Hapytab

A. Approved Indications

• Major Depressive Disorder (MDD):
• Indicated for the treatment of MDD in adults.

B. Clinically Accepted Off-Label Uses

• Generalized Anxiety Disorder (GAD):
• Especially in patients not tolerating SSRIs.
• Vasomotor Symptoms (VMS) of Menopause:
• Relief of hot flashes and night sweats in postmenopausal women.
• Neuropathic Pain:
• Particularly in diabetic peripheral neuropathy, though not formally approved.
• Fibromyalgia:
• For symptomatic relief in select patients.
• Attention Deficit Hyperactivity Disorder (ADHD):
• Studied in adults as adjunctive therapy.

A. Adults

• Major Depressive Disorder:
• Start at 50 mg once daily, with or without food.
• Doses above 50 mg/day are not routinely recommended due to minimal added benefit and increased risk of side effects.
• Maximum dose: 100 mg/day.
• Discontinuation:
• Taper gradually over several days to avoid withdrawal symptoms.

B. Pediatric Use

• Not approved for patients under 18 years.
• Safety and efficacy not established.

C. Elderly

• Start at 50 mg/day.
• May have increased sensitivity to adverse effects; monitor closely for hyponatremia and blood pressure changes.

D. Renal Impairment

• Mild to moderate impairment (CrCl 30–50 mL/min):
• Max dose: 50 mg/day.
• Severe impairment (CrCl <30 mL/min) or ESRD:
• Dose: 50 mg every other day.

E. Hepatic Impairment

• Mild to moderate impairment:
• 50 mg/day recommended.
• Severe impairment:
• Use with caution; consider dose reduction.

Route of Administration: Oral (Extended-release tablet)

Duration of Use: Long-term use should be periodically reassessed for benefit.

Desvenlafaxine is a selective serotonin and norepinephrine reuptake inhibitor (SNRI). It works by inhibiting the reuptake of serotonin (5-HT) and norepinephrine (NE) in the central nervous system by blocking their respective transporters. This increases the synaptic availability of these neurotransmitters, which is thought to improve mood and alleviate depressive symptoms. It has minimal affinity for muscarinic, histaminergic, or α1-adrenergic receptors, contributing to a relatively favorable side effect profile.

• Absorption:
• Oral bioavailability: ≥80%
• Time to peak plasma concentration (Tmax): 7.5 hours
• Distribution:
• Volume of distribution: ~3.4 L/kg
• Plasma protein binding: ~30%
• Metabolism:
• Metabolized primarily by conjugation (glucuronidation)
• Minor metabolism via CYP3A4
• Desvenlafaxine is the active metabolite of venlafaxine
• Elimination:
• Half-life: ~11 hours
• Excreted primarily via urine (≥45% as unchanged drug)

• Pregnancy:
• No FDA letter category under the new labeling system.
• Use during pregnancy only if benefits outweigh risks.
• Risk of neonatal withdrawal symptoms or persistent pulmonary hypertension with third-trimester exposure.
• Lactation:
• Desvenlafaxine is excreted into breast milk.
• Monitor breastfed infants for signs of irritability, feeding difficulty, or poor weight gain.
• Decision to continue breastfeeding should weigh the drug's benefits against potential risks to the infant.

• Primary Class: Antidepressant
• Subclass: Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)
• Generation: Second-generation antidepressant

• Hypersensitivity to desvenlafaxine, venlafaxine, or any component of the formulation
• Concomitant use with MAO inhibitors (MAOIs) or within 14 days of discontinuing an MAOI
• Use of linezolid or IV methylene blue (risk of serotonin syndrome)

• Suicidal Thoughts:
• Increased risk in children, adolescents, and young adults (boxed warning). Monitor closely during initiation.
• Serotonin Syndrome:
• Risk increases with other serotonergic agents. Symptoms: agitation, hallucinations, tachycardia, hyperreflexia.
• Hypertension:
• Dose-dependent increase in blood pressure; monitor regularly.
• Bleeding Risk:
• Increased when combined with NSAIDs, aspirin, anticoagulants.
• Seizures:
• Use with caution in individuals with a history of seizure disorder.
• Glaucoma:
• Can cause mydriasis; caution in narrow-angle glaucoma.
• Hyponatremia/SIADH:
• More common in elderly patients.
• Discontinuation Syndrome:
• Taper dose gradually to avoid withdrawal effects (dizziness, irritability, insomnia).

Common (≥5%):

• Central Nervous System: Dizziness, insomnia, somnolence, anxiety
• Gastrointestinal: Nausea, dry mouth, constipation, decreased appetite
• Sexual Dysfunction: Delayed ejaculation, decreased libido
• Other: Sweating, increased blood pressure, fatigue

Less Common (1–5%):

• Palpitations
• Tremor
• Abnormal dreams
• Visual disturbances

Serious or Rare (<1%):

• Hyponatremia, serotonin syndrome, seizures, suicidal ideation
• Stevens-Johnson syndrome (rare skin reaction)
• Liver function abnormalities

• MAO Inhibitors (e.g., phenelzine, tranylcypromine):
• May lead to serotonin syndrome; contraindicated.
• Serotonergic drugs (SSRIs, SNRIs, triptans, tramadol):
• Increased risk of serotonin syndrome.
• CYP3A4 Inhibitors (e.g., ketoconazole):
• May increase desvenlafaxine levels; monitor for toxicity.
• CYP3A4 Inducers (e.g., rifampin):
• May reduce drug efficacy.
• Alcohol:
• May worsen CNS side effects; avoid.
• Anticoagulants & NSAIDs:
• Enhanced risk of bleeding due to platelet dysfunction.

• American Psychiatric Association (APA) 2023 guidelines endorse desvenlafaxine as a first-line option for MDD, particularly in patients with poor tolerability to SSRIs.
• North American Menopause Society recognizes desvenlafaxine for vasomotor symptom relief, especially for women unable to use hormone therapy.
• FDA labeling updates have further emphasized suicidality monitoring and BP control during long-term therapy.

• Temperature: Store at 20°C to 25°C (68°F to 77°F)
• Humidity: Protect from moisture; store in dry conditions
• Light: Store in original container to protect from light
• Handling Instructions:
• Do not crush, chew, or split extended-release tablets
• Keep out of reach of children
• Use only as prescribed; discard expired medication appropriately