ZIQUANTA Tablets

Indications

• Schistosomiasis caused by Schistosoma mansoni
• Schistosomiasis caused by Schistosoma japonicum
• Tapeworm infections, including Taenia solium and Hymenolepis nana

Mechanism of action

Praziquantel is hypothesized to target the β subunits of voltage-gated Ca2+ channels in parasites such as Schistosoma mansoni and Schistosoma japonicum. This action leads to increased calcium influx, causing rapid contraction and paralysis of the worms. The drug also induces tegumental disintegration and vacuolization in schistosomes, significantly affecting adult worms more than juveniles. Secondary effects include inhibition of glucose uptake and depletion of glycogen levels.

Pharmacodynamics

Praziquantel exhibits a rapid onset of action against trematodes and cestodes, causing significant changes in the permeability of the cell membrane of the parasites. This results in muscle contraction, tegumental damage, and eventual death of the worms. It selectively targets schistosomes and is ineffective against nematodes. The drug's efficacy is notably reduced against juvenile schistosomes and may diminish after a few weeks of treatment.

Pharmacokinetics

Praziquantel is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 1-3 hours post-administration. It undergoes extensive hepatic metabolism, primarily by CYP450 enzymes, and has a half-life of approximately 1-3 hours. The drug is excreted mainly in urine as metabolites, with a small fraction excreted unchanged. The pharmacokinetics can be affected by co-administration with certain other drugs that alter its metabolism.

Adverse effects

• dizziness
• hepatitis
• neutropenia
• seizure
• severe cutaneous adverse reactions

Interactions

• mitotane+praziquantel: Severe (decreases exposure)
• rifampicin+praziquantel: Severe (decreases exposure)
• chloroquine+praziquantel: Moderate (decreases exposure)
• cobicistat+praziquantel: Unknown (increases exposure)
• dexamethasone+praziquantel: Unknown (decreases exposure)
• grapefruit juice+praziquantel: Unknown (increases exposure)
• cimetidine+praziquantel: Unknown (increases exposure)
• idelalisib+praziquantel: Unknown (increases exposure)

Pregnancy

Manufacturer advises avoiding use due to toxicity observed in animal studies.

Breast-feeding

Amount present in milk is too small to be harmful; however, the manufacturer advises avoiding use.

Storage

Store in a cool, dry place away from light.

Formulations

• tablets
• oral suspension

Mechanism of action

Although the exact mechanism of action is unknown, praziquantel was hypothesized to target the β subunits of voltage-gated Ca₂₊ channels, particularly in Schistosoma mansoni and Schistosoma japonicum, due to the lack of two conserved serine residues in these subunits. This is supported by the finding that co-administration of calcium channel blockers like nicarpidine and nifedipine renders 50% of Schistosoma mansoni resistant to praziquantel. Increased exposure of antigens on the worm surface was also observed, but little research has been done to elucidate on the mechanism of action.

Pharmacodynamics

In vitro studies on trematodes and cestodes have shown that praziquantel induces a rapid contraction of schistosomas by a specific effect on the permeability of the cell membrane. The drug further causes vacuolization and disintegration of the schistosome tegument. The effect is more marked on adult worms compared to young worms. An increased Ca2⁺-influx may play an important role. Secondary effects are inhibition of glucose uptake, lowering of glycogen levels and stimulation of lactate release. The action of praziquantel is specific to trematodes and cestodes; nematodes (including filariae) are not affected. Praziquantel is active against schistosoma (for example, Schistosoma mekongi, Schistosoma japonicum, Schistosoma mansoni and Schistosoma hematobium), and infections due to the liver flukes, Clonorchis sinensis/Opisthorchis viverrini. Published in vitro data have shown a potential lack of efficacy of praziquantel against migrating schistosomulae. An interesting quirk of praziquantel is that it is relatively ineffective against juvenile schistosomes. While initially effective, effectiveness against schistosomes decreases until it reaches a minimum at 3-4 weeks. Effectiveness then increases again until it is once again fully effective at 6-7 weeks.