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Tramadol (generic for Ultram)
is a white, bitter, crystalline and odorless powder. Each
Tramadol tablet tablet tablet contains 50 mg of tramadol
hydrochloride and is white in color.
HOW DOES Tramadol WORK? Tramadol
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. Tramadol-induced analgesia
is only partially reversed by the opiate antagonist naloxone
in several animal tests. Tramadol has been shown to inhibit
reuptake of norepinephrine and serotonin in vitro.
These mechanisms may contribute independently to the overall
analgesic profile of Tramadol. Analgesia in humans begins
approximately within one hour after administration and reaches
a peak in approximately two to three hours.
HOW EFFECTIVE IS Tramadol? Tramadol
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 Tramadol 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. Tramadol has been studied in three
long-term controlled trials involving a total of 820 patients,
with 530 patients receiving Tramadol. 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 Tramadol 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 Tramadol?
For the treatment of painful conditions
Tramadol 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 Tramadol 50 mg may be adequate as the initial dose,
and for more severe pain, Tramadol 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 Tramadol 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 Tramadol.
ADVERSE REACTIONS:
Tramadol 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 Tramadol 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 Tramadol 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 Tramadol 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:
Tramadol 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 Tramadol
have been reported.
Tramadol should not be used in opioid-dependent
patients. Tramadol 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 Tramadol is not
recommended.
Tramadol AND SEIZURES:
Seizure Risk:
Seizures have been reported in patients receiving Tramadol
within the recommended dosage range. Concomitant use of Tramadol
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
Tramadol AND DROWZINESS:
Tramadol may impair mental or
physical abilities required for the performance of potentially hazardous
tasks such as driving a car or operating machinery.
Tramadol should not be taken
with alcohol containing beverages.
Tramadol should be used with
caution when taking medications such as tranquilizers, hypnotics
or other opiate containing analgesics.
Tramadol AND PREGNANCY:
Tramadol 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.
Tramadol has been shown to cross
the placenta. Nonetheless, the effect of Tramadol, 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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