Optimax

1. Name Of The Medicinal Product

Optimax Tablets 500 mg

2. Qualitative And Quantitative Composition

Each tablet contains 500 mg L-tryptophan.

For excipients, see section 6.1.

3. Pharmaceutical Form

Tablet

White, capsule-shaped, engraved with 'OPT' on one side, break line on the reverse

4. Clinical Particulars

4.1 Therapeutic Indications

In 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 by hospital specialists. Patients may subsequently be prescribed Optimax in the community by their general practitioner.

4.2 Posology And Method Of Administration

For oral use

Adults: The usual dose is two tablets, 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.

Children: Not recommended. Safety has not been established.

4.3 Contraindications

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.

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

4.4 Special Warnings And Precautions For Use

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. Various investigations have not as yet identified the aetiological factors precisely.

The symptoms of EMS have been reported to include eosinophilia, arthralgia or myalgia, fever, dyspnoea, neuropathy, peripheral oedema 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.

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).

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Where L-tryptophan is combined with an MAO Inhibitor the side effects of the latter may be enhanced. Use of L-tryptophan in combination with a 5HT reuptake inhibitor has the potential for increasing the severity of the adverse effects of the latter and could lead to serotonin syndrome (see Section 4.4).

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

4.6 Pregnancy And Lactation

Safety in pregnancy or lactation has not been established

4.7 Effects On Ability To Drive And Use Machines

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

4.8 Undesirable Effects

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).

4.9 Overdose

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

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Antidepressants

ATC Code: NO6A X 02

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.

5.2 Pharmacokinetic Properties

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.

5.3 Preclinical Safety Data

None reported

6. Pharmaceutical Particulars

6.1 List Of Excipients

Sta-RX Starch,

maize starch,

Explotab,

saccharin sodium,

magnesium stearate,

Aerosil

6.2 Incompatibilities

None known

6.3 Shelf Life

3 years

6.4 Special Precautions For Storage

None

6.5 Nature And Contents Of Container

Polypropylene bottle containing 84 tablets

6.6 Special Precautions For Disposal And Other Handling

Not applicable

7. Marketing Authorisation Holder

Merck Serono Ltd

Bedfont Cross, Stanwell Road

Feltham, Middlesex,

TW14 8NX, UK

8. Marketing Authorisation Number(S)

PL 11648/0084

9. Date Of First Authorisation/Renewal Of The Authorisation

11/01/82 / 08/07/02

10. Date Of Revision Of The Text

9 October 2009