India Product

Nuroace p Tablets

Nuroace p Tablets

Nuroace p Tablets

Why you have been prescribed this medicine?

You have been prescribed this medicine if you have any of the following:
• It is used for neuropathic pain associated with spinal cord injury.
• Diabetic peripheral neuropathy.
• Treatment of fibromyalgia.
• It is also used for treatment of chronic pain, perioperative pain, and migraine.

When you should consult your doctor?

You should consult your doctor if you experience any of the following:

In table 2 below all adverse reactions, which occurred at an incidence greater than placebo and in more than one patient, are listed 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), not known (cannot be estimated from the available data).

System Organ Class

Adverse drug reactions

Infections and infestations

Common

Nasopharyngitis

Blood and lymphatic system disorders

Uncommon

Neutropaenia

Immune system disorders

Uncommon

Hypersensitivity

Rare

Angioedema, allergic reaction

Metabolism and nutrition disorders

Common

Appetite increased

Uncommon

Anorexia, hypoglycaemia

Psychiatric disorders

Common

Euphoric mood, confusion, irritability, disorientation, insomnia, libido decreased

Uncommon

Hallucination, panic attack, restlessness, agitation, depression, depressed mood, elevated mood, aggression, mood swings, depersonalization, word finding difficulty, abnormal dreams, libido increased, anorgasmia, apathy

Rare

 

Disinhibition

Nervous system disorders

Very Common


Dizziness, somnolence, headache

Common

Ataxia, coordination abnormal, tremor, dysarthria, amnesia, memory impairment, disturbance in attention, paraesthesia, hypoaesthesia, sedation, balance disorder, lethargy

Uncommon

Syncope, stupor, myoclonus, loss of consciousness, psychomotor hyperactivity, dyskinesia, dizziness postural, intention tremor, nystagmus, cognitive disorder,mental impairment, speech disorder, hyporeflexia, hyperaesthesia, burning sensation, ageusia, malaise

Rare

Convulsions, parosmia, hypokinesia, dysgraphia

Eye disorders

Common


Vision blurred, diplopia

Uncommon

Peripheral vision loss, visual disturbance, eye swelling, visual field defect, visual acuity reduced, eye pain, asthenopia, photopsia, dry eye, lacrimation increased, eye irritation

Rare

Vision loss, keratitis, oscillopsia, altered visual depth perception, mydriasis, strabismus, visual brightness

Ear and labyrinth disorders

Common

Vertigo

Uncommon

Hyperacusis

Cardiac disorders

Uncommon

Tachycardia, atrioventricular block first degree, sinus bradycardia, congestive heart failure

Rare

QT prolongation, sinus tachycardia, sinus arrhythmia

Vascular disorders

Uncommon

Hypotension, hypertension, hot flushes, flushing, peripheral coldness

Respiratory, thoracic and mediastinal disorders

Uncommon

Dyspnoea, epistaxis, cough, nasal congestion, rhinitis, snoring, nasal dryness

Rare

Pulmonary oedema, throat tightness

Gastrointestinal disorders

Common

Vomiting, nausea, constipation, diarrhoea, flatulence, abdominal distension, dry mouth

Uncommon

Gastrooesophageal reflux disease, salivary hypersecretion, hypoaesthesia oral

Rare

Ascites, pancreatitis, swollen tongue, dysphagia

Skin and subcutaneous tissue disorders

Uncommon

Rash papular, urticaria, hyperhidrosis, pruritus

Rare

Stevens Johnson syndrome, cold sweat

Musculoskeletal and connective tissue disorders

Common

Muscle cramp, arthralgia, back pain, pain in limb, cervical spasm

Uncommon

Joint swelling, myalgia, muscle twitching, neck pain, muscle stiffness

Rare

Rhabdomyolysis

Renal and urinary disorders

Uncommon

Urinary incontinence, dysuria

Rare

Renal failure, oliguria, urinary retention

Reproductive system and breast disorders

Common

Erectile dysfunction

Uncommon

Sexual dysfunction, ejaculation delayed, dysmenorrhoea, breast pain

Rare

Amenorrhoea, breast discharge, breastenlargement, gynaecomastia

General disorders and administration site conditions

Common

Oedema peripheral, oedema, gait abnormal, fall, feeling drunk, feeling abnormal, fatigue

Uncommon

Generalisedoedema, face oedema, chest tightness, pain, pyrexia, thirst, chills, asthenia

Investigations

Common

Weight increased

Uncommon

Blood creatine phosphokinase increased, alanine aminotransferase increased, aspartate aminotransferase increased, blood glucose increased, platelet count decreased, blood creatinine increased, blood potassium decreased, weight decreased

Rare

White blood cell count decreased

After discontinuation of short-term and long-term treatment with pregabalin withdrawal symptoms have been observed in some patients. The following reactions have been mentioned: insomnia, headache, nausea, anxiety, diarrhoea, flu syndrome, convulsions, nervousness, depression, pain, hyperhidrosis and dizziness, suggestive of physical dependence. The patient should be informed about this at the start of the treatment.
Concerning discontinuation of long-term treatment of pregabalin, data suggest that the incidence and severity of withdrawal symptoms may be dose-related.

What to do if you miss a dose?

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to. Otherwise take it as soon as you remember and then go back to taking it as you would normally.

Things you MUST NOT DO while on this medicine?

Pregabalin is contraindicated in patients with known hypersensitivity to pregabalin or any of its components. Vitamin B12 supplementation is generally regarded as safe during pregnancy and lactation.
Methylcobalamin:
It must be used with caution by patients with cardiovascular disease. It was found that after coronary stenting, intravenous loading doses of folic acid, vitamin B6 and vitamin B12, followed by daily oral administration to increase the risk of restenosis (re-narrowing of the blood vessels). Therefore, because of the potential harm, this combination of vitamins cannot be recommended for patients with coronary stents.
It must be used with caution by patients with high blood pressure, as reported on the blood pressure increase after intravenous administration of hydroxycobalamin.
Pregabalin:
Diabetic patients
In accordance with current clinical practice, some diabetic patients who gain weight on pregabalin treatment may need to adjust hypoglycaemic medicinal products.
Hypersensitivity reactions
There have been reports in the postmarketing experience of hypersensitivity reactions, including cases of angioedema. Pregabalin should be discontinued immediately if symptoms of angioedema, such as facial, perioral, or upper airway swelling occur.
Dizziness, somnolence, loss of consciousness, confusion, and mental impairment
Pregabalin treatment has been associated with dizziness and somnolence, which could increase the occurrence of accidental injury (fall) in the elderly population. There have also been postmarketing reports of loss of consciousness, confusion and mental impairment. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medicinal product
Vision-related effects
In controlled trials, a higher proportion of patients treated with pregabalin reported blurred vision than did patients treated with placebo which resolved in a majority of cases with continued dosing. In the clinical studies where ophthalmologic testing was conducted, the incidence of visual acuity reduction and visual field changes was greater in pregabalin-treated patients than in placebo-treated patients; the incidence of fundoscopic changes was greater in placebo-treated patients
In the postmarketing experience, visual adverse reactions have also been reported, including loss of vision, visual blurring or other changes of visual acuity, many of which were transient. Discontinuation of pregabalin may result in resolution or improvement of these visual symptoms.
Renal failure
Cases of renal failure have been reported and in some cases discontinuation of pregabalin did show reversibility of this adverse reaction.
Withdrawal of concomitant anti-epileptic medicinal products
There are insufficient data for the withdrawal of concomitant anti-epileptic medicinal products, once seizure control with pregabalin in the add-on situation has been reached, in order to reach monotherapy on pregabalin.
Withdrawal symptoms
After discontinuation of short-term and long-term treatment with pregabalin, withdrawal symptoms have been observed in some patients. The following events have been mentioned: insomnia, headache, nausea, anxiety, diarrhoea, flu syndrome, nervousness, depression, pain, convulsion, hyperhidrosis and dizziness, suggestive of physical dependence. The patient should be informed about this at the start of the treatment.
Convulsions, including status epilepticus and grand mal convulsions, may occur during pregabalin use or shortly after discontinuing pregabalin.
Concerning discontinuation of long-term treatment of pregabalin, data suggest that the incidence and severity of withdrawal symptoms may be dose-related
Congestive heart failure
There have been post marketing reports of congestive heart failure in some patients receiving pregabalin. These reactions are mostly seen in elderly cardiovascular compromised patients during pregabalin treatment for a neuropathic indication. Pregabalin should be used with caution in these patients. Discontinuation of pregabalin may resolve the reaction.
Treatment of central neuropathic pain due to spinal cord injury
In the treatment of central neuropathic pain due to spinal cord injury the incidence of adverse reactions in general, central nervous system adverse reactions and especially somnolence was increased. This may be attributed to an additive effect due to concomitant medicinal products (e.g. anti-spasticity agents) needed for this condition. This should be considered when prescribing pregabalin in this condition
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 studies 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 pregabalin.
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.
Reduced lower gastrointestinal tract function
There are postmarketing reports of events related to reduced lower gastrointestinal tract function (e.g. intestinal obstruction, paralytic ileus, constipation) when pregabalin was co-administered with medications that have the potential to produce constipation, such as opioid analgesics. When pregabalin and opioids will be used in combination, measures to prevent constipation may be considered (especially in female patients and elderly)
Misuse, abuse potential or dependence
Cases of misuse, abuse and dependence have been reported. Caution should be exercised in patients with a history of substance abuse and the patient should be monitored for symptoms of pregabalin misuse, abuse or dependence (development of tolerance, dose escalation, drug-seeking behaviour have been reported)
Encephalopathy
Cases of encephalopathy have been reported, mostly in patients with underlying conditions that may precipitate encephalopathy.
Lactose intolerance
Nuroace-P contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Fertility, pregnancy and lactation
Women of childbearing potential / Contraception in males and females
As the potential risk for humans is unknown, effective contraception must be used in women of child bearing potential.
Fertility
There are no clinical data on the effects of pregabalin on female fertility.
In a clinical trial to assess the effect of pregabalin on sperm motility, healthy male subjects were exposed to pregabalin at a dose of 600 mg/day. After 3 months of treatment, there were no effects on sperm motility.
A fertilty study in female rats has shown adverse reproductive effects. Fertility studies in male rats have shown adverse reproductive and developmental effects. The clinical relevance of these findings is unknown.
Effects on ability to drive and use machines
Nuroace-P may have minor or moderate influence on the ability to drive and use machines. Nuroace-P may cause dizziness and somnolence and therefore may influence the ability to drive or use machines. Patients are advised not to drive, operate complex machinery or engage in other potentially hazardous activities until it is known whether this medicinal product affects their ability to perform these activities.

 

What to do if you accidentally take too much (overdose) of the medicine?

In the post marketing experience, the most commonly reported adverse reactions observed when pregabalin was taken in overdose included somnolence, confusional state, agitation, and restlessness. In rare occasions, cases of coma have been reported.
Treatment of Neuroace -P overdose should include general supportive measures and may include haemodialysis if necessary.

Is it safe in pregnancy and breast-feeding?

Pregnancy
There are no adequate data from the use of pregabalin in pregnant women.
Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown.
Nuroace-P should not be used during pregnancy unless clearly necessary (if the benefit to the mother clearly outweighs the potential risk to the foetus).
Breast-feeding
Pregabalin is excreted into human milk (see section 5.2). The effect of pregabalin on newborns/infants is unknown.A decision must be made whether to discontinue breast-feeding or to discontinue pregabalin therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Storage Conditions:

Store below 30° C. Keep away from moisture.

Drug Description

Composition:
One Capsule contains
Active substance: Pregabalin………75 mg
Methylcobalamin…………………….750 mcg
Description:
Hard gelatin size ‘4’ capsules with red color cap and opaque white body, containing light pink to pink colored granular powder.

Indications and dosage.

 

Indications

  • It is used for neuropathic pain associated with spinal cord injury.
  • Diabetic peripheral neuropathy.
  •  Treatment of fibromyalgia.
  •  It is also used for treatment of chronic pain, perioperative pain, and migraine.

Dosage:
Route of administration: Oral

Posology
The dose is 1 tablet twice daily.
Neuropathic pain
It should be started as twice daily dose. The dose can be continued till symptoms last.
It should not be stopped suddenly without consultation of physician.
Discontinuation of therapy
In accordance with current clinical practice, if pregabalin has to be discontinued it is recommended this should be done gradually over a minimum of 1 week independent of the indication
Patients with renal impairment
Methylcobalamin does not require any dose adjustment. Dose adjustment should be done as per pregabalin dose.
Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug. As pregabalin clearance is directly proportional to creatinine clearance (see section 5.2), dose reduction in patients with compromised renal function must be individualised according to creatinine clearance (CLcr), as indicated in Table 1 determined using the following formula:
https://www.medicines.org.uk/emc/images/spc~14651~37~113247A.GIF
Pregabalin is removed effectively from plasma by haemodialysis (50% of drug in 4 hours). For patients receiving haemodialysis, the pregabalin daily dose should be adjusted based on renal function. In addition to the daily dose, a supplementary dose should be given immediately following every 4-hour haemodialysis treatment.

Table 1.Pregabalin dose adjustment based on renal function.


Creatinine clearance (CLcr) (ml/min)

Total pregabalin daily dose*

Dose regimen

 

Starting dose (mg/day)

Maximum dose (mg/day)

 

≥ 60

150

600

BID

≥ 30 - < 60

75

300

BID

≥ 15 - < 30

25-50

150

Once daily or BID

< 15

25

75

Once daily

Supplementary dosage following haemodialysis (mg)

 

25

100

Single dose+

BID = Two divided doses
* Total daily dose (mg/day) should be divided as indicated by dose regimen to provide mg/dose
+ Supplementary dose is a single additional dose

Patients with hepatic impairment
No dose adjustment is required for patients with hepatic impairment
Paediatric population
The safety and efficacy of Nuroace-P in children below the age of 12 years and in adolescents (12-17 years of age) have not been established.
Elderly (over 65 years of age) population
Elderly patients may require a dose reduction of pregabalin due to a decreased renal function.
Method of administration
Nuroace-P may be taken with or without food.
Nuroace-P is for oral use only

Children. The medicine is not recommended in children under 17 years.

Side effects and drug interactions.

Side effect
Table 2: Adverse drug reactions

In table 2 below all adverse reactions, which occurred at an incidence greater than placebo and in more than one patient, are listed 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), not known (cannot be estimated from the available data).

 

System Organ Class

Adverse drug reactions

Infections and infestations

Common

Nasopharyngitis

Blood and lymphatic system disorders

Uncommon

Neutropaenia

Immune system disorders

Uncommon

Hypersensitivity

Rare

Angioedema, allergic reaction

Metabolism and nutrition disorders

Common

Appetite increased

Uncommon

Anorexia, hypoglycaemia

Psychiatric disorders

Common

Euphoric mood, confusion, irritability, disorientation, insomnia, libido decreased

Uncommon

Hallucination, panic attack, restlessness, agitation, depression, depressed mood, elevated mood, aggression, mood swings, depersonalisation, word finding difficulty, abnormal dreams, libido increased, anorgasmia, apathy

Rare


Disinhibition

Nervous system disorders

Very Common


Dizziness, somnolence, headache

Common

Ataxia, coordination abnormal, tremor, dysarthria, amnesia, memory impairment, disturbance in attention, paraesthesia, hypoaesthesia, sedation, balance disorder, lethargy

Uncommon

Syncope, stupor, myoclonus, loss of consciousness, psychomotor hyperactivity, dyskinesia, dizziness postural, intention tremor, nystagmus, cognitive disorder,mental impairment, speech disorder, hyporeflexia, hyperaesthesia, burning sensation, ageusia, malaise

Rare

Convulsions, parosmia, hypokinesia, dysgraphia

Eye disorders

Common


Vision blurred, diplopia

Uncommon

Peripheral vision loss, visual disturbance, eye swelling, visual field defect, visual acuity reduced, eye pain, asthenopia, photopsia, dry eye, lacrimation increased, eye irritation

Rare

Vision loss, keratitis, oscillopsia, altered visual depth perception, mydriasis, strabismus, visual brightness

Ear and labyrinth disorders

Common

Vertigo

Uncommon

Hyperacusis

Cardiac disorders

Uncommon

Tachycardia, atrioventricular block first degree, sinus bradycardia, congestive heart failure

Rare

QT prolongation, sinus tachycardia, sinus arrhythmia

Vascular disorders

Uncommon

Hypotension, hypertension, hot flushes, flushing, peripheral coldness

Respiratory, thoracic and mediastinal disorders

Uncommon

Dyspnoea, epistaxis, cough, nasal congestion, rhinitis, snoring, nasal dryness

Rare

Pulmonary oedema, throat tightness

Gastrointestinal disorders

Common

Vomiting, nausea, constipation, diarrhoea, flatulence, abdominal distension, dry mouth

Uncommon

Gastrooesophageal reflux disease, salivary hypersecretion, hypoaesthesia oral

Rare

Ascites, pancreatitis, swollen tongue, dysphagia

Skin and subcutaneous tissue disorders

Uncommon

Rash papular, urticaria, hyperhidrosis, pruritus

Rare

Stevens Johnson syndrome, cold sweat

Musculoskeletal and connective tissue disorders

Common

Muscle cramp, arthralgia, back pain, pain in limb, cervical spasm

Uncommon

Joint swelling, myalgia, muscle twitching, neck pain, muscle stiffness

Rare

Rhabdomyolysis

Renal and urinary disorders

Uncommon

Urinary incontinence, dysuria

Rare

Renal failure, oliguria, urinary retention

Reproductive system and breast disorders

Common

Erectile dysfunction

Uncommon

Sexual dysfunction, ejaculation delayed, dysmenorrhoea, breast pain

Rare

Amenorrhoea, breast discharge, breastenlargement, gynaecomastia

General disorders and administration site conditions

Common

Oedema peripheral, oedema, gait abnormal, fall, feeling drunk, feeling abnormal, fatigue

Uncommon

Generalisedoedema, face oedema, chest tightness, pain, pyrexia, thirst, chills, asthenia

Investigations

Common

Weight increased

Uncommon

Blood creatine phosphokinase increased, alanine aminotransferase increased, aspartate aminotransferase increased, blood glucose increased, platelet count decreased, blood creatinine increased, blood potassium decreased, weight decreased

Rare

White blood cell count decreased

After discontinuation of short-term and long-term treatment with pregabalin withdrawal symptoms have been observed in some patients. The following reactions have been mentioned: insomnia, headache, nausea, anxiety, diarrhoea, flu syndrome, convulsions, nervousness, depression, pain, hyperhidrosis and dizziness, suggestive of physical dependence. The patient should be informed about this at the start of the treatment.
Concerning discontinuation of long-term treatment of pregabalin, data suggest that the incidence and severity of withdrawal symptoms may be dose-related.

Drug interactions
Before taking this medicine tell the doctor about any medical problems an allergies that patient has now or has had.
Usually drug interactions occur when it is taken with another drug or with food. Before you take a medication for a particular ailment, you should inform the health expert about intake of any other medications including non-prescription medications.

Warnings and precautions


Methylcobalamin:
It must be used with caution by patients with cardiovascular disease. It was found that after coronary stenting, intravenous loading doses of folic acid, vitamin B6 and vitamin B12, followed by daily oral administration to increase the risk of restenosis (re-narrowing of the blood vessels). Therefore, because of the potential harm, this combination of vitamins cannot be recommended for patients with coronary stents.
It must be used with caution by patients with high blood pressure, as reported on the blood pressure increase after intravenous administration of hydroxycobalamin.
Pregabalin:
Diabetic patients
In accordance with current clinical practice, some diabetic patients who gain weight on pregabalin treatment may need to adjust hypoglycaemic medicinal products.
Hypersensitivity reactions
There have been reports in the postmarketing experience of hypersensitivity reactions, including cases of angioedema. Pregabalin should be discontinued immediately if symptoms of angioedema, such as facial, perioral, or upper airway swelling occur.
Dizziness, somnolence, loss of consciousness, confusion, and mental impairment
Pregabalin treatment has been associated with dizziness and somnolence, which could increase the occurrence of accidental injury (fall) in the elderly population. There have also been postmarketing reports of loss of consciousness, confusion and mental impairment. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medicinal product
Vision-related effects
In controlled trials, a higher proportion of patients treated with pregabalin reported blurred vision than did patients treated with placebo which resolved in a majority of cases with continued dosing. In the clinical studies where ophthalmologic testing was conducted, the incidence of visual acuity reduction and visual field changes was greater in pregabalin-treated patients than in placebo-treated patients; the incidence of fundoscopic changes was greater in placebo-treated patients
In the postmarketing experience, visual adverse reactions have also been reported, including loss of vision, visual blurring or other changes of visual acuity, many of which were transient. Discontinuation of pregabalin may result in resolution or improvement of these visual symptoms.
Renal failure
Cases of renal failure have been reported and in some cases discontinuation of pregabalin did show reversibility of this adverse reaction.
Withdrawal of concomitant anti-epileptic medicinal products
There are insufficient data for the withdrawal of concomitant anti-epileptic medicinal products, once seizure control with pregabalin in the add-on situation has been reached, in order to reach monotherapy on pregabalin.
Withdrawal symptoms
After discontinuation of short-term and long-term treatment with pregabalin, withdrawal symptoms have been observed in some patients. The following events have been mentioned: insomnia, headache, nausea, anxiety, diarrhoea, flu syndrome, nervousness, depression, pain, convulsion, hyperhidrosis and dizziness, suggestive of physical dependence. The patient should be informed about this at the start of the treatment.
Convulsions, including status epilepticus and grand mal convulsions, may occur during pregabalin use or shortly after discontinuing pregabalin.
Concerning discontinuation of long-term treatment of pregabalin, data suggest that the incidence and severity of withdrawal symptoms may be dose-related
Congestive heart failure
There have been post marketing reports of congestive heart failure in some patients receiving pregabalin. These reactions are mostly seen in elderly cardiovascular compromised patients during pregabalin treatment for a neuropathic indication. Pregabalin should be used with caution in these patients. Discontinuation of pregabalin may resolve the reaction.
Treatment of central neuropathic pain due to spinal cord injury
In the treatment of central neuropathic pain due to spinal cord injury the incidence of adverse reactions in general, central nervous system adverse reactions and especially somnolence was increased. This may be attributed to an additive effect due to concomitant medicinal products (e.g. anti-spasticity agents) needed for this condition. This should be considered when prescribing pregabalin in this condition
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 studies 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 pregabalin.
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.
Reduced lower gastrointestinal tract function
There are postmarketing reports of events related to reduced lower gastrointestinal tract function (e.g. intestinal obstruction, paralytic ileus, constipation) when pregabalin was co-administered with medications that have the potential to produce constipation, such as opioid analgesics. When pregabalin and opioids will be used in combination, measures to prevent constipation may be considered (especially in female patients and elderly)
Misuse, abuse potential or dependence
Cases of misuse, abuse and dependence have been reported. Caution should be exercised in patients with a history of substance abuse and the patient should be monitored for symptoms of pregabalin misuse, abuse or dependence (development of tolerance, dose escalation, drug-seeking behaviour have been reported)
Encephalopathy
Cases of encephalopathy have been reported, mostly in patients with underlying conditions that may precipitate encephalopathy.
Lactose intolerance
Nuroace-P contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Fertility, pregnancy and lactation
Women of childbearing potential / Contraception in males and females
As the potential risk for humans is unknown, effective contraception must be used in women of child bearing potential.
Pregnancy
There are no adequate data from the use of pregabalin in pregnant women.
Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown.
Nuroace-P should not be used during pregnancy unless clearly necessary (if the benefit to the mother clearly outweighs the potential risk to the foetus).
Breast-feeding
Pregabalin is excreted into human milk (see section 5.2). The effect of pregabalin on newborns/infants is unknown.A decision must be made whether to discontinue breast-feeding or to discontinue pregabalin therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Fertility
There are no clinical data on the effects of pregabalin on female fertility.
In a clinical trial to assess the effect of pregabalin on sperm motility, healthy male subjects were exposed to pregabalin at a dose of 600 mg/day. After 3 months of treatment, there were no effects on sperm motility.
A fertilty study in female rats has shown adverse reproductive effects. Fertility studies in male rats have shown adverse reproductive and developmental effects. The clinical relevance of these findings is unknown.
Effects on ability to drive and use machines
Nuroace-P may have minor or moderate influence on the ability to drive and use machines. Nuroace-P may cause dizziness and somnolence and therefore may influence the ability to drive or use machines. Patients are advised not to drive, operate complex machinery or engage in other potentially hazardous activities until it is known whether this medicinal product affects their ability to perform these activities.

Overdosage and Contraindications

In the postmarketing experience, the most commonly reported adverse reactions observed when pregabalin was taken in overdose included somnolence, confusional state, agitation, and restlessness. In rare occasions, cases of coma have been reported.
Treatment of Neuroace -P  overdose should include general supportive measures and may include haemodialysis if necessary.

Clinical pharmacology.

Pharmacotherapeutic group: Anti-epileptics, other anti-epileptics
ATC code: N03AX
Pharmacological properties.
Pharmacodynamics:
It binds to the α2δ (alpha2delta) subunit of the voltage-dependent calcium channel in the central nervous system. It help to decreases the release of neurotransmitters including glutamate, norepinephrine, substance P and calcitonin gene-related peptide. However, unlike anxiolytic compounds (e.g., benzodiazepines) which exert their therapeutic effects through binding to GABA, and benzodiazepine receptors. It neither binds directly to these receptors nor augments GABA currents or affects GABA metabolism. The half life for pregabalin is 6.3 hours. 

Mechanism of action
Combination of Pregabalin and Methylcobalamin not only decreases the release of neurotransmitters but also helps in regeneration of the myelin sheath. Pregabalin also has got analgesic activity which reduces the pain associated with neuropathy. Thus the combination of Pregabalin and Methylcobalamin is useful for arresting the progress of diabetic neuropathy and also helps in relieving the pain associated with neuropathy. Methylcobalamin is a co-factor of methionine synthase, an enzyme that transfers methyl groups to homocysteine to regenerate methionine. Elevated homocysteine levels are a risk factor for coronary artery disease. Methionine can be transformed to S-adenoxylmethionine (SAM) that is involved in a variety of methylation reactions in the body, one of which is alleviating depression. 
Pharmacokinetics:
Pharmacokinetics of Pregabalin
Absorption: Pregabalin is rapidly absorbed when administered on an empty stomach, with peak plasma concentrations occurring within one hour. Pregabalin oral bioavailability is estimated to be greater than or equal to 90% and is independent of dose. The rate of pregabalin absorption is decreased when given with food resulting in a decrease in Cmax by approximately 25 to 30% and a delay in Tmax to approximately 2.5 hours. Administration with food, however, has no clinically significant effect on the extent of absorption. 
Distribution: In humans, the volume of distribution of pregabalin for an orally administered dose is approximately 0.56 L/kg and is not bound to plasma proteins. 
Metabolism: Pregabalin undergoes negligible metabolism in humans. Approximately 98% of the radioactivity recovered in the urine was unchanged pregabalin. The major metabolite is N-methyl pregabalin.
 Excretion: Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug. Renal clearance of pregabalin is 73 mL/minute. 
Pharmacokinetics of Methylcobalamin
Mecobalamin is the neurologically active form of vitamin B12 and occurs as a water-soluble vitamin in the body. It is a cofactor in the enzyme methionine synthase, which functions to transfer methyl groups for the regeneration of methionine from homocysteine. In anaemia, it increases erythrocyte production by promoting nucleic acid synthesis in the bone marrow and by promoting maturation and division of erythrocytes. 
Absorption: Peak plasma concentrations after 3 hr (oral); 0.9 hr (IM); 3 min(IV). 
Excretion: Via urine. 
Shelf life:  2 years.
Storage condition
Store below 30° C. Keep away from moisture.
Package
Capsules are packed in Alu-Alu blister pack.
Conditions of supply
On prescription.

CERTIFICATES

KEEP IN TOUCH

Kusum Healthcare
D-158A, OKHLA,INDUSTRIAL AREA,
PHASE-I, NEW DELHI,
Pin 110020
INDIA
Tel: 011-41005147, 011-40514919
Fax: +91-11-40527575