Page 958 - Basic _ Clinical Pharmacology ( PDFDrive )

944 SECTION VIII Chemotherapeutic Drugs

different parts of the world vary in susceptibility. Oxamniquine has PRAZIQUANTEL
been effective in instances of praziquantel resistance.
Praziquantel is effective in the treatment of schistosome infections
Clinical Uses of all species and most other trematode and cestode infections,
including cysticercosis. The drug’s safety and effectiveness as a
Oxamniquine is safe and effective in all stages of S mansoni single oral dose have also made it useful in mass treatment of
disease, including advanced hepatosplenomegaly. The drug is several infections.
generally less effective in children, who require higher doses than
adults. It is better tolerated with food.
Optimal dosage schedules vary for different regions of the Basic Pharmacology
world. In the western hemisphere and western Africa, the adult Praziquantel is a synthetic isoquinoline-pyrazine derivative. It is rap-
oxamniquine dosage is 12–15 mg/kg given once. In northern and idly absorbed, with a bioavailability of about 80% after oral admin-
southern Africa, standard schedules are 15 mg/kg twice daily for istration. Peak serum concentrations are reached 1–3 hours after a
2 days. In eastern Africa and the Arabian peninsula, standard dos- therapeutic dose. Cerebrospinal fluid concentrations of praziquantel
age is 15–20 mg/kg twice in 1 day. Cure rates are 70–95%, with reach 14–20% of the drug’s plasma concentration. About 80% of
marked reduction in egg excretion in those not cured. In mixed the drug is bound to plasma proteins. Most of the drug is rapidly
schistosome infections, oxamniquine has been successfully used in metabolized to inactive mono- and polyhydroxylated products after
combination with metrifonate. a first pass in the liver. The half-life is 0.8–1.5 hours. Excretion
is mainly via the kidneys (60–80%) and bile (15–35%). Plasma
Adverse Reactions, Contraindications, concentrations of praziquantel increase when the drug is taken
& Cautions with a high-carbohydrate meal or with cimetidine; bioavailability is
markedly reduced by phenytoin, carbamazepine, or corticosteroids.
Mild symptoms occur in more than one-third of patients receiv- Praziquantel appears to increase the permeability of trematode
ing oxamniquine. Central nervous system symptoms (dizziness, and cestode cell membranes to calcium, resulting in paralysis, dis-
headache, drowsiness) are most common; nausea and vomiting, lodgement, and death. In schistosome infections of experimental
diarrhea, colic, pruritus, and urticaria also occur. Infrequent animals, praziquantel is effective against adult worms and immature
adverse effects are low-grade fever, an orange to red discoloration stages, and it has a prophylactic effect against cercarial infection.
of the urine, proteinuria, microscopic hematuria, and transient
leukopenia. Seizures have been reported rarely.
Since the drug makes many patients dizzy or drowsy, it should Clinical Uses
be used with caution in patients whose work or activity requires Praziquantel tablets are taken with liquid after a meal; they should
mental alertness (eg, no driving for 24 hours). It should be used be swallowed without chewing because their bitter taste can
with caution in those with a history of epilepsy. Oxamniquine is induce retching and vomiting.
contraindicated in pregnancy.
1. Schistosomiasis—Praziquantel is the drug of choice for
all forms of schistosomiasis. The dosage is 20 mg/kg per dose
PIPERAZINE for two (S mansoni and S haematobium) or three (S japonicum
and S mekongi) doses at intervals of 4–6 hours. High cure
Piperazine is an alternative for the treatment of ascariasis, with rates (75–95%) are achieved when patients are evaluated at
cure rates over 90% when taken for 2 days, but it is not recom- 3–6 months; there is marked reduction in egg counts in those not
mended for other helminth infections. Piperazine is available as cured. The drug is effective in adults and children and is generally
the hexahydrate and as a variety of salts. It is readily absorbed, well tolerated by patients in the hepatosplenic stage of advanced
and maximum plasma levels are reached in 2–4 hours. Most of disease. There is no standard regimen for acute schistosomiasis
the drug is excreted unchanged in the urine in 2–6 hours, and (Katayama syndrome), but standard doses as described above,
excretion is complete within 24 hours. Piperazine causes paralysis often with corticosteroids to limit inflammation from the acute
of ascaris by blocking acetylcholine at the myoneural junction; live immune response and dying worms, are recommended. Increas-
worms are expelled by peristalsis. ing evidence indicates rare S mansoni drug resistance, which may
For ascariasis, the dosage of piperazine (as the hexahydrate) is be countered with extended courses of therapy (eg, 3–6 days at
75 mg/kg (maximum dose, 3.5 g) orally once daily for 2 days. For standard dosing) or treatment with oxamniquine. Effectiveness
heavy infections, treatment should be continued for 3–4 days or of praziquantel for chemoprophylaxis has not been established.
repeated after 1 week.
Occasional mild adverse effects include nausea, vomiting, 2. Clonorchiasis, opisthorchiasis, and paragonimiasis—
diarrhea, abdominal pain, dizziness, and headache. Neurotoxic- Standard dosing is 25 mg/kg three times daily for 2 days for each
ity and allergic reactions are rare. Piperazine should not be given of these fluke infections.
to pregnant women, patients with impaired renal or hepatic
function, or those with a history of epilepsy or chronic neuro- 3. Taeniasis and diphyllobothriasis—A single dose of pra-
logic disease. ziquantel, 5–10 mg/kg, results in nearly 100% cure rates for