DEMEROL: Package Insert and Label Information (Page 4 of 5)

12.2 Pharmacodynamics

Effects on the Central Nervous System

Meperidine produces respiratory depression by direct action on brain stem respiratory centers. The respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to both increases in carbon dioxide tension and electrical stimulation.

Meperidine causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origins may produce similar findings). Marked mydriasis rather than miosis may be seen due to hypoxia in overdose situations.

Effects on the Gastrointestinal Tract and Other Smooth Muscle

Meperidine causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone may be increased to the point of spasm, resulting in constipation. Other opioid-induced effects may include a reduction in biliary and pancreatic secretions, spasm of sphincter of Oddi, and transient elevations in serum amylase.

Effects of the Cardiovascular System

Meperidine produces peripheral vasodilation which may result in orthostatic hypotension or syncope. Manifestations of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes, and sweating and/or orthostatic hypotension.

Effects on the Endocrine System

Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormones (LH) in humans [see Adverse Reactions (6)]. They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon.

Chronic use of opioids may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may manifest as low libido, impotence, erectile dysfunction, amenorrhea, or infertility. The causal role of opioids in the clinical syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, and psychological stressors that may influence gonadal hormone levels have not been adequately controlled for in studies conducted to date [see Adverse Reactions (6)].

Effects on the Immune System

Opioids have been shown to have a variety of effects on components of the immune system in in vitro and animal models. The clinical significance of these findings is unknown. Overall, the effects of opioids appear to be modestly immunosuppressive.

Concentration–Efficacy Relationships

The minimum effective analgesic concentration will vary widely among patients, especially among patients who have been previously treated with potent agonist opioids. The minimum effective analgesic concentration of meperidine for any individual patient may increase over time due to an increase in pain, the development of a new pain syndrome and/or the development of analgesic tolerance [see Dosage and Administration (2.1, 2.3)].

Meperidine, in 60 mg to 80 mg parenteral doses, is approximately equivalent in analgesic effect to 10 mg of morphine. The onset of action is slightly more rapid than with morphine, and the duration of action is slightly shorter. Meperidine is significantly less effective by the oral than by the parenteral route, but the exact ratio of oral to parenteral effectiveness is unknown.

Concentration–Adverse Reaction Relationships

There is a relationship between increasing meperidine plasma concentration and increasing frequency of dose-related opioid adverse reactions such as nausea, vomiting, CNS effects, and respiratory depression. In opioid-tolerant patients, the situation may be altered by the development of tolerance to opioid-related adverse reactions [see Dosage and Administration (2.1, 2.3)].

12.3 Pharmacokinetics

Elimination

The half-life of meperidine is 2 to 5 hours, and the half-life of normeperidine is 15 to 30 hours.

Metabolism

Meperidine is metabolized through biotransformation. In vitro data show meperidine is metabolized to normeperidine in liver mainly by CYP3A4 and CYP2B6.

Hepatic Impairment

The elimination half-life is 3 to 8 hours in healthy volunteers and is 1.3 to 2 times greater in post-operative or cirrhotic patients.

Excretion

Meperidine and normeperidine are excreted by kidneys.

Age

In clinical studies reported in the literature, changes in several pharmacokinetic parameters with increasing age have been observed. The initial volume of distribution and steady-state volume of distribution may be higher in elderly patients than in younger patients. The free fraction of meperidine in plasma may be higher in patients over 45 years of age than in younger patients.

Drug Interactions Studies

Phenytoin: The hepatic metabolism of meperidine may be enhanced by phenytoin. Concomitant administration resulted in reduced half-life and bioavailability with increased clearance of meperidine in healthy subjects; however, blood concentrations of normeperidine were increased [see Drug Interactions (7)].

Ritonavir: Plasma concentrations of the active metabolite normeperidine may be increased by ritonavir [see Drug Interactions (7)].

Acyclovir: Plasma concentrations of meperidine and its metabolite, normeperidine, may be increased by acyclovir [see Drug Interactions (7)].

Cimetidine: Cimetidine reduced the clearance and volume of distribution of meperidine and also the formation of the metabolite, normeperidine, in healthy subjects [see Drug Interactions (7)].

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Long-term studies in animals to evaluate the carcinogenic potential of meperidine have not been conducted.

Mutagenesis

Studies in animals to evaluate the mutagenic potential of meperidine have not been conducted.

Impairment of Fertility

Studies to determine the effect of meperidine on fertility have not been conducted.

16 HOW SUPPLIED/STORAGE AND HANDLING

For Parenteral Use

DEMEROL (meperidine hydrochloride injection), for subcutaneous, intramuscular, and intravenous use, is clear and colorless, and available as follows:

Unit of Sale Concentration (per total volume)

NDC 0409-1181-30 Carton of 130 mL fill in 30 mL Multiple-dose Vial

1,500 mg/30 mL(50 mg/mL)

NDC 0409-1176-30 Carton of 101 mL fill in 2.5 mL Carpuject Single-dose cartridge with Luer Lock

25 mg/mL

NDC 0409-1178-30 Carton of 101 mL fill in 2.5 mL Carpuject Single-dose cartridge with Luer Lock

50 mg/mL

NDC 0409-1179-30 Carton of 101 mL fill in 2.5 mL Carpuject Single-dose cartridge with Luer Lock

75 mg/mL

NDC 0409-1180-69 Carton of 101 mL fill in 2.5 mL Carpuject Single-dose cartridge with Luer Lock

100 mg/mL

NDC 0409-1362-01 Clamshell of 101 mL fill in 1.5 mL NexJect™ Single-dosePrefilled Syringe with Luer Lock

25 mg/mL

NDC 0409-1418-01 Clamshell of 101 mL fill in 1.5 mL NexJect™ Single-dosePrefilled Syringe with Luer Lock

50 mg/mL

NDC 0409-2033-01 Clamshell of 101 mL fill in 1.5 mL NexJect™ Single-dosePrefilled Syringe with Luer Lock

75 mg/mL

NDC 0409-1377-01 Clamshell of 101 mL fill in 1.5 mL NexJect™ Single-dosePrefilled Syringe with Luer Lock

100 mg/mL

Carpuject Single-dose cartridge are packaged in a Slim-Pak tamper detection package. Note that a needle is not included.

Carpuject and NexJectTM Single-dose products: Discard unused portion.

Multiple-dose vials: Discard unused portion after 28 days.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C to 30°C (59°F to 86°F). [See USP controlled room temperature.]

17 PATIENT COUNSELING INFORMATION

Serotonin Syndrome

Inform patients that opioids could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs. Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop. Instruct patients to inform their health care provider if they are taking, or plan to take serotonergic medications [see Warnings and Precautions (5.7), Drug Interactions (7)].

Constipation

Advise patients of the potential for severe constipation, including management instructions and when to seek medical attention [see Adverse Reactions (6), Clinical Pharmacology (12.1)].

Distributed by Hospira, Inc., Lake Forest, IL 60045 USA

Logo

LAB-0846-7.0

INSTRUCTIONS FOR USE

To Use NexJect™ Syringe

Image
(click image for full-size original)
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(click image for full-size original)
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(click image for full-size original)

NOTE: To prevent needlestick injuries, needles and blunt cannulas should not be recapped, purposely bent, or broken by hand.

Distributed by Hospira, Inc., Lake Forest, IL 60045 USA

Image

LAB-1387-1.0

Revised: 9/2020

PRINCIPAL DISPLAY PANEL — 25 mg/mL Cartridge Label

1 mL Single-dose Carpuject™
Sterile Cartridge Unit with Luer Lock

Rx only
NDC 0409-1176-03

Demerol™
meperidine HCl injection, USP
25 mg/mL
CII

Dist. by Hospira, Inc., Lake Forest, IL 60045 USA
Hospira

PAA193035

LOT #####AAEXP DMMMYYYY

PRINCIPAL DISPLAY PANEL -- 25 mg/mL Cartridge Label
(click image for full-size original)

PRINCIPAL DISPLAY PANEL — 25 mg/mL Cartridge Carton

NDC 0409-1176-30
Contains 10 of NDC 0409-1176-03
Rx only

1 mL Single-dose

10 Carpuject™
Sterile Cartridge Units
with Luer Lock

Needle not included

SLIM-PAK™
Tamper Detection Package

Demerol™
meperidine
hydrochloride
injection, USP
25 mg/mL
CII

For Intramuscular, Subcutaneous, or
Intravenous Use

Carpuject Cartridges are to be used
ONLY with Carpuject Holders.

Dist. by Hospira, Inc.,
Lake Forest, IL60045 USAHospira

PRINCIPAL DISPLAY PANEL -- 25 mg/mL Cartridge Carton
(click image for full-size original)

PRINCIPAL DISPLAY PANEL — 50 mg/mL Cartridge Label

1 mL Single-dose Carpuject™
Sterile Cartridge Unit with Luer Lock

Rx only
NDC 0409-1178-03

Demerol™
meperidine HCl injection, USP
50 mg/mL
CII

Dist. by Hospira, Inc., Lake Forest, IL 60045 USA
Hospira

PAA193036

LOT #####AAEXP DMMMYYYY

PRINCIPAL DISPLAY PANEL -- 50 mg/mL Cartridge Label
(click image for full-size original)

PRINCIPAL DISPLAY PANEL — 50 mg/mL Cartridge Carton

NDC 0409-1178-30
Contains 10 of NDC 0409-1178-03
Rx only

1 mL Single-dose

10 Carpuject™
Sterile Cartridge Units
with Luer Lock

Needle not included

SLIM-PAK™
Tamper Detection Package

Demerol™
meperidine
hydrochloride
injection, USP
50 mg/mL
CII

For Intramuscular, Subcutaneous, or
Intravenous Use

Carpuject Cartridges are to be used
ONLY with Carpuject Holders.

Dist. by Hospira, Inc.
Lake Forest, IL 60045 USAHospira

PRINCIPAL DISPLAY PANEL -- 50 mg/mL Cartridge Carton
(click image for full-size original)

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