Ivermectin/oxibendazole/praziquantel

Ivermectin/oxibendazole/praziquantel Medicine

Contraindications

See also:
What is the most important information I should know about Ivermectin?

Before taking ivermectin, tell your doctor about any other medical conditions that you have, especially liver disease. If you have liver problems, you may not be able to use ivermectin, or you may need a dosage adjustment or special tests during treatment.

Treatment with ivermectin usually involves taking a single dose, which should be taken on an empty stomach with a full glass of water.

To be sure this medication is helping your condition, a sample of your stool (bowel movement) will need to be checked on a regular basis. It is important that you not miss any scheduled visits to your doctor.

Avoid drinking alcohol, which can increase some of the side effects of ivermectin.

You may need to be retreated with ivermectin several months to a year after your single dose.

Call your doctor at once if you have any problems with your eyes or your vision.

See also:
What is the most important information I should know about Praziquantel?

Praziquantel (praziquantel) is contraindicated in patients who previously have shown hypersensitivity to the drug or any of the excipients. Since parasite destruction within the eye may cause irreversible lesions, ocular cysticercosis must not be treated with this compound.

Concomitant administration with strong Cytochrome P450 (P450) inducers, such as rifampin, is contraindicated since therapeutically effective blood levels of praziquantel may not be achieved. In patients receiving rifampin who need immediate treatment for schistosomiasis, alternative agents for schistosomiasis should be considered. However, if treatment with praziquantel is necessary, rifampin should be discontinued 4 weeks before administration of praziquantel. Treatment with rifampin can then be restarted one day after completion of praziquantel treatment.

Undesirable effects

See also:
What are the possible side effects of Ivermectin?

Strongyloidiasis

In four clinical studies involving a total of 109 patients given either one or two doses of 170 to 200 mcg/kg of Ivermectin (ivermectin), the following adverse reactions were reported as possibly, probably, or definitely related to Ivermectin (ivermectin) :

Body as a Whole: asthenia/fatigue (0.9%), abdominal pain (0.9%)

Gastrointestinal: anorexia (0.9%), constipation (0.9%), diarrhea (1.8%), nausea (1.8%), vomiting (0.9%)

Nervous System/Psychiatric: dizziness (2.8%), somnolence (0.9%), vertigo (0.9%), tremor (0.9%)

Skin: pruritus (2.8%), rash (0.9%), and urticaria (0.9%).

In comparative trials, patients treated with Ivermectin (ivermectin) experienced more abdominal distention and chest discomfort than patients treated with albendazole. However, Ivermectin (ivermectin) was better tolerated than thiabendazole in comparative studies involving 37 patients treated with thiabendazole.

The Mazzotti-type and ophthalmologic reactions associated with the treatment of onchocerciasis or the disease itself would not be expected to occur in strongyloidiasis patients treated with Ivermectin (ivermectin).

Laboratory Test Findings

In clinical trials involving 109 patients given either one or two doses of 170 to 200 mcg/kg Ivermectin (ivermectin), the following laboratory abnormalities were seen regardless of drug relationship: elevation in ALT and/or AST (2%), decrease in leukocyte count (3%). Leukopenia and anemia were seen in one patient.

Onchocerciasis

In clinical trials involving 963 adult patients treated with 100 to 200 mcg/kg Ivermectin (ivermectin), worsening of the following Mazzotti reactions during the first 4 days post-treatment were reported: arthralgia/synovitis (9.3%), axillary lymph node enlargement and tenderness (11.0% and 4.4%, respectively), cervical lymph node enlargement and tenderness (5.3% and 1.2%, respectively), inguinal lymph node enlargement and tenderness (12.6% and 13.9%, respectively), other lymph node enlargement and tenderness (3.0% and 1.9%, respectively), pruritus (27.5%), skin involvement including edema, papular and pustular or frank urticarial rash (22.7%), and fever (22.6%).

In clinical trials, ophthalmological conditions were examined in 963 adult patients before treatment, at day 3, and months 3 and 6 after treatment with 100 to 200 mcg/kg Ivermectin (ivermectin). Changes observed were primarily deterioration from baseline 3 days post-treatment. Most changes either returned to baseline condition or improved over baseline severity at the month 3 and 6 visits. The percentages of patients with worsening of the following conditions at day 3, month 3 and 6, respectively, were: limbitis: 5.5%, 4.8%, and 3.5% and punctate opacity: 1.8%, 1.8%, and 1.4%. The corresponding percentages for patients treated with placebo were: limbitis: 6.2%, 9.9%, and 9.4% and punctate opacity: 2.0%, 6.4%, and 7.2%.

In clinical trials involving 963 adult patients who received 100 to 200 mcg/kg Ivermectin (ivermectin), the following clinical adverse reactions were reported as possibly, probably, or definitely related to the drug in ≥ 1% of the patients: facial edema (1.2%), peripheral edema (3.2%), orthostatic hypotension (1.1%), and tachycardia (3.5%). Drug-related headache and myalgia occurred in < 1% of patients (0.2% and 0.4%, respectively). However, these were the most common adverse experiences reported overall during these trials regardless of causality (22.3% and 19.7%, respectively).

A similar safety profile was observed in an open study in pediatric patients ages 6 to 13.

The following ophthalmological side effects do occur due to the disease itself but have also been reported after treatment with Ivermectin (ivermectin) : abnormal sensation in the eyes, eyelid edema, anterior uveitis, conjunctivitis, limbitis, keratitis, and chorioretinitis or choroiditis. These have rarely been severe or associated with loss of vision and have generally resolved without corticosteroid treatment.

Laboratory Test Findings

In controlled clinical trials, the following laboratory adverse experiences were reported as possibly, probably, or definitely related to the drug in ≥ 1% of the patients: eosinophilia (3%) and hemoglobin increase (1%).

Post-Marketing Experience

The following adverse reactions have been reported since the drug was registered overseas:

Onchocerciasis

Conjunctival hemorrhage

All Indications

Hypotension (mainly orthostatic hypotension), worsening of bronchial asthma, toxic epidermal necrolysis, Stevens-Johnson syndrome, seizures, hepatitis, elevation of liver enzymes, and elevation of bilirubin.

See also:
What are the possible side effects of Praziquantel?

Applies to praziquantel: oral tablet

In addition to its needed effects, some unwanted effects may be caused by praziquantel (the active ingredient contained in Praziquantel). In the event that any of these side effects do occur, they may require medical attention.

Major Side Effects

You should check with your doctor immediately if any of these side effects occur when taking praziquantel:

Incidence not known:

  • Abdominal or stomach discomfort with or without nausea
  • abdominal or stomach pain
  • black, tarry stools
  • bloody diarrhea
  • chest pain or discomfort
  • chills
  • convulsions
  • cough
  • dizziness
  • fainting
  • fast, slow, or irregular heartbeat
  • fever
  • hives
  • hoarseness
  • irritation
  • itching
  • joint pain, stiffness, or swelling
  • lightheadedness, dizziness, or fainting
  • painful or difficult urination
  • rash
  • redness of the skin
  • severe abdominal or stomach pain
  • shortness of breath
  • slow or irregular heartbeat
  • sore throat
  • sores, ulcers, or white spots on the lips or in the mouth
  • sweating
  • swelling of the eyelids, face, lips, hands, or feet
  • swollen glands
  • tightness in the chest
  • troubled breathing or swallowing
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • wheezing
Minor Side Effects

Some of the side effects that can occur with praziquantel may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common:

  • Drowsiness
  • increased sweating
  • general feeling of discomfort or illness
  • nausea or vomiting
Less common:
  • Skin rash, hives, or itching
Incidence not known:
  • Difficulty with moving
  • dizziness or lightheadedness
  • feeling of constant movement of self or surroundings
  • headache
  • hives or welts
  • joint pain
  • lack or loss of strength
  • loss of appetite
  • muscle aching or cramping
  • muscle pains or stiffness
  • redness of the skin
  • sensation of spinning
  • sleepiness or unusual drowsiness
  • swollen joints
  • weight loss

Therapeutic indications

An indication is a term used for the list of condition or symptom or illness for which the medicine is prescribed or used by the patient. For example, acetaminophen or paracetamol is used for fever by the patient, or the doctor prescribes it for a headache or body pains. Now fever, headache and body pains are the indications of paracetamol. A patient should be aware of the indications of medications used for common conditions because they can be taken over the counter in the pharmacy meaning without prescription by the Physician.

Ivermectin (ivermectin) is indicated for the treatment of the following infections:

Strongyloidiasis of the intestinal tract. Ivermectin (ivermectin) is indicated for the treatment of intestinal (i.e., nondisseminated) strongyloidiasis due to the nematode parasite Strongyloides stercoralis.

This indication is based on clinical studies of both comparative and open-label designs, in which 64-100% of infected patients were cured following a single 200-mcg/kg dose of ivermectin.

Onchocerciasis. Ivermectin (ivermectin) is indicated for the treatment of onchocerciasis due to the nematode parasite Onchocerca volvulus.

This indication is based on randomized, double-blind, placebo-controlled and comparative studies conducted in 1427 patients in onchocerciasis-endemic areas of West Africa. The comparative studies used diethylcarbamazine citrate (DEC-C).

NOTE: Ivermectin (ivermectin) has no activity against adult Onchocerca volvulus parasites. The adult parasites reside in subcutaneous nodules which are infrequently palpable. Surgical excision of these nodules (nodulectomy) may be considered in the management of patients with onchocerciasis, since this procedure will eliminate the microfilariae-producing adult parasites.

An indication is a term used for the list of condition or symptom or illness for which the medicine is prescribed or used by the patient. For example, acetaminophen or paracetamol is used for fever by the patient, or the doctor prescribes it for a headache or body pains. Now fever, headache and body pains are the indications of paracetamol. A patient should be aware of the indications of medications used for common conditions because they can be taken over the counter in the pharmacy meaning without prescription by the Physician.

Praziquantel (praziquantel) is indicated for the treatment of infections due to: all species of schistosoma (for example, Schistosoma mekongi, Schistosoma japonicum, Schistosoma mansoni and Schistosoma hematobium), and infections due to the liver flukes, Clonorchis sinensis/Opisthorchis viverrini (approval of this indication was based on studies in which the two species were not differentiated).

Ivermectin is used in the treatment of certain worm infections. It is used to treat river blindness (onchocerciasis) and a certain type of diarrhea (strongyloidiasis). It may also be used for some other kinds of worm infections.

Ivermectin appears to work by paralyzing and then killing the offspring of adult worms. It may also slow down the rate at which adult worms reproduce. This results in fewer worms in the skin, blood, and eyes.

Ivermectin is available only with your doctor's prescription.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not included in product labeling, ivermectin is used in certain patients with the following medical condition:

  • Bancroft's filariasis
  • Scabies

Praziquantel is used to treat infections caused by parasites such as liver flukes (worms) or schistosoma (blood fluke). These infections are also known as snail fever, schistosomiasis, or bilharziasis. Praziquantel may also be used for other worm infections as determined by your doctor. However, it will not work for pinworms or other roundworms.

Praziquantel belongs to the family of medicines called anthelmintics. Anthelmintics are used in the treatment of worm infections. Praziquantel works by causing severe spasms and paralysis of the worms' muscles. Some kinds of worms are then passed in the stool. However, you may not notice them since they are sometimes completely destroyed in the intestine.

praziquantel is available only with your doctor's prescription.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not included in the product labeling, praziquantel is used in certain patients with the following medical conditions:

  • Some kinds of fluke infections.
  • Some kinds of tapeworm infections.

Name of the medicinal product

Ivermectin/Oxibendazole/Praziquantel

Qualitative and quantitative composition

Ivermectin is a broad-spectrum anti-parasite medication. It was first marketed under the name Ivermectin® and used against worms (except tapeworms), but, in 2012, it was approved for the topical treatment of head lice infestations in patients 6 months of age and older, and marketed under the name Sklice™ as well. Ivermectin is mainly used in humans in the treatment of onchocerciasis, but is also effective against other worm infestations (such as strongyloidiasis, ascariasis, trichuriasis and enterobiasis).

An anthelmintic used in most schistosome and many cestode infestations. [PubChem]

Special warnings and precautions for use

Use Ivermectin as directed by your doctor. Check the label on the medicine for exact dosing instructions.

  • An extra patient leaflet and instructions for use is available with Ivermectin. Talk to your pharmacist if you have questions about this information.
  • Be sure you understand how to use Ivermectin. Ask your health care provider if you have questions or if you are unsure how to use it.
  • If the patient is a child, an adult should apply Ivermectin.
  • Your hair and scalp should be completely dry before you apply Ivermectin.
  • Apply Ivermectin directly to dry hair, starting with the hair closest to the scalp. Work it outward, toward the ends of your hair. Use enough medicine to completely cover the hair and scalp (up to 1 tube).
  • Rub Ivermectin throughout your hair. Be sure that each hair is coated with medicine from the scalp to the tip.
  • After Ivermectin is applied, leave it on your hair and scalp for 10 minutes (use a timer or clock).
  • After 10 minutes, completely rinse Ivermectin using only water.
  • Wash your hands immediately after using Ivermectin.
  • Ivermectin is for a single use only. Throw away the tube and any unused medicine out of reach of children and away from pets.
  • Only one dose of Ivermectin is required. If you forget to use Ivermectin, use it as soon as you remember.

Ask your health care provider any questions you may have about how to use Ivermectin.

Use praziquantel as directed by your doctor. Check the label on the medicine for exact dosing instructions.

  • Take praziquantel with a full glass of water during meals.
  • Do not crush or chew before swallowing.
  • Take your doses at least 4 hours apart but not more than 6 hours apart unless directed otherwise by your doctor.
  • If you miss a dose of praziquantel, take it as soon as possible. If it less than 4 hours until your next dose, contact your doctor to see if you need to establish a new dosing schedule.

Ask your health care provider any questions you may have about how to use praziquantel.

There are specific as well as general uses of a drug or medicine. A medicine can be used to prevent a disease, treat a disease over a period or cure a disease. It can also be used to treat the particular symptom of the disease. The drug use depends on the form the patient takes it. It may be more useful in injection form or sometimes in tablet form. The drug can be used for a single troubling symptom or a life-threatening condition. While some medications can be stopped after few days, some drugs need to be continued for prolonged period to get the benefit from it.Use: Labeled Indications

Onchocerciasis: Treatment of onchocerciasis due to the immature form of Onchocerca volvulus.

Limitations of use: Ivermectin has no activity against adult Onchocerca volvulus parasites. The adult parasites reside in subcutaneous nodules which are infrequently palpable. Surgical excision may be considered as removal of these nodules will eliminate the microfilariae-producing adult parasites.

Strongyloidiasis, intestinal: Treatment of intestinal (eg, nondisseminated) strongyloidiasis due to Strongyloides stercoralis.

Off Label UsesAscariasis

Data from two clinical trials in patients with intestinal helminths supports the use of ivermectin in the treatment of Ascaris lumbricoides infection. Additional trials may be necessary to further define the role of ivermectin in this condition.

There are specific as well as general uses of a drug or medicine. A medicine can be used to prevent a disease, treat a disease over a period or cure a disease. It can also be used to treat the particular symptom of the disease. The drug use depends on the form the patient takes it. It may be more useful in injection form or sometimes in tablet form. The drug can be used for a single troubling symptom or a life-threatening condition. While some medications can be stopped after few days, some drugs need to be continued for prolonged period to get the benefit from it.Use: Labeled Indications

Helminths: Treatment of infections in patients ≥1 year caused by the following: All species of Schistosoma (eg, Schistosoma mekongi, Schistosoma japonicum, Schistosoma mansoni, Schistosoma haematobium) and the liver flukes Clonorchis sinensis/Opisthorchis viverrini

Off Label UsesNeurocysticercosis, parenchymal

Data from the phase II and phase III portions of a randomized, double blind, placebo-controlled study supports the use of praziquantel (in combination with albendazole) in the treatment of parenchymal neurocysticercosis.

Dosage (Posology) and method of administration

Strongyloidiasis

The recommended dosage of Ivermectin (ivermectin) for the treatment of strongyloidiasis is a single oral dose designed to provide approximately 200 mcg of ivermectin per kg of body weight. See Table 1 for dosage guidelines. Patients should take tablets on an empty stomach with water. In general, additional doses are not necessary. However, follow-up stool examinations should be performed to verify eradication of infection.

Table 1: Dosage Guidelines for Ivermectin (ivermectin) for Strongyloidiasis

Body Weight (kg) Single

Oral Dose

Number of 3-mg Tablets

15-24 1 tablet
25-35 2 tablets
36-50 3 tablets
51-65 4 tablets
66-79 5 tablets
≥ 80 200 mcg/kg
Onchocerciasis

The recommended dosage of Ivermectin (ivermectin) for the treatment of onchocerciasis is a single oral dose designed to provide approximately 150 mcg of ivermectin per kg of body weight. See Table 2 for dosage guidelines. Patients should take tablets on an empty stomach with water. In mass distribution campaigns in international treatment programs, the most commonly used dose interval is 12 months. For the treatment of individual patients, retreatment may be considered at intervals as short as 3 months.

Table 2: Dosage Guidelines for Ivermectin (ivermectin) for Onchocerciasis

Body Weight (kg) Single

Oral Dose

Number of 3-mg Tablets

15-25 1 tablet
26-44 2 tablets
45-64 3 tablets
65-84 4 tablets
≥ 85 150 mcg/kg
How supplied

No. 8495 — Tablets Ivermectin (ivermectin) 3 mg are white, round, flat, bevel-edged tablets coded MSD on one side and 32 on the other side. They are supplied as follows:

NDC 0006-0032-20 unit dose packages of 20.

Storage

Store at temperatures below 30°C (86°F).

Dist. by: MERCK & CO., INC,Whitehouse Station, NJ 08889, USA. Manufactured by: MSD BV Waarderweg 39 2031 BN Haarlem Netherlands. Issued 2009

The dosage recommended for the treatment of schistosomiasis is: 20 mg/kg bodyweight three times a day as a one day treatment, at intervals of not less than 4 hours and not more than 6 hours. The recommended dose for clonorchiasis and opisthorchiasis is: 25 mg/kg bodyweight three times a day as a one day treatment, at intervals of not less than 4 hours and not more than 6 hours. The tablets should be washed down unchewed with water during meals. Keeping the tablets or segments thereof in the mouth can reveal a bitter taste which can promote gagging or vomiting.

How supplied

Praziquantel (praziquantel) is supplied as a 600 mg white to orange tinged, film-coated, oblong tablet with three scores. The tablet is coded with “BAYER” on one side and “LG” on the reverse side. When broken, each of the four segments contains 150 mg of active ingredient so that the dosage can be easily adjusted to the patient's bodyweight.

Segments are broken off by pressing the score (notch) with thumbnails. If ¼ of a tablet is required, this is best achieved by breaking the segment from the outer end.

Praziquantel (praziquantel) is available in bottles of 6 tablets.

Strength NDC
Bottles of 6 600 mg 0085-1747-01

Store below 86°F (30°C).

Manufactured by: Bayer HealthCare Pharmaceuticals Inc. Wayne, NJ 07470. Made in Germany. Distributed and Marketed by: Schering Corporation, a subsidiary of Whitehouse Station, NJ 08889, USA. Revised: 08/10.

Interaction with other medicinal products and other forms of interaction

See also:
What other drugs will affect Ivermectin?

With simultaneous use of Ivermectin Ind-Swift with theophylline, aminophylline, caffeine, there is an increase in their concentration in blood plasma and thus increases the risk of toxic effects.

Erythromycin increases the concentrations of cyclosporine in the blood plasma and may increase the risk of nephrotoxicity.

Drugs that block tubular secretion prolongs T1/2 of erythromycin.

Incompatible with lincomycin, clindamycin and chloramphenicol (antagonism).

Ivermectin Ind-Swift reduces the bactericidal action of beta-lactam antibiotics (penicillins, cephalosporins, carbapenems).

With simultaneous use of erythromycin increases the concentration of theophylline.

At the same time receiving chemotherapy, which is carried metabolism in the liver (carbamazepine, valproic acid, hexobarbital, phenytoin, alfentanil, dizopiramid, lovastatin, bromocriptine), may increase the concentration of these drugs in plasma (an inhibitor of microsomal liver enzymes).

IV injection of erythromycin increases the effects of ethanol (accelerating gastric emptying and decrease the duration of alcohol dehydrogenase in the gastric mucosa).

Erythromycin reduces the clearance of triazolam and midazolam and therefore may increase the pharmacological effects of benzodiazepines.

At the same time taking with terfenadine or astemizole may develop arrhythmias (fibrillation and ventricular flutter, ventricular tachycardia, until death); with dihydroergotamine or non hydrated ergot alkaloids may vasoconstriction to spasm, dysesthesia.

With simultaneous application Ivermectin Ind-Swift slows elimination (increases the effect) of methylprednisolone, felodipine and anticoagulants of cumarine series.

In a joint appointment with lovastatin increased rhabdomyolysis.

Erythromycin increases the bioavailability of digoxin.

Erythromycin reduces the effectiveness of hormonal contraceptives.

See also:
What other drugs will affect Praziquantel?

Concomitant administration of rifampin, a strong P450 inducer, with praziquantel is contraindicated and must be avoided. In a crossover study with a 2-week washout period, 10 healthy subjects ingested a single 40 mg/kg dose of praziquantel following pre-treatment with oral rifampin (600 mg daily for 5 days). Plasma praziquantel concentrations were undetectable in 7 out of 10 subjects. When a single 40 mg/kg dose of praziquantel was administered to these healthy subjects two weeks after discontinuation of rifampin, the mean praziquantel AUC and Cmax were 23% and 35% lower, respectively, than when praziquantel was given alone. In patients receiving rifampin, for example, as part of a combination regimen for the treatment of tuberculosis, alternative agents for schistosomiasis should be considered. However, if treatment with praziquantel is necessary, treatment with rifampin should be discontinued 4 weeks before administration of praziquantel. Treatment with rifampin can then be restarted one day after completion of praziquantel treatment.

Concomitant administration of other drugs that increase the activity of drug metabolizing liver enzymes (P450 inducers), for example, antiepileptic drugs (phenytoin, phenobarbital and carbamazepine), and dexamethasone, may also reduce plasma levels of praziquantel. Concomitant administration of drugs that decrease the activity of drug metabolizing liver enzymes (P 450 inhibitors), for example, cimetidine, ketoconazole, itraconazole, erythromycin may increase plasma levels of praziquantel.

Chloroquine, when taken simultaneously, may lead to lower concentrations of praziquantel in blood. The mechanism of this drug-drug interaction is unclear.

Grapefruit juice was reported to produce a 1.6-fold increase in the Cmax and a 1.9-fold increase in the AUC of praziquantel. However, the effect of this exposure increase on the therapeutic effect and safety of praziquantel has not been systematically evaluated.