PROPOXYPHENE HYDROCHLORIDE- propoxyphene hydrochloride capsule
Bryant Ranch Prepack

DESCRIPTION

Propoxyphene hydrochloride is an odorless, white crystalline powder with a bitter taste. It is freely soluble in water. Chemically, it is (2S ,3R)-(+)-4-(dimethylamino)-3-methyl-1,2- diphenyl-2-butanol propionate (ester) hydrochloride, which can be represented by the following structural formula:

(click image for full-size original)

C₂₂ H₂₉ NO₂ •HCl M.W. 375.94

Each capsule, for oral administration, contains 65 mg propoxyphene hydrochloride. Propoxyphene hydrochloride capsules, USP contain the inactive ingredients corn starch, gelatin, lactose monohydrate, magnesium stearate, titanium dioxide, FD&C yellow #6, and D&C red #33.

CLINICAL PHARMACOLOGY

Pharmacology

Propoxyphene is a centrally acting opiate analgesic. In vitro studies demonstrated propoxyphene and the metabolite norpropoxyphene inhibit sodium channels (local anesthetic effect) with norpropoxyphene being approximately 2 fold more potent than propoxyphene and propoxyphene approximately 10 fold more potent than lidocaine. Propoxyphene and norpropoxyphene inhibit the voltage-gated potassium current carried by cardiac rapidly activating delayed rectifier (hERG) channels with approximately equal potency. It is unclear if the effects on ion channels occur within therapeutic dose range.

Pharmacokinetics

Absorption

Peak plasma concentrations of propoxyphene are reached in 2 to 2.5 h. After a 65 mg oral dose of propoxyphene hydrochloride, peak plasma levels of 0.05 to 0.1 mcg/mL for propoxyphene and 0.1 to 0.2 mcg/mL for norpropoxyphene (major metabolite) are achieved. Repeated doses of propoxyphene at 6 h intervals lead to increasing plasma concentrations, with a plateau after the ninth dose at 48 h. Propoxyphene has a half-life of 6 to 12 h, whereas that of norpropoxyphene is 30 to 36 h.

Distribution

Propoxyphene is about 80% bound to proteins and has a large volume of distribution, 16 L/kg.

Metabolism

Propoxyphene undergoes extensive first-pass metabolism by intestinal and hepatic enzymes. The major route of metabolism is cytochrome CYP3A4 mediated N-demethylation to norpropoxyphene, which is excreted by the kidneys. Ring hydroxylation and glucuronide formation are minor metabolic pathways.

Excretion

In 48 h, approximately 20 to 25% of the administered dose of propoxyphene is excreted via the urine, most of which is free or conjugated norpropoxyphene. The renal clearance rate of propoxyphene is 2.6 L/min.

INDICATIONS AND USAGE

This product is indicated for the relief of mild to moderate pain.

CONTRAINDICATIONS

Propoxyphene hydrochloride capsules are contraindicated in patients with known hypersensitivity to propoxyphene.

Propoxyphene hydrochloride capsules are contraindicated in patients with significant respiratory depression (in unmonitored settings or the absence of resuscitative equipment) and patients with acute or severe asthma or hypercarbia.

Propoxyphene hydrochloride capsules are contraindicated in any patient who has or is suspected of having paralytic ileus.

PRECAUTIONS

Tolerance and Physical Dependence

Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Physical dependence is manifested by withdrawal symptoms after abrupt discontinuation of a drug or upon administration of an antagonist. Physical dependence and tolerance are not unusual during chronic opioid therapy.

The opioid abstinence or withdrawal syndrome is characterized by some or all of the following: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other symptoms also may develop, including: irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. In general, opioids should not be abruptly discontinued (see DOSAGE AND ADMINISTRATION , Cessation of Therapy).

If propoxyphene is abruptly discontinued in a physically dependent patient, an abstinence syndrome may occur (see DRUG ABUSE AND DEPENDENCE). If signs and symptoms of withdrawal occur, patients should be treated by reinstitution of opioid therapy followed by gradual tapered dose reduction of propoxyphene combined with symptomatic support (see DOSAGE AND ADMINISTRATION , Cessation of Therapy).

Use in Pancreatic/Biliary Tract Disease

Propoxyphene may cause spasm of the sphincter of Oddi and should be used with caution in patients with biliary tract disease, including acute pancreatitis. Opioids like propoxyphene may cause increases in the serum amylase level.

Hepatic or Renal Impairment

Insufficient information exists to make appropriate dosing recommendations regarding the use of either propoxyphene in patients with hepatic or renal impairment as a function of degree of impairment. Higher plasma concentrations and/or delayed elimination may occur in case of impaired hepatic function and/or impaired renal function (see CLINICAL PHARMACOLOGY).

If the drug is used in these patients, it should be used with caution because of the hepatic metabolism and renal excretion of propoxyphene metabolites.

Information for Patients/Caregivers

(Also see Medication Guide.)

1. Patients should be advised to report pain and adverse experiences occurring during therapy. Individualization of dosage is essential to make optimal use of this medication.
2. Patients should be advised not to adjust the dose of propoxyphene without consulting the prescribing professional.
3. Patients should be advised that propoxyphene may impair mental and/or physical ability required for the performance of potentially hazardous tasks (e.g., driving, operating heavy machinery).
4. Patients should not combine propoxyphene with central nervous system depressants (e.g., sleep aids, tranquilizers) except by the orders of the prescribing physician, because additive effects may occur.
5. Patients should be instructed not to consume alcoholic beverages, including prescription and over-the-counter medications that contain alcohol, while using propoxyphene because of risk of serious adverse events including death.
6. Women of childbearing potential who become, or are planning to become, pregnant should be advised to consult their physician regarding the effects of analgesics and other drug use during pregnancy on themselves and their unborn child.
7. Patients should be advised that propoxyphene is a potential drug of abuse. They should protect it from theft, and it should never be given to anyone other than the individual for whom it was prescribed.
8. Patients should be advised that if they have been receiving treatment with propoxyphene for more than a few weeks and cessation of therapy is indicated, it may be appropriate to taper the propoxyphene dose, rather than abruptly discontinue it, due to the risk of precipitating withdrawal symptoms. Their physician can provide a dose schedule to accomplish a gradual discontinuation of the medication.