Pantamac

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PANTAMAC (PANTAMAC)

Composition:

Active substance: pantoprazole;

One enteric-coated tablet contains 40 mg of pantoprazole in the form of pantoprazole sodium sesquihydrate;

Excipients: mannite (E 421), crospovidone, anhydrous sodium carbonate, calcium stearate, hypromellose, povidone, titanium dioxide (E 171), yellow iron oxide (E 172), propylene glycol, methacrylate copolymer dispersion, triethyl citrate.

Pharmaceutical form. Enteric-coated tablets.

Main physicochemical properties: yellow, oval, biconvex enteric-coated tablets, smooth on both sides.

Pharmacotherapeutic group. Drugs for treatment of acid-related disorders. Proton pump inhibitors. ATC code A02BC02.

Pharmacological Properties

Pharmacodynamics

Pantoprazole is a proton pump inhibitor (PPI) that suppresses the final step of gastric acid production by covalent binding to the (H+, K+)-ATPase enzyme system at the secretory surface of gastric parietal cells. This results in inhibition of both basal and stimulated gastric acid secretion. Binding to (H+, K+)-ATPase provides prolonged antisecretory action, lasting more than 24 hours for all studied doses. Daily administration of pantoprazole enhances the suppression of gastric acid secretion. After an initial oral dose of 40 mg, mean inhibition reaches 51% at 2.5 hours. With once-daily dosing over 7 days, mean inhibition increases to 85%. Acid secretion was suppressed by more than 95% in half of the subjects studied. Acid secretion returned to normal within one week after the last dose of pantoprazole; no rebound hypersecretion was observed upon discontinuation of the drug.

It has been reported that during 4 weeks of treatment, mean increases in gastrin levels were 7%, 35%, and 72% from baseline values in groups receiving pantoprazole at doses of 10, 20, and 40 mg, respectively. A similar increase in serum gastrin levels was observed at week 8 of treatment, with mean increases of 3%, 26%, and 84%, respectively, in the three dose groups. Median serum gastrin levels remained within normal limits during maintenance therapy. During the first months of pantoprazole treatment at 40 mg/day in clinical trials for gastroesophageal reflux disease (GERD), a 2- to 3-fold mean increase in fasting serum gastrin levels was observed compared to baseline in patients with refractory GERD. Fasting serum gastrin levels generally remained within 2- to 3-fold of baseline values throughout up to 4 years of follow-up in clinical studies. After short-term treatment, elevated gastrin levels returned to normal within at least 3 months.

In most patients, symptoms resolve within 2 weeks. Like other PPIs and H2-receptor antagonists, pantoprazole reduces gastric acidity and thereby increases gastrin secretion proportionally to the reduction in acidity. Increased gastrin secretion is reversible. Since pantoprazole binds to the enzyme distal to the cellular receptor, it can inhibit hydrochloric acid secretion regardless of stimulation by other substances (acetylcholine, histamine, gastrin). The effect is equivalent following oral and intravenous administration. Pantoprazole increases fasting gastrin levels. With short-term use, gastrin levels in most cases do not exceed the upper normal limit. With long-term treatment, gastrin levels typically double. However, marked elevation occurs only in isolated cases. As a result, with prolonged therapy, mild or moderate increase in enterochromaffin-like (ECL) cells in the stomach (similar to adenomatoid hyperplasia) may occasionally be observed. However, according to current studies, development of neuroendocrine tumor precursors (atypical hyperplasia) or gastric neuroendocrine tumors, which were observed in animal studies, has not been reported in humans. Based on animal study results, the influence of long-term (more than one year) pantoprazole treatment on endocrine parameters of the thyroid gland cannot be completely excluded.

Pharmacokinetics

Pantamac is an enteric-coated tablet formulation; therefore, absorption of pantoprazole begins only after the tablet leaves the stomach. Maximum serum concentration (Cmax) and area under the plasma concentration-time curve (AUC) increase proportionally with oral and intravenous doses in the range of 10 to 80 mg. Pantoprazole does not accumulate, and its pharmacokinetics remain unchanged with multiple daily dosing. After oral or intravenous administration, pantoprazole concentration in serum declines biexponentially, with a terminal elimination half-life of approximately one hour.

With enhanced metabolism and normal liver function, oral administration of a 40 mg enteric-coated pantoprazole tablet results in a Cmax of 2.5 µg/mL; time to reach maximum concentration (tmax) is 2.5 hours, and mean total AUC is 4.8 µg•h/mL (range: 1.4–13.3 µg•h/mL). After intravenous administration in subjects with enhanced metabolism, total clearance of pantoprazole ranges from 7.6 to 14.0 L/h, and apparent volume of distribution is 11.0–23.6 L.

Absorption

After single or multiple oral doses of 40 mg Pantamac, maximum plasma concentration of pantoprazole is reached at approximately 2.5 hours, with a Cmax of 2.5 µg/mL. Pantoprazole undergoes minimal first-pass metabolism, resulting in an absolute bioavailability of approximately 77%. Absorption of pantoprazole is not affected by concomitant administration of antacids.

Taking Pantamac with food may delay absorption by up to 2 hours or more, but Cmax and extent of absorption (AUC) remain unchanged. Therefore, Pantamac enteric-coated tablets may be taken independently of food intake.

Distribution

The apparent volume of distribution of pantoprazole is approximately 11.0–23.6 L, with predominant distribution into extracellular fluid. Pantoprazole binds extensively to plasma proteins, primarily albumin, with a binding rate of approximately 98%.

Metabolism

Pantoprazole undergoes extensive hepatic metabolism via the cytochrome P450 (CYP) system. Metabolism of pantoprazole is independent of the route of administration (intravenous or oral). The primary metabolic pathway is demethylation mediated by CYP2C19, followed by sulfation; other metabolic pathways include oxidation via CYP3A4. There is no evidence of significant pharmacological activity of any pantoprazole metabolites.

Excretion

After oral or intravenous administration of a single dose of 14C-labeled pantoprazole to healthy volunteers with normal metabolism, approximately 71% of the dose is excreted in urine and 18% via bile into feces. Unchanged pantoprazole is not excreted by the kidneys.

Elderly Patients

In elderly patients (64–76 years), only slight or moderate increases in AUC (43%) and Cmax (26%) of pantoprazole were observed after multiple oral doses compared to younger subjects. Dose adjustment based on age is not required.

Pediatric Population

The safety and efficacy of pantoprazole for short-term treatment (up to eight weeks) of erosive esophagitis associated with GERD have been evaluated in children aged 1 to 16 years. Efficacy in erosive esophagitis has not been demonstrated in patients under 1 year of age. Therefore, pantoprazole is recommended for short-term treatment of erosive esophagitis associated with GERD in patients with body weight ≥40 kg. The safety and efficacy of pantoprazole in children for conditions other than erosive esophagitis have not been established. Although clinical trial data support the use of pantoprazole for short-term treatment of erosive esophagitis associated with GERD in children aged 1 to 5 years.

Children aged 6 to 16 years

Pharmacokinetics of pantoprazole were evaluated in children aged 6 to 16 years with a clinical diagnosis of GERD. Pharmacokinetic parameters after single oral doses of 20 mg or 40 mg pantoprazole showed high variability (% coefficient of variation ranging from 40 to 80%). Geometric mean AUC, determined by population pharmacokinetic analysis after administration of 40 mg tablets, was approximately 39% and 10% higher in children aged 6–11 and 12–16 years, respectively, compared to adults (see Table 1).

Table 1

Pharmacokinetic parameters in children aged 6–16 years with GERD receiving pantoprazole 40 mg

a Geometric mean values.

b Median values.

Renal impairment

In patients with severe renal impairment, the pharmacokinetic parameters of pantoprazole were the same as in patients with normal renal function. Dose adjustment is not required for patients with renal impairment or for patients undergoing hemodialysis.

Hepatic impairment

In patients with mild to severe hepatic impairment (Child–Pugh classes A to C), the Cmax of pantoprazole was only slightly increased (by a factor of 1.5) compared to healthy volunteers.

Clinical characteristics.

Indications.

Treatment of reflux esophagitis associated with gastroesophageal reflux disease (GERD).

Maintenance of remission of erosive esophagitis.

Treatment of pathological hypersecretory conditions, including Zollinger–Ellison syndrome.

Contraindications.

Hypersensitivity to the active substance, to rilpivirine, benzimidazole derivatives, or to any component of the medicinal product.

Interaction with other medicinal products and other forms of interaction.

Effect of pantoprazole on absorption of other medicinal products. Pantoprazole may reduce the absorption of drugs whose bioavailability is pH-dependent (e.g., certain antifungal agents such as ketoconazole, itraconazole, posaconazole, or other drugs such as erlotinib). Concomitant use of atazanavir or nelfinavir with PPIs is not recommended. Concomitant administration of atazanavir or nelfinavir with PPIs may significantly reduce plasma concentrations of atazanavir or nelfinavir, leading to loss of therapeutic effect and development of drug resistance.

Rilpivirine

Products containing rilpivirine. Concomitant use with the medicinal product Pantamak is contraindicated.

Coumarin anticoagulants. There have been post-marketing reports of increased international normalized ratio (INR) and prothrombin time in patients receiving PPIs, including the medicinal product Pantamak, concomitantly with warfarin or phenprocoumon. Increased INR and prothrombin time may lead to excessive bleeding and even death. Severe outcomes may be prevented by early recognition of symptoms. Therefore, monitoring of INR and prothrombin time is necessary in patients receiving PPIs and warfarin or phenprocoumon concomitantly.

Clopidogrel. Concomitant administration of pantoprazole and clopidogrel in healthy volunteers did not have a clinically significant effect on the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition. When the approved dose of Pantamak is used, no dose adjustment of clopidogrel is required.

Drugs whose bioavailability may be affected by gastric pH

Pantoprazole causes prolonged inhibition of gastric acid secretion. Thus, pantoprazole may affect the absorption of drugs whose bioavailability is pH-dependent (e.g., ketoconazole, ampicillin esters, iron salts).

False-positive urine screening test for tetrahydrocannabinol (THC)

There have been reports of false-positive urine screening tests for THC in patients receiving PPIs. Alternative testing methods should be used to confirm test results.

Methotrexate

Published case reports, population pharmacokinetic studies, and retrospective analyses suggest that concomitant use of PPIs and methotrexate (particularly high doses; see methotrexate prescribing information) may increase serum levels of methotrexate and/or its metabolite hydroxymethotrexate. However, there are no official studies on the interaction between methotrexate and PPIs.

Other interactions. Pantoprazole is extensively metabolized in the liver via the cytochrome P450 enzyme system. The main metabolic pathway is demethylation by CYP2C19, with additional metabolism via CYP3A4. Studies with medicinal products that are also metabolized via these pathways—such as carbamazepine, diazepam, glyburide, nifedipine, phenprocoumon, and oral contraceptives containing levonorgestrel and ethinylestradiol—have not revealed clinically significant interactions. Results from several studies on potential interactions indicate that pantoprazole does not affect the metabolism of active substances metabolized by CYP1A2 (e.g., caffeine, theophylline), CYP2C9 (e.g., piroxicam, diclofenac, naproxen), CYP2D6 (e.g., metoprolol), or CYP2E1 (e.g., ethanol), nor does it affect P-glycoprotein-mediated digoxin absorption. No interaction has been observed with concomitantly administered antacids. Studies have been conducted on the interaction of pantoprazole with concomitantly administered certain antibiotics (clarithromycin, metronidazole, amoxicillin). No clinically significant interactions between these drugs have been identified.

Special precautions for use.

Hepatic impairment. In patients with severe hepatic dysfunction, liver enzymes should be monitored regularly. If liver enzymes are elevated, treatment with the drug should be discontinued.

Concomitant use with NSAIDs. Long-term use of Pantamac for prevention of gastric and duodenal ulcers induced by NSAIDs should be limited to patients prone to frequent ulcer recurrences.

Risk assessment should take into account individual risk factors, including age (>65 years), history of gastric or duodenal ulcer, and gastrointestinal bleeding.

Malignant gastric tumors. Symptom relief during pantoprazole treatment does not exclude the possibility of gastric malignancy. Therefore, additional monitoring and diagnostic evaluation are required in adult patients with inadequate response or early symptomatic relapse after completion of PPI therapy. Endoscopy is also indicated in elderly patients.

Acute interstitial nephritis. Cases of acute interstitial nephritis have been reported in patients taking PPIs, including pantoprazole. Acute interstitial nephritis may occur at any stage of PPI therapy and is usually considered an idiosyncratic hypersensitivity reaction. Pantoprazole treatment should be discontinued if acute interstitial nephritis develops.

Clostridium difficile-associated diarrhea. Published observational studies indicate that PPI therapy, including pantoprazole, may increase the risk of Clostridium difficile-associated diarrhea, particularly in hospitalized patients. This diagnosis should be considered in cases of persistent diarrhea.

Patients should be prescribed the lowest effective PPI dose for the shortest duration necessary to achieve therapeutic goals.

Bone fractures. Several published observational studies suggest that PPI therapy may be associated with an increased risk of osteoporotic fractures of the hip, spine, and wrist. The fracture risk is higher in patients receiving high doses (i.e., multiple daily doses) or long-term PPI therapy (one year or more). Patients should be prescribed lower doses or shorter treatment durations appropriate for their condition. Observational studies indicate that PPI use may increase the overall fracture risk by 10–40%. Risk may be mitigated by co-administration of vitamin D and calcium with pantoprazole therapy. Particular caution is advised when prescribing pantoprazole:

• for long-term use;
• to elderly patients;
• to patients with other risk factors.

Patients should be prescribed the lowest effective PPI dose for the shortest duration appropriate for their indication. Patients at risk of osteoporotic fractures should be managed according to current therapeutic guidelines.

Cutaneous and systemic lupus erythematosus. Cases of cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been observed in patients treated with PPIs, including pantoprazole. These events occurred both as new-onset and as exacerbations of pre-existing autoimmune disease. Cutaneous lupus was more frequently reported during PPI therapy.

The most commonly observed form of CLE in patients on PPI therapy was subacute CLE (SCLE), occurring in patients of various ages (including infants and elderly patients aged 60 years and older). This adverse effect may occur within several weeks or several years after initiation of treatment. Histological findings generally did not indicate internal organ involvement.

SLE was less frequently observed than CLE in patients on PPI therapy. SLE associated with PPIs usually had a milder course compared to non-drug-induced SLE. SLE may appear within several days or several years after starting treatment in patients of all ages, from young adults to the elderly. In most patients, SLE presented with skin rash, although arthralgia and cytopenia were also observed.

The duration of PPI use should strictly correspond to medical indications. If patients receiving pantoprazole develop symptoms suggestive of CLE or SLE, the drug should be discontinued and the patient referred for evaluation by a specialist. In most patients, symptoms improve within 4–12 weeks after discontinuation of PPI therapy. Positive serological test results (e.g., ANA) and elevated serological markers may persist for some time after resolution of clinical symptoms.

Severe cutaneous adverse reactions.

Severe skin adverse reactions have been reported, including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis. The use of Pantamac should be discontinued at the first signs or symptoms of severe skin reactions or other signs of hypersensitivity, and further evaluation should be considered.

Vitamin B12 (cyanocobalamin) deficiency. Long-term daily use (more than 3 years) of drugs that suppress gastric acid secretion may impair absorption of cyanocobalamin (vitamin B12), particularly in the presence of hypo- or achlorhydria. Rare cases of cyanocobalamin deficiency associated with acid-suppressive therapy have been reported in the scientific literature. Therefore, this diagnosis should be considered if clinical symptoms of cyanocobalamin deficiency occur.

Hypomagnesemia. Symptomatic and asymptomatic hypomagnesemia has been rarely observed in patients receiving PPIs for at least three months, and in most cases after one year of therapy. Serious adverse reactions include tetany, arrhythmias, and seizures. Hypomagnesemia may lead to hypocalcemia and/or hypokalemia and may exacerbate underlying hypocalcemia in at-risk patients. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of PPI therapy.

For patients expected to receive long-term therapy or those taking PPIs with medications such as digoxin or other drugs that may cause hypomagnesemia (e.g., diuretics), healthcare providers may consider monitoring magnesium levels before starting PPI therapy and periodically during treatment. Monitoring of magnesium and calcium levels should also be considered before starting Pantamac and periodically during treatment in patients at risk of hypocalcemia (e.g., hypoparathyroidism). Magnesium and/or calcium supplementation may be necessary. If hypocalcemia is refractory to treatment, discontinuation of PPI therapy should be considered.

Fundic gland polyps.

PPI use is associated with an increased risk of fundic gland polyps, with risk increasing with prolonged use, especially beyond one year. Most PPI users who developed fundic gland polyps were asymptomatic, and polyps were detected incidentally during endoscopy. PPIs should be used for the shortest duration appropriate for the condition being treated.

Carcinogenicity. The chronic nature of GERD often requires long-term pantoprazole use. In long-term rodent studies, pantoprazole demonstrated carcinogenic potential and caused rare types of gastrointestinal tumors. The relevance of these findings to human carcinogenesis is unknown.

False-positive urine THC test results (see section "Interaction with other medicinal products and other forms of interaction").

Concomitant use of pantoprazole with methotrexate. According to scientific literature, concomitant use of PPIs with methotrexate (see section "Interaction with other medicinal products and other forms of interaction"), particularly at high doses, may increase serum levels of methotrexate and/or its metabolites, increasing the risk of methotrexate toxicity. High-dose methotrexate therapy may require temporary discontinuation of PPI treatment.

Effect on laboratory test results. PPI use, including pantoprazole, may increase chromogranin A (CgA) levels, which may interfere with neuroendocrine tumor testing. To avoid this interference, Pantamac should be discontinued at least 14 days before CgA measurement.

Excipients. This medicinal product contains lactose. In patients with known intolerance to certain sugars, consultation with a physician is necessary before taking this medicinal product.

Concomitant use with atazanavir. Proton pump inhibitors are not recommended for concomitant use with atazanavir (see section "Interaction with other medicinal products and other forms of interaction"). If combination therapy with Pantamac and atazanavir is necessary, careful clinical monitoring (including viral load measurement) should be performed, along with increasing the atazanavir dose to 400 mg in combination with 100 mg ritonavir. The pantoprazole dose should not exceed 20 mg daily.

Gastrointestinal tract infections caused by bacteria. Pantoprazole, like other PPIs, may increase the number of bacteria normally present in the upper gastrointestinal tract. Treatment with the drug slightly increases the risk of gastrointestinal infections caused by bacteria such as Salmonella and Campylobacter.

Use during pregnancy or breastfeeding.

Pregnancy. Reproductive studies in animals did not reveal fertility impairment or fetal developmental abnormalities caused by pantoprazole. However, there are no adequate and well-controlled studies in pregnant women. Since animal reproductive study results do not always predict human response, this drug should be used during pregnancy only if clearly needed and the benefit to the mother outweighs the potential risk to the fetus.

Breastfeeding period. Animal studies have shown excretion of pantoprazole into breast milk. Data are available on excretion of pantoprazole into human breast milk. The decision to continue/stop breastfeeding or to continue/stop treatment with Pantamac should be made considering the benefits of breastfeeding for the child and the benefits of Pantamac therapy for the mother.

Ability to affect reaction speed when driving or operating machinery.

Possible adverse reactions such as dizziness and visual disturbances should be considered. In such cases, driving or operating machinery should be avoided. Studies on the effect of the drug on the ability to drive vehicles or operate machinery have not been conducted.

Dosage and Administration

Treatment of reflux esophagitis associated with gastroesophageal reflux disease (GERD)

Pantoprazole is indicated in adults for the treatment and relief of symptoms of reflux esophagitis; the treatment course should not exceed 8 weeks. An additional 8-week course of pantoprazole may be considered in adult patients in whom healing has not been achieved after the initial 8-week treatment course. The safety of a second 8-week treatment course has not been established in children.

Pantoprazole is indicated in pediatric patients with body weight ≥40 kg for short-term treatment of erosive esophagitis associated with GERD (see Table 2).

Maintenance treatment of erosive esophagitis

Recommended dosages are provided in Table 2.

Table 2

* Adult patients who have not recovered after 8 weeks of treatment may be prescribed an additional 8-week course of Pantamac.

** Dosage and frequency should be adjusted according to individual patient needs. Therapy should be continued as long as there are clinical indications. Doses up to 240 mg daily have been used.

Table 3

Method of administration

Concomitant use of antacids does not affect the absorption of the tablets.

Elderly patients do not require dose adjustment.

Patients with hepatic impairment. Doses above 40 mg/day have not been studied in patients with liver dysfunction.

Children.

This medicinal formulation of Pantamak is recommended for short-term treatment of erosive esophagitis associated with gastroesophageal reflux disease in patients with body weight ≥ 40 kg.

The medicinal product should be used in children as specified in the sections “Indications” and “Dosage and administration”.

The safety and efficacy of pantoprazole for short-term treatment (up to eight weeks) of erosive esophagitis associated with gastroesophageal reflux disease have been evaluated in children aged 1 to 16 years. Efficacy in erosive esophagitis has not been demonstrated in patients under 1 year of age. The safety and efficacy of pantoprazole in children for the treatment of conditions other than erosive esophagitis have not been evaluated.

Overdose.

Experience with patients taking excessive doses of pantoprazole > 240 mg is limited.

Pantoprazole is extensively protein-bound and cannot be completely removed by dialysis. In case of overdose with clinical signs of intoxication, symptomatic and supportive therapy should be administered.

Side effects

Adverse reactions may be expected to occur in approximately 5% of patients. The most common adverse reactions—diarrhea and headache—occur in 1% of patients.

Adverse reactions are classified by frequency of occurrence as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10000 to < 1/1000), very rare (< 1/10000), frequency not known (cannot be estimated from the available data).

For all adverse reactions reported during the post-marketing period, it is not possible to determine the frequency; therefore, they are listed as having a frequency of "frequency not known". Within each frequency category, adverse reactions are listed in order of decreasing severity.

Blood and lymphatic system disorders

Rare: agranulocytosis.
Very rare: leukopenia, thrombocytopenia, pancytopenia.

Immune system disorders

Rare: hypersensitivity reactions (including anaphylactic reactions, anaphylactic shock).

Metabolism and nutrition disorders

Rare: hyperlipidemia and increased lipid levels (triglycerides, cholesterol), change in body weight.
Frequency not known: hyponatremia, hypomagnesemia (see section "Special precautions"), hypocalcemia (may be associated with the development of hypomagnesemia), hypokalemia (may be associated with the development of hypomagnesemia), cyanocobalamin (vitamin B12) deficiency.

Psychiatric disorders

Uncommon: sleep disorders.
Rare: depression (including exacerbation).
Very rare: confusion (including exacerbation).
Frequency not known: hallucinations, confusion (especially in patients predisposed to such disorders, and exacerbation of these symptoms if pre-existing).

Nervous system disorders

Uncommon: headache, dizziness.
Rare: taste disturbances.
Frequency not known: paraesthesia.

Eye disorders

Rare: visual disturbances/blurred vision.

Gastrointestinal disorders

Common: fundic gland polyps (benign).
Uncommon: Clostridium difficile-associated diarrhea, nausea, vomiting, abdominal distension, constipation, dry mouth, abdominal pain, and discomfort in the abdomen.
Frequency not known: microscopic colitis.

Hepatobiliary disorders

Uncommon: increased liver enzymes (transaminases, γ-glutamyltransferase).
Rare: increased bilirubin levels.
Frequency not known: hepatocellular injury, jaundice, hepatocellular failure.

Skin and subcutaneous tissue disorders

Uncommon: skin rashes, exanthema, pruritus.
Rare: urticaria, angioneurotic edema.
Frequency not known: Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), erythema multiforme, photosensitivity, subacute cutaneous lupus erythematosus (see section "Special precautions"). Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome).

Musculoskeletal and connective tissue disorders

Uncommon: fractures of the femur, wrist, spine (see section "Special precautions").
Rare: arthralgia, myalgia.
Frequency not known: muscle spasms (as a consequence of electrolyte disturbances).

Renal and urinary disorders

Frequency not known: interstitial nephritis (with possible development of renal failure).

Reproductive system and breast disorders

Rare: gynecomastia.

General disorders

Uncommon: asthenia, fatigue, malaise.
Rare: increased body temperature, peripheral edema.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, or their legal representatives should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life

2 years.

Storage conditions

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

Keep out of reach of children.

Packaging

10 tablets in a blister; 3 blisters in a cardboard box.

Prescription status

Prescription only.

Manufacturer

MACLEODS PHARMACEUTICALS LIMITED.

Manufacturer's address and location of operations

Phase II, Plot No. 12, 15, 21, 23, 24, 25, 26, 27, 28 and 30, Survey No. 366, Premier Industrial Estate, Kachigam, Daman, 396210, India.