Page 957 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 53 Clinical Pharmacology of the Antihelminthic Drugs 943

METRIFONATE (TRICHLORFON) Clinical Uses
The adult dose of niclosamide is 2 g once, given in the morning
Metrifonate is a safe, low-cost alternative drug for the treatment on an empty stomach. The tablets must be chewed thoroughly
of Schistosoma haematobium infections. It is not active against and then swallowed with water.
Schistosoma mansoni or Schistosoma japonicum. It is not available
in the USA. 1. Taenia saginata (beef tapeworm), Taenia solium
(pork tapeworm), and Diphyllobothrium latum (fish
Basic Pharmacology tapeworm)—A single 2-g dose of niclosamide results in cure
rates of over 85% for D latum and about 95% for T saginata.
Metrifonate, an organophosphate, is rapidly absorbed after oral It is probably equally effective against T solium. Cysticercosis
administration. After the standard oral dose, peak blood levels can theoretically occur after treatment of T solium infections,
are reached in 1–2 hours; the half-life is about 1.5 hours. Clear- because viable ova are released into the gut lumen after digestion
ance appears to be through nonenzymatic transformation to of segments, but no such cases have been reported.
dichlorvos, its active metabolite. Metrifonate and dichlorvos are
well distributed to the tissues and are completely eliminated in 2. Other tapeworms—Most patients treated with niclosamide
24–48 hours. for Hymenolepis diminuta and Dipylidium caninum infections
The mode of action is thought to be cholinesterase inhibition, are cured with a 7-day course of treatment; a few require a
temporarily paralyzing adult worms, resulting in their transit from second course. Praziquantel is superior for Hymenolepis nana
bladder vasculature to small arterioles in the lungs, where they are (dwarf tapeworm) infection. Niclosamide is not effective against
killed. The drug is not effective against S haematobium eggs; live cysticercosis or hydatid disease.
eggs continue to pass in the urine for several months after all adult
worms have been killed. 3. Intestinal fluke infections—Niclosamide can be used
as an alternative drug in the treatment of Fasciolopsis buski,
Clinical Uses Heterophyes heterophyes, and Metagonimus yokogawai infections.
The standard dose is given every other day for three doses.
In the treatment of S haematobium, an oral dose of 7.5–10 mg/kg
is given three times at 14-day intervals. Cure rates on this schedule
are 44–93%, with marked reductions in egg counts in those not Adverse Reactions, Contraindications,
cured. Metrifonate was also effective as a prophylactic agent when & Cautions
given monthly to children in a highly endemic area, and it has Infrequent, mild, and transitory adverse events include nausea,
been used in mass treatment programs. In mixed infections with vomiting, diarrhea, and abdominal discomfort. Alcohol should
S haematobium and S mansoni, metrifonate has been successfully not be consumed during or for 1 day after treatment. Safety has
combined with oxamniquine.
not been established in pregnancy or for children younger than
2 years.
Adverse Reactions, Contraindications,
& Cautions
Some studies note mild and transient cholinergic symptoms, OXAMNIQUINE
including nausea and vomiting, diarrhea, abdominal pain, bron- Oxamniquine is an alternative to praziquantel for the treat-
chospasm, headache, sweating, fatigue, weakness, dizziness, and ment of S mansoni infections. It has also been used extensively
vertigo. Metrifonate should not be used after recent exposure to for mass treatment. It is not effective against S haematobium or
insecticides or drugs that might potentiate cholinesterase inhibi- S japonicum. It is not available in the USA.
tion. It is contraindicated in pregnancy.
Basic Pharmacology
NICLOSAMIDE
Oxamniquine, a semisynthetic tetrahydroquinoline, is readily
absorbed orally; it should be taken with food. Its plasma half-life
Niclosamide is a second-line drug for the treatment of most tape- is about 2.5 hours. The drug is extensively metabolized to inac-
worm infections, but it is not available in the USA.
tive metabolites and excreted in the urine—up to 75% in the first
Basic Pharmacology 24 hours. Intersubject variations in serum concentration have
been noted, which may explain some treatment failures.
Niclosamide is a salicylamide derivative. It appears to be mini- Oxamniquine is active against both mature and immature stages
mally absorbed from the gastrointestinal tract—neither the drug of S mansoni but does not appear to be cercaricidal. The mechanism
nor its metabolites have been recovered from the blood or urine. of action is unknown. Contraction and paralysis of the worms
Adult worms (but not ova) are rapidly killed, presumably due to results in detachment from terminal venules in the mesentery and
inhibition of oxidative phosphorylation or stimulation of ATPase transit to the liver, where many die; surviving females return to
activity. the mesenteric vessels but cease to lay eggs. Strains of S mansoni in