Zydol

Approved Indications:

• Moderate to Moderately Severe Pain (acute or chronic)
• Postoperative Pain Management
• Osteoarthritis Pain (when NSAIDs are ineffective or contraindicated)
• Musculoskeletal Pain
• Cancer-related Pain
• Neuropathic Pain
• Low Back Pain
• Dental Pain (e.g., tooth extraction, oral surgery)

Clinically Accepted Off-label Uses:

• Fibromyalgia (as adjunct in selected cases)
• Premature Ejaculation (due to its serotonergic activity)
• Diabetic Neuropathy (as second-line agent)
• Pain in Palliative Care (when opioids are titrated for effect)

General Principles:

• Use the lowest effective dose for the shortest duration.
• Titrate slowly to avoid CNS side effects.

Adults (≥18 years):

• Immediate-release (IR):
  50–100 mg orally every 4–6 hours as needed
  Maximum: 400 mg/day
• Extended-release (ER):
  Start at 100 mg once daily
  May titrate by 100 mg every 5 days
  Maximum: 300 mg/day

Geriatric Patients (>75 years):

• IR: 50 mg orally every 6 hours
  Maximum: 300 mg/day
  Use caution with ER forms

Pediatrics (<17 years):

• Not recommended for use due to risk of respiratory depression.

Renal Impairment (CrCl <30 mL/min):

• Increase dosing interval to every 12 hours
  Avoid ER formulations

Hepatic Impairment:

• Use with caution in mild/moderate impairment
• Avoid in severe hepatic dysfunction

Route of Administration:

• Oral tablets/capsules (IR and ER)
• Oral drops
• Injection (IM/IV – rarely used, reserved for inpatient or emergency care)

Tramadol acts as a centrally acting synthetic analgesic with a dual mechanism. It binds weakly to the μ-opioid receptor (after conversion to the active metabolite O-desmethyltramadol), inhibiting ascending pain pathways. Simultaneously, it inhibits the reuptake of norepinephrine and serotonin, enhancing inhibitory effects on pain transmission in the spinal cord. This combined opioid and monoaminergic action provides analgesia, particularly effective in neuropathic and mixed-pain states.

• Absorption: Rapid and nearly complete oral absorption (~75% bioavailability)
• Time to Peak: 2 hours (IR); 12 hours (ER)
• Distribution: Widely distributed (Vd ~2.6–2.9 L/kg); crosses blood-brain barrier
• Protein Binding: ~20%
• Metabolism: Hepatic (CYP2D6 and CYP3A4); active metabolite O-desmethyltramadol contributes to analgesic effects
• Elimination Half-life:
  Parent drug: 5–7 hours
  Active metabolite: ~8 hours
• Excretion: Renal (~90% via urine as metabolites and unchanged drug)

• Pregnancy:
  FDA Pregnancy Category C
  Use only if clearly needed. Prolonged use in late pregnancy may cause neonatal opioid withdrawal syndrome or respiratory depression.
• Lactation:
  Tramadol and its active metabolite are excreted in breast milk in low amounts. Adverse effects in the infant (e.g., drowsiness, respiratory depression) are possible. Avoid prolonged use while breastfeeding.

• Primary Class: Centrally Acting Analgesic
• Subclass: Atypical Opioid / Synthetic Opioid Analgesic
• Additional Mechanism: SNRI (Serotonin-Norepinephrine Reuptake Inhibitor) properties

• Known hypersensitivity to tramadol or its components
• Acute intoxication with alcohol, hypnotics, opioids, or psychotropic drugs
• Patients receiving MAO inhibitors or within 14 days of their discontinuation
• Severe respiratory depression or unmonitored asthma
• Children <12 years of age
• Postoperative pain management in children <18 years after tonsillectomy and/or adenoidectomy

• Seizure Risk: Especially in patients with seizure disorders or on serotonergic drugs
• Serotonin Syndrome: Risk increases with SSRIs, SNRIs, MAOIs, or triptans
• Respiratory Depression: Use caution in elderly, debilitated, or opioid-naïve patients
• Addiction, Abuse, and Misuse: Monitor for opioid use disorder
• Increased Intracranial Pressure: Use with caution in head injury or CNS pathology
• Hepatic/Renal Impairment: Require dose adjustment or avoidance of ER forms
• Impaired Mental or Physical Abilities: Avoid operating machinery until effects are known

Common Adverse Effects:

• CNS: Dizziness, headache, drowsiness, somnolence
• GI: Nausea, constipation, vomiting, dry mouth
• General: Fatigue, sweating, pruritus

Serious or Rare Effects:

• Seizures
• Serotonin syndrome
• Respiratory depression
• Anaphylaxis or angioedema
• Orthostatic hypotension
• Dependency, tolerance, and withdrawal
• Hallucinations or mood alterations (at high doses)

Major Interactions:

• CNS Depressants (e.g., alcohol, benzodiazepines): Additive sedation, respiratory depression
• MAO Inhibitors: Life-threatening interactions—contraindicated
• SSRIs, SNRIs, TCAs, Triptans: ↑ risk of serotonin syndrome
• Carbamazepine: ↓ tramadol efficacy due to increased metabolism
• CYP2D6/CYP3A4 Inhibitors: May ↑ tramadol and active metabolite levels (e.g., fluoxetine, erythromycin)

Enzyme Involvement:

• CYP2D6 – Converts tramadol to its more potent metabolite
• CYP3A4 – Involved in metabolism of parent drug

• FDA Safety Alert: Black box warning updated to highlight risks of addiction, abuse, and life-threatening respiratory depression.
• Pediatric Use: Contraindicated for children <12 years and for <18 years post-tonsillectomy/adenoidectomy.
• WHO Guidelines: Classified as a step 2 analgesic in the WHO pain ladder for moderate pain.

• Temperature: Store below 25°C (77°F)
• Humidity: Protect from excessive moisture
• Light: Store in original packaging to protect from light
• Handling: Keep tightly closed; store securely to prevent misuse
• Oral drops: Shake well before use
• Injectables (if applicable): Do not freeze; inspect for particulate matter before use