| Revised text is in blue, deleted text is in blue and score through
4.3 Contra-indications
Known hypersensitivity to ergot alkaloids, caffeine, or any other components of the formulation.
Patients with impaired peripheral circulation, obliterative vascular disease, coronary heart disease, inadequately controlled hypertension, septic conditions or shock. Impaired hepatic or renal function, temporal arteritis and patients with hemiplegic or basilar migraine are also contraindicated.
Pregnancy or nursing mothers.
Concomitant treatment with macrolide antibiotics, HIV-protease or reverse-transcriptase inhibitors, azole antifungals (see 4.5 Interactions with other medicinal products and other forms of interaction).
Concomitant treatment with vasoconstrictive agents (including ergot alkaloids, sumatriptan and other 5HT1-receptor agonists (see 4.5 Interactions with other medicinal products and other forms of interaction).
4.4 Special warnings and precautions for use
Cafergot is only indicated for the treatment of acute migraine attacks and not for prevention.
Continued daily use of Cafergot or use in excess of the recommended doses must be avoided since this may cause vasospasm.
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.
Patients who are being treated with Cafergot should be informed of the maximum doses allowed and of the first symptoms of over dosage: hypoaesthesia, paraesthesia ( eg 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 are used excessively over years, they may induce fibrotic changes, in particular of the pleura and retroperitoneum. 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.
Rare cases of solitary rectal or anal ulcer have occurred from abuse of ergotamine containing suppositories, usually at higher than recommended doses or with continuous use at the recommended dose for many years.
4.5 Interactions with other medicaments and other forms of interaction
Ergotismfincreased peripheral vasoconstriction)
Several drugs increase the risk of ergotism (vasoconstriction, convulsions, other CNS and GI effects) and concomitant use of the following with Cafergot should be avoided (see section 4.3): -
Antibacterials
· Macrolides (eg erythromycin, azithromycin, clarithromycin, spiramycin) or telithromycin
· quinupristin/dalfopristin
· tetracycline
Antifungals
· lmidazoles (eg ketaconazole, miconazole)
· Triazoles (eg itraconazole, posaconazole, voriconazole)
· Antivirals (eg amprenavir, indinavir, nelfinavir, ritonavir, saquinavir. atazinavir, efavirenz)
5HT1 agonists
· Avoid Cafergot for 6 hours after almotriptan, rizatriptan, sumatriptan or zolmitriptan. Avoid almotriptan, rizatriptan, sumatriptan or zolmitriptan for 24 hours after Cafergot.
· Avoid Cafergot for 24 hours after eletriptan or frovatriptan. Avoid eletriptan or frovatriptan for 24 hours after Cafergot.
Cimetidine
Sympathomimetic agents
Beta-blockers
Other vasoconstrictors - excessive nicotine may enhance vasoconstriction
Other
Anaesthetics
· Halothane reduces the effect of ergometrine on the parturient uterus
Antidepressants
· Reboxetine - possible increase in hypertension in association with ergot
The concomitant use of tetracyclines, sympathomimetics, cimetidonem, cytochrome P450 3A (CYP3A) inhibitors, such as macrolide antibiotics (e.g. troleandomycin, erythromycin, clarithromycin), HIV protease or reverse transcriptase inhibitors (e.g. ritonavir, indinavir, nelfinavir, delaviridine) or azole antifungals (ketocomnazole, itraconazole, voriconazole) and Cafergot must be avoided (see 4.3 Contra-indications), since this can result in an elevated exposure to ergotamine and ergot toxicity (vasospasm and ischemia of the extremities and other tissues). The manufacturers of quinupristin / dalfopristin also recommend against concomitant use with ergotamine. There is a possible risk of hypertension when using ergotamine and reboxetine. Ergot alkaloids have also been shown to be both inhibitors and substrates of CYP3A. No pharmacokinetic interactions involving other cytochrome P450 isoenzymes are known.
The effects of Ergotamine on the parturient uterus are reduced by halothane.
As vasospastic reactions have been reported with beta-blockers alone and in a few patients treated concomitantly with ergotamine and propranolol, caution is advised in the concomitant use of these agents with Cafergot.
Concurrent use of vasoconstrictors agents, including preparations containing ergot alkaloids, sumatriptan and other 5-HT1-receptor agonists, and nicotine (e.g. heavy smoking) must be avoided since this may result in enhanced vasoconstriction (see 4.3 Contraindications).
Ergotamine should not be administered within six hours of therapy with 5-HT1 receptor agonists. In addition, use of 5-HT1 receptor agonists should be avoided for at least 24 hours after the last ergotamine dose.
4.6 Pregnancy and lactation
Ergotamine-containing products are contraindicated in pregnancy due to oxytocic and vasoconstrictor effects on the placenta and umbilical cord.
Ergotamine is excreted in breast milk and may cause symptoms of vomiting, diarrhoea, weak pulse and unstable blood pressure in infants. Thus, Cafergot are contraindicated in nursing mothers.
4.7 Effects on ability to drive and use machinery
None known Dizziness and feelings of anxiety (trembling, sweating etc) have been reported with Cafergot. If a patient is affected they should not drive, operate machinery or take part in activities where these reactions may put themselves or others at risk.
4.8 Undesirable effects
The caffeine component of Cafergot may give rise to unwanted stimulant effects.
Side effects of Cafergot are related in the main to the ergotamine component.
Common (10%- 1%): Nausea, vomiting (not migraine related), abdominal pain and dizziness.
Other adverse reactions under the following frequency headings include:
Uncommon (1% - 0.1%) : Paraesthesia (e.g. tingling), hyopaesthesia (e.g. numbness), pain in extremities, weakness in extremities, cyanosis, peripheral vascoconstriction, diarrhoea.
Rare (0.1% - 0.01%): Hypersensitivity reactions (such as skin rash, face oedema, urticaria and dyspnoea), vertigo, bradycardia, tachycardia, increase in blood pressure, myalgia, absence of pulse and ergotism (defined as an intense arterial vasoconstriction, producing signs and symptoms of peripheral vascular ischemia). Rare cases of intestinal ischaemia have been associated with chronic use and overuse of ergotamine-containing preparations. Rarely, headache may be provoked either by chronic overdosage or by rapid withdrawal of the product.
Very rare (less than 0.01%): Myocardial ischaemia, myocardial infarction and gangrene.
Excessive use of ergotamine-containing products for prolonged periods may result in fibrotic changes, in particular of the pleura and retroperitoneum. Rare cases of fibrosis of cardiac valves have also been reported.
The occurrence of drug induced headaches has been reported during prolonged and uninterrupted treatment with Cafergot (see 4.4 Special Warnings and Precautions).
Rectal and anal ulcers may occur after long term use or use at doses higher than recommended dose of ergotamine containing suppositories (see 4.4 Special Warnings and Precautions).
4.9 Overdose
Symtoms: Nausea, vomiting, drowsiness, confusion, tachycardia, dizziness, respiratory depression, hypotension, convulsion, shock, coma and symptoms and complications of ergotism.
Ergotism is defined as an intense arterial vasoconstriction, producing signs and symptoms of peripheral vascular ischemia such as tingling and numbness in the extremities, cyanosis, absence of pulse and if the condition is allowed to progress untreated, gangrene may result. Most cases of ergotism are associated with chronic intoxication and/or overdose.
Treatment: should be directed to the elimination of ingested material by aspiration and gastric lavage.
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.
|
