Gynergene Caffeine tablet Uses, Dosage, Side Effects& Precautions

Gynergene Caffeine tablet box of 20 >> Generic drug of the therapeutic class: Neurology–psychiatry
active principles: Ergotamine , Caffeine

what is Gynergene Caffeine medication used for and indication?

• This medication is an anti-migraine medication.
• This medication is recommended for the treatment of migraine attacks.

PRESENTATION (S) AVAILABLE FOR GYNERGENE CAFFEINE

2 presentations are available for this medication:

• 1 amber glass vial (s) of 20 tablet (s)
• PVC PVDC aluminum blister pack (s) of 20 tablet (s)

FEATURE	DESCRIPTION
Pharmaceutical class	pain relievers
Active substance (s)	for one tablet: caffeine (100 mg), ergotamine (tartrate) (1 mg)
General medicine	no
Pharmaceutical form	compressed
Route (s) of administration	oral
Social security reimbursement rate	30 %
Laboratory (s)	CENTER SPECIALTIES PHARMACEUTI
Conditions of issue	available by simple prescription

Gynergene Caffeine Dosage

• In adults: 2 tablets at the start of the crisis.
• Do not exceed 6 tablets per day, nor 10 tablets per week.
• In children over 10 years old: 1 tablet at the start of the crisis.
• Do not exceed 3 tablets per day, nor 5 tablets per week.
• IN ALL CASES, STRICTLY COMPLY WITH THE DOCTOR’S ORDER.

Gynergene Caffeine Contraindications

Never take GYNERGENE CAFEINE, tablet in the following cases:

• Allergy to ergotamine, to other rye ergot derivatives or to any of the components;
• Obliterating vascular disorders, peripheral circulation disorders (especially in the fingers and toes), Raynaud’s syndrome, coronary insufficiency (angina pectoris), poorly controlled arterial hypertension, temporal arteritis, serious infectious conditions, shock, history of stroke;
• Severe renal or hepatic insufficiency;
• Hemiplegic migraine (migraine accompanied by paralysis) or basilar migraine;
• In combination with triptans (antimigraine), antibiotics of the macrolide family (except spiramycin), antiproteases (e.g. amprenavir, atazanavir, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir inhibitors), reverse transcriptase (eg delavirdine, efavirenz), voriconazole, triclabendazole, quinupristine-dalfopristine in combination, stiripentol, diltiazem, phenylpropanolamine.

In case of treatment, breast-feeding is contraindicated.

IN CASE OF DOUBT, IT IS ESSENTIAL TO ASK FOR THE OPINION OF YOUR DOCTOR OR YOUR PHARMACIST.

How To Take Gynergene Caffeine ?

Method and route of administration

• Oral route.
• IN ALL CASES, STRICTLY COMPLY WITH THE DOCTOR’S ORDER.

Frequency of administration

• IN ALL CASES, STRICTLY COMPLY WITH THE DOCTOR’S ORDER.

how does Gynergene Caffeine work?

• When administered orally, the absorption of ergotamine is rapid. Maximum plasma concentration is reached 1.5 to 2 hours after administration.
• Oral bioavailability is 62 ± 3%.
• The product has a strong tissue affinity.
• In animals, ergotamine tartrate has extensive hepatic metabolism.
• Elimination from the plasma is biphasic. The half-life of the first alpha phase is 2.7 ± 0.9 h, that of the second beta phase is 21 ± 4 h.
• Urinary elimination is low (4.3 ± 0.4%). The product is eliminated primarily through the bile and faeces.
• The addition of caffeine speeds up the passage through the blood and increases digestive absorption by at least 44%.

How To Store Gynergene Caffeine ?

• Keep this medication out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the box.
• Do not throw away any medicines via a wastewater treatment plant or with household waste. Ask your pharmacist how to throw away the medicines you no longer use. These measures will help protect the environment.
• Store at a temperature not exceeding 25 ° C.

Gynergene Caffeine Side Effects

The most common side effects are nausea and vomiting.

The following side effects have been established from clinical trials and experience since the marketing of GYNERGENE CAFFEINE.

The frequencies in the table below are given as an indication, according to the following categories: very frequent (≥ 1/10); common (≥ 1/100, <1/10); uncommon (≥ 1/1000, <1/100); rare (≥1 / 10,000, <1 / 1,000); very rare (<1 / 10,000); not known (frequency cannot be estimated from the available data). Adverse drug reactions are listed according to MedDRA system organ class.

System organ classes	Side effects
Immune system disorders	Rare: hypersensitivity reactions (such as: rash, facial edema, pruritus, urticaria, dyspnea)
Nervous system disorders	Common: dizziness Uncommon: paresthesia in fingers and toes, hypoaesthesia, headache Frequency not known: dependence, chronic daily headache, worsening headache on discontinuation of treatmenta
Ear and labyrinth disorders	Rare: dizziness
Cardiac disorders	Uncommon: cyanosis Rare: bradycardia, tachycardia Very rare: myocardial ischemia, myocardial infarction Frequency not known: valvular fibrosis
Vascular disorders	Uncommon: peripheral vasoconstrictionb Rare: increased blood pressure Very rare: gangrene
Respiratory, thoracic and mediastinal disorders	Frequency not known: pleuraled fibrosis
Gastrointestinal disorders	Common: nausea and vomiting (not related to migraine), abdominal pain Uncommon: diarrhea Frequency not known: retroperitoneal fibrosis
Musculoskeletal and connective tissue disorders	Uncommon: pain in extremity, weakness in extremity Rare: myalgia
Investigations	Very rare: no pulse
Injury, poisoning and procedural complications	Rare: ergotism

a Prolonged or excessive intake of caffeinated Gynergene can lead to dependence as well as the onset of chronic daily headaches. When treatment is stopped, headache worsening may occur within 24 to 48 hours and may continue for 72 hours or more; these headaches may be accompanied by autonomic disorders such as nausea and vomiting.

b If signs of vasospasm are observed, the intake of caffeinated Gynergene should be discontinued (see sections Warnings and precautions for use and Overdose).

c Depending on the dose of ergotamine, severe arterial vasoconstriction may occur (ergotism). This may cause signs and symptoms of vascular ischemia of the extremities or other tissues (such as renal or cerebral vasospasms) (see sections 4.4 and Overdose).

d Prolonged or excessive use may cause fibrosis (especially pleural or retroperitoneal). Rare cases of heart valve fibrosis have been reported .

Gynergene Caffeine Interactions

Expected interactions leading to a contraindication

Strong CYP3A4 inhibitors

• Concomitant use of cytochrome P450 3A4 (CYP3A4) inhibitors such as macrolide-type antibiotics (eg troleandomycin, erythromycin, clarithromycin), HIV protease or reverse transcriptase inhibitors (eg ritonavir, indinavir, nelfinavir, delavirdine) or azole antifungals (e.g. ketoconazole, itraconazole, voriconazole) and GYNERGEN CAFFEINE should be avoided (see section Contraindications), as this may result in high exposure to ergotamine and ergotism (vasospasm and ischemia of extremities and other tissues).

Vasoconstrictors

• Concomitant use of vasoconstrictor agents, including drugs containing ergot alkaloids, sumatriptan and other 5HT1 receptor agonists or nicotine (e.g. severe smoking), and sympathomimetics should be avoided because this may lead to increased vasoconstriction .

Interactions observed leading to non-recommendation of concomitant use

• Any increase in plasma caffeine concentrations due to interaction with other drug (s) may result in increased absorption of ergotamine. Caffeine undergoes extensive metabolism by CYP1A2 and drugs that increase or decrease enzyme activity may modulate metabolic clearance of caffeine. Fluoroquinolones, mexiletine, fluvoxamine, and oral contraceptives may increase plasma exposure to caffeine. Interactions between caffeine and sympathomimetics can lead to an increase in blood pressure.

Observed interactions to consider

Beta-blockers

• A few cases of vasospastic reactions have been reported in patients concomitantly treated with drugs containing ergotamine and with propranolol.

Expected interactions to take into account

Moderate / weak inhibitors of CYP3A4

• Moderate to weak inhibitors of CYP3A4 such as cimetidine, clotrimazole, fluconazole, grapefruit juice, quinupristin / dalfopristine and zileuton may also increase ergotamine exposure and caution is required when using concomitant.

Serotonin reuptake inhibitors

• The concurrent use of ergotamine and serotonin reuptake inhibitors (e.g. amitriptyline), including selective agents (e.g. sertraline), may result in serotonin syndrome and should be done with caution.

CYP3A4 inducers

• Drugs (eg nevirapine, rifampicin) inducing CYP3A4 may reduce the pharmacological action of ergotamine.

Lack of interaction

• No pharmacokinetic interactions involving other cytochrome P450 isoenzymes are known.

INTERACTIONS RELATED TO ERGOTAMINE

Contraindicated combinations (see section Contraindications)

• Triptans (almotriptan, fovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan, eletriptan): risk of arterial hypertension, coronary arterial vasoconstriction. Observe a period of 24 hours between stopping the triptan and taking the alkaloid.
• Macrolides (except spiramycin): ergotism with the possibility of necrosis of the extremities (reduction in the hepatic elimination of alkaloids from rye ergot).
• Antiproteases (eg amprenavir, atazanavir, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir): ergotism with possible necrosis of the extremities (inhibition of hepatic metabolism of the rye ergot alkaloid).
• Reverse transcriptase inhibitors (delavirdine, efavirenz): ergotism with the possibility of necrosis of the extremities (inhibition of hepatic metabolism of the rye ergot alkaloid).
• Voriconazole: ergotism with possibility of extremity necrosis (inhibition of hepatic metabolism of the rye ergot alkaloid).
• Quinupristine-dalfopristine (associated): ergotism with the possibility of necrosis of the extremities (inhibition of hepatic metabolism of the rye ergot alkaloid).
• Stiripentol: ergotism with the possibility of necrosis of the extremities (inhibition of the hepatic metabolism of ergot alkaloids).
• Diltiazem: ergotism with the possibility of necrosis of the extremities (inhibition of hepatic metabolism of the rye ergot alkaloid).
• Phenylpropanolamine: risk of vasoconstriction and / or hypertensive crises.
• Triclabendazole: ergotism with the possibility of necrosis of the extremities (inhibition of the hepatic metabolism of the alkaloids of rye ergot). Observe a period of 24 hours between stopping treatment and ergotamine and vice versa.

Combinations not recommended (see section Warnings and precautions for use)

• Dopaminergic ergot alkaloids (bromocriptine, cabergoline, pergolide, lisuride): risk of vasoconstriction and / or hypertensive outbreaks.
• Alpha sympathomimetics (oral and / or nasal routes) (etilephrine, midodrine, naphazoline, oxymetazoline, phenylephrine, synephrine, tetryzoline, tuaminoheptane, tymazoline)  : risk of vasoconstriction and / or hypertensive surges.
• Indirect sympathomimetics (except phenylpropanolamine) (ephedrine, phenylephrine, pseudoephedrine): risk of vasoconstriction and / or hypertensive outbreaks.

Combinations subject to precautions for use

• Beta-blockers (propanolol, oxprenolol): ergotism; a few cases of arterial spasm with ischemia of the extremities have been observed (addition of vascular effects). Reinforced clinical monitoring in particular during the first weeks of the combination.

INTERACTIONS RELATED TO CAFEINE

Not recommended associations

• Enoxacin: increase in plasma caffeine concentrations which may lead to excitations and hallucinations by reducing its hepatic metabolism.

Associations to take into account

• Ciprofloxacin, norfloxacin: increase in plasma concentrations of caffeine which may lead to excitations and hallucinations by reducing its hepatic metabolism.
• Mexiletine: increase in plasma caffeine concentrations, by inhibition of its hepatic metabolism by mexiletine.

Effects on ability to Drive and use machines

 Dizziness has been reported as a side effect of treatment. Caution is advised in patients performing tasks requiring skill such as driving or using machines.

Warnings and Precautions

Special warnings

• GYNERGENE CAFEINE is not recommended before the age of 10 years.
• GYNERGENE CAFEINE should under no circumstances be administered as a basic, continuous or prolonged treatment.
• Repeated administration at short intervals requires special monitoring; the possible appearance of clinical signs suggesting poor vascular tolerance requires immediate discontinuation of treatment.
• Concomitant intake of this medication with: dopaminergic rye ergot alkaloids (bromocriptine, cabergoline, pergolide, lisuride), alpha sympathomimetics (oral and / or nasal routes) (etilephrine, midodrine, naphazoline, oxymetazoline, phenylephrine, synephrine, tetry , tuaminoheptane, tymazoline), indirect sympathomimetics (except phenylpropanolamine) (ephedrine, phenylephrine, pseudoephedrine), enoxacin is not recommended.

The patients treated should be informed of the maximum doses not to be exceeded and of the first symptoms of an overdose:

• Blood circulation disorders in the extremities: the occurrence of paresthesias (numbness, tingling), painful phenomena or vasoconstriction, even at usual doses should attract attention,
• nausea and vomiting unrelated to migraine,
• symptoms of cardiac ischemia (severe pain localized in the chest and which may extend to the left arm).
• As soon as symptoms of overdose appear, treatment should be discontinued and the patient should consult their doctor immediately.

Excessive use of anti-migraine therapy may lead to the development of chronic daily headaches requiring transient discontinuation of therapy.

Precautions for use

Prolonged or excessive use should be avoided as it can lead to:

• Vasoconstriction,
• Fibrosis including retroperitoneum and pleura and in rare cases heart valves.

IN CASE OF DOUBT, DO NOT HESITATE TO ASK FOR THE ADVICE OF YOUR DOCTOR OR YOUR PHARMACIST.

PREGNANCY & BREAST-FEEDING & FERTILITY

Pregnancy

• In animals, experimentation shows a teratogenic effect with ergotamine tartrate. These effects can be attributed to a decrease in uteroplacental blood flow (see section Preclinical safety data).
• There are limited data on the use of ergotamine tartrate in pregnancy.
• In addition, this product has vasoconstrictor and oxytocic properties. Therefore, GYNERGENE CAFFEINE should not be used during pregnancy.

Feeding with milk

• Since ergot derivatives pass into breast milk, breast-feeding is contraindicated during the use of this medication.
• Ergotamine and caffeine are excreted in breast milk. Ergotamine can cause symptoms of vomiting, diarrhea, weak heartbeat, and irregular blood pressure in newborns. GYNERGENE CAFFEIN is therefore contraindicated in nursing mothers.

Fertility

• In male rats receiving oral ergotamine and caffeine (1: 100), fertility was not affected (see section Preclinical safety data).

What happens if I overdose from Gynergene Caffeine ?

Ergotism is defined as severe arterial vasoconstriction producing signs and symptoms of ischemia of the extremities or other tissues (such as renal or brain vasospasms). If left untreated, gangrene is possible. Most cases of ergotism are associated with chronic intoxication and / or overdose and / or interaction.

Symptoms

• Abdominal pain, confusion, dizziness, nausea, vomiting, headache, tachycardia or bradycardia associated with hypotension, breathing problems, dizziness, paraesthesia, ischemia, gangrene, convulsion, shock, coma, and also signs and symptoms of vascular ischemia such as numbness , tingling and pain in extremity, cyanosis and lack of pulse. In rare cases, patients may present with a myocardial infarction.

Treatment

• In the event of acute poisoning, gastric lavage and symptomatic treatment should be considered in a hospital setting, under close cardiovascular monitoring.
• Administration of activated charcoal may decrease the digestive passage of ergotamine tartrate.
• If vascular ergotism is confirmed, emergency treatment should be administered in a hospital setting.

What should I do if I miss a dose?

If you forget to take GYNERGENE CAFEINE, tablet

• If you forget to take a dose, use it as soon as possible, unless it is already time to use the next dose. Do not take a double dose to make up for the dose you forgot to take.

What happens if you stop taking Gynergene Caffeine ?

If you stop taking GYNERGENE CAFEINE, tablet

• Not applicable.
• Not applicable.
• Not applicable.
• Not applicable.

What is  Forms and Composition ?

Appearance and shape

Compressed.

• 20 tablets in blister packs (PVC / PVDC / Aluminum).
• 20 tablets in a bottle (brown glass).

Composition

WHAT GYNERGENE CAFEINE CONTAINS, TABLET  ?

The active substances are:

• Ergotamine tartrate …… 1 mg
• Anhydrous caffeine ………. 100 mg

For a tablet.

The other ingredients are:

Tartaric acid, talc, magnesium stearate, pregelatinized corn starch (Starch 1500), microcrystalline cellulose (Avicel PH 102), yellow iron oxide.

WHAT IS GYNERGENE CAFEINE, TABLET AND CONTENTS OF THE OUTER PACKAGING?

This medicine comes in tablet form. Box or bottle of 20 tablets.

NOT’s

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general information:

• Includes a general description of the drug, its use, brand names, FAQs, and relevant news and articles

Additional information:

• General explanation about dealing with the medicine: how to take the medicine, the doses and times of it, the start and duration of its effectiveness, the recommended diet during the period of taking the medicine, the method of storage and storage, recommendations in cases for forgetting the dose and instructions to stop taking the drug and take additional doses.

Special warnings:

• For pregnant and breastfeeding women, the elderly, boys and drivers, and use before surgery.

Side effects:

• It treats possible side effects and drug interactions that require attention and its effect on continuous use.
• The information contained in this medicine is based on medical literature, but it is not a substitute for consulting a doctor.