New Zealand - English - Medsafe (Medicines Safety Authority)
Ergotamine tartrate 1 mg and Caffeine 100 mg Tablets
What is in this leaflet
Please read this leaflet carefully before you start taking Cafergot.
This leaflet answers some common questions about Cafergot tablets
It does not contain all the available information. It does not take the place of talking to
your doctor or pharmacist.
All medicines have risks and benefits. Your doctor has weighed the risks of you
using Cafergot against the benefits it can provide.
If you have any concerns about Cafergot, ask your doctor or pharmacist. Keep this
leaflet with the medicine. You may need to read it again.
What Cafergot is used for
Cafergot is used to treat attacks of migraine with or without aura.
These headaches are thought to be caused by temporary changes in the size of small
blood vessels in the brain. These blood vessels swell, causing the pain and visual
disturbances that often happen during an attack. Cafergot stops the attack by causing
the blood vessels to constrict (shrink) back to normal size.
Cafergot is only taken to treat migraine attacks. It is not taken to prevent attacks from
There are some types of headaches which must not be treated with Cafergot. Your
doctor will determine the best treatment for your headache.
Cafergot tablets contain the active ingredients, ergotamine tartrate and caffeine.
Ergotamine belongs to a group of medicines known as the "ergot alkaloids." Caffeine
helps ergotamine work better and faster by increasing its absorption into the body.
Ask your doctor if you have any questions about why Cafergot has been prescribed
Your doctor may have prescribed Cafergot for another reason.
Cafergot is only available with a doctor's prescription.
There is not enough information to recommend this medicine for children under 6 years
Before you take Cafergot
When you must not take Cafergot
Do not take Cafergot if you have ever had an allergic reaction to any of the
ergotamine or caffeine, the active ingredients in Cafergot tablets
any of the other ingredients listed at the end of this leaflet
any other ergot alkaloids (e.g. Ergodryl
Some of the symptoms of an allergic reaction may include shortness of breath, wheezing
or difficulty breathing; swelling of the face, lips, tongue or other parts of the body; rash,
itching or hives on the skin.
Do not take Cafergot if you have any of the following health problems/medical
problems with your heart, especially if you have angina that is not controlled or
you have had a heart attack
high blood pressure that is not controlled
severe liver or kidney disease
poor blood circulation or other blood vessel disorders (e.g. varicose veins, fluid
buildup in legs or feet, or conditions that make your fingers and toes unusually
sensitive to cold)
you are being treated with mexiletine (a medicine for irregular heartbeats)
you are being treated with fluvoxamine ( a medicine for mental disorder)
you are being treated for cough and cold or increased weight with medicines such
as phenylephrine, amphetamine, cocaine or phentermine
a serious infection
you are being treated for HIV/AIDS with a medicine called ritonavir, nelfinavir,
indinavir or delavirdine
you are taking a contraceptive pill to prevent pregnancy
you are being treated for an infection with a medicine called ketoconazole,
When previously treated with ergotamine derivative, if you had developed scarring and
thickening of any of the following: the abdominal cavity, lungs tissue or lining that
surrounds the lungs, heart tissue or lining that surrounds the heart, do not take this
Do not take Cafergot if you are pregnant or intend to become pregnant.
This medicine may affect your developing baby if you take it while you are pregnant.
Do not breast-feed if you are using Cafergot.
The active ingredients in Cafergot may pass into breast milk and may affect your baby.
Do not take Cafergot after the expiry date printed on the pack or if the packaging is
torn or shows signs of tampering.
In that case, return it to your pharmacist.
Before you start to take Cafergot
Tell your doctor if you smoke.
Nicotine in cigarettes may increase the chance of you having an unwanted side effect
called "ergotism" (excessive constriction of blood vessels). See Side Effects section for
Tell your doctor if you are allergic to any other medicines, foods, dyes or
Your doctor will want to know if you are prone to allergies.
Taking other medicines
Tell your doctor if you are taking any other medicines, including any that you buy
without a prescription from a pharmacy, supermarket or health food store. You
should also tell your health professional who is prescribing a new medication for
you that you are taking Cafergot.
Some medicines and Cafergot may interfere with each other. These include:
some medicines used to treat HIV/AIDS, including ritonavir, nelfinavir, indinavir,
delavirdine, saquinavir or nevirapine
some medicines for infections, including ketoconazole, itraconazole, fluconazole,
troleandomycin, quinupristin, dalfopristim, ciprofloxacin, norfloxacin, ofloxacin
some medicines used to treat mental disorders, including nefazodone, fluoxetine,
fluvoxamine, amitriptyline, sertraline
zileuton, a medicine used to prevent asthma attacks
mexiletene, a medicine used to treat irregular heartbeats
other ergot alkaloids
other medicines used to treat migraine such as sumatriptan
nicotine in medicines used to help you quit smoking, such as nicotine patches or
some medicines for cough and cold or increased weight such as phenylephrine,
amphetamine, cocaine or phentermine
beta-blocker medicines such as propranolol, which are used to prevent migraine
and also to treat heart problems and high blood pressure
any other medicine that can cause blood vessels to contract (shrink).
You may need to take different amounts of your medicines or to take different
medicines while you are taking Cafergot. Your doctor and pharmacist have more
If you have not told your doctor about any of these things, tell him/her before you
start taking Cafergot.
How to use Cafergot
Follow all directions given to you by your doctor and pharmacist carefully.
These directions may differ from the information contained in this leaflet.
If you do not understand the instructions on the label, ask your doctor or
pharmacist for help.
At the first sign of a migraine attack, swallow two Cafergot tablets.
This dose is usually enough to stop an attack but, if the migraine doesn't go away, you
can have another dose every half an hour to a maximum of 6 tablets in one day.
Do not take more than 6 tablets in one day.
Do not take more than 10 tablets in one week.
At the first sign of a migraine attack, swallow one Cafergot tablet.
This dose is usually enough to stop an attack but, if the migraine doesn't go away, you
can have another dose every half an hour to a maximum of 3 tablets in one day.
Do not take more than 5 tablets in one week.
If you take too much Cafergot or if you take it too often, you may have an increased risk
of serious side effects such as "ergotism" or retroperitoneal or pleuropulmonary fibrosis
(see Side Effects section for more information). You may also have side effects such as
headaches, tiredness, runny nose and muscle pain when you stop using it.
Do not take sumatriptan, zolmitriptan or naratriptan or any medicine containing
ergot alkaloids (e.g. Dihydergot
) at the same time as you take
If you wish to take one of these other medicines following a dose of Cafergot, your doctor
or pharmacist can advise you how long to wait before you take it.
Things you must do while taking Cafergot
If you become pregnant while using Cafergot, tell your doctor.
Your doctor can discuss with you the risks of using it while you are pregnant.
If you are about to be started on any new medicine, remind your doctor and
pharmacist that you are using Cafergot.
Tell any other doctor, dentist or pharmacist who treats you that you are using
Things you must not do
Do not take Cafergot to prevent a migraine attack from happening.
This medicine should only be taken to treat a migraine once it has started.
Avoid drinking grapefruit juice while you are using Cafergot.
Grapefruit juice may interfere with the action of Cafergot in your body.
Do not give this medicine to anyone else, even if their condition seems similar to
Do not take it to treat any other complaints unless your doctor tells you to.
This medicine is not appropriate for common 'tension' headaches.
Things to be careful of
Be careful driving, operating machinery or doing jobs that require you to be alert
until you know how Cafergot affects you.
This medicine may
dizziness or vertigo (spinning sensation) in some people.
Make sure you know how it affects you before you drive a car, operate machinery, or do
anything else that could be dangerous.
Tell your doctor or pharmacist as soon as possible if you do not feel well while you
are taking Cafergot, even if you do not think it is connected with the medicine.
All medicines can have side effects. Sometimes they are serious, but most of the time
they are not. You may need medical treatment if you get some of the side effects.
Do not be alarmed by these lists of possible side effects. You may not experience
any of them.
Ask your doctor or pharmacist to answer any questions you may have.
Stop using Cafergot and tell your doctor immediately if you notice any of the
signs of allergy such as rash, itching or hives on the skin; swelling of the face,
lips, tongue or other part of the body; wheezing or troubled breathing
signs of "ergotism" (excessive constriction of blood vessels) such as numbness,
coldness, tingling or a pale or bluish colour in the fingers or toes, pain or spasms
in muscles, chest pain
pain in the lower back or side, associated with difficulty in passing urine or pain
on urinating, which may be a sign of retroperitoneal fibrosis, a thickening of the
abdominal lining that can cause obstruction of the urinary tract
shortness of breath, dry cough, pain in the chest or rib area, which may be a sign
of pleuropulmonary fibrosis, a scarring and thickening of lung tissue
chest pain as this may be a sign of too little blood and oxygen getting to the heart
muscle or in rare cases, a heart attack.
you feel faint or look pale, which could be signs of shock
The above are serious side effects that need medical attention.
Tell your doctor if you notice any of the following and they worry you:
nausea (feeling sick) or vomiting
Intensifying headache with autonomic disturbances after Cafergot withdrawal
fast, slow or irregular heart beat
increase in your blood pressure
muscular pain or spasm
pain or weakness in your arms or legs
Tell your doctor if you notice anything else that is making you feel unwell.
Some people may have other side effects not yet known or mentioned in this leaflet.
Chemicals Information Centre, Dunedin (telephone 0800 POISON OR 0800 764 766),
or go to the Accident and Emergency Department at your nearest hospital if you
think that you or anyone else may have taken too much Cafergot. Do this even if
there are no signs of discomfort or poisoning. Keep the telephone numbers for
these places handy.
Some of the symptoms of an overdose may include nausea, vomiting, fast heart-beat,
numbness or tingling in the fingers and toes, abnormal blue discoloration of the skin and
mucous membranes, weak pulse, dizziness, drowsiness, confusion, difficulty breathing,
low blood pressure, fits and coma.
Keep your medicine in the original container until it is time to take it.
Store it in a cool place where the temperature stays below 25°C.
Do not store Cafergot or any other medicine in the bathroom or near a sink.
Do not leave it in the car or on window sills.
Keep this medicine where children cannot reach it.
A locked cupboard at least one-and-a-half metres above the ground is a good place
If your doctor tells you to stop using Cafergot or the expiry date has passed, ask
your pharmacist what to do with any medicine that is left over.
Cafergot tablets also contain the following inactive ingredients:
iron oxide yellow (E172)
If you want to know more
Talk to your doctor or pharmacist. They will be able to answer your questions.
Cafergot is supplied in New Zealand by:
AFT Pharmaceuticals Ltd.
PO Box 33.203
Date of preparation: 13 February 2018
New Zealand Data Sheet
CAFERGOT (ERGOTAMINE TARTRATE 1 MG AND
CAFFEINE 100 MG TABLET)
ergotamine tartrate 1 mg and caffeine 100 mg tablet
QUALITATIVE AND QUANTITATIVE COMPOSITION
Ergotamine tartrate 1 mg and Caffeine 100 mg
For the full list of excipients, see section 6.1.
Cafergot tablets are round, flat with bevelled edge, 9 mm diameter, speckled
yellow/white, inscribed with a breakline and XL on one side and plain on the other side.
Treatment of acute attacks of migraine with or without aura in adults.
Dose and method of administration
Cafergot should be given at the first signs of a migraine attack.
The first time Cafergot is taken, an initial dose of 2 Cafergot tablets orally, is
recommended. If relief is not obtained within half an hour, a further tablet should be
administered; this may be repeated at half-hourly intervals, but the maximum daily dose
of 6 tablets should not be exceeded.
If the pain persists, take 1 tablet every half an hour up to the maximum daily dose of 6
tablets. The maximum weekly dose is 10 tablets.
Children under 18 years
Maximum dose per attack or per day
Adults: 6 mg ergotamine tartrate = 6 tablets.
Maximum weekly dose
Adults: 10 mg ergotamine tartrate = 10 tablets.
Cafergot is contraindicated in patients with severe renal impairment (see
Cafergot is contraindicated in patients with severe hepatic impairment (see
Contraindications). Patients with mild to moderate hepatic impairment, especially
patients with cholestasis, should be appropriately monitored (see Warnings and
Cafergot is not recommended in children and adolescents under the age of 18 years.
Safety and efficacy have not been established in pediatric patients.
Cafergot is not recommended for patients aged over 65 years. No studies have been
performed in elderly patients (65 years age and above).
Method of administration
The following restriction must be observed
If supplementary antimigraine medication is required, the use of any ergotamine-
containing preparations, intranasal or parenteral dihydroergotamine or sumatriptan or
-receptor agonists must be avoided (see Contraindications).
Taking Cafergot repeatedly over extended periods must be avoided.
The concomitant use of an anti-emetic may enhance the action of the tablets.
Known hypersensitivity to ergot alkaloids, caffeine, or any other components of
Pregnancy and breast-feeding
Impaired peripheral circulation, obliterative vascular disease, coronary heart
disease, inadequately controlled hypertension, septic conditions, shock
Severe renal impairment
Severe hepatic impairment
Hemiplegic or basilar migraine
Concomitant treatment with cytochrome P450 3A4 (CYP3A4) inhibitors such as
transcriptase inhibitors and azole antifungals
Concomitant treatment with vasoconstrictor agents including ergot alkaloids,
sumatriptan, other 5HT
receptor agonists, nicotine (e.g. heavy smoking) and
Concomitant treatment with fluoroquinolones, mexiletine, fluvoxamine, and oral
consequently may translate to increase in absorption of ergotamine
effusion, pleural fibrosis, pericarditis, pericardial effusion or similar condition)
under previous treatment with an ergotamine derivative.
Special warnings and precautions for use
Cafergot is indicated only for the treatment of acute migraine attacks and not for
Continued daily use of Cafergot or its use in excess of the recommended doses must be
avoided since this may cause vasospasm. If signs of vascular spasms are observed,
Cafergot should be discontinued and treatment with a peripheral vasodilator initiated.
Owing to its vasoconstrictor properties, ergotamine may cause myocardial ischaemia or,
in rare cases, infarction, even in patients with no known history of coronary heart
disease. If chest pain occurs treatment should be withdrawn.
Long-term use of ergotamine can cause ergotism, including severe cases of symptoms of
constriction of peripheral blood vessels, with possible fatal outcome.
To avoid the risk of ergotism patients who are being treated with Cafergot should be
informed of the maximum doses allowed and of the first symptoms of overdosage:
hypoaesthesia, paresthesia, e.g. numbness, tingling in the fingers and toes, non-
migraine-related nausea and vomiting, and symptoms of myocardial ischaemia e.g.
precordial pain. If symptoms such as tingling in the fingers or toes occur, the drug
should be discontinued at once and the physician consulted
If, contrary to recommendations, ergotamine-containing drugs including Cafergot are
used excessively over years, they may induce fibrotic changes, including pleural,
retroperitoneal and pulmonary fibrosis. There have also been rare reports of fibrotic
changes of the cardiac valves.
Patients with mild to moderate hepatic impairment, especially cholestatic patients should
be appropriately monitored.
The occurrence of drug-induced headaches has been reported during prolonged and
uninterrupted treatment with Cafergot.
Cases with sudden and transient loss of vision have been reported in post-marketing use.
This adverse event may be related to vasospasm and ischaemic episodes. Patents should
stop using Cafergot immediately if they experience visual disturbances and seek medical
Interaction with other medicines and other forms of interaction
Potent CYP3A4 inhibitors
The concomitant use of Cafergot with cytochrome P450 3A (CYP3A) inhibitors such as
macrolide antibiotics (e.g. troleandomycin, erythromycin, clarithromycin; except
spiramycin); HIV protease or reverse transcriptase inhibitors (e.g. amprenavir,
atazanavir, fosamprenavir, ritonavir, indinavir, lopinavir, nelfinavir, saquinavir,
tipranavir, delavirdine, efavirenz); or azole antifungals (e.g. ketoconazole, itraconazole,
voriconazole) must be avoided (see Contraindications). Concomitant use can result in an
elevated exposure to ergotamine and ergot toxicity (vasospasm and ischemia of the
extremities and other tissues). Ergot alkaloids have also been shown to be both inhibitors
and substrates of CYP3A.
Moderate/weak CYP3A4 inhibitors
Moderate to weak CYP3A4 inhibitors such as cimetidine, fluconazole, quinupristin/
dalfopristin, zileuton and grapefruit juice can also increase exposure to ergotamine and
caution is required for concomitant use.
No pharmacokinetic interactions between ergotamine and cytochrome P450 isoenzymes
Concurrent use of vasoconstrictor agents including preparations containing ergot
alkaloids (bromocriptine, cabergoline, pergolide, lisuride), sumatriptan and other 5HT1
receptor agonists (almotriptan, fovatriptan, naratriptan, rizatriptan, zolmitriptan,
eletriptan), nicotine (e.g. heavy smoking) and sympathomimetics must be avoided since
this may result in enhanced vasoconstriction, (see Contraindications). Allow 24 hours
between the discontinuation of the triptans and the use of the alkaloid.
Drugs (e.g. nevirapine, rifampicin) inducing CYP3A4 can lead to decrease in
pharmacological action of ergotamine.
A few cases of vasospastic reactions have been reported among patients treated
concomitantly with ergotamine-containing preparations and propranolol.
Some antidepressants such as fluoxetine, fluvoxamine or nefazodone may increase the
levels of the ergot derivatives. Concurrent use of ergotamine with serotonin reuptake
inhibitors (e.g. amitriptyline) including selective agents (e.g. sertraline) can lead to
serotonin syndrome, caution is required for concurrent use.
Caffeine undergoes extensive metabolism by CYP1A2. Concurrent use with substances
like fluoroquinolones, mexiletine, fluvoxamine, oral contraceptives and
sympathomimetics, that can reduce CYP1A2 activity may modulate the metabolic
clearance of caffeine and consequently may translate to increase in absorption of
ergotamine, see Contraindications.
Fertility, pregnancy and lactation
Cafergot is contraindicated during pregnancy because ergotamine has oxytocic and
vasoconstrictor effects on the placenta and umbilical cord.
In a reproductive performance study and a peri-/post-natal study in female rats, an
increased number of stillbirths and/or peri-/post-natal mortality were observed following
administration of oral ergotamine/caffeine (1:100). At high oral doses, ergotamine
induced fetal retardation in experimental animals. The observation has been attributed to
reduced uteroplacental blood flow.
Women with the potential to become pregnant must use effective birth control
throughout the treatment period.
Ergotamine and caffeine are excreted in breast milk. Ergotamine may cause symptoms
of vomiting, diarrhoea, weak pulse and unstable blood pressure in infants. Cafergot is
thus contraindicated in nursing mothers.
In male rats receiving the combination of oral ergotamine and caffeine (1:100), fertility
was not impaired.
Effects on ability to drive and use machines
Patients experiencing dizziness, visual disturbance or impaired reactions, should not
drive or operate machinery.
The most common of all side-effects are nausea and vomiting. Depending on the dose of
ergotamine, signs and symptoms of vasoconstriction may occur.
Adverse reactions are listed by MedDRA system organ class and ranked under heading
of frequency, the most frequent first, using the following convention: very common (≥
1/10); common (≥1/100, < 1/10); uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, <
1/1,000), very rare (< 1/10,000), not known (frequency cannot be estimated from the
Immune system disorders
Rare: Hypersensitivity reactions
Nervous system disorders
Uncommon: Paraesthesia (e.g. tingling) in fingers and toes, hypoaesthesia (e.g.
Not known: Somnolence, drug-induced headache, an intensifying headache with
autonomic disturbances occurs within 24-48 hours of ergotamine withdrawal and may
continue for 72 hours or longer. Headache is also a recognised symptom of caffeine
Not known: Visual impairment
Ear and labyrinth disorders
Rare: Bradycardia, tachycardia
Very rare: Myocardial ischaemia, myocardial infarction
Not known: Endocardial fibrosis
Uncommon: Peripheral vasoconstriction
Very rare: Gangrene
Respiratory, thoracic and mediastinal disorders
Not known: Pleural fibrosis
Common: Nausea and vomiting (not migraine related), abdominal pain
Not known: Retroperitoneal fibrosis
Skin and subcutaneous tissue disorders
Rare: Rash, face oedema, urticaria
Musculoskeletal and connective tissue disorders
Uncommon: Pain in extremity, weakness in extremity
Rare: Myalgia, muscle spasms
Rare: Pulse absent
Injury, poisoning and procedural complications
Rare: Ergot poisoning
Hypersensitivity reactions such as skin rash, face oedema, urticaria and dyspnoea.
Ergotism is defined as an intense arterial vasoconstriction, producing signs and
symptoms of peripheral vascular ischemia of the extremities and other tissues.
If ergotamine-containing drugs are used excessively over years, they may induce fibrotic
changes, in particular of the pleura and the retroperitoneum. There have also been rare
reports of fibrotic changes of the cardiac valves (see Special warnings and special
precautions). The occurrence of drug-induced headaches has been reported during
prolonged and uninterrupted treatment with Cafergot.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicine is important. It
allows continued monitoring of the benefit/risk balance of the medicine. Healthcare
professionals are asked to report any suspected adverse reactions
Nausea, vomiting, drowsiness, confusion, tachycardia, dizziness, respiratory depression,
hypotension, convulsion, shock, coma, symptoms and complications of ergotism.
Ergotism is defined as an intense arterial vasoconstriction, producing signs and
symptoms of peripheral vascular ischemia of the extremities such as numbness, tingling
and pain in the extremities, cyanosis, absence of pulse and if the condition is allowed to
progress untreated, gangrene may result. Furthermore ergotism can also involve signs
and symptoms of vascular ischemia of other tissues such as renal or cerebral vasospasm.
Most cases of ergotism are associated with chronic intoxication and/ or overdose.
In the case of orally ingested drug, administration of activated charcoal is recommended.
In the case of very recent oral intake gastric lavage may be considered.
Treatment should be symptomatic. In the event of severe vasospastic reactions, i.v.
administration of a peripheral vasodilator such as nitroprusside, phentolamine or
dihydralazine, local application of warmth to the affected area and nursing care to
prevent tissue damage are recommended. In the event of coronary constriction,
appropriate treatment such as nitroglycerin should be initiated.
For advice on the management of overdose please contact the National Poisons Centre
on 0800 POISON (0800 764766).
Pharmacotherapeutic group: Antimigraine preparations
ATC code: N02CA52
Ergotamine aborts attacks of migraine with or without aura by its specific vasotonic
action on distended extracranial arteries. Ergotamine can cause vasoconstriction by
stimulating alpha-adrenergic and 5-HT receptors. It displays moderate to high affinity
for various serotonin receptor subtypes however its beneficial effect in migraine are
primarily linked to agonist properties at 5-HT
Regional changes to cerebral flows resulting from intracranial arterial vasodilatation
accompany the migraine attack. The mechanism seems to be related to a reduction in
systemic levels of serotonin which, in turn, leads to the vasomotor changes observed.
Because of its direct vasoconstrictive effect on the smooth muscles of the dilated
vessels, ergotamine aborts the migraine attack and vascular headaches. Ergotamine also
acts on the vasomotor centres and leads to the blockage of peripheral alpha-adrenergic
Ergotamine exerts a tonic effect on the smooth vascular musculature and presents a
particular affinity for arterial monoaminergic receptors (NA and HT), especially in the
external carotid network.
Numerous studies performed in animals and humans have amply demonstrated that the
vasoconstrictive action of ergotamine manifests itself selectively at the carotid and
extracranial arteries and is due mainly to stimulation of serotonergic and alpha-
As regards any changes in blood pressure, it has been demonstrated that these depend
mainly on the pre-existing pressures: with Cafergot there is a slight and transient
increase in pressure in normotensive subjects and hypotension in hypertensive subjects.
Caffeine accelerates and increases the enteral absorption of ergotamine. Also caffeine
exerts its analgesic activity through blockade of peripheral pronociceptive actions of
adenosine and the activation of central noradrenergic pathways that constitute an
endogenous pain suppressing system.
Studies using tritium-labelled ergotamine indicate that 62% of an oral dose is absorbed
from the gastrointestinal tract. Peak plasma levels are reached about 2 hours after
Protein binding for ergotamine amounts to 98%.
Ergotamine is extensively metabolized in the liver and is a substrate for the CYP3A4
enzyme system. It has been suggested that the therapeutic effects of the drug are
partially due to active metabolites.
Parent drug and metabolites are mainly excreted in the bile. Their elimination from
plasma is biphasic, with half-lives of 2.7 and 21 hours, respectively.
After oral administration, caffeine is rapidly and almost completely absorbed from the
GI tract, and peak concentrations achieved after oral administration of 175 mg range
between 5 - 10 μg/mL. Peak plasma concentrations are reached in 15-120 minutes.
Plasma protein binding of caffeine is 35%. Caffeine is distributed relatively uniformly
throughout all body tissues, including cerebrospinal fluid, breast milk, salvia, and
semen. The volume of distribution is about 0.7 L/kg. Caffeine crosses the placental
Caffeine is metabolized to a large extent by CYP1A2 to paraxanthine. Paraxanthine is
further metabolised to uracil and uric acid derivatives by demethylation and
The metabolites are excreted mainly in the urine. Plasma elimination half-life is about
3.5 hours. The clearance of caffeine is increased by smoking.
Preclinical safety data
values after single intravenous injection of Cafergot (ergotamine/caffeine 1:50)
were found to be 40 mg/kg in rabbits, 124 mg/kg in rats, and 111 mg/kg in mice. After
single oral administration in mice, LD
was 474 mg/kg.
Chronic and subchronic toxicity
In a 26-week oral safety study in beagle dogs, ergotamine induced vomiting, salivation
and decreased heart rate. In addition, superficial necrosis at the ear margin was
observed, which is a common finding in lop-eared dogs and is due to the marked
vasoconstrictor effect of the drug.
There are no data about the carcinogenic potential of ergotamine.
Studies in rodents showed no carcinogenic activity of caffeine.
Ergotamine showed no evidence for embryonal mortality or teratogenic effects in rabbits
at 1, 3 and 10 mg/kg per day, and in rats at up to 3 mg/kg per day. However, in rats
given 10 mg/kg per day, maternal weight increase was inhibited, fetal ossification
retarded and prenatal mortality increased. High ergotamine doses constricted the uterine
vessels, reduced blood supply and thus induced hypoxia which is known to be
responsible for teratogenic effects in the offspring.
The combination of ergotamine and caffeine (1:100) revealed no teratogenic potential in
pregnant rats and rabbits. At high oral ergotamine doses, developmental toxicity (e.g.
decreased fetal body weight, delayed skeletal ossification or increased prenatal
mortality) was observed in experimental animals. This observation has been attributed to
reduced uteroplacental blood flow resulting from prolonged vasoconstriction of the
uterine vessels and/or increased myometrial tone induced by ergotamine. In a
reproductive performance study in male rats, fertility was not impaired. In a
reproductive performance study and a peri-/post-natal study in female rats, an increased
number of stillbirth and/or peri-/post-natal mortality was observed.
In animal studies, caffeine was found to be teratogenic only at very high doses.
No mutagenicity study was performed with ergotamine/caffeine combinations. In vivo
models showed no evidence of mutagenic activity of ergotamine, and therefore is
considered devoid of genotoxic potential. The overall evidence from numerous genetic
toxicity studies indicates that caffeine has no genotoxic potential at exposures relevant to
List of excipients
Iron oxide yellow (E172)
Special precautions for storage
Protect from light. Store at or below 25°C.
Cafergot must be kept out of the reach and sight of children
Nature and contents of container
Bottles of 100 tablets
Special precautions for disposal and other handling
No special requirements
AFT Pharmaceuticals Ltd
PO BOX 33203
Contact number: 0800 423 823
DATE OF FIRST APPROVAL
Date of publication in the New Zealand Gazette of consent to distribute the medicine:
31 December 1969
DATE OF REVISION OF TEXT
13 February 2018
Summary table of changes
Summary of new information
Datasheet format updated
This section has been updated for addition of adverse
effect as a result of signal detection, Analgesic-induced or
rebound headaches after ergotamine withdrawal.
Pharmacotherapeutic group has been added