RINZAplus (Tablets) Instructions for Use

Marketing Authorization Holder

Johnson & Johnson, LLC (Russia)

Manufactured By

Wrafton Laboratories, Limited (United Kingdom)

ATC Code

N02BE51 (Paracetamol in combination with other drugs, excluding psycholeptics)

Active Substances

Paracetamol (Rec.INN registered by WHO)

Guaifenesin (Rec.INN registered by WHO)

Phenylephrine (Rec.INN registered by WHO)

Dosage Form

RINZAplus

Film-coated tablets, 250 mg+100 mg+5 mg: 16 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white or almost white, biconvex, capsule-shaped, with an engraving “PGP” on one side.

Excipients: povidone K30, microcrystalline cellulose PH 200, stearic acid.

Film coating composition: hypromellose (Methocel E5), hypromellose (Methocel E15), macrogol 3350.

16 pcs. – blisters (1) – cardboard packs.

Clinical-Pharmacological Group

Drug for the relief of symptoms of acute respiratory infections and colds

Pharmacotherapeutic Group

Remedy for the relief of acute respiratory disease and “common cold” symptoms (non-narcotic analgesic + expectorant + alpha-adrenomimetic)

Pharmacological Action

A combined drug, the action of which is due to the composition of its components.

Paracetamol has analgesic and antipyretic effects.

Guaifenesin has a mucolytic effect, facilitates the removal of sputum from the bronchi and promotes the transition of an unproductive cough to a productive one.

Phenylephrine is a sympathomimetic, has pronounced alpha-adrenergic activity, constricts the vessels of the nasal mucosa, and eliminates swelling and hyperemia of the nasal mucosa.

Pharmacokinetics

Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. After oral administration, the C_max of paracetamol in plasma is reached within 10-60 minutes. It is metabolized in the liver and excreted in the urine, mainly in the form of glucuronides and sulfate compounds. T_1/2 is 1-3 hours.

Guaifenesin is rapidly absorbed from the gastrointestinal tract (within 25-30 minutes after oral administration). T_1/2 is 1 hour. It is metabolized in the liver by oxidation to β-(2-methoxyphenoxy)-lactic acid, which is excreted in sputum and by the kidneys as inactive metabolites.

Phenylephrine has irregular absorption from the gastrointestinal tract and at the first stage of metabolism is exposed to monoamine oxidase in the intestine and liver, so oral administration of phenylephrine reduces its bioavailability. It is excreted in the urine as sulfate compounds. C_max in plasma is reached within 1-2 hours, T_1/2 is 2-3 hours.

Indications

Symptoms of colds and flu (headache, sore throat, body and limb pain, nasal congestion, cough with difficult expectoration of viscous sputum, fever).

ICD codes

Dosage Regimen

Adults and children over 12 years are prescribed 1 sachet every 4-6 hours, but not more than 4 doses (sachets)/day. The maximum daily dose is 4 sachets.

The maximum duration of use of the drug without consulting a doctor is no more than 5 days. If after 5 days of treatment there is no improvement, or the symptoms worsen, or new symptoms appear, the patient should consult a doctor.

Adverse Reactions

The frequency of adverse reactions is assessed as follows: very common (≥1/10), common (from ≥1/100 to <1/10), uncommon (from ≥1/1000 to <1/100), rare (from ≥1/10,000 to <1/1000), very rare (<1/10,000), frequency unknown (cannot be estimated from the available data).

Paracetamol

Allergic reactions rarely – urticaria, anaphylaxis, bronchospasm, angioedema.

Skin and subcutaneous tissue disorders rarely – skin rash, frequency unknown – Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), acute generalized exanthematous pustulosis.

Nervous system disorders rarely – dizziness.

Eye disorders rarely – accommodation paresis, increased intraocular pressure, mydriasis.

Blood and lymphatic system disorders rarely – aplastic anemia, methemoglobinemia; very rarely – pathological changes in the blood, such as thrombocytopenia, agranulocytosis, hemolytic anemia, neutropenia, leukopenia, pancytopenia.

Cardiovascular system disorders rarely – increased blood pressure.

Gastrointestinal system disorders rarely – nausea, vomiting, dry mouth, hepatotoxic effect.

Urinary system disorders rarely – urinary retention, nephrotoxicity (papillary necrosis); frequency unknown – interstitial nephritis.

Phenylephrine

Cardiovascular system disorders rarely – tachycardia, arterial hypertension accompanied by headache, vomiting and palpitations.

Nervous system disorders rarely – insomnia, nervousness, tremor, anxiety, agitation, confusion, irritability and headache.

Gastrointestinal system disorders commonly – anorexia, nausea and vomiting.

Allergic reactions rarely – skin rash, urticaria, anaphylaxis and bronchospasm.

Guaifenesin

Nervous system disorders rarely – headache, dizziness and drowsiness.

Gastrointestinal system disorders rarely – gastrointestinal discomfort, nausea, vomiting and diarrhea.

Contraindications

Impaired liver function; severe chronic renal failure; arterial hypertension; hyperthyroidism; diabetes mellitus; phenylketonuria; coronary artery disease (acute myocardial infarction, coronary artery atherosclerosis); aortic stenosis; tachyarrhythmia; peptic ulcer of the stomach and duodenum in the acute stage; prostatic hyperplasia; angle-closure glaucoma; porphyria; pheochromocytoma; age under 12 years; pregnancy, lactation period; simultaneous use of beta-blockers, tricyclic antidepressants, MAO inhibitors (including within 14 days after their withdrawal); simultaneous use of other sympathomimetic drugs; simultaneous use of other drugs containing Paracetamol; sucrase/isomaltase deficiency, fructose intolerance, glucose-galactose malabsorption syndrome; hypersensitivity to guaifenesin, paracetamol, phenylephrine or other components of the drug.

With caution

Glucose-6-phosphate dehydrogenase deficiency, blood diseases, congenital hyperbilirubinemias (Gilbert’s, Dubin-Johnson, Rotor syndromes), hyperoxaluria, bronchial asthma, COPD, mild to moderate renal failure, dehydration, hypovolemia, anorexia, bulimia and cachexia (insufficient glutathione reserves in the liver), viral hepatitis, alcoholic liver disease, alcoholism, Raynaud’s syndrome; simultaneous use of cardiac glycosides, beta-blockers, methyldopa and other antihypertensive agents, elderly age.

Use in Pregnancy and Lactation

The drug should not be used during pregnancy and breastfeeding.

Use in Hepatic Impairment

Contraindicated in case of impaired liver function.

Use in Renal Impairment

Contraindicated in severe chronic renal failure.

With caution: mild to moderate renal failure.

Pediatric Use

Contraindicated for use in children under 12 years of age.

Geriatric Use

The drug should be used with caution in elderly patients.

Special Precautions

It is recommended to take the drug for the shortest possible course and in the minimum effective dose necessary to relieve symptoms.

The drug should not be used simultaneously with other cough, cold, or decongestant medications.

Avoid simultaneous use of the drug with other paracetamol-containing medicines, as this may cause paracetamol overdose.

In patients with alcoholic liver disease, the negative consequences of overdose are more pronounced.

If the drug is used for more than 5 days, peripheral blood counts and liver function should be monitored.

The drug distorts the results of laboratory tests for plasma glucose and uric acid.

It is recommended to take a sufficient amount of fluid during treatment.

Urine may turn pink.

Guaifenesin, which is part of the drug, can give false-positive results in the determination of 5-hydroxyindoleacetic and vanillylmandelic acid in urine due to the influence of guaifenesin metabolites on color (guaifenesin intake should be stopped 48 hours before urine collection for these tests).

The drug contains sodium, which should be taken into account by patients on a sodium-restricted diet.

The drug contains aspartame, which is a source of phenylalanine, which can be toxic to patients with phenylketonuria.

During the use of the drug, it is necessary to refrain from drinking alcohol and taking medicines containing ethanol.

Effect on ability to drive vehicles and mechanisms

When driving vehicles and engaging in other potentially hazardous activities, it must be taken into account that the drug may cause side effects such as dizziness and confusion.

Drug Interactions

Paracetamol

Inducers of microsomal oxidation in the liver (phenytoin, ethanol, barbiturates, flumecinol, rifampicin, phenylbutazone, tricyclic antidepressants) increase the production of hydroxylated active metabolites, which may lead to the development of severe intoxication with a slight overdose.

Long-term use of barbiturates reduces the effectiveness of paracetamol.

Simultaneous use with ethanol increases the risk of acute pancreatitis.

Inhibitors of microsomal oxidation (including cimetidine) reduce the risk of hepatotoxic effects.

When used together with NSAIDs, including salicylates, the nephrotoxic effect of paracetamol increases.

Diflunisal increases the plasma concentration of paracetamol by 50%, which increases the risk of hepatotoxicity.

Metoclopramide and domperidone may increase the absorption rate of paracetamol.

Cholestyramine may reduce the absorption rate of paracetamol.

Isoniazid reduces the clearance of paracetamol by suppressing its metabolic transformation in the liver, which may lead to an increase in the pharmacological effects and/or toxicity of paracetamol.

Probenecid causes an almost 2-fold decrease in the clearance of paracetamol by inhibiting the conjugation of paracetamol with glucuronic acid. When used simultaneously with probenecid, a reduction in the dose of paracetamol should be considered.

Regular use of paracetamol may lead to a possible decrease in the metabolism of zidovudine (increased risk of neutropenia).

Paracetamol may reduce the bioavailability of lamotrigine with a possible decrease in the severity of its effect due to the possible induction of metabolic transformation of lamotrigine in the liver.

Paracetamol enhances the effect of indirect anticoagulants, which increases the risk of bleeding and reduces the activity of uricosuric drugs.

Phenylephrine

Reduces the hypotensive effect of diuretics and antihypertensive drugs (including methyldopa, mecamylamine, guanadrel, guanethidine).

Phenothiazines, alpha-blockers (phentolamine), furosemide and other diuretics reduce the hypertensive effect.

MAO inhibitors (including furazolidone, procarbazine, selegiline), oxytocin, ergot alkaloids, tricyclic antidepressants, methylphenidate, adrenergic stimulants enhance the pressor effect and arrhythmogenicity of phenylephrine.

Beta-blockers reduce the cardiotonic activity; against the background of reserpine, arterial hypertension is possible (due to depletion of catecholamine stores in adrenergic endings, sensitivity to adrenomimetics increases).

Inhalational anesthetics (including chloroform, enflurane, halothane, isoflurane, methoxyflurane) increase the risk of severe atrial and ventricular arrhythmia, as they sharply increase myocardial sensitivity to sympathomimetics.

Ergometrine, ergotamine, methylergometrine, oxytocin, doxapram increase the severity of the vasoconstrictor effect.

Reduces the antianginal effect of nitrates, which in turn can reduce the pressor effect of sympathomimetics and the risk of arterial hypotension (simultaneous use is allowed depending on the achievement of the necessary therapeutic effect).

Thyroid hormones increase (mutually) the effect and the associated risk of coronary insufficiency (especially with coronary atherosclerosis).

Simultaneous use of phenylephrine and other sympathomimetic amines may lead to increased blood pressure and other side effects from the cardiovascular system.

Simultaneous use of cardiac glycosides (e.g., digoxin) and phenylephrine may increase the risk of arrhythmia and myocardial infarction.

Guaifenesin

Codeine impedes the discharge of liquefied sputum.

Compatible with bronchodilators, antimicrobial drugs, cardiac glycosides.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Over-the-Counter

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.