Drugs List

Therapeutic Indications

Uses

Treatment of Parkinson's disease and symptomatic parkinsonism.
Monotherapy to delay the need for levodopa therapy (with or without a decarboxylase inhibitor)
Adjunct therapy in combination with levodopa (with or without a decarboxylase inhibitor).

Administration

For oral administration

Contraindications

Breastfeeding ( see Lactation )
Pregnancy ( see Pregnancy )
Children under 18 years
Gastric ulcer and or duodenal ulcer
Within 5 weeks of discontinuing fluoxetine or 2 weeks of other SSRIs
Within 2 weeks of discontinuing MAOIs
Extrapyramidal disorders not related to dopamine deficiency

Precautions and Warnings

Administer with caution in patients with:
History of peptic ulcer.
Labile hypertension
Cardiac arrhythmias
Severe angina pectoris
Psychosis
Severe renal impairment

In patients with severe hepatic impairment or a history of hepatic dysfunction - caution is recommended. Transient or continuing abnormalities with a tendency for elevated plasma concentrations of liver enzymes have been described during long term therapy with conventional tablets of selegiline.

In higher doses (more than 10mg daily) the selectivity of selegiline begins to diminish resulting in increased inhibition of MAO-A. Thus in higher doses there is a risk of hypertension after ingestion of tyramine rich food.

Concomitant treatment with medicines which inhibit MAO - A, (or non-selective MAO inhibitors) can cause hypotensive reactions. Hypotension, sometimes sudden in onset, has been reported with conventional selegiline.

Since selegiline potentiates the effects of levodopa, the adverse effects of levodopa may be increased. When selegiline is added to the maximum tolerated dose of levodopa, involuntary movements and agitation may occur. Levodopa should be reduced by about 10-30% when selegiline is added to the treatment. When an optimum dose of levodopa is reached, adverse effects from the combination are less than those observed with levodopa on its own. Selegiline in combination with levodopa may not be beneficial in patients who experience fluctuations in response.

Parkinson's disease patients treated with dopamine agonists and other dopaminergic treatments have been reported as exhibiting impulse control disorders and compulsions like pathological gambling, increased libido, hypersexuality, binge eating, shopping and different kinds of compulsive/repetitive activities. These may also be possible with selegiline but very few cases have been reported.

Avoid abrupt withdrawal.

Selegiline is a specified stimulant and is listed in the World Anti-Doping Code 2010 prohibited list as a substance prohibited in competition.

Some formulations contain sucrose, therefore should be used with caution in patients with hereditary fructose intolerance and glucose-galactose malabsorption syndrome.

Different formulations are not bioequivalent.

Patients are advised to avoid alcohol.

Side effects may impair the patients ability to drive and or operate machinery.

Use in Porphyria

Some sources such as NAPOS indicate selegiline as unsuitable for use in porphyria as it probably porphyrinogenic.

Pregnancy and Lactation

Pregnancy

Contraindicated as data is insufficient for risk assessment in human pregnancy. Until additional human data is available, the use of selegiline during pregnancy should be avoided.

It is not known if selegiline crosses the human placenta. The low molecular weight suggests that passage to the embryo and foetus should be expected.

Schaefer (2007) advises that inadvertent use of a Parkinson drug not belonging to the broadly used ergotamine derivatives is not grounds for termination of pregnancy or for invasive diagnostic procedures. Detailed foetal ultrasonography may be considered where first-trimester exposure to less-used drugs has occurred.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Licensed in pregnancy? - No, contraindicated.

Recommended for use in pregnancy? - No.

Lactation

Contraindicated as there is insufficient experience on the use of selegiline during breastfeeding and no data are available on the transfer of selegiline into human milk.

The low molecular weight suggests that excretion into human breast milk should be expected. The effects of this exposure on a nursing infant are unknown. The safest course is to avoid selegiline during breastfeeding until the amount of drug in human milk has been determined. MAO inhibitors require very careful use and have many food-drug and drug-drug interactions that could be dangerous to the mother or child.

Schaefer (2007) recommends that a case-by-case decision on breastfeeding must be made when therapy is urgently needed.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Drug excreted in breast milk? - Unknown but expected.

Considered suitable or recommended by manufacturer? - No.

Drug substance licensed in infants? - No.

Side Effects

Sleep disturbances
Confusion
Hallucinations
Hypersexuality
Dry mouth
Movement disturbances
Dyskinesia
Vertigo
Agitation
Headache
Cardiac arrhythmias
Postural hypotension
Nausea
Increase in aminotransferase level
Skin reactions
Constipation
Diarrhoea
Arthralgia
Myalgia
Chest pain
Akinesia
Angina pectoris
Ankle oedema
Anxiety
Back pain
Blurred vision
Bradykinesia
Decreased appetite
Depression
Dizziness
Dream abnormalities
Dyspnoea
Falls
Fatigue
Hair loss
Hypertension
Hypotension
Increased sweating
Irritability
Leucopenia
Loss of balance
Micturition disorders
Mouth ulcers
Muscle cramps
Myopathy
Nasal congestion
Palpitations
Pharyngitis
Psychosis
Skin eruption
Sore throat
Stomatitis
Thrombocytopenia
Tremor
Mood changes
Bradycardia
Supraventricular tachycardia
Urinary retention
Orthostatic hypertension
Increases in heptaic enzymes

Presentation

Tablets containing 5mg selegiline hydrochloride
Tablets containing 10mg selegiline hydrochloride
Oral solution containing 10mg per 5ml selegiline hydrochloride

Drugs List

Therapeutic Indications

Uses

Treatment of Parkinson's disease and symptomatic parkinsonism.
Monotherapy to delay the need for levodopa therapy (with or without a decarboxylase inhibitor)
Adjunct therapy in combination with levodopa (with or without a decarboxylase inhibitor).

Dosage

Adults

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Administration

For oral administration

Contraindications

Breastfeeding ( see Lactation )
Pregnancy ( see Pregnancy )
Children under 18 years
Gastric ulcer and or duodenal ulcer
Within 5 weeks of discontinuing fluoxetine or 2 weeks of other SSRIs
Within 2 weeks of discontinuing MAOIs
Extrapyramidal disorders not related to dopamine deficiency

Precautions and Warnings

Administer with caution in patients with:
History of peptic ulcer.
Labile hypertension
Cardiac arrhythmias
Severe angina pectoris
Psychosis
Severe renal impairment

In patients with severe hepatic impairment or a history of hepatic dysfunction - caution is recommended. Transient or continuing abnormalities with a tendency for elevated plasma concentrations of liver enzymes have been described during long term therapy with conventional tablets of selegiline.

In higher doses (more than 10mg daily) the selectivity of selegiline begins to diminish resulting in increased inhibition of MAO-A. Thus in higher doses there is a risk of hypertension after ingestion of tyramine rich food.

Concomitant treatment with medicines which inhibit MAO - A, (or non-selective MAO inhibitors) can cause hypotensive reactions. Hypotension, sometimes sudden in onset, has been reported with conventional selegiline.

Since selegiline potentiates the effects of levodopa, the adverse effects of levodopa may be increased. When selegiline is added to the maximum tolerated dose of levodopa, involuntary movements and agitation may occur. Levodopa should be reduced by about 10-30% when selegiline is added to the treatment. When an optimum dose of levodopa is reached, adverse effects from the combination are less than those observed with levodopa on its own. Selegiline in combination with levodopa may not be beneficial in patients who experience fluctuations in response.

Parkinson's disease patients treated with dopamine agonists and other dopaminergic treatments have been reported as exhibiting impulse control disorders and compulsions like pathological gambling, increased libido, hypersexuality, binge eating, shopping and different kinds of compulsive/repetitive activities. These may also be possible with selegiline but very few cases have been reported.

Avoid abrupt withdrawal.

Selegiline is a specified stimulant and is listed in the World Anti-Doping Code 2010 prohibited list as a substance prohibited in competition.

Some formulations contain sucrose, therefore should be used with caution in patients with hereditary fructose intolerance and glucose-galactose malabsorption syndrome.

Different formulations are not bioequivalent.

Patients are advised to avoid alcohol.

Side effects may impair the patients ability to drive and or operate machinery.

Use in Porphyria

Some sources such as NAPOS indicate selegiline as unsuitable for use in porphyria as it probably porphyrinogenic.

Pregnancy and Lactation

Pregnancy

Contraindicated as data is insufficient for risk assessment in human pregnancy. Until additional human data is available, the use of selegiline during pregnancy should be avoided.

It is not known if selegiline crosses the human placenta. The low molecular weight suggests that passage to the embryo and foetus should be expected.

Schaefer (2007) advises that inadvertent use of a Parkinson drug not belonging to the broadly used ergotamine derivatives is not grounds for termination of pregnancy or for invasive diagnostic procedures. Detailed foetal ultrasonography may be considered where first-trimester exposure to less-used drugs has occurred.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Licensed in pregnancy? - No, contraindicated.

Recommended for use in pregnancy? - No.

Lactation

Contraindicated as there is insufficient experience on the use of selegiline during breastfeeding and no data are available on the transfer of selegiline into human milk.

The low molecular weight suggests that excretion into human breast milk should be expected. The effects of this exposure on a nursing infant are unknown. The safest course is to avoid selegiline during breastfeeding until the amount of drug in human milk has been determined. MAO inhibitors require very careful use and have many food-drug and drug-drug interactions that could be dangerous to the mother or child.

Schaefer (2007) recommends that a case-by-case decision on breastfeeding must be made when therapy is urgently needed.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Drug excreted in breast milk? - Unknown but expected.

Considered suitable or recommended by manufacturer? - No.

Drug substance licensed in infants? - No.

Effects on Ability to Drive and Operate Machinery

This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988 (England and Wales). When prescribing this medicine: Advise patient the medicine can affect cognitive function and is likely to affect ability to drive. Advise patient not to drive until they know how the medicine affects them.

Counselling

Advise patients to avoid the concomitant use of alcohol.

Advise patients about tyramine rich foods.

Advise patients that side effects may impair their ability to drive or operate machinery.

Side Effects

Sleep disturbances
Confusion
Hallucinations
Hypersexuality
Dry mouth
Movement disturbances
Dyskinesia
Vertigo
Agitation
Headache
Cardiac arrhythmias
Postural hypotension
Nausea
Increase in aminotransferase level
Skin reactions
Constipation
Diarrhoea
Arthralgia
Myalgia
Chest pain
Akinesia
Angina pectoris
Ankle oedema
Anxiety
Back pain
Blurred vision
Bradykinesia
Decreased appetite
Depression
Dizziness
Dream abnormalities
Dyspnoea
Falls
Fatigue
Hair loss
Hypertension
Hypotension
Increased sweating
Irritability
Leucopenia
Loss of balance
Micturition disorders
Mouth ulcers
Muscle cramps
Myopathy
Nasal congestion
Palpitations
Pharyngitis
Psychosis
Skin eruption
Sore throat
Stomatitis
Thrombocytopenia
Tremor
Mood changes
Bradycardia
Supraventricular tachycardia
Urinary retention
Orthostatic hypertension
Increases in heptaic enzymes

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Shelf Life and Storage

Storage requirements vary according to formulation

Tablets:
Do not store above 25 degrees C.
Store in the original container.
Keep container tightly closed.

Syrup:
No special precautions.

Further Information

Last full review date: January 2013

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Eldepryl Syrup 10mg/5ml. Orion Pharma (UK) Ltd. Revised February 2012.
Summary of Product Characteristics: Eldepryl Tablets 10mg. Orion Pharma (UK) Ltd. Revised February 2012.
Summary of Product Characteristics: Eldepryl Tablets 5mg. Orion Pharma (UK) Ltd. Revised February 2012.

Gov.uk. Government departments. Department for Transport. Publications. Drug driving and medicine: advice for healthcare professionals. Drug driving: Guidance for healthcare professionals on drug driving. Available at: https://www.gov.uk Last accessed: 6 January 2015 New drug driving offence implications for medicines packaging. Medicines Regulatory News. 10 December 2013. Available at: https://www.mhra.gov.uk Last accessed: 6 January 2015

Napos. The drug database for acute porphyria.
Available at https://www.drugs-porphyria.org/languages/UnitedKingdom/s1.php?l=gbr
Selegiline Last revised: October 1, 2004.
Last accessed: November 17, 2011.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 05 September 2017

The World Anti-Doping Code. The 2010 Prohibited list. International Standard.
https://www.wada-ama.org/Documents/World_Anti-Doping_Program/WADP-Prohibited-list/WADA_Prohibited_List_2010_EN.pdf
last accessed 28th July 2010.