Herbessor Tab Info
2
:- HERBESSER 90 SR r= HERBESSER 1q0 SR Capsules (Dilttazem HCI) COMPOSITIOil Herbesser 90 sR capsurei: Each capsure contains Dirtiazem Hydrochloride B.P. 90 mg in sustained release form. Herbesser 180 sR capsules: Each capsule contains Diltiazem . Hydrochloride B.p. 180mg insustainedreleaseform DESCRIPTION Herbesser (diltiazem hydrochloiide) is a calcium ion cellular influx inhibitor (slor channel blocker). PHARMACOLOGICAL PROPES|IES . The therapeutic effects of diltiazem hydrochloride are believed to be related to its. ability to inhibit the celluiar influx of calcium ions during membrane depolarizafion of cardiac and vascutar smooth,rnuscle. - NechanlsmsofAction Hwertension: Diltiazem produces its antihypertensive effect primarily by relaxation of vascular smooth muscle and the resultant decrease in peripheralvascular resistance. The magnitude oibtood pressure reduction is related to the degree of hyflertension: thus hypertensive individuals experience ai antirryf6rtensive efiect, whereas there is onry a modest fail in 6tboo pressure in normotensives. Angina: Diltiazem HCI has been shown to produce increases in exercise tolerance,. probably due to its ability to reduce myocardial oxygen demand. This is accomplished via reductions in heart rate and systemic blood pressure at submaximal and maximal work loads. Diltiazem has been shgwn !o be a potent dilator of coronary arteries, both epicardial and subendocardial. spontaneous ano erionJvine- induced coronary artery spasms are inrrioiteo by diltiazem. " Like other calcium channel antagonists, Herbessei decreases sinoatrial and atrioventricular conduction in isolated tissues and has a negative inotropic effect in isolated preparations. ln man, ueroeiser fre"vents spontaneous and ergonovine-provoked coronary artery spasm. lt causes a decrease in peripheral vascular resistahce and a modest fal I i n -bbod . pre$-.Ewe-in,oeqaot_eqgive ind ividuals ano. in_eierclse tolerance studies in patients with ischemic neirt aiielJilieouC6s tne heart rate-blood pressure product for any given work load. Theie are as yet few data on the interaction of diliiazem and beta-blockers in p.?tr.ents with poor ventricular function. Resting heart rate is usually slightly reduced by diltiazem. Herbesser produces antihypertensive effects both in the supine and standing positions. Postural hypotension is infrequenfly noied upon suddenly assuming.an upright position. No retiex tachycardia is associated with the chronic antihypertensive effects Diltiazem hydrochloride decreaies vascular resistance, increases cardiac output (by increasing stroke volume), and produces a iignt decrease or no change in heart rate. During dynamic e*eici6e, increases in diastolic pressure are inhibit6o wnite maiimu* achievable systolic pressure is usually reduced. chronic therapy with diltiazem hydrochloride produces no ihange or an increase in itisma catecholamines. No increased activity or tne renin-angioiensin- aldosterone axis has been observed. Diltiazem hydrichloride reduces the renal and peripheral effects of angiotensin ll. oiltiaiem- associated.prolongation of theAH intervalis n6t more pronounced in patients with first degree heart block. ln patients with sick sinus syndrome, diltiazem significanfly prorongs sinus cycre rength (up to 50% in some cases). Pharmacodynamics HyBertension: Herbesser demonstrates a dose-rerated antihypertensive response among patients with mild to moderate hypertension; supine diastolic bbob pressure as well as standing diastolic and systolic btood pressuies atso shows statiiiicalri significant linear dose response effects. 4qgina: Herbesser at doses of 120-540 rng/day increases exercise tolerance time. cornpared to baseline, xe-roeiser treated paiients experienced statistically significant reductions in anginal aftatks and decrea.sed nitroglycerin requirements when compired to placebo treated patients. P h a rm a coki netl c s a n d lletabo I i s m Diltiazem is well absorbed from the gastrointestinal tract but undergoes substantial hepatic first-pass 6rect. onty i"t" ii l"t, ot uncianged diltiazem appears in the urine. The plasma elimination half-life of diltiazem is approximatety 3.0 - 4.s h. Drugs which inJr"e T inhibit hepatic microsomal enzymes may ilter diltiazem disposition. Th_erapeutic blood levels of difiiazem ippear to ne in tne range of 40 - 2o0 ng/ml. There is a departure trdi'r rinearity when dose strengths are increased; the hatf-liie is slighfly increii6o witn dose. Jhe tw9 plr?ry rhetabotites of diltiazem are desacetyrdirtiazem and desmethyld i ltiazem. The desacety[ rnetabolite is apprbxima tity zsv" to 50% as potent a coronary vasodilatoras diltiazem'ano is preient in plasma at concentrations of t}yo ,to 2ao/o of pareni iiriiri".; however, recent studies have shown nine diltiazem metauoiit"s ir,at are excreted more slowly. ln vitro binding studies show diltiazem HCI )sl0o/o to g0% bound to plasma proteins. competitive in- vitro ligand binding stuoies nave also shown diltiazem HCr binding ts riot artered 6y tnlrapeltic concenkationq..'of. digoxin, hydrochlorothiazide, phenylbutazone, pnopranolol, salicylic acid, or warfarin. Herbesser.ca_psures: when compared to a regimen of immediate- rerease tablets at steady-state, approximately g3% of drug is absorbed from the Heroesser torlrr[ii"rl when Herbesser was co administered with a high fatcontent bred<fast, the extent of dittiaiem absorption was not affected; Tmax, however, occurred slighfly earlier. I["3qn31"nt elimination half-rife after singre or murtipre o"osingis a to 9.5 nours (mean 6.5 hours). Herbesser demonstrates.non-linear pharmacokinetics. As the daily dose of Herbesser capsuresis inqedseo fro* isdtoUri *g, tilr" was a more than proportional increase in diltiazem -piasma cqocentratio$s.as evidenced by an increase.of AU.e, cmax ana Cmin of 6'8,_6 and 8-6 times, respectivery, fora 4,s times in'crease in ooie. Druglnteractions Due b the potential for additive effecis, caution and careful titration are warranted in patients receiving diltiazem hydrochloride ::i1'l Ellv .ytn other ase nts khorn Io mect ca rdi# conirairil itv additive effects in prolonging AV conduction when using beta- blockers ordigitalis eoncomitanfly with Herbesser. As with alTdrugs, care should be exercised when treating patients with multi[b medications. Diltiazem is both a substrate and an inhibitor of ine cytochrome P-450 3A4 enzyme system. other drugs that are specific substrates, inhibitors, or inducers of the enzyme system may have a significant irnpact on the efficacy and side erea pronre ot aittiazem. Patients. taking other drugs that are substrates of cyp4sO 3A4, especially patients with renal and/or hepatic impairment, may require dosage adjustment wtren star{ing or stopping conc6mitinfly a{rqiqistered diltiazem in order to haintain bptimum therapeutit blood levels. BetaBlockers concomitant use of diltiazem hydrochtoride and beta-blockers is ysualy welltglerated, but available data are not suffcient to predict the effects of concomitant treatment in patients with left veniricular dysfunction or eardiac conduction abnormalities. Administration of diltiazem hydrochloride concomitanfly with propranotol displaced it trg1 ltr binding sites by dittiazem. tf combinationiherapy is initiated or withdrawn in conjunction with propranolol, an adjustment in the propranglol dose may be wananted. Basptroiie:Enhanced effects and increased toxicityof buspirone may !e possibte during concomitant administratio-n with' diltiazem. Subsequent dose adjustments may be necessary Ouiing co_ administratien, and should be based on ctinicalassessment. cimgtidine: Patients cunenfly receiving diltiazem therapy should be oarefully monitored for a change in pharmacological'6ffect when initiating and discontinuing therapy with cimetidine]An adjustment in the diltiazem dose may be waranted. Digitalis: lt is recommended that digoxin levels be monitored when initiating, adjusting,..and discontinuing diltiazem hydrochloride therapy to avoid possible over- or under-digitalization. Q u in id i ne : Monitori ng for quinidine adverse effects may be waranted and the dose adjusted accordingly. fupsthetics: when used concomitanuy, anesthetics and calcium channel blockers should be titrated carefully. Cyclospoiine: tf administered -eohiUrrenty, cyclosporine concentrations should be monitored, especially wh6n diitiazem therapy is initiated, adjusted, or discohtinueii. The effect of cyclosporine on diltiazem plasma concentrations has not been evaluated. Qa-hamazepiqe: Patients receiving these drugs concunenfly should be monitored for a potential drug interaction. Benzgdiazepines: coadministration with diltiazem can result in increased clinical gffects (e.g., prolonged sedation) of both midazolam and triazolam. bvastalin: Diltiazem plasma levels were not significanfly afiected by levestati n or pravastggl Bt!?mpin: Coadministratioi of dittiazem with rifampin or any kndi,vn CYP3A4 inducer should be avoided when possibli, and aliernative therapy eonsidered. INDICATIONS Hyperlension; Herbesser is indicated for the treatment of hypertension. lt may be used alone or in combination with other antihypertensive medications. Angina: Herbesser is indicated for the treatment of chrqnic stable angina. VariantAngina. DOSAGE AND ADITIIN ISTRATION Hypertension .?9o"g" neds to beadjusted bytitration to individuat pa$ent needs. When used as monolherapy, usual starting doses ari laO mg once daily. Maximum antihypertensive effect iJ usually ouserveo.-btr t4 days of chronic therapy; therefore, dosage adjustrnents shouli be scheduled accordingly. The usuat dosage ranle studied in clinical trials was 180 to 540 rrg once daily cunent clinical experience with 540 mg dose is limited; however, the dose may be increased to S40 mgoncedaily. Angina Dosages for the treatment of angina should be adjusted !o each patient's needs, starting with a dose of 1g0 mg once ilaily. lndividuii patients may respond to higher doses of up to 540 mg once daily. When necessa ry titration shou ld be carried out ov'er 7 to i 4 days. Cqocornifap t usa w tttt Q.the r G a rd I ov a s c u I a r Ag e nts sublingual llitroglycerin may be taken as requiieo to abort acute anginalattacks. Prophylactic short & rong acting nitrate therapy may be safery co- administered Beta-blockers are usually well tolerated. Herbesser has an additive antihypertensive effect when used with other antihypertensive agents. Therefore, the dosage of Herbesser or the concomitant antihypertensives may need to G adjusted when adding one to the other. Hypertensive or anginal .patients who are treated with other formuhtions of, Herbesser can safely be switched to Flerbesser capsules at the nearest eguivalent tbtat oalty dose. subsequent titration to higher or lorrer loses may, honev6r, oe neess"r,J anc, should be initiated as clinicafiy indicatdd. GONTRAINDICATIONS Diltiazem iscontrairdicated in . 1. patients with sick sinus syndrome except in the presence oJ a - functioningventricularpacemaker 2. patients with seeond- or third-degree AV block except in the presence of a functioning ventricular pacemakeri 3. patients with severe hypotension (less than 90 mm Hgsystolic), 4. Patientq who havq demonstrated hypgrsensitivity to ihe O*g,';nO patients with acute .rnygqardia[ infarctiqo And pulrn-onary congestion documented by x-ray on admission. STDEEFFECTS serious adverse reactions have been rare in studies with Herbesser. It should be recognized that patients with impaired ventricular function and cardiac conduction abnormalities have usually been excluded from thgse studies. The'adVerse rcactions, whethei or not drug.1.g1r1ra,,r?FgrteA in a n d/or cond u ction. pha rm Jcobg ic stud ies ino lcate tnai irr;;ffi;yd:
description
pharmacology of herbessor
Transcript of Herbessor Tab Info
:- HERBESSER 90 SRr= HERBESSER 1q0 SRCapsules
(Dilttazem HCI)
COMPOSITIOilHerbesser 90 sR capsurei: Each capsure contains DirtiazemHydrochloride B.P. 90 mg in sustained release form.Herbesser 180 sR capsules: Each capsule contains Diltiazem
. Hydrochloride B.p. 180mg insustainedreleaseform
DESCRIPTIONHerbesser (diltiazem hydrochloiide) is a calcium ion cellular influxinhibitor (slor channel blocker).
PHARMACOLOGICAL PROPES|IES. The therapeutic effects of diltiazem hydrochloride are believed to berelated to its. ability to inhibit the celluiar influx of calcium ions duringmembrane depolarizafion of cardiac and vascutar smooth,rnuscle. -NechanlsmsofActionHwertension: Diltiazem produces its antihypertensive effectprimarily by relaxation of vascular smooth muscle and the resultantdecrease in peripheralvascular resistance. The magnitude oibtoodpressure reduction is related to the degree of hyflertension: thushypertensive individuals experience ai antirryf6rtensive efiect,whereas there is onry a modest fail in 6tboo pressure innormotensives.Angina: Diltiazem HCI has been shown to produce increases inexercise tolerance,. probably due to its ability to reduce myocardialoxygen demand. This is accomplished via reductions in heart rateand systemic blood pressure at submaximal and maximal work loads.Diltiazem has been shgwn !o be a potent dilator of coronary arteries,both epicardial and subendocardial. spontaneous ano erionJvine-induced coronary artery spasms are inrrioiteo by diltiazem. "
Like other calciumchannel antagonists, Herbessei decreases sinoatrial andatrioventricular conduction in isolated tissues and has a negativeinotropic effect in isolated preparations. ln man, ueroeiser fre"ventsspontaneous and ergonovine-provoked coronary artery spasm. ltcauses a decrease in peripheral vascular resistahce and a modestfal I i n -bbod . pre$-.Ewe-in,oeqaot_eqgive ind ividuals ano. in_eierclsetolerance studies in patients with ischemic neirt aiielJilieouC6s tneheart rate-blood pressure product for any given work load. Theie areas yet few data on the interaction of diliiazem and beta-blockers inp.?tr.ents with poor ventricular function. Resting heart rate is usuallyslightly reduced by diltiazem.Herbesser produces antihypertensive effects both in the supine andstanding positions. Postural hypotension is infrequenfly noied uponsuddenly assuming.an upright position. No retiex tachycardia isassociated with the chronic antihypertensive effectsDiltiazem hydrochloride decreaies vascular resistance, increasescardiac output (by increasing stroke volume), and produces a iigntdecrease or no change in heart rate. During dynamic e*eici6e,increases in diastolic pressure are inhibit6o wnite maiimu*achievable systolic pressure is usually reduced. chronic therapy withdiltiazem hydrochloride produces no ihange or an increase in itismacatecholamines. No increased activity or tne renin-angioiensin-aldosterone axis has been observed. Diltiazem hydrichloridereduces the renal and peripheral effects of angiotensin ll. oiltiaiem-associated.prolongation of theAH intervalis n6t more pronounced inpatients with first degree heart block. ln patients with sick sinussyndrome, diltiazem significanfly prorongs sinus cycre rength (up to50% in some cases).PharmacodynamicsHyBertension: Herbesser demonstrates a dose-reratedantihypertensive response among patients with mild to moderatehypertension; supine diastolic bbob pressure as well as standingdiastolic and systolic btood pressuies atso shows statiiiicalrisignificant linear dose response effects.
4qgina: Herbesser at doses of 120-540 rng/day increases exercisetolerance time. cornpared to baseline, xe-roeiser treated paiientsexperienced statistically significant reductions in anginal aftatks anddecrea.sed nitroglycerin requirements when compired to placebotreated patients.P h a rm a coki netl c s a n d lletabo I i s mDiltiazem is well absorbed from the gastrointestinal tract butundergoes substantial hepatic first-pass 6rect. onty i"t" ii l"t, otuncianged diltiazem appears in the urine. The plasma eliminationhalf-life of diltiazem is approximatety 3.0 - 4.s h. Drugs which inJr"eT inhibit hepatic microsomal enzymes may ilter diltiazemdisposition. Th_erapeutic blood levels of difiiazem ippear to ne in tnerange of 40 - 2o0 ng/ml. There is a departure trdi'r rinearity whendose strengths are increased; the hatf-liie is slighfly increii6o witndose.
Jhe tw9 plr?ry rhetabotites of diltiazem are desacetyrdirtiazem anddesmethyld i ltiazem. The desacety[ rnetabolite is apprbxima tity zsv"to 50% as potent a coronary vasodilatoras diltiazem'ano is preient inplasma at concentrations of t}yo ,to 2ao/o of pareni iiriiri".;however, recent studies have shown nine diltiazem metauoiit"s ir,atare excreted more slowly.ln vitro binding studies show diltiazem HCI )sl0o/o to g0% bound toplasma proteins. competitive in- vitro ligand binding stuoies navealso shown diltiazem HCr binding ts riot artered 6y tnlrapelticconcenkationq..'of. digoxin, hydrochlorothiazide, phenylbutazone,pnopranolol, salicylic acid, or warfarin.Herbesser.ca_psures: when compared to a regimen of immediate-rerease tablets at steady-state, approximately g3% of drug isabsorbed from the Heroesser torlrr[ii"rl when Herbesser was coadministered with a high fatcontent bred<fast, the extent of dittiaiemabsorption was not affected; Tmax, however, occurred slighfly earlier.
I["3qn31"nt elimination half-rife after singre or murtipre o"osingis a to9.5 nours (mean 6.5 hours).Herbesser demonstrates.non-linear pharmacokinetics. As the dailydose of Herbesser capsuresis inqedseo fro* isdtoUri *g, tilr"was a more than proportional increase in diltiazem -piasma
cqocentratio$s.as evidenced by an increase.of AU.e, cmax ana Cminof 6'8,_6 and 8-6 times, respectivery, fora 4,s times in'crease in ooie.DruglnteractionsDue b the potential for additive effecis, caution and careful titrationare warranted in patients receiving diltiazem hydrochloride::i1'l Ellv .ytn other ase nts khorn Io mect ca rdi# conirairil itv
additive effects in prolonging AV conduction when using beta-blockers ordigitalis eoncomitanfly with Herbesser. As with alTdrugs,care should be exercised when treating patients with multi[bmedications. Diltiazem is both a substrate and an inhibitor of inecytochrome P-450 3A4 enzyme system. other drugs that are specificsubstrates, inhibitors, or inducers of the enzyme system may have asignificant irnpact on the efficacy and side erea pronre ot aittiazem.Patients. taking other drugs that are substrates of cyp4sO 3A4,especially patients with renal and/or hepatic impairment, may requiredosage adjustment wtren star{ing or stopping conc6mitinflya{rqiqistered diltiazem in order to haintain bptimum therapeutitblood levels.BetaBlockersconcomitant use of diltiazem hydrochtoride and beta-blockers isysualy welltglerated, but available data are not suffcient to predictthe effects of concomitant treatment in patients with left veniriculardysfunction or eardiac conduction abnormalities. Administration ofdiltiazem hydrochloride concomitanfly with propranotol displaced ittrg1 ltr binding sites by dittiazem. tf combinationiherapy is initiated orwithdrawn in conjunction with propranolol, an adjustment in thepropranglol dose may be wananted.Basptroiie:Enhanced effects and increased toxicityof buspirone may!e possibte during concomitant administratio-n with' diltiazem.Subsequent dose adjustments may be necessary Ouiing co_administratien, and should be based on ctinicalassessment.cimgtidine: Patients cunenfly receiving diltiazem therapy should beoarefully monitored for a change in pharmacological'6ffect wheninitiating and discontinuing therapy with cimetidine]An adjustment inthe diltiazem dose may be waranted.Digitalis: lt is recommended that digoxin levels be monitored wheninitiating, adjusting,..and discontinuing diltiazem hydrochloridetherapy to avoid possible over- or under-digitalization.Q u in id i ne : Monitori ng for quinidine adverse effects may be warantedand the dose adjusted accordingly.fupsthetics: when used concomitanuy, anesthetics and calciumchannel blockers should be titrated carefully.Cyclospoiine: tf administered -eohiUrrenty, cyclosporineconcentrations should be monitored, especially wh6n diitiazemtherapy is initiated, adjusted, or discohtinueii. The effect ofcyclosporine on diltiazem plasma concentrations has not beenevaluated.Qa-hamazepiqe: Patients receiving these drugs concunenfly shouldbe monitored for a potential drug interaction.Benzgdiazepines: coadministration with diltiazem can result inincreased clinical gffects (e.g., prolonged sedation) of bothmidazolam and triazolam.bvastalin: Diltiazem plasma levels were not significanfly afiected bylevestati n or pravastggl
Bt!?mpin: Coadministratioi of dittiazem with rifampin or any kndi,vnCYP3A4 inducer should be avoided when possibli, and aliernativetherapy eonsidered.
INDICATIONSHyperlension; Herbesser is indicated for the treatment ofhypertension. lt may be used alone or in combination with otherantihypertensive medications.Angina: Herbesser is indicated for the treatment of chrqnic stableangina. VariantAngina.
DOSAGE AND ADITIIN ISTRATIONHypertension
.?9o"g" neds to beadjusted bytitration to individuat pa$ent needs.When used as monolherapy, usual starting doses ari laO mg oncedaily. Maximum antihypertensive effect iJ usually ouserveo.-btr t4days of chronic therapy; therefore, dosage adjustrnents shouli bescheduled accordingly. The usuat dosage ranle studied in clinicaltrials was 180 to 540 rrg once daily cunent clinical experience with540 mg dose is limited; however, the dose may be increased to S40mgoncedaily.AnginaDosages for the treatment of angina should be adjusted !o eachpatient's needs, starting with a dose of 1g0 mg once ilaily. lndividuiipatients may respond to higher doses of up to 540 mg once daily.When necessa ry titration shou ld be carried out ov'er 7 to i 4 days.Cqocornifap t usa w tttt Q.the r G a rd I ov a s c u I a r Ag e ntssublingual llitroglycerin may be taken as requiieo to abort acuteanginalattacks.Prophylactic short & rong acting nitrate therapy may be safery co-administeredBeta-blockers are usually well tolerated.Herbesser has an additive antihypertensive effect when used withother antihypertensive agents. Therefore, the dosage of Herbesseror the concomitant antihypertensives may need to G adjusted whenadding one to the other.Hypertensive or anginal .patients who are treated with otherformuhtions of, Herbesser can safely be switched to Flerbessercapsules at the nearest eguivalent tbtat oalty dose. subsequenttitration to higher or lorrer loses may, honev6r, oe neess"r,J anc,should be initiated as clinicafiy indicatdd.
GONTRAINDICATIONSDiltiazem iscontrairdicated in .
1. patients with sick sinus syndrome except in the presence oJ a
- functioningventricularpacemaker2. patients with seeond- or third-degree AV block except in the
presence of a functioning ventricular pacemakeri3. patients with severe hypotension (less than 90 mm Hgsystolic),4. Patientq who havq demonstrated hypgrsensitivity to ihe O*g,';nO
patients with acute .rnygqardia[ infarctiqo And pulrn-onarycongestion documented by x-ray on admission.
STDEEFFECTSserious adverse reactions have been rare in studies with Herbesser.It should be recognized that patients with impaired ventricularfunction and cardiac conduction abnormalities have usually beenexcluded from thgse studies.The'adVerse rcactions, whethei or not drug.1.g1r1ra,,r?FgrteA in
a n d/or cond u ction. pha rm Jcobg ic stud ies ino lcate tnai irr;;ffi;yd:
patients receiving Herbesser SR up to 360 mg and up to 540 mg areGeneral: dyspepsia, pharyngitis, rash, infection, diarrhea, peripheral
edema, pain, bronchitis, infection, flu syndrome, increase cough, , 'gout, myalgia, impotence, conjunctivitis, rash, abdominalenlargement.
ln addition, the following events have been reported infrequently (less
than Zo/o)in clinical trials with other diltiazem products:
Cardiovascular: peripheral edema, palpitations, dyspnea,arrhythmia, AV block {second- or third-degree), bundle branch block,
congestive heart failure, ECG abnormalities, hypotension,palpitations, syncope, tachycardia, ventricular extra systoles'Nervous System: headache, dizziness, asthenia, Abnormal dreams,
amnesia, depression, gait abnormality, hallucinations, insomnia,
nervousness, paresthesia, personality change, somnolence, tinnitus'tremor.Gastrointestinal: Anorexia, constipation, diarrhea, dry mouth,
dysgeusia, mild elevations of SGOT, SGPT, LDH, and alkalinephoiphatase (see hepaticwarnings), nausea, thirst, vomitin$ weightincrease.Dermatological : Petechiae, photosensitivity, pruritus'
Other: Albuminuria, allergic reaction, amblyopia, CPK increase,
crystallu ria, epistaxis, eye irritation,, hyperglycemia, hyp6ruricemia,
muscle cramps, nasal congestion, neck rigidity, noctuiia,osteoarticular pain, polyuria, rhinitis, gynecomastia.
Very infrequently reported events are: alopecia,. erythemamuliiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxicepidermal necrolysis, extra pyramidal symptoms, gingivalhyperplasia, hemolytic anemia, increased bleeding time, leucopenia,purpura, retinopathy, and thrombocytopenia.
WARNINGS :,
Cardiac ConductionDiltiazem hydrochloride prolongs AV node refractory periods withoutsignificantly prolonging sinus node recovery time, except in patients
with s ick siii us'syndrome. Ttr i s.efiect may rarely resutt i n abnormallyslow heart rates(particularly in patients with sick sinus syndrome) orsecond- or third-degree AV block. concomitant use of diltiazem with
beta-blockers or digitalis may result in additive effects on cardiac
conduction. A patient with Prinzmetal's angina developed periods ofasystole (2 to 5 seconds) after a single dose of 60 mg of diltiazem.
Congestive Heart FailureWorsening of congestive heart failure has been reported in patients
with preeiisting impairment of ventricular function. Experience withthe use of diltiazem hydrochloride in combination with beta-blockers
in patients with impaired ventricular function is limited. cautionshould be exercised when using this combination.HypotenslanDecreases in blood pressure associated with diltiazem hydrochloride
therapy may occasionally result in symptomatic hypotension'Acute Hepatic lnjuryMild elevations of transaminases with and without concomitantelevation in alkaline phosphatase and bilirubin have been observed.
Such elevations were usually transient and frequently resolved even
with continued diltiazem treatment. ln rare instances, significantelevations in enzymes such as alkaline phosphatase, LDH, SGOT'
and SGPT, and other phenomena consistentwith acute hepatic injury
have been noted. These reactions tended to occur early after therapyinitiation (1 to 8 weeks) and have been reversible upon
discontinuation of drug therapy. The relationship to diltiazem
hydrochloride is uncertain in some cases, but probable in some'
PRECAUTIONSGeneralDiltiazem hydrochloride is extensively metabolized by the liver and
excreted by the kidneys and in bile. As with any drug given overprolonged periods, laboratory parameters of renal and hepatic
iunction should be monitored at regular intervals' The drug should be
used with caution in patients with impaired renal or hepatic function.
Dermatological events may be transient and may disappear despite
continued use of diltiazem hydrochloride. However, skin eruptionsprogressing to erythema multiforme and/or exfoliative dermatitishave also b-een infrequently reported. Should a dermatologic reactionpersist, the drug should be discontinued'PediatrlcUseSafety and efiectiveness in children have not been established.GeriatricUseReported clinical experience has not identified differences in
responses between the elderly and younger patients- ln general,
dose selection for an elderly patient should be cautious, usually
starting at the low end of the dosing range, reflecting the greaterfrequency of decreased hepatic, renal, or cardiac function, and ofconcomitant disease or other drug therapy.
P REGNANCY AN D LACTATIONPregnancy category C: use diltiazem hydrochloride in pregnantwomen only it th-e potential benefit justifies the potential risk to thefetus.Diltiazem is excreted in human milk. lf use of Herbesser is deemed
essential, an alternative methodof infantfeeding should be instituted.
OVERDOSEln the event of overdose or exaggerated response, appropriatesupportive measures should be employed in addition togasirointestinal decontamination. Diltiazem does not appear to be
iemoved by peritoneal or hemodialysis' Based on the knownpharmacological effbcts of diltiazem and/or reported clinical
experiences, the following measures may be considered:BradycardiaAdmiirister atropine (0.60 to 1.0 mg). lf there is no redponse to vagal
blockage, administer isoproterenol cautiously.High-DegreeAVBlockTreat as ior bradycardia above. Fixed high-degree AV block should
be treated with cardiac Pacing.CardiacFailureAdminister inotropic agents (isoproterenol, dopamine; ordobutamine) and diuretics.HyptensionViiopressors (e.g. dopamine or levarterenol bitartrate). Actual
treatment and ciosige should depend on the severity of the clinical
situation and the judgment and experience of the treating physician.
ln a few repo(ed mses, overdose with calcium channel blockers has
been associated with hypotension and bradycardia, initially refractory
to airopine but becoming more responsive to this treatment when thepatients received large doses (close to 1 gram/hour for more than 24
hours) of calcium chloride.Due to extensive metabolism, plasma concentrations afier a
standard dose of diltiazem can vary over tenfold, which significantlylimits theirvalue in evaluation cases of overdose.Charcoal hemoperfusion has been used successfully as an adjuncttherapy to hasten drug elimination. Overdoses with as much as 10.8gm of oral diltiazem have been successfully treated using appropriatesupportive care.
STORAGEStore below 25"C in a dry place. Protectfrom light.
PRESENTATION1 . Herbesser 90 SR capsules: Blister pack of 1 X 10 capsules.
2. Herbesser 180 SR capsules: Blister pack of 1 X 10 capsules'
TO BE SOLD ON THE PRESCRIPTION OF A MEDICALPRACTITIONERONLY
KEEPALL MEDICINES OUT OF THE REACH OF CHILDREN
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