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Stool softener

Docusate sodium works by allowing more water to be absorbed by the stool. Docusate does not stay in the gastrointestinal tract, but is absorbed into the bloodstream and excreted via the gallbladder after undergoing extensive metabolism. The effect of docusate may not necessarily be all due to its surfactant properties. Perfusion studies suggest that docusate inhibits fluid absorption or stimulates secretion in the portion of the small intestine known as the jejunum.

Route of administration: Oral.

• Adults and elderly: One to five Docusate Sodium oral preparations should be taken daily in divided doses. Treatment should be commenced with large doses, which should be decreased as the condition of the patient improves.
• For use with barium meals: Four Docusate Sodium oral preparations to be taken with the meal.
• Children under 12 years: Not recommended.

Rarely, Docusate Sodium softgel capsules can cause diarrhea, nausea, abdominal cramps or skin rash.

Docusate Sodium softgel capsule is contra-indicated in patients with hypersensitivity to Docusate Sodium.

Docusate Sodium capsule should not be administered when abdominal pain, nausea, vomiting or intestinal obstruction is present. Patients with rare hereditary problems of fructose intolerance should not take this medicine. Organic disorders should be excluded prior to the administration of any laxative. The treatment of constipation with any medicinal product is only adjuvant to a healthy lifestyle and diet, for example, increased intake of fluids and dietary fiber and advice on appropriate physical activity. If laxatives are needed every day, or if there is persistent abdominal pain, patients need to consult with physicians. Do not use this medicine if patients are intolerant to small quantities of sugar (sorbitol, fructose).

Docusate Sodium softgel capsules should not be taken concurrently with mineral oil.

There are no adequate data from the use of the drug in pregnant women. Animal studies are insufficient with respect to effects on pregnancy and embryonic foetal development. The potential risk for humans is unknown. During wide use, no adverse consequences have been reported. Use in pregnancy only if the benefits outweigh the risks. Docusate sodium is excreted in breast milk and should therefore, be used with caution in lactating mothers.

In rare cases of overdose, excessive loss of water and electrolytes should be treated by encouraging the patient to drink plenty of fluid. Electrolyte loss should be replenished where appropriate.

Store in a cool and dry place, protected from light.

Hepatic viral infections (Hepatitis C)

Sofosbuvir is nucleotide analog inhibitor, which specifically inhibits HCV NS5B (non-structural protein 5B) RNA-dependent RNA polymerase. Following intracellular metabolism to form the pharmacologically active uridine analog triphosphate (GS-461203), sofosbuvir incorporates into HCV RNA by the NS5B polymerase and acts as a chain terminator. More specifically, Sofosbuvir prevents HCV viral replication by binding to the two Mg2+ ions present in HCV NS5B polymerase's GDD active site motif and preventing further replication of HCV genetic material

One 400 mg tablet taken once daily with or without food. Should be used in combination with Ribavirin or in combination with Pegylated Interferon and Ribavirin for the treatment of CHC.

Recommended combination therapy: (HCV Mono-infected and HCV/HIV-1 Co-infected)-

• Genotype 1 or 4: Sofosbuvir + Peginterferon alfa + Ribavirin for 12 weeks
• Genotype 2: Sofosbuvir + Ribavirin for 12 weeks
• Genotype 3: Sofosbuvir + Ribavirin for 24 weeks

Sofosbuvir in combination with Ribavirin for 24 weeks can be considered for CHC patients with genotype 1 infection who are Interferon ineligible

Should be used in combination with Ribavirin for treatment of CHC in patients with hepatocellular carcinoma awaiting liver transplantation for up to 48 weeks or until liver transplantation whichever occurs first

A dose recommendation cannot be made for patients with severe renal impairment or end stage renal disease

The most common adverse events (incidence greater than or equal to 20%, all grades) observed with Sofosbuvir in combination with Ribavirin were fatigue and headache. The most common adverse events observed with Sofosbuvir in combination with Peginterferon alfa and Ribavirin were fatigue, headache, nausea, insomnia, anemia, pruritus, asthenia, rash, decreased appetite, chills, influenza like illness, pyrexia, diarrhea, neutropenia, myalgia, irritability.

When Sofosbivur is used in combination with Ribavirin or Peginterferon alfa/ Ribavirin, the contraindications applicable to those agents are applicable to combination therapies. Sofosbuvir combination treatment with Ribavirin or Peginterferon alfa/Ribavirin is contraindicated in women who are pregnant or may become pregnant and men whose female partners are pregnant, because of the risks for birth defects and fetal death associated with Ribavirin.

Bradycardia with amiodarone co-administration: Serious symptomatic bradycardia may occur in patients taking amiodarone and Sofosbuvir in combination with another direct acting antiviral (DAA), particularly in patients also receiving beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease. Co-administration of amiodarone with Sofosbuvir in combination with another DAA is not recommended. In patients without alternative, viable treatment options, cardiac monitoring is recommended.

Reduced therapeutic effect with drugs that are potent P-gp inducers in the intestine (eg rifampicin, St. John's wort, carbamazepine & phenytoin), modafinil, phenobarb/ oxcarbazepine, rifabutin/ rifapentine. P-gp &/or BCRP inhibitors. May result in serious symptomatic bradycardia when co-administered with amiodarone in combination with another direct acting antiviral.

Pregnancy Category B: Sofosbuvir There are no adequate and well-controlled studies with Sofosbuvir in pregnant women.

Nursing Mothers: It is not known whether Sofosbuvir and its metabolites are present in human breast milk.

Pediatric Use: Safety and effectiveness of Sofosbuvir in children less than 18 years of age have not been established.

Geriatric Use: Sofosbuvir was administered to 90 subjects aged 65 and over. The response rates observed for subjects over 65 years of age were similar to that of younger subjects across treatment groups. No dose adjustment of Sofosbuvir is warranted in geriatric patients.

The highest dose of Sofosbuvir is a single dose of Sofosbuvir 1200 mg. No specific antidote is available for overdose treatment. Treatment of overdose with Sofosbuvir consists of general supportive measures including monitoring of vital signs as well as observation of the clinical status of the patient.

Keep out of the reach of children. Keep in a cool & dry place. Protect from light.

Ledipasvir and Sofosbuvir combination is indicated for the treatment of chronic hepatitis C (CHC) genotype 1, 4 & 6 infection in adults.

Hepatic viral infections (Hepatitis C)

It is a fixed-dose combination tablet containing Ledipasvir and Sofosbuvir for oral administration. Ledipasvir is an HCV NS5A inhibitor and Sofosbuvir is a nucleotide analog inhibitor of HCV NS5B polymerase.

Recommended dosage: One tablet (90 mg of Ledipasvir and 400 mg of Sofosbuvir) taken orally once daily with or without food

Recommended treatment duration:

• Treatment-naive with or without cirrhosis: 12 weeks
• Treatment-experienced without cirrhosis: 12 weeks
• Treatment-experienced with cirrhosis: 24 weeks

A dose recommendation cannot be made for patients with severe renal impairment or end stage renal disease.

The most common adverse reactions with treatment with Ledipasvir and Sofosbuvir combination for 8, 12, or 24 weeks are fatigue and headache.

This combination is contraindicated in patients with Known hypersensitivity to Ledipasvir, Sofosbuvir or any other ingredient in the product.

Bradycardia with Amiodarone coadministration: Serious symptomatic bradycardia may occur in patients taking Amiodarone, particularly in patients also receiving beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease. Coadministration of Amiodarone with Ledipasvir and Sofosbuvir combination is not recommended. In patients without viable treatment options, cardiac monitoring is recommended.

Use with other drugs containing sofosbuvir, is not recommended

Pregnancy Category B. There are no adequate and well-controlled studies with Ledipasvir and Sofosbuvir in pregnant women. Because animal reproduction studies are not always predictive of human response, this should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation: It is not known whether Ledipasvir and Sofosbuvir and its metabolites are present in human breast milk.

Pediatric Use: Safety and effectiveness of Ledipasvir and Sofosbuvir have not been established in pediatric patients.

Geriatric Use: No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. No dosage adjustment of Ledipasvir and Sofosbuvir is warranted in geriatric patients.

No specific antidote is available for overdose

Keep out of the reach of children. Keep in a cool & dry place. Protect from light.

Hepatic viral infections (Hepatitis C)

Sofosbuvir is nucleotide analog inhibitor, which specifically inhibits HCV NS5B (non-structural protein 5B) RNA-dependent RNA polymerase. Following intracellular metabolism to form the pharmacologically active uridine analog triphosphate (GS-461203), sofosbuvir incorporates into HCV RNA by the NS5B polymerase and acts as a chain terminator. More specifically, Sofosbuvir prevents HCV viral replication by binding to the two Mg2+ ions present in HCV NS5B polymerase's GDD active site motif and preventing further replication of HCV genetic material

One 400 mg tablet taken once daily with or without food. Should be used in combination with Ribavirin or in combination with Pegylated Interferon and Ribavirin for the treatment of CHC.

Recommended combination therapy: (HCV Mono-infected and HCV/HIV-1 Co-infected)-

• Genotype 1 or 4: Sofosbuvir + Peginterferon alfa + Ribavirin for 12 weeks
• Genotype 2: Sofosbuvir + Ribavirin for 12 weeks
• Genotype 3: Sofosbuvir + Ribavirin for 24 weeks

Sofosbuvir in combination with Ribavirin for 24 weeks can be considered for CHC patients with genotype 1 infection who are Interferon ineligible

Should be used in combination with Ribavirin for treatment of CHC in patients with hepatocellular carcinoma awaiting liver transplantation for up to 48 weeks or until liver transplantation whichever occurs first

A dose recommendation cannot be made for patients with severe renal impairment or end stage renal disease

The most common adverse events (incidence greater than or equal to 20%, all grades) observed with Sofosbuvir in combination with Ribavirin were fatigue and headache. The most common adverse events observed with Sofosbuvir in combination with Peginterferon alfa and Ribavirin were fatigue, headache, nausea, insomnia, anemia, pruritus, asthenia, rash, decreased appetite, chills, influenza like illness, pyrexia, diarrhea, neutropenia, myalgia, irritability.

When Sofosbivur is used in combination with Ribavirin or Peginterferon alfa/ Ribavirin, the contraindications applicable to those agents are applicable to combination therapies. Sofosbuvir combination treatment with Ribavirin or Peginterferon alfa/Ribavirin is contraindicated in women who are pregnant or may become pregnant and men whose female partners are pregnant, because of the risks for birth defects and fetal death associated with Ribavirin.

Bradycardia with amiodarone co-administration: Serious symptomatic bradycardia may occur in patients taking amiodarone and Sofosbuvir in combination with another direct acting antiviral (DAA), particularly in patients also receiving beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease. Co-administration of amiodarone with Sofosbuvir in combination with another DAA is not recommended. In patients without alternative, viable treatment options, cardiac monitoring is recommended.

Reduced therapeutic effect with drugs that are potent P-gp inducers in the intestine (eg rifampicin, St. John's wort, carbamazepine & phenytoin), modafinil, phenobarb/ oxcarbazepine, rifabutin/ rifapentine. P-gp &/or BCRP inhibitors. May result in serious symptomatic bradycardia when co-administered with amiodarone in combination with another direct acting antiviral.

Pregnancy Category B: Sofosbuvir There are no adequate and well-controlled studies with Sofosbuvir in pregnant women.

Nursing Mothers: It is not known whether Sofosbuvir and its metabolites are present in human breast milk.

Pediatric Use: Safety and effectiveness of Sofosbuvir in children less than 18 years of age have not been established.

Geriatric Use: Sofosbuvir was administered to 90 subjects aged 65 and over. The response rates observed for subjects over 65 years of age were similar to that of younger subjects across treatment groups. No dose adjustment of Sofosbuvir is warranted in geriatric patients.

The highest dose of Sofosbuvir is a single dose of Sofosbuvir 1200 mg. No specific antidote is available for overdose treatment. Treatment of overdose with Sofosbuvir consists of general supportive measures including monitoring of vital signs as well as observation of the clinical status of the patient.

Keep out of the reach of children. Keep in a cool & dry place. Protect from light.

Ledipasvir and Sofosbuvir combination is indicated for the treatment of chronic hepatitis C (CHC) genotype 1, 4 & 6 infection in adults.

Hepatic viral infections (Hepatitis C)

It is a fixed-dose combination tablet containing Ledipasvir and Sofosbuvir for oral administration. Ledipasvir is an HCV NS5A inhibitor and Sofosbuvir is a nucleotide analog inhibitor of HCV NS5B polymerase.

Recommended dosage: One tablet (90 mg of Ledipasvir and 400 mg of Sofosbuvir) taken orally once daily with or without food

Recommended treatment duration:

• Treatment-naive with or without cirrhosis: 12 weeks
• Treatment-experienced without cirrhosis: 12 weeks
• Treatment-experienced with cirrhosis: 24 weeks

A dose recommendation cannot be made for patients with severe renal impairment or end stage renal disease.

The most common adverse reactions with treatment with Ledipasvir and Sofosbuvir combination for 8, 12, or 24 weeks are fatigue and headache.

This combination is contraindicated in patients with Known hypersensitivity to Ledipasvir, Sofosbuvir or any other ingredient in the product.

Bradycardia with Amiodarone coadministration: Serious symptomatic bradycardia may occur in patients taking Amiodarone, particularly in patients also receiving beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease. Coadministration of Amiodarone with Ledipasvir and Sofosbuvir combination is not recommended. In patients without viable treatment options, cardiac monitoring is recommended.

Use with other drugs containing sofosbuvir, is not recommended

Pregnancy Category B. There are no adequate and well-controlled studies with Ledipasvir and Sofosbuvir in pregnant women. Because animal reproduction studies are not always predictive of human response, this should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation: It is not known whether Ledipasvir and Sofosbuvir and its metabolites are present in human breast milk.

Pediatric Use: Safety and effectiveness of Ledipasvir and Sofosbuvir have not been established in pediatric patients.

Geriatric Use: No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. No dosage adjustment of Ledipasvir and Sofosbuvir is warranted in geriatric patients.

No specific antidote is available for overdose

Keep out of the reach of children. Keep in a cool & dry place. Protect from light.

Sofosbuvir and Velpatasvir combination is indicated for the treatment of adult patients with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5 or 6 infection-

• Without cirrhosis or with compensated cirrhosis
• With decompensated cirrhosis for use in combination with ribavirin

Hepatic viral infections (Hepatitis C)

It is a fixed-dose combination tablet containing sofosbuvir and velpatasvir for oral administration. Sofosbuvir is a nucleotide analog HCV NS5B polymerase inhibitor and velpatasvir is an NS5A inhibitor.

The recommended dosage is one tablet (400 mg of Sofosbuvir and 100 mg of Velpatasvir) taken orally once daily. Recommended treatment regimen:

• Patients without cirrhosis and patients with compensated cirrhosis (Child-Pugh A): one tablet once daily for 12 weeks
• Patients with decompensated cirrhosis (Child-Pugh B or C): one tablet once daily and Ribavirin for 12 weeks. The recommended dosage of Ribavirin is based on bodyweight (1000 mg/day for patients < 75 kg and 1200 mg/day for ≥ 75 kg, in two divided dose/day)

The most common side effects of Sofosbuvir and Velpatasvir combination include headache and tiredness. Treatment may result in slowing of the heart rate along with other symptoms when taken with amiodarone (a medicine used to treat certain heart problems).

Sofosbuvir, Velpatasvir and Ribavirin combination regimen is contraindicated in patients for whom Ribavirin is contraindicated.

Serious symptomatic bradycardia may occur in patients taking amiodarone, particularly in patients also receiving beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease. Coadministration of amiodarone with Sofosbuvir and Velpatasvir combination is not recommended. In patients without alternative viable treatment options, cardiac monitoring is recommended.

Drugs may decrease the concentrations of sofosbuvir and/or velpatasvir: Antacids, H2-receptor antagonists, Proton-pump inhibitors etc.

Coadministration is not recommended with: topotecan, Carbamazepine, Phenytoin, Phenobarbital, Oxcarbazepine, Rifabutin, Rifampin, Rifapentine, efavirenz, Tipranavir, Ritonavir, Hypericum perforatum.

Coadministration of Sofosbuvir and Velpatasvir combination, with Rosuvastatin, Atorvastatin may significantly increase the concentration of Rosuvastatin, Atorvastatin.

No adequate human data are available to establish whether or not Sofosbuvir and Velpatasvir combination poses a risk to pregnancy outcomes. If Sofosbuvir and Velpatasvir combination administered with Ribavirin, the combination regimen is contraindicated in pregnant women and in men whose female partner is pregnant or going to be pregnant in next six months.

Renal impairment patient: No dosage recommendation can be given for patients with severe renal impairment (eGFR ≤30 mL/min/1.73 m²) or with ESRD, due to higher exposures of the predominant sofosbuvir metabolite.

If overdose occurs the patient must be monitored for evidence of toxicity. Treatment of overdose includes monitoring of vital signs as well as observation of the clinical status of the patient.

Store in a cool and dry place (preferably below 30° C). Keep out of reach of children.

Hepatic viral infections (Hepatitis C)

Sofosbuvir is nucleotide analog inhibitor, which specifically inhibits HCV NS5B (non-structural protein 5B) RNA-dependent RNA polymerase. Following intracellular metabolism to form the pharmacologically active uridine analog triphosphate (GS-461203), sofosbuvir incorporates into HCV RNA by the NS5B polymerase and acts as a chain terminator. More specifically, Sofosbuvir prevents HCV viral replication by binding to the two Mg2+ ions present in HCV NS5B polymerase's GDD active site motif and preventing further replication of HCV genetic material

One 400 mg tablet taken once daily with or without food. Should be used in combination with Ribavirin or in combination with Pegylated Interferon and Ribavirin for the treatment of CHC.

Recommended combination therapy: (HCV Mono-infected and HCV/HIV-1 Co-infected)-

• Genotype 1 or 4: Sofosbuvir + Peginterferon alfa + Ribavirin for 12 weeks
• Genotype 2: Sofosbuvir + Ribavirin for 12 weeks
• Genotype 3: Sofosbuvir + Ribavirin for 24 weeks

Sofosbuvir in combination with Ribavirin for 24 weeks can be considered for CHC patients with genotype 1 infection who are Interferon ineligible

Should be used in combination with Ribavirin for treatment of CHC in patients with hepatocellular carcinoma awaiting liver transplantation for up to 48 weeks or until liver transplantation whichever occurs first

A dose recommendation cannot be made for patients with severe renal impairment or end stage renal disease

The most common adverse events (incidence greater than or equal to 20%, all grades) observed with Sofosbuvir in combination with Ribavirin were fatigue and headache. The most common adverse events observed with Sofosbuvir in combination with Peginterferon alfa and Ribavirin were fatigue, headache, nausea, insomnia, anemia, pruritus, asthenia, rash, decreased appetite, chills, influenza like illness, pyrexia, diarrhea, neutropenia, myalgia, irritability.

When Sofosbivur is used in combination with Ribavirin or Peginterferon alfa/ Ribavirin, the contraindications applicable to those agents are applicable to combination therapies. Sofosbuvir combination treatment with Ribavirin or Peginterferon alfa/Ribavirin is contraindicated in women who are pregnant or may become pregnant and men whose female partners are pregnant, because of the risks for birth defects and fetal death associated with Ribavirin.

Bradycardia with amiodarone co-administration: Serious symptomatic bradycardia may occur in patients taking amiodarone and Sofosbuvir in combination with another direct acting antiviral (DAA), particularly in patients also receiving beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease. Co-administration of amiodarone with Sofosbuvir in combination with another DAA is not recommended. In patients without alternative, viable treatment options, cardiac monitoring is recommended.

Reduced therapeutic effect with drugs that are potent P-gp inducers in the intestine (eg rifampicin, St. John's wort, carbamazepine & phenytoin), modafinil, phenobarb/ oxcarbazepine, rifabutin/ rifapentine. P-gp &/or BCRP inhibitors. May result in serious symptomatic bradycardia when co-administered with amiodarone in combination with another direct acting antiviral.

Pregnancy Category B: Sofosbuvir There are no adequate and well-controlled studies with Sofosbuvir in pregnant women.

Nursing Mothers: It is not known whether Sofosbuvir and its metabolites are present in human breast milk.

Pediatric Use: Safety and effectiveness of Sofosbuvir in children less than 18 years of age have not been established.

Geriatric Use: Sofosbuvir was administered to 90 subjects aged 65 and over. The response rates observed for subjects over 65 years of age were similar to that of younger subjects across treatment groups. No dose adjustment of Sofosbuvir is warranted in geriatric patients.

The highest dose of Sofosbuvir is a single dose of Sofosbuvir 1200 mg. No specific antidote is available for overdose treatment. Treatment of overdose with Sofosbuvir consists of general supportive measures including monitoring of vital signs as well as observation of the clinical status of the patient.

Keep out of the reach of children. Keep in a cool & dry place. Protect from light.

Hepatic viral infections (Hepatitis C)

Sofosbuvir is nucleotide analog inhibitor, which specifically inhibits HCV NS5B (non-structural protein 5B) RNA-dependent RNA polymerase. Following intracellular metabolism to form the pharmacologically active uridine analog triphosphate (GS-461203), sofosbuvir incorporates into HCV RNA by the NS5B polymerase and acts as a chain terminator. More specifically, Sofosbuvir prevents HCV viral replication by binding to the two Mg2+ ions present in HCV NS5B polymerase's GDD active site motif and preventing further replication of HCV genetic material

One 400 mg tablet taken once daily with or without food. Should be used in combination with Ribavirin or in combination with Pegylated Interferon and Ribavirin for the treatment of CHC.

Recommended combination therapy: (HCV Mono-infected and HCV/HIV-1 Co-infected)-

• Genotype 1 or 4: Sofosbuvir + Peginterferon alfa + Ribavirin for 12 weeks
• Genotype 2: Sofosbuvir + Ribavirin for 12 weeks
• Genotype 3: Sofosbuvir + Ribavirin for 24 weeks

Sofosbuvir in combination with Ribavirin for 24 weeks can be considered for CHC patients with genotype 1 infection who are Interferon ineligible

Should be used in combination with Ribavirin for treatment of CHC in patients with hepatocellular carcinoma awaiting liver transplantation for up to 48 weeks or until liver transplantation whichever occurs first

A dose recommendation cannot be made for patients with severe renal impairment or end stage renal disease

The most common adverse events (incidence greater than or equal to 20%, all grades) observed with Sofosbuvir in combination with Ribavirin were fatigue and headache. The most common adverse events observed with Sofosbuvir in combination with Peginterferon alfa and Ribavirin were fatigue, headache, nausea, insomnia, anemia, pruritus, asthenia, rash, decreased appetite, chills, influenza like illness, pyrexia, diarrhea, neutropenia, myalgia, irritability.

When Sofosbivur is used in combination with Ribavirin or Peginterferon alfa/ Ribavirin, the contraindications applicable to those agents are applicable to combination therapies. Sofosbuvir combination treatment with Ribavirin or Peginterferon alfa/Ribavirin is contraindicated in women who are pregnant or may become pregnant and men whose female partners are pregnant, because of the risks for birth defects and fetal death associated with Ribavirin.

Bradycardia with amiodarone co-administration: Serious symptomatic bradycardia may occur in patients taking amiodarone and Sofosbuvir in combination with another direct acting antiviral (DAA), particularly in patients also receiving beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease. Co-administration of amiodarone with Sofosbuvir in combination with another DAA is not recommended. In patients without alternative, viable treatment options, cardiac monitoring is recommended.

Reduced therapeutic effect with drugs that are potent P-gp inducers in the intestine (eg rifampicin, St. John's wort, carbamazepine & phenytoin), modafinil, phenobarb/ oxcarbazepine, rifabutin/ rifapentine. P-gp &/or BCRP inhibitors. May result in serious symptomatic bradycardia when co-administered with amiodarone in combination with another direct acting antiviral.

Pregnancy Category B: Sofosbuvir There are no adequate and well-controlled studies with Sofosbuvir in pregnant women.

Nursing Mothers: It is not known whether Sofosbuvir and its metabolites are present in human breast milk.

Pediatric Use: Safety and effectiveness of Sofosbuvir in children less than 18 years of age have not been established.

Geriatric Use: Sofosbuvir was administered to 90 subjects aged 65 and over. The response rates observed for subjects over 65 years of age were similar to that of younger subjects across treatment groups. No dose adjustment of Sofosbuvir is warranted in geriatric patients.

The highest dose of Sofosbuvir is a single dose of Sofosbuvir 1200 mg. No specific antidote is available for overdose treatment. Treatment of overdose with Sofosbuvir consists of general supportive measures including monitoring of vital signs as well as observation of the clinical status of the patient.

Keep out of the reach of children. Keep in a cool & dry place. Protect from light.

Penicillinase-resistant penicillins

Flucloxacillin is active against Gram-positive organisms including penicillinase producing strains. It has little activity against Gram-negative bacilli. Flucloxacillin acts by inhibiting the formation of cell wall of bacteria. Flucloxacillin is isoxazolyl penicillin which combined the properties of resistance to hydrolysis by penicillinase, gastric acid stability and activity against gram-positive bacteria. Flucloxacillin is a bactericidal antibiotic that is particularly useful against penicillinase-producing staphylococci. Flucloxacillin kills bacterial cellwall, thus interfering with peptidoglycan synthesis. Peptidoglycan is a heteropolymeric structure that provides the cell wall with its mechanical stability. The final stage of peptidoglycan synthesis involves the completion of the cross-linking with the terminal glycine residue of the pentaglycin bridge linking to the fourth residue of the pentapeptide (D-alanine). The transpeptidase enzyme that performs this step is inhibited by Flucloxacillin. As a result the bacterial cellwall is weakened, the cell swells and then ruptures. Flucloxacillin resists the action of bacterial penicillinase probably because of the steric hindrance induced by the acyl side chain which prevents the opening of the β- lactam ring.

Oral administration:

• Adult: 250 mg four times daily. Dosage may be doubled in severe infections. In osteomyelitis and endocarditis, up to 8 gm daily is used in 6-8 hourly divided doses.
• Children (2-10 years): 1/2 of adult dose.
• Children (Under 2 years): 1/4 of adult dose.

Parenteral administration:
Adult or Elderly:

• Intramuscular Injection: 250 mg four times daily.
• Intravenous Injection: 250 mg-1 g four times daily by slow injection over 3 to 4 minutes or by intravenous infusion.
• All systemic doses may be doubled in severe infections: doses up to 8 g daily have been suggested for endocarditis or osteomyelitis.

Children:

• 2-10 years: half of the adult dose.
• Under 2 years: a quarter of the adult dose.

Oral doses should be administered 1 hour before meal.

There have been some common side effects of gastrointestinal tract such as nausea, vomiting, diarrhoea, dyspepsia and other minor gastrointestinal disturbances. Besides these rashes, urticaria, purpura, fever, interstitial nephritis, hepatitis and cholestatic jaundice have been reported.

Flucloxacillin is contraindicated in penicillin hypersensitive patients.

Flucloxacillin should be used with caution in patients with evidence of hepatic dysfunction. Caution should also be exercised in the treatment of patients with an allergic diathesis.

Concurrent use of Flucloxacillin and may result in increased level of Flucloxacillin in blood for prolonged period.

US FDA Pregnancy Category of Flucloxacillin is B. There are, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Flucloxacillin have been shown to be excreted in human milk. So, caution should be exercised when Flucloxacillin is administered to a lactating mother.

In severe renal failure (creatinine clearance <10 ml/min), a reduction in dose or an extension of dose interval should be considered.

Flucloxacillin has been used in other routes in conjunction with systemic therapy. It has been administered in a dose of 250 mg to 500 mg daily by intraarticular injection, dissolved if necessary in a 0.5% solution of lignocaine hydrochloride, and by intrapleural injection in a dose of 250 mg daily. Using powder for injection, 125 mg-250 mg has been dissolved in 3 ml of sterile water and inhaled by nebuliser four times daily.

Keep in a dry place away from light and heat. Keep out of the reach of children.

Penicillinase-resistant penicillins

Flucloxacillin is active against Gram-positive organisms including penicillinase producing strains. It has little activity against Gram-negative bacilli. Flucloxacillin acts by inhibiting the formation of cell wall of bacteria. Flucloxacillin is isoxazolyl penicillin which combined the properties of resistance to hydrolysis by penicillinase, gastric acid stability and activity against gram-positive bacteria. Flucloxacillin is a bactericidal antibiotic that is particularly useful against penicillinase-producing staphylococci. Flucloxacillin kills bacterial cellwall, thus interfering with peptidoglycan synthesis. Peptidoglycan is a heteropolymeric structure that provides the cell wall with its mechanical stability. The final stage of peptidoglycan synthesis involves the completion of the cross-linking with the terminal glycine residue of the pentaglycin bridge linking to the fourth residue of the pentapeptide (D-alanine). The transpeptidase enzyme that performs this step is inhibited by Flucloxacillin. As a result the bacterial cellwall is weakened, the cell swells and then ruptures. Flucloxacillin resists the action of bacterial penicillinase probably because of the steric hindrance induced by the acyl side chain which prevents the opening of the β- lactam ring.

Oral administration:

• Adult: 250 mg four times daily. Dosage may be doubled in severe infections. In osteomyelitis and endocarditis, up to 8 gm daily is used in 6-8 hourly divided doses.
• Children (2-10 years): 1/2 of adult dose.
• Children (Under 2 years): 1/4 of adult dose.

Parenteral administration:
Adult or Elderly:

• Intramuscular Injection: 250 mg four times daily.
• Intravenous Injection: 250 mg-1 g four times daily by slow injection over 3 to 4 minutes or by intravenous infusion.
• All systemic doses may be doubled in severe infections: doses up to 8 g daily have been suggested for endocarditis or osteomyelitis.

Children:

• 2-10 years: half of the adult dose.
• Under 2 years: a quarter of the adult dose.

Oral doses should be administered 1 hour before meal.

There have been some common side effects of gastrointestinal tract such as nausea, vomiting, diarrhoea, dyspepsia and other minor gastrointestinal disturbances. Besides these rashes, urticaria, purpura, fever, interstitial nephritis, hepatitis and cholestatic jaundice have been reported.

Flucloxacillin is contraindicated in penicillin hypersensitive patients.

Flucloxacillin should be used with caution in patients with evidence of hepatic dysfunction. Caution should also be exercised in the treatment of patients with an allergic diathesis.

Concurrent use of Flucloxacillin and may result in increased level of Flucloxacillin in blood for prolonged period.

US FDA Pregnancy Category of Flucloxacillin is B. There are, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Flucloxacillin have been shown to be excreted in human milk. So, caution should be exercised when Flucloxacillin is administered to a lactating mother.

In severe renal failure (creatinine clearance <10 ml/min), a reduction in dose or an extension of dose interval should be considered.

Flucloxacillin has been used in other routes in conjunction with systemic therapy. It has been administered in a dose of 250 mg to 500 mg daily by intraarticular injection, dissolved if necessary in a 0.5% solution of lignocaine hydrochloride, and by intrapleural injection in a dose of 250 mg daily. Using powder for injection, 125 mg-250 mg has been dissolved in 3 ml of sterile water and inhaled by nebuliser four times daily.

Keep in a dry place away from light and heat. Keep out of the reach of children.

For relief of the symptoms of nappy rash and as a protective water resistant cream for dry, chapped skin.

Emollients & combined preparations

Zinc oxide has a mild antiseptic action, and is useful for relieving the symptoms of nappy rash and other minor skin irritations. The formulation as a whole acts to provide a mildly antiseptic water resistant emollient barrier for dry skin conditions and nappy rash.

Applied directly to the skin. As required, up to four times daily or at each nappy change. The product is suitable for use by adults, children and the elderly.

Known hypersensitivity to any of the ingredients listed.

For external use only. Keep all medicines out of sight and reach of children. Instruct patients not to smoke or go near naked flames– risk of severe burns. Fabric (clothing, bedding, dressings, etc.) that has been in contact with this product burns more easily and is a serious fire hazard. Washing clothing and bedding may reduce product build-up but not totally remove it.

Zinc and Castor Oil Ointment BP contains Arachis Oil (peanut oil) and should not be applied by patients known to be allergic to peanut. As there is a possible relationship between allergy to peanut and allergy to Soya, patients with soya allergy should also avoid Zinc and Castor Oil Ointment. or

Zinc and Castor Oil Cream contains Arachis Oil (peanut oil) and should not be applied by patients known to be allergic to peanut. As there is a possible relationship between allergy to peanut and allergy to Soya, patients with soya allergy should also avoid Zinc and Castor Oil Cream.

May mask x-ray pictures under certain circumstances.

No information is available on the safety of the product when used during pregnancy and lactation.

Overdosage is unlikely. If accidentally ingested treatment should be symptomatic. Oral ingestion of large quantities of castor oil may cause nausea, vomiting, colic and diarrhoea.

Store below 25°C.

General (Inhalation) anesthetics

Sevoflurane is a volatile halogenated general anaesthetic that has a minimum alveolar concentration (MAC) value ranging from 1.4% to 3.3%. It alters the activity of fast synaptic neurotransmitter receptors like nicotinic acetylcholine, GABA, and glutamate. It may depress myocardial contractility and decrease both BP and sympathetic nervous activity. Additionally, it has muscle relaxant properties w/o analgesia.

he concentration of sevoflurane being delivered from a vaporizer during anesthesia should be known. This may be accomplished by using a vaporizer calibrated specifically for sevoflurane. The administration of general anesthesia must be individualized based on the patient's response.

Replacement Of Desiccated CO₂ Absorbents: When a clinician suspects that the CO₂ absorbent may be desiccated, it should be replaced. The exothermic reaction that occurs with sevoflurane and CO₂ absorbents is increased when the CO₂ absorbent becomes desiccated, such as after an extended period of dry gas flow through the CO₂ absorbent canisters

Pre-anesthetic Medication: No specific premedication is either indicated or contraindicated with sevoflurane. The decision as to whether or not to premedicate and the choice of premedication is left to the discretion of the anesthesiologist

Induction: Sevoflurane has a nonpungent odor and does not cause respiratory irritability; it is suitable for mask induction in pediatrics and adults

Maintenance: Surgical levels of anesthesia can usually be achieved with concentrations of 0.5-3% sevoflurane with or without the concomitant use of nitrous oxide. Sevoflurane can be administered with any type of anesthesia circuit

Cardiorespiratory depression, hypotension, bradycardia; laryngospasm, increased cough and salivation; urinary retention, acute renal failure, changes in liver enzyme values, liver damage; nausea, vomiting, delirium, seizure; rash, urticaria, pruritus, dyspnoea, wheezing, chest discomfort, bronchospasm, anaphylactic/anaphylactoid reaction; agitation, dystonic movements (childn).

Sevoflurane can cause malignant hyperthermia. It should not be used in patients with known sensitivity to sevoflurane or to other halogenated agents nor in patients with known or suspected susceptibility to malignant hyperthermia.

Patient with increased intracranial pressure, neuromuscular disease (esp Duchenne muscular dystrophy), mitochondrial disorders. Patient who are hypovolaemic, hypotensive, haemodynamically compromised, at risk of QT prolongation. Hepatic and renal impairment. Childn. Pregnancy and lactation.

Increased metabolism and toxicity with drugs that induce CYP2E1 isoenzyme (e.g. isoniazid). Reduced MAC with benzodiazepines, opioids. May cause ventricular arrhythmia with β-sympathomimetic agents (e.g. isoprenaline), and α- and β-sympathomimetic agents (e.g. adrenaline, noradrenaline). May cause crisis during operation with nonselective MAO inhibitors. May lead to marked hypotension and risk of additive negative inotropic effect with Ca antagonists (esp dihydropyridines).

Pregnancy Category B. Reproduction studies have been performed in rats and rabbits at doses up to 1 MAC (minimum alveolar concentration) without CO2 absorbent and have revealed no evidence of impaired fertility or harm to the fetus due to sevoflurane at 0.3 MAC, the highest nontoxic dose. Developmental and reproductive toxicity studies of sevoflurane in animals in the presence of strong alkalies (i.e., degradation of sevoflurane and production of Compound A) have not been conducted. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, sevoflurane should be used during pregnancy only if clearly needed.

Labor And Delivery: Sevoflurane has been used as part of general anesthesia for elective cesarean section in 29 women. There were no untoward effects in mother or neonate (see Pharmacodynamics - Clinical Trials). The safety of sevoflurane in labor and delivery has not been demonstrated.

Nursing Mothers: The concentrations of sevoflurane in milk are probably of no clinical importance 24 hours after anesthesia. Because of rapid washout, sevoflurane concentrations in milk are predicted to be below those found with many other volatile anesthetics.

Geriatric Use: MAC decreases with increasing age. The average concentration of sevoflurane to achieve MAC in an 80 year old is approximately 50% of that required in a 20 year old.

Pediatric Use: Induction and maintenance of general anesthesia with sevoflurane have been established in controlled clinical trials in pediatric patients aged 1 to 18 years. Sevoflurane has a nonpungent odor and is suitable for mask induction in pediatric patients.

The concentration of sevoflurane required for maintenance of general anesthesia is age dependent. When used in combination with nitrous oxide, the MAC equivalent dose of sevoflurane should be reduced in pediatric patients. MAC in premature infants has not been determined.

The use of sevoflurane has been associated with seizures. The majority of these have occurred in children and young adults starting from 2 months of age, most of whom had no predisposing risk factors. Clinical judgement should be exercised when using sevoflurane in patients who may be at risk for seizures.

In the event of overdosage, or what may appear to be overdosage, the following action should be taken: discontinue administration of sevoflurane, maintain a patent airway, initiate assisted or controlled ventilation with oxygen, and maintain adequate cardiovascular function.

Store between 15-30° C. Protect from light.

Sunblock Preparation

This lotion is a non-greasy, water resistant, protective sun block, which helps prevent sunburn in all types of skin. It provides a high degree of protection against the harmful effects of ultraviolet components of sunlight which are responsible for skin cancer, wrinkling, premature ageing and darkening of the skin due to overexposure.

This provides a sun protection factor (SPF) of 6 against UVA rays and 28 against UVB rays. The SPF describes how much longer you can remain in the sun without being affected by these rays, compared with unprotected skin. This gives you 28 times more natural sunburn protection and maintains its degree of protection up to 60 minutes in water.

This lotion should be applied carefully and evenly on skin before sun exposure. Apply 45 minutes before swimming or sweat producing exercise. A single application may give day-long protection but the product should be re-applied during prolonged periods of sunning and after swimming or excessive sweating.

Signs of irritations (including erythema, burning or rash) may appear when applied to sensitive or broken skin.

Known hypersensitivity to any of its components.

Application to broken skin should be avoided. Contact with the eyes and other mucous membranes should be avoided.

There are no known drug interactions and none well documented.

This lotion should only be used if the anticipated benefits outweigh the risks.

Mebendazole is indicated for the treatment of threadworms, whipworms, roundworms and hookworms.

Anthelmintic

Mebendazole is a synthetic broad-spectrum anthelmintic that is active against most nematodes and some other worms. Mebendazole is principally used in the treatment of intestinal nematode infection. Mebendazole inhibits the formation of the worms' microtubules and causes the worms' glucose depletion. After oral administration about 2-10% of oral dose is absorbed from Gl tract and peak plasma concentration occurs within 30 minutes to 7 hours. Mebendazole is highly bound to plasma protein. Elimination half-life is 2.8 to 9 hours.

Adult and Child over 2 years-

• Threadworms: 100 mg or 1 teaspoonful: Single dose.
• Whipworms, Roundworms, Hookworms: 100 mg or 1 teaspoonful: Twice daily for 3 days.

If reinfection occurs the second dose may be needed after 2 weeks.

Mebendazole is contraindicated in patients with known hypersensitivity to Mebendazole, or to any component of the formulation.

General: Periodic assessment of organ system functions, including haematopoietic and hepatic, is advisable during prolonged therapy.

Information for Patients: Patients should be informed of the potential risk to the foetus in women taking mebendazole during pregnancy, especially during the first trimester. Patients should also be informed that cleanliness is important to prevent reinfection & transmission of the infection.

Preliminary evidence suggests that cimetidine inhibits mebendazole metabolism and may result in an increase in plasma concentration.

Mebendazole is not recommended in pregnant women. It is not known whether mebendazole is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when it is administered to a nursing mother.

Paediatric use: The drug has not been extensively studied in children under two years; therefore, in the treatment of children under two years the relative benefit/risk should be considered.

In the event of accidental overdosage, gastrointestinal complaints lasting up to a few hours may occur. Vomiting and purging should be induced.

Store in a cool (Below 25°C temperature) and dry place, protected from light. Keep out of the reach of children.

Mebendazole is indicated for the treatment of threadworms, whipworms, roundworms and hookworms.

Anthelmintic

Mebendazole is a synthetic broad-spectrum anthelmintic that is active against most nematodes and some other worms. Mebendazole is principally used in the treatment of intestinal nematode infection. Mebendazole inhibits the formation of the worms' microtubules and causes the worms' glucose depletion. After oral administration about 2-10% of oral dose is absorbed from Gl tract and peak plasma concentration occurs within 30 minutes to 7 hours. Mebendazole is highly bound to plasma protein. Elimination half-life is 2.8 to 9 hours.

Adult and Child over 2 years-

• Threadworms: 100 mg or 1 teaspoonful: Single dose.
• Whipworms, Roundworms, Hookworms: 100 mg or 1 teaspoonful: Twice daily for 3 days.

If reinfection occurs the second dose may be needed after 2 weeks.

Mebendazole is contraindicated in patients with known hypersensitivity to Mebendazole, or to any component of the formulation.

General: Periodic assessment of organ system functions, including haematopoietic and hepatic, is advisable during prolonged therapy.

Information for Patients: Patients should be informed of the potential risk to the foetus in women taking mebendazole during pregnancy, especially during the first trimester. Patients should also be informed that cleanliness is important to prevent reinfection & transmission of the infection.

Preliminary evidence suggests that cimetidine inhibits mebendazole metabolism and may result in an increase in plasma concentration.

Mebendazole is not recommended in pregnant women. It is not known whether mebendazole is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when it is administered to a nursing mother.

Paediatric use: The drug has not been extensively studied in children under two years; therefore, in the treatment of children under two years the relative benefit/risk should be considered.

In the event of accidental overdosage, gastrointestinal complaints lasting up to a few hours may occur. Vomiting and purging should be induced.

Store in a cool (Below 25°C temperature) and dry place, protected from light. Keep out of the reach of children.

Vitamin B1, B6 & B12 is indicated for the treatment of vitamin B1, B6 & B12 deficiency syndrome. It is also indicated for the supportive treatment of neuritis & non-inflammatory diseases of the nerves, e.g.- Diabetic neuropathy, Peripheral neuralgin, Lumbago, Myalgia, Optic neuritis, Sciatica, Facial neuralgia, Intercostal neuralgia, Spinal pain.

Specific combined vitamin preparations

Vitamin B1 converts carbohydrates, fatty acids and amino acids into energy, promotes healthy nerves, improves mood, strengthens the heart. Vitamin B6 forms RBCs, helps cells to make proteins, manufactures neurotransmitters e.g. serotonin and releases stored forms of energy, helps to prevent CVS diseases and stroke, helps to lift depression and eases insomnia. Vitamin B12 is essential for cell replication and important for RBC production, prevents anemia, helps to prevent depression, reduces nerve pain, numbness, tingling and lowers the risk of heart diseases.

The vitamin ingredients are absorbed well in per oral reception. It is widely distributed to most tissues and appears in breast milk. Within the cell, thiamine is mostly present as diphosphate. Thiamine is not stored to any appreciable extent in the body and amounts in excess of the body’s requirements are excreted in the urine as unchanged thiamine or as metabolites. Pyridoxine, pyridoxal and pyridoxamine are readily absorbed from the GIT following oral administration and are converted to the active forms of pyridoxal phosphate an pyridoxamine phosphate. They are stored mainly in liver where there is oxidation to 4-pyridoxic acid and other inactive metabolites, which are excreted in urine. As the dose increases, proportionally greater amounts are excreted unchanged in the urine.

Tablet: 1-3 Tablets per day or as advised by the physician.

Injection:

• In severe (acute) cases: 1 injection daily until the acute symptoms subside or taken as advised by the physician.
• In mild cases: 1 injection 2-3 times per week. Ampoules are preferably injected intramuscularly.

Use in children: There is no information on the use of this drug in children.

Generally well tolerated but allergic reactions may be observed in few cases.

Vitamin B1, Vitamin B6 and Vitamin B12 is contraindicated in patients on levodopa therapy, and in patients with hypersensitivity to any of the ingredients of the preparation.

Cyanocobalamin should not be given in patients with subacute degeneration of the spinal cord. Cyanocobalamin is not suitable form of vitamin B12 for the treatment of optic neuropathies associated with raised plasma concentrations of cyanocobalamin.

No drug interaction has been reported yet.

Oral tablet form is recommended but due to the presence of benzyl alcohol, injection is not recommended during pregnancy & lactation.

No overdosage symptoms are to be expected in the recommended dosage. If there is known overdose then treatment is symptomatic & supportive.

Keep out of reach of children. Store in a cool (below 25°C temperature) and dry place, protected from light.

Vitamin B1, B6 & B12 is indicated for the treatment of vitamin B1, B6 & B12 deficiency syndrome. It is also indicated for the supportive treatment of neuritis & non-inflammatory diseases of the nerves, e.g.- Diabetic neuropathy, Peripheral neuralgin, Lumbago, Myalgia, Optic neuritis, Sciatica, Facial neuralgia, Intercostal neuralgia, Spinal pain.

Specific combined vitamin preparations

Vitamin B1 converts carbohydrates, fatty acids and amino acids into energy, promotes healthy nerves, improves mood, strengthens the heart. Vitamin B6 forms RBCs, helps cells to make proteins, manufactures neurotransmitters e.g. serotonin and releases stored forms of energy, helps to prevent CVS diseases and stroke, helps to lift depression and eases insomnia. Vitamin B12 is essential for cell replication and important for RBC production, prevents anemia, helps to prevent depression, reduces nerve pain, numbness, tingling and lowers the risk of heart diseases.

The vitamin ingredients are absorbed well in per oral reception. It is widely distributed to most tissues and appears in breast milk. Within the cell, thiamine is mostly present as diphosphate. Thiamine is not stored to any appreciable extent in the body and amounts in excess of the body’s requirements are excreted in the urine as unchanged thiamine or as metabolites. Pyridoxine, pyridoxal and pyridoxamine are readily absorbed from the GIT following oral administration and are converted to the active forms of pyridoxal phosphate an pyridoxamine phosphate. They are stored mainly in liver where there is oxidation to 4-pyridoxic acid and other inactive metabolites, which are excreted in urine. As the dose increases, proportionally greater amounts are excreted unchanged in the urine.

Tablet: 1-3 Tablets per day or as advised by the physician.

Injection:

• In severe (acute) cases: 1 injection daily until the acute symptoms subside or taken as advised by the physician.
• In mild cases: 1 injection 2-3 times per week. Ampoules are preferably injected intramuscularly.

Use in children: There is no information on the use of this drug in children.

Generally well tolerated but allergic reactions may be observed in few cases.

Vitamin B1, Vitamin B6 and Vitamin B12 is contraindicated in patients on levodopa therapy, and in patients with hypersensitivity to any of the ingredients of the preparation.

Cyanocobalamin should not be given in patients with subacute degeneration of the spinal cord. Cyanocobalamin is not suitable form of vitamin B12 for the treatment of optic neuropathies associated with raised plasma concentrations of cyanocobalamin.

No drug interaction has been reported yet.

Oral tablet form is recommended but due to the presence of benzyl alcohol, injection is not recommended during pregnancy & lactation.

No overdosage symptoms are to be expected in the recommended dosage. If there is known overdose then treatment is symptomatic & supportive.

Keep out of reach of children. Store in a cool (below 25°C temperature) and dry place, protected from light.

Symptomatic treatment of urge incontinence and/or increased urinary frequency and urgency as may occur in patients with overactive bladder syndrome.

Anticholinergics (antimuscarinics)/ Anti-spasmodics, BPH/ Urinary retention/ Urinary incontinence

Solifenacin is a competitive muscarinic receptor antagonist. It has the highest affinity for M3, M1, and M2 muscarinic receptors. 80% of the muscarinic receptors in the bladder are M2, while 20% are M3. Solifenacin's antagonism of the M3 receptor prevents contraction of the detrusor muscle, while antagonism of the M2 receptor may prevent contraction of smooth muscle in the bladder.

The recommended dose for adults and the elderly: Solifenacin Succinate 5 mg once daily. If needed, the dose may be increased to Solifenacin Succinate 10 mg once daily.

Use in children: Safety and effectiveness in children have not yet been established. Therefore, Solifenacin Succinate should not be used in children.

Due to the pharmacological effect of Solifenacin, it may cause anticholinergic undesirable effects of (in general) mild or moderate severity. The frequency of anticholinergic undesirable effects is dose related. The most commonly reported adverse reactionwith Solifenacin is dry mouth. It occurred in 11% of patients treated with 5 mg once daily, in 22% of patients treated with 10 mg once daily and in 4% of placebo-treated patients. The severity of dry mouth was generally mild and only occasionally led to discontinuation of treatment. In general,medicinal product compliance was very high (approximately 99%) and approximately 90% of the patients treated with Solifenacin completed the full study period of 12 weeks treatment.

• Gastrointestinal disorders: very common- dry mouth, common-constipation, nausea, dyspepsia, abdominal pain, uncommon- gastroesophageal reflux diseases, dry throat, rare- colonic obstruction, faecal impaction, very rare- vomiting.
• Infections and infestations: uncommonurinary tract infection, cystitis.
• nervous system disorders: uncommon- somnolence, dysgeusia, very rare-dizziness, headache.
• psychiatric disorders: very rare- hallucinations.
• eye disorders: common- blurred vision, uncommon- dry eyes.
• General disorders and administration site conditions: uncommon- fatigue, peripheral oedema.
• Respiratory, thoracic and mediastinal disorders: uncommon nasal dryness.
• skin and subcutaneous tissue disorders: uncommon- dry skin, very rare- pruritus, rash, urticaria.
• renal and urinary disorders: uncommon- difficulty in micturition, rare- urinary retention.

Solifenacin is contraindicated in patients with hypersensitivity to solifenacin or to any of the excipients. It is also contraindicated in myasthenia gravis, urinary retention, uncontrolled narrow angle glaucoma, severe gastro-intestinal condition (including toxic megacolon), patients undergoing haemodialysis, patients with severe hepatic impairment, patients with severe renal impairment or moderate hepatic impairment and on treatment with a strong CYP3A4 inhibitor, e.g. ketoconazole.

Other causes of frequent urination (heart failure or renal disease) should be assessed before treatment with Solifenacin Succinate. If urinary tract infection is present, an appropriate antibacterial therapy should be started. Solifenacin Succinate should be used with caution in patients with: clinically significant bladder outflow obstruction at risk of urinary retention, gastrointestinal obstructive disorders, risk of decreased gastrointestinal motility, severe renal impairment (creatinine clearance 30 ml/min), moderate hepatic impairment (Child-Pugh score of 7 to 9) and doses should not exceed 5 mg for these patients. Caution should be taken in concomitant use of a potent CYP3A4 inhibitor e.g. Ketoconazole, hiatus hernia/ gastroesophageal reflux and/or who are concurrently taking medicinal products (such as Bisphosphonates) that can cause or exacerbate oesophagitis, autonomic neuropathy. Safety and efficacy have not yet been established in patients with a neurogenic cause for detrusor overactivity. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. The maximum effect of Solifenacin Succinate can be determined after 4 weeks at the earliest.

Concomitant medication with other medicinal products with anticholinergic properties may result in more pronounced therapeutic effects and undesirable effects. An interval of approximately one week should be allowed after stopping treatment with Solifenacin Succinate before commencing other anticholinergic therapy. The therapeutic effect of Solifenacin may be reduced by concomitant administration of cholinergic receptor agonists. Solifenacin can reduce the effect of medicinal products that stimulate the motility of the gastrointestinal tract, such as Metoclopramide and Cisapride. In vitro studies have demonstrated that at therapeutic concentrations, Solifenacin does not inhibit CYP1A1/2, 2C9, 2C19, 2D6, or 3A4 derived from human liver microsomes. Therefore, Solifenacin is unlikely to alter the clearance of drugs metabolized by these CYP enzymes. Solifenacin is metabolized by CYP3A4. Simultaneous administration of Ketoconazole (200 mg/day), a potent CYP3A4 inhibitor, resulted in a two-fold increase of the AUC of Solifenacin, while Ketoconazole at a dose of 400 mg/day resulted in a three-fold increase of the AUC of Solifenacin. Therefore, the maximum dose of Solifenacin Succinate should be restricted to 5 mg when used simultaneously with Ketoconazole or therapeutic doses of other potent CYP3A4 inhibitors (e.g. Ritonavir, Nelfinavir, Itraconazole).

Simultaneous treatment of Solifenacin and a potent CYP3A4 inhibitor is contra-indicated in patients with severe renal impairment or moderate hepatic impairment. The effects of enzyme induction on the pharmacokinetics of Solifenacin and its metabolites have not been studied as well as the effect of higher affinity CYP3A4 substrates on Solifenacin exposure. Since Solifenacin is metabolised by CYP3A4, pharmacokinetic interactions are possible with other CYP3A4 substrates with higher affinity (e.g. Verapamil, Diltiazem) and CYP3A4 inducers (e.g. Rifampicin, Phenytoin, Carbamazepine).

Effect of Solifenacin on the pharmacokinetics of other medicinal products:

• Oral Contraceptives: Intake of Solifenacin showed no pharmacokinetic interaction on combined oral contraceptives (Ethinylestradiol/Levonorgestrel).
• Warfarin: Intake of Solifenacin did not alter the pharmacokinetics of R-warfarin or S-warfarin or their effect on prothrombin time.
• Digoxin: Intake of Solifenacin showed no effect on the pharmacokinetics of digoxin.
• Effects on ability to drive and use machines: Since Solifenacin, like other anticholinergics may cause blurred vision and, uncommonly, somnolence and fatigue, the ability to drive and use machines may be negatively affected.

No clinical data are available from women who became pregnant while taking Solifenacin. Animal studies do not indicate direct harmful effects on fertility, embryonal / foetal development or parturition. The potential risk for humans is unknown. Caution should be exercised when prescribing to pregnant women. No data on the excretion of Solifenacin in human milk are available. In mice, Solifenacin and/or its metabolites was excreted in milk, and caused a dose dependent failure to thrive in neonatal mice. The use of Solifenacin should therefore be avoided during breast-feeding.

Patients with renal impairment: No dose adjustment is necessary for patients with mild to moderate renal impairment (creatinine clearance >30 ml/min). Patients with severe renal impairment (creatinine clearance <30 ml/min) should be treated with caution and receive no more than 5 mg once daily.

Patients with hepatic impairment: No dose adjustment is necessary for patients with mild hepatic impairment. Patients with moderate hepatic impairment (Child-Pugh score of 7 to 9) should be treated with caution and receive no more than 5 mg once daily.

Potent inhibitors of cytochrome P450 3A4: The maximum dose of Solifenacin Succinate should be limited to 5 mg when treated simultaneously with Ketoconazole or therapeutic doses of other potent CYP3A4 inhibitors e.g. Ritonavir, Nelfinavir, Itraconazole. Solifenacin Succinate tablet should be taken orally and should be swallowed whole with liquids. It can be taken with or without food.

Over dosage with Solifenacin Succinate can potentially result in severe anticholinergic effects. The highest dose of Solifenacin Succinate accidentally given to a single patient was 280 mg in a 5 hour period, resulting in mental status changes not requiring hospitalization. In the event of overdose with Solifenacin Succinate, the patient should be treated with activated charcoal. Gastric lavage is useful if performed within 1 hour, but vomiting should not be induced. As for other anticholinergics, symptoms can be treated as follows:

• Severe central anticholinergic effects such as hallucinations or pronounced excitation: treat with physostigmine or carbachol.
• Convulsions or pronounced excitation: treat with benzodiazepines.
• Respiratory insufficiency: treat with artificial respiration.
• Tachycardia: treat with beta-blockers.
• Urinary retention: treat with catheterisation.
• Mydriasis: treat with pilocarpine eye drops and/or place patient in a dark room.

As with other antimuscarinics, in case of overdosing, specific attention should be paid to patients with known risk for QT-prolongation (i.e. hypokalaemia, bradycardia and concurrent administration of medicinal products known to prolong QT interval) and relevant pre-existing cardiac diseases (i.e. myocardial ischaemia, arrhythmia, congestive heart failure).

Store in a cool and dry place, protected from light.

Symptomatic treatment of urge incontinence and/or increased urinary frequency and urgency as may occur in patients with overactive bladder syndrome.

Anticholinergics (antimuscarinics)/ Anti-spasmodics, BPH/ Urinary retention/ Urinary incontinence

Solifenacin is a competitive muscarinic receptor antagonist. It has the highest affinity for M3, M1, and M2 muscarinic receptors. 80% of the muscarinic receptors in the bladder are M2, while 20% are M3. Solifenacin's antagonism of the M3 receptor prevents contraction of the detrusor muscle, while antagonism of the M2 receptor may prevent contraction of smooth muscle in the bladder.

The recommended dose for adults and the elderly: Solifenacin Succinate 5 mg once daily. If needed, the dose may be increased to Solifenacin Succinate 10 mg once daily.

Use in children: Safety and effectiveness in children have not yet been established. Therefore, Solifenacin Succinate should not be used in children.

Due to the pharmacological effect of Solifenacin, it may cause anticholinergic undesirable effects of (in general) mild or moderate severity. The frequency of anticholinergic undesirable effects is dose related. The most commonly reported adverse reactionwith Solifenacin is dry mouth. It occurred in 11% of patients treated with 5 mg once daily, in 22% of patients treated with 10 mg once daily and in 4% of placebo-treated patients. The severity of dry mouth was generally mild and only occasionally led to discontinuation of treatment. In general,medicinal product compliance was very high (approximately 99%) and approximately 90% of the patients treated with Solifenacin completed the full study period of 12 weeks treatment.

• Gastrointestinal disorders: very common- dry mouth, common-constipation, nausea, dyspepsia, abdominal pain, uncommon- gastroesophageal reflux diseases, dry throat, rare- colonic obstruction, faecal impaction, very rare- vomiting.
• Infections and infestations: uncommonurinary tract infection, cystitis.
• nervous system disorders: uncommon- somnolence, dysgeusia, very rare-dizziness, headache.
• psychiatric disorders: very rare- hallucinations.
• eye disorders: common- blurred vision, uncommon- dry eyes.
• General disorders and administration site conditions: uncommon- fatigue, peripheral oedema.
• Respiratory, thoracic and mediastinal disorders: uncommon nasal dryness.
• skin and subcutaneous tissue disorders: uncommon- dry skin, very rare- pruritus, rash, urticaria.
• renal and urinary disorders: uncommon- difficulty in micturition, rare- urinary retention.

Solifenacin is contraindicated in patients with hypersensitivity to solifenacin or to any of the excipients. It is also contraindicated in myasthenia gravis, urinary retention, uncontrolled narrow angle glaucoma, severe gastro-intestinal condition (including toxic megacolon), patients undergoing haemodialysis, patients with severe hepatic impairment, patients with severe renal impairment or moderate hepatic impairment and on treatment with a strong CYP3A4 inhibitor, e.g. ketoconazole.

Other causes of frequent urination (heart failure or renal disease) should be assessed before treatment with Solifenacin Succinate. If urinary tract infection is present, an appropriate antibacterial therapy should be started. Solifenacin Succinate should be used with caution in patients with: clinically significant bladder outflow obstruction at risk of urinary retention, gastrointestinal obstructive disorders, risk of decreased gastrointestinal motility, severe renal impairment (creatinine clearance 30 ml/min), moderate hepatic impairment (Child-Pugh score of 7 to 9) and doses should not exceed 5 mg for these patients. Caution should be taken in concomitant use of a potent CYP3A4 inhibitor e.g. Ketoconazole, hiatus hernia/ gastroesophageal reflux and/or who are concurrently taking medicinal products (such as Bisphosphonates) that can cause or exacerbate oesophagitis, autonomic neuropathy. Safety and efficacy have not yet been established in patients with a neurogenic cause for detrusor overactivity. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. The maximum effect of Solifenacin Succinate can be determined after 4 weeks at the earliest.

Concomitant medication with other medicinal products with anticholinergic properties may result in more pronounced therapeutic effects and undesirable effects. An interval of approximately one week should be allowed after stopping treatment with Solifenacin Succinate before commencing other anticholinergic therapy. The therapeutic effect of Solifenacin may be reduced by concomitant administration of cholinergic receptor agonists. Solifenacin can reduce the effect of medicinal products that stimulate the motility of the gastrointestinal tract, such as Metoclopramide and Cisapride. In vitro studies have demonstrated that at therapeutic concentrations, Solifenacin does not inhibit CYP1A1/2, 2C9, 2C19, 2D6, or 3A4 derived from human liver microsomes. Therefore, Solifenacin is unlikely to alter the clearance of drugs metabolized by these CYP enzymes. Solifenacin is metabolized by CYP3A4. Simultaneous administration of Ketoconazole (200 mg/day), a potent CYP3A4 inhibitor, resulted in a two-fold increase of the AUC of Solifenacin, while Ketoconazole at a dose of 400 mg/day resulted in a three-fold increase of the AUC of Solifenacin. Therefore, the maximum dose of Solifenacin Succinate should be restricted to 5 mg when used simultaneously with Ketoconazole or therapeutic doses of other potent CYP3A4 inhibitors (e.g. Ritonavir, Nelfinavir, Itraconazole).

Simultaneous treatment of Solifenacin and a potent CYP3A4 inhibitor is contra-indicated in patients with severe renal impairment or moderate hepatic impairment. The effects of enzyme induction on the pharmacokinetics of Solifenacin and its metabolites have not been studied as well as the effect of higher affinity CYP3A4 substrates on Solifenacin exposure. Since Solifenacin is metabolised by CYP3A4, pharmacokinetic interactions are possible with other CYP3A4 substrates with higher affinity (e.g. Verapamil, Diltiazem) and CYP3A4 inducers (e.g. Rifampicin, Phenytoin, Carbamazepine).

Effect of Solifenacin on the pharmacokinetics of other medicinal products:

• Oral Contraceptives: Intake of Solifenacin showed no pharmacokinetic interaction on combined oral contraceptives (Ethinylestradiol/Levonorgestrel).
• Warfarin: Intake of Solifenacin did not alter the pharmacokinetics of R-warfarin or S-warfarin or their effect on prothrombin time.
• Digoxin: Intake of Solifenacin showed no effect on the pharmacokinetics of digoxin.
• Effects on ability to drive and use machines: Since Solifenacin, like other anticholinergics may cause blurred vision and, uncommonly, somnolence and fatigue, the ability to drive and use machines may be negatively affected.

No clinical data are available from women who became pregnant while taking Solifenacin. Animal studies do not indicate direct harmful effects on fertility, embryonal / foetal development or parturition. The potential risk for humans is unknown. Caution should be exercised when prescribing to pregnant women. No data on the excretion of Solifenacin in human milk are available. In mice, Solifenacin and/or its metabolites was excreted in milk, and caused a dose dependent failure to thrive in neonatal mice. The use of Solifenacin should therefore be avoided during breast-feeding.

Patients with renal impairment: No dose adjustment is necessary for patients with mild to moderate renal impairment (creatinine clearance >30 ml/min). Patients with severe renal impairment (creatinine clearance <30 ml/min) should be treated with caution and receive no more than 5 mg once daily.

Patients with hepatic impairment: No dose adjustment is necessary for patients with mild hepatic impairment. Patients with moderate hepatic impairment (Child-Pugh score of 7 to 9) should be treated with caution and receive no more than 5 mg once daily.

Potent inhibitors of cytochrome P450 3A4: The maximum dose of Solifenacin Succinate should be limited to 5 mg when treated simultaneously with Ketoconazole or therapeutic doses of other potent CYP3A4 inhibitors e.g. Ritonavir, Nelfinavir, Itraconazole. Solifenacin Succinate tablet should be taken orally and should be swallowed whole with liquids. It can be taken with or without food.

Over dosage with Solifenacin Succinate can potentially result in severe anticholinergic effects. The highest dose of Solifenacin Succinate accidentally given to a single patient was 280 mg in a 5 hour period, resulting in mental status changes not requiring hospitalization. In the event of overdose with Solifenacin Succinate, the patient should be treated with activated charcoal. Gastric lavage is useful if performed within 1 hour, but vomiting should not be induced. As for other anticholinergics, symptoms can be treated as follows:

• Severe central anticholinergic effects such as hallucinations or pronounced excitation: treat with physostigmine or carbachol.
• Convulsions or pronounced excitation: treat with benzodiazepines.
• Respiratory insufficiency: treat with artificial respiration.
• Tachycardia: treat with beta-blockers.
• Urinary retention: treat with catheterisation.
• Mydriasis: treat with pilocarpine eye drops and/or place patient in a dark room.

As with other antimuscarinics, in case of overdosing, specific attention should be paid to patients with known risk for QT-prolongation (i.e. hypokalaemia, bradycardia and concurrent administration of medicinal products known to prolong QT interval) and relevant pre-existing cardiac diseases (i.e. myocardial ischaemia, arrhythmia, congestive heart failure).

Store in a cool and dry place, protected from light.

Symptomatic treatment of urge incontinence and/or increased urinary frequency and urgency as may occur in patients with overactive bladder syndrome.

Anticholinergics (antimuscarinics)/ Anti-spasmodics, BPH/ Urinary retention/ Urinary incontinence

Solifenacin is a competitive muscarinic receptor antagonist. It has the highest affinity for M3, M1, and M2 muscarinic receptors. 80% of the muscarinic receptors in the bladder are M2, while 20% are M3. Solifenacin's antagonism of the M3 receptor prevents contraction of the detrusor muscle, while antagonism of the M2 receptor may prevent contraction of smooth muscle in the bladder.

The recommended dose for adults and the elderly: Solifenacin Succinate 5 mg once daily. If needed, the dose may be increased to Solifenacin Succinate 10 mg once daily.

Use in children: Safety and effectiveness in children have not yet been established. Therefore, Solifenacin Succinate should not be used in children.

Due to the pharmacological effect of Solifenacin, it may cause anticholinergic undesirable effects of (in general) mild or moderate severity. The frequency of anticholinergic undesirable effects is dose related. The most commonly reported adverse reactionwith Solifenacin is dry mouth. It occurred in 11% of patients treated with 5 mg once daily, in 22% of patients treated with 10 mg once daily and in 4% of placebo-treated patients. The severity of dry mouth was generally mild and only occasionally led to discontinuation of treatment. In general,medicinal product compliance was very high (approximately 99%) and approximately 90% of the patients treated with Solifenacin completed the full study period of 12 weeks treatment.

• Gastrointestinal disorders: very common- dry mouth, common-constipation, nausea, dyspepsia, abdominal pain, uncommon- gastroesophageal reflux diseases, dry throat, rare- colonic obstruction, faecal impaction, very rare- vomiting.
• Infections and infestations: uncommonurinary tract infection, cystitis.
• nervous system disorders: uncommon- somnolence, dysgeusia, very rare-dizziness, headache.
• psychiatric disorders: very rare- hallucinations.
• eye disorders: common- blurred vision, uncommon- dry eyes.
• General disorders and administration site conditions: uncommon- fatigue, peripheral oedema.
• Respiratory, thoracic and mediastinal disorders: uncommon nasal dryness.
• skin and subcutaneous tissue disorders: uncommon- dry skin, very rare- pruritus, rash, urticaria.
• renal and urinary disorders: uncommon- difficulty in micturition, rare- urinary retention.

Solifenacin is contraindicated in patients with hypersensitivity to solifenacin or to any of the excipients. It is also contraindicated in myasthenia gravis, urinary retention, uncontrolled narrow angle glaucoma, severe gastro-intestinal condition (including toxic megacolon), patients undergoing haemodialysis, patients with severe hepatic impairment, patients with severe renal impairment or moderate hepatic impairment and on treatment with a strong CYP3A4 inhibitor, e.g. ketoconazole.

Other causes of frequent urination (heart failure or renal disease) should be assessed before treatment with Solifenacin Succinate. If urinary tract infection is present, an appropriate antibacterial therapy should be started. Solifenacin Succinate should be used with caution in patients with: clinically significant bladder outflow obstruction at risk of urinary retention, gastrointestinal obstructive disorders, risk of decreased gastrointestinal motility, severe renal impairment (creatinine clearance 30 ml/min), moderate hepatic impairment (Child-Pugh score of 7 to 9) and doses should not exceed 5 mg for these patients. Caution should be taken in concomitant use of a potent CYP3A4 inhibitor e.g. Ketoconazole, hiatus hernia/ gastroesophageal reflux and/or who are concurrently taking medicinal products (such as Bisphosphonates) that can cause or exacerbate oesophagitis, autonomic neuropathy. Safety and efficacy have not yet been established in patients with a neurogenic cause for detrusor overactivity. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. The maximum effect of Solifenacin Succinate can be determined after 4 weeks at the earliest.

Concomitant medication with other medicinal products with anticholinergic properties may result in more pronounced therapeutic effects and undesirable effects. An interval of approximately one week should be allowed after stopping treatment with Solifenacin Succinate before commencing other anticholinergic therapy. The therapeutic effect of Solifenacin may be reduced by concomitant administration of cholinergic receptor agonists. Solifenacin can reduce the effect of medicinal products that stimulate the motility of the gastrointestinal tract, such as Metoclopramide and Cisapride. In vitro studies have demonstrated that at therapeutic concentrations, Solifenacin does not inhibit CYP1A1/2, 2C9, 2C19, 2D6, or 3A4 derived from human liver microsomes. Therefore, Solifenacin is unlikely to alter the clearance of drugs metabolized by these CYP enzymes. Solifenacin is metabolized by CYP3A4. Simultaneous administration of Ketoconazole (200 mg/day), a potent CYP3A4 inhibitor, resulted in a two-fold increase of the AUC of Solifenacin, while Ketoconazole at a dose of 400 mg/day resulted in a three-fold increase of the AUC of Solifenacin. Therefore, the maximum dose of Solifenacin Succinate should be restricted to 5 mg when used simultaneously with Ketoconazole or therapeutic doses of other potent CYP3A4 inhibitors (e.g. Ritonavir, Nelfinavir, Itraconazole).

Simultaneous treatment of Solifenacin and a potent CYP3A4 inhibitor is contra-indicated in patients with severe renal impairment or moderate hepatic impairment. The effects of enzyme induction on the pharmacokinetics of Solifenacin and its metabolites have not been studied as well as the effect of higher affinity CYP3A4 substrates on Solifenacin exposure. Since Solifenacin is metabolised by CYP3A4, pharmacokinetic interactions are possible with other CYP3A4 substrates with higher affinity (e.g. Verapamil, Diltiazem) and CYP3A4 inducers (e.g. Rifampicin, Phenytoin, Carbamazepine).

Effect of Solifenacin on the pharmacokinetics of other medicinal products:

• Oral Contraceptives: Intake of Solifenacin showed no pharmacokinetic interaction on combined oral contraceptives (Ethinylestradiol/Levonorgestrel).
• Warfarin: Intake of Solifenacin did not alter the pharmacokinetics of R-warfarin or S-warfarin or their effect on prothrombin time.
• Digoxin: Intake of Solifenacin showed no effect on the pharmacokinetics of digoxin.
• Effects on ability to drive and use machines: Since Solifenacin, like other anticholinergics may cause blurred vision and, uncommonly, somnolence and fatigue, the ability to drive and use machines may be negatively affected.

No clinical data are available from women who became pregnant while taking Solifenacin. Animal studies do not indicate direct harmful effects on fertility, embryonal / foetal development or parturition. The potential risk for humans is unknown. Caution should be exercised when prescribing to pregnant women. No data on the excretion of Solifenacin in human milk are available. In mice, Solifenacin and/or its metabolites was excreted in milk, and caused a dose dependent failure to thrive in neonatal mice. The use of Solifenacin should therefore be avoided during breast-feeding.

Patients with renal impairment: No dose adjustment is necessary for patients with mild to moderate renal impairment (creatinine clearance >30 ml/min). Patients with severe renal impairment (creatinine clearance <30 ml/min) should be treated with caution and receive no more than 5 mg once daily.

Patients with hepatic impairment: No dose adjustment is necessary for patients with mild hepatic impairment. Patients with moderate hepatic impairment (Child-Pugh score of 7 to 9) should be treated with caution and receive no more than 5 mg once daily.

Potent inhibitors of cytochrome P450 3A4: The maximum dose of Solifenacin Succinate should be limited to 5 mg when treated simultaneously with Ketoconazole or therapeutic doses of other potent CYP3A4 inhibitors e.g. Ritonavir, Nelfinavir, Itraconazole. Solifenacin Succinate tablet should be taken orally and should be swallowed whole with liquids. It can be taken with or without food.

Over dosage with Solifenacin Succinate can potentially result in severe anticholinergic effects. The highest dose of Solifenacin Succinate accidentally given to a single patient was 280 mg in a 5 hour period, resulting in mental status changes not requiring hospitalization. In the event of overdose with Solifenacin Succinate, the patient should be treated with activated charcoal. Gastric lavage is useful if performed within 1 hour, but vomiting should not be induced. As for other anticholinergics, symptoms can be treated as follows:

• Severe central anticholinergic effects such as hallucinations or pronounced excitation: treat with physostigmine or carbachol.
• Convulsions or pronounced excitation: treat with benzodiazepines.
• Respiratory insufficiency: treat with artificial respiration.
• Tachycardia: treat with beta-blockers.
• Urinary retention: treat with catheterisation.
• Mydriasis: treat with pilocarpine eye drops and/or place patient in a dark room.

As with other antimuscarinics, in case of overdosing, specific attention should be paid to patients with known risk for QT-prolongation (i.e. hypokalaemia, bradycardia and concurrent administration of medicinal products known to prolong QT interval) and relevant pre-existing cardiac diseases (i.e. myocardial ischaemia, arrhythmia, congestive heart failure).

Store in a cool and dry place, protected from light.