Abbott Healthcare Products Limited

FROM:

Film-coated tablet.

Oval, biconvex, scored, white to off-white film-coated tablets imprinted '313' on both sides of the score.

The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.

TO:

Film-coated tablet.

Oval, biconvex, scored, white to off-white film-coated tablets imprinted '313' on both sides of the score.

The tablet can be divided into equal halves.

4.4       Special warnings and precautions for use

From:
Glycaemic control may be disturbed, especially in the early stages of treatment. The dosage of anti-diabetic drugs may need to be adjusted.

To:
Glycaemic control may be disturbed (i.e. hyperglycemia, hypoglycemia, 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.

4.8       Undesirable effects

From:
Endocrine disorders: Inappropriate antidiuretic hormone secretion.

Reproductive system and breast disorders: Anorgasmia.

To:
Endocrine disorders: Hyperprolactinemia, inappropriate antidiuretic hormone secretion.

Reproductive system and breast disorders: Anorgasmia, menstrual disorders (such as amenorrhea, hypomenorrhea, metrorrhagia, menorrhagia).

4.9       Overdose

From:
Treatment
There is no specific antidote to fluvoxamine. In case of overdose the stomach should be emptied as soon as possible after tablet ingestion and symptomatic treatment should be given. The repeated use of medicinal charcoal, if necessary accompanied by an osmotic laxative, is also recommended. Forced diuresis or dialysis are unlikely to be of benefit.

To:
Treatment
There is no specific antidote to fluvoxamine. In case of overdose the stomach should be emptied as soon as possible after tablet ingestion and symptomatic treatment should be given. The repeated use of medicinal charcoal, if necessary accompanied by an osmotic laxative, is also recommended. Forced diuresis or dialysis is unlikely to be of benefit.

6.6       Special precautions for disposal

From:
No special requirements.

To:
No special recommendation.

Section 3:  Solvay corporate logo “S (with triangle”) has been removed.

The following sections have been updated;

Section 4.6: Pregnancy, Breastfeeding & Fertility sub headings introduced, animal reproductive toxicity study data included and related advisory given, neonatal withdrawal symptoms provided

From:

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 1000 pregnancies. In the general population 1 to 2 cases of PPHN per 1000 pregnancies occur.

Reproduction studies in animals at high doses revealed no evidence of impaired fertility, reproductive performance or teratogenic effects in the offspring. Caution should be exercised when prescribing to pregnant women.

Isolated cases of withdrawal symptoms in the newborn child have been described after the use of fluvoxamine at the end of pregnancy.

Fluvoxamine is excreted via human milk in small quantities. Therefore, the drug should not be used by women who breast feed.

To:

Pregnancy

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 1000 pregnancies. In the general population 1 to 2 cases of PPHN per 1000 pregnancies occur.

Reproduction toxicity studies in animals revealed treatment related increases in embryotoxicity (embryofetal death, fetal eye abnormalities). The relevance to humans is unknown.  The safety margin for reproductive toxicity is unknown (see section 5.3).

Faverin should not be used during pregnancy unless the clinical condition of the woman requires treatment with fluvoxamine.

Isolated cases of withdrawal symptoms in the newborn child have been described after the use of fluvoxamine at the end of pregnancy.

Some newborns experience feeding and/ or respiratory difficulties, seizures, temperature instability, hypoglycaemia, tremor, abnormal muscle tone, jitteriness, cyanosis, irritability, lethargy, somnolence, vomiting, difficulty in sleeping and constant crying after third trimester exposure to SSRIs and may require prolonged hospitalization.

Breastfeeding

Fluvoxamine is excreted via human milk in small quantities. Therefore, the drug should not be used by women who breast feed.

Fertility
Reproductive toxicity studies in animals have shown that Faverin impairs male and female fertility. The safety margin for this effect was not identified.  The relevance of these findings to humans is unknown (see section 5.3).

Faverin should not be used in patients attempting to conceive unless the clinical condition of the patient requires treatment with fluvoxamine.

Section 4.8

From :

General disorders and administration site conditions: drug withdrawal syndrome including drug withdrawal syndrome neonatal.

To:

General disorders and administration site conditions: drug withdrawal syndrome including drug withdrawal syndrome neonatal (see section 4.6 Fertility, Pregnancy and Lactation).

Section 5.3

From :

There is no evidence of carcinogenicity, mutagenicity or impairment of fertility with fluvoxamine.

Reproduction studies in animals at high doses revealed no evidence of impaired fertility, reproductive performance or teratogenic effects in the offspring.

The potential for abuse, tolerance and physical dependence has been studied in a non-human primate model. No evidence of dependency phenomena was found.

To:

There is no evidence of carcinogenicity or mutagenicity with fluvoxamine.

Reproductive toxicity studies in rats have shown that fluvoxamine impairs male and female fertility (reduced sperm counts, increased ovary weights and reduced fertility), and is embryotoxic (increased embryofetal death [resorptions], increased fetal eye abnormalities [folded retina], reduced fetal weights and delayed ossification). The effects on fetal weights and ossification are likely to be secondary to maternal toxicity (reduced maternal bodyweight and bodyweight gain). The safety margin for reproductive toxicity is unknown.

The potential for abuse, tolerance and physical dependence has been studied in a non-human primate model. No evidence of dependency phenomena was found.

The following sections have been updated;

Section 4.3

The following has been updated as highlighted;

Faverin tablets are contraindicated in combination with tizanidine and monoamine oxidase inhibitors (MAOIs) (see section 4.5).

Section 4.4

This section has been updated to include sub-headings

Section 4.5

The warfarin section has been moved and given its own sub-heading and subsequent information on cytochrome P-450 isozymes added.

Warfarin:

When given with fluvoxamine, warfarin plasma concentrations were significantly increased and prothrombin times prolonged.

The cytochrome P-450 isozymes involved in the metabolism of warfarin include 2C9, 2C19, 2C8, 2C18, 1A2, and 3A4. 2C9 is likely to be the principal form of human liver P-450 which modulates the in vivo anticoagulant activity of warfarin.

Section 4.6

This section has been updated to include the risk of PPHN.

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 1000 pregnancies. In the general population 1 to 2 cases of PPHN per 1000 pregnancies occur.

Section 4.8

This section has been updated with the SPC guidelines and the undesirable effects tabulated according to the MedDRA system organ class and ranked under headings of frequency.

Additionally, risk of bone fractures and micturition disorders have been added as below;

Renal and urinary disorders: micturition disorder (including urinary retention, urinary incontinence, pollakiura, nocturia and enuresis)

Class effects: Epidemiological studies, mainly conducted in patients 50 years of age and older, show an increased risk of bone fractures in patients receiving Selective Serotonin Reuptake Inhibitors (SSRIs) and Tricyclic Antidepressants (TCAs). The mechanism leading to this risk is unknown.

Section 6.4

Updated as indicated below;

Do not store above 25°C. 

Store in the original package.

In section 7, the name of the Marketing Authorisation Holder has been changed to Abbott Healthcare Products Ltd.