Doxylamine
Encyclopedia
Doxylamine is one of the many sedating antihistamine
s used by itself as a short-term sedative
, and in combination with other drugs as a night-time cold
and allergy
relief drug. It is also used in combination with the analgesics paracetamol
(acetaminophen) and codeine
as an analgesic/calmative preparation, and is prescribed in combination with vitamin B6
(pyridoxine
) to prevent morning sickness
in pregnant
women.
class of antihistamines and has anti-allergy power superior to almost every other antihistamine on the market, with the exception of diphenhydramine
(Benadryl
). It is also the most effective over-the-counter sedative available in the United States
and is more sedating than some prescription hypnotic
s. One study found that doxylamine succinate was more effective than the barbiturate
phenobarbital
for use as a sedative.
The dosage required to induce hypnosis (sleep
) can be as low as 6.25 mg, but is usually effective in dosages of up to 25 mg. Higher doses are not recommended by the United States Food and Drug Administration
, although single dosage recommendations of up to 50 mg are common in some countries, including Australia, where it is marketed under the names Restavit and Dozile.
A recent placebo-controlled, double-blind randomized trial found the formulation of doxylamine and pyridoxine marketed as Diclectin to be effective in controlling nausea and vomiting due to pregnancy.
and has a side-effect
profile common to such drugs, including dry mouth
, ataxia
, urinary retention
, drowsiness, memory problems, inability to concentrate, hallucinations, psychosis, and a marked increased sensitivity to external stimuli. Like many hypnotics, it should not be combined with other antihistamines, such as Zyrtec (cetirizine) or diphenhydramine, as this combination can increase the risk of serious side effects. Using doxylamine over a long period of time is not recommended and can cause dependence. However, the drug is not addictive and withdrawal effects are unlikely to be experienced with prolonged use.
, and death. Fatalities have been reported from doxylamine overdose. These have been characterized by coma, tonic-clonic seizures and cardiorespiratory arrest. Children appear to be at a high risk for cardiorespiratory arrest. A toxic dose for children of more than 1.8 mg/kg has been reported. A 3 year old child died 18 hours after ingesting 1,000 mg doxylamine succinate. Rarely, an overdose results in rhabdomyolysis
and acute renal failure
.
salt, doxylamine succinate.
Antihistamine
An H1 antagonist is a histamine antagonist of the H1 receptor that serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions...
s used by itself as a short-term sedative
Sedative
A sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....
, and in combination with other drugs as a night-time cold
Common cold
The common cold is a viral infectious disease of the upper respiratory system, caused primarily by rhinoviruses and coronaviruses. Common symptoms include a cough, sore throat, runny nose, and fever...
and allergy
Allergy
An Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...
relief drug. It is also used in combination with the analgesics paracetamol
Paracetamol
Paracetamol INN , or acetaminophen USAN , is a widely used over-the-counter analgesic and antipyretic . It is commonly used for the relief of headaches and other minor aches and pains and is a major ingredient in numerous cold and flu remedies...
(acetaminophen) and codeine
Codeine
Codeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
as an analgesic/calmative preparation, and is prescribed in combination with vitamin B6
Vitamin B6
Vitamin B6 is a water-soluble vitamin and is part of the vitamin B complex group. Several forms of the vitamin are known, but pyridoxal phosphate is the active form and is a cofactor in many reactions of amino acid metabolism, including transamination, deamination, and decarboxylation...
(pyridoxine
Pyridoxine
Pyridoxine is one of the compounds that can be called vitamin B6, along with pyridoxal and pyridoxamine. It differs from pyridoxamine by the substituent at the '4' position. It is often used as 'pyridoxine hydrochloride'.-Chemistry:...
) to prevent morning sickness
Morning sickness
Morning sickness, also called nausea gravidarum, nausea, vomiting of pregnancy , or pregnancy sickness is a condition that affects more than half of all pregnant women. Related to increased oestrogen levels, a similar form of nausea is also seen in some women who use hormonal contraception or...
in pregnant
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
women.
Indications
Doxylamine is a member of the ethanolamineEthanolamine
Ethanolamine, also called 2-aminoethanol or monoethanolamine , is an organic chemical compound that is both a primary amine and a primary alcohol . Like other amines, monoethanolamine acts as a weak base...
class of antihistamines and has anti-allergy power superior to almost every other antihistamine on the market, with the exception of diphenhydramine
Diphenhydramine
Diphenhydramine hydrochloride is a first-generation antihistamine possessing anticholinergic, antitussive, antiemetic, and sedative properties which is mainly used to treat allergies. Like most other first-generation antihistamines, the drug also has a powerful hypnotic effect, and for this reason...
(Benadryl
Benadryl
Benadryl is a brand name allergy medicine marketed over-the-counter by Johnson & Johnson subsidiary McNeil Consumer Healthcare. Prior to 2007, Benadryl was marketed by Pfizer Consumer Healthcare...
). It is also the most effective over-the-counter sedative available in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
and is more sedating than some prescription hypnotic
Hypnotic
Hypnotic drugs are a class of psychoactives whose primary function is to induce sleep and to be used in the treatment of insomnia and in surgical anesthesia...
s. One study found that doxylamine succinate was more effective than the barbiturate
Barbiturate
Barbiturates are drugs that act as central nervous system depressants, and can therefore produce a wide spectrum of effects, from mild sedation to total anesthesia. They are also effective as anxiolytics, as hypnotics, and as anticonvulsants...
phenobarbital
Phenobarbital
Phenobarbital or phenobarbitone is a barbiturate, first marketed as Luminal by Friedr. Bayer et comp. It is the most widely used anticonvulsant worldwide, and the oldest still commonly used. It also has sedative and hypnotic properties but, as with other barbiturates, has been superseded by the...
for use as a sedative.
The dosage required to induce hypnosis (sleep
Sleep
Sleep is a naturally recurring state characterized by reduced or absent consciousness, relatively suspended sensory activity, and inactivity of nearly all voluntary muscles. It is distinguished from quiet wakefulness by a decreased ability to react to stimuli, and is more easily reversible than...
) can be as low as 6.25 mg, but is usually effective in dosages of up to 25 mg. Higher doses are not recommended by the United States Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
, although single dosage recommendations of up to 50 mg are common in some countries, including Australia, where it is marketed under the names Restavit and Dozile.
A recent placebo-controlled, double-blind randomized trial found the formulation of doxylamine and pyridoxine marketed as Diclectin to be effective in controlling nausea and vomiting due to pregnancy.
Metabolites
The two main metabolites are desmethyldoxylamine and didesmethyldoxylamine.Side effects
Doxylamine succinate is a potent anticholinergicAnticholinergic
An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicycloverine, and the classic example is atropine....
and has a side-effect
Adverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
profile common to such drugs, including dry mouth
Xerostomia
Xerostomia is the medical term for the subjective complaint of dry mouth due to a lack of saliva. Xerostomia is sometimes colloquially called pasties, cottonmouth, drooth, or doughmouth. Several diseases, treatments, and medications can cause xerostomia. It can also be exacerbated by smoking or...
, ataxia
Ataxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
, urinary retention
Urinary retention
Urinary retention, also known as ischuria, is a lack of ability to urinate. It is a common complication of benign prostatic hyperplasia , although it can also be caused by nerve dysfunction, constipation, infection, or medications...
, drowsiness, memory problems, inability to concentrate, hallucinations, psychosis, and a marked increased sensitivity to external stimuli. Like many hypnotics, it should not be combined with other antihistamines, such as Zyrtec (cetirizine) or diphenhydramine, as this combination can increase the risk of serious side effects. Using doxylamine over a long period of time is not recommended and can cause dependence. However, the drug is not addictive and withdrawal effects are unlikely to be experienced with prolonged use.
Toxicity
Doxylamine succinate is generally safe for administration to healthy adults. Typical preparations that contain doxylamine range from 6.25 mg to 50 mg. The is estimated to be 50–500 mg/kg in humans. Symptoms of overdose may include dry mouth, dilated pupils, insomnia, night terrors, euphoria, hallucinations, seizures, rhabdomyolysisRhabdomyolysis
Rhabdomyolysis is a condition in which damaged skeletal muscle tissue breaks down rapidly. Breakdown products of damaged muscle cells are released into the bloodstream; some of these, such as the protein myoglobin, are harmful to the kidneys and may lead to kidney failure...
, and death. Fatalities have been reported from doxylamine overdose. These have been characterized by coma, tonic-clonic seizures and cardiorespiratory arrest. Children appear to be at a high risk for cardiorespiratory arrest. A toxic dose for children of more than 1.8 mg/kg has been reported. A 3 year old child died 18 hours after ingesting 1,000 mg doxylamine succinate. Rarely, an overdose results in rhabdomyolysis
Rhabdomyolysis
Rhabdomyolysis is a condition in which damaged skeletal muscle tissue breaks down rapidly. Breakdown products of damaged muscle cells are released into the bloodstream; some of these, such as the protein myoglobin, are harmful to the kidneys and may lead to kidney failure...
and acute renal failure
Renal failure
Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
.
Formulations
Doxylamine is primarily used as the succinic acidSuccinic acid
Succinic acid is a dicarboxylic acid. Succinate plays a biochemical role in the citric acid cycle. The name derives from Latin succinum, meaning amber, from which the acid may be obtained....
salt, doxylamine succinate.
- It is the sedating ingredient of NyQuilNyQuilNyQuil is a brand of over the counter medication which is intended to relieve various symptoms of the common cold. Because all of the medications within the NyQuil imprint contain sedating antihistamines, hypnotics, and/or alcohol, they are intended to be taken before sleep...
. - In CommonwealthCommonwealth of NationsThe Commonwealth of Nations, normally referred to as the Commonwealth and formerly known as the British Commonwealth, is an intergovernmental organisation of fifty-four independent member states...
countries, such as AustraliaAustraliaAustralia , officially the Commonwealth of Australia, is a country in the Southern Hemisphere comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands in the Indian and Pacific Oceans. It is the world's sixth-largest country by total area...
, South AfricaSouth AfricaThe Republic of South Africa is a country in southern Africa. Located at the southern tip of Africa, it is divided into nine provinces, with of coastline on the Atlantic and Indian oceans...
and the United KingdomUnited KingdomThe United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
, doxylamine is available prepared with paracetamolParacetamolParacetamol INN , or acetaminophen USAN , is a widely used over-the-counter analgesic and antipyretic . It is commonly used for the relief of headaches and other minor aches and pains and is a major ingredient in numerous cold and flu remedies...
(acetaminophen) and codeineCodeineCodeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
under the brand name Dolased, Propain Plus, Syndol, or Mersyndol, as treatment for tension headacheTension headacheA tension headache is the most common type of primary headache. The pain can radiate from the neck, back, eyes, or other muscle groups in the body. Tension-type headaches account for nearly 90% of all headaches...
and other types of painPainPain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
. - Doxylamine succinate is used in general over-the-counterOver-the-counter drugOver-the-counter drugs are medicines that may be sold directly to a consumer without a prescription from a healthcare professional, as compared to prescription drugs, which may be sold only to consumers possessing a valid prescription...
sleep-aids branded as Somnil, Dozile, Donormyl, Dormidina, Restavit, Unisom-2 and Sleep Aid (generic - Australia),. - In the United StatesUnited StatesThe United States of America is a federal constitutional republic comprising fifty states and a federal district...
doxylamine succinate is the active ingredient in the over-the-counter sleep-aid tablets branded as UnisomUnisomUnisom is the Chattem brand name for an over-the-counter sleep-aid medication. While marketed under a single trademark, the active ingredient may be one of two drugs, depending on the type of preparation...
; however, the gel-cap form contains diphenhydramine hydrochloride instead. - In CanadaCanadaCanada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...
doxylamine succinate is the active ingredient in the over-the-counter sleep-aid tablets branded as UnisomUnisomUnisom is the Chattem brand name for an over-the-counter sleep-aid medication. While marketed under a single trademark, the active ingredient may be one of two drugs, depending on the type of preparation...
2; while UnisomUnisomUnisom is the Chattem brand name for an over-the-counter sleep-aid medication. While marketed under a single trademark, the active ingredient may be one of two drugs, depending on the type of preparation...
contains diphenhydramine hydrochloride as the active ingredient. - It is also available in combination with vitamin B6 and folic acidFolic acidFolic acid and folate , as well as pteroyl-L-glutamic acid, pteroyl-L-glutamate, and pteroylmonoglutamic acid are forms of the water-soluble vitamin B9...
under the brand name Evanorm (marketed by Ion Healthcare). - In CanadaCanadaCanada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...
, doxylamine succinate and pyridoxinePyridoxinePyridoxine is one of the compounds that can be called vitamin B6, along with pyridoxal and pyridoxamine. It differs from pyridoxamine by the substituent at the '4' position. It is often used as 'pyridoxine hydrochloride'.-Chemistry:...
(vitamin B6Vitamin B6Vitamin B6 is a water-soluble vitamin and is part of the vitamin B complex group. Several forms of the vitamin are known, but pyridoxal phosphate is the active form and is a cofactor in many reactions of amino acid metabolism, including transamination, deamination, and decarboxylation...
) are the ingredients of Diclectin, which is used to prevent morning sicknessMorning sicknessMorning sickness, also called nausea gravidarum, nausea, vomiting of pregnancy , or pregnancy sickness is a condition that affects more than half of all pregnant women. Related to increased oestrogen levels, a similar form of nausea is also seen in some women who use hormonal contraception or...
.