Page 954 - Basic _ Clinical Pharmacology ( PDFDrive )

940 SECTION VIII Chemotherapeutic Drugs

combination of albendazole with oxantel pamoate markedly Blood counts and liver function should be monitored during
improved treatment outcomes. long-term therapy. The drug should not be given to patients with
known hypersensitivity to other benzimidazole drugs or to those
2. Hydatid disease—Albendazole is the treatment of choice with cirrhosis. The safety of albendazole in pregnancy and in
for medical therapy and is a useful adjunct to surgical removal or children younger than 2 years has not been established. Exposure
aspiration of cysts. It is more active against Echinococcus granu- to albendazole is increased by dexamethasone, praziquantel, and
losus than against Echinococcus multilocularis. Dosing is 400 mg cimetidine, and decreased by phenytoin, phenobarbital, carbam-
twice daily with meals for 1 month or longer. Daily therapy for azepine, and ritonavir.
up to 6 months has been well tolerated. One reported thera-
peutic strategy is to treat with albendazole and praziquantel, to
assess response after 1 month or more, and, depending on the BITHIONOL
response, to then manage the patient with continued chemo-
therapy or combined surgical and drug therapy. Bithionol is an alternative to triclabendazole for the treatment of
fascioliasis (sheep liver fluke) and an alternative to praziquantel for
the treatment of paragonimiasis.
3. Neurocysticercosis—Indications for medical therapy for neu-
rocysticercosis are controversial, since antihelminthic therapy is
not clearly superior to therapy with corticosteroids alone and may Basic Pharmacology & Clinical Uses
exacerbate neurologic disease. Therapy is probably most appro- After ingestion, bithionol reaches peak blood levels in 4–8 hours.
priate for symptomatic parenchymal or intraventricular cysts. Excretion appears to be mainly via the kidney.
Corticosteroids are usually given with the antihelminthic drug to For treatment of paragonimiasis and fascioliasis, the dos-
decrease inflammation caused by dying organisms. Albendazole age of bithionol is 30–50 mg/kg in two or three divided doses,
is now generally considered the drug of choice over praziquantel given orally after meals on alternate days for 10–15 doses. For
because of its shorter course, lower cost, improved penetration pulmonary paragonimiasis, cure rates are over 90%. For cerebral
into the subarachnoid space, and increased drug levels (as opposed paragonimiasis, repeat courses may be necessary.
to decreased levels of praziquantel) when administered with cor-
ticosteroids. Albendazole is given in a dosage of 400 mg twice Adverse Reactions, Contraindications, &
daily for up to 21 days. Albendazole combined with praziquantel Cautions
improves efficacy in patients with multiple brain cysts.
Adverse effects, which occur in up to 40% of patients, are generally
4. Other infections—Albendazole is the drug of choice in the mild and transient, but occasionally their severity requires inter-
treatment of cutaneous larva migrans (400 mg daily for 3 days), ruption of therapy. These problems include diarrhea, abdominal
visceral larva migrans (400 mg twice daily for 5 days), intestinal cramps, anorexia, nausea, vomiting, dizziness, and headache. Skin
capillariasis (400 mg daily for 10 days), microsporidial infections rashes may occur after a week or more of therapy, suggesting a
(400 mg twice daily for 2 weeks or longer), and gnathostomiasis reaction to antigens released from dying worms. Bithionol should
(400 mg twice daily for 3 weeks). It also has activity against be used with caution in children younger than 8 years because
taeniasis (400 mg daily for 3 days), trichinosis (400 mg twice there has been limited experience in this age group.
daily for 1–2 weeks), and clonorchiasis (400 mg twice daily for
1 week). There have been reports of effectiveness in treatment of DIETHYLCARBAMAZINE CITRATE
opisthorchiasis, toxocariasis, and loiasis. Albendazole is included
in programs to control lymphatic filariasis. It appears to be less Diethylcarbamazine is a drug of choice in the treatment of fila-
active than diethylcarbamazine or ivermectin for this purpose, riasis, loiasis, and tropical eosinophilia. It has been replaced by
but it is included in combination with either of those drugs in ivermectin for the treatment of onchocerciasis.
control programs. Albendazole has been recommended as empiric
therapy to treat those who return from the tropics with persistent Basic Pharmacology
unexplained eosinophilia. Albendazole has activity against giardia-
sis, but with decreased efficacy compared to tinidazole. Diethylcarbamazine, a synthetic piperazine derivative, is rapidly
absorbed from the gastrointestinal tract; after a dose of 0.5 mg/kg,
Adverse Reactions, Contraindications, & peak plasma levels are reached within 1–2 hours. The plasma half-
Cautions life is 2–3 hours in the presence of acidic urine but about 10 hours
if the urine is alkaline, a Henderson-Hasselbalch trapping effect
When used for 1–3 days, albendazole is nearly free of significant (see Chapter 1). The drug rapidly equilibrates with all tissues
adverse effects. Mild and transient epigastric distress, diarrhea, except fat. It is excreted, principally in the urine, as unchanged
headache, nausea, dizziness, lassitude, and insomnia can occur. In drug and the N-oxide metabolite. Dosage should be reduced in
long-term use for hydatid disease, albendazole is well tolerated, patients with renal impairment.
but it can cause abdominal distress, headaches, fever, fatigue, alo- Diethylcarbamazine immobilizes microfilariae and alters their
pecia, increases in liver enzymes, and pancytopenia. surface structure, displacing them from tissues and making them