User:KDS4444/febantel

KDS4444/febantel

Clinical data
Trade names	Biltricide
AHFS/Drugs.com	Monograph
MedlinePlus	a608048
Pregnancy category	Only when clearly needed (lack of sufficient data in humans)
Routes of administration	oral
ATC code	P02BA01 (WHO) QP52AA01 (WHO)
Legal status
Legal status	U.S.: Rx-only (human use), over-the-counter (veterinary use)[1]
Pharmacokinetic data
Bioavailability	relatively small
Metabolism	hepatic
Elimination half-life	0.8 to 1.5 hours (Main Metabolites 4 to 5 hours)
Excretion	mainly in urine
Identifiers
IUPAC name (RS)-2-(Cyclohexylcarbonyl)-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinolin-4-one
CAS Number	58306-30-2 Y
PubChem CID	4891
DrugBank	EXPT02728 N
ChemSpider	4722 Y
UNII	6490C9U457
KEGG	D00471 Y
ChEMBL	ChEMBL976 Y
Chemical and physical data
Formula	C19H24N2O2
Molar mass	312.411 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C4N2C(c1c(cccc1)CC2)CN(C(=O)C3CCCCC3)C4
InChI InChI=1S/C19H24N2O2/c22-18-13-20(19(23)15-7-2-1-3-8-15)12-17-16-9-5-4-6-14(16)10-11-21(17)18/h4-6,9,15,17H,1-3,7-8,10-13H2 Y Key:FSVJFNAIGNNGKK-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Febantel (trade names Drontal Plus and Rintal) is an anthelmintic manufactured by Bayer effective against flatworms. NIKSAN PHARMACEUTICAL are manufacturer and Exporter of Febantel IP/EP/BP Active Pharmaceutical Ingredient

Uses

Febantel is a veterinary anthelmintic (wormer) compound belonging to the chemical class of the benzimidazoles, but is a so-called pro-benzimidazole, i.e. it is transformed into a benzimidazole once it gets into the host's organism. Febantel is transformed into fenbendazole in the stomach and the intestine of the host, shortly after ingestion. Once transformed its behavior is comparable to the one of fenbendazole.

For dogs and cats febantel is available mainly in the form of drenches, tablets, pills, etc, all for oral administration.

For livestock it is used mainly in the form of drenches or feed additives, all for oral administration. There are no injectables or pour-ons with febantel.

For pets it is very often used in combinations that broaden the spectrum of activity. Typical mixtures for dogs and cats include another broad-spectrum nematicide (often pyrantel) and/or another taenicide (e.g. praziquantel).

History

Febantel was developed in the laboratories for parasitological research of Bayer AG in Germany in the late 1970s.

Efficacy of fenbendazole

Febantel itself has no anthelmintic properties. Therefore its efficacy depends on its successful transformation to fenbendazole and to fenbendazole sulfoxide (= oxfendazole).

As fenbendazole it has a broad-spectrum of activity against gastrointestinal roundworms and lungworms of livestock, including adults and L4-larvae of the most important species (e.g. of the genus Bunostomum, Haemonchus, Ostertagia - Teladorsagia, Trichostrongylus, Cooperia, Nematodirus, Chabertia, Oesophagostomum, Trichuris, Dictyocaulus, etc.) as well as arrested larvae of several species. It is also effective against most livestock tapeworms (e.g. Moniezia, Taenia).

It is also effective against the major parasitic roundworms (e.g. Ancylostoma, Toxocara, Trichuris, Uncinaria) and tapeworms (e.g. Echinococcus, Dipylidium, Taenia, etc.) of dogs and cats.

Febantel has only a limited residual effect. This means that a single administration will kill the parasites present in the host at the time of treatment and protect against re-infestations only for a few more days in ruminants, and only for a few hours in non-ruminants.

At the therapeutic dose fenbendazole is not effective against flukes and whatsoever external parasites.

Unfortunately, resistance of several gastrointestinal roundworms to all benzimidazoles, including fenbendazole is already very high and very frequent worldwide in sheep and goats, slightly lower in cattle. For this reason, the risk that benzimidazoles fail to protect ruminants against gastrointestinal roundworms is considerable worldwide. Resistance of worms to benzimidazoles in dogs, cats, pig and poultry are so far not a serious problem.

Pharmacokinetics

Praziquantel is well absorbed (approximately 80%) from the gastrointestinal tract. However, due to extensive first-pass metabolism, only a relatively small amount enters systemic circulation. Praziquantel has a serum half-life of 0.8 to 1.5 hours in adults with normal renal and liver function. Metabolites have a half-life of 4 to 5 hours. In patients with significantly impaired liver function (Child Pugh classes B ll///d C), the serum half-life is increased to 3 to 8 hours. Praziquantel and its metabolites are mainly excreted renally; within 24 hours after a single oral dose, 70 to 80% is found in urine, but less than 0.1% as the unchanged drug. Praziquantel is metabolized through the cytochrome P450 pathway via CYP3A4. Agents that induce or inhibit CYP3A4 such as phenytoin, rifampin, and azole antifungals will affect the metabolism of praziquantel.

Praziquantel has a particularly dramatic effect on patients with schistosomiasis. Studies of those treated have shown that within six months of receiving a dose of praziquantel, up to 90% of the damage done to internal organs due to schistosomiasis infection can be reversed.

Mode of action

Although the mode of action is not exactly known at present, there is experimental evidence that praziquantel increases the permeability of the membranes of schistosome cells towards calcium ions. The drug thereby induces contraction of the parasites, resulting in paralysis in the contracted state. The dying parasites are dislodged from their site of action in the host organism and may enter systemic circulation or may be destroyed by host immune reaction (phagocytosis). Additional mechanisms including focal disintegrations and disturbances of oviposition (laying of eggs) are seen in other types of sensitive parasites.

Another hypothesis concerning the mechanism of action of praziquantel has been recently reported. The drug seems to interfere with adenosine uptake in cultured worms. This effect may have therapeutical relevance given that the schistosome, as the taenia and the echinococcus (other praziquantel sensitive parasites), is unable to synthesize purines such as adenosine de novo.

Bayer's Animal Health Division website states, "Praziquantel is active against cestodes (tapeworms). Praziquantel is absorbed, metabolized in the liver and excreted in the bile. Upon entering the digestive tract from the bile, cestocidal activity is exhibited. Following exposure to praziquantel, the tapeworm loses its ability to resist digestion by the mammalian host. Because of this, whole tapeworms, including the scolices, are very rarely passed after administration of praziquantel. In many instances only disintegrated and partially digested pieces of tapeworms will be seen in the stool. The majority of tapeworms are digested and are not found in the feces."

Side effects

The majority of side effects develop due to the release of the contents of the parasites as they are killed and the consequent host immune reaction. The heavier the parasite burden, the heavier and more frequent the side effects normally are.

• Central nervous system: Frequently occurring side effects are dizziness, headache, and malaise. Drowsiness, somnolence, fatigue, and vertigo have also been seen. Almost all patients with cerebral cysticercosis experience CNS side effects related to the cell-death of the parasites (headache, worsening of pre-existing neurological problems, seizures, arachnoiditis, and meningism). These side effects may be life-threatening and can be reduced by coadministration of corticosteroids. It is strongly recommended that all patients with cerebral cysticercosis are hospitalized during treatment.
• GI Tract: Approximately 90% of all patients have abdominal pain or cramps with or without nausea and vomiting. Diarrhea may develop and may be severe with colic. Sweating, fever, and sometimes bloody stools may occur together with diarrhea.
• Liver: Asymptomatic and transient increases of liver enzymes (AST and ALT) are noted frequently (up to 27%). No case of symptomatic liver damage has ever been seen so far.
• Sensitivity reactions: Urticaria, rash, pruritus and eosinophilia in white blood cell counts
• Other locations/body as a whole: Lower back pain, myalgia, arthralgia, fever, sweating, various cardiac arrhythmias, and hypotension

Febantel Specification

NIKSAN PHARMACEUTICAL supply Febantel as per British Pharmacopoeia and European Pharmacopoeia with following SPECIFICATIONS

Physical Appearance  :- White to almost white crystalline powder.

Solubility  :- Practically insoluble in water, Soluble in acetone, Slightly soluble in anhydrous ethanol.

Identification by IR  :- IR absorption of the sample must be concordant with the standard spectrum.

Loss on drying  :- Not more than 0.50% w/w.

Sulphated Ash  :- Not more than 0.1% w/w.

Heavy metals  :- Not more than 20 ppm.

Impurity A  :- Not more than 0.1% w/w.

Impurity B  :- Not more than 0.1% w/w.

Impurity C  :- Not more than 0.1% w/w.

Unspecified impurity  :- Not more than 0.2% w/w.

Total impurities  :- Not more than 0.5% w/w.

Assay  :- Between 97.5-102%.

Residual Solvent IPA  :- Not more than 5000.

Residual Solvent Toluene :- Not more than 960.

Residual Solvent MDC  :- Not more than 600.

Drug interactions

Antibiotics

A study found that the antibiotic rifampicin decreases plasma concentrations of praziquantel.

Antiepileptics

Carbamazepine and phenytoin are reported to reduce the bioavailability of praziquantel.

Antimalarials

Chloroquine reduces the bioavailability of praziquantel.

Antacids / histamine H₂-antagonists

At least 2 studies indicate the drug cimetidine heightens praziquantel bioavailability.

Dosage

For schistosomiasis, the dose is 20 milligrams/kilogram by mouth every 4–6 hours for one day. For tapeworms, the dose is 5–25 mg/kg by mouth once. For liver fluke, the dose is 25 mg/kg by mouth every 4–6 hours for one day. These dosages are for patients over 4 years old, and are to be taken with food or a few minutes before a meal.

Brand names

• Biltricide (Bayer) 600 mg Tablets (for human use)
• Cesol (Merck) Tablets
• Cestoved (Vedco) both tablets and injectable for veterinary use
• Cysticide (Merck) Tablets
• Droncit (Bayer) for veterinary use
• Drontal (combination with pyrantel pamoate) (Bayer) for veterinary use
• D-Worm (Farnum) for veterinary use; note that D-Worm also makes roundworm medicine containing piperidine which is not effective against tapeworms.
• Kaicide (Taiwan)
• Milbemax (combination with milbemycin oxime) (Novartis) for veterinary use
• Popantel (Jurox)
• PraziPro (Hikari) for aquarium use
• Profender (combination with emodepside) (Bayer) for veterinary use
• Tape Worm Tabs (Trade Winds) for veterinary use
• Zentozide (Berich (Thailand) Co)
• Distoside (Chandra Bhagat Pharma Pvt Ltd) 600mg tablet (for human use)

References

Category:Anthelmintics Category:Antiparasitic agents Category:World Health Organization essential medicines Category:Amides Category:Lactams