Piperaquine
| Evidence Level: L5 | Predicted Indications: 2 |
Table of Contents
Piperaquine: Cystic echinococcosis
One-Sentence Summary
Piperaquine is a bisquinoline antimalarial, originally used to treat malaria. with 19 clinical trials and 20 publications currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Cystic echinococcosis |
| TxGNN Prediction Score | 0.9952 |
| Evidence Level | L5 |
| India Market Status | Listed in a compiled Indian medicine price dataset (1 of 1) – CDSCO approval status is not included in this data |
| Number of Listed Products | 1 (valid: 1) |
| Recommended Decision | Proceed with Guardrails |
Note: The highest-scoring prediction in the data is cystic echinococcosis (0.9952), but it has only a pipeline review and no supporting trials, so it is rated L5 / Hold. The report focuses on Plasmodium vivax malaria, the best-supported prediction.
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Piperaquine is a bisquinoline antimalarial thought to act by inhibiting heme detoxification in the parasite’s digestive vacuole, a mechanism shared with chloroquine. Its efficacy in malaria is established, and it is mainly used together with dihydroartemisinin (DHA-piperaquine).
P. vivax belongs to the same genus as the parasites it is already approved against, so this is closer to an extension of the approved indication than true repurposing. Piperaquine’s long elimination half-life gives post-treatment protection against early relapse. However, it has no activity against the dormant liver stage (hypnozoites). Radical cure of vivax therefore requires an 8-aminoquinoline (primaquine or tafenoquine) given alongside it.
Clinical Trial Evidence
Of the 19 registered trials, the most relevant are listed below. Many involve DHA-piperaquine as the blood-stage backbone with primaquine or tafenoquine added for radical cure, so evidence for piperaquine alone is indirect.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00682578 | Phase 3 | Completed | 1086 | DHA-piperaquine vs first-line drugs for vivax and uncomplicated falciparum malaria in Afghanistan |
| NCT01640574 | Phase 3 | Completed | 680 | 7- vs 14-day primaquine with 3-day DHA-piperaquine or chloroquine for radical cure of vivax |
| NCT01054248 | Phase 3 | Completed | 511 | DHA-piperaquine vs artesunate-mefloquine vs artemether-lumefantrine for uncomplicated malaria in pregnancy |
| NCT01288820 | Phase 3 | Completed | 331 | Artesunate-amodiaquine + primaquine vs DHA-piperaquine + primaquine in vivax malaria in North Sumatra |
| NCT02802501 | Phase 3 | Completed | 150 | Tafenoquine co-administered with DHA-piperaquine for radical cure of vivax (placebo-controlled); piperaquine-containing ACT is the background blood-stage treatment |
| NCT02110784 | Phase 2 | Terminated | 27 | Proof of concept for Eurartesim (DHA-piperaquine) in imported vivax malaria |
| NCT02353494 | N/A | Completed | 130 | Observational efficacy and safety study of DHA-piperaquine in Timika, Indonesia, with 42-day follow-up |
| NCT05788094 | Phase 4 | Recruiting | 606 | Whether artemisinin combination treatment reduces the radical curative efficacy of high-dose tafenoquine |
| NCT04704999 | Phase 4 | Recruiting | 820 | Tafenoquine dose optimization for radical cure in Southeast Asia |
| NCT07060794 | Phase 4 | Not yet recruiting | 507 | Drug interaction of tafenoquine with DHA-piperaquine or artesunate-pyronaridine |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 37236221 | 2023 | RCT | Lancet Infect Dis | INSPECTOR: tafenoquine plus DHA-piperaquine for radical cure of vivax, randomised and placebo-controlled |
| 24312446 | 2013 | Meta-analysis of RCTs | PLoS One | Efficacy and safety of DHA-piperaquine for vivax malaria in endemic countries |
| 34472504 | 2020 | RCT | J Vector Borne Dis | Phase III trial of arterolane maleate plus piperaquine phosphate vs chloroquine in children with vivax malaria in India |
| 35305658 | 2022 | Clinical trial | Malar J | DHA-piperaquine efficacy and safety for falciparum and vivax malaria in Papua and Sumatra, Indonesia |
| 31584960 | 2019 | Systematic review / IPD meta-analysis | PLoS Med | DHA-piperaquine vs artemether-lumefantrine, with and without primaquine, on vivax recurrence |
| 29798745 | 2018 | Clinical study | Emerg Infect Dis | DHA-piperaquine cleared parasites faster than chloroquine, blocked transmission, and prevented recurrence for over 2 months |
| 25163024 | 2014 | Pharmacokinetic study | CPT Pharmacometrics Syst Pharmacol | Population PK/PD of piperaquine in vivax patients in Thailand, assessing whether residual drug delays relapse |
| 41218209 | 2026 | Clinical study | Am J Trop Med Hyg | DHA-piperaquine efficacy for uncomplicated falciparum and vivax malaria in Timika, Papua |
| 32656850 | 2022 | Review | Br J Clin Pharmacol | Advances and roadblocks in malaria treatment, including ACTs |
| 29802605 | 2018 | Review | Drugs | Antimalarial drugs in development, noting resistance to piperaquine in Southeast Asia |
India Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 88117 | Fal-DP Capsule (Zuventus Healthcare Ltd) | Strip of 3 capsules | Not stated in the compiled data |
Cytotoxicity
Not applicable: piperaquine is an antimalarial, not an antineoplastic drug.
Safety Considerations
- QT prolongation: Piperaquine prolongs the QT interval, so QTc monitoring is advised.
- G6PD testing: Required before using an 8-aminoquinoline (primaquine or tafenoquine) for radical cure.
- Special populations and regions: Take care in pregnancy and in regions with chloroquine-resistant vivax.
Package insert warnings and contraindications were not available in the compiled data, and no drug interactions were found. Please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Multiple completed Phase 3 trials and randomised studies support DHA-piperaquine in vivax malaria, and the drug is already marketed in India for malaria. Piperaquine does not clear the dormant liver stage, so it is a blood-stage partner and not a stand-alone radical cure. All other predictions (including cystic echinococcosis, which has the same top score) are unsupported by trial evidence and should remain on Hold.
To proceed, the following is needed:
- Package insert warnings, contraindications and approved indication text for the Indian product (Fal-DP)
- Detailed mechanism of action data
- A protocol pairing piperaquine with an 8-aminoquinoline, with G6PD testing and QTc monitoring
- Review of local chloroquine- and piperaquine-resistance patterns and of use in pregnancy
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.