Nifecain

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT NIFECAINE (NIFECAINE)

Composition:

Active substances: nifedipine, lidocaine hydrochloride;

1 g of cream contains 3 mg of nifedipine and 15 mg of lidocaine hydrochloride;

Excipients: white soft paraffin, propylene glycol, medium-chain triglycerides, macrogol stearate, cetostearyl alcohol (emulsifying type A), glycerol monostearate, sodium methylparaben (sodium methylparahydroxybenzoate), propylparaben (propylparahydroxybenzoate), purified water.

Pharmaceutical form. Rectal cream.

Main physicochemical properties: a homogeneous yellow cream with a slight characteristic odor.

Pharmacotherapeutic group. Agents for treatment of hemorrhoids and anal fissures for local use. Other preparations, combinations.

ATC code C05AX03.

Pharmacological properties.

Pharmacodynamics.

Nifecain has a synergistic mechanism of action. Nifedipine is a dihydropyridine calcium channel blocker which, when applied locally, exerts a relaxing effect on peripheral smooth muscles. Nifedipine acts by reducing hypertonus of the internal anal sphincter.

Pharmacokinetics.

The pharmacokinetic properties of the rectal cream Nifecain were studied in healthy volunteers. Determination of active substances in blood using a validated analytical method yielded negative results, as nifedipine was not detected in serum. Furthermore, only minimal traces of lidocaine were detected in 2 out of 12 patients. These extremely low concentrations (below the quantification limit) are much lower than the concentrations capable of producing a therapeutic effect with systemic administration of lidocaine. Therefore, systemic effects of Nifecain cream due to absorption of active ingredients can be ruled out. This has been confirmed by subsequent clinical studies during which no adverse effects resulting from systemic absorption through the mucous membrane of the anorectal area were observed.

Clinical characteristics.

Indications.

Treatment of anal fissures and proctalgia associated with hypertonicity of the anal sphincter.

Contraindications.

Hypersensitivity to the active substances, particularly to lidocaine and other amide-type local anesthetics such as bupivacaine, etidocaine, mepivacaine, and prilocaine, or to any of the excipients contained in the product.

Suspected or confirmed pregnancy and breastfeeding period (see section "Use during pregnancy or breastfeeding").

Severe hypotension and heart failure.

Interaction with other medicinal products and other forms of interaction.

Interaction studies have not been conducted.

Patients receiving Class I antiarrhythmic agents (e.g., tocainide, mexiletine) or other local anesthetics should be treated with caution, as there is a risk of cumulative systemic effects due to the presence of lidocaine. Monoamine oxidase inhibitors enhance the local analgesic effect of lidocaine.

Treatment with Nifecaine rectal cream may potentiate the effect of antihypertensive agents due to the presence of nifedipine.

Propranolol prolongs the half-life of lidocaine and increases plasma levels of nifedipine.

Cimetidine may increase plasma levels of nifedipine and lidocaine.

Concomitant use of Nifecaine rectal cream in patients taking digoxin may lead to increased plasma levels of digoxin.

Special precautions for use.

Excessive or prolonged use of the medicinal product may lead to sensitization, local hyperemia, and bleeding, which resolve after discontinuation of treatment.

During clinical trials, no adverse effects due to possible systemic absorption of the medicinal product were reported.

Nifekain rectal cream should be used with particular caution in patients with severe mucosal damage and inflammation in the area to be treated, as excessive absorption of the active substances may occur in such cases.

Nifekain should be used cautiously in patients with diabetes mellitus or severe hepatic and/or renal impairment.

Treatment with Nifekain rectal cream in elderly patients, as well as in patients receiving beta-blockers or antihypertensive agents, should be performed under medical supervision.

Arterial pressure should be monitored at the beginning of treatment and periodically throughout therapy.

If treatment proves ineffective (lack of improvement or worsening of symptoms), it should be discontinued and medical advice should be sought.

Additionally, when treating hemorrhoids with Nifekain rectal cream, it is recommended to maintain hygiene of the anal area, follow an active lifestyle, and adhere to a healthy diet to ensure soft bowel movements.

Nifekain rectal cream contains sodium methylparaben (sodium methylparahydroxybenzoate) and propylparaben (propylparahydroxybenzoate), which may cause allergic reactions (possibly delayed). The presence of propylene glycol and cetostearyl alcohol (emulsifying type A) may cause local skin reactions (e.g., contact dermatitis).

Glyceryl monostearate contained in the formulation may exert a mild laxative effect.

Use during pregnancy or breastfeeding.

Nifedipine and lidocaine cross the placental barrier and are excreted in breast milk. Studies in rats and rabbits have shown that nifedipine has teratogenic effects. Lidocaine has not shown any risk to the fetus.

When calcium channel blockers, particularly nifedipine, are used as a tocolytic agent during pregnancy, especially in cases of multiple pregnancies (twins or more), and administered intravenously and/or in combination with beta-2 agonists, acute pulmonary edema has been observed.

Therefore, this medicinal product is not recommended for use in pregnant women or women who are breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

Concomitant intake of nifedipine with alcohol may negatively affect reaction speed.

The medicinal product Nifekain rectal cream is intended for local application and acts locally; therefore, its effect on the ability to drive or operate machinery cannot be predicted.

Method of Administration and Dosage

For endorectal and perianal use. Apply the cream twice daily for at least three weeks.

Method of administration: Lie on your left side, remove the cap from the tube and attach the cannula. Squeeze out a small amount of cream to lubricate the cannula and insert it into the anal opening. Press the end of the tube to extrude approximately one centimeter of cream (one centimeter of tube contains approximately 2.5–3 g of cream).

Children

Not recommended for use in children due to lack of data on safety and efficacy.

Overdose

No cases of systemic toxicity due to overdose following topical application of Nifecain rectal cream have been reported. In the event of poisoning following topical application, systemic effects are expected to be similar to those typically observed with other routes of administration of the active ingredients.

In case of severe intoxication with nifedipine, disorders of consciousness including coma, hypotension, cardiac arrhythmias, and cardiogenic shock may occur.

In case of accidental ingestion of the medicinal product (after swallowing several grams of cream), systemic symptoms caused by lidocaine hydrochloride are expected. Depending on the dose, these may manifest as severe cardiovascular disturbances (hypotension, increased sweating, pallor, bradycardia, arrhythmia, myocardial depression, shock, and in particularly severe cases, cardiac arrest) or reactions related to central nervous system (CNS) disturbances (headache, dizziness, blurred vision, diplopia, tinnitus, drowsiness, limb numbness, chills, restlessness, seizures, dyspnea, and in particularly severe cases, respiratory failure). Methemoglobinemia is possible.

Treatment: In case of overdose, careful monitoring of vital functions and supportive measures to maintain oxygen levels are required, along with symptomatic treatment of CNS and cardiovascular disturbances. For example, beta-sympathomimetic agents may be used in case of bradycardia, atropine, and in case of pronounced hypotension — calcium gluconate (10–20 mL of 10% solution administered slowly intravenously) and possibly dopamine or noradrenaline.

A significant proportion of toxic reactions to local anesthetics and lidocaine involve CNS manifestations, such as dizziness, often accompanied by visual and auditory disturbances, e.g., difficulty with accommodation and tinnitus. In the most severe cases, CNS depression and seizures may occur. Treatment is symptomatic.

Side effects.

Local reactions such as pain, burning, itching, hyperemia, and bleeding may occur. These effects diminish upon discontinuation of treatment.

In very rare cases, local application of preparations containing lidocaine has caused allergic reactions (in severe cases—anaphylactic shock).

During clinical trials, no adverse effects related to possible systemic absorption of the two active ingredients (headache, dizziness, peripheral vasodilation, hypotension, dizziness, and tremor) were observed.

Frequency unknown: pulmonary edema*.

Systemic adverse reactions associated with lidocaine are identical in presentation to those associated with amide-type local anesthetics.

*Cases reported when used as a tocolytic during pregnancy (see section "Use during pregnancy or breastfeeding").

Shelf life. 3 years.

Use within 30 days after opening the tube.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

30 g of cream in a tube with cap; one tube with cannula in a cardboard box.

Prescription category. Prescription only.

Manufacturer.

New.Fa.Dem. S.r.l.

Manufacturer's address and location of business activity.

ZONA INDUSTRIAL - 80014 GIUGLIANO IN CAMPANIA (NA), Italy

INSTRUCTIONS

for medical use of the medicinal product

NIFECAINE

(NIFECAINE)

Composition:

Active substances: nifedipine, lidocaine hydrochloride;

1 g of cream contains nifedipine 3 mg and lidocaine hydrochloride 15 mg;

Excipients: white soft paraffin, propylene glycol, medium-chain triglycerides, macrogol stearate, cetostearyl alcohol (type A) emulsifying, glycerol monostearate, sodium methylparaben (sodium methylparahydroxybenzoate), propylparaben (propylparahydroxybenzoate), purified water.

Pharmaceutical form. Rectal cream.

Main physicochemical properties: homogeneous yellow cream with a slight characteristic odor.

Pharmacotherapeutic group. Agents for treatment of haemorrhoids and anal fissures for local use. Other preparations, combinations.

ATC code C05A X03.

Pharmacological properties.

Pharmacodynamics.

Nifecain has a synergistic mechanism of action. Nifedipine is a dihydropyridine calcium channel blocker; when applied locally, it exerts a relaxant effect on peripheral smooth muscles. Nifedipine acts by reducing the hypertonicity of the internal anal sphincter.

Pharmacokinetics.

The pharmacokinetic properties of the Nifecain rectal cream were studied in healthy volunteers. Determination of active substances in blood using a validated analytical method yielded negative results, as nifedipine was not detected in serum. Furthermore, only minimal traces of lidocaine were detected in 2 out of 12 patients. These extremely low concentrations (below the quantification threshold) are much lower than the concentrations capable of producing a therapeutic effect with systemic administration of lidocaine. Therefore, systemic effects of Nifecain cream due to absorption of active ingredients can be excluded. This was confirmed by subsequent clinical studies, during which no adverse effects resulting from systemic absorption through the anorectal mucosa were observed.

Clinical characteristics.

Indications.

Treatment of anal fissures and proctalgia associated with hypertonicity of the anal sphincter.

Contraindications.

Hypersensitivity to the active substances, particularly to lidocaine and other amide-type local anesthetics such as bupivacaine, etidocaine, mepivacaine, and prilocaine, or to any of the excipients of the product.

Suspected or confirmed pregnancy and breastfeeding period (see section "Use during pregnancy or breastfeeding").

Severe hypotension and heart failure.

Interaction with other medicinal products and other forms of interaction.

Interaction studies have not been conducted.

Patients receiving Class I antiarrhythmic agents (e.g., tocainide, mexiletine) or other local anesthetics should use the product with caution, as there is a risk of cumulative systemic effects due to the presence of lidocaine. Monoamine oxidase inhibitors enhance the local analgesic effect of lidocaine.

Treatment with Nifecain rectal cream may potentiate the effect of antihypertensive agents due to the presence of nifedipine.

Propranolol prolongs the half-life of lidocaine and increases plasma levels of nifedipine.

Cimetidine may increase plasma levels of both nifedipine and lidocaine.

Concomitant use of Nifecain rectal cream in patients taking digoxin may lead to increased plasma levels of digoxin.

Special precautions for use.

Topical application of the medicinal product in excessive doses and/or over a prolonged period may lead to sensitization reactions, local hyperemia, and bleeding, which resolve after discontinuation of treatment.

During clinical trials, no adverse effects due to possible systemic absorption of the medicinal product were recorded.

Nifekaïn rectal cream should be used with particular caution in patients with severe mucosal damage and inflammation in the area to be treated, as excessive absorption of the active substances may occur under such conditions.

Nifekaïn should be used cautiously in patients with diabetes mellitus or severe hepatic and/or renal insufficiency.

Treatment with Nifekaïn rectal cream in elderly patients, as well as in patients receiving beta-blockers or antihypertensive agents, should be carried out under medical supervision.

Blood pressure should be monitored at the beginning of treatment and periodically throughout therapy.

If treatment proves ineffective (lack of improvement or worsening of symptoms), it should be discontinued and the patient should consult a physician.

In addition, when treating hemorrhoids with Nifekaïn rectal cream, it is recommended to maintain hygiene of the anal area, follow an active lifestyle, and adhere to healthy dietary principles to ensure soft bowel movements.

Nifekaïn rectal cream contains sodium methylparaben (sodium methylparahydroxybenzoate) and propylparaben (propylparahydroxybenzoate), which may cause allergic reactions (possibly delayed). The presence of propylene glycol and cetostearyl alcohol (emulsifying type A) may cause local skin reactions (e.g., contact dermatitis).

Glyceryl monostearate contained in the formulation may exert a mild laxative effect.

Use during pregnancy or breastfeeding.

Nifedipine and lidocaine cross the placental barrier and are excreted in breast milk. Studies in rats and rabbits have shown that nifedipine has teratogenic effects. Lidocaine has not shown any risk to the fetus.

When calcium channel blockers, particularly nifedipine, are used as a tocolytic agent during pregnancy, especially in multiple pregnancies (twins or more), and administered intravenously and/or concomitantly with beta-2 agonists, acute pulmonary edema has been observed.

Therefore, this medicinal product is not recommended for use in pregnant women or women who are breastfeeding.

Ability to influence reaction speed when driving or operating machinery.

Concomitant use of nifedipine with alcohol may negatively affect reaction speed.

The medicinal product Nifekaïn, rectal cream, is intended for topical use and acts locally; therefore, its influence on the ability to drive or operate machinery cannot be predicted.

Method of Administration and Dosage.

For endorectal and perianal use. Apply the cream twice daily for at least three weeks.

Method of administration: Lie on your left side, remove the cap from the tube and attach the cannula. Squeeze out a small amount of cream to lubricate the cannula and insert it into the anal opening. Press the end of the tube to extrude approximately one centimeter of cream (one centimeter of cream from the tube contains approximately 2.5–3 g of cream).

Children.

Not recommended for use in children due to lack of data on safety and efficacy.

Overdose.

No cases of systemic toxicity due to overdose following local application of Nifecain rectal cream have been reported. In case of poisoning after local application of the drug, systemic effects are expected to be similar to those usually observed with other routes of administration of the active ingredients.

In case of severe intoxication with nifedipine, disorders of consciousness may occur, including coma, decreased arterial pressure, cardiac arrhythmias, and cardiogenic shock.

In case of accidental ingestion of the medicinal product (after swallowing several grams of cream), systemic symptoms caused by lidocaine hydrochloride are expected. Depending on the dose, these may manifest as severe cardiovascular disturbances (decreased arterial pressure, increased sweating, pallor, bradycardia, arrhythmia, myocardial depression, shock, and in particularly severe cases—cardiac arrest) or reactions related to central nervous system disturbances (headache, dizziness, blurred vision, diplopia, tinnitus, somnolence, numbness of extremities, chills, anxiety, seizures, dyspnea, and in particularly severe cases—respiratory failure). Methemoglobinemia is possible.

Treatment. In case of overdose, careful monitoring of vital functions is required, along with supportive measures to maintain oxygen levels, and symptomatic treatment of disturbances of the central nervous and cardiovascular systems. For example, beta-sympathomimetic agents may be used for bradycardia, atropine, and in case of pronounced hypotension—calcium gluconate (10–20 mL of 10% solution administered slowly intravenously) and possibly dopamine or noradrenaline.

A significant portion of toxic reactions to local anesthetics and lidocaine involve manifestations from the CNS; dizziness often occurs, frequently accompanied by visual and auditory disturbances, such as accommodation difficulties and tinnitus. In the most severe cases, CNS depression and seizures are possible. Treatment is symptomatic.

Side effects

Local reactions such as pain, burning, itching, hyperemia, and bleeding may occur. These effects diminish upon discontinuation of treatment.

In very rare cases, local application of preparations containing lidocaine has caused allergic reactions (in severe cases—anaphylactic shock).

During clinical trials, no adverse effects due to possible systemic absorption of the two active ingredients (headache, dizziness, peripheral vasodilation, hypotension, dizziness, and tremor) were observed.

Frequency unknown: pulmonary edema*.

Systemic side effects associated with lidocaine are clinically indistinguishable from those associated with other amide-type local anesthetics.

*Cases reported when used as a tocolytic during pregnancy (see section "Use in pregnancy or breastfeeding").

Shelf life. 3 years.

Use within 30 days after opening the tube.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

30 g of cream in a tube with cap; 1 tube with cannula in a cardboard box.

Prescription category. Prescription only.

Manufacturer.

VAMFARMA S.R.L.

Manufacturer's address and place of business.

VIA KENNEDY, 5, COMAZZO (LO), 26833, Italy