This is my 48th powerpoint...it deals with the drug profiles of LACOSAMIDE & PREGABALIN (2 anti-epileptic drugs), their pharmacological profiles & role in neuropathic pain.. Happy reading!! :)

1. PRESENTED BY: VISHNU.R.NAIR, FATHIMA SHARIN, MANEESHA DOMINIC
SUBJECT OF INTEREST: PROJECT WORK
NATIONAL COLLEGE OF PHARMACY(NCP).

2. 1. CLASS
2. MECHANISM OF ACTION
3. ADRs
4. CONTRAINDICATIONS & WARNINGS
5. INTERACTIONS
6. PREGNANCY & LACTATION
7. DOSAGE REGIMEN
8. DOSAGE ADJUSTMENTS
9. MONITORING PARAMETERS
10. PATIENT COUNSELLING TIPS

3. PREGABALIN

4. 1. CLASS: ANTI-CONVULSANT, GABA
ANALOGUE.
2. MECHANISM OF ACTION:
- Drug  binds to ALPHA-2-DELTA SUBUNIT OF VOLTAGE-GATED CALCIUM
CHANNELS in CNS  Increases GABA levels  produces ANTI-CONVULSIVE
EFFECTS
- Does NOT AFFECT SODIUM CHANNELS
- Drug  interacts with descending NORADRENERGIC & 5-HT
pathways(originating from brainstem)  REDUCES NEUROPATHIC PAIN
TRANSMISSION from SPINAL CORD.
3. ADRs:
a. Dizziness (8-45%)
b. Somnolence (4-36%)
c. Peripheral edema (16%)

5. d. Ataxia (1-20%)
e. Fatigue (5-11%)
f. Xerostomia (1-15%)
g. Weight gain (16%)
h. Tremor (11%)
i. Blurred vision(1-12%)
j. Diplopia (12 %)
k. Facial edema (1-10%)
l. Euphoria (1-10%).

6. 4. CONTRAINDICATIONS & WARNINGS:
- Hypersensitivity
- Use with CAUTION in the following:
a. CHF
b. Bleeding disorders
c. Patients, with ANGIOEDEMA
- Pregabalin may increase the risk of:
a. PR interval prolongation
b. Rhabdomyolysis
c. Physical dependence.

7. 5. INTERACTIONS:*
a. PREGABALIN + ACE-INHIBITORS, SIROLIMUS, EVEROLIMUS  High
risk of developing ANGIOEDEMA of FACE, MOUTH & NECK  May cause
RESPIRATORY COLLAPSE.
b. PREGABALIN + CLOBAZAM  Increases potential for CNS EFFECTS(High
sedation, respiratory depression).
* Occurs on concomitant administration.

8. 6. PREGNANCY & LACTATION :
- Category “C”
- Excretion of drug through breast milk is unknown thus not recommended in
lactation
7. DOSAGE REGIMEN:
ADULT DOSAGE:
A. For DIABETIC NEUROPATHY: (ORALLY)
- Initially  75 mg BD  Increase dose to 150 mg BD within 1 week  increase
dose to 300 mg BD , after 2-3 weeks(if required)
- Max. dose : 600 mg/day.

9. B. FOR POST-HERPETIC NEURALGIA: (ORALLY)
- Initially  150 mg (in divided doses) BD/TD  Can increase dose to 300 mg/day
(in divided doses) BD/TD, within 1 week  can increase dose to 600 mg/day, in
divided doses, BD/TD, after 2-3 weeks(if required)
- Max. dose: 600 mg/day.
C. FOR PARTIAL SEIZURES(ADJUNCTIVE THERAPY, ORALLY):
- Initially  150 mg/day , in divided doses , BD/TD
- Max. dose : 600 mg/day.
D. FOR FIBROMYALGIA(ORALLY):
- Initially  150 mg/day, in divided doses, BD/TD, within 1 week  increase dose
to 600 mg in divided doses, BD/TD.
- Max. dose: 600 mg/day.
PEDIATRIC DOSAGE: Safety & efficacy have not been established.

10. 8. DOSAGE ADJUSTMENTS:
A. FOR HEPATIC IMPAIRMENT: Not necessary.
B. FOR RENAL IMPAIRMENT:
I. If CrCl = 30-60 ml/min:
- Reduce usual dose by 50%, administered in divided doses (BD/TD)
II. If CrCl = 15-30 ml/min:
- For 150 mg/day dose: reduce dose to 25-50 mg/day, given OD/ in divided
doses(BD/TD)
- For 300 mg/day dose: reduce dose to 75 mg/day, given OD/ in divided
doses(BD/TD)
- For 450 mg/day dose: reduce dose to 100-150 mg/day, given OD/ in divided doses
(BD/TD)
- For 600 mg/day dose: reduce dose to 150 mg/day, given OD/ in divided doses
(BD/TD).

11. III. If CrCl < 15 ml/min:
- For 150 mg/day dose reduce dose to 25 mg/day , OD
- For 300 mg/day dose reduce dose to 25-50 mg/day, OD
- For 450 mg/day dose  reduce dose to 50-75 mg/day, OD
- For 600 mg/day dose  reduce dose to 75 mg/day, OD.
9. MONITORING PARAMETERS:
- Tests required, include:
a. ECG(To monitor PR-Interval)
b. Eye examination
c. Platelet count
d. Serum Creatine Kinase concentration.

12. - Monitor for the following:
a. Seizure activity
b. Dizziness
c. Depression
d. Suicidal ideation
e. Psychotic & behavioral changes
f. Drug abuse
g. Peripheral edema
h. Weight gain
i. Rhabdomyolysis
j. Hypersensitivity.

13. 10. PATIENT COUNSELLING TIPS:
a. Drug can be taken with/without food
b. Avoid alcohol intake
c. Avoid activities, that require mental alertness and motor co-ordination
d. Avoid abrupt drug withdrawal.

14. LACOSAMIDE

15. 1. CLASS :ANTICONVULSANT,
HOMOSERINAMIDE DERIVATIVE.
2. MECHANISM OF ACTION:
- Drug  slowly inactivates voltage-gated SODIUM CHANNELS
- Drug  binds to CRMP-2(Collapsin response mediator protein-2)  produces
anticonvulsive effects
- CRMP-2 is a phosphoprotein, expressed in CNS, involved in NEURONAL
DIFFERENTIATION, and control of axonal outgrowth.

16. 3. ADRs:
A. >10%:
- Headache
- Nausea
- Dizziness
- Diplopia
B. 1-10%:
- Vomiting - Increased ALT levels.
- Flatulence
- Blurred vision
- Tremor
- Memory impairment
- Balance disorder

17. C. <1%:
- Atrial flutter
- Atrial fibrillation
- AV block
- Cerebellar syndrome
- Mood changes
- TEN
- SJS
- Psychosis
- Aggression.

18. 4. CONTRAINDICATIONS & WARNINGS:
- Contraindicated in hypersensitivity to lacosamide, phenylalanine
- Use with caution in the following:
a. Cardiac disease
b. Cardiac function defects
c. Diabetic neuropathy
- High risk of the following:
a. Suicidal thoughts and behavior
b. PR-interval prolongation(Dose-dependent)
c. Dizziness
d. Ataxia.

19. 5. PREGNANCY & LACTATION :
- Pregnancy category: ‘C’
- Excretion in breast milk is unknown  thus not recommended.
6. DRUG INTERACTIONS:
a. Lacosamide + Rifampicin  low levels of former
b. Lacosamide + Deutetrabenazine  increased sedation
c. Lacosamide + Piroxicam  high levels of former  reduce dose of Lacosamide,
when giving concurrently with CYP2C9 INHIBITORS.

20. 7. DOSAGE REGIMEN:
ADULT DOSAGE:
A. FOR PARTIAL-ONSET SEIZURES(MONOTHERAPY; ORALLY/I.V):
- Initially  100 mg BD  Then increase dose to 150-200 mg BD, (by 50 mg every
week)
- Max. dose : 400 mg/day.
B. FOR PARTIAL-ONSET SEIZURES(ADJUNCTIVE THERAPY; ORALLY/I.V):
- Initially  50 mg BD  Then increase dose to 100-200 mg BD, (by 50 mg every
week).
- Max. dose: 400 mg/day.
C. FOR NEUROPATHIC PAIN(ORALLY):
- Initially  50 mg BD  Then increase dose to 200-300 mg BD, subsequently.

21. PEDIATRIC DOSAGE:
A. FOR ADJUNCTIVE TREATMENT OF FOCAL SEIZURES, WITH/WITHOUT
SECONDARY GENERALIZATION(ORALLY):
- Initially  0.5 mg/kg BD  Increase dose every 1-2 weeks by 1 mg/kg/day
- Max. dose: 10 mg/kg/day; or 200 mg BD.
- Restricted for SPECIALIST USE in REFRACTORY EPILEPSY
- Do not stop abruptly.

22. 8. DOSAGE ADJUSTMENTS:
FOR HEPATIC IMPAIRMENT:
- For mild impairment  adjust dose; titrate gradually. Max. dose: 300 mg/day
- For severe impairment  not recommended.
FOR RENAL IMPAIRMENT:
- For mild-moderate impairment  not necessary
- If CrCl <30 ml/min  titrate gradually. Max. dose: 300 mg/day
- For HEMODIALYSIS : Supplement with upto 50% of usual dose, post
hemodialysis.

23. 9. MONITORING PARAMETERS:
- Tests required include:
a. ECG
- Monitor for the following:
a. Depression
b. Suicidal ideation
c. Psychotic & behavioral changes
d. Dizziness
e. Ataxia
f. Syncope(in patients, with diabetic neuropathy)
g. Multi-organ hypersensitivity.

24. 10. PATIENT COUNSELLING TIPS:
a. Can be taken with/without food
b. Avoid alcohol intake
c. Avoid activities, that require mental alertness and motor coordination
d. Avoid abrupt drug withdrawal.

25. THANK YOU !!!!!!