L-Tryptophan (Systemic)


VA CLASSIFICATION
Primary: CN900

Commonly used brand name(s): Alti-Tryptophan.

Another commonly used name is:
Tryptophan Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

*Not commercially available in the U.S.



Category:


Antidepressant therapy adjunct—

antimanic—

Indications

Accepted

Depression, mental (treatment)— L-tryptophan is indicated as an adjunct to antidepressant drug treatment in the management of patients suffering from depressive disorders.{01}

Bipolar disorder (treatment)— L-tryptophan is indicated as an adjunct to treatment with lithium in the management of patients with bipolar disorder. An added effect may be seen when L-tryptophan is given in combination with lithium in bipolar patients with mania or depression for whom lithium alone or in combination with neuroleptics or tricyclics has not been effective. Adjunctive use of L-tryptophan may reduce the need for higher doses of lithium.{01}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    204.23{01}

Solubility
    L-tryptophan is soluble in 11.4 grams in 1 liter of water, slightly soluble in alcohol; practically insoluble in chloroform and ether; soluble in hot alcohol and solutions of dilute acids and alkali hydroxides {01}.


pH
    A 1% solution in water has a pH of 5.5 to 7.0 {01}.

Mechanism of action/Effect:

The antidepressant effects of L-tryptophan are related to it's ability to increase serotonin (5–HT) synthesis in the central nervous system (CNS). Clinical trials have shown that L-tryptophan causes a significant increase in the level of the serotonin metabolite, 5–hydroxyindoleacetic acid, in the lumbar cerebrospinal fluid, indicating an increased turnover of serotonin in the CNS {01}.


Other actions/effects:

L-tryptophan is one of the eight essential amino acids. The minimum daily requirements are thought to be 0.25 grams for males and 0.15 grams for females {01}.

Biotransformation:

The two major metabolic pathways for L-tryptophan result in production of serotonin and nicotinic acid. Approximately 98% of dietary L-tryptophan is metabolized into nicotinic acid and only a very small amount is metabolized into serotonin via the intermediary stage of 5–hydroxy-tryptophan (5–HTP). Tryptophan hydroxylase, the enzyme responsible for this step, is the rate-limiting enzyme for serotonin production and is normally only about half-saturated. Central nervous system serotonin is metabolized by monoamine oxidase to 5–HIAA {01}.


Precautions to Consider

Carcinogenicity/Tumorigenicity

Tests designed to provoke urinary bladder tumors by oral or subcutaneous administration of L-tryptophan or its metabolites, have generally been negative. Male and female rats and mice given large supplements of L-tryptophan for prolonged periods did not show a statistically significant occurrence of neoplasms as compared to controls. Under the bio-assay, L-tryptophan was not carcinogenic for the strains of animals used. L-tryptophan and its tested metabolites have not exhibited intrinsic carcinogenic action. However, L-tryptophan has been reported to promote or inhibit the carcinogenic action of a variety of known carcinogens{01}.

Pregnancy/Reproduction

Pregnancy—
Adequate and well-controlled studies in humans have not been done.

Breast-feeding

It is not known whether L-tryptophan is distributed into breast milk. However, problems in humans have not been documented.

Pediatrics

No information is available on the relationship of age to the effects of L-tryptophan in the pediatric population.


Geriatrics


No information is available on the relationship of age to the effects of L-tryptophan in geriatric patients.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

Fluoxetine or
» Lithium or
» Monoamine oxidase (MAO) inhibitors or
Antidepressants, other    (concurrent use with L-tryptophan may increase the incidence and severity of adverse effects, including serotonin syndrome; lower doses of L-tryptophan and/or the concomitant medicine may be needed {01})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
Achlorhydria or
Malabsorption    (in ruminants, bacterial conversion of L-tryptophan to skatole (3–methylindole) caused pulmonary edema and emphysema; this is normally not a concern in humans except with achlorhydria or malabsorption{01})


Bladder cancer    (to minimize the risk of bladder cancer, vitamin B6 supplements are recommended if L-tryptophan doses are many times in excess of those consumed normally in dietary protein {01})


Cataracts    (photooxidation of L-tryptophan and some of its metabolites, such as kynurenine, may make patients more susceptible to cataract formation, particularly if exposed to ultraviolet light {01})


Diabetes mellitus, history of    (the L-tryptophan metabolite, xanthurenic acid, is diabetogenic in animals; use with caution in patients with a family history of diabetes {01})


» Sensitivity to L-tryptophan


Side/Adverse Effects

Those indicating need for medical attention
    
Serotonin syndrome{01} ( agitation; confusion; diarrhea; fever; increased sweating; mood or behavior changes; overactive reflexes; poor coordination; racing heartbeat; restlessness; shivering or shaking)


Those indicating need for medical attention only if they continue or are bothersome
    
Anorexia {01}(loss of appetite)—occurs with doses greater than 9 grams a day
    
dizziness {01}—occurs with doses greater than 9 grams a day
    
drowsiness {01}— occurs with doses less than 5 grams a day
    
dry mouth {01}—occurs with doses less than 5 grams a day
    
headache {01}—occurs with doses greater than 9 grams a day
    
nausea {01}—occurs with doses greater than 9 grams a day
    
sexual disinhibition {01}(loss of control in sexual behavior)




Overdose
For more information on the management of overdose or unintentional ingestion, contact a poison control center (see Poison Control Center Listing).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
    
Serotonin syndrome {01}(agitation; confusion; diarrhea ; fever; overactive reflexes; poor coordination; restlessness; shivering ; sweating; talking or acting with excitement you cannot control; trembling or shaking; twitching)
    
vomiting {01}


Treatment of overdose
There is no known specific antidote to L-tryptophan. Treatment is generally symptomatic and supportive{01}.
Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, L-Tryptophan (Systemic).
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to L-tryptophan

Carcinogenicity/Tumorigenicity
L-tryptophan may promote or inhibit the carcinogenic action of a variety of known carcinogens
Other medications, especially lithium and monoamine oxidase (MAO) inhibitors
Other medical problems

Proper use of this medication
Take with a low-protein, carbohydrate-rich meal or snack to reduce the incidence of nausea.

» Proper dosing
Taking as soon as possible; not taking if almost time for next scheduled dose; not doubling doses

Proper storage

Precautions while using this medication
Avoid excessive exposure to ultraviolet light to reduce the risk of cataract formation

» Caution if dizziness or drowsiness occurs; not driving, using machines, or doing anything else that requires alertness while taking L-tryptophan and for 24 hours after discontinuing it

Possible dryness of mouth; using sugarless candy or gum, ice or saliva substitute for relief; checking with physician or dentist if dry mouth continues for more than 2 weeks


Side/adverse effects
Signs of potential side effects, especially serotonin syndrome


General Dosing Information
To minimize the risk of bladder cancer, it may be recommended to give vitamin B6 (pyridoxine) supplements if the L-tryptophan doses are many times in excess of those consumed normally in dietary protein {01}.

Diet/Nutrition
Take with a low-protein, carbohydrate-rich meal or snack to reduce the incidence of nausea {01}.


Oral Dosage Forms

L-TRYPTOPHAN * TABLETS

Usual adult and adolescent dose
Depression, mental (treatment adjunct)
Oral, 8 to 12 grams per day, given in 3 to 4 equally divided doses{01}.

Note: The dose and frequency of administration may have to be adjusted to the patient's need and tolerance. Lower doses may be effective in combination with other antidepressants {01}.
Patients on concomitant medication should be monitored for possible reduction of the concomitant medication since L-tryptophan may enhance their efficacy {01}.
When used in conjunction with lithium, L-tryptophan may potentiate some of the side effects associated with lithium. It may be necessary to decrease the lithium dose. Lithium levels should be monitored for at least two weeks after the addition of L-tryptophan{01}.



Usual adult and adolescent prescribing limits
Up to 12 grams per day {01}.

Usual pediatric Dose
Safety and efficacy have not been established

Usual geriatric Dose
See Usual adult and adolescent dose.

Usual geriatric prescribing limits
See Usual adult and adolescent prescribing limits .

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


500 mg (Rx) [Alti-Tryptophan (OTC) (calcium phosphate) (crosscarmelose sodium) (magnesium stearate) (methylcellulose ) (wax solution (white wax, carnauba wax)) (opaspray white) (film coating base solution (includes: acetylated monoglyceride, hydroxy-propylmethyl cellulose, povidone, titanium dioxide))]


1 gram (Rx) [Alti-Tryptophan (OTC) (calcium phosphate) (crosscarmelose sodium) (magnesium stearate) (methylcellulose ) (wax solution (white wax, carnauba wax)) (opaspray white) (film coating base solution (includes: acetylated monoglyceride, hydroxy-propylmethyl cellulose, povidone, titanium dioxide))]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F). Protect from heat and light.{01}

Auxiliary labeling:
   • May cause dizziness or drowsiness.
   • Take with a meal or snack.


L-TRYPTOPHAN * CAPSULES

Usual adult and adolescent dose
See L-tryptophan Tablets

Usual adult and adolescent prescribing limits
See L-tryptophan Tablets

Usual pediatric Dose
Safety and efficacy have not been established

Usual geriatric Dose
See L-tryptophan Tablets

Usual geriatric prescribing limits
See L-tryptophan Tablets

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


500 mg (Rx) [Alti-Tryptophan (OTC) (magnesium stearate) (talc)]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F). Protect from heat and light.{01}

Auxiliary labeling:
   • May cause dizziness or drowsiness.
   • Take with a meal or snack.



Developed: 09/07/2000
Revised: 09/07/2000



References
  1. Product Information: Alti-Tryptophan®, L-tryptophan. AltiMed Pharmaceutical Company, Mississauga, Ontario, Canada, (PI revised 5/1999) reviewed 8/2000.
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