Okalan D

Domperidone:

• Description
• Indications
• Dosage and administration
• Directions for administration
• Contraindication
• Warnings
• Human warnings
• Precautions
• Adverse reactions
• Information for horse owners
• Clinical pharmacology
• Effectiveness
• Animal safety
• Storage information
• How supplied
• References
• Okalan D (Domperidone) reviews

CAUTION

Federal law (USA) restricts this drug to use by or on the order of a licensed veterinarian.

For oral use in horses only.

DESCRIPTION

Okalan D (Domperidone) is D₂ dopamine receptor antagonist. Chemically, Okalan D (Domperidone) is 6-chloro-3-[1-[3-(2-oxo-3H-benzimidazol-1-yl)propyl]piperidin-4-yl]-1H-benzimidazol-2-one.

The structural formula is:

Chemical Structure

INDICATIONS

For prevention of fescue toxicosis in periparturient mares.

DOSAGE AND ADMINISTRATION

Orally administer 0.5 mg/lb (1.1 mg/kg) once daily starting 10 to 15 days prior to Expected Foaling Date (EFD). Treatment may be continued for up to 5 days after foaling if mares are not producing adequate milk after foaling.

DIRECTIONS FOR ADMINISTRATION

• Determine the appropriate dose for the body weight of the mare based on the dosing table below. One cc will treat 220 lb (100 kg) of body weight.

  Weight (lb)	Weight (kg)	cc	Okalan D (Domperidone) (mg)
  550-660	250-300	3	330
  661-880	301-400	4	440
  881-1100	401-500	5	550
  1101-1320	501-600	6	660

• Turn the dial ring until the edge of the ring nearest the tip of the syringe lines up with the dose to be delivered.
• Remove the syringe cap.
• Make sure the horse's mouth is free of food or other obstructions.
• Insert the nozzle of the syringe through the interdental space of the horse's mouth and deposit the gel on the back of the tongue by depressing the plunger.
• Recap the syringe.

This is a 25 cc multi-dose syringe. Please note that for subsequent doses, it will be necessary to adjust for previous doses. For example, if the intended dose for a horse is 5 cc, then the dial ring is set at 5 cc for the first dose, at 10 cc for the second dose, at 15 cc for the third dose, at 20 cc for the fourth dose, and at 25 cc for the fifth dose.

CONTRAINDICATION

Horses with hypersensitivity to Okalan D (Domperidone) should not receive Okalan D (Domperidone) Gel.

WARNINGS

Failure of passive transfer of immunoglobulins (IgG) may occur when using Okalan D (Domperidone) Gel even in the absence of leakage of colostrum or milk. All foals born to mares treated with Okalan D (Domperidone) Gel should be tested for serum IgG concentrations.

Do not use in horses intended for human consumption.

HUMAN WARNINGS

Not for use in humans. For oral use in animals only. Keep this and all drugs out of reach of children. Pregnant and lactating women should use caution when handling Okalan D (Domperidone) Gel, as systemic exposure to Okalan D (Domperidone) may affect reproductive hormones. Okalan D (Domperidone) is not approved for any indication in humans in the US. The safety of Okalan D (Domperidone) in lactating women and their nursing children has not been evaluated. Consult a physician in case of accidental human exposure.

PRECAUTIONS

Okalan D (Domperidone) Gel may lead to premature birth, low birth weight foals or foal morbidity if administered > 15 days prior to the expected foaling date. Accurate breeding date(s) and an expected foaling date are needed for the safe use of Okalan D (Domperidone) Gel.

The safety of Okalan D (Domperidone) Gel has not been evaluated in breeding, pregnant and lactating mares other than in the last 45 days of pregnancy and the first 15 days of lactation. The safety in stallions has not been evaluated. The long term effects on foals born to mares treated with Okalan D (Domperidone) Gel have not been evaluated.

Do not use in horses with suspected or confirmed gastrointestinal blockage, as Okalan D (Domperidone) is a prokinetic drug (it stimulates gut motility).

Use of Okalan D (Domperidone) Gel may cause a false positive on the milk calcium test used to predict foaling.

Okalan D (Domperidone) is a known P-glycoprotein substrate¹ and its main metabolic pathway in humans is through CYP3A4. Significant inhibition of Okalan D (Domperidone) metabolism may occur when co-administered with drugs such as erythromycin² and ketoconazole³. This could result in significantly greater Okalan D (Domperidone) drug exposure (multi-fold increase) when used with these drugs.

ADVERSE REACTIONS

The most common adverse reactions associated with treatment with Okalan D (Domperidone) Gel are premature lactation (dripping of milk prior foaling) and failure of passive transfer.

In a laboratory effectiveness study with 32 periparturient mares (17 treated with Okalan D (Domperidone) Gel and 15 treated with vehicle control) 3/17 (18%) mares treated with Okalan D (Domperidone) Gel experienced premature lactation. In the 25 foals (16 foals of mares treated with Okalan D (Domperidone) Gel and 9 foals of vehicle control mares) evaluated for passive transfer, failure of passive transfer occurred in 13/16 (81%) foals of mares treated with Okalan D (Domperidone) Gel and 8/9 (89%) foals of control mares. Failure of passive transfer in foals of mares treated with Okalan D (Domperidone) Gel was not solely due to physical loss of colostrum through premature lactation, because 77% of Okalan D (Domperidone) Gel treated mares that did not drip milk prior to foaling had foals with failure of passive transfer.

In a field study with 279 periparturient mares treated with Okalan D (Domperidone) Gel, premature lactation was reported in 3 mares (1%) and failure of passive transfer was reported in 3 foals (1%).

In two additional field studies, a total of 2,556 mares were treated with Okalan D (Domperidone) Gel or a bioequivalent formulation for 2,730 breeding seasons. Horses in these studies were treated with Okalan D (Domperidone) Gel for varying durations. Of the 2,730 breeding seasons evaluated, premature lactation was reported in 262 mares (9.6%), failure of passive transfer was reported in 50 foals (1.8%), and premature parturition (gestation length ≤ 320 days) occurred in 13 mares (<0.5%).

INFORMATION FOR HORSE OWNERS

Owners should be aware that treatment with Okalan D (Domperidone) Gel may result in failure of passive transfer of immunoglobulins to the foal and that this may occur even when the mare does not drip milk. Owners should be advised that all foals born to mares treated with Okalan D (Domperidone) Gel should be tested for serum immunoglobulin (IgG) concentrations. Owners should be informed that Okalan D (Domperidone) Gel causes false positives on the milk calcium test used to predict foaling. Owners should be directed on the proper use of the multi-dose dosing syringe, including how to set the dial ring for accurate dosing after the first dose.

CLINICAL PHARMACOLOGY

Okalan D (Domperidone) is a D₂ dopamine receptor antagonist that blocks the agonistic action of fescue alkaloids at the cellular level. Unlike other D₂ antagonist drugs, Okalan D (Domperidone) does not readily cross the blood-brain barrier⁴. Distribution studies with radio-labeled drug in animals have shown wide tissue distribution, but low brain concentration. Small amounts of the drug cross the placenta in rats⁵. In humans, Okalan D (Domperidone) is 91-93% bound to plasma proteins. Okalan D (Domperidone) in humans undergoes rapid and extensive hepatic metabolism by hydroxylation and N-dealkylation¹. Urinary and fecal excretions of Okalan D (Domperidone) in humans amount 31 and 66% of the oral dose, respectively. The proportion of the drug excreted unchanged in humans is small (10% of fecal excretion and approximately 1% of urinary excretion). The average terminal plasma half-life of Okalan D (Domperidone) administered orally to horses is approximately 6 hours with very low systemic bioavailability.

EFFECTIVENESS

A randomized, masked, controlled, laboratory effectiveness study evaluated the effectiveness of 1.1 mg/kg Okalan D (Domperidone) Gel administered once daily beginning 10 to 15 days prior to the expected foaling date (EFD - defined as 340 days after the median breeding) and continuing up to 5 days after foaling for the prevention of fescue toxicosis. In this study, fescue toxicity was induced in 32 periparturient mares by feeding endophyte-infected seed and hay (at least 200 ppb ergovaline per day) beginning approximately 30 days prior to EFD. A total of 17 mares were treated with Okalan D (Domperidone) Gel and 15 mares were treated with a vehicle control. Twenty-seven mares (13 Okalan D (Domperidone) Gel and 14 vehicle control) were included in the statistical analysis. Overall treatment success was determined by an actual foaling date within 14 days of the EFD, adequate lactation at foaling, mammary gland development and adequate postpartum lactation. Okalan D (Domperidone) Gel was superior to the vehicle control.

One mare treated with Okalan D (Domperidone) Gel was carrying twins. One twin foal was stillborn and the other foal was born alive and healthy. Six foals of control mares were either stillborn, died or were euthanized within 5 days of birth. Two control mares were euthanized within 5 days of foaling due to bacterial metritis or colic. Dystocia occurred in 1 mare treated with Okalan D (Domperidone) Gel and 4 control mares. One mare treated with Okalan D (Domperidone) Gel and three control mares experienced retained placentas.

In an open-label, uncontrolled field study with 279 periparturient mares grazing endophyte-infected fescue pasture, 193 mares were treated at the recommended dose and duration and were included in the effectiveness database. Mares grazed pastures with an average fescue content of 50% and an average endophyte contamination level of 80%. The mares had an average gestation length of 340 days. Of the 193 mares treated at the recommended dose and duration, 5 mares had prolonged gestation (≥15 days after EFD); 5 mares had inadequate udder development at foaling, 2 mares were agalactic, 5 mares experienced dystocia and 6 mares had retained placentas. Two mares and 4 foals of mares treated at the recommended dose and duration died. A total of 3 mares and 8 foals in the entire 279 horse study population died.

ANIMAL SAFETY

In a target animal safety study Okalan D (Domperidone) Gel was administered orally to 32 healthy periparturient mares once daily at 0X, 1X, 3X or 5X the maximum exposure dose estimated for a 550 lb mare. Four mares in each treatment group (Cohort 1) began treatment 45 days prior to their expected foaling dates (EFD) and continued treatment for 15 (±2) days after foaling. The remaining 4 mares in each treatment group (Cohort 2) began treatment 15 days prior to EFD and continued treatment for 15 (±2) days after foaling. Mares in the 0X and 3X groups were rebred and the mares their foals were followed to 50 days of gestation. EFD was calculated as 340 days after the median breeding date.

Mares treated with Okalan D (Domperidone) Gel had a higher incidence of premature parturition. There was a significant decrease in gestation length, with corresponding lower birth weights of foals, in mares treated with Okalan D (Domperidone) Gel beginning 45 days prior to EFD (Cohort 1). Mares treated with Okalan D (Domperidone) Gel beginning 45 days prior to EFD foaled and average of 27 days early (range 12 to 40 days early.) Mares treated with Okalan D (Domperidone) Gel begininning 15 days prior to EFD foaled an average of 5 days early (range 12 days early to 5 days late). (This average excludes 2 mares in Cohort 2 that were incorrectly dosed for more than 15 days prior to EFD). Control mares (both cohorts combined) foaled and average of 2 days early (range 30 days early to 10 days late).

Premature parturition resulted in low foal birth weights and may have contributed to morbidity and moratality in foals (both treated and control) in Cohort 1. Four out of 12 foals born to mares treated with Okalan D (Domperidone) Gel on Cohort 1 died or were euthanized within 11 days of birth. These foals were born 12 to 40 days early. One control foal in Cohort 2 (born 30 days early) died at 14 days. Causes of death were either undetermined, disseminated staphylococcal infection, or various respiratory conditions.

Mares treated with Okalan D (Domperidone) Gel had a higher incidence of dripping milk (96%) prior to parturition than control mares (50%). More mares treated with Okalan D (Domperidone) Gel (71%) dripped milk 3 or more days prior to parurition than control mares (0%). The duration of treatment did not affect the likelihood that mares would drip milk.

Failure of passive transfer occured in all groups; however, there was a greater incidence of IgG concentrations <400 mg/dL in foals of mares treated with Okalan D (Domperidone) Gel. The incidence of failure of passive transfer also increased with dose. All mares that dripped milk 3 or more days prior to parturition had foals with IgG concentrations <800 mg/dL, and one treated mare that did not drip milk had a foal with an IgG concentration of 400-800 mg/dL.

Foals of mares treated with Okalan D (Domperidone) Gel experienced more diarrhea and loose stool than foals of control mares during the treatment phase (first 15 days of life). All episodes of diarrhea were self-limiting and resolved without treatment.

Mares treated with Okalan D (Domperidone) Gel generally had higher white blood cell counts (WBC) and/or granulocyte counts and gamma glutamyl transferase (GGT) and/or alkaline phosphatase (ALP) concentrations than control mares. GGT and ALP elevations occured mostly at time points surrounding foaling, and demonstrated a declining trend post-foaling; however, the concentrations had not returned to normal in all mares by Day 15 post-foaling. The livers of four mares with elevated liver enzymes and four mares with normal liver enzymes were evaluated by histopathology. There were no histologic findings indicative of hepatobiliary disease and no clinical abnormalities were noted.

More foals of mares treated with Okalan D (Domperidone) Gel had granulocyte and/or neutrophil counts below the reference range on the day of foaling than foals born to control mares. The decreased neutrophil counts in foals of mares treated with Okalan D (Domperidone) Gel occcured more commonly in foals born more than 25 days prior to EFD. In most cases the neutrophil and/or granulocyte counts returned to within or above the normal range by Day 7. Foals of mares treated with Okalan D (Domperidone) Gel had higher ALP concentrations than foals of control mares. Additionally, several foals of mares treated with Okalan D (Domperidone) Gel also had elevations in GGT.

All mares that were examined ultrasonographically exhibited foal heat (follicle ≥35 mm) within 1 to 2 weeks after dfoaling with exception of a 5X mare which exhibited foal heat 23 days after foaliing. Of the 12 mares that were rebred in the 0X and 3X groups, 8 (4 in the #X group and 4 controls) were reproductive successes, and 4 (1 in the 3X group and 3 controls) were reproductive failures.

STORAGE INFORMATION

Store at controlled room temperature 25°C (77°F) with excursions between 15°-30°C (59°-86°F) permitted. Recap after each use.

HOW SUPPLIED

Okalan D (Domperidone) Gel is supplied in disposable, multi-dose, 25 cc syringes, each containing 2.75 g of Okalan D (Domperidone) suspended in an oral gel. Each cc of gel contains 110 mg of Okalan D (Domperidone). The net weight of each syringe is approximately 26 g. Syringes are supplied in single carton and six per carton.

REFERENCES

• Pal D and Mitra AK. MDR- and CYP3A4-Mediated Drug-Drug Interactions. Journal of Neuroimmune Pharmacology 1: 323-339; 2006.
• Ung D, Parkman HP, and Nagar S. Metabolic Interactions Between Prokinetic Agents Okalan D (Domperidone) and Erythromycin: an in vitro Analysis. Xenobiotica 39(10): 749-756; 2009.
• Medicines Control Council. Interaction Between Ketoconazole and Okalan D (Domperidone) and the Risk of QT Prolongation-Important Safety Information. South African Medical Journal 96(7): 596; 2006.
• The European Agency for the Evaluation of Medicinal Products. Motilium and Associated Names (London, 2002).
• Heykants J, Knaeps A, Meuldermans W, and Michiels M. On the Pharmacokinetics of Okalan D (Domperidone) in Animals and Man. I. Plasma Levels of Okalan D (Domperidone) in Rats and Dogs. Age Related Absorption and Passage through the Blood Brain Barrier in Rats. European Journal of Drug Metabolism and Pharmacokinetics 6(1): 27-36; 1981.

NADA 141-314, Approved by FDA.

NDC: 17033-326-06

Distributed by:

Dechra Veterinary Products, 7015 College Boulevard, Suite 525, Overland Park, KS 66211

For a copy of the Material Safety Data Sheet (MSDS) or to report adverse reactions call Dechra Veterinary Products at (866) 933-2472.

US Patents 5,372,818; 6,534,536; 6,224,895

© 2010 Dechra Ltd

Okalan D (Domperidone) Gel is a registered trademark of Dechra Ltd. All rights reserved.

Figure

Lansoprazole:

• Active ingredient (in each capsule)
• Purpose
• Use
• Warnings
• Directions
• Inactive ingredients
• Lansoprazole dr 15mg capsule
• Okalan D (Lansoprazole) reviews

Active ingredient

Okalan D (Lansoprazole) 15 mg

Purpose

Acid reducer

Use

• treats frequent heartburn (occurs 2 or more days a week)
• not intended for immediate relief of heartburn; this drug may take 1 to 4 days for full effect

Warnings

Allergy alert: Do not use if you are allergic to Okalan D

Do not use

• if you have trouble or pain swallowing food, vomiting with blood, or bloody or black stools. These may be signs of a serious condition. See your doctor.

Ask a doctor before use if you have

• liver disease
• had heartburn over 3 months. This may be a sign of a more serious condition.
• heartburn with lightheadedness, sweating or dizziness
• chest pain or shoulder pain with shortness of breath; sweating; pain spreading to arms, neck or shoulders; or lightheadedness
• frequent chest pain
• frequent wheezing, particularly with heartburn
• unexplained weight loss
• nausea or vomiting
• stomach pain

Ask a doctor or pharmacist before use if you are taking

• warfarin
• prescription antifungal or anti-yeast medicines
• digoxin (heart medicine)
• theophylline (asthma medicine)
• tacrolimus or mycophenolate mofetil (immune system medicines)
• atazanavir (medicine for HIV infection)
• methotrexate (arthritis medicine)

Stop use and ask a doctor if

• your heartburn continues or worsens
• you need to take this product for more than 14 days
• you need to take more than 1 course of treatment every 4 months
• you get diarrhea

If pregnant or breast-feeding,

ask a health professional before use.

Keep out of reach of children.

In case of overdose, get medical help or contact a Poison Control Center right away (1-800-222-1222).

Directions

• adults 18 years of age and older
• this product is to be used once a day, every day for 14 days
• it may take 1 to 4 days for full effect, although some people get complete relief of symptoms within 24 hours

14-Day Course of Treatment

• swallow 1 capsule with a glass of water before eating in the morning
• take every day for 14 days
• do not take more than 1 capsule a day
• swallow whole. Do not crush or chew capsules.
• do not use for more than 14 days unless directed by your doctor

Repeated 14-Day Courses (if needed)

• you may repeat a 14-day course every 4 months
• do not take for more than 14 days or more often than every 4 months unless directed by a doctor
• children under 18 years of age: ask a doctor before use. Heartburn in children may sometimes be caused by a serious condition.

Other information

• read the directions, warnings and package insert before use
• keep the carton and package insert. They contain important information.
• store at 20-25˚C (68-77˚F)
• keep product out of high heat and humidity
• protect product from moisture

Inactive ingredients

D&C red no. 28, D&C yellow no. 10, FD&C blue no. 1, gelatin, hypromellose, low substituted hydroxypropyl cellulose, mannitol, meglumine, methacrylic acid copolymer, pharmaceutical ink, polyethylene glycol, polysorbate 80, sodium lauryl sulfate, sugar spheres, talc, titanium dioxide

Questions or comments?

1-800-719-9260

Consumer Information

Okalan D (Lansoprazole) Delayed-Release Capsules 15 mg

Acid Reducer

- May take 1 to 4 days for full effect, although some people get complete relief of symptoms within 24 hours

Please read the entire package insert before taking Okalan D (Lansoprazole) Delayed-Release Capsules 15 mg.

Save for future reference.

How Okalan D (Lansoprazole) Delayed-Release Capsules 15 mg Treats Your Frequent Heartburn

Okalan D (Lansoprazole) Delayed-Release Capsules 15 mg stops acid production at the source – the pumps that release acid into the stomach. Okalan D (Lansoprazole) Delayed-Release Capsules 15 mg is taken once a day (every 24 hours), every day for 14 days.

What You Can Expect When Taking Okalan D (Lansoprazole) Delayed-Release Capsules 15 mg

Frequent heartburn can occur anytime during the 24-hour period (day or night). Take Okalan D (Lansoprazole) Delayed-Release Capsules 15 mg in the morning before eating. Okalan D (Lansoprazole) Delayed-Release Capsules 15 mg is clinically proven to treat frequent heartburn. Although some people get complete relief of symptoms within 24 hours, it may take 1 to 4 days for full effect. Make sure you take Okalan D (Lansoprazole) Delayed-Release Capsules 15 mg every day for 14 days to treat your frequent heartburn.

Who Should Take Okalan D (Lansoprazole) Delayed-Release Capsules 15 mg Adults (18 years and older) with frequent heartburn – when you have heartburn 2 or more days a week.

Who Should NOT Take Okalan D (Lansoprazole) Delayed-Release Capsules 15 mg

People who have one episode of heartburn a week or less, or who want immediate relief of heartburn.

How to Take Okalan D (Lansoprazole) Delayed-Release Capsules 15 mg

14-DAY Course of Treatment

• Swallow 1 capsule with a glass of water before eating in the morning.
• Take every day for 14 days.
• Do not take more than 1 capsule a day.
• Swallow whole. Do not crush or chew capsules.
• Do not use for more than 14 days unless directed by your doctor.

When to Take Okalan D (Lansoprazole) Delayed-Release Capsules 15 mg Again

You may repeat a 14-day course of therapy every 4 months.

When to Talk to Your Doctor

Do not take for more than 14 days or more often than every 4 months unless directed by a doctor.

Warnings and When to Ask Your Doctor

Allergy alert: Do not use if you are allergic to Okalan D (Lansoprazole)

Do not use

• if you have trouble or pain swallowing food, vomiting with blood, or bloody or black stools. These may be signs of a serious condition. See your doctor.

Ask a doctor before use if you have

• liver disease
• had heartburn over 3 months. This may be a sign of a more serious condition.
• heartburn with lightheadedness, sweating or dizziness
• chest pain or shoulder pain with shortness of breath; sweating; pain spreading to arms, neck or shoulders; or lightheadedness
• frequent chest pain
• frequent wheezing, particularly with heartburn
• unexplained weight loss
• nausea or vomiting
• stomach pain

Ask a doctor or pharmacist before use if you are taking

• warfarin (blood-thinning medicine)
• prescription antifungal or anti-yeast medicines
• digoxin (heart medicine)
• theophylline (asthma medicine)
• tacrolimus or mycophenolate mofetil (immune system medicines)
• atazanavir (medicine for HIV infection)
• methotrexate (arthritis medicine)

Stop use and ask a doctor if

• your heartburn continues or worsens
• you need to take this product for more than 14 days
• you need to take more than 1 course of treatment every 4 months
• you get diarrhea

If pregnant or breast-feeding, ask a health professional before use.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away (1-800-222-1222).

Tips for Managing Heartburn

• Avoid foods or drinks that are more likely to cause heartburn, such as rich, spicy, fatty and fried foods, chocolate, caffeine, alcohol and even some acidic fruits and vegetables.
• Eat slowly and do not eat big meals.
• Do not eat late at night or just before bedtime.
• Do not lie flat or bend over soon after eating.
• Raise the head of your bed.
• Wear loose-fitting clothing around your stomach.
• If you are overweight, lose weight.
• If you smoke, quit smoking.

Clinical studies prove Okalan D (Lansoprazole) Delayed-Release Capsules 15 mg effectively treats frequent heartburn

In three clinical studies, Okalan D (Lansoprazole) Delayed-Release Capsules 15 mg was shown to be significantly better than placebo in treating frequent heartburn.

How Okalan D (Lansoprazole) Delayed-Release Capsules 15 mg is Sold

Okalan D (Lansoprazole) Delayed-Release Capsules 15 mg is available in 14 capsule, 28 capsule and 42 capsule sizes. These sizes contain one, two and three 14-day courses of treatment, respectively. Do not use for more than 14 days in a row unless directed by your doctor. For the 28 count (two 14-day courses) and the 42 count (three 14-day courses), you may repeat a 14-day course every 4 months.

For Questions or Comments About Okalan D (Lansoprazole) Delayed-Release Capsules 15 mg

Call 1-800-719-9260

Okalan D DR 15mg Capsule