Coldact® Flu Plus
Paracetamol
Enhances the effects of MAO inhibitors, sedatives, ethanol.
The risk of hepatotoxic action of paracetamol increases with simultaneous use of barbiturates and phenytoin. phenobarbital, carbamazepine. rifampicin. isoniazid, zidovudine and other inducers of microsomal liver enzymes.
The anticoagulant properties of warfarin and other coumarins may be enhanced by long-term regular use of paracetamol, increasing the risk of bleeding. A single dose of paracetamol does not have this effect.
Metoclopramide increases the rate of absorption of paracetamol and increases the level of paracetamol concentration in the blood plasma to the maximum.
Likewise, domperidone may increase the rate of absorption of paracetamol.
When chloramphenicol and paracetamol are used together, the half-life of chloramphenicol may increase.
Paracetamol may reduce the bioavailability of lamotrigine. with a possible decrease in its effect due to the induction of its hepatic metabolism.
The absorption of paracetamol may be reduced when taken concomitantly with cholestyramine, but this can be avoided if cholestyramine is taken one hour after paracetamol.
Regular use of paracetamol concomitantly with zidovudine may cause neutropenia and increase the risk of liver damage.
Probenecid affects the metabolism of paracetamol. In patients taking probenecid concomitantly, the dose of paracetamol should be reduced.
The hepatotoxicity of paracetamol may be increased by chronic or excessive alcohol consumption.
Paracetamol may interfere with the results of the uric acid test using the phosphotungstate precipitating reagent.
Phenylephrine
Contraindicated in patients who are taking or have taken MAOIs within the past two weeks. Phenylephrine can enhance the effect of MAO inhibitors and cause a hypertensive crisis.
Concomitant use of phenylephrine with other sympathomimetic drugs or tricyclic antidepressants (eg, amitriptyline) may increase the risk of cardiovascular side effects.
Phenylephrine may reduce the effectiveness of beta-blockers and other antihypertensive drugs (eg, debrisoquine, guanethidine, reserpine, methyldopa); the risk of increased blood pressure and other cardiovascular side effects may be increased.
Concomitant use of phenylephrine with digoxin and other cardiac glycosides may increase the risk of arrhythmia or myocardial infarction.
Concomitant use of phenylephrine with ergot alkaloids (ergotamine and methysergide) may increase the risk of ergotism.
Chlorphenamine
Antihistamines, such as chlorphenamine, may enhance the effects of opioid analgesics, anticonvulsants, antidepressants (tricyclics and monoamine oxidase inhibitors), other antihistamines, antiemetics and antipsychotics, anxiolytics, hypnotics, ethanol (alcohol) and other central nervous system depressants.
Because chlorphenamine has some anticholinergic activity, the effects of anticholinergic drugs (eg, some psychotropic drugs, atropine, and urinary incontinence drugs) may be increased by this drug. This can lead to tachycardia and dryness of the oral mucosa. disorders of the gastrointestinal tract (for example, colic), urinary retention and headache.
The metabolism of phenytoin may be inhibited by chlorphenamine, and phenytoin toxicity may develop.
Coldact flu plus sustained release capsules 10 pcs.
Registration Certificate Holder
Sun Pharmaceutical Industries (India)
Dosage form
Medicine - Coldact® FLU Plus (Coldact FLU Plus)
Description
Extended release capsules
1 cap.
phenylephrine hydrochloride 25 mg chlorphenamine (chlorpheniramine) maleate 8 mg paracetamol 200 mg
10 pieces. - blisters (1) - cardboard packs.
Indications
- symptomatic treatment of colds, flu, acute respiratory viral infections (fever, pain, rhinorrhea).
Contraindications for use
- hypersensitivity to any of the components included in the composition;
- severe atherosclerosis of the coronary arteries;
- arterial hypertension;
- diabetes;
- thyrotoxicosis;
- angle-closure glaucoma;
- severe diseases of the liver, kidneys, heart, bladder;
- peptic ulcer of the stomach and duodenum;
- pancreatic diseases;
- difficulty urinating with prostate adenoma;
- diseases of the blood system;
- deficiency of glucose-6-phosphate dehydrogenase;
- children's age up to 12 years.
With caution: congenital hyperbilirubinemia (Gilbert, Dubin-Johnson and Rotor syndromes), bronchial asthma and chronic obstructive pulmonary disease.
pharmachologic effect
Combined drug with prolonged action.
Chlorphenamine has an antiallergic effect, eliminates lacrimation, itching in the eyes and nose.
Paracetamol has an antipyretic and analgesic effect: it reduces the pain syndrome observed during colds - sore throat, headache, muscle and joint pain, and reduces high fever.
Phenylephrine has a vasoconstrictor effect - reduces swelling and hyperemia of the mucous membranes of the upper respiratory tract and paranasal sinuses.
Drug interactions
The risk of developing hematotoxic effects of paracetamol increases with simultaneous use of barbiturates, diphenine, carbamazepine, rifampicin, zidovudine and other inducers of microsomal liver enzymes.
Enhances the effects of sedatives, ethanol, and MAO inhibitors.
Antidepressants, phenothiazine derivatives, antiparkinsonian and antipsychotic drugs increase the risk of developing urinary retention, dry mouth, and constipation.
GCS increase the risk of developing glaucoma.
Paracetamol reduces the effectiveness of uricosuric drugs.
Chlorphenamine combined with furazolidone can lead to hypertensive crisis, agitation, and hyperrexia.
Tricyclic antidepressants enhance the adrenomimetic effect of phenylephrine; simultaneous administration of halothane increases the risk of developing ventricular arrhythmia.
Reduces the hypotensive effect of guanethidine, which in turn enhances the alpha-adrenergic stimulating activity of phenylephrine.
Dosage regimen
Adults and children over 12 years old - 1 capsule every 12 hours for 3-5 days.
Duration of use as an antipyretic is no more than 3 days; as a pain reliever - no more than 5 days.
Overdose
Symptoms caused by paracetamol appear after taking more than 10-15 g: pallor of the skin, decreased appetite, nausea, vomiting, hepatonecrosis, increased activity of liver transaminases, increased prothrombin time.
Treatment: gastric lavage in the first 6 hours, administration of SH-group donors and precursors for the synthesis of glutathione-methionine 8-9 hours after an overdose and N-acetylcysteine after 12 hours. In case of accidental overdose, you should immediately consult a doctor, regardless of what is noted -either symptoms of overdose or not.
Side effect
Increased blood pressure, tachycardia, drowsiness, difficulty falling asleep, dizziness, increased excitability, dry mucous membranes, mydriasis, accommodation paresis, increased intraocular pressure, loss of appetite, nausea, epigastric pain, anemia.
Very rare: urinary retention, allergic reactions (skin rash, itching, urticaria, angioedema).
Rarely: anemia, thrombocytopenia, leukemia, agranulocytosis.
With long-term use in high doses, hepatotoxic and nephrotic effects are possible.
special instructions
Without a doctor's instructions, the drug should not be used by patients undergoing treatment with other medications, in particular MAO inhibitors. If, despite taking the drug, the disease is accompanied by ongoing fever or repeated increases in temperature are observed, you should consult a doctor. Do not take with alcohol or combine with other drugs containing paracetamol. When using Coldact Flu Plus, it is not advisable to use sleeping pills, tranquilizers and other psychotropic drugs.
Distorts laboratory test results in the quantitative determination of glucose and uric acid in plasma. In case of long-term treatment, peripheral blood parameters and the functional state of the liver are monitored.
Impact on the ability to drive vehicles and machinery
During the treatment period, it is necessary to refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
Storage conditions
Store in a dry place at a temperature not exceeding 25°C. Keep out of the reach of children.
Best before date
Shelf life: 2 years. Do not use after expiration date.
Use during pregnancy and breastfeeding
Restrictions during pregnancy - Contraindicated. Restrictions during breastfeeding - Contraindicated. Coldact Flu Plus capsules are not recommended for use during pregnancy and lactation.
Use for renal impairment
Restrictions for impaired renal function - Contraindicated. Contraindicated: severe kidney disease.
Use for liver dysfunction
Restrictions for liver dysfunction - Contraindicated. Contraindicated: severe liver disease.
Use in children
Restrictions for children - Contraindicated. Contraindicated for children under 12 years of age.
Terms of sale
The drug is approved for use as a means of OTC.
Instructions for use NOCLAUD®
Platelet aggregation inhibitors
Cilostazol is a PDE III inhibitor with antiplatelet activity. In clinical studies in healthy volunteers, cilostazol 150 mg twice daily for five days did not prolong the duration of bleeding.
Acetylsalicylic acid (ASA)
Short-term (4 days or less) concomitant use of ASA with cilostazol resulted in a 23-25% increase in inhibition of ADP-induced platelet aggregation ex vivo
compared to ASA used as monotherapy.
In patients receiving cilostazol and ASA, there was no apparent evidence of an increase in the incidence of bleeding adverse events compared with patients receiving placebo and equivalent doses of ASA.
Clopidogrel and other antiplatelet drugs
Concomitant use of cilostazol with clopidogrel had no effect on platelet levels, prothrombin time (PT) and activated partial thromboplastin time (aPTT). All healthy study participants experienced an increase in bleeding time when taking clopidogrel alone, and taking it concomitantly with cilostazol did not have a significant additional effect on bleeding time. Caution is recommended when using cilostazol concomitantly with any drug that inhibits platelet aggregation. Periodic monitoring of bleeding duration should be considered. Treatment with cilostazol is contraindicated in patients taking two or more additional antiplatelet/anticoagulant agents (see Contraindications).
A higher incidence of bleeding events was observed with concomitant use of clopidogrel, ASA and cilostazol in the CASTLE trial.
Oral anticoagulants such as warfarin
In a single-dose clinical study, cilostazol did not suppress the metabolism of warfarin and did not affect coagulation parameters (PT, aPTT, bleeding time). However, cilostazol should be used with caution in patients receiving concomitant treatment with any anticoagulant agents, and frequent monitoring is necessary to reduce the risk of bleeding.
Treatment with cilostazol is contraindicated in patients taking two or more additional antiplatelet/anticoagulant agents (see Contraindications).
Cytochrome P-450 (CYP) enzyme inhibitors
Cilostazol is extensively metabolized by enzymes of the cytochrome CYP system, especially CYP3A4 and CYP2C19, and to a lesser extent by CYP1A2. The dihydro-metabolite, which inhibits platelet aggregation 4-7 times more actively than cilostazol, is apparently formed with the participation of CYP3A4. The 4'-trans-hydroxy metabolite, five times less active than cilostazol, appears to be formed with the participation of CYP2C19. Therefore, drugs that inhibit the activity of CYP3A4 (for example, some macrolides, azole antifungals, protease inhibitors) or CYP2C19 (such as proton pump inhibitors (PPIs)) increase the overall pharmacological activity and may potentially increase the undesirable effects of cilostazol. Therefore, the recommended dose for patients concomitantly taking strong CYP3A4 or CYP2C19 inhibitors is 50 mg twice daily (see Dosage Regimen).
Taking cilostazol with erythromycin (a CYP3A4 inhibitor) resulted in a 72% increase in the AUC of cilostazol, accompanied by a 6% increase in the AUC of the dihydrometabolite and a 119% increase in the AUC of the 4'-trans-hydroxy metabolite.
Taking into account AUC values, the total pharmacological activity of cilostazol increases by 34% when taken together with erythromycin. Based on these data, the recommended dose of cilostazol is 50 mg twice daily when coadministered with erythromycin and similar agents (eg, clarithromycin).
Co-administration of ketoconazole (a CYP3A4 inhibitor) with cilostazol resulted in a 117% increase in the AUC of cilostazol, accompanied by a 15% decrease in the AUC of the dihydro metabolite and an 87% increase in the AUC of the 4'-trans-hydroxy metabolite. Taking into account AUC values, the overall pharmacological activity of cilostazol increases by 35% when used simultaneously with ketoconazole. Based on these data, the recommended dose of cilostazol is 50 mg twice daily when coadministered with ketoconazole and similar agents (eg, itraconazole).
Administration of cilostazol with diltiazem (a weak CYP3A4 inhibitor) resulted in a 44% increase in the AUC of cilostazol, accompanied by a 4% increase in the AUC of the dihydrometabolite and a 43% increase in the AUC of the 4'-trans-hydroxy metabolite.
Taking into account AUC values, the total pharmacological activity of cilostazol increases by 19% when administered concomitantly with diltiazem. Based on these data, no dose adjustment is required.
A single dose of 100 mg of cilostazol with 240 ml of grapefruit juice (an inhibitor of intestinal CYP3A4) did not have a significant effect on the pharmacokinetics of cilostazol. Based on these data, no dose adjustment is required. However, drinking large volumes of grapefruit juice may have a clinically significant effect on the pharmacokinetics of cilostazol.
Taking cilostazol with omeprazole (a CYP2C19 inhibitor) resulted in a 22% increase in cilostazol AUC, accompanied by a 68% increase in the AUC of the dihydrometabolite and a 36% decrease in the AUC of the 4'trans-hydroxy metabolite. Taking into account AUC values, the total pharmacological activity of cilostazol increases by 47% when administered concomitantly with omeprazole. Based on these data, the recommended dose of cilostazol is 50 mg twice daily when taken concomitantly with omeprazole.
Substrates for cytochrome P-450 enzymes
Cilostazol increased the AUC of lovastatin (a sensitive CYP3A4 substrate) and its β-hydroxy acid by 70%.
Cilostazol is recommended to be used with caution when coadministered with CYP3A4 substrates with a narrow therapeutic index (for example, cisapride, halofantrine, pimozide, ergot derivatives). Caution should be exercised when cilostazol is used concomitantly with statins metabolized by CYP3A4 enzymes, such as simvastatin, atorvastatin and lovastatin.
Inducers of cytochrome P-450 enzymes
The effect of inducers of CYP3A4 and CYP2C19 (such as carbamazepine, phenytoin, rifampicin and St. John's wort) on the pharmacokinetics of cilostazol has not been studied. There is a theoretical possibility of a change in the antiplatelet effect, which should be carefully monitored when taking cilostazol concomitantly with inducers of CYP3A4 and CYP2C19.
In clinical trials, smoking (which induces CYP1A2 enzyme activity) resulted in a 18% decrease in cilostazol plasma concentrations.
Other potential interactions
Caution should be exercised when simultaneous use of cilostazol with any other drug that can lower blood pressure, due to the possibility of developing an additive hypotensive effect accompanied by reflex tachycardia.
