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HOW DOES Ultram WORK? Ultram
acts on the central nervous system and unlike codeine and
its derivative medications is a totally synthetic analgesic
compound. Although its mode of action is not completely
understood, from animal tests, at least two complementary
mechanisms appear applicable: the binding of parent compound
and its metabolite to opioid receptors and weak inhibition
of reuptake of norepinephrine and serotonin by nerves located
within the central nervous system. Ultram-induced analgesia
is only partially reversed by the opiate antagonist naloxone
in several animal tests. Ultram has been shown to inhibit
reuptake of norepinephrine and serotonin in vitro.
These mechanisms may contribute independently to the overall
analgesic profile of Ultram. Analgesia in humans begins
approximately within one hour after administration and reaches
a peak in approximately two to three hours.
HOW EFFECTIVE IS Ultram? Ultram
has been given in single oral doses of 50, 75, 100, 150
and 200 mg to patients with pain following surgical procedures
and pain following oral surgery (extraction of impacted
molars). In single-dose models of pain following oral surgery,
pain relief was demonstrated in some patients at doses of
50 mg and 75 mg. A dose of 100 mg of Ultram tended to
provide analgesia superior to codeine sulfate 60 mg, but
it was not effective as the combination of aspirin 650 mg
with codeine phosphate 60 mg. In single-dose models of pain
following surgical procedures, 150 mg provided analgesia
generally comparable to the combination of acetaminophen
650 mg with propoxyphene napsylate 100 mg, with a tendency
toward later peak effect. Ultram has been studied in three
long-term controlled trials involving a total of 820 patients,
with 530 patients receiving Ultram. Patients with a variety
of chronic painful conditions were studied in double-blind
trials of one to three months duration. Average daily doses
of approximately 250 mg of Ultram in divided doses were
generally comparable with five doses of acetaminophen 300
mg with codeine phosphate 30 mg (Tylenol with Codeine #3)
daily, five doses of aspirin 325 mg with codeine phosphate
30 mg daily, or two to three doses of acetaminophen 500
mg with oxycodone hydrochloride 5 mg (Tylox) daily.
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HOW DO I USE Ultram?
For the treatment of painful conditions
Ultram 50 mg to 100 mg can be administered as needed for relief
every four to six hours, not to exceed 400 mg per day. For
moderate pain Ultram 50 mg may be adequate as the initial dose,
and for more severe pain, Ultram 100 mg is usually more effective
as the initial dose.
Individualization of Dose:
Patients 65 to 75 years
of age: No dose adjustment is necessary.
Patients over 75 years
old: No more then 300 mg/day in divided doses
Patients with kidney
impairment: The dosing interval of Ultram should be increased
to 12 hours with a maximum daily dose of 200 mg.
Dialysis patients:
These patients can receive their regular dose on the day of
dialysis.
Patients with cirrhosis:
Recommended dosage is 50 mg every 12 hours.
Patients receiving
chronic carbamazepine: Doses up to 800 mg daily may be required,
this is up to twice the recommended dose of Ultram.
ADVERSE REACTIONS:
Ultram was administered to 550
patients during the double-blind or open-label extension periods
in U.S. studies of chronic nonmalignant pain. Of these patients,
375 were 65 years old or older. TABLE 2 reports the cumulative incidence
rate of adverse reactions by 7, 30 and 90 days for the most frequent
reactions (5% or more by 7 days). The most frequently reported events
were in the central nervous system and gastrointestinal system.
Although the reactions listed in the table are felt to be probably
related to Ultram administration, the reported rates also include
some events that may have been due to underlying disease or concomitant
medication. The overall incidence rates of adverse experiences in
these trials were similar for Ultram and the active control groups,
acetaminophen 300 mg with codeine phosphate 30 mg, and aspirin 325
mg with codeine phosphate 30 mg. (TABLE 2)
| TABLE 2 Cumulative Incidence
of Adverse Reactions for Ultram HCl In Chronic Trials of
Nonmalignant Pain (N = 427) |
| |
Up to 7 Days |
Up to 30 Days |
Up to 90 Days |
| Dizziness/Vertigo |
26% |
31% |
33% |
| Nausea |
24% |
34% |
40% |
| Constipation |
24% |
38% |
46% |
| Headache |
18% |
26% |
32% |
| Somnolence (Sleepiness) |
16% |
23% |
25% |
| Vomiting |
9% |
13% |
17% |
| Pruritus |
8% |
10% |
11% |
| "CNS Stimulation"1 |
7% |
11% |
14% |
| Asthenia (Weakness) |
6% |
11% |
12% |
| Sweating |
6% |
7% |
9% |
| Dyspepsia (Acid Indigestion) |
5% |
9% |
13% |
| Dry Mouth |
5% |
9% |
10% |
| Diarrhea |
5% |
6% |
10% |
| 1 "CNS
Stimulation" is a composite of nervousness, anxiety,
agitation, tremor, spasticity, euphoria, emotional lability
and hallucinations. |
DRUG ABUSE AND DEPENDENCE:
Ultram has a potential
to cause psychic and physical dependence of the morphone-type. The
drug has been associated with craving, drug-seeking behavior and
tolerance development. Cases of abuse and dependence on Ultram
have been reported.
Ultram should not be used
in opioid-dependent patients. Ultram can reinitiate physical dependence
in patients that have been previously dependent or chronically using
other opioids. In patients with a tendency to drug abuse, a history
of drug dependence, or are chronically using opioids, treatment
with Ultram is not recommended.
Ultram AND SEIZURES:
Seizure Risk:
Seizures have been reported in patients receiving Ultram
within the recommended dosage range. Concomitant use of Ultram
increases the seizure risk in patients taking:
Selective serotonin reuptake
inhibitors (SSRI antidepressants or anoretics -phentermine),
Tricyclic antidepressants
and other tricyclic compounds (e.g., cyclobenzaprine,
promethazine, etc.)
Opioids.
MAO inhibitors
Neuroleptics
Any drugs that reduce the
seizure threshold
Epilepsy
Ultram AND DROWZINESS:
Ultram may impair mental
or physical abilities required for the performance of potentially
hazardous tasks such as driving a car or operating machinery.
Ultram should not be taken
with alcohol containing beverages.
Ultram should be used
with caution when taking medications such as tranquilizers,
hypnotics or other opiate containing analgesics.
Ultram AND PREGNANCY:
Ultram should not be used
in pregnant women or nursing mothers, safe use in pregnancy
has not been established.
Chronic use during pregnancy
may lead to physical dependence and post-pregnancy withdrawal
symptoms in the newborn.
Ultram has been shown
to cross the placenta. Nonetheless, the effect of Ultram,
if any, on the later growth, development, and functional maturation
of the child is unknown.
OVERDOSAGE:
Serious potential consequences
of over dosage are respiratory depression and seizure.
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