Trazodone

Registered South African indications: 

• Depression
• Mixed anxiety and depression

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Combined use with other psychotropic medications should only be undertaken with recognition of the possibility for potentiation
• Concurrent administration with monoamine oxidase inhibitors (MAOIs), or within two weeks of discontinuing treatment with these compounds. Administration of MAOIs within one week of stopping trazodone
• Alcohol intoxication and intoxication with hypnotics
• Acute myocardial infarction

Contraindications registered in other jurisdictions

• Hypersensitivity to the active ingredient or any of its excipients
• Alcohol intoxication and intoxication with hypnotics
• Acute myocardial infarction

South African recommendations

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly
• History of suicide-related events, or those exhibiting a significant degree of suicidal ideation
• Epilepsy 
• Cardiac disease
• Hyperthyroidism
• Micturition disorders
• Prostatic hypertrophy
• Acute narrow angle glaucoma
• Raised intraocular pressure
• Schizophrenia 
• Psychotic disorders
• Abrupt withdrawal
• Galactose intolerance
• Lapp lactose deficiency
• Glucose galactose malabsorption 
• Coadministration with antihypertensives
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: cap

South African registered indications and dosages

Depression

• Oral (cap): Initial: 150mg/day, in 3 divided doses for 1 week; Increase to 300-400mg/day, in 3 divided doses according to the clinical response; Optimal dose: 300-400mg/day, in 3 divided doses; Max: 600mg/24hrs in divided doses in hospitalised patients

Mixed anxiety and depression 

• Oral (cap): Initial: 100-150mg/day in 3 divided doses; When depression is the predominant symptom: 300-400mg/day, in 3 divided doses may be required to obtain a satisfactory response

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The dosage is dependent upon the diagnosis and the severity of the condition and the individual patient’s response. The daily dosage is usually administered in three divided doses

Not established for use in children below 18 years

Pregnancy

• Caution
• Data on a limited number (< 200) of exposed pregnancies indicate no adverse effects of trazodone on pregnancy or on the health of the foetus/newborn child. To date, no other relevant epidemiological data are available. The safety of trazodone in human pregnancy has not been established. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development at therapeutic doses. On basic principles, therefore, its use during the first trimester should be avoided
• Caution should be exercised when prescribing to pregnant women. When trazodone is used until delivery, newborns should be monitored for the occurrence of withdrawal symptoms

Breastfeeding

• Caution; not recommended
• Limited data indicate that excretion of trazodone in human breast milk is low, but levels of the active metabolite are not known. Due to the paucity of data, a decision on whether to continue/ discontinue breastfeeding or to continue/ discontinue therapy with trazodone should be made taking into account the benefit of breastfeeding to the child and the benefit of trazodone therapy to the woman

Fertility

• The effect on human fertility has not been evaluated

Renal Impairment

• Caution; no dose adjustment recommended

Hepatic Impairment

• Caution; no dose adjustment recommended

Elderly

• Caution; dose adjustment recommended
  Initial: 100mg, dly; In divided doses or a single night-time dose

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Serotonin syndrome
• Seizures
• Neuroleptic malignant syndrome
• Dizziness
• Vertigo
• Headache
• Drowsiness
• Restlessness
• Decreased alertness
• Tremor
• Memory disturbance
• Myoclonus
• Expressive aphasia
• Paraesthesia
• Dystonia
• Suicidal ideation 
• Suicidal behaviours
• Confusional state
• Insomnia
• Disorientation
• Mania
• Anxiety
• Nervousness
• Agitation
• Delusion
• Aggressive reaction
• Hallucinations
• Nightmares
• Decreased libido 
• Withdrawal syndrome
• Fatigue
• Weakness

Cardiovascular Disorders

• Cardiac arrhythmias
• Bradycardia
• Tachycardia
• ECG abnormalities 
• Ortostatic hypotension
• Hypertension
• Syncope
• Chest pain
• Oedema

Respiratory Disorders

• Nasal congestion
• Dyspnoea

Gastrointestinal Disorders

• Nausea and vomiting
• Dry mouth
• Constipation
• Diarrhoea
• Dyspepsia
• Stomach pain
• Gastroenteritis
• Increased salivation
• Paralytic ileus

Hepatobiliary Disorders

• Hepatic function abnormalities
• Intrahepatic cholestasis

Genitourinary Disorders

• Micturition disorder
• Priapism

Endocrine and Metabolic Disorders

• Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
• Hyponatraemia
• Weight loss
• Anorexia
• Increased appetite

Musculoskeletal Disorders

• Limb pain
• Back pain
• Myalgia
• Arthralgia

Skin and Subcutaneous Tissue Disorders

• Skin rash
• Pruritus
• Hyperhidrosis

Immune, Blood and Lymphatic System Disorders

• Blood dyscrasias
• Allergic reactions
• Fever
• Influenza-like symptoms

Sensory Disorders

• Blurred vision
• Altered taste

• QT prolonging agents
• CYP3A4 inhibitors 
• Antipsychotics
• Hypnotics
• Sedatives
• Anxiolytics
• Antihistamines
• Oral contraceptives
• Phenytoin
• Carbamazepine 
• Barbiturates
• Cimetidine 
• Antipsychotics
• Muscle relaxants 
• Volatile anaesthetics
• Sedative and antidepressant agents
• Alcohol
• Tricyclic antidepressants
• Fluoxetine
• Phenothiazines
• Warfarin
• St Johns wort
• Monoamine oxidase inhibitors
• Levodopa
• Digoxin
• Other psychotropic agents

Hepatic function

Trazodone binds at 5-HT2 receptor, it acts as a serotonin agonist at high doses and a serotonin antagonist at low doses. Like fluoxetine, trazodone's antidepressant activity likely results from blockage of serotonin reuptake by inhibiting serotonin reuptake pump at the presynaptic neuronal membrane. If used for long time periods, postsynaptic neuronal receptor binding sites may also be affected. The sedative effect of trazodone is likely the result of alpha blocking action and modest histamine blockade at H1 receptor. It weakly blocks presynaptic alpha-2 adrenergic receptors and strongly inhibits postsynaptic alpha-1 receptors.

Capsule 50mg

• Aspen Trazodone (Pharmacare)
• Biotech Trazodone (Biotech)
• Molipaxin (Sanofi)
• Sariprev 50 (Strides Pharma)
• Trezot 50 (Zydus Healthcare)
• Zerpas 50 (Strides Pharma)

Capsule 100mg

• Aspen Trazodone (Pharmacare)
• Biotech Trazodone (Biotech)
• Molipaxin (Sanofi)
• Sariprev 100 (Strides Pharma)
• Trezot 100 (Zydus Healthcare)
• Zerpas 100 (Strides Pharma)