Dantrolene

Dantrolene is part of the drug class:

• Dantrolene and derivatives

Common side effects include:

• drowsiness
• dizziness
• weakness
• feeling of discomfort (malaise)
• fatigue
• diarrhea
• loss of grip strength and weakness in the legs (particularly when dantrolene is given by IV injection)

This is not a complete list of dantrolene side effects. Ask your doctor or pharmacist for more information.

Serious side effects have been reported. See "Drug Precautions" section.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Tell your doctor if you are breastfeeding or plan to breastfeed.

Dantrolene has been detected in human breast milk. Because of the possibility for adverse reactions in nursing infants from dantrolene, a choice should be made whether to stop nursing or to stop use of this medication. The importance of the drug to the mother should be considered.

Take dantrolene exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dantrolene dose your doctor recommends will be based on the following:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• how you are receiving dantrolene (orally or intravenously)
• your weight
• your age

​The maximum recommended dantrolene dose is 100 mg taken 4 times daily.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For dantrolene, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to dantrolene or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of dantrolene in children below 5 years of age. Safety and efficacy have not been established.

Geriatric

No information is available on the relationship of age to the effects of dantrolene in geriatric patients.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking dantrolene, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using dantrolene with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Alprazolam
• Amlodipine
• Amobarbital
• Aprobarbital
• Butabarbital
• Butalbital
• Carisoprodol
• Chloral Hydrate
• Chlordiazepoxide
• Chlorzoxazone
• Cinnarizine
• Clevidipine
• Clobazam
• Clonazepam
• Clorazepate
• Dantrolene
• Diazepam
• Diltiazem
• Estazolam
• Ethchlorvynol
• Felodipine
• Flunitrazepam
• Flurazepam
• Halazepam
• Isradipine
• Ketazolam
• Lorazepam
• Lormetazepam
• Medazepam
• Mephenesin
• Mephobarbital
• Meprobamate
• Metaxalone
• Methocarbamol
• Methohexital
• Methotrexate
• Midazolam
• Nicardipine
• Nifedipine
• Nimodipine
• Nisoldipine
• Nitrazepam
• Oxazepam
• Pentobarbital
• Phenobarbital
• Prazepam
• Primidone
• Quazepam
• Secobarbital
• Sodium Oxybate
• Temazepam
• Thiopental
• Triazolam
• Verapamil

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of dantrolene. Make sure you tell your doctor if you have any other medical problems, especially:

• Heart disease or
• Liver disease, history of or
• Lung disease (e.g., emphysema, asthma, bronchitis)—The chance of serious side effects may be increased.

• Liver disease, active (e.g., hepatitis, cirrhosis) or
• Muscle spasms caused by rheumatic disorders—Should not be used in patients with these conditions.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention. Serious side effects are very rare when dantrolene is taken for a short time, for example, when it is used for a few days before, during, or after surgery or anesthesia to prevent or treat malignant hyperthermia. However, serious side effects may occur, especially when the medicine is taken for a long time.

Check with your doctor immediately if any of the following side effects occur:

• Bloody or black, tarry stools
• bloody or dark urine
• bluish color changes in skin color
• changes in speech
• chest pain
• confusion
• constipation
• convulsions (seizures)
• decrease in frequency of urination
• decrease in urine volume
• difficult urination
• difficulty in moving
• difficulty in passing urine (dribbling)
• difficulty in swallowing
• fast, pounding, or irregular heartbeat or pulse
• increased frequency of urination
• increased urge to urinate during the night
• joint pain
• light-colored stools
• lightheadedness
• loss of bladder control
• mental depression
• muscle aching or cramping
• muscle pains or stiffness
• muscle spasm or jerking of all extremities
• nausea and vomiting
• pain in lower back
• pain or burning while urinating
• pain, tenderness, or changes in skin color
• painful urination
• severe stomach pain
• shortness of breath
• skin rash, hives, or itching
• slow or troubled breathing
• sudden decrease in amount of urine
• sudden loss of consciousness
• swelling of foot or leg
• swollen joints
• unusual tiredness or weakness
• upper right abdominal pain
• vomiting of blood or material that looks like coffee grounds
• waking to urinate at night
• yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Diarrhea
• dizziness
• drowsiness
• general feeling of discomfort or illness
• muscle weakness

• Abdominal or stomach cramps or discomfort
• abnormal hair growth
• acne-like rash
• blurred or double vision or any change in vision
• change in taste
• chills and fever
• disturbed color perception
• excessive tearing
• halos around lights
• headache
• itching skin
• loss of appetite
• night blindness
• overbright appearance of lights
• redness of skin
• seeing double
• skin rash, encrusted, scaly and oozing
• sleeplessness
• slurring of speech or other speech problems
• sudden decrease in amount of urine
• sweating
• trouble in sleeping
• tunnel vision
• unable to sleep
• unusual nervousness
• weight loss

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Dantrolene sodium should be used with caution in patients with impaired pulmonary function, particularly those with obstructive pulmonary disease, and in patients with severely impaired cardiac function due to myocardial disease. Dantrolene sodium is associated with pleural effusion with associated eosinophilia. It should be used with caution in patients with a history of previous liver disease or dysfunction (see WARNINGS).

Information for Patients

Patients should be cautioned against driving a motor vehicle or participating in hazardous occupations while taking Dantrolene sodium. Caution should be exercised in the concomitant administration of tranquilizing agents.

Dantrolene sodium might possibly evoke a photosensitivity reaction; patients should be cautioned about exposure to sunlight while taking it.

For Use in Chronic Spasticity

Prior to the administration of Dantrolene sodium capsules, consideration should be given to the potential response to treatment. A decrease in spasticity sufficient to allow a daily function not otherwise attainable should be the therapeutic goal of treatment with Dantrolene sodium capsules. Refer to INDICATIONS AND USAGE section for description of response to be anticipated.

It is important to establish a therapeutic goal (regain and maintain a specific function such as therapeutic exercise program, utilization of braces, transfer maneuvers, etc.) before beginning Dantrolene sodium capsule therapy. Dosage should be increased until the maximum performance compatible with the dysfunction due to underlying disease is achieved. No further increase in dosage is then indicated.

Usual Dosage

It is important that the dosage be titrated and individualized for maximum effect. The lowest dose compatible with optimal response is recommended.

In view of the potential for liver damage in long-term Dantrolene sodium capsule use, therapy should be stopped if benefits are not evident within 45 days.

Adults

The following gradual titration schedule is suggested. Some patients will not respond until higher daily dosage is achieved. Each dosage level should be maintained for seven days to determine the patient's response. If no further benefit is observed at the next higher dose, dosage should be decreased to the previous lower dose.

              25 mg once daily for seven days, then
              25 mg t.i.d. for seven days
              50 mg t.i.d. for seven days
              100 mg t.i.d.

Therapy with a dose four times daily may be necessary for some individuals. Doses higher than 100 mg four times daily should not be used. (See Box Warning.)

Pediatric Patients

The following gradual titration schedule is suggested. Some patients will not respond until higher daily dosage is achieved. Each dosage level should be maintained for seven days to determine the patient's response. If no further benefit is observed at the next higher dose, dosage should be decreased to the previous lower dose.

              0.5 mg/kg once daily for seven days, then
              0.5 mg/kg t.i.d. for seven days
              1 mg/kg t.i.d. for seven days
              2 mg/kg t.i.d.

Therapy with a dose four times daily may be necessary for some individuals. Doses higher than 100 mg four times daily should not be used. (See Box Warning.)

For Malignant Hyperthermia

Administer 4 to 8 mg/kg/day of oral Dantrolene sodium caspules in 3 or 4 divided doses for one or two days prior to surgery, with the last dose being given approximately 3 to 4 hours before scheduled surgery with a minimum of water.

This dosage will usually be associated with skeletal muscle weakness and sedation (sleepiness or drowsiness); adjustment can usually be made within the recommended dosage range to avoid incapacitation or excessive gastrointestinal irritation (including nausea and/or vomiting).

Oral Dantrolene sodium capsules should also be administered following a malignant hyperthermia crisis, in doses of 4 to 8 mg/kg per day in four divided doses, for a one to three day period to prevent recurrence of the manifestations of malignant hyperthermia.

Chronic spasticity: Children ≥5 years and Adolescents: Oral:

Note: Dose should be titrated and individualized for maximum effect; use the lowest dose compatible with optimal response. Some patients may not respond until a higher daily dosage is achieved; each dose level should be maintained for 7 days to determine patient response. If no further benefit observed with the higher dose level, then decrease dosage to previous dose level. Because of the potential for hepatotoxicity, stop therapy if benefits are not evident within 45 days.

Initial: 0.5 mg/kg/dose once daily for 7 days; increase to 0.5 mg/kg/dose 3 times daily for 7 days, increase to 1 mg/kg/dose 3 times daily for 7 days, and then increase to 2 mg/kg/dose 3 times daily; some patients may require 2 mg/kg/dose 4 times daily; maximum dose: 400 mg/day

Malignant hyperthermia (MH): Infants, Children, and Adolescents: Refer to adult dosing.

Concerns related to adverse effects:

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

• Hepatotoxicity: [US Boxed Warning]: Oral: Has potential for hepatotoxicity; symptomatic hepatitis (fatal and nonfatal) has been reported. Higher doses (ie, ≥800 mg/day), even sporadic short courses, may increase the risk of severe hepatic injury although hepatic injury may occur at doses <400 mg/day. Overt hepatitis has been most frequently observed between the third and twelfth month of therapy. The risk of hepatic injury appears to be greater in females, in patients >35 years, and in those taking concurrent medications. A higher incidence of fatal hepatic events have been reported in the elderly, although concurrent disease states and concurrent use of potentially hepatotoxic drugs may have contributed. Idiosyncratic and hypersensitivity reactions (sometimes fatal) of the liver have also occurred. Monitor hepatic function at baseline and as clinically indicated during treatment. Discontinue therapy if symptoms compatible with hepatitis, accompanied with abnormal liver function tests or jaundice occur or benefits are not observed within 45 days when utilized for chronic spasticity. Hepatic function usually reverts to normal upon discontinuation; if reinstitution of therapy is necessary, patients should be hospitalized and the drug initiated in very small and gradual dose increases.

• Muscle weakness: Loss of grip strength, weakness in the legs, dyspnea, respiratory muscle weakness, dysphagia, and decreased inspiratory capacity has occurred with IV dantrolene. Patients should not ambulate without assistance until they have normal strength and balance. Monitor patients for the adequacy of ventilation and for difficulty swallowing/choking.

• Photosensitivity: Oral therapy may cause a photosensitivity reaction; use with caution during exposure to sunlight.

• Pleural effusion: Pleural effusion with associated eosinophilia may occur.

Disease-related concerns:

• Cardiovascular disease: Use oral therapy with caution in patients with severely impaired cardiac function due to myocardial disease.

• Hepatic disease: Use oral therapy with caution in patients with history of hepatic disease or dysfunction; use is contraindicated in patients with active hepatic disease (eg, cirrhosis, hepatitis).

• Respiratory disease: Use oral therapy with caution in patients with impaired pulmonary function (particularly in obstructive pulmonary disease).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Extravasation: Alkaline solution; may cause tissue necrosis if extravasated (vesicant); ensure proper needle or catheter placement prior to and during infusion; avoid extravasation.

• Mannitol: Injection may contain mannitol.

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley, 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer’s labeling.

Other warnings/precautions:

• Appropriate use: IV dantrolene is not the only therapeutic approach for management of malignant hyperthermia. Supportive measures, including discontinuing trigger agents (eg, anesthetic agents), administering oxygen, utilizing cooling methods, and monitoring blood gases, urinary output, urine color, and electrolytes, must also be utilized and individualized. Administer diuretics to prevent late kidney injury due to myoglobinuria.

Adverse events have been observed in animal reproduction studies. Dantrolene crosses the human placenta. Cord blood concentrations are similar to those in the maternal plasma at term. and dantrolene can be detected in the newborn serum at delivery. Adverse events were not observed in the newborn following maternal doses of 100 mg/day administered orally prior to delivery (Shime, 1988). Uterine atony has been reported following dantrolene injection after delivery; however, this may be due in part to the mannitol contained in the IV preparation (Shin, 1995; Weingarten, 1987). Prophylactic use of dantrolene is not routinely recommended in pregnant women susceptible to MH prior to obstetric surgery, if use is needed, close monitoring of the mother and newborn is recommended (Krause 2004; Norman 1995).

For use in controlling the manifestations of clinical spasticity resulting from upper motor neuron disorders: 0.5 mg/kg orally once daily for 7 days, then
0.5 mg/kg three times a day for 7 days, then
1 mg/kg three times a day for 7 days, then
2 mg/kg three times a day.

Dosage should be titrated and individualized for maximum effect. The lowest dose compatible with optimal response is recommended.

Some patients will not respond until higher daily dosage is achieved. Each dosage level should be maintained for seven days to determine the patient's response. If no further benefit is observed at the next higher dose, dosage should be decreased to the previous lower dose.

Therapy with a dose four times daily may be necessary for some individuals. Doses higher than 100 mg four times daily should not be used.

In view of the potential for liver damage in long-term dantrolene use, therapy should be stopped if benefits are not evident within 45 days.