Novigan^® (Tablets) Instructions for Use

Marketing Authorization Holder

Dr. Reddy’s Laboratories Ltd. (India)

Contact Information

Dr. Reddy’s Laboratories Ltd. (India)

ATC Code

M01AE51 (Ibuprofen in combination with other drugs)

Active Substances

Ibuprofen (Rec.INN registered by WHO)

Pitofenone (Rec.INN registered by WHO)

Fenpiverinium bromide (Rec.INN registered by WHO)

Dosage Form

Novigan®

Film-coated tablets 400 mg+5 mg+100 mcg: 10 or 20 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white, round, biconvex, with the embossing “NOVIGAN” on one side; the cross-section shows a core from white to almost white.

Excipients: microcrystalline cellulose, corn starch, glycerol, colloidal silicon dioxide, talc, magnesium stearate.

Film coating composition: hypromellose 6 cps, macrogol 6000, talc, titanium dioxide, polysorbate 80, sorbic acid, dimethicone.

10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (2) – cardboard packs.

Clinical-Pharmacological Group

Spasm analgesic

Pharmacotherapeutic Group

Nonsteroidal anti-inflammatory and antirheumatic agents; propionic acid derivatives

Pharmacological Action

A combined drug with analgesic, anti-inflammatory, and spasmolytic action. It suppresses the synthesis of prostaglandins. The drug contains the NSAID Ibuprofen, the myotropic spasmolytic agent Pitofenone hydrochloride, and the centrally and peripherally acting m-cholinoblocking agent Fenpiverinium bromide.

Ibuprofen is a derivative of phenylpropionic acid. It has analgesic, anti-inflammatory, and antipyretic effects. The main mechanism of action is the inhibition of prostaglandin synthesis – modulators of pain sensitivity, thermoregulation, and inflammation in the CNS and peripheral tissues. In women with primary dysmenorrhea, it reduces the elevated level of prostaglandins in the myometrium and thereby reduces intrauterine pressure and the frequency of uterine contractions.

Pitofenone hydrochloride, similar to papaverine, has a direct myotropic effect on the smooth muscles of internal organs and causes its relaxation.

Fenpiverinium bromide, due to its cholinoblocking action, provides an additional relaxing effect on smooth muscles.

The combination of the three components of the drug leads to a mutual enhancement of their pharmacological action.

Pharmacokinetics

When taken orally, the components of Novigan^® are well absorbed from the gastrointestinal tract. C_max in blood plasma is reached approximately 1-2 hours after taking the drug.

The main component of the drug, Ibuprofen, is 99% bound to plasma proteins, can accumulate in synovial fluid, is metabolized in the liver, and is 90% excreted in the urine as metabolites and conjugates.

A small part of the drug components is excreted with bile. T_1/2 from blood plasma is 2 hours.

Indications

For adults and adolescents over 16 years of age with the following conditions

• Mild or moderately severe pain syndrome with spasms of the smooth muscles of internal organs: renal and biliary colic, biliary dyskinesia, intestinal colic;
• Gynecological diseases – dysmenorrhea;
• Headache, including migraine;
• Short-term symptomatic treatment for joint pain, neuralgia, sciatica, myalgia.

ICD codes

Dosage Regimen

Orally, 1 hour before or 3 hours after a meal. To avoid an irritating effect on the stomach, the drug can be taken immediately after a meal or with milk.

In the absence of special doctor’s instructions, Novigan^® is recommended for spasmodic pain to be taken 1 tab. up to 3 times/day. The maximum daily dose is 3 tablets.

The course of treatment with Novigan^® without consulting a doctor should not exceed 5 days. Longer use is possible under medical supervision with monitoring of peripheral blood counts and the functional state of the liver.

Adverse Reactions

In recommended doses, Novigan^® does not cause side effects.

The frequency of adverse reactions is classified according to WHO recommendations: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000), frequency unknown (cannot be estimated from the available data).

Blood and lymphatic system disorders uncommon – thrombocytopenia and thrombocytopenic purpura; very rare – anemia (including hemolytic, aplastic), agranulocytosis, leukopenia, eosinophilia.

Immune system disorders very rare – angioedema, anaphylactoid reactions, anaphylactic shock, allergic rhinitis.

Nervous system disorders uncommon – headache, dizziness, insomnia, anxiety, nervousness and irritability, psychomotor agitation, drowsiness, depression; very rare – confusion, hallucinations, aseptic meningitis (more often in patients with autoimmune diseases).

Eye disorders uncommon – blurred vision, scotoma, dryness and irritation of the eye, swelling of the conjunctiva and eyelids (of allergic origin), amblyopia; very rare – accommodation paresis, toxic damage to the optic nerve.

Ear and labyrinth disorders: rare – hearing loss, ringing or noise in the ears.

Cardiac disorders uncommon – tachycardia; rare – heart failure.

Vascular disorders uncommon – increased blood pressure.

Respiratory, thoracic and mediastinal disorders rare – dyspnea, bronchospasm.

Gastrointestinal disorders common – NSAID-gastropathy (abdominal pain, nausea, vomiting, heartburn, loss of appetite, diarrhea, flatulence, constipation; uncommon – ulceration of the gastrointestinal mucosa, which in some cases is complicated by perforation and bleeding; irritation or dryness of the oral mucosa, mouth pain, ulceration of the gum mucosa, aphthous stomatitis); very rare – pancreatitis, hepatitis, impaired liver function, hepatotoxicity.

Skin and subcutaneous tissue disorders uncommon – skin rash (usually erythematous or urticarial), skin itching; very rare – exudative erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome); frequency unknown – photosensitivity, acute generalized exanthematous pustulosis.

Renal and urinary disorders uncommon – nephrotic syndrome (edema), oliguria, anuria, polyuria, proteinuria, cystitis, red discoloration of urine; rare – acute renal failure, allergic nephritis.

General disorders and administration site conditions very rare – fever, increased or decreased sweating.

Investigations bleeding time (may increase), serum glucose concentration (may decrease), creatinine clearance (may decrease), hematocrit or hemoglobin (may decrease), serum creatinine concentration (may increase), activity of liver transaminases (may increase).

If the drug causes a change in the patient’s usual condition, the patient should stop taking it and consult a doctor immediately.

Contraindications

• Hypersensitivity to ibuprofen, pitofenone, fenpiverinium bromide or to any of the excipients included in the drug;
• Erosive and ulcerative changes in the gastric or duodenal mucosa, active gastrointestinal bleeding;
• Inflammatory bowel diseases in the acute phase, including ulcerative colitis;
• History of bronchospasm attack, rhinitis, urticaria after taking acetylsalicylic acid or other NSAIDs (complete or incomplete acetylsalicylic acid intolerance syndrome – rhinosinusitis, urticaria, nasal mucosal polyps, bronchial asthma);
• Hepatic insufficiency or active liver disease;
• Renal failure (creatinine clearance less than 30 ml/min), progressive kidney disease;
• Confirmed hyperkalemia;
• Hemophilia and other blood clotting disorders (including hypocoagulation), hemorrhagic diatheses;
• Period after coronary artery bypass surgery;
• Acute intermittent porphyria;
• Granulocytopenia;
• Hematopoiesis disorders;
• Glucose-6-phosphate dehydrogenase deficiency;
• Tachyarrhythmias;
• Closed-angle glaucoma;
• Optic nerve diseases;
• Prostatic hyperplasia;
• Intestinal obstruction;
• Pregnancy;
• Breastfeeding period;
• Age under 16 years.

With caution

• Elderly age;
• Congestive heart failure;
• Cerebrovascular diseases;
• Arterial hypertension;
• Ischemic heart disease;
• Dyslipidemia/hyperlipidemia;
• Diabetes mellitus;
• Peripheral arterial diseases;
• Nephrotic syndrome;
• Creatinine clearance 30-60 ml/min;
• Hyperbilirubinemia;
• Gastric and duodenal ulcer (in history);
• Presence of Helicobacter pylori infection;
• Gastritis, enteritis, colitis;
• Long-term use of NSAIDs;
• Blood diseases of unclear etiology (leukopenia, anemia);
• Smoking;
• Frequent alcohol consumption (alcoholism);
• Severe somatic diseases;
• Concomitant therapy with the following drugs: anticoagulants (e.g., warfarin), antiplatelet agents (e.g., acetylsalicylic acid, clopidogrel), oral glucocorticosteroids (e.g., prednisolone), selective serotonin reuptake inhibitors (e.g., citalopram, fluoxetine, paroxetine, sertraline).

Use in Pregnancy and Lactation

Pregnancy

The use of the drug during pregnancy is contraindicated. NSAIDs should not be used by women from the 20th week of pregnancy due to the possible development of oligohydramnios and/or kidney pathology in newborns (neonatal renal dysfunction).

Breastfeeding period

The use of the drug during breastfeeding is contraindicated. If the drug is prescribed during breastfeeding, the issue of its discontinuation should be decided.

Fertility

There are limited data showing that drugs that inhibit cyclooxygenase/prostaglandin synthesis may cause impaired female fertility by affecting ovulation. These changes are reversible after discontinuation of the drug.

Use in Hepatic Impairment

Contraindicated in hepatic insufficiency or active liver disease

Use in Renal Impairment

Contraindicated in renal failure (creatinine clearance less than 30 ml/min), progressive kidney diseases. With caution – in nephrotic syndrome, creatinine clearance 30-60 ml/min.

Pediatric Use

Contraindicated in children under 16 years of age

Geriatric Use

The drug should be used with caution in elderly patients

Special Precautions

With long-term use, monitoring of peripheral blood counts and the functional state of the liver and kidneys is necessary.

To reduce the risk of adverse events from the gastrointestinal tract, the minimum effective dose should be used. If symptoms of gastropathy appear, careful monitoring is indicated, including esophagogastroduodenoscopy, blood test with determination of hemoglobin and hematocrit, stool test for occult blood.

If it is necessary to determine 17-ketosteroids, the drug should be discontinued 48 hours before the study.

During treatment, alcohol consumption should be avoided.

Influence on the ability to drive vehicles and mechanisms

During the treatment period, the patient should refrain from engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms: abdominal pain, nausea, vomiting, lethargy, drowsiness, depression, headache, tinnitus, metabolic acidosis, coma, acute renal failure, decreased blood pressure, bradycardia, tachycardia, atrial fibrillation, respiratory arrest.

Treatment: gastric lavage (only within one hour after ingestion), activated charcoal, alkaline drinking, forced diuresis, symptomatic therapy (correction of acid-base status, blood pressure). There is no specific antidote.

The indicated dose should not be exceeded. If the patient has exceeded the dose, they should immediately consult a doctor or the nearest medical institution, taking the drug packaging with them.

Drug Interactions

In therapeutic doses, Novigan^® does not enter into significant interactions with widely used drugs.

Inducers of microsomal oxidation enzymes in the liver (phenytoin, ethanol, barbiturates, flumecinol, rifampicin, phenylbutazone, tricyclic antidepressants) increase the production of hydroxylated active metabolites, increasing the risk of severe intoxication.

Inhibitors of microsomal oxidation reduce the risk of hepatotoxic effects.

The drug reduces the hypotensive activity of vasodilators and the natriuretic effect of furosemide and hydrochlorothiazide.

Reduces the effectiveness of uricosuric drugs.

Enhances the effect of indirect anticoagulants, antiplatelet agents, fibrinolytics (which increases the risk of bleeding).

Enhances the side effects of mineralocorticoids, glucocorticosteroids (the risk of gastrointestinal bleeding increases), estrogens, ethanol.

When used simultaneously with oral hypoglycemic agents, it may enhance their effect, thereby contributing to the risk of hypoglycemia.

Antacids and cholestyramine reduce the absorption of ibuprofen.

The drug increases the concentration of digoxin, lithium preparations, methotrexate in the blood.

Enhances the effect of m-cholinoblockers, histamine H₁-receptor blockers, butyrophenones, phenothiazines, amantadine and quinidine.

Simultaneous administration of other NSAIDs increases the frequency of side effects.

Caffeine enhances the analgesic effect.

When used simultaneously, it reduces the anti-inflammatory and antiplatelet effect of acetylsalicylic acid (an increase in the frequency of acute coronary insufficiency is possible in patients receiving small doses of acetylsalicylic acid as an antiplatelet agent after starting Novigan^®).

Cefamandole, cefoperazone, cefotetan, valproic acid, plicamycin increase the frequency of hypoprothrombinemia when administered simultaneously.

Myelotoxic drugs enhance the manifestations of hematotoxicity of the drug.

Cyclosporine and gold preparations enhance the effect of ibuprofen on the synthesis of prostaglandins in the kidneys, which is manifested by an increase in nephrotoxicity.

Ibuprofen increases the plasma concentration of cyclosporine and the likelihood of its hepatotoxic effects.

Drugs that block tubular secretion reduce the excretion and increase the plasma concentration of ibuprofen.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 5 years. Do not use after the expiration date printed on the packaging.

Dispensing Status

The drug is available without a prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.