Butalbital

What is Butalbital? Is Butalbital a barbiturate drug?

Butalbital is a barbiturate drug with intermediate duration of action. Butalbital works as a sedative, decreases anxiety and cause sleepiness and relaxation. It is often used in combination with other drugs, such as aspirin or acetaminophen, and is commonly prescribed for headache (tension headache or migraine) and pain relieving treatment. Those combinations which are known as butalbital containing medicinie (BCM’s) are:

  • Butalbital + acetaminophen (Axocet, Bupap, Bucet, Cephadyn, Dolgic, Phrenilin, Phrenilin Forte, Sedapap)
  • Butalbital + acetaminophen + caffeine (Fioricet, Esgic, Esgic-Plus)
  • Butalbital + aspirin (Axotal)
  • Butalbital + aspirin + caffeine (Fiorinal, Fiortal, Fiormor, Fortabs, Laniroif)
  • Butalbital + acetaminophen + caffeine + codeine phosphate (Fioricet with Codeine)
  • Butalbital + aspirin + caffeine + codeine phosphate (Fiorinal with Codeine)
  • Butalbital + caffeine + ergotamine tartarate + belladonna alkaloids (Cafergot-PB)

butalbital

Butalbital /Acetaminophen combination

Butalbital and Acetaminophen combination is a medicine marketed under different Brand names such as: Allzital, Marten-Tab, Bupap, Triaprin, Phrenilin Forte, Phrenilin, Bucet, Sedapap, Dolgic, Axocet, Cephadyn, Tencon, Prominol, Butex Forte, Orbivan CF, Promacet. This combination is indicated for treating chronic tension headaches. This combination is not for treating acute headaches.

Actaminophen is used as a pain reliever and fever reducer while Butalbital is a sedative used to relax muscles that are involved in a tension headache and also as sleep inducer. However, the role of each component works in the relief ofunited and complex of symptoms known as tension headache is incompletely yet understood and this combination is used as non-specific therapy. Butalbital and Acetaminophen combination are available in the form of tablets in following doses: 25 mg / 325 mg and 50 mg/ 325 mg.

To be sure that you can safely take butalbital and acetaminophen, you should tell your doctor if you have any of these other conditions:

  • liver disease;
  • kidney disease;
  • Patients with porphyria
  • a history of drug or alcohol addiction or
  • a stomach or intestinal disorder

Patients should tell their doctor if they have ever had alcoholic liver disease such as cirrhosis, if they had hepatitis, or if they drink more than 3 alcoholic beverages a day. Such patients may not be able to take this combination as it contains acetaminophen.

Most common side effects that butalbital/acetaminophen combination may cause are:

  • Central Nervous System: dry mouth, hyperhidrosis.
  • Cardiovascular: tachycardia.
  • Gastrointestinal: difficulty swallowing, flatulence, heartburn, constipation.
  • Musculoskeletal: leg pain, muscle fatigue.
  • Genitourinary: diuresis.
  • Other: fever, earache, pruritus, nasal congestion, tinnitus, euphoria, allergic reactions.

Overdose symptoms may also include extreme drowsiness, confusion, fainting, shallow breathing, or no breathing.

Butalbital and Acetaminophen combination

Butalbital /Acetaminophen / Caffeine combination

Butalbital, Acetaminophen and Caffeine combination is a medicine marketed under different Brand names such as: Capacet, Fioricet, Esgic, Medigesic, Margesic, Orbivan, Repan, Vanatol LQ, Zebutal etc. This combination is indicated for the treatment of chronic tension headaches. In this combination acetaminophen is used to relieve the pain from the headache.

Caffeine is stimulant that increases acetaminophen’s effects. Butalbital is a sedative used to relax muscles that are involved in a tension headache and also as sleep inducer. This combination is available in the form of tablets in next dose 50 mg of butalbital, 325 mg of acetaminophen, and 40 mg of caffeine.

Among the most commonly reported side effects that can be caused by this drug combination are:

  • Drowsiness
  • Lightheadedness, dizziness
  • Feeling short of breath
  • Nausea, vomiting, stomach pain

Patients should contact their doctor if they have any of these conditions:

  • drink more than 3 alcohol containing drinks per day
  • heart or circulation problems
  • drug abuse or addiction
  • kidney disease or problems going to the bathroom
  • liver disease
  • hemophilia, von Willebrand’s disease, low platelets, or other bleeding problems
  • lung disease like asthma or emphysema
  • porphyria
  • an unusual or allergic reaction to aspirin or salicylates, butalbital or other barbiturates, caffeine, other medicines, foods, dyes, or preservatives
  • peptic ulcer disease
  • pregnant or trying to get pregnant
  • breast-feeding

Butalbital , Acetaminophen and caffeine

Butalbital/Aspirin/Caffeine combination

Butalbital, Aspirin and Caffeine combination is a medicine marketed under different Brand names such as: Farbital and Fiorinal. This combination is indicated for the treatment of chronic tension headaches. Aspirin is used as a pain reliever, anti-inflammatory agent and as a fever reducer.

Caffeine works as a CNS stimulant constricting blood vessels in the brain and thus redicing blood flow. It may also enhance the effects of aspirin. Butalbital relaxes muscle contractions involved in a tension headache.

Patients should not use this combination if they have a stomach ulcer, porphyria, severe liver disease, a bleeding or blood clotting disorder, or if they are allergic to any NSAID drug. Aspirin may cause stomach or intestinal bleeding, which can be fatal.

Patients should stop using these drugs and should call their doctor immediately if they have: bloody, black or tarry stools, and if they cough up blood or vomit that looks like coffee grounds. Aspirin should never be given to a child or teenager who has a fever. Butalbital may also be habit-forming. Inappropriate use of this meidicine can cause addiction, overdose, or even death.

Butalbital/Aspirin/Caffeine combination

Butalbital with Codeine

There are many products on the market that contain butalbital in combination with codeine. The best known product is Fioricet with codeine. These products are used for the treatment of tension headaches. It may also be used for other conditions as prescribed by your doctor.

Fioricet with Codeine is a barbiturate drug with analgesic, stimulant, and narcotic properties. Acetaminophen and codeine work as pain relievers. Caffeine constricts blood vessels in the brain, which may be helpful to relieve headache pain. Butalbital relaxes contractions of muscles that are involved in a tension headache, reduces anxiety and helps you to relax.

Patients with next conditions have to avoid this combination:

  • Allergy to any ingredient in Fioricet with Codeine
  • Patients with porphyria
  • Patients on a quinidine or sodium oxybate therapy

butalbital-acetaminophen-caffeine-and-codeine-phos-05

Migraine medicine butalbital

Butalbital containing medicine is used for the treatment of tension headaches and migraines as a alternative therapy. Triptans and dihydroergotamine do not work for many patients, for others may not be appropriate or may be limited for use because of finances and insurance. Non-steroidal anti-inflammatory drugs, acetaminophen and aspirin are less effective and may have significant side effects, particularly in elderly.

OTC drugs with caffeine are also modestly effective. Such drugs may cause rebound headaches known as medication overuse headache (MOH) and but also other adverse effects. Isometheptene-containing drugs have limited efficacy in migraine treatment, and may not be well tolerated. Opioids may be overused, may cause addiction, and serious adverse effects.

Butalbital, acetaminophen and caffeine combination seem to work synergistically to relieve various types of headaches.  Fioricet is approved by the FDA for the treatment of tension headaches, post-dural puncture headaches, muscle contraction headaches, but it is also prescribed off-label with efficiacy for migraine treatment.

Acetaminophen is a non-narcotic analgesic used for pain and headache relief. Butalbital is a barbiturate used for its muscle relaxant and sedative effects. Caffeine constricts vascular muscles involved in migraine and may also enhance the activity of different analgesics. Fioricet is also available with codeine. The combination of acetaminophen and codeine produces a greater analgesic effect compared to acetaminophen alone or by higher doses of opiate.

How Butalbital works as antimigraine drug

Butalbital works by imitating the inhibitory effects of GABA neurotransmitter.  This drug binds to the GABAA receptors in the brain within the chloride receptor complex, a site which is separate from that of benzodiazepines place.  By binding to the chloride receptor sites, butalbital results with prolongation of chloride channel opening, allowing a greater amount of chloride ions to enter the neuron cell.

This process induces hyperpolarization of cell membrane thus making it less sensitive to postsynaptic excitatory potentials.  Reduced sensitivity to excitatory stimuli enhances a CNS depressant effect which is characterized with relaxation, sedation, and/or drowsiness and may be related with migraine reduction – especially if the migraines are caused by vasoconstriction.

Many studies found that GABA is very effective in headache attacks suppression and that low GABA levels could be implicated among migraine sufferers. Studies also showed that GABA may affect the neurotransmission of trigeminovascular nociceptive system within the trigeminocervical complex.

Butalbital not only increase GABA transmission in the brain, it can also prevent the occurrence of migraines and lessen the intensity of already-occurring migraines.  So, at all, butalbital’s can modify vasodilation, nociception, and excitatory amino acids likely contribute to its therapeutic efficacy for cases of migraines.

Butalbital for opiate withdrawal

Butalbital is addicitive drug, thus it is not recommended for the therapy of opiate withdrawal as it will likely cause another addiction problem. Opiate recovery should always include abstinence from any other addictive or mood-altering drugs. That includes not only the butalbital, but also alcohol, marijuana etc.

Is butalbital a narcotic drug?

Butalbital belongs to the class of barbiturate drugs, it is habit-forming substance and it is abused.  But it is no opiate drug and not related to morphine and codeine and thus it is not classifies as a narcotic.  There is a warning in the PDR that this drug is only available by prescription under Federal Law.

Is butalbital a controlled substance?

There is a little confusion about the controlled substance status of butalbital and its products. According to DEA listing, Fioricet, which is a combination of acetaminophen, butalbital, and caffeine, is a DEA exempt prescription product.

There is no logical reason for why this is excused from controlled substance listing, but it has been agreed that the butalbital concentrations when it is used together with acetaminophen and caffeine is not so elevated in the blood and allows this as an analgesic combination that the DEA allows exemption to.

However Fioricet’s which is a similar product and contains the same dose of butalbital, but it is combined with aspirin and caffeine instead of acetaminophen and caffeine is listed as DEA Schedule III item. But, Fioricet is listed as Schedule III in only five states (MD, GA, UT, FL and NM).

Butalbital’s side effects

Common side effects that butalbital can cause are following:

  • Dizziness
  • Drowsiness
  • Intoxicated feeling
  • Lightheadedness
  • Sedation

Less common butalbitals side effects are following:

  • Tachycardia
  • Dry mouth, hyperhidrosis
  • Headache, tingling, agitation, shaky feeling, fever, heavy eyelids, fainting, fatigue, high energy, sluggishness, hot spells, numbness, seizure
  • Leg pain, muscle fatigue
  • Difficulty swallowing, heartburn, flatulence, constipation
  • Diuresis
  • Pruritus, tinnitus, euphoria, earache, nasal congestion, allergic reactions

Symptoms of butalbital overdose are following:

  • Confusion as to time, place, or person
  • difficult or painful urination
  • dark urine
  • Fever
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • general feeling of discomfort or illness
  • headache
  • hallucinations
  • holding false beliefs that cannot be changed by fact
  • irregular, fast or slow, or shallow breathing
  • light-colored stools
  • increased sweating
  • pale or blue lips, fingernails, or skin
  • restlessness
  • loss of appetite
  • Sweating
  • sudden decrease in the amount of urine
  • trouble sleeping
  • unusual excitement, nervousness, or restlessness
  • unpleasant breath odor
  • yellow eyes or skin
  • vomiting of blood

Butalbital dosage

Proper butalbital dosage will be given on Fioricet example. Fioricet except butalbital also contain acetaminophen and caffeine as active ingredients.

  • Usual Adult Dose of butalbital for Headache:

Acetaminophen 300 mg, butalbital 50 mg, and caffeine 40 mg:

1 or 2 capsule(s) orally every 4 hours as needed. Maximum daily dose: 6 doses.

Acetaminophen 325 mg, butalbital 50 mg, and caffeine 40 mg:

1 or 2 tablet(s), capsule(s), or tablespoonful(s) orally every 4 hours.

Maximum daily dose: 6 doses

Acetaminophen 500 mg, butalbital 50 mg, and caffeine 40 mg:

1 tablet or capsule orally every 4 hours.

Maximum daily dose: 6 doses

Acetaminophen 750 mg, butalbital 50 mg, and caffeine 40 mg:

1 tablet orally every 4 hours.

Maximum daily dose: 5 tablets

  • Usual Pediatric Dose for Headache (12 years and older):

Acetaminophen 300 mg, butalbital 50 mg, and caffeine 40 mg:

1 or 2 capsule(s) orally every 4 hours as needed.

Maximum daily dose: 6 doses.

Butalbital high

Those who take butalbital or its combinations may experience effects such as: relaxation, psychomotor slowing, mild analgesia and a sense of physiological tranquility.  Combinations with caffeine for example Fioricet may attenuate CNS depression which can be induced by butalbital but it doesn’t fully suppress it.

So those who abuse misuse or overuse butalbital products may experience a neurophysiological “high.”  Except experiencing mild and pleasurable intoxication with effects such as relaxation and pain relief, but also reduced anxiety and sedation, users may be more likely to abuse butalbital drugs in the future.

Butalbital high is similar and its intoxication is very similar to alcohol. Butalbital abusers and those who ingest very high doses may experience a butalbital “high”. Characteristics of butalbital high are following:

  • Anxiety relieve: Many patients with anxiety disorders find butalbital products very helpful. It can decrease anxiety when it is administered in normal doses. However, in high doses anxiety may completely vanish. Butalbital affects and elevates GABA concentrations and effects in the brain and these actions may relieve anxiety and stay beyond its pathophysiology.  Also, butalbital’s abuse in most abusers is mostly related to anxiety reduction.
  • Relaxation: Many individuals use high doses of butalbital products in order to induce physical and/or psychological relaxation. In large amounts, butalbital induces nice feelings of internal calmness, tranquility and peace. Studies found that butalbital relaxation effects can be comparable to benzodiazepine’s ones.
  • Euphoria and mood enhancement: Individuals who experience butalbitals “high” may experience in most cases a mild sensation of euphoria. It happens because of CNS downregulation induced by butalbital. But, after recreational and more frequent use of Fioricet, its euphoria effects will decline.  Newer users are always more likely to experience euphoria compared to chronic users.

Also, a non-euphoric mood enhancement is also reported after butalbitals products administration in large doses.  This may be induced through butalbitals GABAergic effects, but it is suggested that this effect may be facilitated by the other active ingredients in products such as acetaminophen and caffeine.

Caffeine is a stimulant and can enhance mood and acetaminophen reduces inflammation and in this way improves mood.  Perhaps, that combination of adenosine and GABA activities and inflammatory modulation contributes to butalbital’s mood enhancing properties when it is administered in large doses.

  • Drowsiness: It is common for those who take barbiturates in large doses to experience drowsiness. Drowsiness may also occur if recommended doses are taken, but when it is overdosed lethargy, fatigue, and a high sense of drowsiness may be experienced. This happens because GABA is inhibitory neurotransmitter in the brain that causes sedation.
  • Lightheadedness: High-amounts of butalbital may lead to feeling of lightheadedness and dizziness. In some rare and extreme cases, this may end up with fainting as a result of of very high butalbitals dosing.
  • Sleepiness and sedation: Butalbital causes sleepiness in most patients. While Fioricet also contains caffeine in attempt to balance butalbital’s sedating effects, however caffeine may not be enough for some individuals. Rapid caffeine metabolizers experience more stimulation and jitteriness very fast after taking Fioricet, while others may notice no caffeine stimulation and end up feeling drowsy and/or sleepy.
  • Jitteriness: Those who ingest large doses of butalbital may exhibit jitteriness. This may be a result of high caffeine concentrations in the body. Although most of the caffeine stimulatory effects can be beaten by butalbital, caffeine may still provoke jitters. As a result, in some rare cases, recreational users of butalbitals products with caffeine could feel relaxed but also simultaneously jittery.
  • Numbness: Many butalbital abusers claim to enjoy its effects of numbness. This may be a physical numbness, if all pain sensations are relieved, but it could also be emotional numbness. Some abusers experience a mixture of physical and emotional numbness simultaneously.  These happen because GABA is involved in pain-transmiting processes.
  • Slurred speech: Similar to alcohol, barbiturates may also cause slurred speech. Slurring of speech may not occur among all abusers, it is a sign that the recommended doses have been exceeded.
  • Motor incoordiantion: High doses of butalbital and its intoxication may lead to difficulties with motor coordination such as maintaing balance and fine motor skills. The person may stumble when walks and and any physical activity will be compromised. This reminds to alcohol intoxication.
  • Recklessness: High doses of butalbital may some individulas make to feel fearless and engage in reckless or careless behaviors. While everyone is responsible for their behavior, conscious oversight is cast by the wayside as a result of excessive GABA activity.
  • Depersonalization: In some rare cases butalbital and all barbiturates may be very unpleasant for some abusers causing depersonalization effects. Abusers who experimented with high doses of this drug report uncomfortable feelings, characterized by depersonalization, confusion, and sluggishness.

Butalbital abuse

Butalbital and other barbiturates drugs are abused because of their ability to produce sedation, euphoria and in some rare cases paradoxical stimulation. Abusers combine barbiturates with alcohol or heroin or use them to suppress high effects of stimulants such as methamphetamines or cocaine. In high doses, butalbital and other barbiturates can produce slow and shallow breathing and may cause death due to respiratory arrest.

Most butalbital abusers build a tolerance after long-term use thus they need to take higher amounts to experience same effects. Taking higher and higher doses of butalbital increases the overdose risk and combining butalbital with alcohol, other barbiturates, benzodiazepines or other CNS depressants such as heroin or codeine can be fatal in most cases.

Regular use of butalbital can lead to physical and psychological dependence, and butalbital dependents may begin to display patterns of addictive behaviors.

Butalbital addiction

Butalbital like all barbiturates may cause both physical and psychiological dependency. Signs of butalbital physical dependence may vary between each individual. The intensity of dependence symptoms is also influenced by how serious the addiction is. Physical dependence signs and symptoms may include: stomach upset, vomiting, nausea and irritability.

It is never unusual for an abuser but also patient to experience these symptoms between doses. However, the biggest problem is tolerance. Prolonged use of butalbital will in most cases build a person’s tolerance to it. However, psychological symptoms of dependence are usually more powerful than the physical, and may be not as obvious.

Many abusers may notice that they have become preoccupied and obsessed with taking this drug. Prolonged butalbital use will also make an abuser to believe that they are unable to function properly without it.

Signs of butalbital addiction:

  • Spending less time on activities that you once enjoyed.
  • Using more butalbital than you intended.
  • Taking risks to obtain butalbital.
  • Showing poor performance and attendance at work or at school.
  • Making an effort to hide butalbital use from others.
  • Struggling with relationships and receiving complaints from coworkers, supervisors, teachers, or classmates.
  • Building a tolerance to the drug, so that the person needs more and more of it to achieve the same effects as before.
  • Diminishing attention to maintaining hygiene and appearance.
  • Experiencing withdrawal symptoms when use is stopped or reduced.
  • Continuing to use despite negative consequences to one’s career, relationships, or health.

What is butalbital half-life time? How long butalbital stay in your system?

Butalbital is well absorbed after oral administration from the gastrointestinal tract and is expected to distribute to most tissues in the body. It may appear in breast milk and readily cross the placental barrier. Butalbital is bound to plasma and tissue proteins to a varying degree and binding increases directly as a function of lipid solubility.

Butalbital elimination is predominantly through the kidney 60-90% as unchanged drug or as a metabolite. Butalbital’s plasma half-life is about 35 hours. Butalbital is a short-intermediate acting barbiturate. I it can be probably detected in the urine for around 7 to 10 days after administration. Factors such as age, health, weight and metabolism may have an impact on its elimination from the body.

Does butalbital show up on a drug test?

Yes barbiturates can show up on drug tests. Labratories uses immunoassay (EIA) technique for detecting barbiturates in urine. The immunoassays provide cost effective and very sensitive method barbiturate detection.

Gas chromatography/mass spectrometry (GC/MS) is used to further identify and confirm the presence of a particular barbiturate such as butalbital in the sample. The 200 ng/ml cutoff for EIA allows detection of barbiturate administration for up to 72 hours of taken dose. It can be showed in urine, saliva and hair samples.

Butalbital during pregnancy

Butalbital has been given pregnancy category C by the FDA pregnancy category list of drugs. Barbiturates in general have been shown to readily cross the placental barrier. Withdrawal seizures have been reported in a two day old infant whose mother had taken a butalbital containing drug during the last two months of pregnancy.

Butalbital was found in the infant’s serum. Animal reproduction studies have not been conducted. There are also no controlled studies in human pregnancy. Butalbital should be used during pregnancy only if the potential benefit outweighs the potential risk to the infant.

Butalbital Breastfeeding Warnings

It is known that barbiturates pass into breast milk in small amounts. However, the significance of the effects on nursing infants has not been yet reported. Because of the potential serious side effects in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the butalbital use, taking into account the importance of the drug to the mother.

Butalbital interaction with birth control pills

This interaction is serious and may cause harmful side effects. When butalbital is taken together with birth control pills, the body may process and metabolizes estrogen from birth control pills faster. The effects birth control pills may become decreased so breakthrough bleeding, spotting, or pregnancy may be caused. To prevent pregnancy, use an extra form of birth control (eg, condoms).

Butalbital and Alcohol interaction

Butalbital and other barbiturates should never be taken together with alcohol, because alcohol will potentiate the effects of butalbital and thus increase the risk of side effects and CNS depression. Concurrent acute use of barbiturates and alchohol may result in additive CNS effects, including impaired coordination, sedation, respiratory distress and death.

However, studies showed that tolerance may occur with chronic use. The mechanism is related to inhibition of microsomal hepatic enzymes in acute situations and induction of hepatic microsomal enzymes in chronic situations.

Both drugs also work by increasing GABA activity in the brain which is strongest inhibitory neurotransmitter in the body. Fioricet also contains acetaminophen, which may cause liver damage. Drinking alcohol on a chronic manner and taking a medicine such as Fioricet that contains acetaminophen and butalbital, may increase your risk for liver damage.

Butalbital and Xanax interaction

Using butalbital together with Xanax may increase the incidence of side effects such as dizziness, sedation, drowsiness, confusion, and difficulty concentrating. In some people, especially elderly, may experience impairment in judgment, thinking and motor coordination. You should avoid or limit alcohol use while being treated with these drugs.

Activities requiring mental alertness such as driving or operating machinery and driving have to be avoided until you know how the drugs affect you. This combination of drugs may cause respiratory depression and be fatal!

Butalbital and Benadryl interaction

Using Benadryl together with butalbital may increase CNS side effects such as dizziness, confusion, drowsiness, and difficulty concentrating. Some people, especially the elderly and debilitated patients, may also experience impairment in thinking, judgment, and motor coordination. Both drugs are CNS and respiratory depressants and if they are taken together they will work additively and synergistically.

Also, barbiturates such as butalbital may increase the hepatotoxic potential of acetaminophen from Benadryl products and decrease its therapeutic effects. The mechanism may be related to CYP450 increased metabolism of acetaminophen with consequent increase in hepatotoxic metabolites.

This interaction is of greatest concern in cases of acetaminophen overdose. Also there are both butalbital and Benadryl products that also contain acetaminophen, so if they are taken together acetaminophen dose will be doubled and serious hepatic side effects may occur.

Butalbital and Adderall interaction

In general there should be no life-threating interaction between these two drugs. Butalbital has CNS inhibitory effects while Adderall is CNS stimulant. However, many butalbital’s products also contain caffeine which is also CNS stimulant, so there are high chances that stimulant effects may overcome inhibitory especially in persons who are poor metabolizers of caffeine.

Butalbital and Ambien interaction

Using butalbital together with Ambien may increase the incidence of side effects such as dizziness, sedation, drowsiness, confusion, and difficulty concentrating. In some people, especially elderly and debilitated persons may experience impairment in judgment, thinking and motor coordination. You should avoid or limit alcohol use while being treated with these drugs.

Activities requiring mental alertness such as driving or operating machinery and driving have to be avoided until you know how the drugs affect you. Butalbital and zolpidem from Ambien are both central nervous system and respiratory-depressant that works additively or synergistically. This combination of drugs may cause respiratory depression and be fatal!

Butalbital and Hydrocodone or Oxycodone interaction

Using butalbital together with Hydrocodone or Oxycodone may increase the incidence of side effects such as sedation, drowsiness, dizziness, confusion, and difficulty concentrating. Predisposed patients, especially elderly and debilitated persons may experience impairment in judgment, thinking and motor coordination.

Butalbital and hydrocodone and oxycodone are central nervous system and respiratory system depressant that works additively or synergistically. This combination of drugs may cause respiratory depression and be fatal!

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