Desvenlafaxine (Pristiq) is the major active metabolite of venlafaxine. It is used for the treatment of depression. Compared to the parent drug (Venlafaxine), it appears to be less effective in patients with depression.

Indications of Desvenlafaxine:

• Major depressive disorder:
  • The therapy of serious depressive illness is indicated.
• Off Label Use of Desvenlafaxine in Adults:
  • Vasomotor symptoms associated with menopause.

Desvenlafaxine (Pristiq) dose in adults:

Desvenlafaxine (Pristiq) dose in the treatment of major depressive disorder:

• 50 mg per oral once daily;
•  Studies have showed that dosages up to 400 mg once daily are efficient.
• There is no additional benefit at doses >50 mg per day as per the manufacturer.

Desvenlafaxine (Pristiq) dose in the treatment of Vasomotor symptoms associated with menopause (off-label):

• Initial: Titrate to 100 mg once daily from 25 to 50 mg once daily.;
• 150 mg once daily has also been studied and has shown to be effective, but has been associated with treatment discontinuation.
• Titration during the first 1 to 2 weeks of therapy is effective in managing adverse effects at starting therapy.
• Discontinuation of therapy:
  • When discontinuing antidepressant treatment that has lasted for >3 weeks, the dose should be gradually tapered(eg, over 2 to 4 weeks) to minimize withdrawal symptoms and detect reemerging symptoms.
  • Slower titration (eg, over 4 weeks) is needed in cases including the use of a drug with a half-life <24 hours (eg, paroxetine, venlafaxine), prior history of antidepressant withdrawal symptoms, or high doses of antidepressants.
  • The dose should be resumed as the previously prescribed dose and/or dose reduction should be done at a more gradual rate in case of intolerable withdrawal symptoms.
  • Tapering over >3 months is beneficial in patients such as those with a history of discontinuation syndrome) on long-term treatment (>6 months).
  • Evidence supporting ideal taper rates is limited.

MAO inhibitor recommendations:

• Switching to or from an MAO inhibitor intended to treat psychiatric disorders:
  • The time interval between discontinuing an MAO inhibitor intended to treat psychiatric disorders and initiation of desvenlafaxine should be 14 days.
  • The time interval between discontinuing desvenlafaxine and initiation of an MAO inhibitor intended to treat psychiatric disorders should be 7 days.

Desvenlafaxine (Pristiq) use in children:

  Children's medicine safety and effectiveness have not been examined.

Desvenlafaxine (Pristiq) Pregnancy Risk Category: C

• SSRI/SNRI impacts on babies can be non-teratogenic. Apnea, cyanosis, seizures, respiratory distress syndrome, unstable body temperature, trouble eating, vomiting, hypoglycemia or hyper-or hypotonia, hyperreflexia (jitteriness), irritability, continuous crying, and tremor are some of these. These symptoms could be the result of SSRI/SNRI toxicity or a withdrawal episode. They might also be in line with serotonin syndrome therapy.
• On newborn behaviour and development, in utero SNRI/SSRI exposure may have long-term impacts that are unknown.
• During pregnancy, treatment with SSRIs and SNRIs should always be individualized according to ACOG.
• Treatment of depression during pregnancy should involve the skills of the primary healthcare provider, the obstetrician, and the mental healthcare physician.
• The American Psychiatric Association advises weighing the hazards of pharmaceutical use against those of other treatment options and untreated depression.
• Females who have stopped taking antidepressant medication during pregnancy can resume SSRI therapy after giving birth.
• ACOG and APA developed treatment algorithms to manage depression in women during and before pregnancy.
• Desvenlafaxine, the main active metabolite of venlafaxine, is also known as the Venlafaxine monograph.

Use desvenlafaxine while breastfeeding

• Breast milk contains desvenlafaxine.
• One study found that the relative infant dose (RID), of desvenlafaxine was 6.8%, with a range of 5.5% to 8.1% when compared to a maternal dose of 50 to 150mg/day.
• When the RID is less than 10%, breastfeeding is generally acceptable.
• Breastfeeding shouldn't be considered, according to certain authorities, if psychiatric medication has a RID of 5%.
• The authors of a study calculated the mean RID for desvenlafaxine using a milk concentration of 564 mg/L (range 351-777 mcg/L), which provides an estimated daily infant dose via breastmilk of 85 mg/kg/day (range 53-117 mcg/kg/day).
• This information was derived from a study of 10 mothers-infants at 0.9 to 11.2 months postpartum (mean: 4.3% months), following maternal use desvenlafaxine 50 mg or 100 mg extended release tablets once daily, with maternal doses of 50 to 150 mg/day.
• Infant serum could also contain desvenlafaxine.
• Infants of mothers who are on antidepressant therapy must be monitored daily for any changes in sleep, feeding, or behavior.
• The decision to continue or discontinue nursing during therapy will be influenced by the danger of baby exposure, the advantages to the infant, and the mother's health.
• Desvenlafaxine is preferred to alternative agents for the management of depression in breastfeeding women.

Desvenlafaxine (Pristiq) Dose adjustment in renal disease:

Note: Renal function may be estimated using the Cockcroft-Gault formula.

• CrCl >50 mL/minute:
  • No dosage adjustment is necessary.
• CrCl 30 to 50 mL/minute:
  • 50 mg once daily (maximum).
• CrCl <30 mL/minute:
  • 25 mg once daily or 50 mg every other day (maximum).
• End-stage renal disease (ESRD) requiring hemodialysis (HD):
  • 25 mg once daily or 50 mg every other day (maximum). Supplemental doses should not be given after HD.

Desvenlafaxine (Pristiq) dose adjustment in liver disease:

• Mild impairment (Child-Pugh class A):
  • No dosage adjustment is necessary.
• Moderate to severe impairment (Child-Pugh classes B and C):
  • Initial: 50 mg once daily.
  • maximum dose: 100 mg once daily.

Side Effects of Desvenlafaxine (Pristiq):

• Central nervous system:
  • Insomnia
  • Dizziness
• Dermatologic:
  • Hyperhidrosis
• Gastrointestinal:
  • Xerostomia
  • Nausea

Uncommon Side Effects of Desvenlafaxine (Pristiq):

• Cardiovascular:
  • Syncope
  • Hypertension
  • Tachycardia
  • Orthostatic Hypotension
• Central Nervous System:
  • Drowsiness
  • Fatigue
  • Delayed Ejaculation
  • Abnormal Dreams
  • Anorgasmia
  • Jitteriness
  • Vertigo
  • Depersonalization
  • Dystonia
  • Anxiety
  • Seizure
  • Disturbance In Attention
  • Yawning
  • Male Sexual Disorder
• Dermatologic:
  • Skin Rash
  • Skin Photosensitivity
  • Alopecia
• Endocrine & Metabolic:
  • Decreased Libido
  • Increased Serum Cholesterol
  • Increased Serum Prolactin
  • Weight Gain
  • Hot Flash
  • Increased LDL Cholesterol
• Gastrointestinal:
  • Constipation
  • Decreased Appetite
  • Vomiting
  • Bruxism
• Genitourinary:
  • Proteinuria
  • Erectile Dysfunction
  • Urinary Retention
  • Ejaculation Failure
  • Urinary Hesitancy
• Hepatic:
  • Abnormal Hepatic Function Tests
• Hypersensitivity:
  • Angioedema
• Neuromuscular & Skeletal:
  • Tremor
  • Stiffness
  • Weakness
• Ophthalmic:
  • Blurred Vision
  • Mydriasis
• Otic:
  • Tinnitus

Rare Side effects of Desvenlafaxine (Pristiq):

• Cardiovascular:
  • Coronary Occlusion
  • Ischemic Heart Disease
  • Myocardial Infarction

Contraindications to Desvenlafaxine (Pristiq):

• Intolerance to desvenlafaxine, Venlafaxine, or any other active ingredient.
• Psychiatric illnesses may be treated with MAO inhibitors concurrently or within 14 days of quitting the MAO inhibitor.
• Within 7 days of stopping desvenlafaxine, you can start MAO inhibitor therapy to treat psychiatric disorders
• Patients receiving intravenous methyleneblue or linezolid should be administered desvenlafaxine.

Warnings and precautions

• Anxiety/insomnia
  • Antidepressant therapy can cause anxiety, nervousness, insomnia, and other symptoms.
• Bleeding Risk:
  • Increased bleeding can be caused by antidepressant therapy.
  • Concomitant therapy using aspirin and NSAIDs can increase the risk of developing ulcerogenic potential.
  • Limited data are available on the bleeding risk from SNRIs when combined with warfarin and other anticoagulants.
  • The risk of bleeding can be as minor as epistaxis and bruising to severe hemorhage when you take antidepressants.
• Depression in the CNS:
  • SSRIs can lead to impaired motor or cognitive performance.
  • When operating dangerous machinery or driving, patients should be aware.
• Dyslipidemia
  • A deviation in the lipid profile can be observed, which can be dose-related, such as increased total cholesterol, LDL and triglycerides
  • It is important to monitor your surroundings carefully.
• Fractures
  • Antidepressant therapy may lead to bone fractures.
  • Unexplained bone pain, tenderness, swelling or bruising in an antidepressant-treated person should be investigated. Fragility fracture secondary therapy should also be considered.
• Hypertension
  • Antidepressant treatment can cause a dose-related rise in systolic or diastolic blood pressure.
  • It is important to monitor your blood pressure regularly
  • In the event of a significant increase in symptoms, it is worth considering therapy withdrawal or dose reduction.
• Ocular effects
  • It is possible to see a narrow-angle glaucoma secondary or mild pupillary dilation.
  • Patients who have not undergone an iridectomy to reduce the risk of narrow-angle glaucoma should be evaluated.
  • It is not recommended for patients with anatomically narrow angles that aren't being treated.
• Events in the pulmonary system:
  • Venlafaxine is known for causing interstitial pneumonia and eosinophilic pneumonia. This can present as cough, progressive dyspnea or chest pain.
  • It is possible to withdraw or get an urgent evaluation.
• Serotonin syndrome
  • SSRIs may cause fatal serotonin syndrome. This can present with mental state changes (eg. agitation, hallucinations and coma); autonomic stability (eg. tachycardia or labile blood pressure; diaphoresis); neuromuscular modifications (eg. tremors, rigidity, myoclonus); GI symptoms such as nausea, vomiting, diarrhea; and/or seizures.
  • When taken with other serotonergic medications, such as triptans TCAs, fentanyl and buspirone, tramadol or buspirone, tryptophan, St. John's wort or tryptophan, or substances that impair serotonin metabolism, serotonergic medications (such as SSRIs and SNRIs) are more dangerous (eg MAO inhibitors for psychiatric disorders, intravenous methyleneblue, linezolid, intravenous methyleneblue blue, methyleneblue blue, s).
  • Any signs/symptoms should be reported immediately and any other stimulants should be discontinued.
• Sexual dysfunction
  • This may lead to or exacerbate sexual dysfunction.
• SIADH and Hyponatremia

Antidepressant therapy may cause SIADH. Hyponatremia is rare (including severe cases involving serum sodium 110 mg/L).

• • This risk is higher in older age, hypokalemia, concurrent use of diuretics, and/or concomitant use of diuretics.
  • Hyponatremia patients should be stopped from therapy.
• Cardiovascular disease
  • It is possible to see a rise in blood pressure or pulse, and this is often dose-related.
  • Pre-existing hypertension control must be maintained before desvenlafaxine can be started.
  • Patients with preexisting hypertension, heart disease, or cardiovascular problems should be cautious.
• Hepatic impairment
  • Therapy may result in decreased liver clearance and an increase in the average AUC.
  • For patients with mild to severe hepatic impairment, dose reduction is required.
• Hypomania and mania:
  • Patients with bipolar disorder may experience a shift towards mania/hypomania.
  • Patients with bipolar disorder should not take desvenlafaxine as a single agent.
  • Bipolar disorder screening should be performed on patients who have depressed symptoms.
  • The FDA has not authorised desvenlafaxine for the treatment of bipolar disorder.
• Renal impairment
  • In response to treatment, renal clearance may be reduced or plasma concentrations may rise.
  • Patients with end-stage renal disease or severe renal impairment must have lower doses.
• Seizure disorders
  • Patients should use cautious if they have a history of seizure disorders.

Desvenlafaxine: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Blood pressure
• Mental health including suicidal thoughts and despair (especially at the beginning of therapy or when doses are increased or decreased)
• Renal function for dosing purposes.
• Lipid profile (eg, total cholesterol, LDL, triglycerides)
• Signs/symptoms of serotonin syndrome
• Intraocular pressure should be monitored in those with baseline elevations or a history of glaucoma.

How to administer Desvenlafaxine?

• You should take it orally every day at the same time, regardless of whether you are eating. 
• You should swallow the whole tablet without chewing, crushing, or dividing it.
•  You should taper the dose gradually to stop treatment.
• The 25 mg tablet is designed for gradual dose reductions.   

Mechanism of action of Desvenlafaxine:

Desvenlafaxine is a potent and selective serotonin and norepinephrine reuptake inhibitor.

Protein binding:

• 30%

Metabolism:

• It is metabolized in the liver via conjugation (major pathway), and oxidation via CYP3A4 (minor pathway).

Bioavailability:

• 80%

Half-life elimination:

• 10 to 11 hours,
• It is prolonged in renal failure and hepatic failure

Excretion:

• Urine (45% as unchanged drug; ~24% as metabolites)

International Brands of Desvenlafaxine:

• Khedezla
• Pristiq
• APO-Desvenlafaxine
• Bedremine
• D-Veniz
• Desfax
• Desfaxinate
• Deslafax
• Desven
• Fapris
• Ikium
• Nevola
• Pristimood
• Pristiq
• Pristiq SR
• Zyven-OD

Desvenlafaxine Brand Names in Pakistan: