Combigrin dexta®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT COMBIGRIP DEXA® (COMBIGRIP DEXA®)

Composition:

Active substances: paracetamol, caffeine, phenylephrine hydrochloride, chlorpheniramine maleate, dextromethorphan hydrobromide;

1 tablet contains 500 mg paracetamol, 30 mg caffeine, 10 mg phenylephrine hydrochloride, 2 mg chlorpheniramine maleate, 10 mg dextromethorphan hydrobromide;

Excipients: maize starch, microcrystalline cellulose, povidone, magnesium stearate, talc, sodium starch glycolate (type A), sodium croscarmellose, colorant Apple Green (tartrazine (E 102), brilliant blue (E 133)).

Pharmaceutical form. Tablets.

Main physicochemical properties: uncoated green tablets with speckles, oval-shaped, with a score line, bearing the imprints "S" and "L" on the side with the score line.

Pharmacotherapeutic group.

Analgesics and antipyretics. Paracetamol combinations without psychotropic agents.

ATC code N02B E51.

Pharmacological properties.

Pharmacodynamics.

A combined medication for the treatment of influenza and colds. Exerts antitussive effects, and has antipyretic, analgesic, antihistamine, and mild anti-inflammatory properties. Relieves dry, non-productive cough. Alleviates symptoms of nasal congestion, rhinorrhea, lacrimation, sneezing, headache, and improves general well-being.

Paracetamol acts as an analgesic and antipyretic agent. The analgesic and antipyretic effects of paracetamol are associated with its influence on the thermoregulatory center in the hypothalamus and its ability to inhibit prostaglandin synthesis.

Phenylephrine hydrochloride acts as a vasoconstrictor, reducing swelling of the nasal mucosa and paranasal sinuses.

Chlorpheniramine maleate exerts antihistamine effects, relieving lacrimation and nasal itching.

Caffeine exerts a stimulant effect on the central nervous system (CNS), primarily on the cerebral cortex, respiratory center, and vasomotor center. It enhances mental and physical performance, reduces drowsiness and fatigue, and counteracts the effects of CNS depressants.

Decimetorphan hydrobromide is a centrally-acting antitussive agent. It reduces receptor sensitivity and increases the threshold of sensitivity of the cough center to stimuli from the respiratory tract. Therapeutically alleviates symptoms of dry cough and reduces irritation of the respiratory tract.

Pharmacokinetics.

Paracetamol is rapidly absorbed from the gastrointestinal tract and binds to plasma proteins. The plasma half-life is 1–4 hours. It is metabolized in the liver, forming glucuronide and sulfate conjugates of paracetamol. It is excreted by the kidneys, primarily as conjugation products, with less than 5% excreted unchanged.

Caffeine and its water-soluble salts are rapidly absorbed in the intestine (including the large intestine). The plasma half-life is approximately 5 hours, and up to 10 hours in some individuals. The majority is demethylated and oxidized. About 10% is excreted unchanged by the kidneys. Elimination is slower in full-term newborns and infants (1.5–2 months of age), with a half-life (T1/2) ranging from 80 to 26.3 hours, respectively.

Phenylephrine hydrochloride has low bioavailability due to inconsistent absorption and the effect of monoamine oxidase (MAO) in the gastrointestinal tract and liver during first-pass metabolism. It is excreted by the kidneys as metabolites. Acidification of urine accelerates its elimination from the body.

Chlorpheniramine maleate is absorbed relatively slowly from the gastrointestinal tract, with maximum plasma concentration reached 2.5–6 hours after oral administration. Bioavailability is low, ranging from 25% to 50% of the administered dose. Chlorpheniramine undergoes hepatic first-pass metabolism. Chlorpheniramine maleate is extensively metabolized in the liver, forming metabolites such as desmethyl- and didesmethylchlorpheniramine. Approximately 70% binds to plasma proteins. Chlorpheniramine distributes into all organs and tissues and crosses the blood-brain barrier. The unchanged component and metabolites are primarily excreted in urine; excretion depends on urine pH and degree of ionization, with only trace amounts found in feces. Duration of action ranges from 4 to 6 hours. More rapid and extensive absorption, faster elimination, and a shorter half-life are observed in children.

Decimetorphan hydrobromide is rapidly absorbed from the gastrointestinal tract. After oral administration, decimetorphan undergoes rapid and extensive first-pass metabolism in the liver. Genetically controlled O-demethylation (CYP2D6) is the main factor determining decimetorphan pharmacokinetics in humans.

Different phenotypes of this oxidation process have been identified, leading to significant differences in pharmacokinetics among individuals. Unmetabolized decimetorphan, along with three demethylated metabolites—dextrorphan (also known as 3-hydroxy-N-methylmorphinan), 3-hydroxymorphinan, and 3-methoxymorphinan—have been identified as conjugated products in urine.

The primary metabolite is dextrorphan, which also possesses antitussive activity. In some individuals, metabolism is slower, resulting in unchanged decimetorphan predominating in blood and urine. The half-life of decimetorphan hydrobromide is 4 hours.

Clinical characteristics.

Indications.

Treatment of symptoms of influenza and acute respiratory viral infections (fever, headache, nasal congestion, cough) in adults and children aged 12 years and older.

Contraindications.

Hypersensitivity to any component of the drug, other xanthine derivatives (theophylline, theobromine), opioids, antihistamines, sympathomimetic amines.

Severe cardiovascular diseases, including decompensated heart failure, ventricular tachycardia, acute myocardial infarction, conduction disorders, arrhythmias, severe atherosclerosis, tendency to vascular spasm, severe form of ischemic heart disease; severe arterial hypertension; peripheral arterial thrombosis.

Severe impairment of liver and kidney function.

Stenosing peptic ulcer of the stomach and duodenum, pyloroduodenal obstruction; acute pancreatitis, hepatitis, congenital hyperbilirubinemia.

Prostatic adenoma with difficult urination, bladder neck obstruction.

Epilepsy, alcoholism, increased excitability, sleep disorders.

Hyperthyroidism, diabetes mellitus, pheochromocytoma.

Bronchial asthma, emphysema, chronic obstructive pulmonary disease.

Closed-angle glaucoma.

Blood disorders (including severe anemia, leukopenia), glucose-6-phosphate dehydrogenase deficiency. Elderly age (60 years and older).

Concomitant use with tricyclic antidepressants, ß-blockers, serotonin reuptake inhibitors, MAO inhibitors, and within 2 weeks after discontinuation of these drugs.

Contraindicated in patients at risk of developing respiratory failure.

Interaction with other medicinal products and other types of interactions.

Metoclopramide and domperidone increase, while cholestyramine decreases, the absorption rate of paracetamol. When used concomitantly with paracetamol, the following interactions may occur: delayed elimination of antibiotics from the body; tetracycline increases the risk of anemia and methemoglobinemia caused by paracetamol; antacids and food reduce paracetamol absorption. With prolonged concomitant use, the anticoagulant effect of coumarins (e.g., warfarin) is enhanced. Barbiturates reduce the antipyretic effect of paracetamol. Anticonvulsant drugs (phenytoin, barbiturates, carbamazepine) that stimulate hepatic microsomal enzymes and isoniazid may enhance the hepatotoxicity of paracetamol. Concomitant use of paracetamol with hepatotoxic agents increases the toxic effect of drugs on the liver. Paracetamol reduces the efficacy of diuretics.

Caution should be exercised when using paracetamol concomitantly with flucloxacillin, as such concomitant use has been associated with metabolic acidosis with a high anion gap due to pyroglutamic acidosis, especially in patients with risk factors (see section "Special precautions").

Use of phenylephrine hydrochloride with MAO inhibitors, tricyclic antidepressants, indomethacin, and bromocriptine may cause severe arterial hypertension; with sympathomimetic amines, digoxin, and cardiac glycosides – increases the risk of arrhythmias and myocardial infarction.

It may reduce the effectiveness of ß-blockers and other antihypertensive drugs (reserpine, methyldopa), increasing the risk of arterial hypertension and adverse cardiovascular reactions.

Alkaloids of Rauwolfia reduce the therapeutic effect of phenylephrine hydrochloride; α-adrenergic blockers (phentolamine), phenothiazines, furosemide, and other diuretics counteract vasoconstriction.

Chlorpheniramine maleate enhances the anticholinergic effect of atropine, spasmolytics, tricyclic antidepressants, and CNS depressants (tranquilizers, barbiturates), antiparkinsonian agents.

Do not use concomitantly with alcohol. Chlorpheniramine maleate and alcohol potentiate each other's effects when used together.

Concomitant use with hypnotics, barbiturates, sedatives, neuroleptics, tranquilizers, anesthetics, narcotic analgesics, and alcohol enhances the effect of chlorpheniramine maleate.

Maprotiline (a tetracyclic antidepressant) and other drugs with anticholinergic effects: the anticholinergic effect of these drugs or antihistamines such as chlorpheniramine may be intensified.

Caffeine, when used concomitantly, enhances the effect of analgesic-antipyretic drugs (improves bioavailability), xanthine derivatives, α- and β-adrenomimetics, psychostimulants, thyrotropic agents, ergotamine (improves absorption of ergotamine from the gastrointestinal tract).

Cimetidine, hormonal contraceptives, and isoniazid enhance the effect of caffeine.

Caffeine increases the likelihood of liver damage by hepatotoxic drugs.

Caffeine reduces the effect of opioid analgesics, anxiolytics, hypnotics, and sedatives; it is an antagonist of anesthetic agents and other drugs that depress the CNS, a competitive antagonist of adenosine and ATP; reduces blood lithium concentration.

Dextromethorphan hydrobromide should not be taken together with enzyme inhibitors, including amiodarone, fluoxetine, haloperidol, paroxetine, propafenone, and thioridazine, as this increases its concentration and the risk of adverse effects.

Dextromethorphan is metabolized by CYP2D6 and undergoes extensive first-pass metabolism. Concomitant use of potent inhibitors of the CYP2D6 enzyme may increase dextromethorphan concentrations in the body to levels many times higher than normal. This increases the patient's risk of toxic effects of dextromethorphan (excitation, confusion, tremor, insomnia, diarrhea, and respiratory depression) and the development of serotonin syndrome. Potent inhibitors of the CYP2D6 enzyme include fluoxetine, paroxetine, quinidine, and terbinafine. When used concomitantly with quinidine, plasma concentrations of dextromethorphan increased almost 20-fold, intensifying the drug's adverse effects on the CNS. Amiodarone, flecainide, propafenone, sertraline, bupropion, methadone, cinacalcet, haloperidol, perphenazine, and thioridazine also have a similar effect on dextromethorphan metabolism. If concomitant use of CYP2D6 inhibitors and dextromethorphan is necessary, the patient should be monitored, and it may be necessary to reduce the dose of dextromethorphan.

Ototoxic and photosensitizing drugs may enhance adverse effects when used concomitantly.

Special precautions.

Do not exceed the recommended doses or duration of treatment.

Do not use concurrently medications containing paracetamol, as this may lead to paracetamol overdose, potentially causing liver failure. Prolonged use of high doses of the drug may result in liver and kidney damage. Patients with liver disease have an increased risk of hepatotoxic effects of paracetamol. In patients with severe infections such as sepsis, which are associated with reduced glutathione levels, administration of paracetamol increases the risk of metabolic acidosis. Symptoms of metabolic acidosis include deep, rapid, or labored breathing, nausea, vomiting, and loss of appetite. If these symptoms occur, seek immediate medical attention.

Cases of high anion gap metabolic acidosis due to 5-oxoproline (pyroglutamic) acidosis have been reported in critically ill patients, such as those with severe renal failure and sepsis, as well as in patients with malnutrition or other causes of glutathione deficiency (e.g., chronic alcoholism) who received paracetamol at therapeutic doses for prolonged periods or a combination of paracetamol and flucloxacillin. If high anion gap metabolic acidosis due to pyroglutamic acidosis is suspected, immediate discontinuation of paracetamol is recommended, along with careful monitoring of the patient. Measurement of 5-oxoproline levels in urine may be helpful in identifying pyroglutamic acidosis as the underlying cause of high anion gap metabolic acidosis in patients with multiple risk factors.

Consult a physician regarding the possibility of using the drug in patients with mild to moderate renal or hepatic impairment.

Multiple concomitant medications, alcoholism, alcoholic liver disease, sepsis, or diabetes mellitus may increase the risk of hepatotoxicity of paracetamol (acetaminophen) even at therapeutic doses.

Concurrent use of this drug with other cold remedies, sedatives, or hypnotics is not recommended. The risk of overdose is increased in patients with alcoholic liver disease. Alcohol consumption and use of the aforementioned medications should be avoided during treatment, as they may enhance the sedative effect of chlorpheniramine maleate and the hepatotoxic potential of paracetamol.

If symptoms of illness persist or headache becomes persistent, consult a physician. In case of high body temperature or prolonged fever lasting more than 3 days despite treatment, or if signs of superinfection appear, seek medical advice.

Cases of abuse and dependence on dextromethorphan have been reported. Particular caution is advised in adolescents and young adults, as well as in patients with a history of drug or psychoactive substance abuse.

Dextromethorphan is metabolized by hepatic cytochrome P450 2D6. The activity of this enzyme is genetically determined. Approximately 10% of the population are poor metabolizers of CYP2D6. Poor metabolizers and patients concurrently taking CYP2D6 inhibitors may experience enhanced and/or prolonged effects of dextromethorphan. Therefore, caution is advised in patients who are poor CYP2D6 metabolizers or who are taking CYP2D6 inhibitors (see also section "Interaction with other medicinal products and other forms of interaction").

When dextromethorphan is used concomitantly with serotonergic agents, such as selective serotonin reuptake inhibitors (SSRIs), drugs that interfere with serotonin metabolism (particularly monoamine oxidase inhibitors [MAOIs]), or CYP2D6 inhibitors, serotonergic effects have been reported, including the development of potentially life-threatening serotonin syndrome.

Serotonin syndrome may include mental status changes, autonomic instability, neuromuscular abnormalities, and/or gastrointestinal symptoms.

If serotonin syndrome is suspected, treatment with the drug should be discontinued immediately.

Very rarely, severe skin reactions have been reported. If skin redness, rash, blisters, or skin peeling occur, discontinue paracetamol use immediately and seek urgent medical attention.

Before prescribing the drug, ensure that the underlying cause of cough has been identified and that suppression of cough will not increase the risk of clinical or physiological complications.

During treatment, avoid excessive consumption of coffee, strong tea, other stimulant beverages, and medications containing caffeine, as this may lead to sleep disturbances, tremor, tension, irritability, and palpitations.

Use with caution in patients with compensated heart failure; in patients with congenital long QT interval or those on long-term treatment with drugs that may prolong the QT interval; in patients at risk of seizures; and in patients with chronic obstructive pulmonary disease, persistent or chronic cough due to smoking or pulmonary emphysema, particularly when cough is associated with excessive sputum production. Ensure that the underlying cause of cough is established and that reducing cough intensity will not increase the risk of clinical or physiological complications.

The drug may affect laboratory test results for blood glucose and uric acid levels. Chlorpheniramine may mask symptoms of hypersensitivity and interfere with skin test results. Use of the drug may lead to a positive doping test result. The drug should be discontinued several days before undergoing the aforementioned procedures.

Patients taking warfarin or similar anticoagulant drugs, as well as those with renal or hepatic impairment, should consult a physician before using the drug.

Phenylephrine may cause increased heart rate, dizziness, or strong palpitations; patients should be warned about these possible effects.

The tablets contain the azo dye tartrazine (E 102), which may cause allergic reactions.

In case of accidental overdose, seek immediate medical attention even if symptoms are not apparent.

Use during pregnancy or breastfeeding.

Do not use during pregnancy or breastfeeding.

Ability to affect reaction speed when operating vehicles or machinery.

During treatment, avoid driving, operating machinery, or engaging in other potentially hazardous activities.

Method of Administration and Dosage.

For adults and children aged 12 years and older – 1 tablet 4 times daily, no more frequently than every 3–4 hours. The drug should be taken at least 30 minutes after food.

Duration of treatment – no more than 5 days.

Children.

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

Overdose.

Symptoms of overdose.

In patients with risk factors, therapeutic doses of paracetamol may cause symptoms of overdose when used concomitantly with certain medications or in diseases that increase oxidative stress and deplete glutathione stores in the liver (prolonged fasting, sepsis, diabetes mellitus).

Paracetamol in large doses causes hepatonecrosis. Clinical and biochemical signs of liver damage appear within 12–48 hours. Disorders of glucose metabolism and metabolic acidosis may occur. During the first 24 hours after overdose, symptoms may include pallor, nausea, vomiting, anorexia, and abdominal pain. Increased activity of liver transaminases, elevated bilirubin concentration, and decreased prothrombin levels may be observed. Ingestion of 10 g or more of paracetamol by adults or more than 150 mg of paracetamol per kg of body weight by children may lead to hepatocellular necrosis, resulting in encephalopathy with impaired consciousness, hepatic coma, and fatal outcome. In isolated cases, acute renal failure with acute tubular necrosis has been reported, manifested by lumbar pain, hematuria, proteinuria, and nephrotoxicity (renal colic, interstitial nephritis, papillary necrosis). Cardiac arrhythmias have also been observed. With prolonged use of high doses, aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, thrombocytopenia, and myocardial dystrophy are possible.

In case of overdose, increased sweating, dizziness, psychomotor excitation or CNS depression, drowsiness, impaired consciousness, cardiac rhythm disturbances, tachycardia, extrasystoles, tremor, hyperreflexia, seizures, pancreatitis, and sleep disturbances may occur.

In patients with risk factors (long-term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John's wort, or other drugs inducing liver enzymes; regular consumption of excessive amounts of ethanol; glutathione cachexia (digestive disorders, cystic fibrosis, HIV infection, fasting, cachexia)), ingestion of 5 g or more of paracetamol may lead to liver damage.

Symptoms of overdose due to phenylephrine and chlorpheniramine maleate: headache, hyperhidrosis, drowsiness, insomnia, behavioral changes, arrhythmias, tremor, seizures, hyperreflexia, dizziness, nausea, vomiting, irritability, restlessness.

In overdose with chlorpheniramine maleate, the condition may vary from depressed to excited (restlessness and seizures). Anticholinergic-like symptoms may occur, including mydriasis, photophobia, dryness of skin and mucous membranes, elevated body temperature, intestinal atony; CNS depression may be accompanied by respiratory disorders and cardiovascular system dysfunction.

Symptoms reported in caffeine overdose include: dehydration, hyperthermia, tinnitus, epigastric pain, increased frequency of diuresis, extrasystoles, tachycardia or cardiac arrhythmia, and CNS stimulation (dizziness, insomnia, excitement, irritability, psychomotor agitation, affective state, anxiety, tremor, vomiting, seizures, agitation, nervousness, delirium, increased tactile or pain sensitivity). Clinically significant symptoms of caffeine overdose may also be associated with liver damage caused by paracetamol.

Symptoms of dextromethorphan hydrobromide overdose may include: dystonia, drowsiness, confusion, stupor, cardiotoxicity (tachycardia, ECG abnormalities, particularly QTc interval prolongation), ataxia, toxic psychosis with visual hallucinations, hyperexcitability, dizziness, blurred vision, nystagmus, nausea, vomiting, irritability, hyperactivity, excitement, and psychiatric disturbances. With significant overdose, symptoms such as coma, respiratory depression, and seizures may occur. After a single intake of 300 mg of dextromethorphan, toxic psychosis (hyperactivity and hallucinations) has been observed.

Treatment of overdose.

In case of paracetamol overdose, immediate medical attention is required. The patient should be taken to hospital immediately, even if early symptoms of overdose are absent. Symptoms may be limited to nausea and vomiting or may not reflect the severity of organ damage. Administration of activated charcoal should be considered if an excessive dose of paracetamol was ingested within the past hour. Gastric lavage should be performed within the first hours after suspected overdose. Plasma paracetamol concentration should be measured 4 hours or later after ingestion (earlier concentrations are unreliable). Treatment with N-acetylcysteine may be administered within 24 hours after paracetamol ingestion, but maximum protective effect is achieved when administered within 8 hours after ingestion. The efficacy of the antidote decreases sharply after this time. If necessary, N-acetylcysteine should be administered intravenously according to the established dosing schedule. In the absence of vomiting, oral methionine may be used as an appropriate alternative in remote areas outside the hospital setting.

In case of dextromethorphan overdose, activated charcoal may be administered to asymptomatic patients who have ingested large doses of dextromethorphan within the previous hour. For patients who have taken dextromethorphan and are in a sedated or comatose state, naloxone in usual doses for opioid overdose treatment may be considered. Benzodiazepines may be used to treat seizures; benzodiazepines and external cooling may be used in case of hyperthermia due to "serotonin syndrome."

There is no specific antidote for caffeine, but supportive measures such as the use of β-adrenergic antagonists may help alleviate cardiotoxic effects. Gastric lavage is required; oxygen therapy is recommended; diazepam should be administered in case of seizures. Symptomatic therapy is indicated.

Adverse Reactions

Immune system disorders: hypersensitivity reactions, including pruritus, skin and mucous membrane rashes (generalized, erythematous, urticaria), anaphylactic shock, angioedema, Stevens–Johnson syndrome (including other forms of multiform exudative erythema), toxic epidermal necrolysis.

Central nervous system disorders: psychomotor agitation and disorientation, restlessness, behavioral changes, feelings of fear, anxiety, irritability, sleep disturbances, insomnia, somnolence, dizziness, confusion, hallucinations, depressive states, tremor, paresthesia and heaviness in limbs, tinnitus, headache; in rare cases – coma, seizures, dyskinesia.

Respiratory system disorders: bronchospasm in patients sensitive to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs.

Visual disorders: visual disturbances and accommodation disorders, mydriasis, increased intraocular pressure, dry eyes.

Gastrointestinal disorders: loss of appetite, nausea, vomiting, dry mouth, hypersalivation, heartburn, epigastric discomfort and pain, exacerbation of peptic ulcer, flatulence, diarrhea, constipation.

Hepatobiliary system disorders: liver function abnormalities, increased liver enzyme activity (usually without jaundice), hepatonecrosis (with high-dose use), hepatotoxicity.

Endocrine system disorders: hypoglycemia, up to hypoglycemic coma.

Blood and lymphatic system disorders: anemia, including hemolytic anemia, bruising or bleeding; sulfhemoglobinemia and methemoglobinemia (cyanosis, dyspnea, chest pain); with prolonged high-dose use – aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, thrombocytopenia.

Renal and urinary system disorders: with high-dose use – nephrotoxicity (including papillary necrosis), urinary disturbances, urinary retention and difficulty in urination, dysuria, interstitial nephritis, increased creatinine clearance, increased excretion of sodium and calcium, sterile pyuria, renal colic.

Cardiovascular system disorders: arterial hypertension, tachycardia or reflex bradycardia, arrhythmia, dyspnea, chest pain.

Metabolism and nutrition disorders: metabolic acidosis with high anion gap (frequency unknown).

Other: general weakness, increased sweating, hypoglycemia which may progress to hypoglycemic coma, nasal congestion, possible false elevation of blood uric acid levels when measured by the Bittner method; slight increase in urinary 5-hydroxyindoleacetic acid, vanillylmandelic acid, and catecholamines.

Concomitant use of the drug at recommended doses with products containing caffeine may enhance caffeine-related adverse effects such as dizziness, increased excitability, insomnia, restlessness, anxiety, irritability, headache, gastrointestinal disturbances, and tachycardia.

Description of selected adverse reactions.

Metabolic acidosis with high anion gap. Cases of metabolic acidosis with high anion gap due to pyroglutamic acidosis have been observed in patients with risk factors who were taking paracetamol (see section "Special precautions"). Pyroglutamic acidosis may occur due to low glutathione levels in these patients.

Reporting of adverse reactions after drug registration is highly important. It enables continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, and their legal representatives are encouraged to report all suspected adverse reactions and lack of efficacy via the automated pharmacovigilance information system at: https://aisf.dec.gov.ua

Shelf life. 4 years.

Storage conditions.

Store in original packaging at a temperature not exceeding 25 °C.

Keep out of reach and sight of children.

Packaging.

4 tablets in a blister made of aluminum foil and polyvinyl chloride film. 1 blister per cardboard box. 20 boxes packed in an outer cardboard carton.

8 tablets in a blister made of aluminum foil and polyvinyl chloride film. 1 blister per cardboard box. 10 boxes packed in an outer cardboard carton.

4 tablets in an aluminum foil blister. 1 blister per cardboard box. 20 boxes packed in an outer cardboard carton.

8 tablets in an aluminum foil blister. 1 blister per cardboard box. 10 boxes packed in an outer cardboard carton.

4 tablets in an aluminum foil blister. 1 blister placed in a paper envelope. 20 envelopes packed in a cardboard box.

Prescription status. Over-the-counter (without prescription).

Manufacturer.

Evertogen Life Sciences Limited.

Manufacturer's address:

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.