CLINICAL PHARMACOLOGY
Mechanism of Action
Suprenza is a sympathomimetic amine with pharmacologic activity similar to the prototype drugs of this class used in obesity, amphetamine (d- and dll-amphetamine). Drugs of this class used in obesity are commonly known as “anorectics” or “anorexigenics.” It has not been established that the primary action of such drugs in treating obesity is one of appetite suppression since other central nervous system actions, or metabolic effects, may also be involved.
Pharmacodynamics
Typical actions of amphetamines include central nervous system stimulation and elevation of blood pressure. Tachyphylaxis and tolerance have been demonstrated with all drugs of this class in which these phenomena have been looked for.
Pharmacokinetics
In terms of rate and extent of exposure, phentermine orally disintegrating tablets are equivalent to phentermine capsules and tablets administered under fasting conditions.
Following the administration of the oral disintegrating tablet (ODT), phentermine reaches peak concentrations (Cmax) after 3.0 to 4.4 hours. Swallowing the ODT after disintegration with or without water did not affect the extent (AUC) of phentermine exposure.
Administration of the ODT after a high fat/high calorie breakfast decreased the Cmax of phentermine by approximately 5% and the AUC by approximately 12%. Despite the decrease in Cmax and AUC, phentermine ODT can be administered with or without food.
Swallowing the ODT without prior disintegration decreased the Cmax of phentermine by approximately 7% and the AUC by approximately 8% compared to swallowing the ODT after disintegration.
Drug Interactions
In a single-dose study comparing the exposures after oral administration of a combination capsule of 15 mg phentermine and 92 mg topiramate to the exposures after oral administration of a 15 mg phentermine capsule or a 92 mg topiramate capsule, there is no significant topiramate exposure change in the presence of phentermine. However in the presence of topiramate, phentermine Cmax and AUC increase 13% and 42%, respectively.
Specific Populations
Renal Impairment
Suprenza was not studied in patients with renal impairment. The literature reported cumulative urinary excretion of phentermine under uncontrolled urinary pH conditions is 62%-85%. Exposure increases can be expected in patients with renal impairment. Use caution when administering Suprenza to patients with renal impairment.
NONCLINICAL TOXICOLOGY
Carcinogenesis, Mutagenesis, Impairment of Fertility
Studies have not been performed with Suprenza to determine the potential for carcinogenesis, mutagenesis or impairment of fertility.
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