Components:
Gabapentin
Method of action:
Analgesic, Anticonvulsant, Antiepileptic
Available in countries
See all
close

Name of the medicinal product

Gatiraban

Qualitative and quantitative composition

Gabapentin

Therapeutic indications

The information provided in Therapeutic indications of Gatiraban is based on data of another medicine with exactly the same composition as the Gatiraban of the medicine (Gabapentin). Be careful and be sure to specify the information on the section Therapeutic indications in the instructions to the drug Gatiraban directly from the package or from the pharmacist at the pharmacy.
more... close

Epilepsy

Gatiraban is indicated as adjunctive therapy in the treatment of partial seizures with and without secondary generalization in adults and children aged 6 years and above .

Gatiraban is indicated as monotherapy in the treatment of partial seizures with and without secondary generalization in adults and adolescents aged 12 years and above.

Treatment of peripheral neuropathic pain

Gatiraban is indicated for the treatment of peripheral neuropathic pain such as painful diabetic neuropathy and post-herpetic neuralgia in adults.

Dosage (Posology) and method of administration

The information provided in Dosage (Posology) and method of administration of Gatiraban is based on data of another medicine with exactly the same composition as the Gatiraban of the medicine (Gabapentin). Be careful and be sure to specify the information on the section Dosage (Posology) and method of administration in the instructions to the drug Gatiraban directly from the package or from the pharmacist at the pharmacy.
more... close
Capsule; Capsule, hard; Capsules; Film-coated tablet; Solution
Substance; Substance-powder

Posology

For all indications a titration scheme for the initiation of therapy is described in Table 1, which is recommended for adults and adolescents aged 12 years and above. Dosing instructions for children under 12 years of age are provided under a separate sub-heading later in this section.

Table 1

DOSING CHART – INITIAL TITRATION

Day 1

Day 2

Day 3

300 mg once a day

300 mg two times a day

300 mg three times a day

Discontinuation of gabapentin

In accordance with current clinical practice, if gabapentin has to be discontinued it is recommended this should be done gradually over a minimum of 1 week independent of the indication.

Epilepsy

Epilepsy typically requires long-term therapy. Dosage is determined by the treating physician according to individual tolerance and efficacy.

Adults and adolescents

In clinical trials, the effective dosing range was 900 to 3600 mg/day. Therapy may be initiated by titrating the dose as described in Table 1 or by administering 300 mg three times a day (TID) on Day 1. Thereafter, based on individual patient response and tolerability, the dose can be further increased in 300 mg/day increments every 2-3 days up to a maximum dose of 3600 mg/day. Slower titration of gabapentin dosage may be appropriate for individual patients. The minimum time to reach a dose of 1800 mg/day is one week, to reach 2400 mg/day is a total of 2 weeks, and to reach 3600 mg/day is a total of 3 weeks. Dosages up to 4800 mg/day have been well tolerated in long-term open-label clinical studies. The total daily dose should be divided in three single doses, the maximum time interval between the doses should not exceed 12 hours to prevent breakthrough convulsions.

Children aged 6 years and above

The starting dose should range from 10 to 15 mg/kg/day and the effective dose is reached by upward titration over a period of approximately three days. The effective dose of gabapentin in children aged 6 years and older is 25 to 35 mg/kg/day. Dosages up to 50 mg/kg/day have been well tolerated in a long-term clinical study. The total daily dose should be divided in three single doses, the maximum time interval between doses should not exceed 12 hours.

It is not necessary to monitor gabapentin plasma concentrations to optimize gabapentin therapy. Further, gabapentin may be used in combination with other antiepileptic medicinal products without concern for alteration of the plasma concentrations of gabapentin or serum concentrations of other antiepileptic medicinal products.

Peripheral neuropathic pain

Adults

The therapy may be initiated by titrating the dose as described in Table 1. Alternatively, the starting dose is 900 mg/day given as three equally divided doses. Thereafter, based on individual patient response and tolerability, the dose can be further increased in 300 mg/day increments every 2-3 days up to a maximum dose of 3600 mg/day. Slower titration of gabapentin dosage may be appropriate for individual patients. The minimum time to reach a dose of 1800 mg/day is one week, to reach 2400 mg/day is a total of 2 weeks, and to reach 3600 mg/day is a total of 3 weeks.

In the treatment of peripheral neuropathic pain such as painful diabetic neuropathy and post-herpetic neuralgia, efficacy and safety have not been examined in clinical studies for treatment periods longer than 5 months. If a patient requires dosing longer than 5 months for the treatment of peripheral neuropathic pain, the treating physician should assess the patient's clinical status and determine the need for additional therapy.

Instruction for all areas of indication

In patients with poor general health, i.e., low body weight, after organ transplantation etc., the dose should be titrated more slowly, either by using smaller dosage strengths or longer intervals between dosage increases.

Elderly (over 65 years of age)

Elderly patients may require dosage adjustment because of declining renal function with age (see Table 2). Somnolence, peripheral oedema and asthenia may be more frequent in elderly patients.

Renal impairment

Dosage adjustment is recommended in patients with compromised renal function as described in Table 2 and/or those undergoing haemodialysis. Gabapentin 100 mg capsules can be used to follow dosing recommendations for patients with renal insufficiency.

Table 2

DOSAGE OF GABAPENTIN IN ADULTS BASED ON RENAL FUNCTION

Creatinine Clearance (mL/min)

Total Daily Dosea (mg/day)

≥80

900-3600

50-79

600-1800

30-49

300-900

15-29

150b-600

<15c

150b-300

a Total daily dose should be administered as three divided doses. Reduced dosages are for patients with renal impairment (creatinine clearance < 79 mL/min).

b To be administered as 300 mg every other day.

c For patients with creatinine clearance <15 mL/min, the daily dose should be reduced in proportion to creatinine clearance (e.g., patients with a creatinine clearance of 7.5 mL/min should receive one-half the daily dose that patients with a creatinine clearance of 15 mL/min receive).

Use in patients undergoing haemodialysis

For anuric patients undergoing haemodialysis who have never received gabapentin, a loading dose of 300 to 400 mg, then 200 to 300 mg of gabapentin following each 4 hours of haemodialysis, is recommended. On dialysis-free days, there should be no treatment with gabapentin.

For renally impaired patients undergoing haemodialysis, the maintenance dose of gabapentin should be based on the dosing recommendations found in Table 2. In addition to the maintenance dose, an additional 200 to 300 mg dose following each 4-hour haemodialysis treatment is recommended.

Method of administration

For oral use.

Gabapentin can be given with or without food and should be swallowed whole with sufficient fluid-intake (e.g. a glass of water).

Posology

For all indications a titration scheme for the initiation of therapy is described in Table 1, which is recommended for adults and adolescents aged 12 years and above. Dosing instructions for children under 12 years of age are provided under a separate sub-heading later in this section.

Table 1

DOSING CHART – INITIAL TITRATION

Day 1

Day 2

Day 3

300 mg once a day

300 mg two times a day

300 mg three times a day

Discontinuation of Gatiraban

In accordance with current clinical practice, if Gatiraban has to be discontinued it is recommended this should be done gradually over a minimum of 1 week independent of the indication.

Epilepsy

Epilepsy typically requires long-term therapy. Dosage is determined by the treating physician according to individual tolerance and efficacy.

Adults and adolescents

In clinical trials, the effective dosing range was 900 to 3600 mg/day. Therapy may be initiated by titrating the dose as described in Table 1 or by administering 300 mg three times a day (TID) on Day 1. Thereafter, based on individual patient response and tolerability, the dose can be further increased in 300 mg/day increments every 2-3 days up to a maximum dose of 3600 mg/day. Slower titration of Gatiraban dosage may be appropriate for individual patients. The minimum time to reach a dose of 1800 mg/day is one week, to reach 2400 mg/day is a total of 2 weeks, and to reach 3600 mg/day is a total of 3 weeks.

Dosages up to 4800 mg/day have been well tolerated in long-term open-label clinical studies. The total daily dose should be divided in three single doses, the maximum time interval between the doses should not exceed 12 hours to prevent breakthrough convulsions.

Children aged 6 years and above

The starting dose should range from 10 to 15 mg/kg/day and the effective dose is reached by upward titration over a period of approximately three days. The effective dose of Gatiraban in children aged 6 years and older is 25 to 35 mg/kg/day. Dosages up to 50 mg/kg/day have been well tolerated in a long-term clinical study. The total daily dose should be divided in three single doses, the maximum time interval between doses should not exceed 12 hours.

It is not necessary to monitor Gatiraban plasma concentrations to optimize Gatiraban therapy. Further, Gatiraban may be used in combination with other antiepileptic medicinal products without concern for alteration of the plasma concentrations of Gatiraban or serum concentrations of other antiepileptic medicinal products.

Peripheral neuropathic pain

Adults

The therapy may be initiated by titrating the dose as described in Table 1. Alternatively, the starting dose is 900 mg/day given as three equally divided doses. Thereafter, based on individual patient response and tolerability, the dose can be further increased in 300 mg/day increments every 2-3 days up to a maximum dose of 3600 mg/day. Slower titration of Gatiraban dosage may be appropriate for individual patients. The minimum time to reach a dose of 1800 mg/day is one week, to reach 2400 mg/day is a total of 2 weeks, and to reach 3600 mg/day is a total of 3 weeks.

In the treatment of peripheral neuropathic pain such as painful diabetic neuropathy and post-herpetic neuralgia, efficacy and safety have not been examined in clinical studies for treatment periods longer than 5 months. If a patient requires dosing longer than 5 months for the treatment of peripheral neuropathic pain, the treating physician should assess the patient's clinical status and determine the need for additional therapy.

Instruction for all areas of indication

In patients with poor general health, i.e., low body weight, after organ transplantation etc., the dose should be titrated more slowly, either by using smaller dosage strengths or longer intervals between dosage increases.

Elderly (over 65 years of age)

Elderly patients may require dosage adjustment because of declining renal function with age (see Table 2). Somnolence, peripheral oedema and asthenia may be more frequent in elderly patients.

Renal impairment

Dosage adjustment is recommended in patients with compromised renal function as described in Table 2 and/or those undergoing haemodialysis. Gatiraban 100 mg capsules can be used to follow dosing recommendations for patients with renal insufficiency.

Table 2

DOSAGE OF Gatiraban IN ADULTS BASED ON RENAL FUNCTION

Creatinine Clearance (mL/min)

Total Daily Dosea (mg/day)

≥ 80

900-3600

50-79

600-1800

30-49

300-900

15-29

150b-600

< 15c

150b-300

a Total daily dose should be administered as three divided doses. Reduced dosages are for patients with renal impairment (creatinine clearance < 79 mL/min).

b To be administered as 300 mg every other day.

c For patients with creatinine clearance < 15 mL/min, the daily dose should be reduced in proportion to creatinine clearance (e.g., patients with a creatinine clearance of 7.5 mL/min should receive one-half the daily dose that patients with a creatinine clearance of 15 mL/min receive).

Use in patients undergoing haemodialysis

For anuric patients undergoing haemodialysis who have never received Gatiraban, a loading dose of 300 to 400 mg, then 200 to 300 mg of Gatiraban following each 4 hours of haemodialysis, is recommended. On dialysis-free days, there should be no treatment with Gatiraban.

For renally impaired patients undergoing haemodialysis, the maintenance dose of Gatiraban should be based on the dosing recommendations found in Table 2. In addition to the maintenance dose, an additional 200 to 300 mg dose following each 4-hour haemodialysis treatment is recommended.

Method of administration

For oral use.

Gatiraban can be given with or without food and should be swallowed whole with sufficient fluid- intake (e.g. a glass of water).

Contraindications

The information provided in Contraindications of Gatiraban is based on data of another medicine with exactly the same composition as the Gatiraban of the medicine (Gabapentin). Be careful and be sure to specify the information on the section Contraindications in the instructions to the drug Gatiraban directly from the package or from the pharmacist at the pharmacy.
more... close
<

Special warnings and precautions for use

The information provided in Special warnings and precautions for use of Gatiraban is based on data of another medicine with exactly the same composition as the Gatiraban of the medicine (Gabapentin). Be careful and be sure to specify the information on the section Special warnings and precautions for use in the instructions to the drug Gatiraban directly from the package or from the pharmacist at the pharmacy.
more... close
Capsule; Capsule, hard; Capsules; Film-coated tablet; Solution
Substance; Substance-powder

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS)

Severe, life-threatening, systemic hypersensitivity reactions such as Drug rash with eosinophilia and systemic symptoms (DRESS) have been reported in patients taking antiepileptic drugs including gabapentin .

It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately. Gabapentin should be discontinued if an alternative etiology for the signs or symptoms cannot be established.

Anaphylaxis

Gabapentin can cause anaphylaxis. Signs and symptoms in reported cases have included difficulty breathing, swelling of the lips, throat, and tongue, and hypotension requiring emergency treatment. Patients should be instructed to discontinue gabapentin and seek immediate medical care should they experience signs or symptoms of anaphylaxis .

Suicidal ideation and behaviour

Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents in several indications. A meta-analysis of randomised placebo controlled trials of anti-epileptic drugs has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for gabapentin.

Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.

Acute pancreatitis

If a patient develops acute pancreatitis under treatment with gabapentin, discontinuation of gabapentin should be considered .

Seizures

Although there is no evidence of rebound seizures with gabapentin, abrupt withdrawal of anticonvulsants in epileptic patients may precipitate status epilepticus .

As with other antiepileptic medicinal products, some patients may experience an increase in seizure frequency or the onset of new types of seizures with gabapentin.

As with other anti-epileptics, attempts to withdraw concomitant anti-epileptics in treatment refractive patients on more than one anti-epileptic, in order to reach gabapentin monotherapy have a low success rate.

Gabapentin is not considered effective against primary generalized seizures such as absences and may aggravate these seizures in some patients. Therefore, gabapentin should be used with caution in patients with mixed seizures including absences.

Gabapentin treatment has been associated with dizziness and somnolence, which could increase the occurrence of accidental injury (fall). There have also been post-marketing reports of confusion, loss of consciousness and mental impairment. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medication.

Concomitant use with opioids

Patients who require concomitant treatment with opioids should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence, sedation and respiratory depression. Patients who use gabapentin and morphine concomitantly may experience increases in gabapentin concentrations. The dose of gabapentin or opioids should be reduced appropriately .

Respiratory depression

Gabapentin has been associated with severe respiratory depression. Patients with compromised respiratory function, respiratory or neurological disease, renal impairment, concomitant use of CNS depressants and the elderly might be at higher risk of experiencing this severe adverse reaction. Dose adjustments might be necessary in these patients.

Elderly (over 65 years of age)

No systematic studies in patients 65 years or older have been conducted with gabapentin. In one double blind study in patients with neuropathic pain, somnolence, peripheral oedema and asthenia occurred in a somewhat higher percentage in patients aged 65 years or above, than in younger patients. Apart from these findings, clinical investigations in this age group do not indicate an adverse event profile different from that observed in younger patients.

Paediatric population

The effects of long-term (greater than 36 weeks) gabapentin therapy on learning, intelligence, and development in children and adolescents have not been adequately studied. The benefits of prolonged therapy must therefore be weighed against the potential risks of such therapy.

Abuse and dependence

Cases of abuse and dependence have been reported in the post-marketing database. Carefully evaluate patients for a history of drug abuse and observe them for possible signs of gabapentin abuse e.g. drug-seeking behaviour, dose escalation, development of tolerance.

Laboratory tests

False positive readings may be obtained in the semi-quantitative determination of total urine protein by dipstick tests. It is therefore recommended to verify such a positive dipstick test result by methods based on a different analytical principle such as the Biuret method, turbidimetric or dye-binding methods, or to use these alternative methods from the beginning.

Gatiraban hard capsules contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS)

Severe, life-threatening, systemic hypersensitivity reactions such as Drug rash with eosinophilia and systemic symptoms (DRESS) have been reported in patients taking antiepileptic drugs including Gatiraban .

It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately. Gatiraban should be discontinued if an alternative etiology for the signs or symptoms cannot be established.

Anaphylaxis

Gatiraban can cause anaphylaxis. Signs and symptoms in reported cases have included difficulty breathing, swelling of the lips, throat, and tongue, and hypotension requiring emergency treatment. Patients should be instructed to discontinue Gatiraban and seek immediate medical care should they experience signs or symptoms of anaphylaxis .

Suicidal ideation and behaviour

Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents in several indications. A meta-analysis of randomised placebo controlled trials of anti-epileptic drugs has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for Gatiraban.

Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.

Acute pancreatitis

If a patient develops acute pancreatitis under treatment with Gatiraban, discontinuation of Gatiraban should be considered .

Seizures

Although there is no evidence of rebound seizures with Gatiraban, abrupt withdrawal of anticonvulsants in epileptic patients may precipitate status epilepticus .

As with other antiepileptic medicinal products, some patients may experience an increase in seizure frequency or the onset of new types of seizures with Gatiraban.

As with other anti-epileptics, attempts to withdraw concomitant anti-epileptics in treatment refractive patients on more than one anti-epileptic, in order to reach Gatiraban monotherapy have a low success rate.

Gatiraban is not considered effective against primary generalized seizures such as absences and may aggravate these seizures in some patients. Therefore, Gatiraban should be used with caution in patients with mixed seizures including absences.

Gatiraban treatment has been associated with dizziness and somnolence, which could increase the occurrence of accidental injury (fall). There have also been post-marketing reports of confusion, loss of consciousness and mental impairment. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medication.

Concomitant use with opioids

Patients who require concomitant treatment with opioids should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence, sedation and respiratory depression. Patients who use Gatiraban and morphine concomitantly may experience increases in Gatiraban concentrations. The dose of Gatiraban or opioids should be reduced appropriately .

Respiratory depression

Gatiraban has been associated with severe respiratory depression. Patients with compromised respiratory function, respiratory or neurological disease, renal impairment, concomitant use of CNS depressants and the elderly might be at higher risk of experiencing this severe adverse reaction. Dose adjustments might be necessary in these patients.

Elderly (over 65 years of age)

No systematic studies in patients 65 years or older have been conducted with Gatiraban. In one double blind study in patients with neuropathic pain, somnolence, peripheral oedema and asthenia occurred in a somewhat higher percentage in patients aged 65 years or above, than in younger patients. Apart from these findings, clinical investigations in this age group do not indicate an adverse event profile different from that observed in younger patients.

Paediatric population

The effects of long-term (greater than 36 weeks) Gatiraban therapy on learning, intelligence, and development in children and adolescents have not been adequately studied. The benefits of prolonged therapy must therefore be weighed against the potential risks of such therapy.

Abuse and dependence

Cases of abuse and dependence have been reported in the post-marketing database. Carefully evaluate patients for a history of drug abuse and observe them for possible signs of Gatiraban abuse, e.g. drug-seeking behaviour, dose escalation, development of tolerance.

Laboratory tests

False positive readings may be obtained in the semi-quantitative determination of total urine protein by dipstick tests. It is therefore recommended to verify such a positive dipstick test result by methods based on a different analytical principle such as the Biuret method, turbidimetric or dye-binding methods, or to use these alternative methods from the beginning.

Gatiraban hard capsules contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Effects on ability to drive and use machines

The information provided in Effects on ability to drive and use machines of Gatiraban is based on data of another medicine with exactly the same composition as the Gatiraban of the medicine (Gabapentin). Be careful and be sure to specify the information on the section Effects on ability to drive and use machines in the instructions to the drug Gatiraban directly from the package or from the pharmacist at the pharmacy.
more... close
Capsule; Capsule, hard; Capsules; Film-coated tablet; Solution
Substance; Substance-powder

Gabapentin may have minor or moderate influence on the ability to drive and use machines. Gabapentin acts on the central nervous system and may cause drowsiness, dizziness or other related symptoms. Even, if they were only of mild or moderate degree, these undesirable effects could be potentially dangerous in patients driving or operating machinery. This is especially true at the beginning of the treatment and after increase in dose.

Gatiraban may have minor or moderate influence on the ability to drive and use machines. Gatiraban acts on the central nervous system and may cause drowsiness, dizziness or other related symptoms. Even, if they were only of mild or moderate degree, these undesirable effects could be potentially dangerous in patients driving or operating machinery. This is especially true at the beginning of the treatment and after increase in dose.

Undesirable effects

The information provided in Undesirable effects of Gatiraban is based on data of another medicine with exactly the same composition as the Gatiraban of the medicine (Gabapentin). Be careful and be sure to specify the information on the section Undesirable effects in the instructions to the drug Gatiraban directly from the package or from the pharmacist at the pharmacy.
more... close
Capsule; Capsule, hard; Capsules; Film-coated tablet; Solution
Substance; Substance-powder

The adverse reactions observed during clinical studies conducted in epilepsy (adjunctive and monotherapy) and neuropathic pain have been provided in a single list below by class and frequency: very common (≥ 1/10); common (≥ 1/100 to< 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000). Where an adverse reaction was seen at different frequencies in clinical studies, it was assigned to the highest frequency reported.

Additional reactions reported from post-marketing experience are included as frequency Not known (cannot be estimated from the available data) in italics in the list below.

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

System organ class

Adverse drug reactions

Infections and infestations

Very Common

viral infection

Common

pneumonia, respiratory infection, urinary tract infection, infection, otitis media

Blood and the lymphatic system disorders

Common

leucopenia

Not known

Thrombocytopenia

Immune system disorders

Uncommon

allergic reactions (e.g. urticaria)

Not known

hypersensitivity syndrome (a systemic reaction with a variable presentation that can include fever, rash, hepatitis, lymphadenopathy, eosinophilia, and sometimes other signs and symptoms), anaphylaxis

Metabolism and nutrition disorders

Common

anorexia, increased appetite

Uncommon

hyperglycaemia (most often observed in patients with diabetes)

Rare

hypoglycaemia (most often observed in patients with diabetes)

Not known

hyponatraemia

Psychiatric disorders

Common

hostility, confusion and emotional lability, depression, anxiety, nervousness, thinking abnormal

Uncommon

agitation

Not known

hallucinations

Nervous system disorders

Very Common

somnolence, dizziness, ataxia

Common

convulsions, hyperkinesias, dysarthria, amnesia, tremor, insomnia, headache, sensations such as paresthesia, hypaesthesia, coordination abnormal, nystagmus, increased, decreased, or absent reflexes

Uncommon

hypokinesia, mental impairment

Rare

loss of consciousness

Not known

other movement disorders (e.g. choreoathetosis, dyskinesia, dystonia)

Eye disorders

Common

visual disturbances such as amblyopia, diplopia

Ear and labyrinth disorders

Common

vertigo

Not known

tinnitus

Cardiac disorders

Uncommon

palpitations

Vascular disorders

Common

hypertension, vasodilatation

Respiratory, thoracic and mediastinal disorders

Common

dyspnoea, bronchitis, pharyngitis, cough, rhinitis

Rare

respiratory depression

Gastrointestinal disorders

Common

vomiting, nausea, dental abnormalities, gingivitis, diarrhoea, abdominal pain, dyspepsia, constipation, dry mouth or throat, flatulence

Not known

pancreatitis

Hepatobiliary disorders

Not known

hepatitis, jaundice

Skin and subcutaneous tissue disorders

Common

facial oedema, purpura most often described as bruises resulting from physical trauma, rash, pruritus, acne

Not known

Stevens-Johnson syndrome, angioedema, erythema multiforme, alopecia, drug rash with eosinophilia and systemic symptoms

Musculoskeletal and connective tissue disorders

Common

arthralgia, myalgia, back pain, twitching

Not known

rhabdomyolysis, myoclonus

Renal and urinary disorder

Not known

acute renal failure, incontinence

Reproductive system and breast disorders

Common

impotence

Not known

breast hypertrophy, gynaecomastia, sexual dysfunction (including changes in libido, ejaculation disorders and anorgasmia)

General disorders and administration site conditions

Very Common

fatigue, fever

Common

peripheral oedema, abnormal gait, asthenia, pain, malaise, flu syndrome

Uncommon

generalized oedema

Not known

withdrawal reactions (mostly anxiety, insomnia, nausea, pains, sweating), chest pain. Sudden unexplained deaths have been reported where a causal relationship to treatment with gabapentin has not been established.

Investigations

Common

WBC (white blood cell count) decreased, weight gain

Uncommon

elevated liver function tests SGOT (AST), SGPT (ALT) and bilirubin

Not known

blood creatine phosphokinase increased

Injury, poisoning and procedural complications

Common

accidental injury, fracture, abrasion

Uncommon

fall

Under treatment with gabapentin cases of acute pancreatitis were reported. Causality with gabapentin is unclear .

In patients on haemodialysis due to end-stage renal failure, myopathy with elevated creatine kinase levels has been reported.

Respiratory tract infections, otitis media, convulsions and bronchitis were reported only in clinical studies in children. Additionally, in clinical studies in children, aggressive behaviour and hyperkinesias were reported commonly.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard.

The adverse reactions observed during clinical studies conducted in epilepsy (adjunctive and monotherapy) and neuropathic pain have been provided in a single list below by class and frequency: (very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to ≤ 1/100); rare (≥ 1/10,000 to ≤ 1/1,000); very rare (< 1/10,000).

Where an adverse reaction was seen at different frequencies in clinical studies it was assigned to the highest frequency reported.

Additional reactions reported from post-marketing experience are included as frequency Not known (cannot be estimated from the available data) in italics in the list below.

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

System organ class

Adverse drug reactions

Infections and infestations

Very common

viral infection

Common

pneumonia, respiratory infection, urinary tract infection, infection, otitis media

Blood and the lymphatic system disorders

Common

leucopenia

Not known

thrombocytopenia

Immune system disorders

Uncommon

allergic reactions (e.g. urticaria)

Not known

hypersensitivity syndrome (a systemic reaction with a variable presentation that can include fever, rash, hepatitis lymphadenopathy, eosinophilia and sometimes other signs and symptoms), anaphylaxis .

Metabolism and nutrition disorders

Common

anorexia, increased appetite

Uncommon

hyperglycaemia (most often observed in patients with diabetes)

Rare

hypoglycaemia (most often observed in patients with diabetes)

Not known

hyponatraemia

Psychiatric disorders

Common

hostility, confusion and emotional lability, depression, anxiety, nervousness, thinking abnormal

Uncommon

agitation

Not known

hallucinations

Nervous system disorders

Very common

somnolence, dizziness, ataxia

Common

convulsions, hyperkinesias, dysarthria, amnesia, tremor, insomnia, headache, sensations such as paresthesia, hypaesthesia, coordination abnormal, nystagmus, increased, decreased, or absent reflexes

Uncommon

hypokinesia, mental impairment

Rare

loss of consciousness

Not known

other movement disorders (e.g. choreoathetosis, dyskinesia, dystonia)

Eye disorders

Common

visual disturbances such as amblyopia, diplopia

Ear and labyrinth disorders

Common

vertigo

Not known

tinnitus

Cardiac disorders

Uncommon

palpitations

Vascular disorders

Common

hypertension, vasodilatation

Respiratory, thoracic and mediastinal disorders

Common

dyspnoea, bronchitis, pharyngitis, cough, rhinitis

Rare

respiratory depression

Gastrointestinal disorders

Common

vomiting, nausea, dental abnormalities, gingivitis, diarrhoea, abdominal pain, dyspepsia, constipation, dry mouth or throat, flatulence

Not known

pancreatitis

Hepatobiliary disorders

Not known

hepatitis, jaundice

Skin and subcutaneous tissue disorders

Common

facial oedema, purpura most often described as bruises resulting from physical trauma, rash, pruritus, acne

Not known

Stevens-Johnson syndrome, angioedema, erythema multiforme, alopecia, drug rash with eosinophilia and systemic symptoms

Musculoskeletal and connective tissue disorders

Common

arthralgia, myalgia, back pain, twitching

Not known

rhabdomyolysis, myoclonus

Renal and urinary disorders

Not known

acute renal failure, incontinence

Reproductive system and breast disorders

Common

impotence

Not known

breast hypertrophy, gynaecomastia, sexual dysfunction (including changes in libido, ejaculation disorders and anorgasmia)

General disorders and administration site conditions

Very common

fatigue, fever

Common

peripheral oedema, abnormal gait, asthenia, pain, malaise, flu syndrome

Uncommon

generalised oedema

Not known

withdrawal reactions (mostly anxiety, insomnia, nausea, pains, sweating), chest pain. Sudden unexplained deaths have been reported where a causal relationship to treatment with Gatiraban has not been established.

Investigations

Common

WBC (white blood cell count) decreased, weight gain

Uncommon

elevated liver function tests SGOT (AST), SGPT (ALT) and bilirubin

Not known

blood creatine phosphokinase increased

Injury, poisoning and procedural complications

Common

accidental injury, fracture, abrasion

Uncommon

fall

Under treatment with Gatiraban cases of acute pancreatitis were reported. Causality with Gatiraban is unclear .

In patients on haemodialysis due to end-stage renal failure, myopathy with elevated creatine kinase levels has been reported.

Respiratory tract infections, otitis media, convulsions and bronchitis were reported only in clinical studies in children. Additionally, in clinical studies in children, aggressive behaviour and hyperkinesias were reported commonly.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

Overdose

The information provided in Overdose of Gatiraban is based on data of another medicine with exactly the same composition as the Gatiraban of the medicine (Gabapentin). Be careful and be sure to specify the information on the section Overdose in the instructions to the drug Gatiraban directly from the package or from the pharmacist at the pharmacy.
more... close
Capsule; Capsule, hard; Capsules; Film-coated tablet; Solution
Substance; Substance-powder

Acute, life-threatening toxicity has not been observed with gabapentin overdoses of up to 49 g. Symptoms of the overdoses included dizziness, double vision, slurred speech, drowsiness, loss of consciousness, lethargy and mild diarrhoea. All patients recovered fully with supportive care. Reduced absorption of gabapentin at higher doses may limit drug absorption at the time of overdosing and, hence, minimize toxicity from overdoses.

Overdoses of gabapentin, particularly in combination with other CNS depressant medications, may result in coma.

Although gabapentin can be removed by haemodialysis, based on prior experience it is usually not required. However, in patients with severe renal impairment, haemodialysis may be indicated.

An oral lethal dose of gabapentin was not identified in mice and rats given doses as high as 8000 mg/kg. Signs of acute toxicity in animals included ataxia, laboured breathing, ptosis, hypoactivity, or excitation.

Acute, life-threatening toxicity has not been observed with Gatiraban overdoses of up to 49 g. Symptoms of the overdoses included dizziness, double vision, slurred speech, drowsiness, loss of consciousness, lethargy and mild diarrhoea. All patients recovered fully with supportive care. Reduced absorption of Gatiraban at higher doses may limit drug absorption at the time of overdosing and, hence, minimize toxicity from overdoses.

Overdoses of Gatiraban, particularly in combination with other CNS depressant medication, may result in coma.

Although Gatiraban can be removed by haemodialysis, based on prior experience it is usually not required. However, in patients with severe renal impairment, haemodialysis may be indicated.

An oral lethal dose of Gatiraban was not identified in mice and rats given doses as high as 8000 mg/kg. Signs of acute toxicity in animals included ataxia, laboured breathing, ptosis, hypoactivity, or excitation.

Pharmacodynamic properties

The information provided in Pharmacodynamic properties of Gatiraban is based on data of another medicine with exactly the same composition as the Gatiraban of the medicine (Gabapentin). Be careful and be sure to specify the information on the section Pharmacodynamic properties in the instructions to the drug Gatiraban directly from the package or from the pharmacist at the pharmacy.
more... close
Capsule; Capsule, hard; Capsules; Film-coated tablet; Solution
Substance; Substance-powder

Pharmacotherapeutic groups: Other antiepileptics ATC code: N03AX12

Mechanism of action

Gabapentin readily enters the brain and prevents seizures in a number of animal models of epilepsy. Gabapentin does not possess affinity for either GABAA or GABAB receptor nor does it alter the metabolism of GABA. It does not bind to other neurotransmitter receptors of the brain and does not interact with sodium channels. Gabapentin binds with high affinity to the α2δ (alpha-2-delta) subunit of voltage-gated calcium channels and it is proposed that binding to the α2δ subunit may be involved in gabapentin's anti-seizure effects in animals. Broad panel screening does not suggest any other drug targets other than α2δ.

Evidence from several pre-clinical models inform that the pharmacological activity of gabapentin may be mediated via binding to α2δ through a reduction in release of excitatory neurotransmitters in regions of the central nervous system. Such activity may underlie gabapentin's anti-seizure activity. The relevance of these actions of gabapentin to the anticonvulsant effects in humans remains to be established.

Gabapentin also displays efficacy in several pre-clinical animal pain models. Specific binding of gabapentin to the α2δ subunit is proposed to result in several different actions that may be responsible for analgesic activity in animal models. The analgesic activities of gabapentin may occur in the spinal cord as well as at higher brain centers through interactions with descending pain inhibitory pathways. The relevance of these pre-clinical properties to clinical action in humans is unknown.

Clinical efficacy and safety

A clinical trial of adjunctive treatment of partial seizures in paediatric subjects ranging in age from 3 to 12 years, showed a numerical but not statistically significant difference in the 50% responder rate in favour of the gabapentin group compared to placebo. Additional post-hoc analyses of the responder rates by age did not reveal a statistically significant effect of age, either as a continuous or dichotomous variable (age groups 3-5 and 6-12 years). The data from this additional post-hoc analysis are summarised in the table below:

Response (≥ 50% Improved) by Treatment and Age MITT* Population

Age Category

Placebo

Gabapentin

P-Value

< 6 Years Old

4/21 (19.0%)

4/17 (23.5%)

0.7362

6 to 12 Years Old

17/99 (17.2%)

20/96 (20.8%)

0.5144

*The modified intent to treat population was defined as all patients randomised to study medication who also had evaluable seizure diaries available for 28 days during both the baseline and double-blind phases.

Pharmacotherapeutic groups: Antiepileptics, Other antiepileptics

ATC code: N03AX12

Mechanism of action

Gatiraban readily enters the brain and prevents seizures in a number of animal models of epilepsy. Gatiraban does not possess affinity for either GABAA or GABAB receptor nor does it alter the metabolism of GABA. It does not bind to other neurotransmitter receptors of the brain and does not interact with sodium channels. Gatiraban binds with high affinity to the α2δ (alpha-2-delta) subunit of voltage-gated calcium channels and it is proposed that binding to the α2δ subunit may be involved in Gatiraban's anti-seizure effects in animals. Broad panel screening does not suggest any other drug target other than α2δ.

Evidence from several pre-clinical models inform that the pharmacological activity of Gatiraban may be mediated via binding to α2δ through a reduction in release of excitatory neurotransmitters in regions of the central nervous system. Such activity may underlie Gatiraban's anti-seizure activity. The relevance of these actions of Gatiraban to the anticonvulsant effects in humans remains to be established.

Gatiraban also displays efficacy in several pre-clinical animal pain models. Specific binding of Gatiraban to the α2δ subunit is proposed to result in several different actions that may be responsible for analgesic activity in animal models. The analgesic activities of Gatiraban may occur in the spinal cord as well as at higher brain centers through interactions with descending pain inhibitory pathways. The relevance of these pre-clinical properties to clinical action in humans is unknown.

Clinical efficacy and safety

A clinical trial of adjunctive treatment of partial seizures in paediatric subjects, ranging in age from 3 to 12 years, showed a numerical but not statistically significant difference in the 50% responder rate in favour of the Gatiraban group compared to placebo. Additional post-hoc analyses of the responder rates by age did not reveal a statistically significant effect of age, either as a continuous or dichotomous variable (age groups 3-5 and 6-12 years).

The data from this additional post-hoc analysis are summarised in the table below:

Response (≥ 50% Improved) by Treatment and Age MITT* Population

Age Category

Placebo

Gatiraban

P-Value

< 6 Years Old

4/21 (19.0%)

4/17 (23.5%)

0.7362

6 to 12 Years Old

17/99 (17.2%)

20/96 (20.8%)

0.5144

*The modified intent to treat population was defined as all patients randomised to study medication who also had evaluable seizure diaries available for 28 days during both the baseline and double-blind phases.

Pharmacokinetic properties

The information provided in Pharmacokinetic properties of Gatiraban is based on data of another medicine with exactly the same composition as the Gatiraban of the medicine (Gabapentin). Be careful and be sure to specify the information on the section Pharmacokinetic properties in the instructions to the drug Gatiraban directly from the package or from the pharmacist at the pharmacy.
more... close
Capsule; Capsule, hard; Capsules; Film-coated tablet; Solution
Substance; Substance-powder

Absorption

Following oral administration, peak plasma gabapentin concentrations are observed within 2 to 3 hours. Gabapentin bioavailability (fraction of dose absorbed) tends to decrease with increasing dose. Absolute bioavailability of a 300 mg capsule is approximately 60%. Food, including a high-fat diet, has no clinically significant effect on gabapentin pharmacokinetics.

Gabapentin pharmacokinetics are not affected by repeated administration. Although plasma gabapentin concentrations were generally between 2 μg/mL and 20 μg/mL in clinical studies, such concentrations were not predictive of safety or efficacy. Pharmacokinetic parameters are given in Table 3.

Table 3

SUMMARY OF GABAPENTIN MEAN (%CV) STEADY-STATE PHARMACOKINETIC PARAMETERS FOLLOWING EVERY EIGHT HOURS ADMINISTRATION

Pharmacokinetic parameter

300 mg

(N=7)

400 mg

(N=14)

800 mg

(N=14)

Mean

%CV

Mean

%CV

Mean

%CV

Cmax (μg/mL)

4.02

(24)

5.74

(38)

8.71

(29)

tmax (hr)

2.7

(18)

2.1

(54)

1.6

(76)

T1/2 (hr)

5.2

(12)

10.8

(89)

10.6

(41)

AUC (0-8) μg•hr/mL)

24.8

(24)

34.5

(34)

51.4

(27)

Ae% (%)

NA

NA

47.2

(25)

34.4

(37)

Cmax = Maximum steady state plasma concentration

tmax = Time for Cmax

T1/2 = Elimination half-life

AUC(0-8) = Steady state area under plasma concentration-time curve from time 0 to 8 hours postdose

Ae% = Percent of dose excreted unchanged into the urine from time 0 to 8 hours postdose

NA = Not available

Distribution

Gabapentin is not bound to plasma proteins and has a volume of distribution equal to 57.7 litres. In patients with epilepsy, gabapentin concentrations in cerebrospinal fluid (CSF) are approximately 20% of corresponding steady-state trough plasma concentrations. Gabapentin is present in the breast milk of breast-feeding women.

Biotransformation

There is no evidence of gabapentin metabolism in humans. Gabapentin does not induce hepatic mixed function oxidase enzymes responsible for drug metabolism.

Elimination

Gabapentin is eliminated unchanged solely by renal excretion. The elimination half-life of gabapentin is independent of dose and averages 5 to 7 hours.

In elderly patients, and in patients with impaired renal function, gabapentin plasma clearance is reduced. Gabapentin elimination-rate constant, plasma clearance, and renal clearance are directly proportional to creatinine clearance.

Gabapentin is removed from plasma by haemodialysis. Dosage adjustment in patients with compromised renal function or undergoing haemodialysis is recommended .

Gabapentin pharmacokinetics in children were determined in 50 healthy subjects between the ages of 1 month and 12 years. In general, plasma gabapentin concentrations in children > 5 years of age are similar to those in adults when dosed on a mg/kg basis.

In a pharmacokinetic study in 24 healthy paediatric subjects aged between 1 month and 48 months, an approximately 30% lower exposure (AUC), lower Cmax and higher clearance per body weight have been observed in comparison to available reported data in children older than 5 years.

Linearity/non-linearity

Gabapentin bioavailability (fraction of dose absorbed) decreases with increasing dose which imparts non-linearity to pharmacokinetic parameters which include the bioavailability parameter (F) e.g. Ae%, CL/F, Vd/F. Elimination pharmacokinetics (pharmacokinetic parameters which do not include F such as CLr and T1/2), are best described by linear pharmacokinetics. Steady state plasma gabapentin concentrations are predictable from single-dose data.

Absorption

Following oral administration, peak plasma Gatiraban concentrations are observed within 2 to 3 hours. Gatiraban bioavailability (fraction of dose absorbed) tends to decrease with increasing dose. Absolute bioavailability of a 300 mg capsule is approximately 60%. Food, including a high-fat diet, has no clinically significant effect on Gatiraban pharmacokinetics.

Gatiraban pharmacokinetics are not affected by repeated administration. Although plasma Gatiraban concentrations were generally between 2 μg/mL and 20 μg/mL in clinical studies, such concentrations were not predictive of safety or efficacy. Pharmacokinetic parameters are given in Table 3.

TABLE 3

Summary of Gatiraban mean (%cv) steady-state pharmacokinetic parameters following every eight hours administration

Pharmacokinetic parameter

300 mg

(N = 7)

400 mg

(N = 14)

800 mg

(N=14)

Mean

%CV

Mean

%CV

Mean

%CV

Cmax μg/mL)

4.02

(24)

5.74

(38)

8.71

(29)

tmax (hr)

2.7

(18)

2.1

(54)

1.6

(76)

T1/2 (hr)

5.2

(12)

10.8

(89)

10.6

(41)

AUC (0-8)

μg•hr/mL)

24.8

(24)

34.5

(34)

51.4

(27)

Ae% (%)

NA

NA

47.2

(25)

34.4

(37)

Cmax = Maximum steady state plasma concentration

tmax = Time for Cmax

T1/2 = Elimination half-life

AUC(0-8) = Steady state area under plasma concentration-time curve from time 0 to 8 hours post-dose

Ae% = Percent of dose excreted unchanged into the urine from time 0 to 8 hours post-dose

NA = Not available

Distribution

Gatiraban is not bound to plasma proteins and has a volume of distribution equal to 57.7 litres. In patients with epilepsy, Gatiraban concentrations in cerebrospinal fluid (CSF) are approximately 20% of corresponding steady-state trough plasma concentrations. Gatiraban is present in the breast milk of breast-feeding women.

Biotransformation

There is no evidence of Gatiraban metabolism in humans. Gatiraban does not induce hepatic mixed function oxidase enzymes responsible for drug metabolism.

Elimination

Gatiraban is eliminated unchanged solely by renal excretion. The elimination half-life of Gatiraban is independent of dose and averages 5 to 7 hours.

In elderly patients, and in patients with impaired renal function, Gatiraban plasma clearance is reduced. Gatiraban elimination-rate constant, plasma clearance, and renal clearance are directly proportional to creatinine clearance.

Gatiraban is removed from plasma by haemodialysis. Dosage adjustment in patients with compromised renal function or undergoing haemodialysis is recommended .

Gatiraban pharmacokinetics in children were determined in 50 healthy subjects between the ages of 1 month and 12 years. In general, plasma Gatiraban concentrations in children > 5 years of age are similar to those in adults when dosed on a mg/kg basis.

In a pharmacokinetic study in 24 healthy paediatric subjects aged between 1 month and 48 months, an approximately 30% lower exposure (AUC), lower Cmax and higher clearance per body weight have been observed in comparison to available reported data in children older than 5 years.

Linearity/Non-linearity

Gatiraban bioavailability (fraction of dose absorbed) decreases with increasing dose which imparts non-linearity to pharmacokinetic parameters which include the bioavailability parameter (F) e.g. Ae%, CL/F, Vd/F. Elimination pharmacokinetics (pharmacokinetic parameters which do not include F such as CLr and T1/2), are best described by linear pharmacokinetics. Steady state plasma Gatiraban concentrations are predictable from single-dose data.

Preclinical safety data

The information provided in Preclinical safety data of Gatiraban is based on data of another medicine with exactly the same composition as the Gatiraban of the medicine (Gabapentin). Be careful and be sure to specify the information on the section Preclinical safety data in the instructions to the drug Gatiraban directly from the package or from the pharmacist at the pharmacy.
more... close
Capsule; Capsule, hard; Capsules; Film-coated tablet; Solution
Substance; Substance-powder

Carcinogenesis

Gabapentin was given in the diet to mice at 200, 600, and 2000 mg/kg/day and to rats at 250, 1000, and 2000 mg/kg/day for two years. A statistically significant increase in the incidence of pancreatic acinar cell tumors was found only in male rats at the highest dose. Peak plasma drug concentrations in rats at 2000 mg/kg/day are 10 times higher than plasma concentrations in humans given 3600 mg/day. The pancreatic acinar cell tumors in male rats are low-grade malignancies, did not affect survival, did not metastasize or invade surrounding tissue, and were similar to those seen in concurrent controls. The relevance of these pancreatic acinar cell tumors in male rats to carcinogenic risk in humans is unclear.

Mutagenesis

Gabapentin demonstrated no genotoxic potential. It was not mutagenic in vitro in standard assays using bacterial or mammalian cells. Gabapentin did not induce structural chromosome aberrations in mammalian cells in vitro or in vivo, and did not induce micronucleus formation in the bone marrow of hamsters.

Impairment of fertility

No adverse effects on fertility or reproduction were observed in rats at doses up to 2000 mg/kg (approximately five times the maximum daily human dose on a mg/m2 of body surface area basis).

Teratogenesis

Gabapentin did not increase the incidence of malformations, compared to controls, in the offspring of mice, rats, or rabbits at doses up to 50, 30 and 25 times respectively, the daily human dose of 3600 mg, (four, five or eight times, respectively, the human daily dose on a mg/m2 basis).

Gabapentin induced delayed ossification in the skull, vertebrae, forelimbs, and hindlimbs in rodents, indicative of fetal growth retardation. These effects occurred when pregnant mice received oral doses of 1000 or 3000 mg/kg/day during organogenesis and in rats given 2000 mg/kg prior to and during mating and throughout gestation. These doses are approximately 1 to 5 times the human dose of 3600 mg on a mg/m2 basis.

No effects were observed in pregnant mice given 500 mg/kg/day (approximately 1/2 of the daily human dose on a mg/m2 basis).

An increased incidence of hydroureter and/or hydronephrosis was observed in rats given 2000 mg/kg/day in a fertility and general reproduction study, 1500 mg/kg/day in a teratology study, and 500, 1000, and 2000 mg/kg/day in a perinatal and postnatal study. The significance of these findings is unknown, but they have been associated with delayed development. These doses are also approximately 1 to 5 times the human dose of 3600 mg on a mg/m2 basis.

In a teratology study in rabbits, an increased incidence of post-implantation fetal loss, occurred in doses given 60, 300, and 1500 mg/kg/day during organogenesis. These doses are approximately 1/4 to 8 times the daily human dose of 3600 mg on a mg/m2 basis.

Carcinogenesis

Gatiraban was given in the diet to mice at 200, 600, and 2000 mg/kg/day and to rats at 250, 1000, and 2000 mg/kg/day for two years. A statistically significant increase in the incidence of pancreatic acinar cell tumours was found only in male rats at the highest dose. Peak plasma drug concentrations in rats at 2000 mg/kg/day are 10 times higher than plasma concentrations in humans given 3600 mg/day. The pancreatic acinar cell tumours in male rats are low-grade malignancies, did not affect survival, did not metastasize or invade surrounding tissue, and were similar to those seen in concurrent controls. The relevance of these pancreatic acinar cell tumours in male rats to carcinogenic risk in humans is unclear.

Mutagenesis

Gatiraban demonstrated no genotoxic potential. It was not mutagenic in vitro in standard assays using bacterial or mammalian cells. Gatiraban did not induce structural chromosome aberrations in mammalian cells in vitro or in vivo, and did not induce micronucleus formation in the bone marrow of hamsters.

Impairment of Fertility

No adverse effects on fertility or reproduction were observed in rats at doses up to 2000 mg/kg (approximately five times the maximum daily human dose on a mg/m2 of body surface area basis).

Teratogenesis

Gatiraban did not increase the incidence of malformations, compared to controls, in the offspring of mice, rats, or rabbits at doses up to 50, 30 and 25 times respectively, the daily human dose of 3600 mg, (four, five or eight times, respectively, the human daily dose on a mg/m2 basis).

Gatiraban induced delayed ossification in the skull, vertebrae, forelimbs, and hindlimbs in rodents, indicative of foetal growth retardation. These effects occurred when pregnant mice received oral doses of 1000 or 3000 mg/kg/day during organogenesis and in rats given 2000 mg/kg prior to and during mating and throughout gestation. These doses are approximately 1 to 5 times the human dose of 3600 mg on a mg/m2 basis.

No effects were observed in pregnant mice given 500 mg/kg/day (approximately 1/2 of the daily human dose on a mg/m2 basis).

An increased incidence of hydroureter and/or hydronephrosis was observed in rats given 2000 mg/kg/day in a fertility and general reproduction study, 1500 mg/kg/day in a teratology study, and 500, 1000, and 2000 mg/kg/day in a perinatal and postnatal study. The significance of these findings is unknown, but they have been associated with delayed development. These doses are also approximately 1 to 5 times the human dose of 3600 mg on a mg/m2 basis.

In a teratology study in rabbits, an increased incidence of post-implantation foetal loss, occurred in doses given 60, 300, and 1500 mg/kg/day during organogenesis. These doses are approximately 1/4 to 8 times the daily human dose of 3600 mg on a mg/m2 basis.

Incompatibilities

The information provided in Incompatibilities of Gatiraban is based on data of another medicine with exactly the same composition as the Gatiraban of the medicine (Gabapentin). Be careful and be sure to specify the information on the section Incompatibilities in the instructions to the drug Gatiraban directly from the package or from the pharmacist at the pharmacy.
more... close

Not applicable.

Special precautions for disposal and other handling

The information provided in Special precautions for disposal and other handling of Gatiraban is based on data of another medicine with exactly the same composition as the Gatiraban of the medicine (Gabapentin). Be careful and be sure to specify the information on the section Special precautions for disposal and other handling in the instructions to the drug Gatiraban directly from the package or from the pharmacist at the pharmacy.
more... close

No special requirements.