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Asmanex (Mometasone Furoate Inhalation) - Drug Interactions, Contraindications, Overdosage, etc

 
 



DRUG INTERACTIONS

Carcinogenesis, Mutagenesis, Impairment of Fertility

In a 2-year carcinogenicity study in Sprague Dawley rats, mometasone furoate demonstrated no statistically significant increase in the incidence of tumors at inhalation doses up to 67 mcg/kg (approximately 8 times the maximum recommended daily inhalation dose in adults on an AUC basis). In a 19-month carcinogenicity study in Swiss CD-1 mice, mometasone furoate demonstrated no statistically significant increase in the incidence of tumors at inhalation doses up to 160 mcg/kg (approximately 10 times the maximum recommended daily inhalation dose in adults on an AUC basis).

Mometasone furoate increased chromosomal aberrations in an in vitro Chinese hamster ovary cell assay, but did not have this effect in an in vitro Chinese hamster lung cell assay. Mometasone furoate was not mutagenic in the Ames test or mouse lymphoma assay, and was not clastogenic in an in vivo mouse micronucleus assay, a rat bone marrow chromosomal aberration assay, or a mouse male germ-cell chromosomal aberration assay. Mometasone furoate also did not induce unscheduled DNA synthesis in vivo in rat hepatocytes.

In reproductive studies in rats, impairment of fertility was not produced by subcutaneous doses up to 15 mcg/kg (approximately 6 times the maximum recommended daily inhalation dose in adults on an AUC basis).

Pregnancy

Teratogenic Effects

Pregnancy Category C

When administered to pregnant mice, rats, and rabbits, mometasone furoate increased fetal malformations. The doses that produced malformations also decreased fetal growth, as measured by lower fetal weights and/or delayed ossification. Mometasone furoate also caused dystocia and related complications when administered to rats during the end of pregnancy.

In mice, mometasone furoate caused cleft palate at subcutaneous doses of 60 mcg/kg and above (less than the maximum recommended daily inhalation dose in adults on a mcg/m2 basis). Fetal survival was reduced at 180 mcg/kg (approximately equal to the maximum recommended daily inhalation dose in adults on a mcg/m2 basis). No toxicity was observed at 20 mcg/kg (less than the maximum recommended daily inhalation dose in adults on a mcg/m2 basis).

In rats, mometasone furoate produced umbilical hernia at topical dermal doses of 600 mcg/kg and above (approximately 6 times the maximum recommended daily inhalation dose in adults on a mcg/m2 basis). A dose of 300 mcg/kg (approximately 3 times the maximum recommended daily inhalation dose in adults on a mcg/m2 basis) produced delays in ossification, but no malformations.

In rabbits, mometasone furoate caused multiple malformations (eg, flexed front paws, gallbladder agenesis, umbilical hernia, hydrocephaly) at topical dermal doses of 150 mcg/kg and above (approximately 3 times the maximum recommended daily inhalation dose in adults on a mcg/m2 basis). In an oral study, mometasone furoate increased resorptions and caused cleft palate and/or head malformations (hydrocephaly and domed head) at 700 mcg/kg (less than the maximum recommended daily inhalation dose in adults on an AUC basis). At 2800 mcg/kg (approximately 2 times the maximum recommended daily inhalation dose in adults on an AUC basis) most litters were aborted or resorbed. No toxicity was observed at 140 mcg/kg (less than the maximum recommended daily inhalation dose in adults on an AUC basis).

When rats received subcutaneous doses of mometasone furoate throughout pregnancy or during the later stages of pregnancy, 15 mcg/kg (approximately 6 times the maximum recommended daily inhalation dose in adults on an AUC basis) caused prolonged and difficult labor and reduced the number of live births, birth weight, and early pup survival. Similar effects were not observed at 7.5 mcg/kg (approximately 3 times the maximum recommended daily inhalation dose in adults on an AUC basis).

There are no adequate and well-controlled studies in pregnant women. The ASMANEX TWISTHALER, like other corticosteroids, should be used during pregnancy only if the potential benefits justify the potential risks to the fetus. Experience with oral corticosteroids since their introduction in pharmacologic, as opposed to physiologic, doses suggests that rodents are more prone to teratogenic effects from corticosteroids than humans. In addition, because there is a natural increase in corticosteroid production during pregnancy, most women will require a lower exogenous corticosteroid dose and many will not need corticosteroid treatment during pregnancy.

OVERDOSAGE

The potential for acute toxic effects following overdose with the ASMANEX TWISTHALER inhaler is low. Because of low systemic bioavailability and an absence of acute drug-related systemic findings in clinical studies, overdose is unlikely to require any treatment other than observation. If used at excessive doses for prolonged periods, systemic effects such as hypercorticism may occur. Single daily doses as high as 1200 mcg per day for 28 days were well-tolerated and did not cause a significant reduction in plasma cortisol AUC (94% of placebo AUC). Single oral doses up to 8000 mcg have been studied on human volunteers with no adverse events reported.

CONTRAINDICATIONS

ASMANEX TWISTHALER therapy is contraindicated in the primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required.

Hypersensitivity to any of the ingredients of this preparation contraindicates its use (see DESCRIPTION).

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