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
• Instead, initial dosages of 50 to 100 mg per day are recommended by depression therapy guidelines.
• Increase the dose gradually from 100 to 200 mg per day (in two divided doses) and intervals of up to one week to the typical range of 150 to 600 mg per day in two divided doses, depending on response and tolerability.

• Discontinuation of therapy:

  • Reduce withdrawal symptoms and spot reemerging symptoms by tapering the dose gradually (e.g., over 2 to 4 weeks) when stopping antidepressant treatment after more than 3 weeks.
  • The usage of a medication with a half-life less than 24 hours (e.g., paroxetine, venlafaxine), a prior history of antidepressant withdrawal symptoms, or high doses of antidepressants are causes for a slower titration (e.g., over 4 weeks).
  • If unpleasant withdrawal symptoms develop,
  • Tapering over more than three months may be beneficial for some individuals receiving long-term treatment (>6 months), such as those with a history of discontinuation syndrome.
  • There is little data to support appropriate taper rates.

• Switching antidepressants:

  • The most successful antidepressant switching techniques are not supported by enough evidence.
  • Straight changeover and cross-titration are two strategies. Cross-titration involves progressively reducing the prior antidepressant while gradually increasing the new antidepressant (abruptly discontinuing the first antidepressant & then starting the new antidepressant at an equivalent dose or lower dose and increasing it gradually).
  • Cross-titration is not advised when switching to or from a monoamine oxidase inhibitor (e.g., over 1 to 4 weeks depending on sensitivity to withdrawal symptoms and side effects) (MAOI).
  • A direct move to a different medication in the same or closely similar class (for instance, switching between two SSRIs) may be necessary if the antidepressant to be discontinued has been used for less than a week or if the discontinuation is due to side effects.
  • While choosing a switch strategy, take into account the likelihood of withdrawal symptoms, the potential for drug interactions, other antidepressant characteristics (including half-life, unwanted effects, and pharmacodynamics), as well as the necessary level of symptom control.

• Switching to or from an MAOI:

  • Nefazodone should be begun at least 14 days after stopping an MAOI.
  • After quitting nefazodone, it is advised to wait at least 7 days before resuming an MAOI.

Serzone (Nefazodone) Dose in Children

Not recommended for use in children.

Pregnancy Risk Factor C

• Some studies on animal reproduction showed adverse effects.
• Individualized antidepressant therapy is advised by ACOG for use while pregnant.
• 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 guidelines for depressive pregnant and postpartum women have been developed by the APA and ACOG.

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
• Modification is unlikely, nevertheless, because renal impairment has little effect on the steady-state plasma concentrations of nefazodone.

Serzone (Nefazodone) Dose in Liver disease:

• Modifying the dosage is not mentioned in the manufacturer's label.
• Use caution because patients with cirrhosis had 25% higher AUCs for nefazodone (and its metabolites).
• Nefazodone is not recommended for people who have had liver damage as a result of prior therapies.
• Patients with active liver disease and increased baseline blood transaminases should cease taking nefazodone.

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 drugs, as well as any chemical in the formulation (phenylpiperazines).
  damage to the liver caused by previous nefazodone treatments
• use in conjunction with cisapride, carbamazepine, terfenadine, or astemizole.
• The use of triazolam combined with other medications is normally prohibited (the dosage of triazolam must be halved; this may not be possible with all dosage forms).

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 drug has extremely little anticholinergic blocking activity when 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.
  • Sedation is not as intense as it is with other antidepressants.
• Fractures
  • Bone fractures have been proven to be related to antidepressant therapy.
  • Antidepressant users who develop unexplained bone pain, discomfort, swelling, or bruising may have 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).
  •  
• Sexual dysfunction
  • Rare cases of priapism are reported.
  • Nefazodone has a lower incidence of sexual dysfunction than other SSRIs.
• Cardiovascular disease
  • Individuals who have had cardiovascular problems in the past, such as a stroke, a MI, or tachycardia, should exercise caution.
  • This agent has very low risk of conduction abnormalities compared to antidepressants.
• Hepatic impairment: [US-Boxed Warning]
  • In general, patients with active liver disease and/or increased baseline blood transaminases shouldn't begin nefazodone medication.
  • Hepatic patients need to exercise caution.
• Hypomania and mania:
  • Maniacal or hypomania may be experienced by bipolar illness patients.
  • Monotherapy is not advised for those with bipolar disorder.
  • Bipolar disorder testing should be performed on patients who have depressed symptoms. This contains information regarding the family history of mental illness, attempted suicides, bipolar disorder, depression, and other conditions.
  • 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 
• Mental health
• Suicide ideation
• 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.