Desvenlafaxine succinate, Pristiq®

• Pristiq®

• Antidepressant
• Serotonin–norepinephrine reuptake inhibitors (SNRIs)

• Tablets: 50 and 100 mg extended-release 

• Adults: symptomatic relief of major depressive disorder.
• Pediatrics: Not recommended in less than 18 years old

Pharmacodynamics:

• Mechanism of action:

It is a major active metabolite of venlafaxine a serotonin and norepinephrine reuptake inhibitor (SNRI)

Pharmacokinetics:

Absorption:

• Bioavailability: 80%
• Peak plasma time: 7.5 hr
• Plasma concentration: 4-5days

Distribution:

• Protein bound: 30%
• Volume of distribution (Vd): 3.4L/kg

Metabolism:

• Metabolized in liver by CYP3A4

Elimination and excretion:

• Half-life: 11 hr
• Long-term efficacy of Pristiq is 26 weeks
• Excretion: urine (45%)

Acute Major Depression:

• Initial dose=> 50 mg/day, Maximum standard dose => 100mg/day
• Administration: Swallow with liquids

Renal impairment dose adjustment:

In severe renal impairment (24-hr CrCl<30mL/min) or end-stage renal disease (ESRD) the recommended dose is 50 mg/day.

Hepatic impairment dose adjustment:

No dosage adjustment is needed.

*Note:

• The patient should be reevaluate periodically to ascertain any need for maintenance treatment.
• It’s recommended to taper this drug or any other antidepressant (if you want to switch to Pristiq) gradually to reduce the possibility of discontinuation symptoms (dizziness, nausea, headache, irritability, diarrhea, anxiety, abnormal dreams, fatigue, and hyperhidrosis).
• There should be at least 14days between discontinuation of MAOI and starting Pristiq, moreover it should be 7days after stopping Pristiq and initiation of MAOI.

1. Selective serotonin reuptake inhibitor (SSRI)

2. Serotonin norepinephrine reuptake inhibitor (SNRI)

3. Lithium

4. Sibutramine

5. Fentanyl and its analogues

6. Dextromethorphan

7. Tramadol, Tapentadol

8. Meperidine, Methadone and Pentazocine

9. MAOIs and Linezolid, Methylene blue => May impair serotonin metabolism

• may set the stage for a life-threatening situation which is serotonin syndrome or Neuroleptic Malignant Syndrome (NMS)-Like Reactions (tremor, myoclonus, diaphoresis, nausea, vomiting, flushing, dizziness, hyperthermia, seizures, rigidity, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes).

10. NSAIDs: Non-steroidal anti-inflammatory drugs

11. ASA and other anticoagulants:

• Drugs that interfere with hemostasis and consequently cause bleeding (because serotonin mechanism is a key role in hemostasis and Pristiq impair this process)

1. More frequent:

• Gastrointestinal disorders (Nausea, Dry mouth, Constipation, Vomiting)
• General disorders (Fatigue, Chills, asthenia, Feeling jittery)
• Decreased appetite, Dizziness, dizziness, insomnia, Hyperhydrosis

2. Less Frequent: 

• Cardiac disorders (Blood pressure increased, palpitations, tachycardia)
• Nervous system disorders (Somnolence, Tremor, and Disturbance in attention)
• Psychiatric disorders (Insomnia, Anxiety, Nervousness, Abnormal dreams)
• Special Senses (Vision blurred, Mydriasis, Vertigo, Tinnitus, Dysgeusia)
• Urinary hesitation, Yawning, Hot flush.
• Sexual Function (in men: erectile dysfunction and ejaculation delayed, Anorgasmia, Libido decreased, and Orgasm abnormal- in women: Anorgasmia)

Serious and sometimes fatal when it is used concurrently with:

1. Monoamine oxidase inhibitors (MAOIs) or patients who have treated with MAOIs since 14 days => Its recommended to give a 7-day period after stopping desvenlafaxine (regarding its half-life) and then start an MAOI.
2. Linezolid 
3. A dye in some surgeries
4. Known hypersensitivity to the medication.

• Pregnancy: Category C
• Lactation:Not recommended in nursing mother

1. Pediatrics=>Increase the risk of suicidality:

• Administration under 18 year-old might be followed by behavioral and emotional changes, including self-harm or suicide.

2. Adults: Prescribe with caution in these conditions:

• Allergic Reactions, Bone Fracture Risk, syndrome of inappropriate antidiuretic hormone (SIADH), possibility of gastrointestinal obstruction, abnormal bleeding, seizure
• Increase in blood pressure, cholesterol, and triglycerides
• It’s suggested that sudden give up in this drug may cause discontinuation symptoms (dysphoric mood, irritability, agitation, dizziness, sensory disturbances, and et al.)
• Narrow angle glaucoma
• Agitation, akathisia, agitation, disinhibition, emotional lability, hostility, aggression, depersonalization
• The patient should be reevaluate periodically to ascertain any need for maintenance treatment.
• Interference with Cognitive and Motor Performance >>>Patients should be cautioned about operating hazardous machinery, avoid driving
• Patients with history of drug abuse.
• CNS-Active Drugs: caution is advised.
• Overdose:
• • Symptoms: paresthesia, sleepiness, dizziness, nausea, hot-cold spells.
  • Overdose Management:
    • General measures: Provide adequate airway, oxygenation, and ventilation, monitor cardiac rhythm and vital signs
    • Gastric lavage:
      • Indicated soon after ingestion,
      • Symptomatic patients.
    • Activated charcoal
    • Antidote: No specific antidotes
• Discontinuing Desvenlafaxine:
  • Taper gradually to minimize the risk of discontinuation symptoms >>> No abrupt discontinuation:
    • abrupt discontinuation symptoms: aggression, agitation, anorexia, anxiety, asthenia, confusion, convulsions, impaired coordination and balance, diarrhea, dizziness, dry mouth, dysphoric mood, fasciculation, fatigue, flu-like symptoms, headache, hypomania, insomnia, nausea, nightmares, nervousness, paresthesia, electric shock sensations, sensory disturbances (including shock like electrical sensations), sleep disturbances, somnolence, sweating, tinnitus, vertigo, and vomiting.
• Geriatrics (> 65 years of age): Caution in treating the elderly is advised