Consumer medicine information

Luvox

Fluvoxamine maleate

BRAND INFORMATION

Brand name

Luvox

Active ingredient

Fluvoxamine maleate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Luvox.

What is in this leaflet

This leaflet answers some of the common questions about Luvox. It does not contain all of the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Luvox against the benefits they expect it will have for you.

If you have any concerns about using this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What Luvox is used for

Luvox belongs to a family of medicines known as selective serotonin reuptake inhibitors (SSRIs) and is used for treatment of the conditions listed below, or your doctor may prescribe Luvox for another reason.

Depression
Luvox is used to treat depression in adults only. It is not recommended for treatment of this condition in children and adolescents as the safety and effectiveness of this medicine, when used for depression in this age group, have not been established.

Depression is longer lasting and/or more severe than the "low moods" everyone has from time to time due to the stress of everyday life. It can affect your whole body and can cause emotional and physical symptoms such as feeling low in spirit, loss of interest in activities, being unable to enjoy life, poor appetite or overeating, disturbed sleep, often waking up early, loss of sex drive, lack of energy and feeling guilty for no reason.

Obsessive compulsive disorder (OCD)
Luvox is also used to treat a condition known as obsessive compulsive disorder (OCD) in adults and children eight years of age or older.

People with OCD can have two types of symptoms - obsessions and compulsions. Obsessions are unwanted repeated thoughts or feelings, which are ongoing. Compulsions are the need to repeat actions over and over. The symptoms of OCD can vary from patient to patient.

Both of these conditions are thought to be caused by a chemical imbalance in parts of the brain. Luvox corrects this chemical imbalance and may help relieve the symptoms of depression and OCD.

Ask your doctor if you have any questions about why Luvox has been prescribed for you. Your doctor may have prescribed it for another purpose.

There is no evidence that this medicine is addictive.

Luvox is only available with a doctor's prescription.

Before you take Luvox

When you must not take it

Do not take Luvox if you have an allergy to:

  • any medicine containing fluvoxamine
  • any of the ingredients listed at the end of this leaflet

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin

Do not take Luvox if:

  • you are taking another antidepressant medicine called a monoamine oxidase inhibitor (MAOI) (e.g. moclobemide and selegiline) or have been taking it within the last 14 days. Taking Luvox with these types of medicines may cause a serious reaction with a sudden increase in body temperature, extremely high blood pressure and severe convulsions.
  • you are taking any of the following medicines:
    - pimozide
    - cisapride
    - tizanidine
    - ramelteon

Ask your doctor or pharmacist if you are not sure if you have been taking one of these medicines.

Do not breast-feed if you are taking this medicine. The active ingredient in Luvox passes into breast milk and there is a possibility that your baby may be affected.

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if:

  • you are allergic to any other medicines, foods, dyes or preservatives
  • you have, or have had, any other medical conditions, including:
    - bipolar disorder or mania
    - any other mental illness
    - liver problems
    - kidney problems
    - epilepsy or convulsive disorders
    - a history of bleeding disorders
    - diabetes
    - glaucoma, an eye condition

Tell your doctor if you are pregnant or plan to become pregnant or are breast-feeding. Your doctor can discuss with you the risks and benefits involved.

You should avoid drinking alcohol while taking Luvox.

If you have not told your doctor about any of the above, tell him/ her before you start taking Luvox.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and Luvox may interfere with each other. Some of these include:

  • other medicines for the treatment of depression called monoamine oxidase inhibitors (MAOIs), such as moclobemide and selegiline. Taking Luvox with or within 14 days of stopping a MAOI may cause a serious reaction with sudden increase in body temperature, extremely high blood pressure, and convulsions
  • medicines used to treat depression, obsessive compulsive disorder, anxiety disorders, mood disorders, or other psychoses such as sertraline, amitriptyline, clomipramine, imipramine, clozapine, olanzapine, quetiapine, lithium, pimozide and haloperidol
  • medicines used for strong pain management such as tramadol
  • some benzodiazepine medicines such as alprazolam, triazolam, midazolam and diazepam
  • medicines called NSAIDs used to relieve pain, swelling and inflammation including arthritis such as ibuprofen and diclofenac
  • medicines used to help control epilepsy such as carbamazepine or phenytoin
  • medicines used to treat migraine such as sumatriptan, zolmitriptan or eletriptan
  • medicines used to help stop the blood from clotting such as warfarin, aspirin or clopidogrel
  • cisapride, a medicine used to treat gastroesophageal reflux disease
  • tizanidine, a medicine used as a muscle relaxant
  • ramelteon, a medicine used to treat insomnia
  • terfenadine and astemizole, medicines used to treat symptoms of allergic reaction
  • phentermine, a medicine used to assist weight loss
  • theophylline, a medicine used to treat breathing conditions such as asthma
  • ciclosporin, a medicine used for immunosuppression
  • methadone, a medicine used for opioid detoxification
  • any herbal remedies that include St John's Wort or tryptophan

There are many other medicines not listed here which could interfere with Luvox and vice versa. Always tell your doctor or pharmacist that you are taking Luvox before taking a new medication or complementary health product. These medicines may be affected by Luvox or may affect how well it works. You may need to take different amounts of your medicine or you may need to take different medicines.

Some combinations of medicines (including herbal and other remedies) can interact with Luvox and increase the risk of side effects, some of which can be potentially life-threatening.

Your doctor or pharmacist may have more information on medicines to avoid while taking Luvox.

How to take Luvox

Follow all directions given to you by your doctor or pharmacist carefully. These directions may differ from the information contained in this leaflet.

If you do not understand the instructions on the box, ask your doctor or pharmacist for help.

How much to take

Your doctor or pharmacist will tell you how many Luvox tablets to take each day. These will be printed on the pharmacy label on the container.

To treat depression:
Adults: The usual starting dose is 50 mg each day, but your doctor may adjust the number of tablets or the strength of the tablets you are taking until the desired response is achieved up to a maximum of 300 mg per day. If a daily dose of more than 150 mg is needed, the dose should be divided and taken 2 or 3 times per day.

To treat OCD:
Adults: The usual starting dose is 50 mg each day, but your doctor may adjust the number of tablets or the strength of the tablets you are taking until the desired response is achieved up to a maximum of 300 mg per day. If a daily dose of more than 150 mg is needed, the dose should be divided and taken 2 or 3 times per day. Children & Adolescents: The usual starting dose is 25 mg each day. The doctor will probably adjust the dose until the desired response is achieved.

How to take it

Swallow the tablet with a full glass of water. Do not chew the tablets.

Take Luvox with or without food.

If you have any concerns about how to take this medicine, ask your doctor or pharmacist.

How long to take it

Even if you feel better, continue taking your medicine until your doctor tells you to stop.

The length of treatment will depend on how quickly your symptoms improve. Most antidepressants take time to work, so don't be discouraged if you don't feel better right away. Some of your symptoms may improve in 1 or 2 weeks but it can take up to 4 or 6 weeks to feel any real improvement. Even when you feel well, you will usually have to take Luvox for several months or even longer to make sure the benefits are maintained.

In general, antidepressant medication should be continued for at least 6 months following recovery of a depressive episode.

This medicine should not be stopped abruptly (unless you develop a severe side effect to Luvox (see 'Side Effects' below).

If your Luvox treatment needs to be stopped, your doctor or pharmacist will provide you with instructions to reduce the dose gradually over a period of at least one or two weeks.

If you forget to take it

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to. Otherwise, take it as soon as you remember, then go back to taking it as you would normally.

Do not take a double dose to make up for the dose you missed.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

If you take too much (Overdose)

Immediately telephone your doctor or Poisons Information Centre (telephone 13 11 26 Australia or 0800 764 766 New Zealand), or go to Accident and Emergency at your nearest hospital, if you think you or anyone else may have taken too much Luvox.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention. The most common symptoms are nausea (feeling sick), vomiting and diarrhoea. You could also experience drowsiness and dizziness, rapid or irregular heartbeats, tremors or feel faint.

If possible, show the doctor the pack of tablets.

While you are taking Luvox

Things you must do

If you are about to start or stop any medicine, including any that you buy without a prescription from your pharmacy, supermarket or health food shop, tell your doctor and pharmacist that you are taking Luvox.

Tell all doctors, dentists and pharmacists who are treating you that you are taking Luvox.

Tell your doctor if, for any reason, you have not taken your medicine exactly as prescribed. Otherwise, your doctor may think that it was not effective and change your treatment unnecessarily.

Tell your doctor if you feel the tablets are not helping your condition.

If you are being treated for depression, be sure to discuss with your doctor any problems you may have and how you feel, especially any feelings of severe sadness or bursts of unusual energy or anger. This will help your doctor to determine the best treatment for you.

Tell your doctor immediately if you become pregnant while taking Luvox.

Be sure to keep all of your appointments with your doctor so that your progress can be checked.

Your doctor may want to take some blood tests and check your heart and blood pressure from time to time. This helps prevent unwanted side effects.

Things to be careful of

Tell your doctor immediately if you have any suicidal thoughts or other mental/mood changes. Care givers should consider all mentions of suicide or violence, which must be taken seriously.

Immediately contact your doctor or go to the nearest hospital for help if you or someone you know who are being treated for depression (or for any other condition) are demonstrating any of the warning signs of suicide.

Families and caregivers of children and adolescents who are taking Luvox should be especially watchful of the warning signs associated with suicide listed below.

The warning signs include:

  • Thoughts or talk of death or suicide
  • Thoughts or talk of self-harm or harm to others
  • Any recent attempts of self-harm
  • Mood changes such as an increase in aggressive or unusual behaviour, anxiety, irritability, agitation, panic attacks, insomnia, impulsivity, restlessness, or worsening of depressive symptoms.

Be especially careful of any suicidal thoughts or other mental/mood changes in the first few months of taking Luvox or when the dose is changed. There is a greater risk of suicide in people with history of suicidal thoughts prior to starting Luvox, and in those aged less than 24 years, including those not being treated for depression.

Be careful driving or operating machinery until you know how Luvox affects you. It may cause drowsiness, dizziness or sleepiness in some people and affect alertness.

Although drinking moderate amounts of alcohol is unlikely to affect your response to Luvox, your doctor may suggest avoiding alcohol while you are being treated for depression.

You should minimise your intake of caffeine-containing beverages (e.g. coffee or tea) while taking Luvox. Luvox can increase the effects of caffeine. People having large amounts of caffeine whilst on Luvox can experience tremor (shaking), palpitations (fast or irregular heart beat), nausea, restlessness and trouble or inability to sleep.

Older people may become confused when taking Luvox. Families and carers should be aware of this. Special care may be needed.

You should be careful for 1 or 2 weeks after stopping this medicine, because it will still be in your blood stream.

Things you must not do

Do not stop taking Luvox, increase or lower the dose, without first checking with your doctor. Do not let yourself run out of medicine over the weekend or on holidays. Suddenly stopping it may cause headache, nausea, dizziness and anxious feelings.

Do not give this medicine to anyone else, even if their symptoms seem similar to yours or if they have the same condition as you.

Do not use Luvox to treat any other complaints unless your doctor tells you to.

Side Effects

Check with your doctor as soon as possible if you do not feel well while you are taking Luvox, even if you do not think the problems are connected with the medicine or are not listed in this leaflet.

Like other medicines, Luvox can cause some side effects. If they occur, most are likely to be minor and temporary. However, some may be serious and need medical attention.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

Tell your doctor if you notice any of the following and they worry you:

  • nausea, vomiting, stomach pain, constipation, diarrhoea, heart burn, loss of appetite, dry mouth
  • drowsiness, difficulty sleeping, dizziness, nervousness, feeling anxious, headache
  • muscle weakness, muscular pains, pins and needles
  • abnormal taste
  • faster heartbeat, sweating
  • weight gain, weight loss
  • restlessness, pacing, swinging of the legs while seated, rocking from foot to foot

Tell your doctor immediately if you notice any of the following:

  • Muscle spasms or twitches
  • Significant bleeding or bruising

Stop taking Luvox and tell your doctor immediately, or go to Accident and Emergency at your nearest hospital if any of the following happens:

  • Allergic reaction including swelling of limbs, face, lips, mouth or throat which may cause difficulty swallowing or breathing
  • Sudden onset of prolonged muscular spasm, affecting the eyes, head, neck and body
  • Sudden increase in body temperature, severe convulsions
  • Fast heartbeat, sweating, racing thoughts and restlessness
  • Severe blisters and bleeding in the lips, eyes, mouth, nose and genitals
  • Severe skin reaction with painful red areas, large blisters and peeling skin. This may be accompanied by fever and chills, aching muscles and generally feeling unwell.

These are very serious, though rare, side effects.

Other side effects observed more frequently in children are: abnormal thoughts or behaviour, cough, increased period pain, nose bleeds, increased restlessness, infection and sinusitis.

Tell your doctor if you notice anything else that is making you feel unwell including any suicidal thoughts or other mental/mood changes (see 'Things to be careful of'). Other side effects not listed above may occur in some patients.

Ask your doctor or pharmacist to answer any questions you may have.

After using Luvox

Storage

Keep your tablets in their original pack until it is time to take them.

Keep the pack in a cool, dry place (below 25°C). Do not store Luvox in the bathroom, near a sink or leave it in the car on hot days. Heat and dampness can destroy some medicines.

Keep Luvox where young children cannot reach it. A locked cupboard at least one-and-a half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking Luvox, or the tablets have passed their expiry date, ask your pharmacist what to do with any medicine that is left over.

Return any unused medicine to your pharmacist.

Product description

What it looks like

Luvox 50 mg tablets are round, biconvex, white film coated tablets marked with "291" on either side of the score line and no embossing on the other side. Packs of 30 tablets.

Luvox 100 mg tablets are oval, biconvex, white film coated tablets marked with "313" on either side of the score line, with no embossing on the other side. Packs of 30 tablets.

Ingredients

Active ingredient:

  • Luvox 50 mg tablets - fluvoxamine maleate 50 mg
  • Luvox 100 mg tablets - fluvoxamine maleate 100 mg

Inactive ingredients:

  • mannitol
  • maize starch
  • pregelatinised potato starch
  • sodium stearyl fumarate
  • colloidal anhydrous silica
  • hypromellose
  • macrogol 6000
  • purified talc
  • titanium dioxide

Luvox does not contain lactose, sucrose, gluten, or tartrazine.

Sponsor

Luvox is manufactured in France and supplied in Australia by:

Mylan Health Pty Ltd
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.mylan.com.au
Phone: 1800 314 527

This leaflet was prepared in April 2020.

Australian Registration Number:

50 mg: AUST R 57632

100 mg: AUST R 57633

Luvox_cmi\Apr20/00

Published by MIMS June 2020

BRAND INFORMATION

Brand name

Luvox

Active ingredient

Fluvoxamine maleate

Schedule

S4

 

1 Name of Medicine

Fluvoxamine maleate.

6.7 Physicochemical Properties

Chemical structure.


MW: 434.4.
Fluvoxamine maleate is chemically identified as (E)-5-methoxy-4' -trifluoro-methylvalerophenone O-2- aminoethyloxime maleate.
Fluvoxamine maleate is a white to slightly off-white, odourless, crystalline powder, sparingly soluble in water, freely soluble in ethanol and chloroform, practically insoluble in diethylether. It has a partition coefficient (n-octanol/water, own pH) P = 38.7.

CAS number.

61718-82-9.

2 Qualitative and Quantitative Composition

Each tablet of Luvox contains 50 mg or 100 mg of fluvoxamine maleate.
Fluvoxamine is a member of a class of antidepressant agents known as selective serotonin reuptake inhibitors (SSRIs). It is chemically unrelated to the tricyclic antidepressants, and to other serotonin reuptake inhibitors as it is a monocyclic compound.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Luvox (fluvoxamine maleate) 50 mg: round, biconvex, scored white film-coated tablets inscribed with '291' on one side, on either side of the score.
Luvox (fluvoxamine maleate) 100 mg: oval, biconvex, scored, white film-coated tablet, inscribed with '313' on one side, on either side of the score.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Fluvoxamine has two isomeric forms: an E isomer which is pharmacologically active, and a Z isomer which is nonactive. Luvox tablets contain only the E isomer.
The mechanism of action of fluvoxamine is believed to be related to its ability to selectively inhibit presynaptic reuptake of serotonin, and thus increase the serotonin concentrations within the synaptic cleft. This is accompanied by minimal interference with the noradrenergic and dopaminergic processes.
Unlike tricyclic antidepressants, fluvoxamine has limited affinity for alpha adrenergic, beta adrenergic, histaminergic, muscarinic, dopaminergic or serotonergic receptors. Antagonism of these postsynaptic receptors are believed to be associated with some of the cardiovascular, anticholinergic and sedative effects of classical tricyclic antidepressant drugs.
Dose dependent decreases in rapid eye movement (REM) sleep and increased REM latency were found with fluvoxamine. These effects are similar to those of other antidepressant drugs.

Clinical trials.

Depression.

In depression, the efficacy of fluvoxamine was established in 15 three way trials in which fluvoxamine (≥ 100 mg/day) was compared with both placebo and a tricyclic antidepressant (imipramine ≥ 150 mg/day or desipramine ≥ 100 mg/day) generally over a period of 6 weeks and using HAM-D, CGI severity and MADRS as the main efficacy criteria. Of these studies, seven showed conclusive results: four were positive for both fluvoxamine and active reference therapy, whereas the other three studies showed only efficacy for active reference therapy. In a pooled analysis of the results of all these studies, both fluvoxamine (n = 837) and active reference therapy (n = 779) were found to be more effective than placebo (n = 837). HAM-D improvements (LOCF) after 6 weeks were 39.1%, 41.9% and 33.9%, respectively. In these studies, the effective dose range for fluvoxamine was determined to lie between 100 mg and 300 mg per day. Using various definitions of response based on HAM-D or CGI criteria, there were no statistically significant differences in response rates between fluvoxamine and active reference therapy. Statistical analyses of the data did not reveal any patient features (such as age, sex, race etc.) which predict treatment response to fluvoxamine.

Prevention of relapse of depression.

A study of depressed outpatients who had responded to fluvoxamine (MADRS ≤ 10) during an initial 26 week open treatment phase (n = 204) and were then double blind randomised to continuation on fluvoxamine (100 mg/day) or placebo for 1 year demonstrated a significantly lower relapse rate for fluvoxamine (13%) compared to those on placebo (35%).

Obsessive compulsive disorder (OCD).

Adult OCD studies.

The effectiveness of fluvoxamine in the treatment of obsessive compulsive disorder (OCD) was demonstrated in two 10 week placebo controlled studies (studies 1 and 2). The results of two 10 week clomipramine controlled studies (studies 3 and 4) support the effectiveness of fluvoxamine in the treatment of OCD.
Studies 1 and 2 were flexible dose double blind parallel group, multicentre studies in which patients with moderate to severe OCD received fluvoxamine in doses up to 300 mg/day or placebo. 157 patients received fluvoxamine versus 158 patients who received placebo. Improvements from baseline in Yale-Brown Obsessive Compulsive Disorder (Y-BOCS) and NIMH-OC scores and the CGI improvement score were significantly greater in fluvoxamine treated patients. In these studies, the overall response rates were 36% for fluvoxamine and 12% for placebo, and the effective dosage range for fluvoxamine was between 100 mg and 300 mg daily. In open extension studies, efficacy in OCD was demonstrated to be maintained in a total of 72 patients treated for a total of 46 weeks or more.
Studies 3 and 4 were flexible dose double blind parallel group multicentre studies comparing fluvoxamine (100 - 300 mg/day) with clomipramine (100 mg - 250 mg/day). 69 patients received fluvoxamine versus 76 patients who received clomipramine. Fluvoxamine and clomipramine were equally efficacious on the Y-BOCS, NIMH-OC and CGI improvement scores.

Paediatric OCD study.

The effectiveness of fluvoxamine for the treatment of OCD was also demonstrated in a 10 week multicentre, parallel group, placebo controlled study in a paediatric outpatient population (children and adolescents, ages 8-17) followed by an open label extension of up to two years.
In the double blind phase of the study, patients were titrated to a total daily fluvoxamine dose of approximately 100 mg/day over the first two weeks of the trial, following which the dose was adjusted within a range of 50-200 mg/day (on a b.i.d. schedule) on the basis of response and tolerance. All patients had moderate to severe OCD (DSM-III-R) with mean baseline ratings on the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), total score of 24. Patients receiving fluvoxamine maleate experienced mean reductions of approximately 6 units on the CY-BOCS total score, compared to a 3 unit reduction for placebo patients.
Table 2 provides the outcome classification by treatment group on the global improvement item of the clinical global impression (CGI) scale for the paediatric study.
Post hoc exploratory analyses for gender effects on outcomes did not suggest any differential responsiveness on the basis of gender. Further exploratory analyses revealed a prominent treatment effect in the 8-11 age group and essentially no effect in the 12-17 age group. The reason for the difference in these results is unknown. However, follow-up data from the open extension of the study showed a further improvement as demonstrated by a decrease of an additional 3 to 6 units on the CY-BOCS in young, as well as adolescent, patients. This improvement was sustained over a one year period in 54 of the 98 patients who completed the one year extension and in 12 of the 22 patients who completed the two-year extension.

5.2 Pharmacokinetic Properties

Absorption and bioavailability.

Fluvoxamine is almost completely absorbed following oral administration. The absolute bioavailability is 53% (90% confidence interval: 44-62%). Absorption is unaffected by the presence of food.

Distribution.

Maximum plasma levels occur within 3-8 hours of dosing. Steady-state levels are usually achieved within one week. The mean plasma half-life is approximately 12-13 hours after a single dose and approximately 22 hours following repeated dosing. In vitro binding of fluvoxamine to human plasma proteins is 80%, and the volume of distribution is estimated to be 20 L/kg.

Metabolism.

The pharmacokinetics of fluvoxamine is linear between single oral doses of 25-100 mg. During multiple dosing in the range of 100-300 mg per day, the higher doses produced disproportionally higher plasma concentrations than predicted from data obtained with the lower dose.

Excretion.

Fluvoxamine undergoes extensive hepatic transformation, mainly via oxidative demethylation, into at least 9 metabolites. Less than 4% of the dose is excreted in the urine as unchanged parent compound, while approximately 94% of the dose is recovered in the urine as metabolites. The two principal metabolites exhibit negligible pharmacological activity. In view of the structures of the other metabolites, it is not expected that the other metabolites would be pharmacologically active.
The pharmacokinetics of fluvoxamine in patients with renal dysfunction do not appear to differ significantly from those in healthy, young volunteers. The area under the plasma concentration time curve (AUC) and half-life were greater, however, in patients with liver dysfunction. Patients suffering from renal or hepatic insufficiency should be carefully monitored when treated with fluvoxamine. Upward dose titration should be carried out more slowly in this patient population.

Paediatric subjects.

The multiple dose pharmacokinetics of fluvoxamine was determined in male and female children (ages 6-11) and adolescents (ages 12-17). The clearance of fluvoxamine in children was approximately half that observed in adolescents. AUC and Cmax in children were 1.5 to 2.7-fold higher than that in adolescents. As in adults, both children and adolescents exhibited nonlinear multidose pharmacokinetics. Female children showed significantly lower clearance values and higher AUC(0-12) and Cmax compared to male children and, therefore, lower doses of Luvox may produce therapeutic benefit. No gender differences were observed in adolescents. Bodyweight adjusted mean clearance at a dose of 300 mg/day was approximately 50% higher in adolescents compared to adults in previous studies.

5.3 Preclinical Safety Data

Genotoxicity.

No evidence of mutagenicity or chromosomal damage was observed in vitro. An in vivo test for chromosomal damage in mice (micronucleus test) gave no clear evidence of clastogenic activity.

Carcinogenicity.

In animal studies, there was no evidence of carcinogenic activity when fluvoxamine was given to rats at dietary doses up to 211 mg/kg/day for 30 months (approximately 2-5 times the maximum human exposure, based on plasma AUC), or to hamsters at about the same dose level for 112 weeks (male) and 85 weeks (female) (approximately two thirds the maximum human exposure, based on plasma AUC).

4 Clinical Particulars

4.1 Therapeutic Indications

Luvox (fluvoxamine maleate) is indicated for the treatment of major depression in adults.
Luvox (fluvoxamine maleate) is also indicated for the treatment of obsessive compulsive disorder (OCD) in children aged 8 years of age and older, adolescents and adults.

4.3 Contraindications

Fluvoxamine is contraindicated in combination with tizanidine.
Fluvoxamine should not be used in combination with monoamine oxidase inhibitors (MAOIs) or reversible MAOIs (RIMAs), moclobemide or linezolid, or within 14 days of discontinuing treatment with a MAOI. Similarly, at least one week should be allowed after stopping fluvoxamine before starting a MAOI. Cases of serious reactions, such as potentially life threatening serotonin syndrome (characterised by neuromuscular excitation, altered mental status and autonomic dysfunction) have been reported in patients receiving an SSRI in combination with MAOIs and RIMA, and in patients who have recently discontinued an SSRI and have started on a MAOI (see Section 4.4 Special Warnings and Precautions for Use).
Fluvoxamine immediate release tablets should not be used in combination with pimozide and ramelteon.
Fluvoxamine is contraindicated in combination with cisapride.
Luvox tablets are contraindicated in patients with hypersensitivity to any component of the product (see Section 6.1 List of Excipients).
Fluvoxamine has been shown to increase postnatal mortality in rats at doses greater than 1 mg/kg/day, and should not be used by nursing mothers.

4.4 Special Warnings and Precautions for Use

Bipolar disorder.

A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/ manic episode in patients at risk of bipolar disorder. Prior to initiating treatment with an antidepressant, patients should be adequately screened to determine if they are a risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder and depression.

Clinical worsening and suicide risk associated with psychiatric disorders.

The risk of suicide attempt is inherent in depression and may persist until significant remission occurs. This risk must be considered in all depressed patients.
Patients with depression may experience worsening of their depressive symptoms and/or the emergence of suicidal ideation and behaviours (suicidality) whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored for clinical worsening and suicidality, especially at the beginning of a course of treatment or at the time of dose changes, either increases or decreases. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse or whose emergent suicidality is severe, abrupt in onset, or was not part of the patient's presenting symptoms.
Patients (and caregivers of patients) should be alerted about the need to monitor for any worsening of their condition and/or the emergence of suicidal ideation/ behaviour or thoughts of harming themselves and to seek medical advice immediately if these symptoms present. Patients with co-morbid depression associated with other psychiatric disorders being treated with antidepressants should be similarly observed for clinical worsening and suicidality.
Obsessive compulsive disorders may also be associated with an increased risk of suicide related events. The same precautions should, therefore, be observed for these patients.
Patients with a history of suicide related events or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment, are at a greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment.
Pooled analyses of 24 short-term (4 to 16 weeks), placebo controlled trials of nine antidepressant medicines (SSRIs and others) in 4400 children and adolescents with major depressive disorder (16 trials), obsessive compulsive disorder (4 trials), or other psychiatric disorders (4 trials) have revealed a greater risk of adverse events representing suicidal behaviour or thinking (suicidality) during the first few months of treatment in those receiving antidepressants. The average risk of such events in patients treated with an antidepressant was 4%, compared with 2% of patients given placebo. There was considerable variation in risk among the antidepressants, but there was a tendency towards an increase for almost all antidepressants studied. The risk of suicidality was most consistently observed in the major depressive disorder trials, but there were signals of risk arising from trials in other psychiatric indications (obsessive compulsive disorder and social anxiety disorder) as well. No suicides occurred in these trials. It is unknown whether the suicidality risk in children and adolescent patients extends to use beyond several months. The nine antidepressant medicines in the pooled analyses included five SSRIs (citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) and four non-SSRIs (bupropion, mirtazapine, nefazodone, venlafaxine).
Pooled analysis of short-term studies of antidepressant medications have also shown an increased risk of suicidality in young adults aged 18 to 24 during initial treatment (generally the first one to two months). Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond the age of 24 years; there was a reduction with antidepressants compared to placebo in adults aged 65 years and older.
Symptoms of anxiety, agitation, panic attacks, insomnia, irritability, hostility (aggressiveness), impulsivity, akathisia (psychomotor restlessness), hypomania and mania have been reported in adults, adolescents and children being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and non-psychiatric. Although a causal link between the emergence of such symptoms and either worsening of depression and/or emergence of suicidal impulses has not been established, there is concern that such symptoms may be precursors of emerging suicidality.
Families and caregivers of children and adolescents being treated with antidepressants for major depressive disorder or for any other condition (psychiatric or non-psychiatric) should be informed about the need to monitor these patients for the emergence of agitation, irritability, unusual changes in behaviour and other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers. It is particularly important that monitoring be undertaken during the initial few months of antidepressant treatment or at times of dose increase or decrease.
Prescriptions of Luvox should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.

Akathisia/ psychomotor restlessness.

The use of fluvoxamine has been associated with the development of akathisia. This is most likely to occur within the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may be detrimental.
The presentation of akathisia may be variable and comprises subjective complaints of restlessness and an overwhelming urge to move and either distress or motor phenomena such as pacing, swinging of the legs while seated, rocking from foot to foot, or both. Particular attention should be paid to the monitoring for such symptoms and signs as, left untreated, akathisia is associated with poor compliance and an increased risk of relapse.

Nervous system disorders.

Although in animal studies, fluvoxamine has no pro-convulsive properties, caution is recommended when the drug is administered to patients with a history of convulsive disorders. Fluvoxamine should be avoided in patients with unstable epilepsy and patients with controlled epilepsy should be carefully monitored. Treatment with fluvoxamine should be discontinued if seizures occur or if seizure frequency increases.

Metabolism and nutrition disorders.

As with other SSRIs, hyponatraemia has been rarely reported, and appears to be reversible when fluvoxamine is discontinued. Some cases were possibly due to the syndrome of inappropriate antidiuretic hormone secretion. The majority of reports were associated with older patients.
Glycaemic control may be disturbed (i.e. hyperglycaemia, hypoglycaemia, decreased glucose tolerance), especially in the early stages of treatment. When fluvoxamine is given to patients with a known history of diabetes mellitus, the dosage of anti-diabetic drugs may need to be adjusted.

Eye disorders.

Mydriasis has been reported in association with SSRIs such as fluvoxamine. Therefore, caution is recommended when prescribing fluvoxamine for patients with raised intraocular pressure or those at risk of acute narrow angle glaucoma.

Haematological disorders.

There have been reports of cutaneous bleeding abnormalities, such as ecchymoses and purpura, as well as other haemorrhagic manifestations such as gastrointestinal bleeding or gynaecological haemorrhage with SSRIs. Caution is advised in patients taking SSRIs, particularly in elderly patients and in patients who concomitantly use drugs known to affect platelet function (e.g. atypical antipsychotics and phenothiazines, most tricyclic antidepressants, aspirin and NSAIDs) or drugs that increase risk of bleeding, as well as in patients with a history of bleeding disorders, and in those with predisposing conditions (e.g. thrombocytopenia, or coagulation disorders). If any significant bleeding or bruising is observed, it is recommended that a platelet count should be performed.

Cardiac disorders.

When combined with fluvoxamine, plasma concentrations of terfenadine, astemizole or cisapride may be increased, resulting in an increased risk for QT prolongation/ torsades de pointes. Therefore, fluvoxamine should not be co-administered with these agents.
Fluvoxamine may cause an insignificant decrease in heartbeat (2-6 beats per minute).

Dermatological effects.

Serious skin reactions, some of them fatal, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in association with fluvoxamine (see Section 4.8 Adverse Effects (Undesirable Effects)). Patients appear to be at highest risk of these reactions early in the course of therapy. If skin reactions occur, fluvoxamine should be discontinued immediately, and the patient should be closely monitored.

Electroconvulsive therapy (ECT).

There is limited clinical experience of concomitant administration of fluvoxamine and ECT; therefore, caution is advisable.

Serotonin syndrome.

Development of serotonin syndrome or neuroleptic malignant syndrome-like events may occur in association with treatment with SSRIs, particularly when given in combination with MAOIs or other serotonergic and/or neuroleptic agents. Symptoms and signs of serotonin syndrome include rapid onset of neuromuscular excitation (hyperreflexia, incoordination, myoclonus, tremor), altered mental status (confusion, agitation, hypomania) and autonomic dysfunction (diaphoresis, diarrhoea, fever, shivering and rapidly fluctuating vital signs). Treatment with fluvoxamine should be discontinued if such events occur and supportive symptomatic treatment initiated.

Discontinuation/ withdrawal symptoms (see Section 4.2 Dose and Method of Administration).

The onset of symptoms may occur one to three days after abrupt discontinuation of SSRI therapy and (rarely) after dosage lowering. It is important but may be difficult to distinguish the discontinuation symptoms from a recurrence of the underlying disease. Both may present with disturbances of the equilibrium and of the sensory system. However, they may differ in view of the severity, onset and duration of the symptoms.
Discontinuation symptoms rarely occur after treatment of less than 5 weeks' duration and usually last from one day to three weeks.
The most commonly reported symptoms in association with withdrawal of the medicine include: dizziness, sensory disturbances (including paraesthesia, visual disturbances and electric shock sensations), sleep disturbances (including insomnia and intense dreams), agitation, irritability, confusion, emotional stability, headache, nausea and/or vomiting, diarrhoea, sweating, palpitations, tremor and anxiety (see Section 4.8 Adverse Effects (Undesirable Effects)). Generally, these effects are mild to moderate and are self limiting; however, in some patients they may be severe and/or prolonged. They usually occur within the first few days of discontinuing treatment.
It is advised that in accordance with clinical experience and individual need of a patient the dosage should be gradually tapered over a couple of weeks when discontinuing treatment (see Section 4.2 Dose and Method of Administration).

Mania/ hypomania.

Fluvoxamine should be used with caution in patients with a history of mania/ hypomania. Fluvoxamine should be discontinued in any patient entering a manic phase.

Use in hepatic impairment.

Patients suffering from hepatic insufficiency should start on a low dose and be carefully monitored when treated with fluvoxamine. Upward dose titration should be carried out more slowly in this patient population. Clearance of fluvoxamine is slower in patients with hepatic impairment (e.g. cirrhosis).
Treatment with fluvoxamine has rarely been associated with an increase in hepatic enzymes, generally accompanied by clinical symptoms. In such cases, treatment should be discontinued.

Use in renal impairment.

Patients suffering from renal insufficiency should start on a low dose and be carefully monitored when treated with fluvoxamine. Upward dose titration should be carried out more slowly in this patient population.

Use in the elderly.

Data in elderly subjects gives no indication of clinically significant differences in pharmacokinetics compared with younger subjects. Nevertheless, upward dose titration should be carried out more slowly in this patient population, and dosing should always be handled with caution.

Paediatric use.

Fluvoxamine should not be used in children and adolescents (age < 18 years) for the treatment of major depressive disorder as the efficacy and safety of the medicine in these patients for this condition has not been satisfactorily investigated.
Decreased appetite and weight loss have been observed in association with the use of fluvoxamine as well as with other SSRIs. Although no detrimental effect on growth, development and maturation was apparent in the long-term, open label clinical studies in children, regular monitoring of weight and growth is recommended if treatment of a child with an SSRI is to be continued long term.

Effects on laboratory tests.

Rarely, treatment with fluvoxamine has been associated with an increase in hepatic enzymes, mostly accompanied by clinical symptoms. In these cases, treatment should be discontinued.
Effects on other laboratory tests have not been established.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The concurrent use of fluvoxamine with tizanidine, or cisapride is contraindicated (see Section 4.3 Contraindications).
Fluvoxamine immediate-release tablets should not be used in combination with ramelteon (see Section 4.3 Contraindications).

Pharmacodynamic interactions.

Fluvoxamine is a serotonergic drug and it can potentiate the effects of other serotonergic and/or neuroleptic drugs. In rare cases, this could lead to the development of a serotonin syndrome or neuroleptic malignant syndrome (NMS)-like events. As these syndromes may result in potentially life threatening conditions, treatment with fluvoxamine should be discontinued if such events (characterised by clusters of symptoms such as hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, mental status changes including confusion, hypomania, extreme agitation progressing to delirium and coma) occur and supportive symptomatic treatment should be initiated.
Fluvoxamine should not be used in combination with monoamine oxidase inhibitors (MAOIs), including linezolid, due to risk of serotonin syndrome (see Section 4.3 Contraindications). It should be used with caution in combination with other SSRIs, tricyclic antidepressants, tryptophan, triptans, phentermine or tramadol.
Although fluvoxamine has been used in combination with lithium in the treatment of severely ill, drug resistant patients, possible potentiation of serotonergic effect should be kept in mind.
As with other SSRIs, possible potentiation of an increased serotonergic effect should be considered where preparations containing St. John's wort are used in combination with fluvoxamine.
As with other psychotropic drugs, patients should be advised to avoid using alcohol while taking fluvoxamine.
When fluvoxamine was co-administered with warfarin for 2 weeks, plasma prothrombin times were prolonged. This can be ascribed to the intrinsic ability of SSRIs to lower the serotonin concentration in blood platelets (which can lead to prolonged bleeding in sensitive patients), and to fluvoxamine increasing the warfarin plasma concentrations (see below). As the risk for haemorrhage may increase, patients receiving anticoagulants should have their prothrombin time monitored and their anticoagulant dose adjusted accordingly when administered fluvoxamine.

Pharmacokinetic interactions.

Fluvoxamine is metabolised in the liver, mostly via the cytochrome P450 system. While the specific enzymes involved are not definitively known, it would appear, based on available in vitro data, that CYP1A2 is the main isoenzyme involved. To a much lesser extent, CYP3A4 and CYP2C19 may also be involved in the metabolism of fluvoxamine.
In addition, fluvoxamine can inhibit the metabolism of drugs metabolised by certain P450 isoenzymes. A strong inhibition of CYP1A2 and CYP2C19 is demonstrated in in vitro and in vivo studies. CYP2C9, CYP2D6 and CYP3A4 are inhibited to a lesser extent.
Fluvoxamine increases or decreases (e.g. in case of prodrugs like clopidogrel) the plasma concentrations of active substance/ metabolites of drugs which are largely metabolised via these isoenzymes.
Fluvoxamine has only a weak inhibitory effect on CYP2D6, and is, therefore, not likely to increase plasma concentrations of drugs metabolised by CYP2D6 to a clinically relevant extent.
Concomitant therapy of fluvoxamine and these drugs should be initiated at or adjusted to the low end of their dosage range. Plasma concentrations, effects or adverse effects of co-administered drugs should be monitored and their dosage should be reduced if necessary. This is particularly relevant for drugs with a narrow therapeutic index.

CYP1A2.

Tricyclic antidepressants and neuroleptics.

An increase in previously stable plasma levels of those tricyclic antidepressants (such as clomipramine, amitriptyline and imipramine) and neuroleptics (or antipsychotics such as clozapine, olanzapine, quetiapine), which are largely metabolised through CYP1A2, has been reported when used together with fluvoxamine. The combination of fluvoxamine with these drugs is not recommended.

Compounds with a narrow therapeutic index.

Patients co-administered fluvoxamine and CYP1A2 metabolised drugs with a narrow therapeutic index (such as tacrine, theophylline, methadone, mexiletine, phenytoin, carbamazepine and ciclosporin) should be carefully monitored when these agents are metabolized exclusively or by a combination of CYPs inhibited by fluvoxamine. If necessary, dose adjustment of these drugs is recommended.
Due to the narrow therapeutic index of pimozide and its known ability to prolong QT interval, concomitant use of pimozide and fluvoxamine is contraindicated (see Section 4.3 Contraindications).

Cases of increased side effects.

Isolated cases of cardiac toxicity have been reported when fluvoxamine was combined with thioridazine. Caffeine plasma levels are likely to be increased during co-administration with fluvoxamine. Thus, patients who consume high quantities of caffeine containing beverages should lower their intake when fluvoxamine is administered and adverse caffeine effects (like tremor, palpitations, nausea, restlessness, insomnia) are observed.
Side effects may be increased when fluvoxamine is used in combination with terfenadine, astemizole, cisapride and sildenafil (see Section 4.4 Special Warnings and Precautions for Use).

CYP3A4.

When combined with fluvoxamine, plasma concentrations of cisapride may be increased, resulting in an increased risk of QT prolongation/ torsades de pointes. Therefore, fluvoxamine should not be coadministered with cisapride.
The plasma concentrations of benzodiazepines metabolised by oxidation (such as triazolam, midazolam, alprazolam and diazepam) are likely to increase when co-administered with fluvoxamine. The dosages of these benzodiazepines should be reduced during co-administration with fluvoxamine. For benzodiazepines metabolised by glucuronidation (lorazepam, lormetazepam, oxazepam, temazepam) or nitro-reduction (clonazepam, nitrazepam) such an effect is not likely to occur.
Increased serum concentrations of haloperidol have also been reported after concomitant use of haloperidol and fluvoxamine.
Patients co-administered fluvoxamine and CYP3A4 metabolised drugs with a narrow therapeutic index (e.g. ciclosporin, methadone or carbamazepine) should be carefully monitored and, if necessary, dose adjustments of these drugs is recommended.

CYP2C.

Patients co-administered fluvoxamine and CYP2C metabolised drugs with a narrow therapeutic index (such as phenytoin) should be carefully monitored and, if necessary, dose adjustments of these drugs is recommended.

Cases of increased plasma concentration.

As plasma concentrations of ropinirole may be increased in combination with fluvoxamine thus increasing the risk of overdose, surveillance and reduction in the dosing of ropinirole during fluvoxamine treatment and after its withdrawal may be required.
As plasma concentrations of propranolol are increased in combination with fluvoxamine, the propranolol dose may need to be lowered.
When given with fluvoxamine, warfarin plasma concentrations were significantly increased and prothrombin time prolonged.

Other.

No interactions were seen with digoxin or atenolol, which are renally excreted.
After a single oral dose, fluvoxamine plasma concentrations were lower in smokers than in non-smokers.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No evidence of impairment of fertility in male or female rats was observed with fluvoxamine at oral doses up to 80 mg/kg/day.
Reproduction studies in animals revealed impaired fertility (note: at doses exceeding 2 times the maximum recommended human dosage), increased embryofoetal death, decreased foetal body weight and increased incidences of foetal eye abnormalities (folded retina) in fluvoxamine doses which markedly exceed maximum recommended human dose.
The potential risk for humans is unknown.
Fluvoxamine should not be used in patients attempting to conceive unless the clinical condition of the patient requires treatment with fluvoxamine.
(Category C)
Epidemiological data have suggested that the use of selective serotonin reuptake inhibitors (SSRIs) in pregnancy, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). The observed risk was approximately 5 cases per 100 pregnancies. In the general population 1 to 2 cases of PPHN occur per 1000 pregnancies.
There was no evidence of teratogenic effects following administration of fluvoxamine at oral doses up to 80 mg/kg/day to rats and rabbits during the period of organogenesis, with rat exposure (based on plasma AUC) similar to human exposure at the maximum recommended human dose. Oral administration of fluvoxamine to rats at doses of 5-160 mg/kg/day during late gestation and lactation was associated with increased postnatal pup mortality.
Fluvoxamine should not be used during pregnancy unless the clinical condition of the woman requires such treatment. Cases of withdrawal symptoms in the newborn child have been described after the use of fluvoxamine at the end of pregnancy. Neonates exposed to Luvox, other SNRIs (serotonin and norepinephrine reuptake inhibitors) or SSRIs (selective serotonin reuptake inhibitors) late in the third trimester have developed complications requiring prolonged hospitalisation, respiratory support and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycaemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, lethargy, somnolence, difficulty in sleeping, irritability and constant crying. These features are consistent with either a direct effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome.
Oral administration of fluvoxamine to rats at doses greater than 1 mg/kg/day during late gestation and lactation was associated with increased postnatal pup mortality. Since fluvoxamine is excreted in human milk, the drug should not be used by lactating women (see Section 4.3 Contraindications).

4.8 Adverse Effects (Undesirable Effects)

Nausea, sometimes accompanied by vomiting, is the most frequently observed symptom associated with fluvoxamine treatment. This side effect usually diminishes within the first two weeks of treatment. Other adverse events, observed in clinical studies at frequencies listed below (database size approx. - 35,000 patients; dose range 50-300 mg/day), are often associated with the illness and are not necessarily related to treatment.
Events are listed within body systems and categorised by frequency according to the following definitions.
Frequency estimate: very common (> 10%), common (> 1 and < 10%), uncommon (≥ 0.1% and < 1%), rare (≥ 0.01% and < 0.1%), very rare (< 0.01%), not known (cannot be estimated from the available data). See Table 1.

Withdrawal symptoms seen on discontinuation of fluvoxamine treatment.

Discontinuation of fluvoxamine treatment (particularly when abrupt) commonly leads to withdrawal symptoms. It is therefore advised that when fluvoxamine treatment is no longer required, gradual discontinuation by dose tapering should be carried out (see Section 4.2 Dose and Method of Administration; Section 4.4 Special Warnings and Precautions for Use).

Post-marketing data.

Haemorrhage, ecchymoses, purpura and gastrointestinal bleeding have been reported (see Section 4.4 Special Warnings and Precautions for Use).
Changes in weight (weight gain or weight loss), and hyperprolactinaemia have also been reported.
Very rarely, paresthesia, taste perversion, visual disturbance and hepatitis have been reported.

Urogenital.

Very rare: anorgasmia and impotence.

Skin.

Uncommon: cutaneous hypersensitivity reaction (including angioedema).

Reproductive system and breast disorders.

Anorgasmia, menstrual disorders (such as amenorrhea, hypomenorrhea, metrorrhagia, menorrhagia).

Class effects.

Epidemiological studies, mainly conducted in patients 50 years of age and older, show an increased risk of bone fractures in patients receiving SSRIs and TCAs. The mechanism leading to this risk is unknown.

Other adverse events in OCD paediatric population.

In paediatric patients (N = 57) treated with fluvoxamine the overall profile of adverse events was generally similar to that seen in adult studies. However, the following events not appearing above have been reported in two or more of the paediatric patients and were more frequent with fluvoxamine than placebo: abnormal thinking, cough increase, dysmenorrhoea, emotional lability, epistaxis, hyperkinesia, infection and sinusitis.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

Depression.

The recommended starting dose of fluvoxamine is 50 mg per day for one week, given as a single dose in the evening. Doses should be gradually increased (by 50 mg per week) until an effective dose is reached, with a maximum of 300 mg per day (the usually effective dose is 100 mg/day). Doses up to 150 mg can be given as a single dose. It is recommended that total daily doses of greater than 150 mg be given in 2 or 3 divided doses.
If no improvement is observed within 6 weeks of initiation of therapy, treatment with fluvoxamine should be reconsidered. It is important to ascertain that an adequate therapeutic dose has been maintained throughout this period.
In agreement with the consensus statement of the WHO, antidepressant medication should be continued for at least 6 months after recovery from a depressive episode.

Obsessive compulsive disorder.

Adults.

The recommended starting dose of fluvoxamine is 50 mg per day for 3 to 4 days. The dosage should be increased gradually (i.e. by 50 mg every 4 to 6 days) until an effective dose is achieved, with a maximum of 300 mg per day. (The usually effective dose is in the range of 100-300 mg/day.) Doses up to 150 mg per day can be given as a single dose, preferably in the evening. It is recommended that a total daily dose of more than 150 mg is given in 2 or 3 divided doses.

Children and adolescents (8-17 years).

The recommended starting dose of fluvoxamine in paediatric populations (ages 8-17 years) is 25 mg administered as a single daily dose at bedtime. In a controlled clinical trial establishing the effectiveness of Luvox in OCD, paediatric patients (ages 8-17) were titrated within a dose range of 50 to 200 mg/day. The dose should be increased in 25 mg increments every 4 to 7 days, as tolerated, until maximum therapeutic benefit is achieved. Physicians should consider age and gender differences when dosing paediatric patients. The maximum dose should not exceed 200 mg/day. Therapeutic effect in female children may be achieved with lower doses. It is advisable that a total daily dose of more than 50 mg should be given in two divided doses. If the two divided doses are not equal, the larger dose should be given at bedtime.
If a good therapeutic response is achieved, treatment can be continued at the required dosage. There are no systematic studies which address the issue of the length of treatment. However, since obsessive compulsive disorder (OCD) is a chronic condition, it is reasonable to consider continuation beyond 10 weeks in responding patients. Data from the long-term (up to two years) open extension phase of the placebo controlled study in children supports sustained efficacy of the medicine. Dosage adjustments should be made carefully, on an individual patient basis, throughout therapy to maintain the patient at the lowest effective dose. The need for treatment should be reassessed periodically.
Some clinicians advocate concomitant behavioural psychotherapy in conjunction with pharmacotherapy.
If no improvement is observed within 10 weeks of initiation of therapy, treatment with fluvoxamine should be reconsidered. It is important to ascertain that an adequate therapeutic dose has been maintained throughout this period.

Administration.

Luvox (fluvoxamine maleate) tablets should be swallowed with water, without chewing.

Withdrawal symptoms seen on discontinuation of fluvoxamine.

Abrupt discontinuation should be avoided. When stopping treatment with fluvoxamine, the dose should be gradually reduced over a period of at least one or two weeks in order to reduce the risk of withdrawal reactions (see Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects)). If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose, but at a more gradual rate.

4.7 Effects on Ability to Drive and Use Machines

Fluvoxamine at doses up to 150 mg per day exhibited no effect on psychomotor skills associated with driving and operating machinery in healthy volunteers. However, somnolence has been reported during treatment with fluvoxamine. Therefore, caution is recommended until the individual response to the drug has been determined.

4.9 Overdose

Symptoms.

The most common symptoms of overdose include gastrointestinal complaints (nausea, vomiting and diarrhoea). Somnolence and dizziness, cardiac events (tachycardia, bradycardia, hypotension), liver function disturbances, convulsions and coma have also been reported.
More than 300 cases of deliberate overdosage with fluvoxamine have been reported to date.
The highest documented dose of fluvoxamine ingested by a patient is 12 grams. This patient recovered completely.
Occasionally, more serious complications have been observed in cases of deliberate overdosage of fluvoxamine in combination with other drugs. Six deaths due to an overdose of fluvoxamine alone have been reported.

Treatment.

There is no specific antidote to fluvoxamine. Treatment should consist of general measures employed in the management of overdose along with general symptomatic and supportive measures.
For information on the management of overdose, contact the Poison Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

The inactive ingredients are: mannitol, maize starch, pregelatinised potato starch, sodium stearylfumarate, colloidal anhydrous silica, hypromellose, macrogol 6000, purified talc, titanium dioxide.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. Keep out of reach of children.

6.5 Nature and Contents of Container

Luvox tablets are available in blister packs (PVC/PVDC/Al).
50 mg tablets: packs of 60*, 30 and 10 (sample pack).
100 mg tablets: packs of 30 and 10 (sample pack).
* Not distributed in Australia.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

Summary Table of Changes