Tramadol Precautions Respiratory Depression When large doses of Ultram are administered with anesthetic medications or alcohol, respiratory depression may result. Cases of intraoperative respiratory depression, usually with large intravenous doses of tramadol and with concurrent administration of respiratory depressants, , have been reported in foreign experience. Such cases should be treated as overdoses (see OVERDOSAGE). Ultram should be administered cautiously in patients at risk for respiratory depression, hydrocodone with apap 10 500. Increased Intracranial Pressure or Head Trauma Ultram should be used with caution in patients with increased intracranial pressure or head injury. Pupillary changes (miosis) from tramadol may obscure the existence, extent or course of intracranial pathology. Clinicians should also maintain a high index of suspicion for adverse drug reaction when evaluating mental status in these patients if they are receiving Ultram. Acute Abdominal Conditions The administration of Ultram may complicate the clinical assessment of patients with acute abdominal conditions, tramadol information and side effects. Patients Physically Dependent on Opioids Ultram is not recommended for patients who are dependent on opioids. Patients who have recently taken substantial amounts of opioids may experience withdrawal symptoms. Because of the difficulty in assessing dependence in patients who have previously received substantial amounts of opioid medication, hydrocodone with apap 10 500, caution should be used in the administration of Ultram to such patients. Use in Renal and Hepatic Disease Impaired renal function results in a decreased rate and extent of excretion of tramadol and its active metabolite M1. In patients with creatinine clearances of less than 30 ml/min dosing reduction is recommended (see DOSAGE AND ADMINISTRATION), can tramadol treat tension headache. Metabolism of tramadol and M1 is reduced in patients with advanced cirrhosis of the liver. In cirrhotic patients, dosing reduction is recommended (see DOSAGE AND ADMINISTRATION). With the prolonged half-life in these conditions, achievement of steady state is delayed, so that it may take several days for elevated plasma concentrations to develop, how to quit taking tramadol. Information for Patients Patients being treated with Ultram should receive the following information: Ultram may impair mental or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. Carcinogenesis, hydrocodone with apap 10 500, Mutagenesis, Impairment of Fertility Tramadol was not mutagenic in the following assays: Ames Salmonella microsomal activation test, CHO/HPRT mammalian cell assay, mouse lymphoma assay (in the absence of metabolic activation), dominant lethal mutation tests in mice, hydrocodone with apap 10 500, chromosome aberration test in Chinese hamsters, , and bone marrow micronucleus tests in mice and Chinese hamsters. Weakly mutagenic results occurred in the presence of metabolic activation in the mouse lymphoma assay and micronucleus test in rats. Overall, hydrocodone with apap 10 500, the weight of evidence from these tests indicates that tramadol does not pose a genotoxic risk to humans. A slight, but statistically significant, increase in two common murine tumors, hydrocodone with apap 10 500, pulmonary and hepatic, was observed in a mouse carcinogenicity study, hydrocodone with apap 10 500, particularly in aged mice (dosing orally up to 30 mg/kg for approximately two years, , although the study was not done with the Maximum Tolerated Dose). This finding is not believed to suggest risk in humans, tramadol when became available. No such finding occurred in a rate carcinogenicity study. No effects on fertility were observed for tramadol at oral dose levels up to 50 mg/kg in male rats and 75 mg/kg in female rats, can tramadol treat tension headache. Teratogenic Effects: Usage in Pregnancy Pregnancy Category C There are no adequate and well-controlled studies in pregnant women. Ultram should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Tramadol has been shown to be embryotoxic and fetotoxic in mice, rats and rabbits and maternally toxic doses 3 to 15 times the maximum human dose or higher (120 mg/kg in mice, 25 mg/kg or higher in rats and 75 mg/kg or higher in rabbits), but was not teratogenic at these dose levels. No harm to the fetus due to tramadol was seen at doses that were not maternally toxic. No drug-related teratogenic effects were observed in progeny of mice, hydrocodone with apap 10 500, rats or rabbits treated with tramadol by various routes (up to 140 mg/kg for mice, 80 mg/kg for rats or 300 mg/kg for rabbits). Embryo and fetal toxicity consisted primarily of decreased fetal weights, skeletal ossification and increased supemumerary ribs at maternally toxic dose levels. Transient delays in developmental or behavioral parameters were also seen in pups in rat dams allowed to deliver, tramadol information and side effects. Embryo and fetal lethality were reported only in one rabbit study at 300 mg/kg, a dose that would cause extreme maternal toxicity in the rabbit. In peri- and post-natal studies in rats, progeny of dams receiving oral (gavage) dose levels of 50 mg/kg or greater had decreased weights, and pup survival was decreased early in lactation at 80 mg/kg (6 to 10 times the maximum human dose). No toxicity was observed for progeny of dams receiving 8, 10, 20, , 25 or 40 mg/kg. Maternal toxicity was observed at all dose levels, but effects on progeny were evident only at higher dose levels where maternal toxicity was more severe. Labor and Delivery Ultram should not be used in pregnant women prior to or during labor unless the potential benefits outweigh the risks, , because safe use in pregnancy has not been established. Tramadol has been shown to cross the placenta. The mean ratio of serum tramadol in the umbilical veins compared to maternal veins was for 40 women given tramadol during labor, hydrocodone with apap 10 500. The effect of Ultram, if any, hydrocodone with apap 10 500, on the later growth, , development, hydrocodone with apap 10 500, and functional maturation of the child is unknown. Nursing Mothers Ultram is not recommended for obstetrical preoperative medication or for post-delivery analgesia in nursing mothers because its safety in infants and newborns has not been studied. Following a single 100 mg dose of tramadol, the cumulative excretion in breast milk within 16 hours postdose was 100 µg of tramadol (0.1% of the maternal dose) and 27 µg of M1. Pediatric Use The pediatric use of Ultram (tramadol hydrochloride) is not recommended because safety and efficacy in patients under 16 years of age have not been established. Use in the Elderly In subjects over the age of 75 years, serum concentrations are slightly elevated and the elimination half-life is slightly elevated and the elimination half-life is slightly prolonged. The aged also can be expected to vary more widely in their ability to tolerate adverse drug effects. Daily doses in excess of 300 mg are not recommended in patients over 75 
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Tramadol hydrochloride (Ultram, Tramal others below) is a centrally acting opioid analgesic, used in treating moderate to severe pain, how to quit taking tramadol. The drug has a wide range of applications, hydrocodone with apap 10 500, including treatment for restless leg syndrome and fibromyalgia. It was developed by the pharmaceutical company Grünenthal GmbH in the late 1970s. Tramadol possesses weak agonist actions at the μ-opioid receptor, releases serotonin, and inhibits the reuptake of norepinephrine. Tramadol is a synthetic analog of the phenanthrene alkaloid codeine and, as such, is an opioidand also a prodrug (codeine is metabolized to morphine, tramadol is converted to O-desmethyltramadol), tramadol information and side effects. Opioids are chemical compounds which act upon one or more of the human opiate receptors. The euphoria and respiratory depression are mainly caused by the μ1and μ2 receptors; the addictive nature of the drug is due to these effects as well as its serotonergic/noradrenergic effects, hydrocodone with apap 10 500. The opioid agonistic effect of tramadol and its major metabolite(s) are almost exclusively mediated by the substance's action at the μ-opioid receptor. This characteristic distinguishes tramadol from many other substances (including morphine) of the opioid drug class, hydrocodone with apap 10 500, which generally do not possess tramadol's degree of subtype selectivity. Uses Tramadol is used similarly to codeine, to treat moderate to moderately severe pain and most types of neuralgia, including trigeminal neuralgia. Tramadol is somewhat pharmacologically similar to levorphanol (albeit with much lower μ-agonism), , as both opioids are also NMDA-antagonists which also have SNRI activity (other such opioids to do the same aredextropropoxyphene (Darvon) & M1-like molecule tapentadol (Nucynta, a new synthetic atypical opioid made to mimic the agonistic properties of tramadol's metabolite, M1(O-Desmethyltramadol). Tramadol is also molecularly similar to Effexor (Venlafaxine) and has similar SNRI effects, with antinociceptive effects also observed. It has been suggested that tramadol could be effective for alleviating symptoms of depression, anxiety, and phobias because of its action on the noradrenergic and serotonergic systems, such as its "atypical" opioid ver, health professionals have not endorsed its use for these disorders, claiming it may be used as a unique treatment (only when other treatments failed), and must be used under the control of a psychiatrist. In May 2009, hydrocodone with apap 10 500, the United States Food and Drug Administration issued a Warning Letter to Johnson & Johnson, alleging that a promotional website commissioned by the manufacturer had "overstated the efficacy" of the drug, and "minimized the serious risks". The company which produced it, the German pharmaceutical company Grünenthal GmbH, were the ones alleged to be guilty of "minimizing" the addictive nature and proposed efficacy of the drug, , although it showed little abuse liability in preliminary tests, hydrocodone with apap 10 500. The 2010 Physicians Desk Reference contains several warnings from the manufacturer, which were not present in prior years. The warnings include more compelling language regarding the addictive potential of tramadol, the possibility of difficulty breathing while on the medication, hydrocodone with apap 10 500, a new list of more serious side effects, and a notice that tramadol is not to be used in place of opiate medications for addicts. Tramadol is also not to be used in efforts to wean addict patients from opiate drugs, nor to be used to manage long-term opiate addiction. Availability and Usage Tramadol is usually marketed as the hydrochloride salt (tramadol hydrochloride); the tartrate is seen on rare occasions, and rarely (in the US at least) tramadol is available for both injection (intravenous and/or intramuscular) and oral administration. The most well known dosing unit is the 50 mg generic tablet made by several manufacturers. It is also commonly available in conjunction with APAP (Paracetamol, Acetaminophen) as Ultracet, , in the form of a smaller dose of mg tramadol and 325 mg of APAP. The solutions suitable for injection are used in patient-controlled analgesia pumps under some circumstances, either as the sole agent or along with another agent such as morphine. Tramadol comes in many forms, including:
capsules (regular and extended release)
tablets (regular, extended release, chewable, , low-residue and/or uncoated tablets that can be taken by the sublingual and buccal routes)
suppositories
effervescent tablets and powders
ampules of sterile solution for SC, IM, and IV injection
preservative-free solutions for injection by the various spinal routes (epidural, intrathecal, caudal, hydrocodone with apap 10 500, and others)
powders for compounding
liquids both with and without alcohol for oral and sub-lingual administration, available in regular phials and bottles, dropper bottles, bottles with a pump similar to those used with liquid soap and phials with droppers built into the cap
tablets and capsules containing (acetaminophen/APAP), aspirin and other agents.
Tramadol has been experimentally used in the form of an ingredient in multi-agent topical gels, creams, , and solutions for nerve pain, hydrocodone with apap 10 500, rectal foam, , concentrated retention enema, and a skin plaster (transdermal patch) quite similar to those used with lidocaine. Tramadol has a characteristic and unpleasant taste which is mildly bitter but much less so than morphine and codeine. Oral and sublingual drops and liquid preparations come with and without added flavoring. Its relative effectiveness via transmucosal routes (i.e. sublingual, hydrocodone with apap 10 500, buccal, rectal) is similar to that of codeine, and, , like codeine, it is also metabolized in the liver to stronger metabolites (see below). The maximum dosage per day is 400Â mg for oral use and 600Â mg for parenteral use. Certain manufacturers or formulations have lower maximum doses. For example, Ultracet (37.5Â mg/325Â mg tramadol/APAP tablets) is capped at 8 tablets per day (300Â mg/day) due to its acetaminophen content. Ultram ER is available in 100, 200, and 300Â mg/day doses and is explicitly capped at 300Â mg/day as well. Patients taking SSRIs (Prozac, Zoloft, etc.), , SNRIs (Effexor, etc.), TCAs, MAOIs, or other strong opioids (oxycodone, hydrocodone with apap 10 500, methadone, fentanyl, morphine), as well as the elderly (> 75 years old), pediatric (< 18 years old), and those with severely reduced renal (kidney) or hepatic (liver) function should consult their doctor regarding adjusted dosing or whether to use Tramadol at all.
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