ANTIGAL FAIBLE

Benzyl benzoate is one of the older preparations used to treat scabies.

Scabies is a skin infection caused by the mite sarcoptes scabiei.

It is characterised by severe itching (particularly at night), red spots, and may lead to a secondary infection.

Benzyl benzoate is lethal to this mite and so is useful in the treatment of scabies.

It is also used to treat lice infestation of the head and body.

Benzyl benzoate is not the treatment of choice for scabies due to its irritant properties.

Used to kill lice and the mites responsible for the skin condition scabies.

Benzyl benzoate exerts toxic effects on the nervous system of the parasite, resulting in its death.

It is also toxic to mite ova, though its exact mechanism of action is unknown.

In vitro, benzyl benzoate has been found to kill the Sarcoptes mite within 5 minutes.

No data are available on percutaneous absorption of benzyl benzoate.

Some older studies have suggested some percutaneous absorption, however the amount was not quantified.

Rapidly hydrolyzed to benzoic acid and benzyl alcohol, which is further oxidized to benzoic acid.

The benzoic acid is conjugated with glycine to form hippuric acid.

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Oral, rabbit: LD 50 = 1680 mg/kg; Skin, rabbit: LD 50 = 4000 mg/kg. Symptoms of overdose include blister formation, crusting, itching, oozing, reddening, or scaling of skin; difficulty in urinating (dribbling); jerking movements; sudden loss of consciousness.

is contraindicated in patients with: Ischemic coronary artery disease (angina pectoris, history of myocardial infarction, or documented silent ischemia), or other significant underlying cardiovascular disease.

Coronary artery vasospasm including

Prinzmetal's angina.

History of stroke or transient ischemic attack (TIA) .

Peripheral vascular disease (PVD) .

Ischemic bowel disease.

Uncontrolled hypertension.

Recent use (i.e., within 24 hours) of another 5-HT 1 agonist, ergotamine-containing medication, or ergot-type medication (such as dihydroergotamine or methysergide) .

Hemiplegic or basilar migraine.

Concurrent administration or recent discontinuation (i.e., within 2 weeks) of a MAO-A inhibitor.

Hypersensitivity to rizatriptan or any of the excipients (angioedema and anaphylaxis seen) .

History of ischemic heart disease or coronary artery vasospasm History of stroke or transient ischemic attack Peripheral vascular disease Ischemic bowel disease Uncontrolled hypertension Recent (within 24 hours) use of another 5-HT 1 agonist (e.g., another triptan), or of an ergotamine-containing medication Hemiplegic or basilar migraine MAO-A inhibitor used in the past 2 weeks Hypersensitivity to rizatriptan or any of the excipients.

Although rizatriptan benzoate 5 mg tablets and orally disintegrating tablets are available in the marketplace, MAXALT Tablets and MAXALT-MLT Orally Disintegrating Tablets are no longer marketed in the 5 mg strength.

Adults: 5 or 10 mg single dose; separate repeat doses by at least two hours; maximum dose in a 24-hour period: 30 mg Pediatric patients to 17 years: 5 mg single dose in patients less than 40 kg (88 lb); 10 mg single dose in patients 40 kg (88 lb) or more Adjust dose if co-administered with propranolol 2.1 Dosing Information in Adults The recommended starting dose of rizatriptan benzoate is either 5 mg or 10 mg for the acute treatment of migraines in adults.

The 10-mg dose may provide a greater effect than the 5-mg dose, but may have a greater risk of adverse reactions.

Although the effectiveness of a second dose or subsequent doses has not been established in placebo-controlled trials, if the migraine headache returns, a second dose may be administered 2 hours after the first dose.

The maximum daily dose should not exceed 30 mg in any 24-hour period.

The safety of treating, on average, more than four headaches in a 30-day period has not been established. 2.2 Dosing Information in Pediatric Patients (Age to 17 Years) Dosing in pediatric patients is based on the patient's body weight.

The recommended dose of rizatriptan benzoate is 5 mg in patients weighing less than 40 kg (88 lb), and 10 mg in patients weighing 40 kg (88 lb) or more.

The efficacy and safety of treatment with more than one dose of rizatriptan benzoate within 24 hours in pediatric patients to 17 years of age have not been established. 2.3 Administration of MAXALT-MLT Orally Disintegrating Tablets For MAXALT-MLT Orally Disintegrating Tablets, administration with liquid is not necessary.

Orally disintegrating tablets are packaged in a blister within an outer aluminum pouch and patients should not remove the blister from the outer pouch until just prior to dosing.

The blister pack should then be peeled open with dry hands and the orally disintegrating tablet placed on the tongue, where it will dissolve and be swallowed with the saliva. 2.4 Dosage Adjustment for Patients on Propranolol Adult Patients In adult patients taking propranolol, only the 5-mg dose of rizatriptan benzoate is recommended, up to a maximum of 3 doses in any 24-hour period (15 mg) .

For pediatric patients weighing 40 kg (88 lb) or more, taking propranolol, only a single 5-mg dose of rizatriptan benzoate is recommended (maximum dose of 5 mg in a 24-hour period).

Rizatriptan benzoate should not be prescribed to propranolol-treated pediatric patients who weigh less than 40 kg (88 lb) .

Tablets, 10 mg, are pale pink, capsule-shaped, compressed tablets coded MAXALT on one side and MRK on the other: NDC 78206-142-01, carton of 18 tablets.

Tablets, 10 mg, are white to off-white, round lyophilized orally disintegrating tablets debossed with a modified square on one side, and measuring 12.0-13.8 mm (side-to-side) with a peppermint flavor.

Each orally disintegrating tablet is individually packaged in a blister inside an aluminum pouch (sachet).

They are supplied as follows

NDC 78206-143-01, 6 × unit of use carrying case of 3 orally disintegrating tablets (18 tablets total).

Tablets at room temperature, 15°C-30°C (59°F-86°F).

Tablets at room temperature, 15°C-30°C (59°F-86°F).

Risk Summary Available human data on the use of MAXALT in pregnant women are not sufficient to draw conclusions about drug-associated risk for major birth defects and miscarriage.

In animal studies, developmental toxicity was observed following oral administration of rizatriptan during pregnancy (decreased fetal body weight in rats) or throughout pregnancy and lactation (increased mortality, decreased body weight, and neurobehavioral impairment in rat offspring) at maternal plasma exposures greater than that expected at therapeutic doses in humans.

In the

U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

The reported rate of major birth defects among deliveries to women with migraine range from 2.2% to 2.9% and the reported rate of miscarriage was 17%, which are similar to rates reported in women without migraine.

Maternal and/or Embryo/Fetal Risk In women with migraine, there is an increased risk of adverse perinatal outcomes in the mother, including pre-eclampsia and gestational hypertension.

Data Human Data The Pregnancy Registry for MAXALT did not identify any pattern of congenital anomalies or other adverse birth outcomes over the period of to 2018.

However, the lack of identification of any pattern should be viewed with caution, as the number of prospective reports with outcome information was low and did not provide sufficient power to detect an increased risk of individual birth defects associated with the use of MAXALT.

Additionally, there was significant loss to follow-up in the prospective pregnancy reports, further complicating this assessment of an association between MAXALT and any pattern of congenital anomalies or other adverse birth outcomes.

In a study using data from the Swedish Medical Birth Register, live births to women who reported using triptans or ergots during pregnancy were compared with those of women who did not.

Of the 157 births with first-trimester exposure to rizatriptan, 7 infants were born with malformations (relative risk 1.01 [95% CI: 0.40 to 2.08]).

A study using linked data from the Medical Birth Registry of Norway to the Norwegian Prescription Database compared pregnancy outcomes in women who redeemed prescriptions for triptans during pregnancy, as well as a migraine disease comparison group who redeemed prescriptions for triptans before pregnancy only, compared with a population control group.

Of the 310 women who redeemed prescriptions for rizatriptan during the first trimester, 10 had infants with major congenital malformations (OR 1.03 [95% CI: 0.55 to 1.93]), while for the 271 women who redeemed prescriptions for rizatriptan before, but not during, pregnancy, 12 had infants with major congenital malformations (OR 1.48 [95% CI: 0.83 to 2.64]), each compared with the population comparison group.

When rizatriptan (0, 2, 10, or 100 mg/kg/day) was administered orally to pregnant rats throughout organogenesis, a decrease in fetal body weight was observed at the highest doses tested.

At the mid dose (10 mg/kg/day), which was a no-effect dose for adverse effects on embryofetal development, plasma exposure (AUC) was approximately 15 times that in humans at the maximum recommended human dose (MRHD) of 30 mg/day. When rizatriptan (0, 5, 10, or 50 mg/kg/day) was administered orally to pregnant rabbits throughout organogenesis, no adverse fetal effects were observed.

Plasma exposure (AUC) at the highest dose tested was 115 times that in humans at the MRHD.

Placental transfer of drug to the fetus was demonstrated in both species.

Oral administration of rizatriptan (0, 2, 10, or 100 mg/kg/day) to female rats prior to and during mating and continuing throughout gestation and lactation resulted in reduced body weight in offspring from birth and throughout lactation at all but the lowest dose tested (2 mg/kg/day).

Plasma exposure (AUC) at the no-effect dose (2 mg/kg/day) for adverse effects on postnatal development was similar to that in humans at the MRHD.

Oral administration of rizatriptan (0, 5, 100, or 250 mg/kg/day) throughout organogenesis and lactation resulted in neonatal mortality, reduced body weight (which persisted into adulthood), and impaired neurobehavioral function in offspring at all but the lowest dose tested.

Plasma exposure (AUC) at the no-effect dose for adverse effects on postnatal development (5 mg/kg/day) was approximately 8 times that in humans at the MRHD.

Safety and effectiveness in pediatric patients under 6 years of age have not been established.

The efficacy and safety of

MAXALT in the acute treatment of migraine in patients aged to 17 years was established in an adequate and well-controlled study.

The incidence of adverse reactions reported for pediatric patients in the acute clinical trial was similar in patients who received MAXALT to those who received placebo.

The adverse reaction pattern in pediatric patients is expected to be similar to that in adults.

Clinical studies of

MAXALT did not include sufficient numbers of subjects aged and over to determine whether they respond differently from younger subjects.

Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Although the pharmacokinetics of rizatriptan were similar in elderly (aged ≥65 years) and in younger adults (n=17), in general, dose selection for an elderly patient should be cautious, starting at the low end of the dosing range.

This reflects the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Geriatric patients who have other cardiovascular risk factors (e.g., diabetes, hypertension, smoking, obesity, strong family history of coronary artery disease) should have a cardiovascular evaluation prior to receiving MAXALT.