Tramadol

From Anvita Health Wiki

Contents 1 Introduction 2 Contraindications 3 Dosage 4 Dosage-adjustment-in-renal-failure 5 Pharmacokinetics 6 Adverse-effects 7 Drug-interactions 8 Laboratory 9 Mechanism-of-action 10 More General Terms 11 Additional Terms 12 Internet Database 13 References

Introduction

• Tradename: Ultram.

Contraindications

• Caution: avoid in opioid-dependent individuals
  

• pregnancy category = c
• safety in lactation = -

Dosage

• 50-100 mg <A3880>PO</A3880> every 4-6 hours, max 400 <A4650>mg/day</A4650>
• elderly (< 75 years): 50 mg every 6 hours, max 300 <A4650>mg/day</A4650>

• extended release

• <A3861>QD</A3861> dosing, maximum 300 <A4650>mg/day</A4650>
• use with caution in the elderly

• Tabs: () 50 mg
• Tabs: (extended release) 100, 200, 300 mg

Dosage-adjustment-in-renal-failure

• indicated for creatinine clearance < 30 mL/min

• 50-100 mg BID ( tabs)
• maximum 200 mg QD
• extended release tabs should not be used

Pharmacokinetics

• oral doses rapidly absorbed
• peak serum levels within 2-3 hours
• bioavailability 60% after a single oral dose, but approaches 100% with regular scheduled use
• protein binding 20%
• volume of distribution: 2.5-3 L/kg
• metabolism in the liver by cyt P450 2D6

• necessary for conversion to an active analgesic metabolite [3]
• 11 metabolites, only 1 is active

• t1/2 6.3 hours (parent), 7.4 hours active metabolite
• excreted in urine (30% as unchanged drug, 60% as metabolites)
  

• elimination via liver
• elimination via kidney

Adverse-effects

• central nervous system

• drowsiness
• dizziness
• headache
• fatigue
• restlessness
• seizures [4]

• gastrointestinal ( GI) system

• nausea/vomiting
• constipation
• dry mouth

• diaphoresis
• minimal respiratory depression
• low potential for producing psychological/ physical dependence
• withdrawal symptoms may occur with abrupt discontinuation

• anxiety, sweating, insomnia, rigors, pain, nausea, tremors, diarrhea, upper respiratory symptoms, hallucinations (rarely).
• no specific taper recommendations [5]

• risk of suicide for patients who are addiction prone, or taking antidpressants or tranquilizers [7,8]

Drug-interactions

• concurrent administration of antidepressants (especially tricyclic antidepressants, bupropion) may induce seizures
• coadministration with selective serotonin reuptake inhibitors SSRI may result in serotonin syndrome
• any drug that inhibits cyt P450 2D6 may increase levels of tramadol &/or may interfere with analgesic effect
• coadministration of tranquilizers or antidepressants may increase risk of suicide [7]

Laboratory

• Therapeutic range: 100-300 ng/mL (monitoring not required)

Mechanism-of-action

• binds to opioid mu receptors in CNS

• inhibits ascending pain pathways
• alters perception & response to pain

• inhibits reuptake of norepinephrine & serotonin

• modifies ascending response pathway

More General Terms

• analgesic (antalgic)

Additional Terms

• cytochrome P450 2D6 (cytochrome P450 2D, cytochrome P450 DB1, debrisoquine-4-hydroxylase, CYP2D6)

Internet Database

PubChem: 19472
PubChem: 33741
PubChem: 5523
PubChem: 63013
PubChem: 63014

References

1. Drugdex Drug Evaluation
2. Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
3. Medications Can Cause Seizures Prescriber's Letter 10(3):16 2003 Detail-Document#: [1] (subscription needed) [2]
4. Department of Veterans Affairs, VA National Formulary
5. Prescriber's Letter 15(12): 2008 Common Oral Medications that May Need Tapering Detail-Document#: [3] (subscription needed) [4]
6. Lexi-Comp, Inc 2009
7. FDA MedWatch Ultram (tramadol hydrochloride), Ultracet (tramadol hydrochloride/acetaminophen): Label Change [5]
8. Prescriber's Letter 17(7): 2010 New Abuse and Safety Warnings for Tramadol Detail-Document#: [6] (subscription needed) [7]
9. Prescriber's Letter 19(3): 2012 Drug Interactions with Tramadol Detail-Document#: [8] (subscription needed) [9]

tramadol (Ultram)