Combination of analgetic and M-anticholinergic agents
The Order of Ministry of Health
15.09.2016 № 973
for medical use of the preparation
Active substance: paracetamol, dicyclomine hydrochloride;
1 tablet contains paracetamol 500 mg and dicyclomine hydrochloride 20 mg;
Excipients: maize starch, gelatine, sodium methylparaben (E 219), sodium propylparaben (E 217), sodium metabisulfite (E 223), polyvinylpyrrolidone (K-30), magnesium stearate, talc, sodium starch.
Dosage form. Tablets.
Main physical and chemical properties: round, flat tablets with scoreline on one side and facet on the other, white or almost white color.
Pharmacotherapeutical group. Analgesics and antipyretics. Paracetamol combinations excluding psycholeptics. ATC code: N02B E51.
Paracetamol has an analgesic and antipyretic effect. Analgesic and antipyretic action of paracetamol (non-opiate, non-salicylate analgesics) is connected with its influence on thermoregulatory center in the hypothalamus and the ability to inhibit the synthesis of prostaglandins.
Dicyclomine hydrochloride is a tertiary amine. It has an anticholinergic activity and reduces the tonus of smooth muscles, eliminates pain, blocks an antagonist activity. Dicyclomine hydrochloride selectively paralyzes M-cholinoreactive structures, by blocking the transmission of impulses of postganglionic cholinergic nerves to innervate effector organs. It causes relaxation of smooth muscles, by exhibiting antispasmodic effect in smooth muscle spasms of the stomach, intestine, biliary tract, urogenital and circulatory systems.
Pain syndromes with spastic component of different etiology:
- Muscle pain, neuralgia;
- Rheumatic pain, radiculitis;
- Renal colic;
- Menstrual pain.
Glaucoma, tachycardia, urinary tract obstruction, myasthenia gravis, hypersensitivity to the preparation components, severe renal and/or liver failure, glucose-6-phosphatedehydrogenase deficiency, alcoholism, blood disorders including anemia and leukopenia. Obstructive gastrointestinal, urogenital, biliary diseases. Peptic ulcer of the stomach or duodenum. Reflux esophagitis. Acute hemorrhage. Benign prostatic hypertrophy with a tendency to urinary retention. Dynamic ileus. Severe liver and renal diseases. Congenital hyperbilirubinemia (Gilbert syndrome, Dubin-Johnson and Rotor syndromes).
Interaction with other medicinal products and other forms of interaction.
Peculiarities of interaction of the drug are caused by the properties of its components.
Paracetamol, which enters into the composition of the drug, reduces the diuretics efficacy and increases the risk of hepatotoxic reactions in co-administration of barbiturates, biphenyl, carbamazepine, rifampicin and other inducers of microsomal liver enzymes and anticonvulsants. The rate of absorption of paracetamol may be increased in concomitant use of metoclopramide and domperidone, and decreased in concomitant use of cholestyramine. The effect of paracetamol is enhanced in concomitant use of codeine, ascorbic acid, scopolamine, chlorphenamine, propyphenazonum and caffeine. Concomitant use of paracetamol with azidothymidine may lead to neutropenia. Anticoagulant effect of warfarin and other coumarins is enhanced due to prolonged regular use of paracetamol. Increased risk of bleeding. Periodic intake is not important. Concomitant use of paracetamol with NSAIDs increases the risk of complications in the kidneys. Concomitant use of paracetamol with hepatotoxic agents increases the toxic effect on the liver. Dicyclomine hydrochloride effect is enhanced by amantadine, antipsychotic agents, benzodiazepines, MAO inhibitors, narcotic analgesics, nitrates and nitrites, sympathomimetic, tricyclic antidepressants, anticholinergics, corticosteroids; and it is reduced by antacids. Dicyclomine hydrochloride increases digoxin activity.
Precautions for use.
It is necessary to consult your doctor regarding the use for patients with impaired renal and liver function.
If the patient uses warfarin or similar drugs that have anticoagulant effect then you should consult a doctor before using the drug.
It is necessary to monitor the picture of peripheral blood and functional state of the liver. Do not use paracetamol in combination with other drugs containing acetaminophen, because of the possibility of exceeding recommended dose.
When prescribing the drug for more than three days a medical observation of the patient is required.
Caution should be taken when used in elderly patients and persons who abuse alcohol.
Caution should be taken for patients with heart failure, pyloric gastric stenosis, renal and liver dysfunction.
Gastroesophageal reflux may be increased.
Risk of hepatotoxic effect of paracetamol is increased in patients with alcohol-induced liver injury.
Paracetamol may affect the results of blood glucose tests and uric acid tests.
The drug should be prescribed with caution to patients with hypotension, a tendency to bronchospasm, as well as hypersensitivity to NSAIDs. In prolonged use cellular composition of peripheral blood and renal function status should be monitored.
Dicyclomine should be used with caution in patients with ulcerative colitis (risk of paralytic obstruction), hernia of gastrointestinal aperture of diaphragm associated with reflux esophagitis.
Psychosis, confusion, ataxia, coma, euphoria, fatigue, insomnia, agitation, inappropriate emotional manifestations (the symptoms are reduced within 12-24 hours since the dose was reduced) may occur in patients who treated with anticholinergic drugs.
The drug should be prescribed with caution at high ambient temperature (the likelihood of heat stroke and hyperthermia is increased due to decreased sweating).
Patients with mild arthritis, who take analgesics every day, should consult a doctor.
Do not exceed recommended dose.
If the symptoms persist, you should consult a doctor.
If the headache is constant, you should consult a doctor.
Pregnancy and lactation.
Do not use for pregnant and breastfeeding women
Effects on ability to drive and use machines.
Considering that the drug may reduce the speed of psychomotor reactions in sensitive patients therefore during the therapy you should refrain from driving vehicles and work with other machines that require concentration.
Method of administration and dosage.
Take the drug orally and drink water (200 ml).
Adults and children over 15 years of age: 1 tablet depending on degree of pain, 1 to 4 times per day.
Children aged 7 to 13 years: ½ tablet 1 to 2 times per day;
Children aged 13 to 15 years: 1 tablet 1 to 3 times a day.
The maximum daily dose for adults is 2 tablets 4 times a day.
Duration of treatment is determined by the physician individually depending on the condition and response of the patient.
Do not use for children under 7 years old.
Symptoms of paracetamol overdose. Liver damage is possible in adults who have taken paracetamol 10 g or more and in children who have taken 150 mg/kg of body weight. The use of paracetamol 5 g or more may cause liver damage in patients with risk factors (long-term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, tutsan or other drugs that induce liver enzymes; regular excessive alcohol consumption; glutathione cachexia (digestive disorders, mucoviscidosis, HIV infection, starvation, cachexia ).
Symptoms of paracetamol overdose in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours after overdose. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, hemorrhage, hypoglycaemia, cerebral oedema, and death. Acute renal failure with acute tubular necrosis, strongly suggested by loin pain, haematuria and proteinuria, may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.
Aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, thrombocytopenia may be developed in hematopoiesis organs due to prolonged use of the drug in high doses. High doses may affect the central nervous and urinary systems with following disorders: dizziness, psychomotor agitation, disorientation and nephrotoxicity (renal colic, interstitial nephritis, capillary necrosis).
Immediate treatment is essential in the management of paracetamol overdose. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention. Symptoms may be limited to nausea or vomiting and may not reflect the severity of overdose or the risk of organ damage.Treatment with activated charcoal should be considered if the overdose has been taken within 1 hour. Plasma paracetamol concentration should be measured at 4 hours or later after ingestion (earlier concentrations are unreliable). Treatment with N-acetylcysteine may be used up to 24 hours after ingestion of paracetamol however, the maximum protective effect is obtained up to 8 hours post ingestion. The effectiveness of antidote is sharply decreased after this time. If required the patient should be given intravenous-N-acetylcysteine, in line with the established dosage schedule. If vomiting is not a problem, oral methionine may be a suitable alternative for remote areas, outside hospital.
Symptoms of dicyclomine hydrochloride overdose are: tachycardia, bradycardia, arrhythmia, changes in respiratory rate, dry mouth, agitation, drowsiness, loss of accommodation, photophobia and seizures.
Overdose has two stages: The first stage is characterized by a stimulation of the central nervous system with manifestations of anxiety, illusions, hallucinations, stable mydriasis, tachycardia and hypertension. On the second stage there is CNS depression up to coma.
Pale skin, nausea, anorexia, vomiting and abdominal pain may occur in the first 24 hours. Kidney and liver damage with the development of liver failure (increase of liver transaminases, dehydrogenase, increased bilirubin concentration, prothrombin), tachycardia, arrhythmias; change of respiratory rate; pancreatitis may occur in 12-48 hours.
Dryness of skin and mucous membranes, increased intraocular pressure, headache, dizziness, stimulation of the central nervous system and urinary retention may occur.
Treatment: gastric lavage followed by the use of activated charcoal, symptomatic therapy. Prescription of methionine since 8-9 hours of overdose and N-acetylcysteine since 12 hours of overdose (as an antidote to of paracetamol), monitoring of the respiratory and circulatory systems (do not use epinephrine) should be carried out. In the case of convulsions diazepam is prescribed.
Caused by paracetamol.
Gastrointestinal disorders: rare – nausea, vomiting, loss of appetite, constipation, diarrhea or flatulence, increased hepatic enzymes activity, usually without development of jaundice, hepatonecrosis (dose-dependent effect). Epigastric pain and hepatotoxic effects may occur in the long-term intake of high doses of the drug.
Blood system disorders: very rare – hemolytic anemia, sulphohemoglobinemia and methemoglobinemia (cyanosis, shortness of breath, pain in the heart), thrombocytopenia; in rare cases - aplastic anemia, pancytopenia, neutropenia, agranulocytosis, leukopenia.
Renal and urinary disorders: renal colic, aseptic pyuria, interstitial glomerulonephritis, very rare - nephrotoxicity, papillary necrosis.
Allergic reactions: rare – skin rash, rash on the mucous membranes (usually generalized rash, urticaria), itching, hyperemia; very rare – bronchial obstruction, multiforme exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome); in rare cases - anaphylactic shock, angioedema.
Central nervous system disorders: dizziness, psychomotor agitation and disorientation (usually develops when taking high doses).
Endocrine system disorders: in rare cases – hypoglycaemia and hypoglycemic.
Respiratory, thoracic and mediastinal disorders: bronchospasm in patients that are sensitive to aspirin and other NSAIDs.
General disorders: in rare cases - general weakness, hyperhidrosis.
Caused by dicyclomine hydrochloride.
Skin and subcutaneous tissue disorders: allergic reactions, skin redness.
Gastrointestinal disorders: nausea, dry mouth, dysgeusia, thirst, dyspepsia, constipation, anorexia, increased hepatic enzymes activity, usually without development of jaundice, hepatonecrosis (dose-dependent effect), vomiting, abdominal pain, flatulence.
Eye disorders: pupil dilation with loss of accommodation and light sensitivity, increased intraocular pressure, blurred vision, diplopia, mydriasis, cycloplegia (paralysis of accommodation).
Central nervous system disorders: dizziness, drowsiness, headache, paresthesia, disturbance of sensitivity, nervousness, dyskinesia, lethargy, insomnia, weakness, increased fatigue, syncope (loss of consciousness), numbness, gait disturbance.
Allergic reactions: itching, skin rash, urticaria, dry skin and other dermatological manifestations of severe allergic reactions or drug idiosyncrasy reaction, including anaphylaxis.
Cardiovascular disorders: temporary bradycardia, tachycardia, arrhythmia, palpitation, hot flushes.
Renal and urinary disorders: urination disorders, urinary incontinence, urinary retention, impotence.
Psychiatric disorders: speech disorders, confusion and/or emotional arousal, hallucinations, mood changes.
Musculoskeletal and connective tissue disorders: weakness in muscles.
Respiratory, thoracic and mediastinal disorders: dyspnea, apnea, asphyxia, nasal congestion, sneezing, hyperemia of throat.
Endocrine system disorders: suppression of lactation.
Shelf-life. 3 years.
Storage conditions. Store in the original package at temperature not exceeding 30 °С. Keep out of the reach of children.
Package. 10 tablets in a blister, 1-10 blisters in a pack.
Terms of dispensing.
No prescription – tablets № 10.
On prescription – tablets № 100.
Flamingo Pharmaceuticals Ltd.
Manufacturer’s registered address.
E-28, Opp. Fire Brigade, M.I.D.C., Taloja, Dist. Raigad, Maharashtra, IN-410208, India.
Flamingo Pharmaceuticals Ltd.
Applicant’s registered address.
7/1, Corporate Park, Sion-Trombay Road, Chembur, Mumbai - 400071, India
Ananta Medicare Ltd.
Marketing company’s registered address.
Suite 1, 2 Station Court, Imperial Wharf, Townmead Road, Fulham, SW6 2PY, London, United Kingdom.
Date of last update. 15.09.2016