Tramadol dosing

Isolated seizures that are not epilepsy can be caused by stroke, central nervous system trauma, central nervous system infections, metabolic disturbances (e.g., hyponatremia and hypoglycemia), and hypoxia. If these underlying causes of seizures are not corrected, they may lead to the development of recurrent seizures I or epilepsy. Medications can also cause seizures. Some drugs that are commonly associated with seizures include tramadol, bupropion, theophylline, some antidepressants, some antipsy-chotics, amphetamines, cocaine, imipenem, lithium, excessive doses of penicillins or cephalosporins, and sympathomimetics or stimulants. 

Tramadol is a reasonable option for patients with contraindications to NSAIDs or failure to respond to other oral therapies. For the treatment of hip or knee OA, tramadol is as effective as NSAIDs. The addition of tramadol to NSAIDs or acetaminophen may augment the analgesic effects of a failing regimen, thereby securing sufficient pain relief in some patients. Moreover, concomitant tramadol may permit the use of lower NSAID doses. 

Dizziness, vertigo, nausea, vomiting, constipation, and lethargy are all relatively common adverse events. These effects are more pronounced for several days after initiation and following upward dose titration. Seizures have been reported rarely the risk is dose-related and appears to increase with concomitant use of antidepressants, such as tricyclic antidepressants or selective serotonin reuptake inhibitors. Tramadol should be avoided in patients receiving monoamine oxidase (MAO) inhibitors because tramadol inhibits the uptake of norepinephrine and serotonin. 

Tramadol should be initiated at a lower dose (100 mg/day in divided doses) and may be titrated as needed for pain control to a dose of 200 mg/ day. It is available in a combination tablet with acetaminophen and as a sustained-release tablet. 

TRAMADOL Individualize dose based on the lowest effective dose. Starting at the lowest possible dose and titrating upward as needed has resulted in increased tolerability and fewer discontinuations. Can be administered without regard to meals. 

Dosages and routes of administration Tramadol is used in single doses of 50-100 mg up to daily doses of 300-400 mg. The compound has high oral bio-availability and can be given by mouth, rectally or by intramuscular, subcutaneous or slow intravenous injection or infusion (Lintzet al. 1981). 

Side-effects Typical side-effects of tramadol are nausea, sweating and dizziness. In rare cases seizures after high i.v. doses are reported, mostly in combination with other proconvulsant componds or in patients with reduced seizure theshold (Gardner et al., 2000). Tramadol shows a reduced level of opioid side-effects, especially respiratory depression and constipation are less frequent and severe than with standard opioids such as morphine. Tramadol has a very limited abuse potential and is not subject to narcotic control (Cossmann et al., 1997). 

The success of prolonged-release morphine prompted the development of prolonged-release formulations for other opioids, for example the matrix made of hydrophobic and hydrophilic matrix formers, for example on hydrocodeine (DHC retard with cetostearyl alcohol and hydroxyethyl-cellulose), oxycodone (oxygesic with stearyl alcohol and polyacrylate) and tramadol (tramundin with cetostearyl alcohol and ethylcellulose). By virtue of the oblong shape of hydrocodeine and tramadol tablets the prolonged-release tablets can be divided, whereby compared with whole tablets release from the divided tablets is slightly accelerated. The difference with these forms is that with increasing dose the release slows down. 

A purely hydrophilic matrix of hypromellose prolongs the release of tramadol from Tramal long (Fig. 3) developed by Gruenenthal. The tablets have the same dimensions, resulting in an identical release profile for all dosages (100, 150, 200 mg, see Fig. 4). For a titrated effect linear pharmacokinetics on increasing doses produce dose-proportional blood levels at any time. External influences, such as pH value, mechanical stress, surface-active... 

Figure 4 Dose-independent in-vitro release of tramadol hydrochloride from Tramal / Contramal /Adolonta long 100, 150 and 200 mg (medium up to 0.5 h artificial gastric juice pH 1.2 up to 2 h pH 2.3 up to 3 h pH 6.8 up to 12 h pH 7.4).

Tramadol is available as drops, capsules, and sustained-release formulations for oral use, suppositories for rectal use, and solution for intramuscular, intravenous, and subcutaneous injection. After oral administration, tramadol is rapidly and almost completely absorbed. Sustained-release tablets release the active ingredient over a period of 12 h, reach peak concentrations after 4.9 h, and have a bioavailability of 87 to 95% compared with capsules. One 100-mg dose given to healthy volunteers resulted in plasma levels of 375 ng/ml at 1.5 h.55 Tramadol is 20% bound to plasma protein and it is rapidly distributed in the body it is mainly metabolized by O- and A-demethylation forming glucuronides and sulfates that are excreted by the kidney. 

A 47-year-old man with a long history of depression had been stable on a combination of venlafaxine 300 mg/day and mirtazapine 30 mg/day for 3 months. He started to take tramadol for a chronic pain syndrome and the dose was titrated up to 300 mg/day over the next 4 weeks. The dose was then increased to 400 mg/day, and 8 days later he developed shivering, sweating, myoclonus, hyper-reflexia, and mydriasis. His medications were withdrawn, but over the next 4 hours he developed a fever (39.2°C) and a tachycardia. He was given intravenous hydration and closely monitored, and the symptoms resolved over the next 36 hours. Venlafaxine and mirtazapine were restarted and he remained symptom free. 

Tramadol (25, Tramol), another cyclohexane with opioid properties, has trans l-m-methoxyphenyl,2-dimethylaminomethyl substituents and is in clinical use in West Germany. It was extensively described in a supplement of Arneimittel Forschung.(39) In animal tests its potency is closer to that of codeine than morphine and relatively high clinical doses (50-100 mg) are necessary for pain relief. Side elTects are generally minor and the compound... 

Tramadol 70% following single dose, 90% at steady state [48] 20 6 30 Not significant [49] N- and O-demethylation via CYP3A4 and CYP2D6 followed by glucuronidation or sulphation First-pass metabolism of 20-30% [49] Yes. CYP2D6 O-demethylation produces active metabolite... 

There is one published report of unintentional tramadol overdose causing acute fulminant hepatic necrosis and death. The exact amount taken was not known, but may have been more than twice the maximum daily dose of 100 mg four times a day for a period of days. Hepatitis and liver failure are listed as possible adverse effects in some US, but no UK product information [54]. 

DIGOXIN OPIOIDS T concentrations of digoxin may occur with tramadol Uncertain at present Watch for digoxin toxicity check levels and i the dose of digoxin as necessary... 

TCAs OPIOIDS 1. Risk of t respiratory depression and sedation 2. t levels of morphine 3. Case reports of seizures when tramadol was co-administered with TCAs 4. TCAs may t codeine, fentanyl, pethidine and tramadol levels 1. Additive effect 2. Uncertain likely t bioavailability of morphine 3. Unknown 4. TCAs inhibit CYP2D6-mediated metabolism of these opioids 1. Warn patients of this effect. Titrate doses carefully 2. Warn patients of this effect. Titrate doses carefully 3. Consider an alternative opioid 4. Watch for excessive narcotization... 

CARBAMAZEPINE ANALGESICS - OPIOIDS 1.1 efficacy of fentanyl and methadone 2.1 tramadol levels 1. t hepatic metabolism of fentanyl and methadone, and possibly an effect at the opioid receptor 2. t metabolism of tramadol 1. Be aware that the dose of fentanyl and methadone may need to be t 2. Watch for poor effect of tramadol. Consider using an alternative opioid... 

IMATINIB ANALGESICS-OPIOIDS May cause t plasma concentrations, with a risk of toxic effects of codeine, dextromethorphan, hydroxycodone, methadone, morphine, oxycodone, pethidine and tramadol Inhibition of CYP2D6-mediated metabolism of these opioids Monitor for clinical efficacy and toxicity. Warn patients to report t drowsiness, malaise or anorexia. Measure amylase and lipase levels if toxicity is suspected. Tramadol causes less respiratory depression than other opiates, but need to monitor BP and blood counts, and advise patients to report wheezing, loss of appetite and fainting attacks. Need to consider 1 dose. Methadone may cause Q-T prolongation the CHM has recommended that patients with heart and liver disease who are on methadone should be carefully monitored for heart conduction abnormalities such as Q-T prolongation on ECG as they may lead to sudden death. Also need to monitor patients on more than 100 mg methadone daily and thus an t in plasma concentrations necessitates close monitoring of cardiac and respiratory function... 

ALFENTANIL, BUPRENORPHINE, FENTANYL, TRAMADOL PROTEASE INHIBITORS Possibly t adverse effects when buprenorphine is co administered with indinavir, ritonavir (with or without lopinavir) or saquinavir Inhibition of CYP3A4 (CYP2D6 in the case of tramadol) Halve the starting dose and titrate to effect. For single injection of fentanyl, monitor sedation and respiratoiy function closely. If continued use of fentanyl, i dose may be required. Concomitant use of ritonavir and transdermal fentanyl is not recommended... 

O-monodesmethyltramadol, A, 0-didesmethyl tramadol and their conjugates, and A-monodesmethyltramadol. O-Monodes-methyltramadol is an active metabolite and has a greater analgesic activity than the parent drug. About 90% of an oral dose is excreted in the urine in 3 days, about 30% of the dose as unchanged drug, and the rest as metabolites. The remainder of the dose is eliminated in the faeces. ... 

---