To request medical information or to report SUSPECTED
ADVERSE REACTIONS, contact Hawthorn Pharmaceuticals , Inc., at (800) 793-2145
or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Potential effects of high dosage are also listed in the
Cardio-renal: Bradycardia, cardiac arrest,
circulatory collapse, renal toxicity, renal tubular necrosis, hypotension.
Central Nervous System/Psychiatric: Anxiety,
dizziness, drowsiness, dysphoria, euphoria, fear, general malaise, impairment
of mental and physical performance, lethargy, light-headedness, mental clouding,
mood changes, psychological dependence, sedation, somnolence progressing to
stupor or coma.
Endocrine: Hypoglycemic coma.
Gastrointestinal System: Abdominal pain,
constipation, gastric distress, heartburn, hepatic necrosis, hepatitis, occult
blood loss, nausea, peptic ulcer, and vomiting.
Genitourinary System: Spasm of vesical sphincters,
ureteral spasm, and urinary retention.
Hematologic: Agranulocytosis, hemolytic anemia,
iron deficiency anemia, prolonged bleeding time, thrombocytopenia.
Hypersensitivity: Allergic reactions.
Musculoskeletal: Skeletal muscle flaccidity.
Respiratory Depression: Acute airway obstruction,
apnea, dose-related respiratory depression (see OVERDOSAGE), shortness
Special Senses : Cases of hearing impairment or
permanent loss have been reported predominantly in patients with chronic
Skin: Cold and clammy skin, diaphoresis, pruritus,
Drug Abuse And Dependence
Misuse, Abuse, And Diversion Of Opioids
ZYFREL contains hydrocodone, an opioid agonist, and is a
Schedule II controlled substance. ZYFREL, and other opioids, used in analgesia
can be abused and are subject to criminal diversion.
Addiction is a primary, chronic, neurobiologic disease,
with genetic, psychosocial, and environmental factors influencing its
development and manifestations. It is characterized by behaviors that include
one or more of the following: impaired control over drug use, compulsive use,
continued use despite harm, and craving. Drug addiction is a treatable disease
utilizing a multidisciplinary approach, but relapse is common.
“Drug seeking” behavior is very common in
addicts and drug abusers. Drug-seeking tactics include emergency calls or
visits near the end of office hours, refusal to undergo appropriate
examination, testing or referral, repeated “loss” of prescriptions,
tampering with prescriptions and reluctance to provide prior medical records or
contact information for other treating physician(s). “Doctor
shopping” to obtain additional prescriptions is common among drug abusers
and people suffering from untreated addiction.
Abuse and addiction are separate and distinct from
physical dependence and tolerance. Physical dependence usually assumes
clinically significant dimensions only after several weeks of continued opioid
use, although a mild degree of physical dependence may develop after a few days
of opioid therapy. Tolerance, in which increasingly large doses are required in
order to produce the same degree of analgesia, is manifested initially by a
shortened duration of analgesic effect, and subsequently by decreases in the
intensity of analgesia. The rate of development of tolerance varies among
patients. Physicians should be aware that abuse of opioids can occur in the
absence of true addiction and is characterized by misuse for nonmedical
purposes, often in combination with other psychoactive substances. ZYFREL, like
other opioids, may be diverted for non-medical use. Record-keeping of prescribing
information, including quantity, frequency, and renewal requests is strongly
Proper assessment of the patient, proper prescribing
practices, periodic reevaluation of therapy, and proper dispensing and storage
are appropriate measures that help to limit abuse of opioid drugs.