Almotriptan Orifarm 12,5 mg Filmdragerad tablett

Sverige - svenska - Läkemedelsverket (Medical Products Agency)

Bipacksedel Bipacksedel (PIL)

20-04-2018

Produktens egenskaper Produktens egenskaper (SPC)

21-01-2020

Aktiva substanser:
almotriptanmalat
Tillgänglig från:
Orifarm Generics A/S
ATC-kod:
N02CC05
INN (International namn):
almotriptanmalat
Dos:
12,5 mg
Läkemedelsform:
Filmdragerad tablett
Sammansättning:
almotriptanmalat 17,5 mg Aktiv substans; mannitol Hjälpämne
Receptbelagda typ:
Receptbelagt
Produktsammanfattning:
Förpacknings: Blister, 2 tabletter; Blister, 3 tabletter; Blister, 4 tabletter; Blister, 6 tabletter; Blister, 7 tabletter; Blister, 9 tabletter; Blister, 12 tabletter; Blister, 14 tabletter; Blister, 18 tabletter
Bemyndigande status:
Godkänd
Godkännandenummer:
55088
Tillstånd datum:
2017-08-21

Dokument på andra språk

Bipacksedel Bipacksedel - engelska

06-07-2017

Produktens egenskaper Produktens egenskaper - engelska

21-01-2020

Offentlig bedömningsrapport Offentlig bedömningsrapport - engelska

21-08-2017

Läs hela dokumentet

Package leaflet: Information for the user

Almotriptan Orifarm 12. 5 mg film-coated tablets

almotriptan

Read all of this leaflet carefully before you start taking this medicine because it contains important

information for you.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor, pharmacist or nurse.

This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if

their signs of illness are the same as yours.

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side

effects not listed in this leaflet. See section 4.

What is in this leaflet

What Almotriptan Orifarm is and what it is used for

What you need to know before you take Almotriptan Orifarm

How to take Almotriptan Orifarm

Possible side effects

How to store Almotriptan Orifarm

Contents of the pack and other information

1.

What Almotriptan Orifarm is and what it is used for

Almotriptan Orifarm is an antimigraine agent which belongs to a class of compounds known as selective

serotonin receptor agonists. Almotriptan Orifarm is believed to reduce the inflammatory response associated

with migraines by binding to the serotonin receptors in the brain (cranial) blood vessels and causing them to

narrow.

Almotriptan Orifarm is used to relieve headaches associate d with migraine attacks with or without aura.

2.

What you need to know before you take Almotriptan Orifarm

Do not take Almotriptan Orifarm:

if you are allergic to almotriptan or any of the other ingredients of this medicine (listed in section 6).

if you have or have ever suffered from diseases that restrict the blood supply to the heart such as:

- heart

attack

- chest pain or discomfort that normally occurs with activity or

stress

- heart problems without

pain

- chest pain that occurs when you are

resting

- severe hypertension (severe high blood

pressure)

- uncontrolled mild or moderate high blood

pressure.

if you have had a stroke or experienced a reduction in the blood flow to the brain

if you have had obstruction of the large arteries in the arms or legs (peripheral vascular disease)

if you are taking other medicines used to treat migraines including ergotamine, dihydroergotamine and

methysergide or other serotonin agonists (e.g. sumatriptan)

if you suffer from

severe

liver disease

Warnings and precautions

Talk to your doctor, pharmacist or nurse before taking Almotriptan Orifarm:

if your type of migraine has not been diagnosed

if you are allergic (hypersensitive) to antibacterial medicines mainly used for treatment of urinary

tract

infections

(sulphonamides)

if your headache symptoms are different from your usual attacks i.e. you have a noise in your ears

vertigo, you have short lived paralysis of one side of the body or paralysis of the muscles that control

movement or if you have any new

symptoms

if you are at risk of heart disease, this includes uncontrolled high blood pressure, high cholesterol, obesity,

diabetes, smoking, clear family history of heart disease , postmenopausal females or males over the age of 40

if you have mild to moderate liver

disease

if you suffer from

severe

kidney

disease

if you are over 65 years of age (as you are more likely to experience blood pressure increases)

If you are taking anti-depressants SSRIs (selective serotonin reuptake inhibitors) or SNRIs

(serotonin

noradrenaline reuptake inhibitors). Also see

Other medicines and Almotriptan Orifarm

below.

It has been suggested that excessive use of an anti-migraine medicinal product can lead to daily chronic

headache.

Children and adolescents

Children under the age of 18 should not take Almotriptan Orifarm.

Elderly (over the age of 65 years)

If you are over 65 years of age you should speak to your doctor before using this medicinal product.

Other medicines and Almotriptan Orifarm

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Please tell your doctor:

if you are taking medicines used to treat depression such as monoamino oxidase inhibitors (e.g. moclobemide),

selective serotonin reuptake inhibitors (e.g. fluoxetine) or serotonin noradrenaline reuptake inhibitors (e.g.

venlafaxine), as these may cause serotonin syndrome , a potentially life- threatening drug reaction. The

symptoms of serotonin syndrome include; confusion, restlessness, fever, sweating, uncoordinated movements of

the limbs or eyes, uncontrollable muscle twitches or diarrhoea.

if you are taking herbal St John’s Wort (

Hypericum perforatum

) as this may increase the likelihood of side

effects.

Almotriptan Orifarm should not be taken at the same time as ergotamine -containing medicines, which are

also used to treat migraine. However, the medicines may be taken after one another: provided a suitable

amount of time is left between taking each medicine

following use of almotriptan, it is advised to wait at least 6 hours before taking ergotamine.

following use of ergotamine, it is advised to wait at least 24 hours before taking

almotriptan.

Almotriptan Orifarm with food and drink

Almotriptan Orifarm should be swallowed with liquid (e.g. water) and can be taken with or without

food.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your

doctor or pharmacist for advice before taking this medicine.

Only very limited data is available for almotriptan in pregnant patients. Almotriptan Orifarm should only be

used during pregnancy if instructed by your doctor and only after they have carefully considered the benefits

and risks.

Caution should be taken when using this medicine whilst breast-feeding. You should avoid breast-feeding for

24 hours after taking this medicine.

Driving and using machines

Almotriptan Orifarm may cause drowsiness. If you are affected, you should not drive or use any tools or

machines.

3.

How to take Almotriptan Orifarm

Almotriptan Orifarm should only be used to treat an actual migraine attack and not to prevent migraine

attacks or headaches.

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or

pharmacist if you are not sure.

The recommended dose is:

Adults (18-65 years old)

The recommended dose is one 12.5 mg tablet which should be taken as early as possible after the onset of the

migraine attack. If your migraine attack does not subside, do not take more than one tablet for the same

attack.

If you experience a second migraine attack within 24 hours, a second 12.5 mg tablet can be taken but you

must leave

at least

two hours between your first and second tablet.

The maximum daily dose is two (12.5 mg) tablets within 24 hours.

Tablet(s) should be swallowed with liquid (e.g. water) and can be taken with or without food.

You should take Almotriptan Orifarm as soon as possible after the onset of the migraine, although it is still

effective if taken at a later stage.

Severe kidney disease

If you have severe kidney disease do not take more than one 12.5 mg tablet every 24 hours.

Use in children and adolescents

The use in children below the age of 18 is not recommended.

If you take more Almotriptan Orifarm than you should

If you accidentally take too many tablets, or if someone else or a child takes this medicine, talk to a doctor or

pharmacist immediately.

If you forget to take Almotriptan Orifarm

Take Almotriptan Orifarm as you have been prescribed. Do not take a double dose to make up for a forgotten

dose.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

4.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

During treatment with Almotriptan Orifarm, tell your doctor straight away:

if you have chest pain, tightness in your chest or throat, or any other symptoms that resembles a heart

attack (may affect up to 1 in 10,000 people). Please tell your doctor straight away and do not take any

more Almotriptan Orifarm tablets.

Common side effects

(may affect up to 1 in 10 people):

dizziness

sleepiness (somnolence)

nausea

vomiting

tiredness

Uncommon side effects

(may affect up to 1 in 100 people):

sensation of tingling, pricking or numbness of the skin (paraesthesia)

headache

ringing, roaring or clicking noise in the ears (tinnitus)

heart pounding (palpitations)

tightening of the throat

diarrhea

discomfort when digesting food (dyspepsia)

dry mouth

muscle pain (myalgia)

bone pain

chest pain

feeling weak (asthenia)

Very rare side effects

(may affect up to 1 in 10,000 people):

spasm of the heart blood vessels (coronary vasospasm)

increased heart rate (tachycardia)

Not known

(frequency cannot be estimated from the available data):

allergic reactions (hypersensitivity reactions) including mouth, throat or hand edema (angioedema)

severe allergic reactions (anaphylactic reactions)

convulsion (seizure)

visual impairment, vision blurred (visual disorder may also occur during a migraine attack itself)

spasms of intestinal blood vessels, which may lead to the intestine becomes damaged (intestinal

ischemia). You may get stomach ache and bloody diarrhea.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects

not listed in this leaflet. You can also report side effects directly via the national reporting system listed in

Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5.

How to store Almotriptan Orifarm

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the blister and the carton after EXP. The

expiry date refers to the last day of that month.

This medicinal product does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw

away medicines you no longer use. These measures will help protect the environment.

6.

Contents of the pack and other information

What Almotriptan Orifarm contains

The active substance is almotriptan 12.5 mg (as 17.5 mg almotriptan malate).

The other ingredients are:

Core:

Microcrystalline cellulose, mannitol (E421), povidone, sodium starch glycolate and sodium

stearyl fumarate.

Film-coating:

Hypromellose, titanium dioxide (E171), macrogol and carnauba wax.

What Almotriptan Orifarm looks like and contents of the pack

White, round, biconvex film-coated tablet.

Tablet size: approximately 6 mm in diameter.

Almotriptan Orifarm is available in blister packs containing 2, 3, 4, 6, 7, 9, 12, 14 or 18 film-coated tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

[To be completed nationally]

This medicinal product is authorised in the Member States of the EEA under the following names:

Finland, Norway, Sweden: Almotriptan Orifarm

This leaflet was last revised in

2017-07-06

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NAME OF THE MEDICINAL PRODUCT

Almotriptan Orifarm 12.5 mg film-coated tablets.

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each film-coated tablet contains almotriptan malate equivalent to 12.5 mg almotriptan.

For the full list of excipients, see section 6.1.

3.

PHARMACEUTICAL FORM

Film-coated tablet.

Plain white, round, biconvex film-coated tablet.

Tablet size: approximately 6 mm in diameter.

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

Acute treatment of the headache phase of migraine attacks with or without aura.

4.2

Posology and method of administration

Posology

Almotriptan Orifarm should be taken with liquids as early as possible after the onset of migraine-

associated headache but it is also effective when taken at a later stage.

Almotriptan should not be used for migraine prophylaxis.

Adults (18-65 years of age)

The recommended dose is one tablet containing 12.5 mg of almotriptan. A second dose may be

taken if the symptoms reappear within 24 hours. This second dose may be taken provided that

there is a minimum interval of two hours between the two doses.

The efficacy of a second dose for the treatment of the same attack when an initial dose is

ineffective has not been examined in controlled trials. Therefore if a patient does not respond to the

first dose, a second dose should not be taken for the same attack.

The maximum recommended dose is two doses in 24 hours.

Elderly (over 65 years of age)

No dosage adjustment is required in the elderly. The safety and effectiveness of almotriptan in

patients older than 65 years has not been systematically evaluated.

Renal Impairment

Dosage adjustment is not required in patients with mild or moderate renal impairment. Patients

with severe renal impairment should take no more than one 12.5 mg tablet in a 24 hour period.

Hepatic Impairment

There are no data concerning the use of almotriptan in patients with hepatic impairment (see

Section 4.3 Contraindications and 4.4 Special warning and precautions for use).

Paediatric population

Children and adolescents (under 18 years of age):

There are no data concerning the use of almotriptan in children and adolescents, therefore its use in

this age group is not recommended.

Method of administration

Oral use.

Almotriptan Orifarm should be taken with liquids. The tablets can be taken with or without food.

4.3

Contraindications

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

As with other 5-HT

1B/1D

receptor agonists, almotriptan should not be used in patients with a

history, symptoms or signs of ischaemic heart disease (myocardial infarction, angina pectoris,

documented silent ischaemia, Prinzmetal’s angina) or severe hypertension and uncontrolled mild

or moderate hypertension.

Patients with a previous cerebrovascular accident (CVA) or transient ischaemic attack (TIA).

Peripheral vascular disease.

Concomitant administration with ergotamine, ergotamine derivatives (including methysergide) and

other 5-HT

1B/1D

agonists is contraindicated.

Patients with severe hepatic impairment (see Section 4.2 Posology and method of administration).

4.4

Special warnings and precautions for use

Almotriptan should only be used where there is a clear diagnosis of migraine. It should not be used

to treat basilar, hemiplegic or ophthalmoplegic migraine.

As with other acute migraine therapies, before treating headaches in patients not previously

diagnosed as migraine sufferers and in migraine sufferers who present atypical symptoms, care

should be taken to exclude other potentially serious neurological conditions. Cerebrovascular

accidents have been reported in patients treated with 5- HT

1B/1D

agonists. It should be noted that

migraineurs may be at increased risk of certain cerebrovascular events (e.g. cerebrovascular

accident, transient ischemic attack).

In very rare cases, as with other 5-HT

1B/1D

receptor agonists, coronary vasospasm and myocardial

infarction have been reported. Therefore almotriptan should not be administered to patients who

could have an undiagnosed coronary condition without prior evaluation of potential underlying

cardiovascular disease. Such patients include postmenopausal women, males over 40 and patients

with other risk factors for coronary disease such as uncontrolled hypertension,

hypercholesterolemia, obesity, diabetes, smoking or a clear family history of cardiovascular

disease.

These evaluations however, may not identify every patient who has cardiac disease and in very rare

case, serious cardiac events have occurred in patients without underlying cardiovascular disease

when 5-HT

agonists have been administered.

Following administration, almotriptan can be associated with transient symptoms including chest

pain and tightness which may be intense and involve the throat (see Section 4.8 Undesirable

effects). Where such symptoms are thought to indicate ischaemic heart disease, no further dose

should be taken and appropriate evaluation should be carried out.

Caution should be exercised when prescribing almotriptan to patients with known hypersensitivity

to sulphonamides.

Serotonin syndrome (including altered mental status, autonomic instability and neuromuscular

abnormalities) has been reported following concomitant treatment with triptans and selective

serotonin reuptake inhibitors (SSRIs) or serotonin noradrenaline reuptake inhibitors (SNRIs).

These reactions can be severe. If concomitant treatment with almotriptan and a SSRI or SNRI is

clinically warranted, appropriate observation of the patient is advised, particularly during treatment

initiation, with dose increases, or with addition of another serotoninergic medication (See Section

4.5).

It is advised to wait at least 6 hours following use of almotriptan before administering ergotamine.

At least 24 hours should elapse after the administration of an ergotamine-containing preparation

before almotriptan is given. Although additive vasospastic effects were not observed in a clinical

trial in which 12 healthy subjects received oral almotriptan and ergotamine, such additive effects

are theoretically possible (see Section 4.3 Contraindications).

Patients with severe renal impairment should not take more than one 12.5 mg tablet in a 24 hour

period.

Caution is recommended in patients with mild to moderate hepatic disease and treatment is

contraindicated in patients with severe hepatic disease (see section 5.2 Pharmacokinetic

properties).

Undesirable effects may be more common during concomitant use of triptans and herbal

preparations containing St John’s Wort (

Hypericum perforatum

As with other 5-HT

1B/1D

receptor agonists, almotriptan may cause mild, transient increases in

blood pressure, which may be more pronounced in the elderly.

Medication overuse headache (MOH)

Prolonged use of any painkiller for headaches can make them worse. If this situation is

experienced or suspected, medical advice should be obtained and treatment should be

discontinued. The diagnosis of MOH should be suspected in patients who have frequent or daily

headaches despite (or because of) the regular use of headache medications.

The maximum recommended dose of almotriptan should not be exceeded.

4.5

Interaction with other medicinal products and other forms of interaction

Interaction studies were performed with monoamine oxidase A inhibitors, beta -blockers, selective

serotonin re-uptake inhibitors, calcium channel blockers or inhibitors of Cytochrome P450

isoenzymes 3A4 and 2D6. There are no in vivo interaction studies assessing the effect of

almotriptan on other drugs.

As with other 5-HT

agonists, the potential risk of a serotoninergic syndrome due to a

pharmacodynamic interaction in case of concomitant treatment with MAOIs cannot be ruled out.

There have been reports describing patients with symptoms compatible with serotonin syndrome (including

altered mental status, autonomic instability and neuromuscular abnormalities) following the use of selective

serotonin reuptake inhibitors (SSRIs) or serotonin noradrenaline reuptake inhibitors (SNRIs) and triptans

(see Section 4.4).

Multiple dosing with the calcium channel blocker verapamil, a substrate of CYP3A4, resulted in a 20%

increase in C

and AUC of almotriptan. The increase is not considered clinically relevant. No clinically

significant interactions were observed.

Multiple dosing with propranolol did not alter the pharmacokinetics of almotriptan. No clinically significant

interactions were observed.

In vitro studies performed to evaluate the ability of almotriptan to inhibit the major CYP enzymes in human

liver microsomes and human monoamine oxidase (MAO) showed that almotriptan would not be expected to

alter the metabolism of drugs metabolised by CYP or MAO-A and MAO-B enzymes.

4.6

Fertility, pregnancy and lactation

Pregnancy

For almotriptan, very limited data on pregnant patients are available. Animal studies do not indicate direct or

indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal

development (see section 5.3).

Caution should be exercised when prescribing almotriptan to pregnant women.

Breast-feeding

There are no data regarding excretion of almotriptan in human milk. Studies in rats have shown that

almotriptan and/or its metabolites are excreted in milk.

Caution should therefore be exercised when prescribing during lactation. Infant exposure may be minimised

by avoiding breast feeding for 24 hours after treatment.

4.7

Effects on ability to drive and use machines

There are no studies on the effect of almotriptan on the ability to drive or operate machinery. However, since

somnolence may occur during a migraine attack and has been reported as a side effect of treatment with

almotriptan, caution is recommended in patients performing skilled tasks.

4.8

Undesirable effects

Almotriptan was evaluated in over 2700 patients for up to one year in clinical trials. The most common

adverse reactions at the therapeutic dose were dizziness, somnolence, nausea, vomiting and fatigue. None of

the adverse reactions had an incidence superior to 1.5%.

The following adverse reactions have been evaluated in clinical studies and/or reported in post-marketing

experience. They have been listed by System Organ Class (SOC) and in descending order of frequency.

Frequencies are defined as: very common (>1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to

<1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the

available data).

System Organ Class

Common

Uncommon

Very rare

Not known

Immune system

disorders

Hypersensitivity

reactions

(including

angioedema),

anaphylactic

reactions.

Nervous system

disorders

Dizziness,

somnolence.

Paraesthesia,

headache.

Seizures.

Eye disorder

Visual

impairment

vision blurred

Ear and labyrinth

disorders

Tinnitus.

Cardiac disorders

Palpitations.

Coronary

vasospasm,

myocardial

infarction,

tachycardia.

Respiratory, thoracic

and mediastinal

disorders

Throat

tightness.

Gastrointestinal

disorders

Nausea,

vomiting.

Diarrhoea,

dyspepsia,

mouth.

Intestinal

ischemia.

Musculoskeletal,

connective tissue and

bone disorders

Myalgia,

bone

pain.

General disorders

Fatigue.

Chest

pain,

asthenia.

*

However visual disorders may also occur during a migraine attack

itself.

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 national reporting system listed in Appendix V.

4.9

Overdose

The most frequently reported adverse event in patients receiving 150 mg (the highest dose administered to

patients) was somnolence.

Overdose should be treated symptomatically and vital functions should be maintained. Since the elimination

half-life is around 3.5 hours monitoring should continue for at least 12 hours or while symptoms or signs

persist.

5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Antimigraine, ATC code: N02CC05. Selective 5-HT

receptor agonist.

Mechanism of action

Almotriptan is a selective 5-HT

and 5-HT

receptor agonist. These receptors mediate vasoconstriction of

certain cranial vessels, as demonstrated in studies using isolated human tissue preparations. Almotriptan also

interacts with the trigeminovascular system, inhibiting extravasation of plasma proteins from dural vessels

following trigeminal ganglionic stimulation, which is a feature of neuronic inflammation that seems to be

involved in the physiopathology of migraine. Almotriptan has no significant activity on other 5-HT receptor

subtypes and no significant affinity for adrenergic, adenosine, angiotensin, dopamine, endothelin or

tachykinin binding sites.

Pharmacodynamic effects

The efficacy of almotriptan in the acute treatment of migraine attacks was established in four multicentres,

placebo-controlled clinical trials including more than 700 patients who were administered 12.5 mg. The

decrease in pain began 30 minutes after administration, and the percentage of response (reduction of

headache from moderate -severe to mild or absent) after 2 hours was 57-70% with almotriptan and 32-42%

after placebo. In addition, almotriptan relieved nausea, photophobia and photophobia associated with

migraine attacks.

5.2

Pharmacokinetic properties

Almotriptan is well absorbed, with an oral bioavailability of about 70%. Maximum plasma concentrations

) occur approximately between 1.5 and 3.0 hours after administration. The rate and extent of absorption

is unaffected by concomitant ingestion of food. In healthy subjects administered single oral doses ranging

from 5 mg to 200 mg, C

and AUC were proportional to dose, indicating linear pharmacokinetic

behaviour. The elimination half-life (t

) is about 3.5 h in healthy subjects. There is no evidence of any

gender-related effect on the pharmacokinetics of almotriptan.

More than 75% of the dose administered is eliminated in urine, and the remainder in faeces. Approximately,

the 50% of the urinary and faecal excretion is unchanged almotriptan. The major biotransformation route is

via monoamine oxidase (MAO-A) mediated oxidative deamination to the indole acetic metabolite.

Cytochrome P450 (3A4 and 2D6 isozymes) and flavin mono-oxygenase are other enzymes involved in the

metabolism of almotriptan. None of the metabolites is significantly active pharmacologically.

After an intravenous dose of almotriptan administered to healthy volunteers the average values for the

distribution volume, total clearance and elimination half-life were 195 L, 40L/h and 3.4 h respectively. Renal

clearance (CL

) accounted for about two-thirds of total clearance and renal tubular secretion is probably also

involved. The CL

correlates well with renal function in patients with mild (creatinine clearance: 60-90

ml/min), moderate (creatinine clearance: 30-59 ml/min) and severe (creatinine clearance: < 30 ml/min) renal

impairment. The increase of the mean t

(up to 7 hours) is statistically and clinically significant in the case

of patients with severe renal impairment only. Compared with healthy subjects, the increase in the maximum

plasma concentration (C

) of almotriptan was 9%, 84% and 72% respectively for patients with slight,

moderate and severe renal impairment, whereas the increase in exposure (AUC) was 23%, 80% and 195%

respectively. According to these results, the reduction of the total clearance of almotriptan was -20%, -40%

and -65% respectively for patients with slight, moderate and severe renal impairment. As expected, total

(CL) and renal (CL

) clearances were reduced but without clinical relevance in healthy elderly volunteers

compared with a young control group.

Based on the mechanisms of almotriptan clearance in man, approximately 45% of almotriptan elimination

appears to be due to hepatic metabolism. Therefore, even if these clearance mechanisms were totally blocked

or impaired, plasma almotriptan levels would be increased a maximum of two-fold over the control state,

assuming that renal function (and almotriptan renal clearance) are not altered by hepatic impairment. In

patients with severe renal impairment, C

is increased twofold, and AUC is increased approximately

threefold relative to healthy volunteers. Maximal changes in pharmacokinetic parameters in patients with

significant hepatic impairment would not exceed these ranges. For this reason, no study of the

pharmacokinetics of almotriptan in patients with hepatic impairment was performed.

5.3

Preclinical safety data

In safety pharmacology, repeated dose toxicity and reproduction toxicity studies, adverse effects were

observed only at exposures well above the maximum human exposure.

Almotriptan did not show any mutagenic activity in a standard battery of in vitro and in vivo genotoxicity

studies, and no carcinogenic potential was revealed in studies conducted in mice and rats.

As occurs with other 5-HT

1B/1D

receptor agonists, almotriptan binds to melanin. However, no ocular adverse

effects associated with the drug have been observed in dogs after treatment for up to one year.

6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Core:

Microcrystalline cellulose

Mannitol (E 421)

Povidone

Sodium starch glycolate

Sodium stearyl fumarate

Film-coating:

Hypromellose

Titanium dioxide (E171)

Macrogol

Carnauba wax

6.2

Incompatibilities

Not applicable.

6.3

Shelf life

4 years.

6.4

Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5

Nature and contents of container

Aluminium lidding foil blisters (OPA/ Alu/PVC laminate).

Pack sizes: 2, 3, 4, 6, 7, 9, 12, 14 or 18 film-coated tablets.

Not all pack sizes may be marketed.

6.6

Special precautions for disposal <and other handling>

No special requirements.

7.

MARKETING AUTHORISATION HOLDER

[To be completed nationally]

8.

MARKETING AUTHORISATION NUMBER(S)

[To be completed nationally]

9.

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: [To be completed nationally]

10.

DATE OF REVISION OF THE TEXT

2020-01-20

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