Optimax

Optimax 500 mg capsules

Each capsule contains 500 mg L-tryptophan.

For the full list of excipients, see section 6.1

Capsule, hard.

White hard gelatin capsules (size 00), filled with white to off-white granular powder.

Treatment-resistant depression after trials of standard antidepressant drug treatments and as an adjunct to other anti-depressant medication.

Treatment with Optimax should only be initiated in adults by hospital specialists. Patients may subsequently be prescribed Optimax in the community by their general practitioner.

Posology

For oral use.

Paediatric population

The safety and efficacy of Optimax in children have not been established.

Adults

The usual dose is two capsules, three times daily; for some patients, up to 6g L- tryptophan may be required.

Elderly

A lower dose may be appropriate, especially where there is evidence of renal or hepatic impairment.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Patients with a previous history of eosinophilia myalgia syndrome (EMS) following the use of L-tryptophan. This syndrome, which is a multisystem disorder, is characterised by raised eosinophils (>1.0 x 10⁹/L), and severe myalgia in the absence of either an infectious or neoplastic cause. (see sections 4.4 and 4.8)

Patients with a known hypersensitivity to the active substance or any of the excipients.

Suicide/suicidal thoughts or clinical worsening

Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.

Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old.

Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.

Eosinophilia Myalgia Syndrome

Eosinophilia Myalgia Syndrome (EMS) has been reported in association with the use of oral L-tryptophan-containing products. It is a multisystem disorder which is usually reversible but, rarely, fatal. Products containing contaminants such as 1,1′- ethylidenebis[l-tryptophan] are suspected to cause EMS. An immunogenetic susceptibility can not be ruled out. Various investigations have not as yet identified the aetiological factors precisely.

The symptoms of EMS have been reported to include eosinophilia, arthralgia, myalgia, myopathy, fever, dyspnoea, neuropathy, sedation, somnolence, drowsiness, peripheral oedema, asthenia, fatigue, increase of hepatic transaminases, rash and skin lesions which can include sclerosis or papular and urticarial lesions.

Caution should be exercised with patients who experience some but not all of the symptoms of EMS after taking L-tryptophan. Treatment should be withheld and the symptoms investigated until the possibility of EMS can be excluded. (see sections 4.3 and 4.8)

Serotonin syndrome

The possible interaction between L-tryptophan and 5HT reuptake inhibitors could lead to the “serotonin syndrome” characterised by a combination of agitation, restlessness and gastro-intestinal symptoms including diarrhoea. Combinations with 5HT reuptake inhibitors should only be used with care (see Section 4.5).

Where L-tryptophan is combined with MAO Inhibitors such as phenelzine, moclobemide and tranylcypromine the side effects of the latter may be enhanced.

Use of L-tryptophan in combination with SSRI such as dapoxitine, citalopram fluoxetine, and paroxetine has the potential for increasing the severity of the adverse effects of SSRIs and could lead to serotonin syndrome (see Section 4.4). The potential for this may also occurs with SNRIs such as duloxetine, and the appetite suppressant sibutramine.

Plasma levels of levodopa have been reduced significantly when L-tryptophan (1g) was used concurrently with levodopa (500mg).

In patients taking L-tryptophan in conjunction with phenothiazines or benzodiazepines there have been isolated reports of sexual disinhibition

No clinical data on exposed pregnancies are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/ fetal development, parturition or postnatal development (see section 5.3).

Caution should be exercised when prescribing to pregnant women.

Due to the absence of any clinical data relating to the use of Optimax in nursing mothers, Optimax should not be taken during breast feeding.

No data relating to fertility are available for Optimax.

L-tryptophan may produce drowsiness. Patients who drive and operate machinery should be warned of the possible hazard.

In some patients, L-tryptophan may cause a slight feeling of nausea which usually disappears within 2 or 3 days. Such nausea can be minimised by giving L-tryptophan after food. Other adverse reactions include headache and light-headedness.

Cases of suicidal ideation and suicidal behaviours (frequency not known) have been reported during L-tryptophan therapy or early after treatment discontinuation (see section 4.4).

Cases of Eosinophilia Myalgia Syndrome (EMS) (see section 4.4) have been reported. Please refer to section 4.4 for additional symptoms associated with the development of EMS. The frequency of these events is unclear from the available data but no further new reported instances have appeared for over 20 years.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Drowsiness and vomiting may occur; supportive measures should be employed.

Pharmacotherapeutic group: Antidepressants

ATC Code: N06AX02

L-tryptophan is an essential dietary amino acid and, following hydroxylation and decarboxylation, is the major source of 5-hydroxytryptamine (5-HT). L-tryptophan, 5-HT and 5-HT metabolite levels are lower than normal in patients with depression.

Administration of L-tryptophan re-establishes the inhibitory action of 5-HT on the amygdaloid nuclei, thereby reducing feelings of anxiety and depression.

L-tryptophan is readily absorbed after oral administration. The elimination half-life when administered orally or intravenously to healthy humans is in the range of 1-3 hours. L-tryptophan is bound to plasma proteins to a large extent and is eliminated primarily by metabolism.

There are no preclinical data of relevance to the prescriber, which are additional to those already included in other sections of the SmPC.

Povidone K30

Sodium starch glycolate

Silica colloidal anhydrous

Magnesium stearate

Capsule excipients:

Gelatin

Titanium dioxide (E171)

None known.

2 years.

Use within three months of the first opening.

None

Polypropylene container, with a low-density polyethylene cap, of 84 capsules.

Not applicable

Esteve Pharmaceuticals Ltd,

The Courtyard Barns,

Choke Lane, Cookham Dean,

Maidenhead,

Berkshire,

SL6 6PT,

UNITED KINGDOM

PLGB 17509/0093

24/05/2022

27/10/2022