Gripeks aktiv max

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT GRIPEX® ACTIVE MAX (GRIPEX® ACTIVE MAX)

Composition:

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

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

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

Pharmaceutical form. Tablets.

Main physicochemical properties: uncoated tablets of green color with specks, oval-shaped, with a score line, having imprints «G» and «R» on the side with the score line.

Pharmacotherapeutic group. Analgesics and antipyretics. Anilides. Paracetamol, combinations without psychotropic agents. ATC code N02BE51.

Pharmacological Properties

The pharmacological effect is due to the action of all components of the drug.

Pharmacodynamics

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.

Caffeine is a central nervous system stimulant. It stimulates the respiratory center, increasing the rate and depth of lung oxygenation, enhances skeletal muscle tone, and reduces the threshold for hypercapnia. To achieve the same analgesic effect without caffeine, a dose approximately 40% higher would be required compared to when it is combined with caffeine. Thus, caffeine is used as an adjuvant to paracetamol.

Phenylephrine hydrochloride stimulates postsynaptic alpha-adrenergic receptors. It constricts pulmonary vessels and increases pressure in the pulmonary artery. As a vasoconstrictor, it exerts an anti-congestive effect: it reduces edema and hyperemia of the nasal mucosa, diminishes exudative manifestations, and restores free breathing.

Chlorpheniramine maleate is an H1-blocker that inhibits the response of smooth muscle to histamine. It has antiallergic properties and reduces lacrimation and nasal itching.

Dextromethorphan hydrobromide is a centrally-acting antitussive agent. It suppresses the cough center by direct action upon it and increases the cough center's threshold to irritant stimuli.

Pharmacokinetics

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

Caffeine and its water-soluble salts are rapidly absorbed in the intestine (including the colon). 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.

Phenylephrine hydrochloride has low bioavailability due to uneven absorption and the effect of monoamine oxidase 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 a component that reduces the characteristic effects of histamines, which is particularly important for preventing and alleviating many allergic symptoms. It is absorbed relatively slowly from the gastrointestinal tract, with maximum plasma concentration reached 2.5 to 6 hours after oral administration. Bioavailability is low, ranging from 25% to 50% of the administered dose. Chlorpheniramine undergoes extensive first-pass metabolism in the liver. Chlorpheniramine maleate is largely metabolized in the liver, forming desmethyl- and didesmethylchlorpheniramine metabolites. Approximately 70% binds to plasma proteins. Chlorpheniramine distributes into all organs and tissues and crosses the blood-brain barrier. The unchanged component and its metabolites are primarily excreted in urine; excretion depends on urine pH and degree of ionization, with only traces found in feces. Duration of action ranges from 4 to 6 hours.

Dextromethorphan hydrobromide is rapidly absorbed from the gastrointestinal tract. The half-life of dextromethorphan hydrobromide is 4 hours. After oral administration, dextromethorphan undergoes rapid and extensive first-pass metabolism in the liver. Genetically controlled O-demethylation (CYP2D6) is the main determinant of dextromethorphan pharmacokinetics in volunteers.

There are likely different phenotypes of this oxidation process, leading to differences in pharmacokinetics among individuals. Unmetabolized dextromethorphan, along with three demethylated morphinan metabolites—dextrorphan (also known as 3-hydroxy-N-methylmorphinan), 3-hydroxymorphinan, and 3-methoxymorphinan—have been identified as related substances in urine.

Dextrorphan, which also exerts antitussive activity, is the primary metabolite. In some individuals, metabolism is slower, and unchanged dextromethorphan predominates in blood and urine.

Clinical characteristics.

Indications.

Treatment of influenza and acute respiratory viral infection (ARVI) symptoms (fever, headache, rhinitis, cough) in adults and children aged 12 years and older.

Contraindications.

The drug is contraindicated in patients with hypersensitivity to any of its components.

Alcoholism, prostatic hyperplasia, severe forms of atherosclerosis, arterial hypertension, acute pancreatitis and hepatitis, peripheral arterial thrombosis, decompensated heart failure; severe forms of ischemic heart disease, conduction disorders, ventricular tachycardia, closed-angle glaucoma, pronounced renal and hepatic dysfunction, bronchial asthma, chronic obstructive pulmonary disease (COPD), pheochromocytoma, hyperthyroidism, glucose-6-phosphate dehydrogenase deficiency, blood disorders, pronounced leukopenia, anemia, congenital hyperbilirubinemia, Dubin-Johnson syndrome, diabetes mellitus, elevated intraocular pressure. Predisposition to vascular spasm, urinary retention, bladder neck obstruction. Stenosing gastric and duodenal ulcers, pyloroduodenal obstruction; epilepsy, increased excitability, sleep disorders, emphysema, acute myocardial infarction. Age over 60 years. Concurrent use with tricyclic antidepressants, β-blockers. Do not use concurrently with monoamine oxidase inhibitors (MAOIs) or within 2 weeks after discontinuation of MAOIs.

Special precautions.

Before prescribing the drug, ensure that the underlying cause of cough has been identified and that reducing cough intensity will not increase the risk of clinical or physiological complications. Use with caution in cases of persistent or chronic cough caused by smoking or pulmonary emphysema, when cough is associated with excessive sputum production, and in patients with congenital prolonged QT interval or those undergoing long-term treatment with drugs that may prolong the QT interval.

Consult a physician regarding the possibility of using the drug in patients with renal or hepatic impairment. Consult a physician before use if the patient is taking warfarin or similar anticoagulant agents.

Alcohol consumption must be avoided during treatment, as alcohol enhances the sedative effect of chlorpheniramine maleate and increases the hepatotoxic potential of paracetamol.

Consider that patients with alcoholic liver damage have an increased risk of paracetamol-induced hepatotoxicity; the drug may affect laboratory test results for blood glucose and uric acid levels.

In patients with severe infections such as sepsis, associated with reduced glutathione levels, the risk of metabolic acidosis increases during paracetamol administration. Symptoms of metabolic acidosis include deep, rapid, or labored breathing, nausea, vomiting, and loss of appetite. Seek immediate medical attention if these symptoms occur.

Cases of high anion gap metabolic acidosis (HAGMA) due to 5-oxoproline (pyroglutamic) acidosis have been reported in critically ill patients, such as those with severe renal failure or sepsis, or in patients with malnutrition or other sources of glutathione deficiency (e.g., chronic alcoholism), who were treated with therapeutic doses of paracetamol over a prolonged period or in combination with flucloxacillin. If HAGMA due to pyroglutamic acidosis is suspected, immediate discontinuation of paracetamol and close monitoring of the patient are recommended. Measurement of 5-oxoproline levels in urine may be useful in identifying pyroglutamic acidosis as the underlying cause of HAGMA in patients with multiple risk factors.

Patients who take analgesics daily for mild arthritis should consult a physician.

Do not exceed the recommended doses.

Do not take the drug with other products containing paracetamol.

If symptoms persist, consult a physician.

If headache becomes persistent, consult a physician.

Caffeine reduces the effect of sedatives and narcotic drugs. Excessive consumption of caffeine-containing beverages (such as coffee and tea) is not recommended during treatment, as it may cause sleep disturbances, tremor, and chest discomfort due to palpitations.

Phenylephrine may cause increased pulse rate, dizziness, or pronounced palpitations; patients should be warned about this.

Cases of dextromethorphan abuse and dependence have been reported. Use with particular caution in children and young adults, as well as in patients with a history of drug or psychoactive substance abuse.

Serotonin syndrome.

Serotonergic effects, including potentially life-threatening serotonin syndrome, have been observed with concomitant use of dextromethorphan and serotonergic agents such as selective serotonin reuptake inhibitors (SSRIs), drugs affecting serotonin metabolism, including monoamine oxidase inhibitors (MAOIs) and CYP2D6 inhibitors.

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

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

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

Use with caution in hepatic and renal diseases, arterial hypertension, and compensated heart failure.

The use of the drug may result in a positive analytical finding in doping control tests.

Interaction with other medicinal products and other forms of interaction.

Avoid concomitant use of the drug with other medicinal products containing paracetamol or other active ingredients present in Gripex Active Max.

The interaction profile of the drug is determined by the properties of its components.

Gripex Active Max potentiates the effects of MAO inhibitors, sedatives, and ethanol. Additionally, MAO inhibitors and furazolidone used concomitantly with Gripex Active Max may cause agitation, hypertensive crisis, and hyperpyrexia (due to chlorpheniramine maleate). Concurrent use with antidepressants, antiparkinsonian agents, neuroleptics may result in anticholinergic effects (manifested as dry mouth, urinary retention, constipation).

The risk of glaucoma increases when Gripex Active Max is used concomitantly with glucocorticoids. Paracetamol, a component of the drug, reduces the effectiveness of diuretics and increases the risk of hepatotoxic reactions when used concomitantly with barbiturates, diphenyl, carbamazepine, rifampicin, and other inducers of microsomal liver enzymes, as well as anticonvulsants. The absorption rate of paracetamol may be increased when used concomitantly with metoclopramide and domperidone, and decreased when used concomitantly with cholestyramine. Concurrent use of paracetamol with zidovudine may lead to neutropenia. The anticoagulant effect of warfarin and other coumarins is enhanced with prolonged regular use of paracetamol, increasing the risk of bleeding. Single doses do not show significant effects. Concurrent use of paracetamol with nonsteroidal anti-inflammatory drugs increases the risk of renal complications. Concurrent use of paracetamol with hepatotoxic agents increases the toxic effects of drugs on the liver.

Barbiturates reduce the antipyretic effect of paracetamol. Anticonvulsants (including phenytoin, barbiturates, carbamazepine), which stimulate microsomal liver enzyme activity, may enhance the hepatotoxic effect of paracetamol due to increased conversion of the drug into hepatotoxic metabolites. Concurrent use of high doses of paracetamol with isoniazid increases the risk of hepatotoxic syndrome.

Paracetamol should be used with caution when administered concomitantly with flucloxacillin, as concurrent use has been associated with high anion gap metabolic acidosis due to pyroglutamic acidosis, particularly in patients with risk factors (see section "Special precautions").

One of the components of the drug, phenylephrine hydrochloride, exhibits adrenomimetic effects when used with tricyclic antidepressants; concurrent use with haloperidol increases the risk of ventricular arrhythmia. Gripex Active Max reduces the hypotensive effect of guanethidine, which in turn enhances the α-adrenomimetic activity of phenylephrine hydrochloride. Phenylephrine may cause adverse reactions when combined with indomethacin and bromocriptine (severe arterial hypertension). Use of phenylephrine hydrochloride with sympathomimetic amines, digoxin, and cardiac glycosides increases the risk of arrhythmias and myocardial infarction. Alkaloids of Rauwolfia reduce the therapeutic effect of phenylephrine hydrochloride; β-adrenergic blockers (phentolamine), phenothiazines, furosemide, and other diuretics counteract vasoconstriction. Phenylephrine may reduce the effectiveness of beta-blockers and other antihypertensive drugs (reserpine, methyldopa, etc.), increasing the risk of arterial hypertension and other cardiovascular adverse reactions.

Chlorpheniramine enhances the anticholinergic effect of atropine, antispasmodics, tricyclic antidepressants, MAO inhibitors, antiparkinsonian agents. Chlorpheniramine maleate enhances the effects of central nervous system depressants (tranquilizers, barbiturates), antiparkinsonian agents.

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

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

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

Caffeine enhances the effect (improves bioavailability) of analgesic-antipyretic agents, potentiates the effects of xanthine derivatives, alpha- and beta-adrenergic agonists, psychostimulants. Cimetidine, hormonal contraceptives, isoniazid enhance the effect of caffeine. Caffeine reduces the effect of opioid analgesics, anxiolytics, hypnotics, and sedatives, acts as an antagonist of anesthetic agents and other drugs that depress the central nervous system, and as a competitive antagonist of adenosine, ATP. Concurrent use of caffeine with ergotamine improves ergotamine absorption from the gastrointestinal tract, and with thyrotropic agents increases thyroid effect. Caffeine reduces blood lithium concentration.

Dextromethorphan hydrobromide. Dextromethorphan is metabolized by CYP2D6 and undergoes extensive first-pass metabolism. Concurrent intake of potent inhibitors of the CYP2D6 enzyme may increase dextromethorphan concentration in the body to levels many times higher than normal. This increases the risk of toxic effects of dextromethorphan (agitation, confusion, tremor, insomnia, diarrhea, respiratory depression), the possibility of serotonin syndrome, and may affect cognitive abilities. Potent inhibitors of the CYP2D6 enzyme include fluoxetine, paroxetine, quinidine, and terbinafine. Concurrent use with quinidine has been shown to increase plasma dextromethorphan concentration up to 20-fold, intensifying the drug's adverse effects on the CNS. Amiodarone, flecainide, propafenone, sertraline, bupropion, methadone, cinacalcet, haloperidol, perphenazine, and thioridazine have similar effects on dextromethorphan metabolism. If concomitant use of CYP2D6 inhibitors and dextromethorphan is necessary, the patient should be closely monitored, and a dose reduction of dextromethorphan may be required. Ototoxic and photosensitizing drugs may enhance adverse effects when used concomitantly.

Special precautions for use.

Use during pregnancy or breastfeeding.

The drug is contraindicated during pregnancy or breastfeeding.

Ability to affect reaction rate when driving or operating machinery.

Since the drug may reduce psychomotor reaction speed in sensitive patients, which is necessary for performing potentially hazardous activities, it is advisable to refrain from driving vehicles, operating machinery, or performing other tasks requiring concentration of attention during drug administration.

Dosage and Administration

The medicine is intended for oral administration.

For adults and children aged 12 years and older: 1 tablet up to 4 times daily. The interval between doses should be no less than 4 hours. The duration of treatment should be determined by a physician. The maximum duration of use without medical consultation is 3 days. Do not exceed the recommended dose. Do not take together with other medicinal products containing paracetamol.

Children

Do not administer this medicine to children under 12 years of age.

Overdose

Symptoms and signs of overdose related to individual components of Gripex Aktiv Maks can be described as follows:

Symptoms of paracetamol overdose. Overdose is usually caused by paracetamol and manifests as pallor, anorexia, nausea, vomiting, abdominal pain, hepatonecrosis, elevated liver transaminase activity, and increased prothrombin index. In cases of overdose, excessive sweating, psychomotor agitation or depression of the central nervous system, drowsiness, impaired consciousness, cardiac arrhythmia, tachycardia, extrasystoles, tremor, hyperreflexia, and seizures may occur. Liver damage may become apparent 12–48 hours after overdose. Glucose metabolism disturbances and metabolic acidosis may also occur. In severe poisoning, liver failure may progress and lead to toxic encephalopathy with impaired consciousness, in some cases resulting in death. Acute kidney dysfunction with acute tubular necrosis may present as severe lumbar pain, hematuria, proteinuria, and may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have also been reported. Liver damage is possible in adults who have ingested 10 g or more of paracetamol, and in children who have ingested more than 150 mg/kg body weight. Ingestion of 5 g or more of paracetamol may lead to liver damage in patients with risk factors (long-term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John's wort, or other drugs inducing liver enzymes; chronic excessive ethanol consumption; glutathione depletion (digestive disorders, cystic fibrosis, HIV infection, fasting, cachexia)).

Symptoms of caffeine overdose. High doses of caffeine may cause headache, epigastric pain, vomiting, diuresis, rapid breathing, extrasystoles, tachycardia or cardiac arrhythmia, and affect the central nervous system (dizziness, insomnia, nervous excitement, irritability, emotional lability, anxiety, tremor, seizures). Clinically significant symptoms of caffeine overdose may also be associated with paracetamol-induced liver damage.

Symptoms of overdose related to potentiation of the anticholinergic effect of the antihistamine component and the sympathomimetic effect of phenylephrine. Drowsiness, possibly followed by excitation (especially in children); visual disturbances; nausea, vomiting, headache; circulatory disturbances; coma; behavioral changes; arterial hypertension; bradycardia; atropine-like psychosis. Overdose due to phenylephrine may cause excessive sweating, psychomotor agitation or depression of the central nervous system, pallor, dizziness, insomnia, cardiac arrhythmia, tachycardia, extrasystoles, tremor, hyperreflexia, irritability, and restlessness. In severe cases, impaired consciousness, hallucinations, seizures, and arrhythmias may occur.

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

Symptoms and signs of dextromethorphan overdose

Dextromethorphan overdose may be accompanied by nausea, vomiting, dystonia, agitation, confusion, drowsiness, stupor, nystagmus, cardiotoxicity (tachycardia, ECG abnormalities including QT interval prolongation), ataxia, dizziness, lethargy, toxic psychosis with visual hallucinations, and increased excitability.

Treatment. In case of overdose, immediate medical assistance 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 overdose or risk of organ damage. Activated charcoal may be administered to asymptomatic patients within 1 hour after excessive dextromethorphan intake. Plasma paracetamol concentration should be measured 4 hours or later after ingestion (earlier measurements are unreliable). Treatment with N-acetylcysteine may be administered within 24 hours after paracetamol intake, but the maximum protective effect is achieved when administered within 8 hours after ingestion. The efficacy of the antidote decreases significantly after this time. If necessary, intravenous N-acetylcysteine should be administered according to the established dosage regimen. In the absence of vomiting, oral methionine may be used as an alternative in remote areas outside hospital settings. In cases of dextromethorphan overdose, for patients in a sedative or comatose state, naloxone in standard doses should be considered for the treatment of opioid overdose. Benzodiazepines, including those indicated for seizure treatment, and external cooling measures in case of hyperthermia due to serotonin syndrome may also be used.

Adverse Reactions

In most cases, the drug is well tolerated. Adverse effects related to the components of the drug were rarely observed, usually as a result of prolonged use of the drug in large doses.

Paracetamol.

Gastrointestinal disorders: Rarely – nausea, vomiting, decreased appetite, constipation, diarrhea, or flatulence, epigastric discomfort. With long-term use of high doses – epigastric pain, hepatotoxic effects; hepatonecrosis (with high-dose use).

Blood and lymphatic system disorders: Very rarely – hemolytic anemia, bruising or bleeding, methemoglobinemia (cyanosis, dyspnea, chest pain), thrombocytopenia; in isolated cases – aplastic anemia, pancytopenia, sulfhemoglobinemia, neutropenia, agranulocytosis, leukopenia.

Respiratory system disorders: Bronchospasm in patients sensitive to acetylsalicylic acid and other NSAIDs.

Renal and urinary disorders: Renal colic, sterile pyuria, interstitial glomerulonephritis; very rarely – nephrotoxic effects, papillary necrosis, micturition disorders, dysuria.

Immune system disorders: Anaphylaxis, hypersensitivity reactions including skin pruritus, skin and mucous membrane rashes (usually generalized rash, erythematous, urticaria), angioneurotic edema, erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome).

Hepatobiliary disorders: Liver function abnormalities, increased liver enzyme activity, usually without development of jaundice.

Metabolism and nutrition disorders: Frequency unknown (cannot be estimated from available data) – metabolic acidosis with high anion gap.

Other: In isolated cases – hypoglycemia up to hypoglycemic coma, general weakness, increased sweating, visual disturbances, dry eyes. Increased creatinine clearance, increased excretion of sodium and calcium, nasal congestion, possible false increase in blood uric acid measured by the Buttner method; slight increase in 5-hydroxyindoleacetic acid, vanillylmandelic acid, and catecholamines in urine.

Caffeine.

Central nervous system disorders: Rarely – headache, fear, general weakness, dizziness; in isolated cases – psychomotor agitation and disorientation, insomnia, restlessness, irritability or nervousness, tremor, confusion, depressive states, tingling and heaviness in extremities, tinnitus, epileptic seizures, coma, anxiety, hallucinations, dyskinesia.

Cardiovascular disorders: In isolated cases – palpitations, tachycardia, arrhythmia, increased blood pressure (especially in patients with arterial hypertension).

Gastrointestinal disorders: Rarely – nausea, vomiting, exacerbation of peptic ulcer disease.

Phenylephrine hydrochloride.

Nervous system disorders: Rarely – headache, insomnia, dizziness, confusion.

Cardiovascular disorders: In isolated cases – tachycardia, reflex bradycardia, dyspnea, chest pain, increased blood pressure (especially in patients with arterial hypertension), arrhythmia.

Gastrointestinal disorders: Nausea, diarrhea.

Chlorpheniramine maleate.

Gastrointestinal disorders: Nausea, vomiting, epigastric pain, dryness of mouth or throat.

Eye disorders: Very rarely – mydriasis, accommodation disorders, increased intraocular pressure.

Cardiovascular disorders: In isolated cases – tachycardia.

Central nervous system disorders: Rarely – drowsiness, headache, tremor.

Renal and urinary disorders: Very rarely – urinary retention and stranguria (difficult urination).

The excipient yellow azo dye FCF (E 110) may cause allergic reactions.

Adverse effects with dextromethorphan are rare, but gastrointestinal disturbances and dizziness have occasionally been reported.

Description of individual adverse reactions

Metabolic acidosis with high anion gap

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

Shelf life. 4 years.

Storage conditions.

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

Keep out of reach of children.

Packaging.

4 tablets in a blister; in a cardboard box.

10 tablets in a blister; in a cardboard box.

12 tablets in a blister; in a cardboard box.

20 (10×2) tablets in blisters; in a cardboard box.

24 (12×2) tablets in blisters; in a cardboard box.

Prescription status. Over-the-counter.

Manufacturer.

Evertogen Life Sciences Limited.

Manufacturer's address and place of business.

Plot No S-8, S-9, S-13 & S-14, APIIC, Pharma Sez, Green Industrial Park, Polepally (V), Jadcherla (M), Mahabubnagar, In-509 301, India.

Marketing Authorization Holder.

Unilab, LP, USA.

Address of the Marketing Authorization Holder and/or its representative.

966 Hungerford Drive, Suite ZB, Rockville, Maryland 20850, USA.