For the prophylaxis of chronic stable angina pectoris, the treatment of Raynaud's phenomenon and essential hypertension.
For patients suffering from essential hypertension or chronic stable angina pectoris, and treated with fast release forms of nifedipine (Epilat capsules), a dose dependent increase in the risk of cardiovascular complications (e.g., myocardial infarction) and mortality may occur. Due to this, Epilat capsules should only be used for treatment of patients with essential hypertension or chronic stable angina pectoris if no other treatment is appropriate.

Posology
Method of administration: Oral use.
Epilat capsules should be swallowed whole with a little liquid, either with or without food.
Epilat capsules should not be taken with grapefruit juice.
Dosage regimen:
The maximum total daily dose is 60 mg. The recommended starting dose is 5 mg every eight hours with subsequent titration of dose according to response permitting an increase to a maximum of 20 mg every eight hours.
Co-administration with CYP 3A4 inhibitors or CYP 3A4 inducers may result in the recommendation to adapt the nifedipine dose or not to use nifedipine at all.
Duration of treatment:
Treatment may be continued indefinitely.
Additional information for special populations:
Children and adolescents:
The safety and efficacy of Epilat capsules in children below 18 years of age has not been established.
Geriatric patients:
The pharmacokinetics of Epilat capsules are altered in the elderly so that lower maintenance doses of nifedipine may be required compared to younger patients.
Patients with hepatic impairment:
Nifedipine is metabolised primarily by the liver and therefore patients with liver dysfunction should be carefully monitored, and in severe cases, a dose reduction may be necessary.
Patients with renal impairment:
Based on pharmacokinetic data, no dosage adjustment is required in patients with renal impairment.

- Epilat capsules must not be administered to patients with known hypersensitivity to nifedipine, or to other dihydropyridines because of the theoretical risk of cross-reactivity, or to any of the excipients. - Epilat capsules are contraindicated in pregnancy before week 20 and during breastfeeding. - Epilat capsules must not be used in cases of cardiogenic shock, clinically significant aortic stenosis, unstable angina, or during or within 4 weeks of an acute myocardial infarction. - Epilat capsules should not be used for the treatment of acute attacks of angina. - The safety of Epilat capsules in malignant hypertension has not been established. - Epilat capsules should not be used for secondary prevention of myocardial infarction. Epilat capsules should not be administered concomitantly with rifampicin since effective plasma levels of nifedipine may not be achieved owing to enzyme induction.

- Epilat capsules must not be administered to patients with known hypersensitivity to nifedipine, or to other dihydropyridines because of the theoretical risk of cross-reactivity, or to any of the excipients.
- Epilat capsules are contraindicated in pregnancy before week 20 and during breastfeeding.
- Epilat capsules must not be used in cases of cardiogenic shock, clinically significant aortic stenosis, unstable angina, or during or within 4 weeks of an acute myocardial infarction.
- Epilat capsules should not be used for the treatment of acute attacks of angina.
- The safety of Epilat capsules in malignant hypertension has not been established.
- Epilat capsules should not be used for secondary prevention of myocardial infarction.
Epilat capsules should not be administered concomitantly with rifampicin since effective plasma levels of nifedipine may not be achieved owing to enzyme induction.

Drugs that affect nifedipine:
Nifedipine is metabolised via the cytochrome P450 3A4 system, located both in the intestinal mucosa and in the liver. Drugs that are known to either inhibit or to induce this enzyme system may therefore alter the first pass (after oral administration) or the clearance of nifedipine.
The extent as well as the duration of interactions should be taken into account when administering nifedipine together with the following drugs:
Rifampicin: Rifampicin strongly induces the cytochrome P450 3A4 system. Upon co-administration with rifampicin, the bioavailability of nifedipine is distinctly reduced and thus its efficacy weakened. The use of nifedipine in combination with rifampicin is therefore contraindicated.
Upon co-administration of known inhibitors of the cytochrome P450 3A4 system the blood pressure should be monitored and, if necessary, a reduction in the nifedipine dose considered. In the majority of these cases, no formal studies to assess the potential for a drug interaction between nifedipine and the drug(s) listed have been undertaken, thus far.
Drugs increasing nifedipine exposure:
- macrolide antibiotics (e.g., erythromycin)
- anti-HIV protease inhibitors (e.g., ritonavir)
- azole anti-mycotics (e.g., ketoconazole)
- fluoxetine
- nefazodone
- quinupristin/dalfopristin
- cisapride
- valproic acid
- cimetidine
- diltiazem
Upon co-administration of inducers of the cytochrome P450 3A4 system, the clinical response to nifedipine should be monitored and, if necessary, an increase in the nifedipine dose considered. If the dose of nifedipine is increased during co-administration of both drugs, a reduction of the nifedipine dose should be considered when the treatment is discontinued.
Drugs decreasing nifedipine exposure:
- rifampicin (see above)
- phenytoin
- carbamazepine
- phenobarbital
Effects of nifedipine on other drugs:
Nifedipine may increase the blood pressure lowering effect of concomitant applied antihypertensives.
When nifedipine is administered simultaneously with beta-receptor blockers the patient should be carefully monitored, since deterioration of heart failure is also known to develop in isolated cases.
Digoxin: The simultaneous administration of nifedipine and digoxin may lead to reduced digoxin clearance and, hence, an increase in the plasma digoxin level. The patient should therefore be subjected to precautionary checks for symptoms of digoxin overdosage and, if necessary, the glycoside dose should be reduced.
Quinidine: Co-administration of nifedipine with quinidine may lower plasma quinidine levels, and after discontinuation of nifedipine, a distinct increase in plasma quinidine levels may be observed in individual cases. Consequently, when nifedipine is either additionally administered or discontinued, monitoring of the quinidine plasma concentration, and if necessary, adjustment of the quinidine dose are recommended. Blood pressure should be carefully monitored and, if necessary, the dose of nifedipine should be decreased.
Tacrolimus: Tacrolimus is metabolised via the cytochrome P450 3A4 system. Published data indicate that the dose of tacrolimus administered simultaneously with nifedipine may be reduced in individual cases. Upon co-administration of both drugs, the tacrolimus plasma concentrations should be monitored and, if necessary, a reduction in the tacrolimus dose considered.
Drug food interactions:
Grapefruit juice inhibits the cytochrome P450 3A4 system. Administration of nifedipine together with grapefruit juice thus results in elevated plasma concentrations and prolonged action of nifedipine due to a decreased first pass metabolism or reduced clearance. As a consequence, the blood pressure lowering effect of nifedipine may be increased. After regular intake of grapefruit juice, this effect may last for at least three days after the last ingestion of grapefruit juice.
Ingestion of grapefruit/grapefruit juice is therefore to be avoided while taking nifedipine.
Other forms of interaction:
Nifedipine may increase the spectrophotometric values of urinary vanillylmandelic acid falsely. However, HPLC measurements are unaffected.

Epilat capsules are contra-indicated in pregnancy before week 20.
There are no adequate and well-controlled studies in pregnant women.
The available information is inadequate to rule out adverse drug effects on the unborn and newborn child. Therefore any use in pregnancy after week 20 requires a very careful individual risk benefit assessment and should only be considered if all other treatment options are either not indicated or have failed to be efficacious.
Nifedipine passes into the breast milk. As there is no experience of possible effects on infants, breastfeeding should first be stopped if nifedipine treatment becomes necessary during the breastfeeding period.

Reactions to the drug, which vary in intensity from individual to individual, may impair the ability to drive or to operate machinery. This applies particularly at the start of treatment, on changing the medication and in combination with alcohol.

	Common > 1% to <10%	Uncommon > 0.1% to <1%	Rare > 0.01% to <0.1%	Frequency Not Known
Immune System Disorders		Allergic reaction. Allergic oedema / angioedema (incl. larynx oedema*)	Pruritus. Urticaria. Rash.	Anaphylactic/ anaphylactoid reaction.
Psychiatric Disorders		Anxiety reactions. Sleep disorders
Nervous System Disorders	Headache	Vertigo Migraine Dizziness Tremor	Par-/Dysaesthesia
Eye Disorders		Visual disturbances
Cardiac Disorders		Tachycardia Palpitations
Vascular Disorders	Oedema Vasodilatation	Hypotension Syncope
Respiratory, Thoracic and Mediastinal Disorders		Nasal congestion Nosebleed		Dyspnoea
Gastrointestinal Disorders	Constipation	Gastrointestinal and abdominal pain Nausea Dyspepsia Flatulence Dry mouth	Gingival hyperplasia	Vomiting
Hepatobiliary Disorders		Transient increase in liver enzymes
Skin and Subcutaneous Tissue Disorders		Erythema
Musculoskeletal, Connective Tissue and Bone Disorders		Muscle cramps Joint swelling
Renal and Urinary Disorders		Polyuria Dysuria
Reproductive System and Breast Disorders		Erectile dysfunction
General Disorders and Administration Site Conditions	Feeling unwell	Unspecific pain Chills

* = may result in life-threatening outcome

Symptoms:
The following symptoms are observed in cases of severe nifedipine intoxication:
Disturbances of consciousness to the point of coma, a drop in blood pressure, tachycardia, bradycardia, hyperglycaemia, metabolic acidosis, hypoxia, cardiogenic shock with pulmonary oedema.
Treatment:
As far as treatment is concerned, elimination of nifedipine and the restoration of stable cardiovascular conditions have priority. Elimination must be as complete as possible, including the small intestine, to prevent the otherwise inevitable subsequent absorption of the active substance.
The benefit of gastric decontamination is uncertain.
1. Consider activated charcoal (50 g for adults, 1 g/kg for children) if the patient presents within 1 hour of ingestion of a potentially toxic amount.
Although it may seem reasonable to assume that late administration of activated charcoal may be beneficial for sustained release (SR, MR) preparations there is no evidence to support this.
2. Alternatively consider gastric lavage in adults within 1 hour of a potentially life-threatening overdose.
3. Consider further doses of activated charcoal every 4 hours if a clinically significant amount of a sustained release preparation has been ingested with a single dose of an osmotic laxative (e.g. sorbitol, lactulose or magnesium sulphate).
4. Asymptomatic patients should be observed for at least 4 hours after ingestion and for 12 hours if a sustained release preparation has been taken.
Haemodialysis serves no purpose as nifedipine is not dialysable.
Hypotension as a result of cardiogenic shock and arterial vasodilatation can be treated with calcium (10-20 ml of a 10 % calcium gluconate solution administered intravenously over 5-10 minutes). If the effects are inadequate, the treatment can be continued, with ECG monitoring. If an insufficient increase in blood pressure is achieved with calcium, vasoconstricting sympathomimetics such as dopamine or noradrenaline should be administered. The dosage of these drugs should be determined by the patient's response.
Symptomatic bradycardia may be treated with atropine, beta-sympathomimetics or a temporary cardiac pacemaker, as required.
Additional fluids should be administered with caution to avoid cardiac overload.

Nifedipine is a calcium antagonist of the 1, 4-dihydropyridine type. Calcium antagonists reduce the transmembranal influx of calcium ions through the slow calcium channel into the cell. As a specific and potent calcium antagonist, nifedipine acts particularly on the cells of the myocardium and the smooth muscle cells of the coronary arteries and the peripheral resistance vessels. The main action of Epilat capsules is to relax arterial smooth muscle both in the coronary and peripheral circulation.
In angina pectoris, Epilat capsules relax peripheral arteries so reducing the load on the left ventricle. Additionally, Epilat capsules dilate submaximally both clear and pre-stenotic coronary arteries, and stenotic and post-stenotic coronary arteries, thus protecting the heart against coronary artery spasm and improving perfusion to the ischaemic myocardium.
Epilat capsules reduce the frequency of painful attacks and ischaemic ECG changes, irrespective of the relative contribution from coronary artery spasm or atherosclerosis.
Epilat capsules cause a reduction in blood pressure such that the percentage lowering is directly related to its initial level. In normotensive individuals, Epilat capsules have little or no effect on blood pressure.

Absorption:
After oral administration nifedipine is almost completely absorbed. The systemic availability of orally administered nifedipine immediate release formulation (Epilat capsules) is 45 – 56 % owing to a first pass effect. Maximum plasma and serum concentrations are reached at 30 to 60 minutes. Simultaneous food intake leads to delayed, but not reduced absorption.
Distribution:
Nifedipine is about 95 % bound to plasma protein (albumin). The distribution half-life after intravenous administration has been determined to be 5 to 6 minutes.
Biotransformation:
After oral administration nifedipine is metabolized in the gut wall and in the liver, primarily by oxidative processes. These metabolites show no pharmacodynamic activity. Nifedipine is excreted in the form of its metabolites predominantly via the kidneys and about 5 – 15 % via the bile in the faeces. The unchanged substance is recovered only in traces (below 0.1 %) in the urine.
Elimination:
The terminal elimination half-life is 1.7 to 3.4 hours. No accumulation of the substance after the usual dose was reported during long-term treatment.
In cases of impaired kidney function no substantial changes have been detected in comparison with healthy volunteers. In cases of impaired liver function the elimination half-life is distinctly prolonged and the total clearance is reduced. A dose reduction may be necessary in severe cases.

None stated.

Inactive ingredients:
• glyverine
• Polyethylene glycol 400
• Peppermint oil
• Polysorbate80
• Purified water
• Gelatin Powder
• Methyl Paraben sodium
• Propyl Paraben sodium
• Sunset yellow E110
• Titanium dioxide
• Glycerin

Not Applicable.

3 years.

Store in the original container. The capsules should be protected from strong light.
Store at temp. not exceeding 30°C.

carton box containing a brown glass (type II) bottle of 30 soft gelatin capsules with pilfer proof aluminum cap and an inner leaflet.

No special requirements.