Serzone (Nefazodone) is an atypical antidepressant that belongs to the class called SARI (Serotonin antagonist and reuptake inhibitors).

Serzone (Nefazodone) Uses:

• Depression:

  • Used for treatment of depression

Serzone (Nefazodone) Dose in Adults

Serzone (Nefazodone) Dose in the treatment of Depression:

Oral: Initial:

• 100 mg twice a day
• Alternatively, depression treatment guidelines suggest starting doses of 50 to 100 mg per day.
• Depending on response and tolerability, gradually increase the dose of 100 to 200 mg per day (in 2 divided doses) and intervals ≥1 week to a usual dose of 150 to 600 mg per day in 2 divided doses.

• Discontinuation of therapy:

  • When discontinuing antidepressant treatment that has lasted for more than 3 weeks, taper the dose gradually  (eg, over 2 to 4 weeks) to minimize withdrawal symptoms and to detect reemerging symptoms.
  • Reasons for a slower titration (eg, over 4 weeks) include the use of a drug with a half-life less than 24 hours (eg, paroxetine, venlafaxine), prior history of antidepressant withdrawal symptoms, or high doses of antidepressants.
  • If intolerable withdrawal symptoms occur, resume the previously prescribed dose &/or decrease dose at a more gradual rate.
  • Selective patients (eg, those with a history of discontinuation syndrome) on long-term treatment (>6 months) may benefit from tapering over >3 months.
  • Evidence supporting ideal taper rates is limited.

• Switching antidepressants:

  • Limited evidence is available for ideal antidepressant switching strategies
  • Strategies include cross-titration (gradually discontinuing the first antidepressant while at the same time gradually increasing the new antidepressant) & direct switch (abruptly discontinuing the first antidepressant & then starting the new antidepressant at an equivalent dose or lower dose and increasing it gradually).
  • Cross-titration (eg, over 1 to 4 weeks depending upon sensitivity to discontinuation symptoms and adverse effects) is standard for most switches but is contraindicated when switching to or from a monoamine oxidase inhibitor (MAOI).
  • A direct switch may be an appropriate approach when switching to another agent in the same or similar class (eg, when switching between two SSRIs) when the antidepressant to be discontinued has been used for less than 1 week, or when the discontinuation is for adverse effects.
  • When choosing the switch strategy, consider the risk of discontinuation symptoms, the potential for drug interactions, other antidepressant properties (eg, half-life, adverse effects, and pharmacodynamics), & the degree of symptom control desired.

• Switching to or from an MAOI:

  • Fourteen days should be allowed to elapse between discontinuing an MAOI and initiation of nefazodone.
  • At least 7 days should be allowed to elapse between discontinuing nefazodone and initiation of an MAOI.

Serzone (Nefazodone) Dose in Childrens

Not recommended for use in children.

Pregnancy Risk Factor C

• Some studies on animal reproduction showed adverse effects.
• ACOG recommends that antidepressant therapy during pregnancy should be individualized
• Depression during pregnancy can be treated with the clinical expertise of an obstetrician and primary care provider as well as a mental health specialist.
• The American Psychiatric Association states that medication treatment is not a good option for treating depression.
• It is worth considering the use of agents that have safety data during pregnancy.
• Women who have stopped taking antidepressant medication during pregnancy and are at risk of postpartum depression can resume their medications after delivery.
• Treatment algorithms have been developed by the ACOG and APA for women with depression during pregnancy and before conception.

Use of Nefazodone while breastfeeding

• Breast milk contains nefazodone as well as its active metabolites.
• Be careful.

serzone (Nefazodone) Dose in Kidney Disease:

• There are no dosage adjustments in the labeling of the manufacturer
• Adjustment is unlikely, however, as steady-state plasma concentrations of nefazodone are not affected by renal impairment.

Serzone (Nefazodone) Dose in Liver disease:

• There are no dosage adjustments in the labeling of the manufacturer
• Use caution as the AUC of Nefazodone (and its metabolites) is 25% higher in patients suffering from cirrhosis.
• Patients with liver injury from previous nefazodone treatments are contraindicated.
• Nefazodone should be stopped in patients with active liver disease and elevated baseline serum transaminases.

Common Side Effects of Serzone (Nefazodone):

• Central Nervous System:

  • Headache
  • Drowsiness
  • Dizziness
  • Insomnia
  • Agitation

• Gastrointestinal:

  • Xerostomia
  • Nausea
  • Constipation

• Neuromuscular & Skeletal:

  • Weakness

Less Common Side Effects of Serzone (Nefazodone):

• Cardiovascular:

  • Orthostatic Hypotension
  • Vasodilation
  • Peripheral Edema
  • Hypotension
  • Bradycardia

• Central Nervous System:

  • Confusion
  • Memory Impairment
  • Paresthesia
  • Abnormal Dreams
  • Lack Of Concentration
  • Ataxia
  • Chills
  • Psychomotor Retardation
  • Hypertonia

• Dermatologic:

  • Pruritus
  • Skin Rash

• Endocrine & Metabolic:

  • Decreased Libido
  • Increased Thirst

• Gastrointestinal:

  • Dyspepsia
  • Diarrhea
  • Increased Appetite
  • Dysgeusia
  • Vomiting
  • Gastroenteritis

• Genitourinary:

  • Urinary Frequency
  • Urinary Retention
  • Mastalgia
  • Impotence

• Hematologic & Oncologic:

  • Decreased Hematocrit

• Infection:

  • Infection

• Neuromuscular & Skeletal:

  • Tremor
  • Arthralgia
  • Neck Stiffness

• Ophthalmic:

  • Visual Disturbance
  • Blurred Vision
  • Visual Field Defect
  • Eye Pain

• Otic:

  • Tinnitus

• Respiratory:

  • Pharyngitis
  • Cough
  • Flu-Like Symptoms
  • Bronchitis
  • Dyspnea

• Miscellaneous:

  • Fever

Contraindications to Serzone (Nefazodone):

• Hypersensitivity to nefazodone and related compounds (phenylpiperazines), as well as any component of the formulation
• Liver injury due to previous nefazodone treatments
• Use with terfenadine or astemizole in conjunction with carbamazepine and cisapride.
• Concurrent treatment with triazolam (dosage must decrease by 75% for triazolam; this may not be possible with all available dosage forms) is generally against the law.

Warnings and precautions

• Anticholinergic effects
  • Possible anticholinergic side effects: constipation, xerostomia and blurred vision.
  • Patients with reduced gastrointestinal motility, paralytic and ileus, urinary retentions, BPH, xerostomia, and visual impairments should be cautious.
  • This agent produces a very low level of anticholinergic blocking compared to other antidepressants.
• Depression in the CNS:
  • CNS depression can lead to mental or physical impairments.
  • It is important to warn patients about tasks that require mental alertness, such as driving or operating machinery.
  • The degree of sedation relative to other antidepressants is moderate.
• Fractures
  • Antidepressant treatment has been shown to be associated with bone fractures.
  • Unexplained bone pain, tenderness, swelling or bruising in an antidepressant-treated person may indicate a fragility fracture.
• Hepatic failure
  • Patients treated with nefazodone have experienced life-threatening hepatic impairment.
  • American statistics show that there is an average of 1 case per 250,000 to 300,000. patient-years of nefazodone therapy of liver failure leading to death or transplant. This is three to four times the background rate.
  • Preexisting liver disease does not increase the chance of developing liver failure.
  • Baseline abnormalities can, however, complicate patient monitoring.
  • Time taken to heal liver damage in severe cases was reported to be between 2 and 6 months
  • Some cases did not show a clear prodromal onset.
  • Patients with liver disease, or elevated serum transaminases should not be treated.
  • Although there is no evidence to suggest that regular monitoring of serum transaminases can prevent severe hepatic injuries, it can be useful in the early detection of symptoms.
  • If you have signs and symptoms such as anorexia, jaundice, GI problems, malaise or elevated serum AST/ALT levels >=3x the ULN, discontinue Nefazodone.
  • Patients who have developed symptoms while taking nefazodone should not be treated again.
  • Hepatotoxicity has been linked to low doses of 100 mg per day.
• Ocular effects
  • Mild pupillary dilation may occur, which can in some cases lead to narrow-angle glaucoma.
  • Patients who have not undergone an iridectomy to reduce the risk of narrow-angle glaucoma should be evaluated.
• Orthostatic hypotension
  • Orthostatic hypotension may occur (risk is low in comparison to other antidepressants).
  • Patients at high risk for this effect and those who cannot tolerate hypovolemia (dehydration, cardiovascular disease, cerebrovascular disease, or concurrent medication use that may lead to hypotension or bradycardia) should be used with caution.
• Sexual dysfunction
  • Rare cases of priapism are reported.
  • Nefazodone has a lower incidence of sexual dysfunction than other SSRIs.
• Cardiovascular disease
  • Patients with a history or cardiovascular disease (including stroke, MI, or tachycardia) should be cautious.
  • This agent has very low risk of conduction abnormalities compared to antidepressants.
• Hepatic impairment: [US-Boxed Warning]
  • Normally, nefazodone treatment should not be started in patients with active liver disease and/or elevated baseline serum transaminases.
  • Patients with hepatic impairment should be cautious.
• Hypomania and mania:
  • Patients with bipolar disorder might experience maniacal or hypomania.
  • Patients with bipolar disorder should not be given monotherapy.
  • Patients with depressive symptoms need to be tested for bipolar disorder. This includes details about family history, suicide attempts, bipolar disorder, depression, and other mental health issues.
  • Nefazodone has not been approved by the FDA for bipolar depression.
• Renal impairment
  • Patients with impaired renal function should be cautious.
• Seizure disorder
  • Patients at high risk of seizures should be treated with caution, especially those who have had seizures in the past, are brain damaged, suffered from head trauma or who are taking concurrent medication that could lower their seizure threshold.

Nefazodone: 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:

• Liver function tests (baseline and then periodically) If AST/ALT rise >=3 times the ULN, discontinue using the drug & don't reintroduce it.
• Mental health
• Suicide ideation, especially at the start of therapy or when dosages are increased/ decreased
• Anxiety
• Social functioning
• Mania
• Panic attacks or unusual behavior changes

How to administer Serzone (Nefazodone)?

• You can take it with or without food.
• After meals, taking a drink may reduce lightheadedness and postural hypotension. However, it may also cause decreased absorption and effectiveness.

Mechanism of action of Serzone (Nefazodone):

• Neuronal reuptake inhibition of serotonin, norepinephrine.
• Also blocks alpha-1 and 5-HT2 receptors
• It does not have a significant affinity for alpha-2 or beta-adrenergic receptors, 5-HT-1A, cholinergic, dopaminergic or benzodiazepine.

Absorption:

• Rapid
• Well absorbed
• Food delays absorption by ~20%

Protein binding:

• >99%

Metabolism:

• Hepatic by n-dealkylation and aliphatic and aromatic hydroxylation to at least three metabolites: Triazoledione, hydroxynefazodone (active), and m-chlorophenylpiperazine (mCPP; active)

Bioavailability:

• 20% (variable)
• food decreases bioavailability by ~20%; AUC increased by 25% in patients with cirrhosis of the liver

Half-life elimination: Note:

• Active metabolites persist longer in all populations.
• Children: 4.1 hours
• Adolescents: 3.9 hours
• Adults: Parent drug: 2 to 4 hours; Active metabolites: 1.4 to 8 hours

Time to peak serum concentrations: Note: Prolonged in presence of food

• Children and Adolescents: 0.5 to 1 hour
• Adults: 1 hour

Excretion:

• Primarily urine (~55%; as metabolites)
• Feces (~20% to 30%)

International Brands of Nefazodone:

• Deprefax
• Dutonin
• Fazodone
• Menfazona
• Nefadar
• Nefaril
• Nefazodone ”BMS”
• Reseril
• Rulivan
• Serzone

Nefazodone Brand Names in Pakistan:

No Brands Available in Pakistan.