Combispazm® gastrokofort

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Combispasm® GastroComfort (Combispasm® GastroComfort)

Composition:

Active substances: simethicone, dicyclomine hydrochloride;

One film-coated tablet contains simethicone 40 mg, dicyclomine hydrochloride 20 mg;

Excipients: maize starch, microcrystalline cellulose, povidone, light magnesium carbonate, magnesium stearate, talc, colloidal anhydrous silicon dioxide, sodium starch glycolate, sodium croscarmellose, hypromellose, polyethylene glycol 6000, titanium dioxide (E 171).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: white, round, biconvex film-coated tablets.

Pharmacotherapeutic group.

Spasmolytics and anticholinergics in combination with other drugs. Spasmolytics in combination with other drugs. ATC code A03ED.

Pharmacological properties.

Pharmacodynamics.

Dicycloverine hydrochloride exerts a spasmolytic effect (relieves smooth muscle spasm in the gastrointestinal tract, abdominal pain associated with this spasm or with stretching of the gastrointestinal wall) and antisecretory effect on exocrine glands. The action of dicycloverine is due to its specific anticholinergic (antimuscarinic) effect on acetylcholine receptors, as well as a direct spasmolytic effect on smooth muscles.

Simethicone is a surface-active substance, an antifoaming agent. Its mechanism of action is based on reducing the surface tension of gas bubbles, thereby facilitating free gas elimination from the gastrointestinal tract or its absorption by the intestinal wall. Simethicone improves the quality of X-ray and ultrasound images and ensures better distribution of contrast agents on the intestinal mucosa.

Pharmacokinetics.

Dicycloverine hydrochloride is rapidly absorbed from the gastrointestinal tract following oral administration; maximum plasma concentration is reached within 60–90 minutes. It is excreted predominantly in the urine (79.5% of the administered dose), and partially in feces (8.4%). The mean elimination half-life is 1.8 hours. The mean volume of distribution is 3.65 L/kg.

Simethicone is physiologically and chemically inert; it is not absorbed and is excreted unchanged after passing through the gastrointestinal tract.

Clinical characteristics.

Indications.

• Treatment of conditions associated with smooth muscle spasm of the gastrointestinal tract and meteorism, as well as abdominal pain related to these conditions.
• Treatment of spastic conditions of the gastrointestinal tract, including colitis, intestinal colic, irritable bowel syndrome, spastic constipation.
• In complex therapy of organic diseases of the gastrointestinal tract such as colitis, diverticulitis, enteritis, gastritis, and peptic ulcers.

Contraindications.

Hypersensitivity to the active substances or to any of the excipients of the medicinal product, intestinal obstruction, obstructive uropathy, benign prostatic hyperplasia with urinary retention, renal insufficiency, obstructive gastrointestinal disorders, severe ulcerative colitis or toxic megacolon, reflux esophagitis, unstable cardiovascular status in acute bleeding, glaucoma, myasthenia gravis, thyrotoxicosis, cardiac failure.

Interaction with other medicinal products and other forms of interaction.

Amantadine, Class I antiarrhythmic agents (e.g. quinidine), antihistamines, antipsychotics (e.g. phenothiazines), benzodiazepines, monoamine oxidase inhibitors (MAO inhibitors), narcotic analgesics (e.g. meperidine), nitrates and nitrites, sympathomimetics, tricyclic antidepressants, corticosteroids, and other drugs with anticholinergic activity may enhance the effects or adverse reactions of dicyclomine.

Anticholinergic agents, including dicyclomine, may counteract the effects of antiglaucoma agents; therefore, the drug should be used with caution in patients with elevated intraocular pressure and during concomitant corticosteroid therapy.

Anticholinergic agents, including dicyclomine, may alter gastrointestinal absorption of certain drugs, particularly prolonged-release digoxin, potentially leading to increased plasma digoxin concentrations.

Dicyclomine may counteract the effects of drugs affecting gastrointestinal motility, such as metoclopramide.

Since antacids may reduce absorption of anticholinergic agents, including dicyclomine, their concomitant use should be avoided.

The inhibitory effect of anticholinergic agents, including dicyclomine, on gastric hydrochloric acid secretion may counteract drugs used in the treatment of achlorhydria and in studies of gastric secretion.

Dicyclomine hydrochloride may enhance the effects of monoamine oxidase inhibitors (e.g. imipramine, amitriptyline), sedatives (e.g. sodium bromide, valerian tincture), and ethyl alcohol.

The inhibitory effect of dicyclomine on gastric hydrochloric acid secretion may counteract drugs used in the treatment of achlorhydria and in studies of gastric secretion.

The drug enhances the effects of salicylic acid, pyrazolone, codeine, and caffeine. It potentiates the action of spasmolytics.

Intestinal absorption of levothyroxine may be impaired when administered concomitantly with simethicone.

Special precautions for use

The medicinal product should be used with caution in patients with autonomic neuropathy, liver or kidney disease, ulcerative colitis (administration of high doses may cause paralytic intestinal obstruction and development or exacerbation of a serious complication such as toxic megacolon), arterial hypertension, ischemic heart disease, congestive heart failure, tachyarrhythmias, hiatal hernia, and prostate hyperplasia.

In conditions of high ambient temperature during treatment, overheating of the body is possible (elevated body temperature and heat stroke due to reduced sweating). If such symptoms occur, the drug should be discontinued and medical advice should be sought.

Diarrhea may be an early sign of incomplete intestinal obstruction, especially in patients with ileostomy or colostomy. In such cases, treatment with the drug is inappropriate and potentially harmful.

In individuals with individual hypersensitivity to anticholinergic agents, the drug may cause central nervous system effects such as confusion, disorientation, ataxia, increased fatigue, or, conversely, euphoria, excitement, insomnia, and affective disturbances. These symptoms usually resolve within 12–24 hours after discontinuation of the drug.

Dicyclomine hydrochloride may exacerbate gastroesophageal reflux.

Dicyclomine should be prescribed with caution in patients with hiatal hernia associated with reflux esophagitis.

In conditions of high ambient temperature, dicyclomine hydrochloride, by reducing sweating, may cause an increase in body temperature with a risk of heat stroke. If such symptoms occur, the drug should be discontinued and medical advice should be sought.

Use during pregnancy or breastfeeding

The safety of using the drug during pregnancy has not been established; therefore, it should not be used during pregnancy.

Since dicyclomine hydrochloride passes into breast milk, the drug is contraindicated during breastfeeding.

Ability to affect reaction speed when driving or operating machinery

Dicyclomine hydrochloride may cause drowsiness and blurred vision. Patients should not drive or operate machinery while taking this drug.

Method of administration and dosage.

Adults and children aged 12 years and older: the drug is administered 1 tablet up to 4 times daily, taken either before or after meals. The maximum daily dose is 4 tablets. Treatment duration should not exceed 5 days.

Children.

The drug is indicated for children aged 12 years and older.

Overdose.

Symptoms: tachycardia, bradycardia, arrhythmia, changes in respiratory rate, dry mouth, excitement, drowsiness, loss of accommodation, photophobia, seizures, dryness of the skin and mucous membranes, increased intraocular pressure, headache, dizziness, central nervous system stimulation, urinary retention, psychomotor agitation, disorientation.

Overdose develops in two stages: initially, central nervous system stimulation occurs, manifested by restlessness, hallucinations, persistent mydriasis, tachycardia, and arterial hypertension. This is then followed by a phase of central nervous system depression progressing to coma.

In the first hours (up to 1 day), pallor of the skin, nausea, anorexia, vomiting, and abdominal pain may occur. During the second to third day, kidney and liver damage may develop, leading to hepatic failure (increased activity of liver transaminases and dehydrogenase, increased bilirubin and prothrombin concentrations), as well as tachycardia, arrhythmias, changes in respiratory rate, and pancreatitis.

Treatment: symptomatic therapy. In the first hours, induction of vomiting and gastric lavage are indicated.

There is no specific antidote for dicyclomine hydrochloride. To manage psychomotor agitation, diazepam (0.5% solution, 2 ml) may be administered.

Adverse Reactions

Gastrointestinal system: dry mouth, taste disturbances, anorexia, nausea, vomiting, digestive disturbances, bloating, abdominal pain, constipation.

Central nervous system: tinnitus, headache, drowsiness, weakness, nervousness, psychosis, numbness, dizziness, coma, confusion and/or excitement (especially in elderly patients), dyskinesia, insomnia, disorientation, transient memory loss, hallucinations, dysarthria, ataxia, euphoria, inappropriate emotional responses (symptoms subside within 12–24 hours after dose reduction), fatigue, impaired gait stability, tingling sensation, dysphasia, mood changes, lethargy, loss of consciousness.

Eye disorders: blurred vision, diplopia, mydriasis, accommodation paralysis, increased intraocular pressure (short-term atropine-like effects, which resolve after discontinuation of cyclobenzaprine).

Skin and hypersensitivity reactions: hypersensitivity reactions including allergic dermatitis, pruritus, rash, urticaria, erythema, drug idiosyncrasy, angioneurotic edema, anaphylactic shock.

Urinary and reproductive system: difficulty in urination, urinary incontinence, urinary retention.

Cardiovascular system: tachycardia, arrhythmia, palpitations.

Respiratory system: asthma, apnea, nasal congestion.

Musculoskeletal and connective tissue disorders: muscle weakness.

Respiratory system and thoracic organs: dyspnea, apnea, asphyxia, nasal congestion, sneezing, pharyngeal hyperemia.

Endocrine system: inhibition of lactation, impotence.

Other: sensation of warmth, decreased sweating.

Reporting of adverse reactions after drug registration is of great importance. It enables continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of drug efficacy via the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua

Shelf life. 4 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging.

10 film-coated tablets in a blister made of aluminum foil and aluminum film; 1 or 2 blisters per cardboard box.

Prescription status.

Over-the-counter (without prescription).

Manufacturer.

Evertogen Life Sciences Limited.

Manufacturer's address and place of business.

Plot No: S-8, S-9, S-13/P & S-14/P TSIIC, Pharma SEZ, Green Industrial Park, Polepally (V), Jadcherla (M), Mahabubnagar, Telangana, IN-509 301, India