Drugs List

Therapeutic Indications

Uses

Acute treatment of migraine attacks with or without aura

Contraindications

Children under 18 years
Suspected ischaemic heart disease
Coronary vasospasm
Galactosaemia
History of cerebrovascular accident
History of myocardial infarction
History of transient ischaemic attack
Ischaemic heart disease
Moderate hypertension
Peripheral vascular disease
Prinzmetal's angina
Severe hepatic impairment
Uncontrolled hypertension

Precautions and Warnings

Patients over 65 years
Predisposition to ischaemic heart disease
Breastfeeding
Glucose-galactose malabsorption syndrome
Lactose intolerance
Pregnancy

Not for prophylactic use
Not indicated in hemiplegic, ophthalmoplegic or basilar migraine
Advise ability to drive/operate machinery may be affected by side effects
Avoid ergotamine-type medication for 24 hrs before/after treatment
Evaluate patients for cardiovascular disease prior to treatment
Exclude other potentially serious neurological conditions
Contains lactose
Only for use where a clear diagnosis of migraine has been established
Excessive use may increase frequency of headache, may require withdrawal
Discontinue if cardiac ischaemic pain occurs
Discontinue treatment if skin rash or other allergic reaction occurs
If angina-like symptoms occur, discontinue treatment and investigate.
Avoid repeated or prolonged use
Advise patient not to take St John's wort concurrently
Patients should not exceed recommended dose

Migraineurs may be at increased risk of certain cerebrovascular events (eg CVA or TIA).

Patients at risk of coronary artery disease (CAD) including heavy smokers or users of nicotine substitution therapy without a prior cardiovascular evaluation. Special attention should be given to post-menopausal women and to men over 40 years of age presenting with these risk factors.

Prolonged, too frequent use (repeated administration several days in a row corresponding to a misuse of the product) can lead to an accumulation of the active substance and an increase in the side effects.

Pregnancy and Lactation

Pregnancy

Use frovatriptan with caution in pregnancy.

At the time of writing, there are insufficient data available to establish the safety of frovatriptan use in pregnancy, the manufacture recommends the use of frovatriptan only when its clearly necessary. It is not know if frovatriptan crosses the placenta but its molecular weight is low enough that this should be expected. Minimal protein binding and prolonged elimination half-life suggest foetal exposure is likely.

Animal studies have shown reproductive toxicity in rats; oral doses from 130 to 1300 times the maximum recommended human dose increased the incidence of dilated ureters, unilateral and bilateral pelvic cavitation, hydronephrosis and hydroureter, and skeletal variations. In pregnant rabbits, no effects on foetal development were observed at doses less than 210 times the maximum human dose.

The animal data suggest low risk, but the actual risk cannot be accurately determined due to the lack of experience in human pregnancy. Non-drug therapies such as relaxation are preferred when treating migraine in pregnancy. Paracetamol is the analgesic of choice, with ibuprofen or aspirin also suitable for the first 30 weeks.

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 to 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 ). .

Lactation

Use frovatriptan with caution in breastfeeding.

At the time of writing, no data on the transfer of frovatriptan into human milk are available, but the molecular weight, low plasma protein binding and long elimination half-life suggest it is likely. Frovatriptan and/or its metabolites are excreted in the milk of lactating rats with the maximum concentration in milk being four-fold higher than maximum blood levels.

Since frovatriptan has a half life of 25 to 30 hours, LactMed suggests using a shorter-acting alternative in preference. Sumatriptan may be preferred since there is data to suggest that both milk levels and bioavailability are low. The manufacturer advises that the administration of frovatriptan to lactating women is not recommended unless clearly needed, in which case a 24 hour interval should be observed. LactMed states that if frovatriptan is required, it is not a reason to discontinue breastfeeding.

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

Side Effects

Abdominal distension
Abdominal pain
Agitation
Amnesia
Anxiety
Arterial spasm
Arthralgia
Asthenia
Attention disturbances
Bradycardia
Breast tenderness
Chest discomfort
Confusion
Constipation
Dehydration
Depersonalisation
Depression
Dizziness
Dream abnormalities
Dry mouth
Dysaesthesia
Dysgeusia
Dyspepsia
Dysphagia
Ear disorder
Epistaxis
Eructation
Erythema
Eye irritation
Eye pain
Fatigue
Feeling hot
Flushing
Gastroesophageal reflux
Gastrointestinal disorder
Headache
Hyperacusis
Hyperaesthesia
Hyperbilirubinaemia
Hyperhidrosis
Hypersensitivity reactions
Hypertension
Hypertonia
Hyperventilation
Hypoaesthesia
Hypocalcaemia
Hypoglycaemia
Hyporeflexia
Hypotonia
Increased energy
Insomnia
Involuntary muscle contractions
Irritable bowel syndrome(IBS)
Laryngitis
Lethargy
Lip blister
Lymphadenopathy
Malaise
Movement disturbances
Musculoskeletal pain
Myocardial infarction
Nausea
Nervousness
Night blindness
Nocturia
Oesophageal spasm
Oral mucosal blistering
Pain
Pain in salivary glands
Palpitations
Paraesthesia
Peptic ulceration
Peripheral coldness
Personality disorder
Pharyngitis
Photophobia
Piloerection
Pollakiuria
Polyuria
Pruritus
Purpura
Pyrexia
Renal pain
Respiratory disorders
Rhinitis
Sedation
Sinusitis
Somnolence
Stomatitis
Tachycardia
Thirst
Throat irritation
Throat tightness
Tinnitus
Tooth ache
Tremor
Urinary abnormalities
Urticaria
Vertigo
Visual disturbances

Presentation

Tablets containing frovatriptan

Drugs List

Therapeutic Indications

Uses

Acute treatment of migraine attacks with or without aura

Dosage

It is advisable that frovatriptan be given as early as possible after the onset of a migraine headache, but is also effective when taken at a later stage.

Adults

Elderly

Contraindications

Children under 18 years
Suspected ischaemic heart disease
Coronary vasospasm
Galactosaemia
History of cerebrovascular accident
History of myocardial infarction
History of transient ischaemic attack
Ischaemic heart disease
Moderate hypertension
Peripheral vascular disease
Prinzmetal's angina
Severe hepatic impairment
Uncontrolled hypertension

Precautions and Warnings

Patients over 65 years
Predisposition to ischaemic heart disease
Breastfeeding
Glucose-galactose malabsorption syndrome
Lactose intolerance
Pregnancy

Not for prophylactic use
Not indicated in hemiplegic, ophthalmoplegic or basilar migraine
Advise ability to drive/operate machinery may be affected by side effects
Avoid ergotamine-type medication for 24 hrs before/after treatment
Evaluate patients for cardiovascular disease prior to treatment
Exclude other potentially serious neurological conditions
Contains lactose
Only for use where a clear diagnosis of migraine has been established
Excessive use may increase frequency of headache, may require withdrawal
Discontinue if cardiac ischaemic pain occurs
Discontinue treatment if skin rash or other allergic reaction occurs
If angina-like symptoms occur, discontinue treatment and investigate.
Avoid repeated or prolonged use
Advise patient not to take St John's wort concurrently
Patients should not exceed recommended dose

Migraineurs may be at increased risk of certain cerebrovascular events (eg CVA or TIA).

Patients at risk of coronary artery disease (CAD) including heavy smokers or users of nicotine substitution therapy without a prior cardiovascular evaluation. Special attention should be given to post-menopausal women and to men over 40 years of age presenting with these risk factors.

Prolonged, too frequent use (repeated administration several days in a row corresponding to a misuse of the product) can lead to an accumulation of the active substance and an increase in the side effects.

Pregnancy and Lactation

Pregnancy

Use frovatriptan with caution in pregnancy.

At the time of writing, there are insufficient data available to establish the safety of frovatriptan use in pregnancy, the manufacture recommends the use of frovatriptan only when its clearly necessary. It is not know if frovatriptan crosses the placenta but its molecular weight is low enough that this should be expected. Minimal protein binding and prolonged elimination half-life suggest foetal exposure is likely.

Animal studies have shown reproductive toxicity in rats; oral doses from 130 to 1300 times the maximum recommended human dose increased the incidence of dilated ureters, unilateral and bilateral pelvic cavitation, hydronephrosis and hydroureter, and skeletal variations. In pregnant rabbits, no effects on foetal development were observed at doses less than 210 times the maximum human dose.

The animal data suggest low risk, but the actual risk cannot be accurately determined due to the lack of experience in human pregnancy. Non-drug therapies such as relaxation are preferred when treating migraine in pregnancy. Paracetamol is the analgesic of choice, with ibuprofen or aspirin also suitable for the first 30 weeks.

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 to 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 ). .

Lactation

Use frovatriptan with caution in breastfeeding.

At the time of writing, no data on the transfer of frovatriptan into human milk are available, but the molecular weight, low plasma protein binding and long elimination half-life suggest it is likely. Frovatriptan and/or its metabolites are excreted in the milk of lactating rats with the maximum concentration in milk being four-fold higher than maximum blood levels.

Since frovatriptan has a half life of 25 to 30 hours, LactMed suggests using a shorter-acting alternative in preference. Sumatriptan may be preferred since there is data to suggest that both milk levels and bioavailability are low. The manufacturer advises that the administration of frovatriptan to lactating women is not recommended unless clearly needed, in which case a 24 hour interval should be observed. LactMed states that if frovatriptan is required, it is not a reason to discontinue breastfeeding.

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

Counselling

Migraine itself or treatment with frovatriptan may cause somnolence. Patients should be advised to evaluate their ability to perform complex tasks such as driving during migraine attacks and following administration of frovatriptan.

Patients should be advised not to exceed the recommended dose.

Patients should be advised not to use products containing St John's wort.

Side Effects

Abdominal distension
Abdominal pain
Agitation
Amnesia
Anxiety
Arterial spasm
Arthralgia
Asthenia
Attention disturbances
Bradycardia
Breast tenderness
Chest discomfort
Confusion
Constipation
Dehydration
Depersonalisation
Depression
Dizziness
Dream abnormalities
Dry mouth
Dysaesthesia
Dysgeusia
Dyspepsia
Dysphagia
Ear disorder
Epistaxis
Eructation
Erythema
Eye irritation
Eye pain
Fatigue
Feeling hot
Flushing
Gastroesophageal reflux
Gastrointestinal disorder
Headache
Hyperacusis
Hyperaesthesia
Hyperbilirubinaemia
Hyperhidrosis
Hypersensitivity reactions
Hypertension
Hypertonia
Hyperventilation
Hypoaesthesia
Hypocalcaemia
Hypoglycaemia
Hyporeflexia
Hypotonia
Increased energy
Insomnia
Involuntary muscle contractions
Irritable bowel syndrome(IBS)
Laryngitis
Lethargy
Lip blister
Lymphadenopathy
Malaise
Movement disturbances
Musculoskeletal pain
Myocardial infarction
Nausea
Nervousness
Night blindness
Nocturia
Oesophageal spasm
Oral mucosal blistering
Pain
Pain in salivary glands
Palpitations
Paraesthesia
Peptic ulceration
Peripheral coldness
Personality disorder
Pharyngitis
Photophobia
Piloerection
Pollakiuria
Polyuria
Pruritus
Purpura
Pyrexia
Renal pain
Respiratory disorders
Rhinitis
Sedation
Sinusitis
Somnolence
Stomatitis
Tachycardia
Thirst
Throat irritation
Throat tightness
Tinnitus
Tooth ache
Tremor
Urinary abnormalities
Urticaria
Vertigo
Visual disturbances

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 ).

Further Information

Last Full Review Date: December 2014

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.

Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press Accessed on 18 December 2014.

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

Paediatric Formulary Committee. BNF for Children (online) London: BMJ Group, Pharmaceutical Press, and RCPCH Publications Accessed on 18 December 2014.

Summary of Product Characteristics: Migard. Goldshield Pharmaceuticals Ltd. Revised November 1998.

Summary of Product Characteristics: Migard. A.Menarini Farmaceutica Internazionale S.R.L. Revised November 2014.

Summary of Product Characteristics: Mylatrip. Mylan. Revised January 2016.

Clinical Knowledge Summaries - Migraine
Scenario: Pregnant or breastfeeding women
Available at: https://cks.nice.org.uk/migraine
Last accessed: 18 December 2014

UK Drugs in Lactation Advisory Service.
Available at: https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Last accessed: 18 December 2014

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Frovatriptan Last revised: 07 September 2013
Last accessed: 18 December 2014