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For oral administration
Rx only
DESCRIPTION
Tofranil-PM® (imipramine pamoate capsules), is a tricyclic antidepressant, available as capsules for oral administration. The 75-, 100-, 125-, and 150-mg capsules contain imipramine pamoate equivalent to 75, 100, 125, and 150 mg of imipramine hydrochloride. Imipramine pamoate is 5-[3-(dimethylamino)propyl]-10,11-dihydro-5 H -dibenz[b,f]azepine 4, 4'-methylenebis-(3-hydroxy-2-naphthoate) (2:1), and its structural formula is
Imipramine pamoate is a fine, yellow, tasteless, odorless powder. It is soluble in ethanol, in acetone, in ether, in chloroform, and in carbon tetrachloride, and is insoluble in water.
Inactive Ingredients. D&C Red No. 28, FD&C Blue No. 1, FD&C Yellow No. 6, D&C Yellow No. 10 (100 mg and 125 mg capsules only), gelatin, magnesium stearate, parabens, starch, talc, and titanium dioxide.
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CLINICAL PHARMACOLOGY
The mechanism of action of imipramine is not definitely known. However, it does not act primarily by stimulation of the central nervous system. The clinical effect is hypothesized as being due to potentiation of adrenergic synapses by blocking uptake of norepinephrine at nerve endings.
ANIMAL PHARMACOLOGY & TOXICOLOGY
A . Acute: Oral LD50:
Mouse 2185 mg/kg
Rat (F) 1142 mg/kg
(M) 1807 mg/kg
Rabbit 1016 mg/kg
Dog 693 mg/kg (Emesis ED50)
B. Subacute:
Two three-month studies in dogs gave evidence of an adverse drug effect on the testes, but only at the highest dose level employed, i.e., 90 mg/kg (10 times the maximum human dose). Depending on the histological section of the testes examined, the findings consisted of a range of degenerative changes up to and including complete atrophy of the seminiferous tubules, with spermatogenesis usually arrested.
Human studies show no definitive effect on sperm count, sperm motility, sperm morphology or volume of ejaculate.
Rat
One three-month study was done in rats at dosage levels comparable to those of the dog studies. No adverse drug effect on the testes was noted in this study, as confirmed by histological examination.
C. Reproduction/Teratogenic:
Oral: Imipramine pamoate was fed to male and female albino rats for 28 weeks through two breeding cycles at dose levels of 15 mg/kg/day and 40 mg/kg/day (equivalent to 2 1/2 and 7 times the maximum human dose).
No abnormalities which could be related to drug administration were noted in gross inspection. Autopsies performed on pups from the second breeding likewise revealed no pathological changes in organs or tissues; however, a decrease in mean litter size from both matings was noted in the drug-treated groups and significant growth suppression occurred in the nursing pups of both sexes in the high group as well as in the females of the low-level group. Finally, the lactation index (pups weaned divided by number left to nurse) was significantly lower in the second litter of the high-level group.
Tofranil and Tofranil-PM are registered trademarks of Mallinckrodt Inc.
 is a registered trademark of Mallinckrodt Inc.
Manufactured by
Patheon Inc.
Whitby, Ontario, Canada
L1N 5Z5
Manufactured for
Mallinckrodt Inc.
Hazelwood, MO 63042 U.S.A.
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