Omeprazole adalah obat yang digolongkan sebagai penghambat pompa proton/proton pump inhibitor (PPI).

Omeprazole berfungsi sebagai obat untuk penyakit-penyakit yang disebabkan oleh kelebihan produksi asam
lambung. Obat ini menekan sekresi asam lambung dengan cara menghambat secara spesifik dan irreversibel
sistem pompa asam dalam mukosa lambung.

Indikasi

Kegunaan omeprazole adalah untuk pengobatan kondisi-kondisi berikut :

Omeprazole digunakan dalam pengobatan gastroesophageal reflux disease (GERD). GERD adalah
penyakit dimana penderita mengalami sensasi terbakar di area dada dan kerongkongan karena asam
lambung naik ke kerongkongan dan terjadi iritasi.

Untuk mengobati tukak lambung dan tukak usus besar. Tukak lambung biasanya disebabkan oleh
infeksi bakteri Helicobacter pylori dan pemakaian obat-obat NSAID dalam jangka waktu panjang. Untuk
tujuan ini omeprazole biasanya diberikan dalam kombinasi dengan amoxicillin dan Clarithromycin.

obat ini juga berguna untuk menangani erosif esophagitis suatu kondisi dimana kerongkongan
(esophagus) mengalami peradangan karena iritasi asam lambung, infeksi virus atau jamur, dan
penggunaan alkohol serta obat-obatan tertantu.

Bermanfaat juga untuk pengobatan zollinger ellison syndrome, suatu penyakit langka yang terjadi
karena tumor pankreas atau usus besar melepaskan hormon yang menyebabkan terjadinya kelebihan
produksi asam lambung.

Kontra indikasi

jangan menggunakan omeprazole untuk pasien yang memiliki riwayat hipersensitif.

Efek samping

Secara umum omeprazole bisa ditoleransi dengan baik, selama diberikan pada dosis yang dianjurkan. Berikut
adalah beberapa efek samping yang mungkin terjadi :

Efek samping ringan pada saluran pencernaan misalnya diare, nyeri perut, sembelit, mual dan muntah.
Polip lambung dan hiperplasia dilaporkan terjadi pada penggunaan jangka panjang.

Efek samping pada organ hati adalah terjadinya peningkatan serum transaminase, alkali fosfatase, dan
bilirubin. Kejadian-kejadian seperti hepatitis, ensefalopati hati, gagal hati fulminan sangat jarang terjadi.

Efek samping pada ginjal relatif jarang. Namun pada penggunaan jangka panjang dan dosis yang
besar, omeprazole dapat meningkatkan kreatinin serum dan resiko kerusakan ginjal, termasuk gagal
ginjal akut.

Omeprazole menyebabkan pusing, sakit kepala dan vertigo pada beberapa orang yang sensitif.

Efek samping pada saluran pernafasan yang diketahui adalah batuk.

Telah ada laporan-laporan terjadinya anemia hemolitik, trombositopenia, agranulositosis dan

leukositosis pada pemakaian jangka panjang.

Reaksi hipersensitivitas akibat pemakaian obat ini sangat jarang, namun jika terjadi pertolongan medis
harus segera diberikan karena bisa menyebabkan syok anafilaksis yang berakibat fatal

Perhatian

Pemakaian omeprazole harus dihentikan jika tanda-tanda awal reaksi alergi seperti ruam, gatal, sakit
tenggorokan, demam, arthralgia, pucat, atau tanda-tanda lainnya muncul, karena jika terjadi bisa
berakibat fatal.

omeprazole diketahui ikut keluar bersama air susu ibu (ASI) meskipun dalam jumlah yang kecil
terutama setelah 3 jam pemakaian. Namun obat ini didegradasi dengan sangat cepat oleh kondisi
asam, sehingga sejumlah kecil obat yang masuk ke air susu ibu dan terminum oleh bayi akan rusak
sebelum diabsorpsi. Namun jika anda ragu, berkonsultasilah dengan dokter anda.

Obat-obat golongan pompa proton inhibitor (PPI) termasuk omeprazole, harus diberikan secara hatihati pada pasien penderita hipokalsemia atau hipoparatiroidisme.

Omeprazole menyebabkan terjadinya difisiensi vitamin B12 dan malabsorpsi zat besi, terutama pada
pemakaian jangka panjang. Ada baiknya jika pemakaian obat ini dilakukan secara jangka panjang
dibarengi dengan suplemen vitamin B12.

Obat-obat PPI seperti omeprazole diketahui meningkatkan resiko terjadinya patah tulang karena
osteoporosis terutama pada pinggul, pergelangan tangan, atau tulang belakang. Resiko ini semakin
meningkat pada pemakaian jangka panjang dan dosis yang lebih tinggi dari yang dianjurkan. Pasien
yang memiliki resiko ini, harus diberikan dosis terendah dari omeprazole.

Keamanan dan efektivitas obat ini pada anak usia kurang dari 1 tahun masih belum diketahui.

Hati-hati menggunakan obat ini pada pasien dengan gangguan fungsi hati dan ginjal.

obat ini bisa menyebabkan pusing. Jangan mengemudi atau menyalakan mesin selama menggunakan
obat ini.

Toleransi terhadap kehamilan

Penelitian pada reproduksi hewan telah menunjukkan efek buruk pada janin dan tidak ada studi yang memadai
dan terkendali dengan baik pada manusia, namun jika potensi keuntungan dapat dijamin, penggunaan obat
pada ibu hamil dapat dilakukan meskipun potensi resiko sangat besar.

interaksi obat

Berikut adalah interaksi omeprazole dengan obat-obat lain :

Omeprazole menurunkan efek farmakologis clopidogrel jika diberikan secara bersamaan.

Omeprazole menghambat kerja enzim CYP3A4, oleh karena itu obat-obat yang dimetabolisme oleh
enzim CYP3A4 seperti benzodiazepin, escitalopram, warfarin, oxycodone, tramadol, dan oxymorphone
konsentrasinya dalam plasma akan meningkat.

Obat-obat yang kerjanya tergantung oleh asam lambung seperti ketokonazole, atazanavir, dan ester
ampicillin, penyerapannya akan menurun sehingga mengurangi efektivitasnya.

Sedangkan obat-obat yang labil dalam kondisi asam seperti erythromycin, dan digoxin penyerapannya
akan meningkat.

Obat-obat yang dimetabolisme oleh proses oksidasi di dalam hati seperti diazepam, warfarin, dan
fenitoin eliminasinya diperpanjang jika diberikan secara bersamaan dengan omprazole sehingga
meningkatkan efek farmakologi obat-obat tersebut.

Dosis

omeprazole

omeprazole diberikan dengan dosis sebagai berikut :

Dosis lazim dewasa untuk tukak usus besar.

20 mg oral sekali sehari sebelum makan. Kebanyakan pasien sembuh dalam 4-8 minggu.

Dosis lazim dewasa untuk infeksi H. pylori.

Kombinasi dengan clarithromycin : omeprazole 40 mg 1 x sehari + clarithromycin 500 mg 3 x sehari selama 14

hari. Pada hari ke 15-28, omeprazole 20 mg 1 x sehari. Obat diberikan secara oral.

Kombinasi dengan clarithromycin + amoxicillin : omeprazole 20 mg + clarithromycin 500 mg + + amoxicillin

1000 mg, 2 x sehari selama 10 hari. Jika disertai maag, teruskan omeprazole dengan dosis 20 mg 1 x sehari
untuk 18 hari ke depan.

Dosis lazim dewasa untuk tukak lambung atau maag

40 mg 1 x sehari selama 4-8 minggu. Obat diberikan secara oral sebelum makan.

Dosis lazim dewasa untuk erosif esofagitis

20 mg 1 x sehari. Dapat ditingkatkan sampai 40 mg/hari. Obat diberikan secara oral sebelum makan.
Pengobatan bisa dilakukan hingga 12 bulan tergantung hasil yang diperoleh berdasarkan evaluasi dokter.

Dosis lazim dewasa untuk Zollinger-Ellison Syndrome

dosis awal : 60 mg 1 x sehari. Obat diberikan secara oral.

Pemeliharaan : 80 mg/hari dibagi dalam 2-3 x dosis.

Dosislazim dewasa untuk gastroesophageal reflux disease (GERD)

dosis awal : 20 mg 1 x sehari selama 4-8 minggu. Obat diberikan secara oral sebelum makan. Dosis dapat
dinaikkan sampai 40 mg/hari.

Dosis lazim dewasa untuk dispepsia

20 mg 1 x sehari selama 14 hari. Obat diberikan secara oral sebelum makan.

Dosis lazim

anak

Anak-anak

untuk

dan

berat

badan

10

kg

kg
20

erosif esofagitis

Remaja

10
kg

1-16

kg
:

:
10

5
mg

berat badan > 20 kg : 20 mg 1 x sehari.

Dosis lazim anak untuk infeksi H. pylori.

Berat badan 15-30 kg : 10 mg 2 x sehari.

Berat badan > 30kg : 20 mg 2 x sehari.
15 sampai 30 kg: 10 mg dua kali sehari.
Lebih besar dari 30 kg: 20 mg dua kali sehari

Dosis lazim anak untuk gastroesophageal reflux disease (GERD).

mg

tahun:
1

x
x

sehari.
sehari.

Berat badan 5-10 kg : 5 mg 1 x sehari.

Berat badan 10-20 kg : 10 mg 1 x sehari.
Berat badan > 20 kg : 20 mg 1 x sehari.

Major Side Effects

If any of the following side effects occur while taking omeprazole, check with your doctor
immediately:
Rare

Back, leg, or stomach pain

bleeding or crusting sores on the lips

blisters

bloody or cloudy urine

chills

continuing ulcers or sores in the mouth

difficult, burning, or painful urination

fever

frequent urge to urinate

general feeling of discomfort or illness

joint pain

loss of appetite

muscle aches or cramps

pain

red or irritated eyes

redness, tenderness, itching, burning, or peeling of the skin

skin rash or itching

sore throat

sores, ulcers, or white spots on the lips, in the mouth, or on the genitals

unusual bleeding or bruising

unusual tiredness or weakness

Incidence not known:

Drowsiness

fast, racing, or uneven heartbeat

mood or mental changes

muscle spasms (tetany) or twitching seizures

nausea or vomiting

trembling

If any of the following symptoms of overdose occur while taking omeprazole, get
emergency help immediately:
Symptoms of overdose:

Blurred vision

confusion

dryness of the mouth

flushing

headache

increased sweating

Minor Side Effects

Some omeprazole side effects may not need any medical attention. As your body gets used to
the medicine these side effects may disappear. Your health care professional may be able to help
you prevent or reduce these side effects, but do check with them if any of the following side
effects continue, or if you are concerned about them:
Less common:

Body aches or pain

chest pain

constipation

cough

diarrhea or loose stools

difficulty with breathing

dizziness

ear congestion

gas

heartburn

loss of voice

muscle pain

nasal congestion

runny nose

sneezing

unusual drowsiness

Obat Generik :
Omeprazole

Obat Bermerek :
Contral, Dudencer, Inhipump, Lokev, Loklor, Losec, Meisec, Norsec, Omevell, OMZ, Onic, Opm,
Oprezol, Ozid, Prilos, Prohibit, Promezol, Protop, Pumpitor, Redusec, Regasec, Rocer, Socid,
Stomacer, Ulzol, Zepral, Zollocid.

KOMPOSISI
Omeprazole 20 mg : Tiap kapsul mengandung Omeprazole 20 mg.
Omeprazole 10 mg : Tiap kapsul mengandung Omeprazole 10 mg.

FARMAKOLOGI
Omeprazole bekerja menghambat sekresi asam lambung dengan cara berikatan pada pompa
H+K+ATPase (pompa proton) dan mengaktifkannya sehingga terjadi pertukaran ion kalium dan
ion hydrogen dalam lumen sel. Omeprazole berikatan pada enzim ini secara irreversibel, tetapi
reseptor-H2 tidak dipengaruhi. Secara klinis, tidak terdapat efek farmakodinamik yang berarti
selain efek obat ini terhadap sekresi asam. Pemberian melalui oral dari obat ini menghambat
sekresi asam lambung dan stimulasi pentagastrik.

CARA KERJA :
Omeprazol menghambat sekresi asam lambung dengan cara berikatan pada pompa H + K +
ATPase dan mengaktifkannya sehingga terjadi pertukaran ion kalium dan ion hydrogen dalam
lumen sel. Omeprazole berikatan pada enzim ini secara irreversibel, tetapi reseptor-H2 tidak
dipengaruhi. Secara klinis, tidak terdapat efek farmakodinamik yang berarti selain efek obat ini
terhadap sekresi asam. Pemberian melalui oral dari obat ini menghambat basal dan sekresi asam
yang distimulasi oleh pentagastrin.IndikasiOmeprazol diindikasikan untuk pengobatan jangka
pendek tukak lambung, tukak duodenum dan refluks esofagitis; pengobatan sindroma ZollingerEllison.

INDIKASI

Pengobatan jangka pendek tukak duodenal dan yang tidak responsif terhadap obat-obat
antagonis reseptor H2.
Pengobatan jangka pendek tukak lambung.
Pengobatan refluks esofagitis erosif / ulseratif yang telah didiagnosa melalui endoskopi.
Pengobatan jangka lama pada sindroma Zollinger Ellison.

KONTRAINDIKASI
Omeprazole sebaiknya tidak diberikan pada penderita hipersensitif terhadap omeprazole.

DOSIS DAN ATURAN PAKAI

Dosis yang dianjurkan 20 mg atau 40 mg, sekali sehari.

Penderita dengan gejala tukak duodenal : lama pengobatan memerlukan waktu 2 minggu, dan
dapat diperpanjang sampai 2 minggu lagi.

Penderita dengan gejala tukak lambung atau refluks esofagitis erosif/ulseratif : lama

pengobatan memerlukan waktu 4 mimggu, dan dapat diperpanjang sampai 4 minggu lagi.
Penderita yang sukar disembuhkan dengan pengobatan lain, diperlukan 40 mg sekali sehari.
Penderita sindroma Zollinger Ellison dosis awal 20-160 mg sekali sehari, dosis ini harus

disesuaikan untuk masing-masing penderita. Untuk dosis lebih dari 80 mg sehari, dosis harus
dibagi 2 kali sehari.
Kapsul harus ditelan utuh dengan air (kapsul tidak dibuka, dikunyah, atau dihancurkan).
Sebaiknya diminum sebelum makan.

DOSIS :
Dewasa:

Tukak lambung dan tukak duodenum (termasuk yang komplikasi terapi AINS), 20 mg satu kali

sehari selama 4 minggu pada tukak duodenum atau 8 minggu pada tukak lambung; pada kasus
yang berat atau kambuh tingkatkan menjadi 40 mg sehari;
Pemeliharaan untuk tukak duodenum yang kambuh, 20 mg sehari; pencegahan kambuh tukak

duodenum, 10 mg sehari dan tingkatkan sampai 20 mg sehari bila gejala muncul kembali.
Tukak lambung atau tukak duodenum karena AINS dan erosi gastroduodenum, 20 mg sehari

selama 4 minggu, diikuti 4 minggu berikutnya bila tidak sepenuhnya sembuh;

Profilaksis pada pasien dengan riwayat tukak lambung atau tukak duodenum, lesi

gastroduodenum, atau gejala dispepsia karena AINS yang memerlukan pengobatan AINS yang
berkesinambungan, 20 mg sehari.
Tukak duodenum karena H. Pylori menggunakan regimen eradikasi.
Sindrom Zollinger Ellison, dosis awal 60 mg sekali sehari; kisaran lazim 20-120 mg sehari (di

atas 80 mg dalam 2 dosis terbagi).

Pengurangan asam lambung selama anestesi umum (profilaksis aspirasi asam), 40 mg pada

sore hari, satu hari sebelum operasi kemudian 40 mg 2-6 jam sebelum operasi.
Penyakit refluks gastroesofagal, 20 mg sehari selama 4 minggu diikuti 4-8 minggu berikutnya

jika tidak sepenuhnya sembuh; 40 mg sekali sehari telah diberikan selama 8 minggu pada
penyakit refluks gastroesofagal yang tidak dapat disembuhkan dengan terapi lain; dosis
pemeliharaan 20 mg sekalis sehari.
Penyakit refluks asam (Penatalaksanaan jangka panjang), 10 mg sehari meningkat sampai 20

mg sehari jika gejala muncul kembali.

Dispepsia karena asam lambung, 10-20 mg sehari selama 2-4 minggu sesuai respons.
Esofagitis refluks yang menyebabkan kondisi tukak yang parah (obati selama 4-12 minggu)
ANAK di atas 1 tahun, berat badan 10-20 kg, 10 mg sekali sehari, jika perlu ditingkatkan
menjadi 20 mg sekali sehari; Berat badan di atas 20 kg, 20 mg sekali sehari jika perlu
ditingkatkan menjadi 40 mg sehari; Pemberian harus diawali oleh dokter anak di rumah sakit.

ANAK:

Neonatus 700 mcg/kg bb satu kali sehari, ditingkatkan jika perlu setelah 7-14 hari menjadi 1,4

mg/kg bb, beberapa neonatus memerlukan hingga 2,8 mg/kg bb satu kali sehari;
Usia 1 bulan 2 tahun: 700 mcg/kg bb satu kali sehari, ditingkatkan jika perlu menjadi 3 mg/kg

bb (maks. 20 mg) satu kali sehari;

Berat badan 10-20 kg, 10 mg satu kali sehari ditingkatkan jika perlu menjadi 20 mg satu kali

sehari (pada kasus refluks esofagitis ulseratif yang parah, maks. 12 minggu dengan dosis lebih
tinggi);
Berat badan > 20 kg, 20 mg satu kali sehari ditingkatkan jika perlu menjadi 40 mg satu kali

sehari (pada kasus refluks esofagitis ulseratif, maks. 12 minggu dengan dosis lebih tinggi)
Eradikasi H.pylori pada anak (dalam kombinasi dengan antibakteri:
Usia 1-12 tahun, 1-2 mg/kg bb (maks. 40 mg) satu kali sehari;
Usia 12-18 tahun: 40 mg satu kali sehari.

Injeksi intravena diberikan selama 5 menit atau melalui infus intravena; profilaksis aspirasi

asam, 40 mg harus telah diberikan seluruhnya, 1 jam sebelum operasi.

Refluks gastroesofagal, tukak duodenum dan tukak lambung, 40 mg sekali sehari hingga

pemberian oral dimungkinkan.

ANAK. Injeksi intravena selama 5 menit atau dengan infus intravena: Usia 1 bulan12 tahun:

dosis awal 500 mikrogram/kg bb (maks. 20 mg) satu kali sehari, ditingkatkan menjadi 2 mg/kg
bb (maks. 40 mg) jika diperlukan.; Usia 12-18 tahun, 40 mg satu kali sehari.
Saran: Telan seluruh kapsul, larutkan tablet dalam air atau campur isi kapsul dengan sari buah

atau yoghurt.
Pemberian pada anak: Oral, sama dengan dewasa.
Enteral: Buka kapsul omeprazol, larutkan omeprazol dalam sejumlah air secukupnya atau
dalam 10 mL Natrium bikarbonat 8,4% (1mmol Na+/mL). Biarkan selama 10 menit sebelum
diberikan). Infus intermiten intravena, encerkan larutan rekonstitusi pada kadar 400
mikrogram/mL dengan glukosa 5% atau natrium klorida 0,9%, berikan selama 20-30 menit.

EFEK SAMPING

Diare, mual, sakit kepala, sembelit dan perut kembung pernah dilaporkan tetapi jarang. Pada

sejumlah pasien, ruam kulit mungkin terjadi. Efek samping yang terjadi biasanya ringan.
Omeprazole umumnya dapat ditoleransi dengan baik.
Pada dosis besar dan penggunaan yang lama, kemungkinan dapat menstimulasi pertumbuhan

sel ECL (enterochromaffin-likecells).

Pada penggunaan jangka panjang perlu diperhatikan adanya pertumbuhan bakteri yang
berlebihan di saluran pencernaan.

PERINGATAN DAN PERHATIAN

Kemungkinan malignansi sebaiknya dihindarkan sebelum penggunaan Omeprazole pada

pasien tukak lambung karena dapat menutupi gejala-gejalanya dan menghambat diagnosis.
Belum ada pengalaman penggunaan Omeprazol untuk anak-anak.
Obat ini sebaiknya tidak digunakan selama kehamilan dan menyusui kecuali memang
dianggap penting.

INTERAKSI OBAT

Omeprazol menghambat metabolisme obat-obat yang dimetabolisme oleh sistem enzim

sitokrom P450 hati dan memperpanjang waktu paruh diazepam, warfarin dan fenitoin.

Pada wanita hamil, wanita menyusui dan anakanak sebaiknya dihindari bila penggunaannya
dianggap tidak cukup penting.

KEMASAN

Omeprazole 20 mg, box, 3 strip x 10 kapsul.

Omeprazole 10 mg.

Epidemiological data do not show an increased risk of major birth defects after maternal use of omeprazole
during pregnancy.[20]
No clinical trials have deeply evaluated the potential consequences of the use of omeprazole in breastfeeding.
However, the pharmacokinetics of omeprazole molecule strongly suggest the safety of omeprazole use during
breastfeeding:

Omeprazole has a high plasma protein binding rate (95%),[21] indicating that little amount of drug is
transferred to the milk duct during breast milk formation.

Omeprazole needs to be administrated in an enteric-coated formulation due to its rapid degradation in

the acidic conditions of the stomach. This suggests that most of the free molecules ingested by the infant
are likely degraded before being absorbed.[citation needed]

Omeprazole at normal doses is likely safe during breastfeeding

Although the potential for drug interactions is high, clinically important drug interactions are rare. [23][24]
However, the most significant major drug interaction concern is the decreased activation of clopidogrel when
taken together with omeprazole.[25] Although still controversial,[26]this may increase the risk of stroke or heart
attack in people taking clopidogrel to prevent these events.
The mechanism by which this potential interaction occurs is because omeprazole is an inhibitor of the
enzymes CYP2C19 and CYP3A4.[27] Clopidogrel is an inactive prodrug that partially depends on CYP2C19 for
conversion to its active form. Inhibition of CYP2C19 may block the activation of clopidogrel, which could
reduce its effects.[28][29]
Almost all benzodiazepines are metabolised by the CYP3A4 and CYP2D6 pathway, and inhibition of these
enzymes results in a higher AUC (i.e. the total effect over time of a given dose). Other examples of drugs
dependent on CYP3A4 for their metabolism are escitalopram,[30] warfarin,[31] oxycodone, tramadol,
and oxymorphone. The concentrations of these drugs may increase if they are used concomitantly with
omeprazole.[32]
Omeprazole is also a competitive inhibitor of p-glycoprotein, as are other PPIs.[33]
Drugs that depend on an acidic stomach environment (such as ketoconazole or atazanavir) may be poorly
absorbed, whereas acid-labile antibiotics (such as erythromycin which is a very strong CYP3A4 inhibitor) may
be absorbed to a greater extent than normal due to the more alkaline environment of the stomach. [32]
St. John's wort (Hypericum perforatum) and Gingko biloba significantly reduce plasma concentrations of
omeprazole through induction of CYP3A4 and CYP2C19.[34]
Proton-pump inhibitors like omeprazole have been found to increase the plasma concentrations
of methotrexate.

Pharmacology[edit]
Pharmacodynamics[edit]
Mechanism of action[edit]
Omeprazole is a selective and irreversible proton pump inhibitor. It suppresses stomach acid secretion by
specific inhibition of the H+/K+-ATPase system found at the secretory surface of gastric parietal cells. Because
this enzyme system is regarded as the acid (proton, or H+) pump within the gastric mucosa, omeprazole
inhibits the final step of acid production.[citation needed]
Omeprazole also inhibits both basal and stimulated acid secretion irrespective of the stimulus. [36]
The inhibitory effect of omeprazole occurs within 1 hour after oral administration. The maximum effect occurs
within 2 hours. The duration of inhibition is up to 72 hours. When omeprazole is stopped, baseline stomach

acid secretory activity returns after 3 to 5 days. The inhibitory effect of omeprazole on acid secretion will
plateau after 4 days of repeated daily dosing.[37]

Pharmacokinetics[edit]
The absorption of omeprazole takes place in the small intestine and is usually completed within 3 to 6 hours.
The systemic bioavailability of omeprazole after repeated dose is about 60%.[citation needed]
Omeprazole, as well as other PPIs, are only effective on active H+/K+-ATPase pumps. These pumps are
stimulated in the presence of food to aid in digestion. For this reason, patients should be advised to take
omeprazole with a glass of water on an empty stomach.[38][39] Additionally, most sources recommend that after
taking omeprazole, at least 30 minutes should be allowed to elapse before eating [40][41] (at least 60 minutes for
immediate-release omeprazole plus sodium bicarbonate products, such as Zegerid), [42] though some sources
say that with delayed-release forms of omeprazole, waiting before eating after taking the medication is not
necessary.[43]
Omeprazole is completely metabolized by the cytochrome P450 system, mainly in the liver. Identified
metabolites are the sulfone, the sulfide, and hydroxy-omeprazole, which exert no significant effect on acid
secretion. About 80% of an orally given dose is excreted as metabolites in the urine, and the remainder is
found in the feces, primarily originating from bile secretion.[citation needed]

Chemistry[edit]

(S)-() and (R)-(+)-enantiomers of omeprazole, aracemate (1:1 mixture of both enantiomers)

Omeprazole contains a tricoordinated sulfinyl sulfur in a pyramidal structure and therefore can exist as either
the (S)- or (R)-enantiomers. Omeprazole is a racemate, an equal mixture of the two. In the acidic conditions of
the canaliculi of parietal cells, both enantiomers are converted to achiral products (sulfenic
acid and sulfenamide configurations) which react with a cysteine group in H+/K+ ATPase, thereby inhibiting the
ability of the parietal cells to produce gastric acid.[citation needed]

AstraZeneca has also developed esomeprazole (Nexium) which is a eutomer, purely the (S)-enantiomer,
rather than a racemate like omeprazole.
Omeprazole undergoes a chiral shift in vivo which converts the inactive (R)-enantiomer to the active (S)enantiomer, doubling the concentration of the active form.[44] This chiral shift is accomplished by
the CYP2C19 isozyme of cytochrome P450, which is not found equally in all human populations. Those
who do not metabolize the drug effectively are called "poor metabolizers". The proportion of the poor
metabolizer phenotype varies widely between populations, from 2.02.5% in African Americans and white
Americans to >20% in Asians; several pharmacogenomics studies have suggested that PPI treatment
should be tailored according to CYP2C19 metabolism status.[45]

Measurement in body fluids[edit]

Omeprazole may be quantified in plasma or serum to monitor therapy or to confirm a diagnosis of
poisoning in hospitalized patients. Plasma omeprazole concentrations are usually in a range of 0.2
1.2 mg/l in persons receiving the drug therapeutically by the oral route and 16 mg/l in victims of acute
overdose. Enantiomeric chromatographic methods are available to distinguish esomeprazole from racemic
omeprazole.[46]

History[edit]
Omeprazole was first marketed in the United States in 1989 by Astra AB, now AstraZeneca, under the
brand name Losec. In 1990, at the request of the U.S. Food and Drug Administration, the brand name
Losec was changed to Prilosec to avoid confusion with the diuretic Lasix (furosemide).[47] The new name
led to confusion between omeprazole (Prilosec) and fluoxetine (Prozac), an antidepressant.[47]
When Prilosec's U.S. patent expired in April 2001, AstraZeneca introduced esomeprazole (Nexium) as a
patented replacement drug.[48] Many companies introduced generics as AstraZeneca's patents expired
worldwide, which are available under many brand names.

Dosage forms[edit]

Omeprazole 10-mg, from UK

Omeprazole is available as tablets and capsules (containing omeprazole or omeprazole magnesium) in

strengths of 10, 20, 40, and in some markets 80 mg; and as a powder (omeprazole sodium)
for intravenous injection. Most oral omeprazole preparations are enteric-coated, due to the rapid
degradation of the drug in the acidic conditions of the stomach. This is most commonly achieved by
formulating enteric-coated granules within capsules, enteric-coated tablets, and the multiple-unit pellet
system (MUPS).[49] An immediate release formulation was approved by the FDA in the United States,
[50]

which does not require enteric coating.

It is also available for use in injectable form (IV) in Europe, but not in the U.S. The injection pack is a
combination pack consisting of a vial and a separate ampule of reconstituting solution. Each 10-ml clear
glass vial contains a white to off-white lyophilised powder consisting of omeprazole sodium 42.6 mg,
equivalent to 40 mg of omeprazole.
Omeprazole is also available as an oral suspension of enteric-coated beads in the UK as an unlicensed
product. Oral suspensions are predominantly used for children, but can also be used by those with
difficulty swallowing or those using a feeding tube.

METOCLOPRAMIDE INDUCED EXTRAPYRAMI-DAL SIGNS AND

SYMPTOMS BRIEF REVIEW OF LITERATURE AND CASE REPORT.
Mirena Valkova1, Boyko Stamenov1, Dora Peychinska1, Ivanka Veleva2, Pepa Dimitrova2, Pavlina
Radeva2.
1) Clinic of Neurology, UMHAT Dr G. Stranski, Pleven, Bulgaria
2) Psychiatric Department, Medical University - Pleven, Bulgaria

Journal of IMAB - Annual Proceeding (Scientific Papers) 2014, vol. 20, issue 6
Journal of IMAB
ISSN: 1312-773X
http://www.journal-imab-bg.org

ABSTRACT:
Introduction: Metoclopramide is a dopamine receptor agonist and well known antiemetic and
gastrokynetic agent. Its usage has been restricted by Euro-pean Medicines Agency (EMA), because of
acute and chronic neurological adverse events. Extrapyramidal syn-dromes, including parkinsonism,
tardive dyskinesia, akathisia and acute dystonias, are the most reported and most often drug side
effects.
Contingent and methods: We present a case of 23 years old woman with a 3-year history of
Metoclopramide-induced recurrent oculogyric crises.
Results: The patient suffered from examinophobia, with minimal benzodiazepine symptoms
relief. She willfully took small dosages of oral Metoclopramide for nausea relief before her
examinations, which lead to recur-rent oculogyric crises, short after the drug intake. After a detailed
explanation of drug side effects and medicine dis-continuation, they disappeared. She had no
significant medical and family history of neurological and psychiat-ric conditions. Laboratory data
were normal.
Conclusions: Metoclopramide could induce acute or chronic neurological conditions and its
usage should be restricted in general population to some specific conditions. Some of its adverse
reactions are often misdiagnosed and improperly treated. Critical drug anamnesis with a focus on
Metoclopramide usage in some cases could enhance di-agnosis.
Key words: Metoclopramide side effects, dopamine antagonist, oculogyric crises.
INTRODUCTION:
Metoclopramide is well known antiemetic and gastrokynetic agent, used for treatment of
nausea, vomit-ing, gastroparesis, gastro-esophageal reflux disease and migraine [1, 2, 3, 4]. It is a
dopamine (D2) receptor an-tagonist with short life and mixed 5HT 3 receptor antago-nist and 5HT4
receptor agonist [5, 6, 7]. Although its sig-nificant effect on nausea and vomiting and widely usage in
practice, on 24 October 2013 European Medicines Agencys Committee on Medical Products for

Human Use recommended changes of metoclopramide containing medicines use, due to the potential
risk of serious neuro-logical side effects. [8]
Extrapyramidal side effects due to metoclopamide are the most common ones. Reported incidence is
approxi-mately 0.2%, but in aged and young patients this incidence increases up to as high as 25%,
the risk in children is 6 times higher than in adults [8, 9].
They may occur earlier after treatment (most often within the first 24-72 hours), but most likely after
several dosages [8, 9, 10]. Risk factors for serious neurological events are high dosages, long
treatment period, and treat-ment of children or elderly patients [8, 9, 10]. Tardive dys-kinesia and
Parkinsonism are generally seen after long-term use, whereas dystonia and akathisia can occur after a
sin-gle dose of metoclopramide [10].
Although the possible reason of extrapyramidal side effects presentation is a blockage of striatal D2
receptor, their exact mechanism remains unclear [9].
The most often types of extrapyramidal side effects due to Metoclopramide usage are parkinsonism,
tardive dyskinesia, acute dystonias and akathisia. Metoclopramide-induced parkinsonism is not
uncommon, risk factors are long-term usage, female sex, advanced age, diabetes mellitus and
polypharmacy [10, 11]. Tardive dyskinesia is a syndrome characterized by persistent, potentially
irrevers-ible involuntary movements. Metoclopramide tardive dys-kinesia incidence is likely to be
<1%. [12, 13]. Risk fac-tors are long term use of the medicine, increased age, fe-male gender, preexisting abnormal movements, diabetes mellitus, organic brain dysfunction and atrophy, psychiatric disorders, family history of tardive dyskinesia, polypragmasia [13]. Early syndrome recognition
may im-prove the likelihood of remission [14]; however the treat-ment in some cases may be
unsuccessful. Several medicines, though with variable effects could be used for the symp-toms relief;
they are Amantadine, Tetrabenazine, Benzo-diazepines (limited results), Melatonin (high dosages at
long treatment period could be effective), Vitamine E (lim-ited results) [14]. Surgical interventions and
Deep brain stimulation may be used in treatment resistant cases [14].
Incidence of acute dystonias due to metoclopramide is about 0.2% with female preponderance
[15]. They are usually presented as buccolingual, torticollic, oculogyric and opisthotonic forms [15].
Risk factors are unclear, al-though parenteral usage and high dosages are believed to be more likely
associated with acute dystonias [15]. The mechanism of their development remains unclear, but
theduration of these symptoms corresponds to T1/2 of the drug [15]. Intravenous diphenhydramine
may be used for dys-tonia reversion [15, 16]. Sometimes the clinical picture may imitate acute
encephalitis or other brain diseases [15].
The incidence of metoclopramide induced akathisia is unknown, because of under recognition,
al-though it is believed to be about 20-25% [17, 18]. It may present with varying grades of severity
[17, 18]. Benzodia-zepines, betablockers, 2-agonists, opioids, and anti-cholinergics may be used for
treating syndrome [17, 18].
CONTINGENT AND METHODS:
We present a case of 23 years old woman with Meto-clopramide-induced oculogyric crises
misdiagnosed as panic attacks. History of disease, general, neurological and psychological
examinations, laboratory data are applied.
RESULTS:
The patient (23 years old student) was presented at our department with a 3- year history of
unexplained ocu-logyric crises during some of her examinations. She suf-fered from long term
examinophobia with anxiety and mod-erate autonomic signs, including nausea and vomiting,
tachycardia and pallor. Small dosage of benzodiazepine (Rivotril) for acute symptom prevention was
prescribed with minimal effect and she willfully stopped it. At first she complained of unexpected
oculogyric crises with short duration (2 minutes), during her examination 3 years ago. This sign
troubled her and she visited her outpatient psy-chiatrist, who diagnosed severe panic attack and sent
her to psychologist. Psychotherapy was not conducted, because of patients refusal. The same
syndrome she had many times, irregularly, during some of her examinations, however the syndrome
worsened with every appearance the duration and severity of signs increased and she was unable to
sit for her exams. She had no symptoms between examinations, no other significant medical or family
history. At first she denied substance abuse and unprescribed medicine usage. Laboratory data were
normal. She was kindly asked again for using unprescribed medications of all kinds, with a fo-cus on
dopamine-agonists. The patient confessed that she had taken 1 or 2 tablets (10-20 mg)
Metoclopramide be-fore examinations for nausea suppression. Metoclopramide side effects were
explained to the patient and the medica-tion was discontinued. Proton-pump inhibitor was prescribedpre-scribed for her nausea; she refused benzodiapine treatment and psychotherapy. The
patient had no more oculogyric cri-ses after the previously mentioned corrections and she passed her
exams session with success.
DISCUSSION:

Oculogyric crisis is an acute dystonic reaction [15], characterized by prolonged involuntary upward
deviation of the eyes, which can be associated with some drugs us-age - neuroleptics and other
dopamine antagonist (includ-ing Metoclopramide), carbamazepine, chloroquine, cisplatin, lithium,
domperidone, nifedipine, pemoline, phencyclidine, etc. or with brain diseases. It could be re-current
and triggered by different factors (including stress and drug exposure). The syndrome is often
misdisgnosed. In many cases it can mimic some neurological and psychi-atric diseases, particularly in
cases with short duration and mild severity, it is underdiagnosed [15]. Our patient had long history of
recurrent acute Metoclopramide-induced oculogyric crises, misdiagnosed as panic attacks, with worsening of signs that lead to severe, although short-time func-tional disabilities and psychological
distress. The signs occurred early after taking medication and disappeared without treatment,
similarly to that notified by Arumugam [15]. Our patient had other psychiatric illness
examinophobia, but no history of co-morbid neurological and psychiatric conditions, no family history
of dyskinesia or other neurological diseases and no polypragmasia. The explanation of drug-side
effects to the patient appeared to be of great importance, because, because she obviously took and
stopped medications herself, without visiting phy-sician or reading drug instructions. In this clinical
case we diagnosed the Metoclopramide induced adverse drug re-action after a 2- month clear
period and no oculogyric cri-ses during the whole exams session. The patient remained under medical
observation and according to us should un-dergo a psychological treatment.
CONCLUSIONS:
Metoclopramide induces acute or chronic neurologi-cal side effects and its usage in general
population should be restricted to some specific conditions. Some of its ad-verse reactions are often
misdiagnosed and improperly treated. In some cases the thorough drug history with a fo-cus on
Metoclopramide usage enhances diagnosis.
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