feces with a negligible amount in the urine
Dosage regimen

Indication:
Uncomplicated malaria disease caused by P. falciparum &/or P. vivax
malaria

Dosage :
Day 1-3:
≥15 years, ≥60 kg : 4 tab
≥15 years, 41-59 kg : 3 tab
10-14 years, 31-40 kg : 2 tab
5-9 years, 18-30 kg : 1.5 tab
1-4 years, 11-17 kg : 1 tab
2-11 months, 6-10 kg : 0.5 tab
1.1 month, <5 kg : 0.25 tab.

Administration:
Should be taken with food

Contraindication:
1. Hypersensitivity to dihydroartemisinin & piperaquine phosphate
2. Severe renal damage, liver disease & blood disorders
3. Severe malaria
4. Patients taking drugs that prolong QTc interval
5. Symptomatic cardiac arrhythmias
6. Severe hypertension
7. Left ventricular hypertrophy eg, hypertrophic cardiomyopathy
8. Congestive cardiac failure accompanied by reduced left ventricle
ejection fraction
9. Electrolyte disturbance eg, hypokalemia, hypocalcemia or
hypomagnesaemia
10. Pregnancy

Adverse reaction:
1. Nausea, vomiting, stomachache, diarrhea & loss of appetite
2. Dizziness, headache, insomnia
3. Allergic reaction eg, rash, pruritus
4. Transient decrease of peripheral erythrocyte
5. Trancient increased of SGPT, SGOT & blood creatinine