Duloxetine Zentiva 30 mg 60mg gastro-resistant hard capsules

4.4     Special warnings and precautions for use

Serotonin syndrome

As with other serotonergic agents, serotonin syndrome, a potentially life-threatening condition, may occur with duloxetine treatment, particularly with concomitant use of other serotonergic agents (including SSRIs, SNRIs tricyclic antidepressants or triptans), with agents that impair metabolism of serotonin such as MAOIs, with antipsychotics or other dopamine antagonists or with buprenorphine (with or without naloxone), tramadol and pethidine that may affect the serotonergic neurotransmitter systems (see sections 4.3 and 4.5).

 

Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g. hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea).

4.5     Interaction with other medicinal products and other forms of interaction

 

Serotonergic agents

In rare cases, serotonin syndrome has been reported in patients using SSRIs/SNRIs concomitantly with serotonergic agents. Caution is advisable if duloxetine is used concomitantly with serotonergic agents like SSRIs, SNRIs, tricyclic antidepressants like clomipramine or amitriptyline, MAOIs like moclobemide or linezolid, St. John’s wort (Hypericum perforatum) or triptans, buprenorphine, tramadol, pethidine and tryptophan (see section 4.4).

 

 

If concomitant treatment with duloxetine and other serotonergic agents that may affect the serotonergic and/or dopaminergic neurotransmitter systems is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases.

 

If serotonin syndrome is suspected, a dose reduction or discontinuation of therapy should be considered depending on the severity of the symptoms.

 

4.6     Fertility, pregnancy and lactation

 

Fertility

In animal studies, duloxetine had no effect on male fertility, and effects in females were only evident at doses that caused maternal toxicity.

 

Pregnancy

Studies in animals have shown reproductive toxicity at systemic exposure levels (AUC) of duloxetine lower than the maximum clinical exposure (see section 5.3).

 

Two large observational studies do not suggest an overall increased risk of major congenital malformation (one from the US including 2,500 exposed to duloxetine during the first trimester and one from the EU including 1,500 exposed to duloxetine during the first trimester). The analysis on specific malformations such as cardiac malformations shows inconclusive results.

 

In the EU study, maternal exposure to duloxetine during late pregnancy (at any time from 20 weeks gestational age to delivery) was associated with an increased risk for preterm birth (less than 2-fold, corresponding to approximately 6 additional premature births per 100 women treated with duloxetine late in pregnancy). The majority occurred between 35 and 36 weeks of gestation. This association was not seen in the US study.

 

The US observational data have provided evidence of an increased risk (less than 2-fold) of postpartum haemorrhage following duloxetine exposure within the month prior to birth.